On the evening of July 30, 1945, a U.S. battleship traveling from Guam to the Philippines was spotted in the Philippine Sea by a Japanese submarine crew. Six torpedoes sped across the black water with devastating effect.

Three hundred sailors died immediately as the stricken ship sank. Another 900 men were left floating in an oil slick in the shark-infested Pacific Ocean for four days.1

The events that led to the sinking represent a classic tale of systems failures. They ring familiar to any physician who has closely examined modern medical error.

The communication breakdown that prevented the ship’s captain from being aware of submarine activity on the same route four days before is no different than communication breakdowns in complex hospital systems. The bureaucratic decision by a remote administrator to withhold the safety measure of an escort to prevent such an attack on the grounds that it “lacked necessity” likely resonates with physicians who have struggled with getting authorization for care.

Why did those sailors remain in the water four days before rescue? Despite being only a two-hour flight from the nearest base, they were not recovered—or even missed—for what must have seemed an endless amount of time.

In the end, slightly more than 300 men were alive when they were spotted by a plane that happened to fly past. The rest succumbed to dehydration, exposure, and sharks. The failure of the Navy to rescue the sailors offers lessons to the clinician trying to improve transitions of care more than a half a century later.

The Feedback Loop

Hospital discharge is a complex process initiated by physician orders on charts, prescription pads, and patient instructions. Most often, the things we assume will be done out of our direct view are carried out satisfactorily. However, any hospitalist can easily recount stories of tests or follow-up that didn’t happen as ordered. Patients who fall through the cracks at discharge—like the stranded sailors of the USS Indianapolis—are, in part, the story of a simple omitted step: the feedback loop.

A feedback loop occurs when the results or consequences of an action are returned as an input loop to the initiating step in order to modify subsequent actions. This fundamental engineering concept can keep complex systems on course. The feedback loop allows the lack of completion of a portion of a process to be recognized—and corrective measures taken—before additional harm occurs.

In Guam, the island base from which the USS Indianapolis departed, the marker indicating the ship on the plotting board was removed when the ship left. Later, the Philippine port of Leyte failed to note that the ship didn’t arrive. Policy at the time was that all ships that left port were presumed to have arrived at their destination unless a call indicating trouble was received. The junior officer who noticed that the ship hadn’t arrived assumed there had been an order to divert to an alternate port. The Navy had no feedback mechanism to communicate between the two ports and raise an alarm when a ship did not arrive. In fact, a Navy directive discouraged communicating the arrival of combat ships as a matter of military secrecy. As a result, no rescue mission was launched—and the sharks began to arrive.

A closer examination of usual hospitalist discharge practice reveals too much similarity for comfort. Similar to how the USS Indianapolis was removed from the plotting board on Guam, discharged patients are removed from the hospitalist’s census list. Follow-up becomes the responsibility of the patient and primary care physician.

Communication with the primary care provider is recognized as a best practice for discharge, but research suggests direct communication occurs less than 20% of the time.2 These dismal statistic suggests the “port of arrival” is unaware our patients are expected in a significant percentage of discharges. Outpatient physicians, like the junior port director in Leyte, may assume that patients who do not call or arrive for appointments have been readmitted, seen by another physician, or otherwise diverted.

Even a superficial review reveals significant deficits in the feedback provided by our current discharge practice. When patients don’t arrive at follow-up appointments, most hospitalists lack any ability to recognize this failure of their transition plan. The assumption in most hospitalist groups is that patients who leave the hospital will achieve follow-up as directed. This “presumption of success” is ill-founded and may expose the patient to potential harm—and the physician to liability.

The case of Shirk v. Kelsey offers parallels to discharge situations hospitalists commonly encounter.3 In this malpractice case, a procedure was unsuccessful in terminating a patient’s pregnancy. The performing physician left follow-up of the pathology results to the patient’s usual outpatient obstetrical provider. The patient’s lack of follow-up was not recognized by the discharging obstetrician. This provider—not the practitioner with whom follow-up was intended—was found liable.

The American Medical Asso­ciation’s code of ethics states: “Once having undertaken a case, the physician should not neglect the patient.” Hospitalists form physician-patient relationships with hospitalized patients that usually terminate on discharge. Our duty to not abandon or neglect a patient diminishes significantly after discharge, when we are no longer responsible for ongoing hospital care or exchanging information with patients on a daily basis.

But our duty does not disappear. Certainly, the responsibility falls to the hospitalist to be aware of and ensure a follow-up plan for important results such as pathology reports that return after discharge.

Allegations of improper post-discharge communication or failure to pass along critical results that become available once the patient has left the hospital, are common in medical malpractice claims.

Most are settled out of court, and many do not find the physician liable for malpractice. However, legal consequences are far less relevant than the safety and quality of care compromised when patients are failed by a system that lacks feedback loops to ensure safe transitions.

The ultimate goal of medicine is to improve the health and quality of life of our patients. Whether or not a lawsuit results, we need to recognize the commonality of patients who have their care compromised, delayed, or mismanaged because of our inability to recognize a foundering transition plan. Instead of looking at this as a failure of individual physicians to communicate, the problem needs to be addressed by creating effective, reliable systems.

Solutions

Providers discharging patients with follow-up needs should have a mechanism to identify those at highest risk for problems with transition. For these patients, follow-up with a post-discharge telephone call may be an effective feedback step.

One study looking at post-discharge phone contact found that 20% of patients had not filled new discharge prescriptions. Another post-discharge study revealed that a quarter of patients had medication questions that required clarification.4,5 Other research indicates more than one in 10 patients had new or worsening symptoms in the first five days after leaving the hospital.6 Despite these symptoms, 39% of these patients did not have a follow-up appointment established.

An integrated informatics system that prompts hospitalists and primary care physicians when patients do not arrive at expected follow-up or when test results return after discharge would be optimal. But a simple phone call to identify problems can be effective. Some hospitalist groups have incorporated routine post-discharge telephone contact into their practice—but most have not. Research identifying which patients would benefit is needed to allow targeted use of resources.7

While it’s understood that not all patient discharges will go smoothly, just as not all battleships will arrive at port without incident, there is frequently an opportunity to recover when things begin to go awry. A change in the common attitude that hospitalist responsibility ends when the patient leaves the hospital is necessary.

An element of the solution lies in the creation of feedback loops to identify patients who are not obtaining follow-up as expected. This step requires a commitment of resources—something our fragmented medical system, with location-based reimbursement, does not provide incentives for.

Creation of a feedback loop may be as complex as integrated medical informatics systems, or as simple as a follow-up phone call, but it is incumbent on each hospitalist to examine the environment in which they practice and ensure this vital element of a safe and reliable system is being addressed. TH

Drs. Cumbler and Egan are assistant professors in the Section of Hospital Medicine at the University of Colorado at Denver.

References

1. Stanton D. In harms way: the sinking of the USS Indianapolis and the extraordinary story of its survivors. New York, NY: Henry Holt and Company LLC; 2001.
2. Kripalani S, LeFevre F, Phillips F, Williams M, Basaviah P, Baker D. Deficits in communication and information transfer between hospital-based and primary care physicians: implications for patient safety and continuity of care. JAMA. 2007;297(8):831-841.
3. Alpers A. Key legal principles for hospitalists. Am J Med. 1999;111(9):5-9.
4. Dudas V, Bookwalter T, Kerr KM, Pantilat SZ. The impact of follow-up telephone calls to patients after hospitalization. Am J Med. 2001;111:26S-30S.
5. Boockvar K, LaCorte H, Giambanco V, Fridman B, Siu A. Medication reconciliation for reducing drug
6. discrepancy adverse events. Am J Geriatr Pharmacother. 2006;4:236-243.
7. Epstein K, Juarez E, Loya K, Gorman MJ, Singer A. Frequency of new or worsening symptoms in the posthospitalization period. JHM. 2007;2:58-68.
8. Mistiaen P, Poot E. Telephone follow-up, initiated by a hospital-based health professional, for postdischarge problems in patients discharged from hospital to home. Cochrane Database of Systemic Reviews 2006; 4. Article No.:CD004510. DOI:10.1002/14651858.CD004510.pub3.

On the evening of July 30, 1945, a U.S. battleship traveling from Guam to the Philippines was spotted in the Philippine Sea by a Japanese submarine crew. Six torpedoes sped across the black water with devastating effect.

Three hundred sailors died immediately as the stricken ship sank. Another 900 men were left floating in an oil slick in the shark-infested Pacific Ocean for four days.1

The events that led to the sinking represent a classic tale of systems failures. They ring familiar to any physician who has closely examined modern medical error.

The communication breakdown that prevented the ship’s captain from being aware of submarine activity on the same route four days before is no different than communication breakdowns in complex hospital systems. The bureaucratic decision by a remote administrator to withhold the safety measure of an escort to prevent such an attack on the grounds that it “lacked necessity” likely resonates with physicians who have struggled with getting authorization for care.

Why did those sailors remain in the water four days before rescue? Despite being only a two-hour flight from the nearest base, they were not recovered—or even missed—for what must have seemed an endless amount of time.

In the end, slightly more than 300 men were alive when they were spotted by a plane that happened to fly past. The rest succumbed to dehydration, exposure, and sharks. The failure of the Navy to rescue the sailors offers lessons to the clinician trying to improve transitions of care more than a half a century later.

The Feedback Loop

Hospital discharge is a complex process initiated by physician orders on charts, prescription pads, and patient instructions. Most often, the things we assume will be done out of our direct view are carried out satisfactorily. However, any hospitalist can easily recount stories of tests or follow-up that didn’t happen as ordered. Patients who fall through the cracks at discharge—like the stranded sailors of the USS Indianapolis—are, in part, the story of a simple omitted step: the feedback loop.

A feedback loop occurs when the results or consequences of an action are returned as an input loop to the initiating step in order to modify subsequent actions. This fundamental engineering concept can keep complex systems on course. The feedback loop allows the lack of completion of a portion of a process to be recognized—and corrective measures taken—before additional harm occurs.

In Guam, the island base from which the USS Indianapolis departed, the marker indicating the ship on the plotting board was removed when the ship left. Later, the Philippine port of Leyte failed to note that the ship didn’t arrive. Policy at the time was that all ships that left port were presumed to have arrived at their destination unless a call indicating trouble was received. The junior officer who noticed that the ship hadn’t arrived assumed there had been an order to divert to an alternate port. The Navy had no feedback mechanism to communicate between the two ports and raise an alarm when a ship did not arrive. In fact, a Navy directive discouraged communicating the arrival of combat ships as a matter of military secrecy. As a result, no rescue mission was launched—and the sharks began to arrive.

A closer examination of usual hospitalist discharge practice reveals too much similarity for comfort. Similar to how the USS Indianapolis was removed from the plotting board on Guam, discharged patients are removed from the hospitalist’s census list. Follow-up becomes the responsibility of the patient and primary care physician.

Communication with the primary care provider is recognized as a best practice for discharge, but research suggests direct communication occurs less than 20% of the time.2 These dismal statistic suggests the “port of arrival” is unaware our patients are expected in a significant percentage of discharges. Outpatient physicians, like the junior port director in Leyte, may assume that patients who do not call or arrive for appointments have been readmitted, seen by another physician, or otherwise diverted.

Even a superficial review reveals significant deficits in the feedback provided by our current discharge practice. When patients don’t arrive at follow-up appointments, most hospitalists lack any ability to recognize this failure of their transition plan. The assumption in most hospitalist groups is that patients who leave the hospital will achieve follow-up as directed. This “presumption of success” is ill-founded and may expose the patient to potential harm—and the physician to liability.

The case of Shirk v. Kelsey offers parallels to discharge situations hospitalists commonly encounter.3 In this malpractice case, a procedure was unsuccessful in terminating a patient’s pregnancy. The performing physician left follow-up of the pathology results to the patient’s usual outpatient obstetrical provider. The patient’s lack of follow-up was not recognized by the discharging obstetrician. This provider—not the practitioner with whom follow-up was intended—was found liable.

The American Medical Asso­ciation’s code of ethics states: “Once having undertaken a case, the physician should not neglect the patient.” Hospitalists form physician-patient relationships with hospitalized patients that usually terminate on discharge. Our duty to not abandon or neglect a patient diminishes significantly after discharge, when we are no longer responsible for ongoing hospital care or exchanging information with patients on a daily basis.

But our duty does not disappear. Certainly, the responsibility falls to the hospitalist to be aware of and ensure a follow-up plan for important results such as pathology reports that return after discharge.

Allegations of improper post-discharge communication or failure to pass along critical results that become available once the patient has left the hospital, are common in medical malpractice claims.

Most are settled out of court, and many do not find the physician liable for malpractice. However, legal consequences are far less relevant than the safety and quality of care compromised when patients are failed by a system that lacks feedback loops to ensure safe transitions.

The ultimate goal of medicine is to improve the health and quality of life of our patients. Whether or not a lawsuit results, we need to recognize the commonality of patients who have their care compromised, delayed, or mismanaged because of our inability to recognize a foundering transition plan. Instead of looking at this as a failure of individual physicians to communicate, the problem needs to be addressed by creating effective, reliable systems.

Solutions

Providers discharging patients with follow-up needs should have a mechanism to identify those at highest risk for problems with transition. For these patients, follow-up with a post-discharge telephone call may be an effective feedback step.

One study looking at post-discharge phone contact found that 20% of patients had not filled new discharge prescriptions. Another post-discharge study revealed that a quarter of patients had medication questions that required clarification.4,5 Other research indicates more than one in 10 patients had new or worsening symptoms in the first five days after leaving the hospital.6 Despite these symptoms, 39% of these patients did not have a follow-up appointment established.

An integrated informatics system that prompts hospitalists and primary care physicians when patients do not arrive at expected follow-up or when test results return after discharge would be optimal. But a simple phone call to identify problems can be effective. Some hospitalist groups have incorporated routine post-discharge telephone contact into their practice—but most have not. Research identifying which patients would benefit is needed to allow targeted use of resources.7

While it’s understood that not all patient discharges will go smoothly, just as not all battleships will arrive at port without incident, there is frequently an opportunity to recover when things begin to go awry. A change in the common attitude that hospitalist responsibility ends when the patient leaves the hospital is necessary.

An element of the solution lies in the creation of feedback loops to identify patients who are not obtaining follow-up as expected. This step requires a commitment of resources—something our fragmented medical system, with location-based reimbursement, does not provide incentives for.

Creation of a feedback loop may be as complex as integrated medical informatics systems, or as simple as a follow-up phone call, but it is incumbent on each hospitalist to examine the environment in which they practice and ensure this vital element of a safe and reliable system is being addressed. TH

Drs. Cumbler and Egan are assistant professors in the Section of Hospital Medicine at the University of Colorado at Denver.

References

1. Stanton D. In harms way: the sinking of the USS Indianapolis and the extraordinary story of its survivors. New York, NY: Henry Holt and Company LLC; 2001.
2. Kripalani S, LeFevre F, Phillips F, Williams M, Basaviah P, Baker D. Deficits in communication and information transfer between hospital-based and primary care physicians: implications for patient safety and continuity of care. JAMA. 2007;297(8):831-841.
3. Alpers A. Key legal principles for hospitalists. Am J Med. 1999;111(9):5-9.
4. Dudas V, Bookwalter T, Kerr KM, Pantilat SZ. The impact of follow-up telephone calls to patients after hospitalization. Am J Med. 2001;111:26S-30S.
5. Boockvar K, LaCorte H, Giambanco V, Fridman B, Siu A. Medication reconciliation for reducing drug
6. discrepancy adverse events. Am J Geriatr Pharmacother. 2006;4:236-243.
7. Epstein K, Juarez E, Loya K, Gorman MJ, Singer A. Frequency of new or worsening symptoms in the posthospitalization period. JHM. 2007;2:58-68.
8. Mistiaen P, Poot E. Telephone follow-up, initiated by a hospital-based health professional, for postdischarge problems in patients discharged from hospital to home. Cochrane Database of Systemic Reviews 2006; 4. Article No.:CD004510. DOI:10.1002/14651858.CD004510.pub3.

On the evening of July 30, 1945, a U.S. battleship traveling from Guam to the Philippines was spotted in the Philippine Sea by a Japanese submarine crew. Six torpedoes sped across the black water with devastating effect.

Three hundred sailors died immediately as the stricken ship sank. Another 900 men were left floating in an oil slick in the shark-infested Pacific Ocean for four days.1

The events that led to the sinking represent a classic tale of systems failures. They ring familiar to any physician who has closely examined modern medical error.

The communication breakdown that prevented the ship’s captain from being aware of submarine activity on the same route four days before is no different than communication breakdowns in complex hospital systems. The bureaucratic decision by a remote administrator to withhold the safety measure of an escort to prevent such an attack on the grounds that it “lacked necessity” likely resonates with physicians who have struggled with getting authorization for care.

Why did those sailors remain in the water four days before rescue? Despite being only a two-hour flight from the nearest base, they were not recovered—or even missed—for what must have seemed an endless amount of time.

In the end, slightly more than 300 men were alive when they were spotted by a plane that happened to fly past. The rest succumbed to dehydration, exposure, and sharks. The failure of the Navy to rescue the sailors offers lessons to the clinician trying to improve transitions of care more than a half a century later.

The Feedback Loop

Hospital discharge is a complex process initiated by physician orders on charts, prescription pads, and patient instructions. Most often, the things we assume will be done out of our direct view are carried out satisfactorily. However, any hospitalist can easily recount stories of tests or follow-up that didn’t happen as ordered. Patients who fall through the cracks at discharge—like the stranded sailors of the USS Indianapolis—are, in part, the story of a simple omitted step: the feedback loop.

A feedback loop occurs when the results or consequences of an action are returned as an input loop to the initiating step in order to modify subsequent actions. This fundamental engineering concept can keep complex systems on course. The feedback loop allows the lack of completion of a portion of a process to be recognized—and corrective measures taken—before additional harm occurs.

In Guam, the island base from which the USS Indianapolis departed, the marker indicating the ship on the plotting board was removed when the ship left. Later, the Philippine port of Leyte failed to note that the ship didn’t arrive. Policy at the time was that all ships that left port were presumed to have arrived at their destination unless a call indicating trouble was received. The junior officer who noticed that the ship hadn’t arrived assumed there had been an order to divert to an alternate port. The Navy had no feedback mechanism to communicate between the two ports and raise an alarm when a ship did not arrive. In fact, a Navy directive discouraged communicating the arrival of combat ships as a matter of military secrecy. As a result, no rescue mission was launched—and the sharks began to arrive.

A closer examination of usual hospitalist discharge practice reveals too much similarity for comfort. Similar to how the USS Indianapolis was removed from the plotting board on Guam, discharged patients are removed from the hospitalist’s census list. Follow-up becomes the responsibility of the patient and primary care physician.

Communication with the primary care provider is recognized as a best practice for discharge, but research suggests direct communication occurs less than 20% of the time.2 These dismal statistic suggests the “port of arrival” is unaware our patients are expected in a significant percentage of discharges. Outpatient physicians, like the junior port director in Leyte, may assume that patients who do not call or arrive for appointments have been readmitted, seen by another physician, or otherwise diverted.

Even a superficial review reveals significant deficits in the feedback provided by our current discharge practice. When patients don’t arrive at follow-up appointments, most hospitalists lack any ability to recognize this failure of their transition plan. The assumption in most hospitalist groups is that patients who leave the hospital will achieve follow-up as directed. This “presumption of success” is ill-founded and may expose the patient to potential harm—and the physician to liability.

The case of Shirk v. Kelsey offers parallels to discharge situations hospitalists commonly encounter.3 In this malpractice case, a procedure was unsuccessful in terminating a patient’s pregnancy. The performing physician left follow-up of the pathology results to the patient’s usual outpatient obstetrical provider. The patient’s lack of follow-up was not recognized by the discharging obstetrician. This provider—not the practitioner with whom follow-up was intended—was found liable.

The American Medical Asso­ciation’s code of ethics states: “Once having undertaken a case, the physician should not neglect the patient.” Hospitalists form physician-patient relationships with hospitalized patients that usually terminate on discharge. Our duty to not abandon or neglect a patient diminishes significantly after discharge, when we are no longer responsible for ongoing hospital care or exchanging information with patients on a daily basis.

But our duty does not disappear. Certainly, the responsibility falls to the hospitalist to be aware of and ensure a follow-up plan for important results such as pathology reports that return after discharge.

Allegations of improper post-discharge communication or failure to pass along critical results that become available once the patient has left the hospital, are common in medical malpractice claims.

Most are settled out of court, and many do not find the physician liable for malpractice. However, legal consequences are far less relevant than the safety and quality of care compromised when patients are failed by a system that lacks feedback loops to ensure safe transitions.

The ultimate goal of medicine is to improve the health and quality of life of our patients. Whether or not a lawsuit results, we need to recognize the commonality of patients who have their care compromised, delayed, or mismanaged because of our inability to recognize a foundering transition plan. Instead of looking at this as a failure of individual physicians to communicate, the problem needs to be addressed by creating effective, reliable systems.

Solutions

Providers discharging patients with follow-up needs should have a mechanism to identify those at highest risk for problems with transition. For these patients, follow-up with a post-discharge telephone call may be an effective feedback step.

One study looking at post-discharge phone contact found that 20% of patients had not filled new discharge prescriptions. Another post-discharge study revealed that a quarter of patients had medication questions that required clarification.4,5 Other research indicates more than one in 10 patients had new or worsening symptoms in the first five days after leaving the hospital.6 Despite these symptoms, 39% of these patients did not have a follow-up appointment established.

An integrated informatics system that prompts hospitalists and primary care physicians when patients do not arrive at expected follow-up or when test results return after discharge would be optimal. But a simple phone call to identify problems can be effective. Some hospitalist groups have incorporated routine post-discharge telephone contact into their practice—but most have not. Research identifying which patients would benefit is needed to allow targeted use of resources.7

While it’s understood that not all patient discharges will go smoothly, just as not all battleships will arrive at port without incident, there is frequently an opportunity to recover when things begin to go awry. A change in the common attitude that hospitalist responsibility ends when the patient leaves the hospital is necessary.

An element of the solution lies in the creation of feedback loops to identify patients who are not obtaining follow-up as expected. This step requires a commitment of resources—something our fragmented medical system, with location-based reimbursement, does not provide incentives for.

Creation of a feedback loop may be as complex as integrated medical informatics systems, or as simple as a follow-up phone call, but it is incumbent on each hospitalist to examine the environment in which they practice and ensure this vital element of a safe and reliable system is being addressed. TH

Drs. Cumbler and Egan are assistant professors in the Section of Hospital Medicine at the University of Colorado at Denver.

References

1. Stanton D. In harms way: the sinking of the USS Indianapolis and the extraordinary story of its survivors. New York, NY: Henry Holt and Company LLC; 2001.
2. Kripalani S, LeFevre F, Phillips F, Williams M, Basaviah P, Baker D. Deficits in communication and information transfer between hospital-based and primary care physicians: implications for patient safety and continuity of care. JAMA. 2007;297(8):831-841.
3. Alpers A. Key legal principles for hospitalists. Am J Med. 1999;111(9):5-9.
4. Dudas V, Bookwalter T, Kerr KM, Pantilat SZ. The impact of follow-up telephone calls to patients after hospitalization. Am J Med. 2001;111:26S-30S.
5. Boockvar K, LaCorte H, Giambanco V, Fridman B, Siu A. Medication reconciliation for reducing drug
6. discrepancy adverse events. Am J Geriatr Pharmacother. 2006;4:236-243.
7. Epstein K, Juarez E, Loya K, Gorman MJ, Singer A. Frequency of new or worsening symptoms in the posthospitalization period. JHM. 2007;2:58-68.
8. Mistiaen P, Poot E. Telephone follow-up, initiated by a hospital-based health professional, for postdischarge problems in patients discharged from hospital to home. Cochrane Database of Systemic Reviews 2006; 4. Article No.:CD004510. DOI:10.1002/14651858.CD004510.pub3.

It was just before 7:30 p.m. Feb. 7 when a huge explosion in the small Georgia town of Port Wentworth shook the community to its core.

It proved to be a night no one would soon forget. It also tested the young hospitalist program at Memorial University Medical Center (MUMC) in Savannah, a few miles from Port Wentworth.

At least 12 people were killed and more than 40 seriously or critically injured in the blast at the Imperial Sugar Refinery, better known to locals as the Dixie Crystal Sugar Refinery, a Savannah-area landmark for more than 100 years.

The Place to Go

MUMC is an academic medical center with a Level 1 trauma center that serves a 35-county area in southeast Georgia and southern South Carolina. It is often said that if a patient is in a serious accident, MUMC is the place to go.

We started a hospitalist program at MUMC in September 2006, with three hospitalists and an average census of four patients. We now have seven hospitalists, expanding to 10 in July, and an average census of 65. Though still a fledgling department, we grew a lot the night of Feb. 7 and played a significant role in helping disaster victims. Immediate response, flexibility, and focus were paramount in defining our reaction to the crisis. Here’s how events unfolded that difficult night:

7:30 p.m.

We got the call and mobilized all five hospitalists in the emergency department (ED) 20 minutes later. It was organized chaos as trauma surgeons and ED physicians attended to the rapidly increasing number of victims arriving by ambulance and helicopter. Before the blast, the ED waiting room was packed with about 45 patients who needed attention.

8:15 p.m.

Many victims suffered serious burns from the explosion. Burn specialists from the Joseph M. Still Burn Center in Augusta arrived by helicopter. Space in the ED became desperately crowded with the seemingly endless number of victims, so we were all busily tending to the existing ED patients in every capacity possible to try and get them out of the ED. We sutured wounds, started and removed IVs, treated pregnant patients, triaged every medical patient, transported patients, and did whatever else was required. In about 90 minutes we had essentially cleared the entire ED. At this point, some of the trauma victims were moved upstairs to the intensive care unit (ICU).

9 p.m.

Victims were still arriving with burns over 40% to 80% of their bodies. After we’d cleared the ED as much as possible to make room for new patients, we focused on the immediate need for medical-surgical beds. MUMC was almost at capacity before the explosion, and suddenly a large number of patients were being emergently triaged out of the ICUs to make way for the burn victims.

The teamwork throughout the hospital was amazing to watch. From the ED to the medical floor, everyone worked together with precision as if this happened every day. Several patients were held in the ICU awaiting helicopter fight to the Augusta Burn Center; extra staff were assigned to those patients. Patient-care technicians began taking water and blankets to family members who had arrived at the hospital.

Our team began leading a massive effort to discharge and transfer noncritical patients from the medical floors. We called our coordinator Deborah Haywood, RN, BSN, who was at central command and told her we could use some of the nurses and case managers who were showing up to offer help. We took our census and identified patients who could possibly be discharged. We turned on televisions in patients’ rooms to show and explain to patients what was happening with the explosion. With the aid of arriving nurses we arranged discharge, follow-up, and transportation for every patient who could leave.

9:45 p.m.

Victims stopped arriving at the hospital. As the first of our patients from the floors began to leave, the internal medicine and family medicine residents came to offer help. We quickly went through the census and helped them figure out which patients could be discharged.

Amazingly, our coordinator located and directed case managers, psychiatric nurse managers, and intake personnel to us. They paired with the residents to help them transfer and discharge patients. We were fortunate that some of the smaller community hospitals opened their doors and accepted some of the less-critical patients in transfer.

10:30 p.m.

Several burn victims received emergent escharotomies. Helicopters transported the most severely burned to the Augusta burn center. Patients transferred from the ICU and holding areas around the ED began to occupy the medical-surgical beds we had created.

Clearly we needed more beds. We went back, reviewed the census on each floor, and found more patients willing and able to leave. Within two hours we discharged 22 patients. Our coordinator took their names, and patient relations called to ensure proper follow-up and thanks to the patients for helping in a time of crisis.

12:45 a.m.

When we finally got together and looked at the clock it was 12:45 a.m. The ED was clear and beds were available. Staff started to go home. Many of us had been working with minimal break time since 7 a.m.

We either went home or found a call room to rest in because we all knew the next day would be a long one. It had been a swift and busy night, but the true journey for the victims and our community had really just begun.

It was with tremendous sadness that we watched this event unfold on local and national news. None of us knew the extent of the damage done at the plant, and it was difficult to comprehend and empathize with what the victims had just suffered. Several victims were in such pain and emotional shock that it took them several days to describe to us what had happened.

It was also with a heightened sense of purpose that we went to work after this disaster. MUMC staff should be proud of the work, coordination, and precision with which such a large number of people came together and saved lives. The trauma teams, ED, and ICU staff, and countless others from every department at MUMC along with staff from the Joseph M. Still Burn Center in Augusta demonstrated competence and coordination.

As a group, MUMC Hospitalists played an important role, helping people in their hour of need. We believed in our team and our hospital’s ability to respond to an unforeseen crisis. We had defined our role instantly and spontaneously. We took a leadership position in a much-needed, albeit not so obvious, area.

We appreciated the fact that our relatively young hospitalist program was recognized for its contribution that night. We were part of the hospital’s debriefing and have become an integral part of the institution’s official disaster team.

While we certainly hope never to have to respond to such a devastating situation again, we know we are an important part of the team—and that our dedication and commitment will allow us to rise to any occasion. TH

The authors are members of Memorial Health Hospitalists, the hospitalist program at Memorial University Medical Center in Savannah, Ga.

It was just before 7:30 p.m. Feb. 7 when a huge explosion in the small Georgia town of Port Wentworth shook the community to its core.

It proved to be a night no one would soon forget. It also tested the young hospitalist program at Memorial University Medical Center (MUMC) in Savannah, a few miles from Port Wentworth.

At least 12 people were killed and more than 40 seriously or critically injured in the blast at the Imperial Sugar Refinery, better known to locals as the Dixie Crystal Sugar Refinery, a Savannah-area landmark for more than 100 years.

The Place to Go

MUMC is an academic medical center with a Level 1 trauma center that serves a 35-county area in southeast Georgia and southern South Carolina. It is often said that if a patient is in a serious accident, MUMC is the place to go.

We started a hospitalist program at MUMC in September 2006, with three hospitalists and an average census of four patients. We now have seven hospitalists, expanding to 10 in July, and an average census of 65. Though still a fledgling department, we grew a lot the night of Feb. 7 and played a significant role in helping disaster victims. Immediate response, flexibility, and focus were paramount in defining our reaction to the crisis. Here’s how events unfolded that difficult night:

7:30 p.m.

We got the call and mobilized all five hospitalists in the emergency department (ED) 20 minutes later. It was organized chaos as trauma surgeons and ED physicians attended to the rapidly increasing number of victims arriving by ambulance and helicopter. Before the blast, the ED waiting room was packed with about 45 patients who needed attention.

8:15 p.m.

Many victims suffered serious burns from the explosion. Burn specialists from the Joseph M. Still Burn Center in Augusta arrived by helicopter. Space in the ED became desperately crowded with the seemingly endless number of victims, so we were all busily tending to the existing ED patients in every capacity possible to try and get them out of the ED. We sutured wounds, started and removed IVs, treated pregnant patients, triaged every medical patient, transported patients, and did whatever else was required. In about 90 minutes we had essentially cleared the entire ED. At this point, some of the trauma victims were moved upstairs to the intensive care unit (ICU).

9 p.m.

Victims were still arriving with burns over 40% to 80% of their bodies. After we’d cleared the ED as much as possible to make room for new patients, we focused on the immediate need for medical-surgical beds. MUMC was almost at capacity before the explosion, and suddenly a large number of patients were being emergently triaged out of the ICUs to make way for the burn victims.

The teamwork throughout the hospital was amazing to watch. From the ED to the medical floor, everyone worked together with precision as if this happened every day. Several patients were held in the ICU awaiting helicopter fight to the Augusta Burn Center; extra staff were assigned to those patients. Patient-care technicians began taking water and blankets to family members who had arrived at the hospital.

Our team began leading a massive effort to discharge and transfer noncritical patients from the medical floors. We called our coordinator Deborah Haywood, RN, BSN, who was at central command and told her we could use some of the nurses and case managers who were showing up to offer help. We took our census and identified patients who could possibly be discharged. We turned on televisions in patients’ rooms to show and explain to patients what was happening with the explosion. With the aid of arriving nurses we arranged discharge, follow-up, and transportation for every patient who could leave.

9:45 p.m.

Victims stopped arriving at the hospital. As the first of our patients from the floors began to leave, the internal medicine and family medicine residents came to offer help. We quickly went through the census and helped them figure out which patients could be discharged.

Amazingly, our coordinator located and directed case managers, psychiatric nurse managers, and intake personnel to us. They paired with the residents to help them transfer and discharge patients. We were fortunate that some of the smaller community hospitals opened their doors and accepted some of the less-critical patients in transfer.

10:30 p.m.

Several burn victims received emergent escharotomies. Helicopters transported the most severely burned to the Augusta burn center. Patients transferred from the ICU and holding areas around the ED began to occupy the medical-surgical beds we had created.

Clearly we needed more beds. We went back, reviewed the census on each floor, and found more patients willing and able to leave. Within two hours we discharged 22 patients. Our coordinator took their names, and patient relations called to ensure proper follow-up and thanks to the patients for helping in a time of crisis.

12:45 a.m.

When we finally got together and looked at the clock it was 12:45 a.m. The ED was clear and beds were available. Staff started to go home. Many of us had been working with minimal break time since 7 a.m.

We either went home or found a call room to rest in because we all knew the next day would be a long one. It had been a swift and busy night, but the true journey for the victims and our community had really just begun.

It was with tremendous sadness that we watched this event unfold on local and national news. None of us knew the extent of the damage done at the plant, and it was difficult to comprehend and empathize with what the victims had just suffered. Several victims were in such pain and emotional shock that it took them several days to describe to us what had happened.

It was also with a heightened sense of purpose that we went to work after this disaster. MUMC staff should be proud of the work, coordination, and precision with which such a large number of people came together and saved lives. The trauma teams, ED, and ICU staff, and countless others from every department at MUMC along with staff from the Joseph M. Still Burn Center in Augusta demonstrated competence and coordination.

As a group, MUMC Hospitalists played an important role, helping people in their hour of need. We believed in our team and our hospital’s ability to respond to an unforeseen crisis. We had defined our role instantly and spontaneously. We took a leadership position in a much-needed, albeit not so obvious, area.

We appreciated the fact that our relatively young hospitalist program was recognized for its contribution that night. We were part of the hospital’s debriefing and have become an integral part of the institution’s official disaster team.

While we certainly hope never to have to respond to such a devastating situation again, we know we are an important part of the team—and that our dedication and commitment will allow us to rise to any occasion. TH

The authors are members of Memorial Health Hospitalists, the hospitalist program at Memorial University Medical Center in Savannah, Ga.

It was just before 7:30 p.m. Feb. 7 when a huge explosion in the small Georgia town of Port Wentworth shook the community to its core.

It proved to be a night no one would soon forget. It also tested the young hospitalist program at Memorial University Medical Center (MUMC) in Savannah, a few miles from Port Wentworth.

At least 12 people were killed and more than 40 seriously or critically injured in the blast at the Imperial Sugar Refinery, better known to locals as the Dixie Crystal Sugar Refinery, a Savannah-area landmark for more than 100 years.

The Place to Go

MUMC is an academic medical center with a Level 1 trauma center that serves a 35-county area in southeast Georgia and southern South Carolina. It is often said that if a patient is in a serious accident, MUMC is the place to go.

We started a hospitalist program at MUMC in September 2006, with three hospitalists and an average census of four patients. We now have seven hospitalists, expanding to 10 in July, and an average census of 65. Though still a fledgling department, we grew a lot the night of Feb. 7 and played a significant role in helping disaster victims. Immediate response, flexibility, and focus were paramount in defining our reaction to the crisis. Here’s how events unfolded that difficult night:

7:30 p.m.

We got the call and mobilized all five hospitalists in the emergency department (ED) 20 minutes later. It was organized chaos as trauma surgeons and ED physicians attended to the rapidly increasing number of victims arriving by ambulance and helicopter. Before the blast, the ED waiting room was packed with about 45 patients who needed attention.

8:15 p.m.

Many victims suffered serious burns from the explosion. Burn specialists from the Joseph M. Still Burn Center in Augusta arrived by helicopter. Space in the ED became desperately crowded with the seemingly endless number of victims, so we were all busily tending to the existing ED patients in every capacity possible to try and get them out of the ED. We sutured wounds, started and removed IVs, treated pregnant patients, triaged every medical patient, transported patients, and did whatever else was required. In about 90 minutes we had essentially cleared the entire ED. At this point, some of the trauma victims were moved upstairs to the intensive care unit (ICU).

9 p.m.

Victims were still arriving with burns over 40% to 80% of their bodies. After we’d cleared the ED as much as possible to make room for new patients, we focused on the immediate need for medical-surgical beds. MUMC was almost at capacity before the explosion, and suddenly a large number of patients were being emergently triaged out of the ICUs to make way for the burn victims.

The teamwork throughout the hospital was amazing to watch. From the ED to the medical floor, everyone worked together with precision as if this happened every day. Several patients were held in the ICU awaiting helicopter fight to the Augusta Burn Center; extra staff were assigned to those patients. Patient-care technicians began taking water and blankets to family members who had arrived at the hospital.

Our team began leading a massive effort to discharge and transfer noncritical patients from the medical floors. We called our coordinator Deborah Haywood, RN, BSN, who was at central command and told her we could use some of the nurses and case managers who were showing up to offer help. We took our census and identified patients who could possibly be discharged. We turned on televisions in patients’ rooms to show and explain to patients what was happening with the explosion. With the aid of arriving nurses we arranged discharge, follow-up, and transportation for every patient who could leave.

9:45 p.m.

Victims stopped arriving at the hospital. As the first of our patients from the floors began to leave, the internal medicine and family medicine residents came to offer help. We quickly went through the census and helped them figure out which patients could be discharged.

Amazingly, our coordinator located and directed case managers, psychiatric nurse managers, and intake personnel to us. They paired with the residents to help them transfer and discharge patients. We were fortunate that some of the smaller community hospitals opened their doors and accepted some of the less-critical patients in transfer.

10:30 p.m.

Several burn victims received emergent escharotomies. Helicopters transported the most severely burned to the Augusta burn center. Patients transferred from the ICU and holding areas around the ED began to occupy the medical-surgical beds we had created.

Clearly we needed more beds. We went back, reviewed the census on each floor, and found more patients willing and able to leave. Within two hours we discharged 22 patients. Our coordinator took their names, and patient relations called to ensure proper follow-up and thanks to the patients for helping in a time of crisis.

12:45 a.m.

When we finally got together and looked at the clock it was 12:45 a.m. The ED was clear and beds were available. Staff started to go home. Many of us had been working with minimal break time since 7 a.m.

We either went home or found a call room to rest in because we all knew the next day would be a long one. It had been a swift and busy night, but the true journey for the victims and our community had really just begun.

It was with tremendous sadness that we watched this event unfold on local and national news. None of us knew the extent of the damage done at the plant, and it was difficult to comprehend and empathize with what the victims had just suffered. Several victims were in such pain and emotional shock that it took them several days to describe to us what had happened.

It was also with a heightened sense of purpose that we went to work after this disaster. MUMC staff should be proud of the work, coordination, and precision with which such a large number of people came together and saved lives. The trauma teams, ED, and ICU staff, and countless others from every department at MUMC along with staff from the Joseph M. Still Burn Center in Augusta demonstrated competence and coordination.

As a group, MUMC Hospitalists played an important role, helping people in their hour of need. We believed in our team and our hospital’s ability to respond to an unforeseen crisis. We had defined our role instantly and spontaneously. We took a leadership position in a much-needed, albeit not so obvious, area.

We appreciated the fact that our relatively young hospitalist program was recognized for its contribution that night. We were part of the hospital’s debriefing and have become an integral part of the institution’s official disaster team.

While we certainly hope never to have to respond to such a devastating situation again, we know we are an important part of the team—and that our dedication and commitment will allow us to rise to any occasion. TH

The authors are members of Memorial Health Hospitalists, the hospitalist program at Memorial University Medical Center in Savannah, Ga.

Case

A 69-year-old female with metastatic ovarian cancer and chronic pain syndrome presented to the hospital with seven days of progressively worsening abdominal pain. The pain had been similar to her chronic cancer pain but more severe. She has acute renal failure secondary to volume depletion from poor intake. A CT scan of the abdomen and pelvis reveal progression of her cancer with acute pathology. What is the best method of treating this patient’s pain?

Overview

Pain is pandemic. It is the most common reason patients seek healthcare.1 Almost one-third of Americans will experience severe chronic pain at some point in their lives. Every year, approximately 25 million Americans experience acute pain and 50 million experience chronic pain. Only one in four patients with pain receives appropriate therapy and control of their pain.

Pain is the most common symptom experienced by hospitalized adults.2 Acute or chronic pain can be particularly challenging to treat because these patients are frequently opioid dependent and have many psychosocial factors. No one method of pain control is superior to another. However, one method to gain rapid control of an acute pain crisis in a patient with chronic pain is to use patient-controlled analgesia (PCA).

Review of the Data

The first commercially available PCA pumps became available in 1976.3 They were created after studies in the 1960s demonstrated that small doses of opioids given intravenously provided more effective pain relief than conventional intramuscular injections.

The majority of studies on PCAs are in the postoperative patient, with cancer pain being next most commonly studied. PCAs utilize microprocessor-controlled infusion pumps that deliver a preprogrammed dose of opioid when the patient pushes the demand button. They allow programming of dose (demand dose), time between doses (lockout interval), background infusion rate (basal rate), and nurse-initiated dose (bolus dose).

The PCA paradigm is based on the opioid pharmacologic concept of minimum effective analgesic concentration (MEAC).4,5 The MEAC is the smallest serum opioid concentration at which pain is relieved. The dose-response curve to opioids is sigmoidal such that minimal analgesia is achieved until the MEAC is reached, after which minute increases in opioid concentrations produce analgesia, until further increases produce no significant increased analgesic effect.

PCAs allow individualized dosing and titration to achieve the MEAC, with small incremental doses administered whenever the serum concentration falls below the MEAC. A major goal of PCA technology is to regulate drug delivery to rapidly achieve and maintain the MEAC.

Advantages of PCAs

• More individual dosing and titration of pain medications to account for inter-individual and intra-individual variability in the response to opioids;
• Negative feedback control system, an added safety measure to avoid respiratory depression. As patients become too sedated from opioids, they are no longer able to push the button to receive further opioids;
• Higher patient satisfaction with pain control, a major determinant being personal control over the delivery of pain relief;6-8 and
• Greater analgesic efficacy vs. conventional analgesia.

Disadvantages of PCAs

Select patient populations: Not all patients are able to understand and retain the required instructions necessary to safely or effectively use self-administered opioids (e.g., cognitively impaired patients).

Potential for opioid dosing errors: These are related to equipment factors, medical personnel prescribing or programming errors.

Increased cost: PCAs have been shown to be more expensive in comparison with intramuscular (IM) injections, the prior standard of care.9-10

PCA Prescribing

The parameters programmed into the PCA machine include the basal rate, demand (or incremental) dose, lockout interval, nurse-initiated bolus dose, and choice of opioid.

Basal rate: The continuous infusion of opioid set at an hourly rate. Most studies that compare PCA use with and without basal rates (in postoperative patients) do not show improved pain relief or sleep with basal rates.11 Basal rates have been associated with increased risk of sedation and respiratory depression.12

The routine use of basal rates is not recommended initially, unless a patient is opioid-tolerant (i.e., on chronic opioid therapy). For patients on chronic opioids, their 24-hour total opioid requirement is converted by equianalgesic dosing to the basal rate. Steady state is not achieved for eight to 12 hours of continuous infusion; therefore, it is not recommended to change the basal rate more frequently than every eight hours.13

Demand dose: The dose patients provide themselves by pushing the button. Studies on opioid-naïve patients using morphine PCAs have shown that 1 mg IV morphine was the optimal starting dose, based on good pain relief without respiratory depression. Lower doses, such as 0.5 mg IV morphine, are generally used in the elderly as opioid requirements are known to decrease with patient age.14

For patients with a basal rate, the demand dose is often set at 50% to 100% of the basal rate. The demand dose is the parameter that should be titrated up for acute pain control. World Health Organization guidelines recommend increasing the dose by 25% to 50% for mild to moderate pain, and 50% to 100% for moderate to severe pain.15

Lockout interval: Minimal allowable time between demand doses. This time is based on the time to peak effect of IV opioids and can vary from five to 15 minutes. The effects of varying lockout intervals—seven to 11 minutes for morphine and five to eight minutes for fentanyl—had no effect on pain levels or side effects.16 Ten minutes is a standard lockout interval.

Bolus dose: The nurse-initiated dose that may be given initially to achieve pain control and later to counteract incidental pain (e.g., that caused by physical therapy, dressing changes, or radiology tests). A recommended dose is equivalent to the basal rate or twice the demand dose.

Choice of opioid: Morphine is the standard opioid because of its familiarity, cost, and years of study. Although inter-individual variability exists, there are no major differences in side effects among the different opioids. Renal and hepatic insufficiency can increase the effects of opioids. Morphine is especially troublesome in renal failure because it has an active metabolite—morphine-6-glucuronide—that can accumulate and increase the risk of sedation and respiratory depression.

click for large version

Other Concerns

PCA complications: The most well-studied adverse effects of PCAs are nausea and respiratory depression. There is no difference between PCAs and conventional analgesia in rates of nausea or respiratory depression.17

Nausea is the most common side effect in postoperative patients on PCAs. Patients rapidly develop tolerance to nausea over a period of days. However, many clinicians are concerned about respiratory depression and the risk of death. The overall incidence of respiratory depression with PCAs is less than 1% (range from 0.1 to 0.8%), similar to conventional analgesia. However, the incidence is significantly higher when basal rates are used, rising to 1.1 to 3.9%. Other factors predisposing a patient to increased risk of respiratory depression are older age, obstructive sleep apnea, hypovolemia, renal failure, and the concurrent use of other sedating medications.18

Medication errors are also common. The overall incidence of medication mishaps with PCAs is 1.2%.19 More than 50% of these occur because of operator-related errors (e.g., improper loading, programming errors, and documentation errors). Equipment malfunction is the next most common error.

Opioid equianalgesic dosing conversions: The equianalgesic dose ratio is the ratio of the dose of two opioids required to produce the same analgesic effect. (See Table 1, right.) For example, IV morphine is three times as potent as oral morphine, with an equianalgesic dose ratio of 1:3. Equianalgesic dose tables vary somewhat in their values, which have been largely determined by single-dose administration studies.20 The generalizability of these tables to chronic opioid administration is not well studied.

Incomplete cross tolerance: When switching from one opioid to another, lower doses can be used to control pain.21, 22 Tolerance to one opioid does not completely transfer to the new opioid. Starting at half to two-thirds of the new opioid dose is generally recommended to avoid opioid-specific tolerance and inter-individual variability.23,24

Back to the Case

Opioids are the mainstay of pharmacological management of moderate-to-severe cancer pain. Evaluation of the patient reveals that her acute increase in pain is likely due to progression of her cancer. She had been taking morphine (sustained-release, 90 mg oral) twice daily for her pain and had been using approximately five doses per day of immediate-release oral morphine 20 mg for breakthrough pain. This is equivalent to a total 24-hour opioid requirement of 280 mg oral morphine.

She should be started on a PCA for rapid pain control and titration. Hydromorphone (Dilaudid) is a better PCA choice than morphine because she has acute renal failure. The equianalgesic dose ratio of oral morphine to IV hydromorphone is approximately 30:1.5. The total 24-hour opioid dose of 280 mg oral morphine is equivalent to 14 mg IV hydromorphone ([280mg morphine per day ÷ 30] x 1.5 = 14).

After adjusting for 60% incomplete cross tolerance, the total 24-hour opioid dose is reduced to 8.4 mg IV hydromorphone (14 mg x 0.6 = 8.4 mg). This is approximately equivalent to 0.4 mg IV hydromorphone/hour (8.4 mg ÷ 24 hours), which is her initial basal rate. The demand dose should be set at 0.2 mg (50% the basal rate) with a lockout interval of 10 minutes.

Over a period of several days, the patient’s pain was controlled and her opioid requirements stabilized. She was on a basal rate of 1.4 mg/hour and a demand dose of 1 mg with a 10-minute lockout. Her total 24-hour opioid requirement was 44 mg of IV hydromorphone. As her renal function improved but did not completely normalize, oxycodone was chosen over morphine when converting her back to oral pain medications (less active renal metabolites). The equianalgesic dose ratio of oral oxycodone to IV hydromorphone is approximately 20:1.5. Her total 24-hour opioid dose of 44 mg IV hydromorphone is equivalent to 587 mg oral oxycodone (44 ÷ 1.5) x 20. After adjusting for 60% incomplete cross tolerance, the total 24-hour opioid dose is reduced to 352 mg oral oxycodone or 180 mg of sustained-release oxycodone twice daily (352 mg ÷ 2 ≈ 180 mg). For breakthrough pain she should receive 40 mg of immediate-release oxycodone every hour as needed (10% to 15% of the 24-hour opioid requirement). TH

Dr. Youngwerth is a hospitalist and instructor of medicine, University of Colorado at Denver, assistant director, Palliative Care Consult Service, associate director, Colorado Palliative Medicine Fellowship Program, and medical director, Hospice of Saint John.

References

1. American Pain Society. Pain: Current understanding of assessment, management, and treatments. National Pharmaceutical Council 2006;1-79.
2. Morrison RS, Meier DE, Fischberg D, et al. Improving the management of pain in hospitalized adults. Arch Intern Med. 2006;166:1033-1039.
3. Grass JA. Patient-controlled analgesia. Anesth Analg. 2005;101:S44-S61.
4. Etches RC. Patient-controlled analgesia. Surg Clinics N Amer. 1999;79:297-312.
5. Nolan MF and Wilson M-C B. Patient-controlled analgesia: A method for the controlled self-administration of opioid pain medications. Phys Ther. 1995;75:374-379.
6. Ballantyne JC, Carr DB, Chalmers TC, Dear KBG, Angelillo IF, Mosteller F. Postoperative patient-controlled analgesia: Meta-analyses of initial randomized control trials. J Clin Anesth. 1993;5:182-193.
7. Hudcova J, McNicol E, Quah C, Lau J, Carr DB. Patient controlled opioid analgesia versus conventional opioid analgesia for postoperative pain. Cochrane Database of Systematic Reviews. 2006;4:1-10.
8. Sidebotham D, Dijkhuizen MRJ, Schug SA. The safety and utilization of patient-controlled analgesia. J Pain Symptom Manage. 1997;14:202-209.
9. Macintyre PE. Safety and efficacy of patient-controlled analgesia. Br J Anaesth. 2001;87:36-46.
10. Manon C, Rittenhouse BE, Perreault S, et al. Efficacy and costs of patient-controlled analgesia versus regularly administered intramuscular opioid therapy. Amer Soc Anesth Inc. 1998;89:1377-1388.
11. Krenn H, Oczenski W, Jellinek H, Krumpl-Ströher M, Schweitzer E, Fitzgerald RD. Nalbuphine by PCA-pump for analgesia following hysterectomy: Bolus application versus continuous infusion with bolus application. Eur J Pain. 2001;5:219-226.
12. Lehmann KA. Recent developments in patient-controlled analgesia. J Pain Symptom Manage. 2005;29:S72-S89.
13. American Pain Society. Principles of analgesic use in the treatment of acute pain and cancer pain. 5th ed. 2003:1-73.
14. Macintyre PC, Jarvis DA. Age is the best predictor of postoperative morphine requirements. Pain. 1995;64:357-364.
15. National Comprehensive Cancer Network. Clinical practice guidelines in oncology: Adult cancer pain. Version 2.2005:1-30.
16. Ginsberg B, Gil KM, Muir M, Sullivan F, Williams DA, Glass PSA. The influence of lockout intervals and drug selection on patient-controlled analgesia following gynecological surgery. Pain. 1995;62:95-100.
17. Walder B, Schafer M, Henzi I, Tramer MR. Efficacy and safety of patient-controlled opioid analgesia for acute postoperative pain. Acta Anaesthesiol Scand. 2001;45:795-804.
18. Etches RC. Respiratory depression associated with patient-controlled analgesia: a review of eight cases. Can J Anaesth. 1994;41:125-132.
19. Oswalt KE, Shrewsbury P, Stanton-Hicks M. The incidence of medication mishaps in 3,299 PCA patients. Pain. 1990;S5;S152.
20. Pereira J, Lawlor P, Vigano A, Dorgan M, Bruera E. Equianalgesic dose rations for opioids: A critical review and proposals for long-term dosing. J Pain Symptom Manage. 2001;22:672-687.
21. Ballantyne JC, Mao J. Opioid therapy for chronic pain. N Engl J Med. 2003;349:1943-1953.
22. Mercandante S. Opioid rotation for cancer pain. Cancer. 1999;86:1856-1866.
23. Mehta V, Langford RM. Acute pain management for opioid dependent patients. Anaesthesia. 2006;61:269-276.
24. Pasternak GW. Incomplete cross tolerance and multiple mu opioid peptide receptors. Trends Pharm Sciences. 2001;22:67-70.

Case

A 69-year-old female with metastatic ovarian cancer and chronic pain syndrome presented to the hospital with seven days of progressively worsening abdominal pain. The pain had been similar to her chronic cancer pain but more severe. She has acute renal failure secondary to volume depletion from poor intake. A CT scan of the abdomen and pelvis reveal progression of her cancer with acute pathology. What is the best method of treating this patient’s pain?

Overview

Pain is pandemic. It is the most common reason patients seek healthcare.1 Almost one-third of Americans will experience severe chronic pain at some point in their lives. Every year, approximately 25 million Americans experience acute pain and 50 million experience chronic pain. Only one in four patients with pain receives appropriate therapy and control of their pain.

Pain is the most common symptom experienced by hospitalized adults.2 Acute or chronic pain can be particularly challenging to treat because these patients are frequently opioid dependent and have many psychosocial factors. No one method of pain control is superior to another. However, one method to gain rapid control of an acute pain crisis in a patient with chronic pain is to use patient-controlled analgesia (PCA).

Review of the Data

The first commercially available PCA pumps became available in 1976.3 They were created after studies in the 1960s demonstrated that small doses of opioids given intravenously provided more effective pain relief than conventional intramuscular injections.

The majority of studies on PCAs are in the postoperative patient, with cancer pain being next most commonly studied. PCAs utilize microprocessor-controlled infusion pumps that deliver a preprogrammed dose of opioid when the patient pushes the demand button. They allow programming of dose (demand dose), time between doses (lockout interval), background infusion rate (basal rate), and nurse-initiated dose (bolus dose).

The PCA paradigm is based on the opioid pharmacologic concept of minimum effective analgesic concentration (MEAC).4,5 The MEAC is the smallest serum opioid concentration at which pain is relieved. The dose-response curve to opioids is sigmoidal such that minimal analgesia is achieved until the MEAC is reached, after which minute increases in opioid concentrations produce analgesia, until further increases produce no significant increased analgesic effect.

PCAs allow individualized dosing and titration to achieve the MEAC, with small incremental doses administered whenever the serum concentration falls below the MEAC. A major goal of PCA technology is to regulate drug delivery to rapidly achieve and maintain the MEAC.

Advantages of PCAs

• More individual dosing and titration of pain medications to account for inter-individual and intra-individual variability in the response to opioids;
• Negative feedback control system, an added safety measure to avoid respiratory depression. As patients become too sedated from opioids, they are no longer able to push the button to receive further opioids;
• Higher patient satisfaction with pain control, a major determinant being personal control over the delivery of pain relief;6-8 and
• Greater analgesic efficacy vs. conventional analgesia.

Disadvantages of PCAs

Select patient populations: Not all patients are able to understand and retain the required instructions necessary to safely or effectively use self-administered opioids (e.g., cognitively impaired patients).

Potential for opioid dosing errors: These are related to equipment factors, medical personnel prescribing or programming errors.

Increased cost: PCAs have been shown to be more expensive in comparison with intramuscular (IM) injections, the prior standard of care.9-10

PCA Prescribing

The parameters programmed into the PCA machine include the basal rate, demand (or incremental) dose, lockout interval, nurse-initiated bolus dose, and choice of opioid.

Basal rate: The continuous infusion of opioid set at an hourly rate. Most studies that compare PCA use with and without basal rates (in postoperative patients) do not show improved pain relief or sleep with basal rates.11 Basal rates have been associated with increased risk of sedation and respiratory depression.12

The routine use of basal rates is not recommended initially, unless a patient is opioid-tolerant (i.e., on chronic opioid therapy). For patients on chronic opioids, their 24-hour total opioid requirement is converted by equianalgesic dosing to the basal rate. Steady state is not achieved for eight to 12 hours of continuous infusion; therefore, it is not recommended to change the basal rate more frequently than every eight hours.13

Demand dose: The dose patients provide themselves by pushing the button. Studies on opioid-naïve patients using morphine PCAs have shown that 1 mg IV morphine was the optimal starting dose, based on good pain relief without respiratory depression. Lower doses, such as 0.5 mg IV morphine, are generally used in the elderly as opioid requirements are known to decrease with patient age.14

For patients with a basal rate, the demand dose is often set at 50% to 100% of the basal rate. The demand dose is the parameter that should be titrated up for acute pain control. World Health Organization guidelines recommend increasing the dose by 25% to 50% for mild to moderate pain, and 50% to 100% for moderate to severe pain.15

Lockout interval: Minimal allowable time between demand doses. This time is based on the time to peak effect of IV opioids and can vary from five to 15 minutes. The effects of varying lockout intervals—seven to 11 minutes for morphine and five to eight minutes for fentanyl—had no effect on pain levels or side effects.16 Ten minutes is a standard lockout interval.

Bolus dose: The nurse-initiated dose that may be given initially to achieve pain control and later to counteract incidental pain (e.g., that caused by physical therapy, dressing changes, or radiology tests). A recommended dose is equivalent to the basal rate or twice the demand dose.

Choice of opioid: Morphine is the standard opioid because of its familiarity, cost, and years of study. Although inter-individual variability exists, there are no major differences in side effects among the different opioids. Renal and hepatic insufficiency can increase the effects of opioids. Morphine is especially troublesome in renal failure because it has an active metabolite—morphine-6-glucuronide—that can accumulate and increase the risk of sedation and respiratory depression.

click for large version

Other Concerns

PCA complications: The most well-studied adverse effects of PCAs are nausea and respiratory depression. There is no difference between PCAs and conventional analgesia in rates of nausea or respiratory depression.17

Nausea is the most common side effect in postoperative patients on PCAs. Patients rapidly develop tolerance to nausea over a period of days. However, many clinicians are concerned about respiratory depression and the risk of death. The overall incidence of respiratory depression with PCAs is less than 1% (range from 0.1 to 0.8%), similar to conventional analgesia. However, the incidence is significantly higher when basal rates are used, rising to 1.1 to 3.9%. Other factors predisposing a patient to increased risk of respiratory depression are older age, obstructive sleep apnea, hypovolemia, renal failure, and the concurrent use of other sedating medications.18

Medication errors are also common. The overall incidence of medication mishaps with PCAs is 1.2%.19 More than 50% of these occur because of operator-related errors (e.g., improper loading, programming errors, and documentation errors). Equipment malfunction is the next most common error.

Opioid equianalgesic dosing conversions: The equianalgesic dose ratio is the ratio of the dose of two opioids required to produce the same analgesic effect. (See Table 1, right.) For example, IV morphine is three times as potent as oral morphine, with an equianalgesic dose ratio of 1:3. Equianalgesic dose tables vary somewhat in their values, which have been largely determined by single-dose administration studies.20 The generalizability of these tables to chronic opioid administration is not well studied.

Incomplete cross tolerance: When switching from one opioid to another, lower doses can be used to control pain.21, 22 Tolerance to one opioid does not completely transfer to the new opioid. Starting at half to two-thirds of the new opioid dose is generally recommended to avoid opioid-specific tolerance and inter-individual variability.23,24

Back to the Case

Opioids are the mainstay of pharmacological management of moderate-to-severe cancer pain. Evaluation of the patient reveals that her acute increase in pain is likely due to progression of her cancer. She had been taking morphine (sustained-release, 90 mg oral) twice daily for her pain and had been using approximately five doses per day of immediate-release oral morphine 20 mg for breakthrough pain. This is equivalent to a total 24-hour opioid requirement of 280 mg oral morphine.

She should be started on a PCA for rapid pain control and titration. Hydromorphone (Dilaudid) is a better PCA choice than morphine because she has acute renal failure. The equianalgesic dose ratio of oral morphine to IV hydromorphone is approximately 30:1.5. The total 24-hour opioid dose of 280 mg oral morphine is equivalent to 14 mg IV hydromorphone ([280mg morphine per day ÷ 30] x 1.5 = 14).

After adjusting for 60% incomplete cross tolerance, the total 24-hour opioid dose is reduced to 8.4 mg IV hydromorphone (14 mg x 0.6 = 8.4 mg). This is approximately equivalent to 0.4 mg IV hydromorphone/hour (8.4 mg ÷ 24 hours), which is her initial basal rate. The demand dose should be set at 0.2 mg (50% the basal rate) with a lockout interval of 10 minutes.

Over a period of several days, the patient’s pain was controlled and her opioid requirements stabilized. She was on a basal rate of 1.4 mg/hour and a demand dose of 1 mg with a 10-minute lockout. Her total 24-hour opioid requirement was 44 mg of IV hydromorphone. As her renal function improved but did not completely normalize, oxycodone was chosen over morphine when converting her back to oral pain medications (less active renal metabolites). The equianalgesic dose ratio of oral oxycodone to IV hydromorphone is approximately 20:1.5. Her total 24-hour opioid dose of 44 mg IV hydromorphone is equivalent to 587 mg oral oxycodone (44 ÷ 1.5) x 20. After adjusting for 60% incomplete cross tolerance, the total 24-hour opioid dose is reduced to 352 mg oral oxycodone or 180 mg of sustained-release oxycodone twice daily (352 mg ÷ 2 ≈ 180 mg). For breakthrough pain she should receive 40 mg of immediate-release oxycodone every hour as needed (10% to 15% of the 24-hour opioid requirement). TH

Dr. Youngwerth is a hospitalist and instructor of medicine, University of Colorado at Denver, assistant director, Palliative Care Consult Service, associate director, Colorado Palliative Medicine Fellowship Program, and medical director, Hospice of Saint John.

References

1. American Pain Society. Pain: Current understanding of assessment, management, and treatments. National Pharmaceutical Council 2006;1-79.
2. Morrison RS, Meier DE, Fischberg D, et al. Improving the management of pain in hospitalized adults. Arch Intern Med. 2006;166:1033-1039.
3. Grass JA. Patient-controlled analgesia. Anesth Analg. 2005;101:S44-S61.
4. Etches RC. Patient-controlled analgesia. Surg Clinics N Amer. 1999;79:297-312.
5. Nolan MF and Wilson M-C B. Patient-controlled analgesia: A method for the controlled self-administration of opioid pain medications. Phys Ther. 1995;75:374-379.
6. Ballantyne JC, Carr DB, Chalmers TC, Dear KBG, Angelillo IF, Mosteller F. Postoperative patient-controlled analgesia: Meta-analyses of initial randomized control trials. J Clin Anesth. 1993;5:182-193.
7. Hudcova J, McNicol E, Quah C, Lau J, Carr DB. Patient controlled opioid analgesia versus conventional opioid analgesia for postoperative pain. Cochrane Database of Systematic Reviews. 2006;4:1-10.
8. Sidebotham D, Dijkhuizen MRJ, Schug SA. The safety and utilization of patient-controlled analgesia. J Pain Symptom Manage. 1997;14:202-209.
9. Macintyre PE. Safety and efficacy of patient-controlled analgesia. Br J Anaesth. 2001;87:36-46.
10. Manon C, Rittenhouse BE, Perreault S, et al. Efficacy and costs of patient-controlled analgesia versus regularly administered intramuscular opioid therapy. Amer Soc Anesth Inc. 1998;89:1377-1388.
11. Krenn H, Oczenski W, Jellinek H, Krumpl-Ströher M, Schweitzer E, Fitzgerald RD. Nalbuphine by PCA-pump for analgesia following hysterectomy: Bolus application versus continuous infusion with bolus application. Eur J Pain. 2001;5:219-226.
12. Lehmann KA. Recent developments in patient-controlled analgesia. J Pain Symptom Manage. 2005;29:S72-S89.
13. American Pain Society. Principles of analgesic use in the treatment of acute pain and cancer pain. 5th ed. 2003:1-73.
14. Macintyre PC, Jarvis DA. Age is the best predictor of postoperative morphine requirements. Pain. 1995;64:357-364.
15. National Comprehensive Cancer Network. Clinical practice guidelines in oncology: Adult cancer pain. Version 2.2005:1-30.
16. Ginsberg B, Gil KM, Muir M, Sullivan F, Williams DA, Glass PSA. The influence of lockout intervals and drug selection on patient-controlled analgesia following gynecological surgery. Pain. 1995;62:95-100.
17. Walder B, Schafer M, Henzi I, Tramer MR. Efficacy and safety of patient-controlled opioid analgesia for acute postoperative pain. Acta Anaesthesiol Scand. 2001;45:795-804.
18. Etches RC. Respiratory depression associated with patient-controlled analgesia: a review of eight cases. Can J Anaesth. 1994;41:125-132.
19. Oswalt KE, Shrewsbury P, Stanton-Hicks M. The incidence of medication mishaps in 3,299 PCA patients. Pain. 1990;S5;S152.
20. Pereira J, Lawlor P, Vigano A, Dorgan M, Bruera E. Equianalgesic dose rations for opioids: A critical review and proposals for long-term dosing. J Pain Symptom Manage. 2001;22:672-687.
21. Ballantyne JC, Mao J. Opioid therapy for chronic pain. N Engl J Med. 2003;349:1943-1953.
22. Mercandante S. Opioid rotation for cancer pain. Cancer. 1999;86:1856-1866.
23. Mehta V, Langford RM. Acute pain management for opioid dependent patients. Anaesthesia. 2006;61:269-276.
24. Pasternak GW. Incomplete cross tolerance and multiple mu opioid peptide receptors. Trends Pharm Sciences. 2001;22:67-70.

Case

A 69-year-old female with metastatic ovarian cancer and chronic pain syndrome presented to the hospital with seven days of progressively worsening abdominal pain. The pain had been similar to her chronic cancer pain but more severe. She has acute renal failure secondary to volume depletion from poor intake. A CT scan of the abdomen and pelvis reveal progression of her cancer with acute pathology. What is the best method of treating this patient’s pain?

Overview

Pain is pandemic. It is the most common reason patients seek healthcare.1 Almost one-third of Americans will experience severe chronic pain at some point in their lives. Every year, approximately 25 million Americans experience acute pain and 50 million experience chronic pain. Only one in four patients with pain receives appropriate therapy and control of their pain.

Pain is the most common symptom experienced by hospitalized adults.2 Acute or chronic pain can be particularly challenging to treat because these patients are frequently opioid dependent and have many psychosocial factors. No one method of pain control is superior to another. However, one method to gain rapid control of an acute pain crisis in a patient with chronic pain is to use patient-controlled analgesia (PCA).

Review of the Data

The first commercially available PCA pumps became available in 1976.3 They were created after studies in the 1960s demonstrated that small doses of opioids given intravenously provided more effective pain relief than conventional intramuscular injections.

The majority of studies on PCAs are in the postoperative patient, with cancer pain being next most commonly studied. PCAs utilize microprocessor-controlled infusion pumps that deliver a preprogrammed dose of opioid when the patient pushes the demand button. They allow programming of dose (demand dose), time between doses (lockout interval), background infusion rate (basal rate), and nurse-initiated dose (bolus dose).

The PCA paradigm is based on the opioid pharmacologic concept of minimum effective analgesic concentration (MEAC).4,5 The MEAC is the smallest serum opioid concentration at which pain is relieved. The dose-response curve to opioids is sigmoidal such that minimal analgesia is achieved until the MEAC is reached, after which minute increases in opioid concentrations produce analgesia, until further increases produce no significant increased analgesic effect.

PCAs allow individualized dosing and titration to achieve the MEAC, with small incremental doses administered whenever the serum concentration falls below the MEAC. A major goal of PCA technology is to regulate drug delivery to rapidly achieve and maintain the MEAC.

Advantages of PCAs

• More individual dosing and titration of pain medications to account for inter-individual and intra-individual variability in the response to opioids;
• Negative feedback control system, an added safety measure to avoid respiratory depression. As patients become too sedated from opioids, they are no longer able to push the button to receive further opioids;
• Higher patient satisfaction with pain control, a major determinant being personal control over the delivery of pain relief;6-8 and
• Greater analgesic efficacy vs. conventional analgesia.

Disadvantages of PCAs

Select patient populations: Not all patients are able to understand and retain the required instructions necessary to safely or effectively use self-administered opioids (e.g., cognitively impaired patients).

Potential for opioid dosing errors: These are related to equipment factors, medical personnel prescribing or programming errors.

Increased cost: PCAs have been shown to be more expensive in comparison with intramuscular (IM) injections, the prior standard of care.9-10

PCA Prescribing

The parameters programmed into the PCA machine include the basal rate, demand (or incremental) dose, lockout interval, nurse-initiated bolus dose, and choice of opioid.

Basal rate: The continuous infusion of opioid set at an hourly rate. Most studies that compare PCA use with and without basal rates (in postoperative patients) do not show improved pain relief or sleep with basal rates.11 Basal rates have been associated with increased risk of sedation and respiratory depression.12

The routine use of basal rates is not recommended initially, unless a patient is opioid-tolerant (i.e., on chronic opioid therapy). For patients on chronic opioids, their 24-hour total opioid requirement is converted by equianalgesic dosing to the basal rate. Steady state is not achieved for eight to 12 hours of continuous infusion; therefore, it is not recommended to change the basal rate more frequently than every eight hours.13

Demand dose: The dose patients provide themselves by pushing the button. Studies on opioid-naïve patients using morphine PCAs have shown that 1 mg IV morphine was the optimal starting dose, based on good pain relief without respiratory depression. Lower doses, such as 0.5 mg IV morphine, are generally used in the elderly as opioid requirements are known to decrease with patient age.14

For patients with a basal rate, the demand dose is often set at 50% to 100% of the basal rate. The demand dose is the parameter that should be titrated up for acute pain control. World Health Organization guidelines recommend increasing the dose by 25% to 50% for mild to moderate pain, and 50% to 100% for moderate to severe pain.15

Lockout interval: Minimal allowable time between demand doses. This time is based on the time to peak effect of IV opioids and can vary from five to 15 minutes. The effects of varying lockout intervals—seven to 11 minutes for morphine and five to eight minutes for fentanyl—had no effect on pain levels or side effects.16 Ten minutes is a standard lockout interval.

Bolus dose: The nurse-initiated dose that may be given initially to achieve pain control and later to counteract incidental pain (e.g., that caused by physical therapy, dressing changes, or radiology tests). A recommended dose is equivalent to the basal rate or twice the demand dose.

Choice of opioid: Morphine is the standard opioid because of its familiarity, cost, and years of study. Although inter-individual variability exists, there are no major differences in side effects among the different opioids. Renal and hepatic insufficiency can increase the effects of opioids. Morphine is especially troublesome in renal failure because it has an active metabolite—morphine-6-glucuronide—that can accumulate and increase the risk of sedation and respiratory depression.

click for large version

Other Concerns

PCA complications: The most well-studied adverse effects of PCAs are nausea and respiratory depression. There is no difference between PCAs and conventional analgesia in rates of nausea or respiratory depression.17

Nausea is the most common side effect in postoperative patients on PCAs. Patients rapidly develop tolerance to nausea over a period of days. However, many clinicians are concerned about respiratory depression and the risk of death. The overall incidence of respiratory depression with PCAs is less than 1% (range from 0.1 to 0.8%), similar to conventional analgesia. However, the incidence is significantly higher when basal rates are used, rising to 1.1 to 3.9%. Other factors predisposing a patient to increased risk of respiratory depression are older age, obstructive sleep apnea, hypovolemia, renal failure, and the concurrent use of other sedating medications.18

Medication errors are also common. The overall incidence of medication mishaps with PCAs is 1.2%.19 More than 50% of these occur because of operator-related errors (e.g., improper loading, programming errors, and documentation errors). Equipment malfunction is the next most common error.

Opioid equianalgesic dosing conversions: The equianalgesic dose ratio is the ratio of the dose of two opioids required to produce the same analgesic effect. (See Table 1, right.) For example, IV morphine is three times as potent as oral morphine, with an equianalgesic dose ratio of 1:3. Equianalgesic dose tables vary somewhat in their values, which have been largely determined by single-dose administration studies.20 The generalizability of these tables to chronic opioid administration is not well studied.

Incomplete cross tolerance: When switching from one opioid to another, lower doses can be used to control pain.21, 22 Tolerance to one opioid does not completely transfer to the new opioid. Starting at half to two-thirds of the new opioid dose is generally recommended to avoid opioid-specific tolerance and inter-individual variability.23,24

Back to the Case

Opioids are the mainstay of pharmacological management of moderate-to-severe cancer pain. Evaluation of the patient reveals that her acute increase in pain is likely due to progression of her cancer. She had been taking morphine (sustained-release, 90 mg oral) twice daily for her pain and had been using approximately five doses per day of immediate-release oral morphine 20 mg for breakthrough pain. This is equivalent to a total 24-hour opioid requirement of 280 mg oral morphine.

She should be started on a PCA for rapid pain control and titration. Hydromorphone (Dilaudid) is a better PCA choice than morphine because she has acute renal failure. The equianalgesic dose ratio of oral morphine to IV hydromorphone is approximately 30:1.5. The total 24-hour opioid dose of 280 mg oral morphine is equivalent to 14 mg IV hydromorphone ([280mg morphine per day ÷ 30] x 1.5 = 14).

After adjusting for 60% incomplete cross tolerance, the total 24-hour opioid dose is reduced to 8.4 mg IV hydromorphone (14 mg x 0.6 = 8.4 mg). This is approximately equivalent to 0.4 mg IV hydromorphone/hour (8.4 mg ÷ 24 hours), which is her initial basal rate. The demand dose should be set at 0.2 mg (50% the basal rate) with a lockout interval of 10 minutes.

Over a period of several days, the patient’s pain was controlled and her opioid requirements stabilized. She was on a basal rate of 1.4 mg/hour and a demand dose of 1 mg with a 10-minute lockout. Her total 24-hour opioid requirement was 44 mg of IV hydromorphone. As her renal function improved but did not completely normalize, oxycodone was chosen over morphine when converting her back to oral pain medications (less active renal metabolites). The equianalgesic dose ratio of oral oxycodone to IV hydromorphone is approximately 20:1.5. Her total 24-hour opioid dose of 44 mg IV hydromorphone is equivalent to 587 mg oral oxycodone (44 ÷ 1.5) x 20. After adjusting for 60% incomplete cross tolerance, the total 24-hour opioid dose is reduced to 352 mg oral oxycodone or 180 mg of sustained-release oxycodone twice daily (352 mg ÷ 2 ≈ 180 mg). For breakthrough pain she should receive 40 mg of immediate-release oxycodone every hour as needed (10% to 15% of the 24-hour opioid requirement). TH

Dr. Youngwerth is a hospitalist and instructor of medicine, University of Colorado at Denver, assistant director, Palliative Care Consult Service, associate director, Colorado Palliative Medicine Fellowship Program, and medical director, Hospice of Saint John.

References

1. American Pain Society. Pain: Current understanding of assessment, management, and treatments. National Pharmaceutical Council 2006;1-79.
2. Morrison RS, Meier DE, Fischberg D, et al. Improving the management of pain in hospitalized adults. Arch Intern Med. 2006;166:1033-1039.
3. Grass JA. Patient-controlled analgesia. Anesth Analg. 2005;101:S44-S61.
4. Etches RC. Patient-controlled analgesia. Surg Clinics N Amer. 1999;79:297-312.
5. Nolan MF and Wilson M-C B. Patient-controlled analgesia: A method for the controlled self-administration of opioid pain medications. Phys Ther. 1995;75:374-379.
6. Ballantyne JC, Carr DB, Chalmers TC, Dear KBG, Angelillo IF, Mosteller F. Postoperative patient-controlled analgesia: Meta-analyses of initial randomized control trials. J Clin Anesth. 1993;5:182-193.
7. Hudcova J, McNicol E, Quah C, Lau J, Carr DB. Patient controlled opioid analgesia versus conventional opioid analgesia for postoperative pain. Cochrane Database of Systematic Reviews. 2006;4:1-10.
8. Sidebotham D, Dijkhuizen MRJ, Schug SA. The safety and utilization of patient-controlled analgesia. J Pain Symptom Manage. 1997;14:202-209.
9. Macintyre PE. Safety and efficacy of patient-controlled analgesia. Br J Anaesth. 2001;87:36-46.
10. Manon C, Rittenhouse BE, Perreault S, et al. Efficacy and costs of patient-controlled analgesia versus regularly administered intramuscular opioid therapy. Amer Soc Anesth Inc. 1998;89:1377-1388.
11. Krenn H, Oczenski W, Jellinek H, Krumpl-Ströher M, Schweitzer E, Fitzgerald RD. Nalbuphine by PCA-pump for analgesia following hysterectomy: Bolus application versus continuous infusion with bolus application. Eur J Pain. 2001;5:219-226.
12. Lehmann KA. Recent developments in patient-controlled analgesia. J Pain Symptom Manage. 2005;29:S72-S89.
13. American Pain Society. Principles of analgesic use in the treatment of acute pain and cancer pain. 5th ed. 2003:1-73.
14. Macintyre PC, Jarvis DA. Age is the best predictor of postoperative morphine requirements. Pain. 1995;64:357-364.
15. National Comprehensive Cancer Network. Clinical practice guidelines in oncology: Adult cancer pain. Version 2.2005:1-30.
16. Ginsberg B, Gil KM, Muir M, Sullivan F, Williams DA, Glass PSA. The influence of lockout intervals and drug selection on patient-controlled analgesia following gynecological surgery. Pain. 1995;62:95-100.
17. Walder B, Schafer M, Henzi I, Tramer MR. Efficacy and safety of patient-controlled opioid analgesia for acute postoperative pain. Acta Anaesthesiol Scand. 2001;45:795-804.
18. Etches RC. Respiratory depression associated with patient-controlled analgesia: a review of eight cases. Can J Anaesth. 1994;41:125-132.
19. Oswalt KE, Shrewsbury P, Stanton-Hicks M. The incidence of medication mishaps in 3,299 PCA patients. Pain. 1990;S5;S152.
20. Pereira J, Lawlor P, Vigano A, Dorgan M, Bruera E. Equianalgesic dose rations for opioids: A critical review and proposals for long-term dosing. J Pain Symptom Manage. 2001;22:672-687.
21. Ballantyne JC, Mao J. Opioid therapy for chronic pain. N Engl J Med. 2003;349:1943-1953.
22. Mercandante S. Opioid rotation for cancer pain. Cancer. 1999;86:1856-1866.
23. Mehta V, Langford RM. Acute pain management for opioid dependent patients. Anaesthesia. 2006;61:269-276.
24. Pasternak GW. Incomplete cross tolerance and multiple mu opioid peptide receptors. Trends Pharm Sciences. 2001;22:67-70.

Little information is available on how teaching outcomes involving academic hospitalists and resident physicians affect patient safety and error rates—particularly under duty-hour restrictions on residents by the Accreditation Council for Graduate Medical Education (ACGME).

But data show that when medical errors occur they are often connected with residents’ errors in judgment, lack of technical competence, inadequate supervision by senior physicians, and a breakdown in teamwork.1 In a study of 889 cases resulting in error and injury, 240 involved trainees with at least a “moderately important” role. Among the findings:

• Residents were involved in 208 of those 240 cases;
• 168 of the cases occurred in the inpatient setting;
• 80 of the cases involved obstetrics-gynecology residents, and 45 involved general surgery residents;
• Trainees “lacked technical competence or knowledge” of diagnosis in 67 cases; and
• Attending physicians were involved in 106 supervision failures.

Based on this information, how can academic hospitalists best supervise residents to reduce errors and optimize patient safety and treatment while enhancing residents’ training and satisfaction? Academic hospitalists across the United States grapple with this question daily. And a few have come up with ways that meet the needs of patients and residents.

Oversight vs. Hindsight

Reflecting on his residency, Eric Siegal, MD, a regional medical director with Cogent Healthcare in Madison, Wis., and chair of SHM’s Public Policy Committee, says he recalls times when he did not receive sufficient oversight from senior physicians. Consequently, he and his patients suffered, he says.

“We were thrown into things with little or no supervision, and we were told to sink or swim,” he says. “The good news is that we learned a ton on our own. The bad news is we hurt people in the process. So, the question is how do you walk a line of creating house staff who are autonomous and competent while protecting the patient?”

As an attending physician at the University of Wisconsin, Dr. Siegal says he gave his residents autonomy to make decisions. But there were things he did not let them do alone or without first asking. “The obvious thing was procedures,” he notes. “When residents did procedures, I was standing right there next to them. The extent to which I got involved was entirely dependent on the extent to which the resident was competent.”

Likewise, Alpesh Amin, MD, MBA, professor and chief, division of general internal medicine and executive director of the hospitalist program at the University of California, Irvine, says he gives residents oversight but doesn’t hover. “Otherwise they’re not learning from experience by only doing what someone else tells them to do,” he says. “But without oversight, you don’t prevent errors.”

Dr. Amin, a member of SHM’s Board of Directors, says that as an attending he begins the month with an orientation, reviewing items that help prevent hospital errors. For example, he urges residents before giving medicine to think about possible renal insufficiency and drug interactions. He says he also stresses the importance of preventive techniques.

Developing a system that allows residents to feel comfortable approaching their attending with questions is also vital, says Dr. Amin. Meanwhile, the attending needs to feel he can ask residents pointed questions, yet allow them to think things through.

Dr. Siegal maintained a dialogue with residents regarding the degree of supervision they needed. “A week into the rotation, I asked them how they felt,” he recalls. “Are you getting enough supervision? Too much? Most residents have a reasonable sense of what their deficiencies and discomforts are.”

Joseph Li, MD, director of the hospital medicine program at Boston’s Beth Israel Deaconess Medical Center and assistant professor of medicine at Harvard Medical School, and Kenneth Epstein, MD, MBA, a hospitalist and director of medical affairs and clinical research at IPC-The Hospitalist Company, agree. Dr. Li, also an SHM board member, says not only are residents seeking the right amount of supervision, they’re also seeking the right type of supervision based on their strengths and weaknesses. He says residents also are looking for something else—a medical model. “I think they look for someone to model themselves after,” he suggests. “I think all of us do throughout life, sometimes on purpose but also without intending to do so to better ourselves and learn how to do things.”

Culture Change

Once an atmosphere rife with assigning blame for medical errors, teaching hospitals are changing how errors are found and disclosed, says Michael Lukela, MD, director of the pediatrics program at the University of Michigan and assistant professor of internal medicine and pediatrics.

“The focus is now on patient safety and looking more broadly at how medical errors come about,” he says. “The focus is shifting away from the individual while not overlooking the personal responsibility. There should be safeguards in place, which should prevent errors from occurring, so errors are not just about one person.

“Trainees want to know about the culture. What if they do make an error? Who should they talk with? Their attending? Many are fearful, but these fears don’t have basis. It’s based on what they experience in medical school, saw on TV, and learned from observing others.”

Instead, Dr. Lukela says residents should be saying: “ ‘I don’t understand how my patient got this wrong medication. How can we prevent that?’ It’s up to us as educators to step back and say, ‘That’s a great question’ and get them to think about why errors happen.”

Residents want to focus on the big picture—to learn the art of practicing medicine and get support to do what they need to do, says Dr. Amin. And attendings are looking for residents motivated to learn. “It takes time, energy, and motivation to teach—just like it takes time, energy, and motivation to take care of patients,” he says. “And the hospitalist is in the perfect position to do that.”

Hand-Off Errors

Although hand-offs long have been a part of hospital medicine, the ACGME’s recent resident work-hour limit has raised questions concerning its benefits and drawbacks.

“The concept of 80 hours [a week] is a very good one, but practically it has meant increasing the number of hand-offs,” says Dr. Lukela. “And when you’re increasing the number of handoffs, there’s an increased potential in increasing errors.”

To prevent errors, Dr. Amin says it’s essential to develop a culture around proper hand-offs. “Taking care of patients is not just about getting a history and giving patients drugs or doing surgery,” he cautions. “It’s also thinking about potential errors that can occur and minimizing them through the process of care.”

Dr. Lukela agrees, saying the key part of the hand-off that affects efficiency, quality of care, and error reduction is the thought process of the physician handing off. What is the patient’s history? What tests are pending? What is the action plan? And from day one in the hospital, he says, there needs to be a discharge plan so residents know what direction the patient is going in.

Residents also need to learn that information needs to be meticulously transmitted when there is a transition of care from hospital to nursing facility or from hospital to home. “Residents may view life in the academic center as a vacuum from the outside primary care world,” says Dr. Epstein. “The residents may see the care as what they did in the hospital, but the care is part of a continuum from the primary care, the person’s doctor,” he says.

Team Approach

For hospitalist Julia Wright, MD, associate clinical professor of medicine and director of hospital medicine at the University of Wisconsin School of Medicine and Public Health in Madison, teamwork coupled with redundancy has proven an effective method of teaching residents while delivering first-rate patient care.

“I structure the learning environment so that each person knows what level of responsibility he has within the healthcare team,” she says.

Dr. Wright requires that medical students learn how wards work, that interns learn more about diagnosis and management, and that residents learn how to assign responsibility to the patient team while taking responsibility for patient care. Meanwhile, the attending makes sure the proper diagnosis has been made, and the treatment plan has been carried out.

This arrangement she finds helps her teach and helps prevent errors. “What happens is that there’s some duplication of effort within the medical team,” says Dr. Wright. “But you want more than one person checking to make sure things are getting done, and that way it’s not only excellent care for the patient, but it’s a learning environment.”

The Bottom Line

Dr. Wright says she favors training residents by teaching them about each patient being cared for and that patient’s particular manifestation of a disease. “This method fits in very well with the whole idea of how each one of us is working to help this patient with this condition. I like to pool information and actually take care of the patient as we talk about a condition: helping that patient improve, helping make the diagnosis, helping decide on a treatment. The bottom line is the patient, getting the patient excellent care,” says Dr. Wright.

“As teachers, we try to teach with emotions,” says Dr. Li. “When we teach trainees to care for patients we try to think about how to make it memorable for them—and you remember something that’s emotional,” “So, despite some of the challenges we face, I think we’re at a better place than we were 10 years ago, having hospitalists on the wards. And I think 10 years from now, we’re going to be in an even better place. We’ll have the luxury of 10 more years of clinical experience and emotional experience to impart to trainees.” TH

Robin Tricoles is a medical writer based in New Jersey.

Reference

1. Singh H, Thomas EJ, Peterson LA, et al. Medical errors involving trainees. A study of closed malpractice claims from 5 insurers. Arch Intern Med. 2007 Oct;167(19):2030-2036.

Little information is available on how teaching outcomes involving academic hospitalists and resident physicians affect patient safety and error rates—particularly under duty-hour restrictions on residents by the Accreditation Council for Graduate Medical Education (ACGME).

But data show that when medical errors occur they are often connected with residents’ errors in judgment, lack of technical competence, inadequate supervision by senior physicians, and a breakdown in teamwork.1 In a study of 889 cases resulting in error and injury, 240 involved trainees with at least a “moderately important” role. Among the findings:

• Residents were involved in 208 of those 240 cases;
• 168 of the cases occurred in the inpatient setting;
• 80 of the cases involved obstetrics-gynecology residents, and 45 involved general surgery residents;
• Trainees “lacked technical competence or knowledge” of diagnosis in 67 cases; and
• Attending physicians were involved in 106 supervision failures.

Based on this information, how can academic hospitalists best supervise residents to reduce errors and optimize patient safety and treatment while enhancing residents’ training and satisfaction? Academic hospitalists across the United States grapple with this question daily. And a few have come up with ways that meet the needs of patients and residents.

Oversight vs. Hindsight

Reflecting on his residency, Eric Siegal, MD, a regional medical director with Cogent Healthcare in Madison, Wis., and chair of SHM’s Public Policy Committee, says he recalls times when he did not receive sufficient oversight from senior physicians. Consequently, he and his patients suffered, he says.

“We were thrown into things with little or no supervision, and we were told to sink or swim,” he says. “The good news is that we learned a ton on our own. The bad news is we hurt people in the process. So, the question is how do you walk a line of creating house staff who are autonomous and competent while protecting the patient?”

As an attending physician at the University of Wisconsin, Dr. Siegal says he gave his residents autonomy to make decisions. But there were things he did not let them do alone or without first asking. “The obvious thing was procedures,” he notes. “When residents did procedures, I was standing right there next to them. The extent to which I got involved was entirely dependent on the extent to which the resident was competent.”

Likewise, Alpesh Amin, MD, MBA, professor and chief, division of general internal medicine and executive director of the hospitalist program at the University of California, Irvine, says he gives residents oversight but doesn’t hover. “Otherwise they’re not learning from experience by only doing what someone else tells them to do,” he says. “But without oversight, you don’t prevent errors.”

Dr. Amin, a member of SHM’s Board of Directors, says that as an attending he begins the month with an orientation, reviewing items that help prevent hospital errors. For example, he urges residents before giving medicine to think about possible renal insufficiency and drug interactions. He says he also stresses the importance of preventive techniques.

Developing a system that allows residents to feel comfortable approaching their attending with questions is also vital, says Dr. Amin. Meanwhile, the attending needs to feel he can ask residents pointed questions, yet allow them to think things through.

Dr. Siegal maintained a dialogue with residents regarding the degree of supervision they needed. “A week into the rotation, I asked them how they felt,” he recalls. “Are you getting enough supervision? Too much? Most residents have a reasonable sense of what their deficiencies and discomforts are.”

Joseph Li, MD, director of the hospital medicine program at Boston’s Beth Israel Deaconess Medical Center and assistant professor of medicine at Harvard Medical School, and Kenneth Epstein, MD, MBA, a hospitalist and director of medical affairs and clinical research at IPC-The Hospitalist Company, agree. Dr. Li, also an SHM board member, says not only are residents seeking the right amount of supervision, they’re also seeking the right type of supervision based on their strengths and weaknesses. He says residents also are looking for something else—a medical model. “I think they look for someone to model themselves after,” he suggests. “I think all of us do throughout life, sometimes on purpose but also without intending to do so to better ourselves and learn how to do things.”

Culture Change

Once an atmosphere rife with assigning blame for medical errors, teaching hospitals are changing how errors are found and disclosed, says Michael Lukela, MD, director of the pediatrics program at the University of Michigan and assistant professor of internal medicine and pediatrics.

“The focus is now on patient safety and looking more broadly at how medical errors come about,” he says. “The focus is shifting away from the individual while not overlooking the personal responsibility. There should be safeguards in place, which should prevent errors from occurring, so errors are not just about one person.

“Trainees want to know about the culture. What if they do make an error? Who should they talk with? Their attending? Many are fearful, but these fears don’t have basis. It’s based on what they experience in medical school, saw on TV, and learned from observing others.”

Instead, Dr. Lukela says residents should be saying: “ ‘I don’t understand how my patient got this wrong medication. How can we prevent that?’ It’s up to us as educators to step back and say, ‘That’s a great question’ and get them to think about why errors happen.”

Residents want to focus on the big picture—to learn the art of practicing medicine and get support to do what they need to do, says Dr. Amin. And attendings are looking for residents motivated to learn. “It takes time, energy, and motivation to teach—just like it takes time, energy, and motivation to take care of patients,” he says. “And the hospitalist is in the perfect position to do that.”

Hand-Off Errors

Although hand-offs long have been a part of hospital medicine, the ACGME’s recent resident work-hour limit has raised questions concerning its benefits and drawbacks.

“The concept of 80 hours [a week] is a very good one, but practically it has meant increasing the number of hand-offs,” says Dr. Lukela. “And when you’re increasing the number of handoffs, there’s an increased potential in increasing errors.”

To prevent errors, Dr. Amin says it’s essential to develop a culture around proper hand-offs. “Taking care of patients is not just about getting a history and giving patients drugs or doing surgery,” he cautions. “It’s also thinking about potential errors that can occur and minimizing them through the process of care.”

Dr. Lukela agrees, saying the key part of the hand-off that affects efficiency, quality of care, and error reduction is the thought process of the physician handing off. What is the patient’s history? What tests are pending? What is the action plan? And from day one in the hospital, he says, there needs to be a discharge plan so residents know what direction the patient is going in.

Residents also need to learn that information needs to be meticulously transmitted when there is a transition of care from hospital to nursing facility or from hospital to home. “Residents may view life in the academic center as a vacuum from the outside primary care world,” says Dr. Epstein. “The residents may see the care as what they did in the hospital, but the care is part of a continuum from the primary care, the person’s doctor,” he says.

Team Approach

For hospitalist Julia Wright, MD, associate clinical professor of medicine and director of hospital medicine at the University of Wisconsin School of Medicine and Public Health in Madison, teamwork coupled with redundancy has proven an effective method of teaching residents while delivering first-rate patient care.

“I structure the learning environment so that each person knows what level of responsibility he has within the healthcare team,” she says.

Dr. Wright requires that medical students learn how wards work, that interns learn more about diagnosis and management, and that residents learn how to assign responsibility to the patient team while taking responsibility for patient care. Meanwhile, the attending makes sure the proper diagnosis has been made, and the treatment plan has been carried out.

This arrangement she finds helps her teach and helps prevent errors. “What happens is that there’s some duplication of effort within the medical team,” says Dr. Wright. “But you want more than one person checking to make sure things are getting done, and that way it’s not only excellent care for the patient, but it’s a learning environment.”

The Bottom Line

Dr. Wright says she favors training residents by teaching them about each patient being cared for and that patient’s particular manifestation of a disease. “This method fits in very well with the whole idea of how each one of us is working to help this patient with this condition. I like to pool information and actually take care of the patient as we talk about a condition: helping that patient improve, helping make the diagnosis, helping decide on a treatment. The bottom line is the patient, getting the patient excellent care,” says Dr. Wright.

“As teachers, we try to teach with emotions,” says Dr. Li. “When we teach trainees to care for patients we try to think about how to make it memorable for them—and you remember something that’s emotional,” “So, despite some of the challenges we face, I think we’re at a better place than we were 10 years ago, having hospitalists on the wards. And I think 10 years from now, we’re going to be in an even better place. We’ll have the luxury of 10 more years of clinical experience and emotional experience to impart to trainees.” TH

Robin Tricoles is a medical writer based in New Jersey.

Reference

1. Singh H, Thomas EJ, Peterson LA, et al. Medical errors involving trainees. A study of closed malpractice claims from 5 insurers. Arch Intern Med. 2007 Oct;167(19):2030-2036.

Little information is available on how teaching outcomes involving academic hospitalists and resident physicians affect patient safety and error rates—particularly under duty-hour restrictions on residents by the Accreditation Council for Graduate Medical Education (ACGME).

But data show that when medical errors occur they are often connected with residents’ errors in judgment, lack of technical competence, inadequate supervision by senior physicians, and a breakdown in teamwork.1 In a study of 889 cases resulting in error and injury, 240 involved trainees with at least a “moderately important” role. Among the findings:

• Residents were involved in 208 of those 240 cases;
• 168 of the cases occurred in the inpatient setting;
• 80 of the cases involved obstetrics-gynecology residents, and 45 involved general surgery residents;
• Trainees “lacked technical competence or knowledge” of diagnosis in 67 cases; and
• Attending physicians were involved in 106 supervision failures.

Based on this information, how can academic hospitalists best supervise residents to reduce errors and optimize patient safety and treatment while enhancing residents’ training and satisfaction? Academic hospitalists across the United States grapple with this question daily. And a few have come up with ways that meet the needs of patients and residents.

Oversight vs. Hindsight

Reflecting on his residency, Eric Siegal, MD, a regional medical director with Cogent Healthcare in Madison, Wis., and chair of SHM’s Public Policy Committee, says he recalls times when he did not receive sufficient oversight from senior physicians. Consequently, he and his patients suffered, he says.

“We were thrown into things with little or no supervision, and we were told to sink or swim,” he says. “The good news is that we learned a ton on our own. The bad news is we hurt people in the process. So, the question is how do you walk a line of creating house staff who are autonomous and competent while protecting the patient?”

As an attending physician at the University of Wisconsin, Dr. Siegal says he gave his residents autonomy to make decisions. But there were things he did not let them do alone or without first asking. “The obvious thing was procedures,” he notes. “When residents did procedures, I was standing right there next to them. The extent to which I got involved was entirely dependent on the extent to which the resident was competent.”

Likewise, Alpesh Amin, MD, MBA, professor and chief, division of general internal medicine and executive director of the hospitalist program at the University of California, Irvine, says he gives residents oversight but doesn’t hover. “Otherwise they’re not learning from experience by only doing what someone else tells them to do,” he says. “But without oversight, you don’t prevent errors.”

Dr. Amin, a member of SHM’s Board of Directors, says that as an attending he begins the month with an orientation, reviewing items that help prevent hospital errors. For example, he urges residents before giving medicine to think about possible renal insufficiency and drug interactions. He says he also stresses the importance of preventive techniques.

Developing a system that allows residents to feel comfortable approaching their attending with questions is also vital, says Dr. Amin. Meanwhile, the attending needs to feel he can ask residents pointed questions, yet allow them to think things through.

Dr. Siegal maintained a dialogue with residents regarding the degree of supervision they needed. “A week into the rotation, I asked them how they felt,” he recalls. “Are you getting enough supervision? Too much? Most residents have a reasonable sense of what their deficiencies and discomforts are.”

Joseph Li, MD, director of the hospital medicine program at Boston’s Beth Israel Deaconess Medical Center and assistant professor of medicine at Harvard Medical School, and Kenneth Epstein, MD, MBA, a hospitalist and director of medical affairs and clinical research at IPC-The Hospitalist Company, agree. Dr. Li, also an SHM board member, says not only are residents seeking the right amount of supervision, they’re also seeking the right type of supervision based on their strengths and weaknesses. He says residents also are looking for something else—a medical model. “I think they look for someone to model themselves after,” he suggests. “I think all of us do throughout life, sometimes on purpose but also without intending to do so to better ourselves and learn how to do things.”

Culture Change

Once an atmosphere rife with assigning blame for medical errors, teaching hospitals are changing how errors are found and disclosed, says Michael Lukela, MD, director of the pediatrics program at the University of Michigan and assistant professor of internal medicine and pediatrics.

“The focus is now on patient safety and looking more broadly at how medical errors come about,” he says. “The focus is shifting away from the individual while not overlooking the personal responsibility. There should be safeguards in place, which should prevent errors from occurring, so errors are not just about one person.

“Trainees want to know about the culture. What if they do make an error? Who should they talk with? Their attending? Many are fearful, but these fears don’t have basis. It’s based on what they experience in medical school, saw on TV, and learned from observing others.”

Instead, Dr. Lukela says residents should be saying: “ ‘I don’t understand how my patient got this wrong medication. How can we prevent that?’ It’s up to us as educators to step back and say, ‘That’s a great question’ and get them to think about why errors happen.”

Residents want to focus on the big picture—to learn the art of practicing medicine and get support to do what they need to do, says Dr. Amin. And attendings are looking for residents motivated to learn. “It takes time, energy, and motivation to teach—just like it takes time, energy, and motivation to take care of patients,” he says. “And the hospitalist is in the perfect position to do that.”

Hand-Off Errors

Although hand-offs long have been a part of hospital medicine, the ACGME’s recent resident work-hour limit has raised questions concerning its benefits and drawbacks.

“The concept of 80 hours [a week] is a very good one, but practically it has meant increasing the number of hand-offs,” says Dr. Lukela. “And when you’re increasing the number of handoffs, there’s an increased potential in increasing errors.”

To prevent errors, Dr. Amin says it’s essential to develop a culture around proper hand-offs. “Taking care of patients is not just about getting a history and giving patients drugs or doing surgery,” he cautions. “It’s also thinking about potential errors that can occur and minimizing them through the process of care.”

Dr. Lukela agrees, saying the key part of the hand-off that affects efficiency, quality of care, and error reduction is the thought process of the physician handing off. What is the patient’s history? What tests are pending? What is the action plan? And from day one in the hospital, he says, there needs to be a discharge plan so residents know what direction the patient is going in.

Residents also need to learn that information needs to be meticulously transmitted when there is a transition of care from hospital to nursing facility or from hospital to home. “Residents may view life in the academic center as a vacuum from the outside primary care world,” says Dr. Epstein. “The residents may see the care as what they did in the hospital, but the care is part of a continuum from the primary care, the person’s doctor,” he says.

Team Approach

For hospitalist Julia Wright, MD, associate clinical professor of medicine and director of hospital medicine at the University of Wisconsin School of Medicine and Public Health in Madison, teamwork coupled with redundancy has proven an effective method of teaching residents while delivering first-rate patient care.

“I structure the learning environment so that each person knows what level of responsibility he has within the healthcare team,” she says.

Dr. Wright requires that medical students learn how wards work, that interns learn more about diagnosis and management, and that residents learn how to assign responsibility to the patient team while taking responsibility for patient care. Meanwhile, the attending makes sure the proper diagnosis has been made, and the treatment plan has been carried out.

This arrangement she finds helps her teach and helps prevent errors. “What happens is that there’s some duplication of effort within the medical team,” says Dr. Wright. “But you want more than one person checking to make sure things are getting done, and that way it’s not only excellent care for the patient, but it’s a learning environment.”

The Bottom Line

Dr. Wright says she favors training residents by teaching them about each patient being cared for and that patient’s particular manifestation of a disease. “This method fits in very well with the whole idea of how each one of us is working to help this patient with this condition. I like to pool information and actually take care of the patient as we talk about a condition: helping that patient improve, helping make the diagnosis, helping decide on a treatment. The bottom line is the patient, getting the patient excellent care,” says Dr. Wright.

“As teachers, we try to teach with emotions,” says Dr. Li. “When we teach trainees to care for patients we try to think about how to make it memorable for them—and you remember something that’s emotional,” “So, despite some of the challenges we face, I think we’re at a better place than we were 10 years ago, having hospitalists on the wards. And I think 10 years from now, we’re going to be in an even better place. We’ll have the luxury of 10 more years of clinical experience and emotional experience to impart to trainees.” TH

Robin Tricoles is a medical writer based in New Jersey.

Reference

1. Singh H, Thomas EJ, Peterson LA, et al. Medical errors involving trainees. A study of closed malpractice claims from 5 insurers. Arch Intern Med. 2007 Oct;167(19):2030-2036.

As hospitalist groups evolve, they seek ways to make the best use of support staff to improve patient care and efficiency.

A look at hospitalist groups around the country shows there is no one perfect formula for putting together the best support staff. Rather, the choices groups make are tailored to their specific needs and their relationship with their hospitals.

Support staff members can include secretaries, clerical workers, case managers, social workers, administrators and administrative assistants, office managers, nurses, nurse practitioners, and physician’s assistants.

New Approaches

One trend is the use of registered nurses in hybrid nursing/administrative roles that require medical knowledge and hospital savvy.

Brian Bossard, MD, created a nurse coordinator role in 2003 to provide support to the 18 hospitalists he directs at Inpatient Physician Associates, a group that provides care to patients at BryanLGH Medical Center in Lincoln, Neb.

The group’s three nurse coordinators serve as liaisons with patients and their families and with the hospital’s nursing staff and ancillary staff. The nurse coordinators expedite discharge management by initiating discharge orders, justifying medications, and fielding any questions or issues that need to be discussed with doctors. They keep track of the group’s 18 hospitalists and determine who is available to take on new admissions. It’s an often-complex process of knowing who’s where on rounds and whether they’re busy with difficult cases.

Before the nurse coordinator roles were established, physicians were in charge of figuring out who would take the next patient. “That physician would take all the information, but that may not be the physician available to take care of the patient,” says Dr. Bossard. “That physician would have to call another physician and give the same information—which occupied our doctors’ time. The nurse coordinators are really a time-saving feature.”

At the hospital medicine program at Temple University School of Medicine in Philadelphia, six clinical care coordinators, all trained RNs, play a similar role for the program’s 23 hospitalists.

William Ford, MD, medical director for Cogent Healthcare directing the program at Temple University, credits the clinical care coordinators, who help maintain communication with patients’ primary care physician during and after discharge, for cutting the hospital’s 30-day and 72-hour readmission rate in half within a year’s time. He says coordinators have played a significant role in boosting the group’s overall efficiency. “Our doctors can see three to five more patients a day because of the time the clinical care coordinators save them,” he says.

Some companies providing hospitalist services have relied mainly on office manager-type staff members to take care of clerical tasks and ensure the flow of information between hospitalists and primary care physicians. “Practice coordinators” play this role at the seven hospitalist groups run by The Schumacher Group’s Hospital Medicine Division of Lafayette, La.

David Grace, MD, area medical officer for Schumacher’s hospital medicine division, says practice coordinators are also in charge of collecting data on patients’ length of stay and level of satisfaction and ensuring accuracy in coding and documentation of diagnoses.

Practice coordinators are not required to have nursing degrees, as the job doesn’t include direct patient care. But he looks for applicants with a background in healthcare and an understanding of medical terminology. “Although practice coordinators don’t provide clinical care, the position improves the care delivered by the hospitalists,” he says.

Strike a Balance

One trap hospitalist groups fall into is hiring more support staff than they need, says John Nelson, MD, a principal in Nelson/Flores, a hospitalist management consulting firm, and the medical director of the hospitalist practice at Overlake Hospital Medical Center in Bellevue, Wash.

In his consulting work, Dr. Nelson has seen secretaries file huge volumes of reports and spend their time creating charts and spreadsheets no one will look at again. “It’s very unusual for a hospitalist group to need any sort of medical records kept separately from the hospital,” he says. “So support staff may be doing busy work that doesn’t benefit the practice.”

His advice? “Think critically about whether adding that person is really likely to make the practice better. Challenge yourself to justify any support person you’re considering adding. Make sure every element of the job description contributes to the practice.”

The need for support staff often depends on the hospitalist group’s working relationship to the hospital. Julia Wright, MD, is director of hospital medicine at the University of Wisconsin Hospitals and Clinics (UWHC) in Madison, an academic hospital medicine group of 11 physicians and one advanced practice nurse practitioner. She says the group is assisted by support staff working within the Department of Medicine.

Her part-time program assistant, who tends to secretarial duties such as setting up meetings and assisting with policy development and scheduling, is employed by the primary care department. “We have a benevolent arrangement with the hospital,” she says. “It allows us to do more research and teaching. When we want to put forward an initiative, we usually have the person power and interest and the support to do it.”

Another trend in hiring among hospitalist groups is employing midlevel practitioners, such as nurse practitioners and physician’s assistants. Dr. Ford worked with a physician’s assistant when he was a hospitalist at Union Hospital, a 120-bed community hospital in Elkton, Md. He called midlevel practitioners, who make $70,000 to $90,000 a year —about half the average pay for a hospitalist—a “windfall.”

“They see less-acute patients,” he says. “Patients with stable pneumonia still generate the same billing code as a sicker patient who takes more time and expertise, so midlevels can be more efficient providers from that aspect.”

But this strategy can backfire, according to Dr. Nelson. “On paper, giving nurse practitioners patients who are less sick is logical,” he says. “But in practice, it’s hard to divide up the responsibilities efficiently every day, and there is often a lot of inefficient or unnecessary overlap in work done by the MD and the NP.”

At UWHC, Dr. Wright has found it useful to create a specific definition of the advanced practice nurse practitioner’s role, using feedback from the nurse practitioner and the group’s hospitalists. “We came up with a document that looked at patient complexity, diagnoses, patient volume, and the nondirect patient care issues she is able to help with,” Dr. Wright says. “It’s posted so everyone can remember what kinds of things she can do.”

Sometimes, hospitalist groups can’t make full use of nurse practitioners and other midlevel providers because of hospital regulations. Matthew Szvetecz, MD, head of the hospitalist program at Kadlec Medical Center in Richland, Wash., says he would like to hire nurse practitioners, but hospital bylaws prevent nurse practitioners from writing orders. “If we have to give that kind of direct level of supervision, we might as well take care of them ourselves,” he says.

Dr. Szvetecz’s program has 13 adult hospitalists, four intensivists, and four pediatric physicians. Support staff members include a coordinator in charge of secretarial and administrative assistant duties, a coder who helps with billing, a nurse coordinator, and an executive director. He says the support staff helps contain costs and prevents physicians from spending too much time on administrative duties.

But as a group, “it’s understood that we may not break even or generate positive cash flow,” he says. “Like most hospitalist groups, we have to be subsidized as far as the upfront cash flow, but there are benefits on the back end as far as reduced lengths of stay and better documentation.”

Caveats

Dr. Bossard cautions against letting support staff take over certain duties. The group has avoided letting anyone but physicians take calls from referring primary care physicians, or make calls to primary care physicians at the time of discharge.

“We want to market ourselves as service oriented and felt that placing an intermediary in the communications process isn’t a good thing to do,” he says. “We don’t think it’s good to have secretaries triage calls from physicians. It takes a lot of the physicians’ time, but that’s time well spent.”

Dr. Wright says efficiency and cost containment can improve according to how well the hospitalist group works with the hospital infrastructure and how invested hospitalists and support staff feel in the success of their program. “If they know they’re valued and they feel like they have a say in the work they do, they’ll be more invested in the work they do,” she says. “That usually leads to more efficiency, in my experience.”

Though it’s important for hospitalist groups to work closely with hospitals, Dr. Nelson warns hospitalists not to copy the administrative structures and systems they see in hospitals. “It’s too easy for practices to make mistakes based on what is going on in hospitals,” he says. “They need to critically think about what’s needed in their practice.” TH

Lisa Phillips is a medical writer based in New York.

As hospitalist groups evolve, they seek ways to make the best use of support staff to improve patient care and efficiency.

A look at hospitalist groups around the country shows there is no one perfect formula for putting together the best support staff. Rather, the choices groups make are tailored to their specific needs and their relationship with their hospitals.

Support staff members can include secretaries, clerical workers, case managers, social workers, administrators and administrative assistants, office managers, nurses, nurse practitioners, and physician’s assistants.

New Approaches

One trend is the use of registered nurses in hybrid nursing/administrative roles that require medical knowledge and hospital savvy.

Brian Bossard, MD, created a nurse coordinator role in 2003 to provide support to the 18 hospitalists he directs at Inpatient Physician Associates, a group that provides care to patients at BryanLGH Medical Center in Lincoln, Neb.

The group’s three nurse coordinators serve as liaisons with patients and their families and with the hospital’s nursing staff and ancillary staff. The nurse coordinators expedite discharge management by initiating discharge orders, justifying medications, and fielding any questions or issues that need to be discussed with doctors. They keep track of the group’s 18 hospitalists and determine who is available to take on new admissions. It’s an often-complex process of knowing who’s where on rounds and whether they’re busy with difficult cases.

Before the nurse coordinator roles were established, physicians were in charge of figuring out who would take the next patient. “That physician would take all the information, but that may not be the physician available to take care of the patient,” says Dr. Bossard. “That physician would have to call another physician and give the same information—which occupied our doctors’ time. The nurse coordinators are really a time-saving feature.”

At the hospital medicine program at Temple University School of Medicine in Philadelphia, six clinical care coordinators, all trained RNs, play a similar role for the program’s 23 hospitalists.

William Ford, MD, medical director for Cogent Healthcare directing the program at Temple University, credits the clinical care coordinators, who help maintain communication with patients’ primary care physician during and after discharge, for cutting the hospital’s 30-day and 72-hour readmission rate in half within a year’s time. He says coordinators have played a significant role in boosting the group’s overall efficiency. “Our doctors can see three to five more patients a day because of the time the clinical care coordinators save them,” he says.

Some companies providing hospitalist services have relied mainly on office manager-type staff members to take care of clerical tasks and ensure the flow of information between hospitalists and primary care physicians. “Practice coordinators” play this role at the seven hospitalist groups run by The Schumacher Group’s Hospital Medicine Division of Lafayette, La.

David Grace, MD, area medical officer for Schumacher’s hospital medicine division, says practice coordinators are also in charge of collecting data on patients’ length of stay and level of satisfaction and ensuring accuracy in coding and documentation of diagnoses.

Practice coordinators are not required to have nursing degrees, as the job doesn’t include direct patient care. But he looks for applicants with a background in healthcare and an understanding of medical terminology. “Although practice coordinators don’t provide clinical care, the position improves the care delivered by the hospitalists,” he says.

Strike a Balance

One trap hospitalist groups fall into is hiring more support staff than they need, says John Nelson, MD, a principal in Nelson/Flores, a hospitalist management consulting firm, and the medical director of the hospitalist practice at Overlake Hospital Medical Center in Bellevue, Wash.

In his consulting work, Dr. Nelson has seen secretaries file huge volumes of reports and spend their time creating charts and spreadsheets no one will look at again. “It’s very unusual for a hospitalist group to need any sort of medical records kept separately from the hospital,” he says. “So support staff may be doing busy work that doesn’t benefit the practice.”

His advice? “Think critically about whether adding that person is really likely to make the practice better. Challenge yourself to justify any support person you’re considering adding. Make sure every element of the job description contributes to the practice.”

The need for support staff often depends on the hospitalist group’s working relationship to the hospital. Julia Wright, MD, is director of hospital medicine at the University of Wisconsin Hospitals and Clinics (UWHC) in Madison, an academic hospital medicine group of 11 physicians and one advanced practice nurse practitioner. She says the group is assisted by support staff working within the Department of Medicine.

Her part-time program assistant, who tends to secretarial duties such as setting up meetings and assisting with policy development and scheduling, is employed by the primary care department. “We have a benevolent arrangement with the hospital,” she says. “It allows us to do more research and teaching. When we want to put forward an initiative, we usually have the person power and interest and the support to do it.”

Another trend in hiring among hospitalist groups is employing midlevel practitioners, such as nurse practitioners and physician’s assistants. Dr. Ford worked with a physician’s assistant when he was a hospitalist at Union Hospital, a 120-bed community hospital in Elkton, Md. He called midlevel practitioners, who make $70,000 to $90,000 a year —about half the average pay for a hospitalist—a “windfall.”

“They see less-acute patients,” he says. “Patients with stable pneumonia still generate the same billing code as a sicker patient who takes more time and expertise, so midlevels can be more efficient providers from that aspect.”

But this strategy can backfire, according to Dr. Nelson. “On paper, giving nurse practitioners patients who are less sick is logical,” he says. “But in practice, it’s hard to divide up the responsibilities efficiently every day, and there is often a lot of inefficient or unnecessary overlap in work done by the MD and the NP.”

At UWHC, Dr. Wright has found it useful to create a specific definition of the advanced practice nurse practitioner’s role, using feedback from the nurse practitioner and the group’s hospitalists. “We came up with a document that looked at patient complexity, diagnoses, patient volume, and the nondirect patient care issues she is able to help with,” Dr. Wright says. “It’s posted so everyone can remember what kinds of things she can do.”

Sometimes, hospitalist groups can’t make full use of nurse practitioners and other midlevel providers because of hospital regulations. Matthew Szvetecz, MD, head of the hospitalist program at Kadlec Medical Center in Richland, Wash., says he would like to hire nurse practitioners, but hospital bylaws prevent nurse practitioners from writing orders. “If we have to give that kind of direct level of supervision, we might as well take care of them ourselves,” he says.

Dr. Szvetecz’s program has 13 adult hospitalists, four intensivists, and four pediatric physicians. Support staff members include a coordinator in charge of secretarial and administrative assistant duties, a coder who helps with billing, a nurse coordinator, and an executive director. He says the support staff helps contain costs and prevents physicians from spending too much time on administrative duties.

But as a group, “it’s understood that we may not break even or generate positive cash flow,” he says. “Like most hospitalist groups, we have to be subsidized as far as the upfront cash flow, but there are benefits on the back end as far as reduced lengths of stay and better documentation.”

Caveats

Dr. Bossard cautions against letting support staff take over certain duties. The group has avoided letting anyone but physicians take calls from referring primary care physicians, or make calls to primary care physicians at the time of discharge.

“We want to market ourselves as service oriented and felt that placing an intermediary in the communications process isn’t a good thing to do,” he says. “We don’t think it’s good to have secretaries triage calls from physicians. It takes a lot of the physicians’ time, but that’s time well spent.”

Dr. Wright says efficiency and cost containment can improve according to how well the hospitalist group works with the hospital infrastructure and how invested hospitalists and support staff feel in the success of their program. “If they know they’re valued and they feel like they have a say in the work they do, they’ll be more invested in the work they do,” she says. “That usually leads to more efficiency, in my experience.”

Though it’s important for hospitalist groups to work closely with hospitals, Dr. Nelson warns hospitalists not to copy the administrative structures and systems they see in hospitals. “It’s too easy for practices to make mistakes based on what is going on in hospitals,” he says. “They need to critically think about what’s needed in their practice.” TH

Lisa Phillips is a medical writer based in New York.

As hospitalist groups evolve, they seek ways to make the best use of support staff to improve patient care and efficiency.

A look at hospitalist groups around the country shows there is no one perfect formula for putting together the best support staff. Rather, the choices groups make are tailored to their specific needs and their relationship with their hospitals.

Support staff members can include secretaries, clerical workers, case managers, social workers, administrators and administrative assistants, office managers, nurses, nurse practitioners, and physician’s assistants.

New Approaches

One trend is the use of registered nurses in hybrid nursing/administrative roles that require medical knowledge and hospital savvy.

Brian Bossard, MD, created a nurse coordinator role in 2003 to provide support to the 18 hospitalists he directs at Inpatient Physician Associates, a group that provides care to patients at BryanLGH Medical Center in Lincoln, Neb.

The group’s three nurse coordinators serve as liaisons with patients and their families and with the hospital’s nursing staff and ancillary staff. The nurse coordinators expedite discharge management by initiating discharge orders, justifying medications, and fielding any questions or issues that need to be discussed with doctors. They keep track of the group’s 18 hospitalists and determine who is available to take on new admissions. It’s an often-complex process of knowing who’s where on rounds and whether they’re busy with difficult cases.

Before the nurse coordinator roles were established, physicians were in charge of figuring out who would take the next patient. “That physician would take all the information, but that may not be the physician available to take care of the patient,” says Dr. Bossard. “That physician would have to call another physician and give the same information—which occupied our doctors’ time. The nurse coordinators are really a time-saving feature.”

At the hospital medicine program at Temple University School of Medicine in Philadelphia, six clinical care coordinators, all trained RNs, play a similar role for the program’s 23 hospitalists.

William Ford, MD, medical director for Cogent Healthcare directing the program at Temple University, credits the clinical care coordinators, who help maintain communication with patients’ primary care physician during and after discharge, for cutting the hospital’s 30-day and 72-hour readmission rate in half within a year’s time. He says coordinators have played a significant role in boosting the group’s overall efficiency. “Our doctors can see three to five more patients a day because of the time the clinical care coordinators save them,” he says.

Some companies providing hospitalist services have relied mainly on office manager-type staff members to take care of clerical tasks and ensure the flow of information between hospitalists and primary care physicians. “Practice coordinators” play this role at the seven hospitalist groups run by The Schumacher Group’s Hospital Medicine Division of Lafayette, La.

David Grace, MD, area medical officer for Schumacher’s hospital medicine division, says practice coordinators are also in charge of collecting data on patients’ length of stay and level of satisfaction and ensuring accuracy in coding and documentation of diagnoses.

Practice coordinators are not required to have nursing degrees, as the job doesn’t include direct patient care. But he looks for applicants with a background in healthcare and an understanding of medical terminology. “Although practice coordinators don’t provide clinical care, the position improves the care delivered by the hospitalists,” he says.

Strike a Balance

One trap hospitalist groups fall into is hiring more support staff than they need, says John Nelson, MD, a principal in Nelson/Flores, a hospitalist management consulting firm, and the medical director of the hospitalist practice at Overlake Hospital Medical Center in Bellevue, Wash.

In his consulting work, Dr. Nelson has seen secretaries file huge volumes of reports and spend their time creating charts and spreadsheets no one will look at again. “It’s very unusual for a hospitalist group to need any sort of medical records kept separately from the hospital,” he says. “So support staff may be doing busy work that doesn’t benefit the practice.”

His advice? “Think critically about whether adding that person is really likely to make the practice better. Challenge yourself to justify any support person you’re considering adding. Make sure every element of the job description contributes to the practice.”

The need for support staff often depends on the hospitalist group’s working relationship to the hospital. Julia Wright, MD, is director of hospital medicine at the University of Wisconsin Hospitals and Clinics (UWHC) in Madison, an academic hospital medicine group of 11 physicians and one advanced practice nurse practitioner. She says the group is assisted by support staff working within the Department of Medicine.

Her part-time program assistant, who tends to secretarial duties such as setting up meetings and assisting with policy development and scheduling, is employed by the primary care department. “We have a benevolent arrangement with the hospital,” she says. “It allows us to do more research and teaching. When we want to put forward an initiative, we usually have the person power and interest and the support to do it.”

Another trend in hiring among hospitalist groups is employing midlevel practitioners, such as nurse practitioners and physician’s assistants. Dr. Ford worked with a physician’s assistant when he was a hospitalist at Union Hospital, a 120-bed community hospital in Elkton, Md. He called midlevel practitioners, who make $70,000 to $90,000 a year —about half the average pay for a hospitalist—a “windfall.”

“They see less-acute patients,” he says. “Patients with stable pneumonia still generate the same billing code as a sicker patient who takes more time and expertise, so midlevels can be more efficient providers from that aspect.”

But this strategy can backfire, according to Dr. Nelson. “On paper, giving nurse practitioners patients who are less sick is logical,” he says. “But in practice, it’s hard to divide up the responsibilities efficiently every day, and there is often a lot of inefficient or unnecessary overlap in work done by the MD and the NP.”

At UWHC, Dr. Wright has found it useful to create a specific definition of the advanced practice nurse practitioner’s role, using feedback from the nurse practitioner and the group’s hospitalists. “We came up with a document that looked at patient complexity, diagnoses, patient volume, and the nondirect patient care issues she is able to help with,” Dr. Wright says. “It’s posted so everyone can remember what kinds of things she can do.”

Sometimes, hospitalist groups can’t make full use of nurse practitioners and other midlevel providers because of hospital regulations. Matthew Szvetecz, MD, head of the hospitalist program at Kadlec Medical Center in Richland, Wash., says he would like to hire nurse practitioners, but hospital bylaws prevent nurse practitioners from writing orders. “If we have to give that kind of direct level of supervision, we might as well take care of them ourselves,” he says.

Dr. Szvetecz’s program has 13 adult hospitalists, four intensivists, and four pediatric physicians. Support staff members include a coordinator in charge of secretarial and administrative assistant duties, a coder who helps with billing, a nurse coordinator, and an executive director. He says the support staff helps contain costs and prevents physicians from spending too much time on administrative duties.

But as a group, “it’s understood that we may not break even or generate positive cash flow,” he says. “Like most hospitalist groups, we have to be subsidized as far as the upfront cash flow, but there are benefits on the back end as far as reduced lengths of stay and better documentation.”

Caveats

Dr. Bossard cautions against letting support staff take over certain duties. The group has avoided letting anyone but physicians take calls from referring primary care physicians, or make calls to primary care physicians at the time of discharge.

“We want to market ourselves as service oriented and felt that placing an intermediary in the communications process isn’t a good thing to do,” he says. “We don’t think it’s good to have secretaries triage calls from physicians. It takes a lot of the physicians’ time, but that’s time well spent.”

Dr. Wright says efficiency and cost containment can improve according to how well the hospitalist group works with the hospital infrastructure and how invested hospitalists and support staff feel in the success of their program. “If they know they’re valued and they feel like they have a say in the work they do, they’ll be more invested in the work they do,” she says. “That usually leads to more efficiency, in my experience.”

Though it’s important for hospitalist groups to work closely with hospitals, Dr. Nelson warns hospitalists not to copy the administrative structures and systems they see in hospitals. “It’s too easy for practices to make mistakes based on what is going on in hospitals,” he says. “They need to critically think about what’s needed in their practice.” TH

Lisa Phillips is a medical writer based in New York.

With recent changes in Medicare rules making reimbursement even trickier for patients who aren’t well enough to be sent home quickly but aren’t sick enough to move to an inpatient bed, hospitalists are increasingly being tapped to set up observation units at medical centers around the country.

These patients, experts say, are the ones hospitals are most likely to lose money on. That’s because the Centers for Medicare and Medicaid Services (CMS) won’t pay unless a patient meets stringent guidelines for admission to the hospital. And while recently rewritten rules allow payment for 24 hours of observation, they also can also lead to denial of claims when patients aren’t considered sick enough to have been admitted.

When they’re well run, observation units can even help cover losses from emergency departments (ED) that have trouble collecting on bills because most of their patient population is uninsured or underinsured.

But the drive to create observation units isn’t just about money, says Frank W. Peacock, MD, vice chair of the emergency department at the Cleveland Clinic in Ohio. Studies have shown that death rates drop when hospitals add observation units, Dr. Peacock says.

Despite these clear benefits, experts estimate that a mere 20% of medical centers around the nation have observation units.

This may in part be because creating such a unit—also known as clinical decision unit—takes a lot of planning to start up, says William T. Ford, MD, medical director for Nashville, Tenn.-based Cogent Healthcare and chief of the section of hospital medicine at Temple University in Philadelphia. Without proper planning, observation units can fail to flourish—or just fail.

That’s what happened at Temple, Dr. Ford says. “The original observation unit got bogged down in its own infrastructure,” he explains. “It wasn’t cost effective.”

After that first attempt failed, Temple reached out to Cogent and Dr. Ford for help in developing an observation unit that would be financially viable.

Observation Origins

Classically, Dr. Ford says, observation units were developed and staffed by emergency department physicians. But these days, the units are increasingly being designed and run by hospitalists, he says, adding that this change makes a lot of sense.

“Emergency department physicians don’t have the time or the resources to monitor patients for long periods of time,” Dr. Ford says. “That’s why I think some of the early ones failed—they didn’t work as efficiently and were staffed by the wrong people.”

Hospitalist Jason Napolitano, MD, agrees with the choice to staff observation units with hospitalists. “We want our emergency department physicians to be able to focus on life-or-death issues and on the stabilization of very sick patients,” says Dr. Napolitano, medical director of the observation unit at the University of California at Los Angeles Medical Center. “These are things that ED physicians do spectacularly well. But when it gets down to management and reassessment of patients over time, we wanted a dedicated staff of hospitalists who were trained in internal medicine.”

It made sense that many of the early observation units were staffed by ED doctors, says Mark Flitcraft, a nurse and unit director of nursing at UCLA. That’s because the units were originally adjuncts to the ED. These early units were initially seen as a way to take the pressure off overcrowded, overworked EDs, Flitcraft says. “They were a way for hospitals to avoid [diverting patients] as the beds in the ED started filing up,” he adds.

Avoiding such diversions is still one of the main justifications for adding an observation unit, Dr. Ford says. “The observation unit helps increase throughput time.”

Still, he says, if you’re going to create an observation unit staffed by hospitalists, “you need to make sure that the emergency department buys in to the concept. They should be your best friends. Go over and meet with them. If they don’t buy into the idea, then you’re going to have problems.”

Time Is of the Essence

For an observation unit to work well, the staff needs to think about time in a different way, Flitcraft says.

“It’s more of an outpatient designation from a Medicare standpoint,” he explains. “The focus has to be hours rather than days. You really need to know that the clock is ticking and work on rapid turnaround.” Take discharge, for example, Flitcraft says. Normally a hospitalist would wait for morning to send a patient home. “But there are patients we might discharge at 10 p.m.,” he says. “When they are stable they go home.”

In the observation unit, staff members always have the end in sight, agrees Robin J. Trupp, a grad student at Ohio State University, expert on observation units, and president of The American Association of Heart Failure Nurses. “You know what your goal is,” she adds. “There’s a 24-hour clock and it’s always ticking. At the end of 24 hours you have to make a treatment decision: admit the patient or send him home.”

Because observation units are generally limited to treating a select group of medical conditions, they can be more efficient. Some observation units are limited to only one or two diagnoses (e.g., chest pain and heart failure). Others see a slightly broader spectrum of illnesses, including asthma, stomach pain, and pneumonia.

One byproduct of limiting the number of conditions treated in the unit is ending up with a staff that can become specialized in treating those ailments, experts say.

“In the observation unit you’re not looking at urinary tract infections or doing stitches,” Trupp says. “You’re just working on this population. You become an expert on how it’s treated and managed.”

And that offers another advantage: the possibility of doing more patient education.

She points to the example of a unit dedicated to treating heart failure patients.

“You can take advantage of the fact that at this moment, the patient can clearly see cause and effect and maybe you’ll have a chance at getting some behavior changes,” Trupp says. “It’s the case of having put their hand in the fire and feeling and having learned it’s hot; they’ll learn not to do it again. They might learn that the symptoms that landed them in the ED came from excess salt load due to eating Chinese food or chips and salsa.”

Ultimately, for certain conditions, observation units can provide better care. Studies have shown that in the three months following a visit to the hospital, heart failure patients are far less likely to return if they’ve been seen in the observation unit rather than being treated as inpatients.

And if that weren’t enough of an inducement to administrators to create observation units, Dr. Peacock offers one other: The units can do more than pay for themselves.

“We are in an urban environment, and our patient population is not well insured,” he says. “There are years when the ED loses money. The observation unit never loses money. In fact, it’s saved us a few times. That was a pleasant surprise.” TH

Linda Carroll is a medical writer based in New Jersey.

With recent changes in Medicare rules making reimbursement even trickier for patients who aren’t well enough to be sent home quickly but aren’t sick enough to move to an inpatient bed, hospitalists are increasingly being tapped to set up observation units at medical centers around the country.

These patients, experts say, are the ones hospitals are most likely to lose money on. That’s because the Centers for Medicare and Medicaid Services (CMS) won’t pay unless a patient meets stringent guidelines for admission to the hospital. And while recently rewritten rules allow payment for 24 hours of observation, they also can also lead to denial of claims when patients aren’t considered sick enough to have been admitted.

When they’re well run, observation units can even help cover losses from emergency departments (ED) that have trouble collecting on bills because most of their patient population is uninsured or underinsured.

But the drive to create observation units isn’t just about money, says Frank W. Peacock, MD, vice chair of the emergency department at the Cleveland Clinic in Ohio. Studies have shown that death rates drop when hospitals add observation units, Dr. Peacock says.

Despite these clear benefits, experts estimate that a mere 20% of medical centers around the nation have observation units.

This may in part be because creating such a unit—also known as clinical decision unit—takes a lot of planning to start up, says William T. Ford, MD, medical director for Nashville, Tenn.-based Cogent Healthcare and chief of the section of hospital medicine at Temple University in Philadelphia. Without proper planning, observation units can fail to flourish—or just fail.

That’s what happened at Temple, Dr. Ford says. “The original observation unit got bogged down in its own infrastructure,” he explains. “It wasn’t cost effective.”

After that first attempt failed, Temple reached out to Cogent and Dr. Ford for help in developing an observation unit that would be financially viable.

Observation Origins

Classically, Dr. Ford says, observation units were developed and staffed by emergency department physicians. But these days, the units are increasingly being designed and run by hospitalists, he says, adding that this change makes a lot of sense.

“Emergency department physicians don’t have the time or the resources to monitor patients for long periods of time,” Dr. Ford says. “That’s why I think some of the early ones failed—they didn’t work as efficiently and were staffed by the wrong people.”

Hospitalist Jason Napolitano, MD, agrees with the choice to staff observation units with hospitalists. “We want our emergency department physicians to be able to focus on life-or-death issues and on the stabilization of very sick patients,” says Dr. Napolitano, medical director of the observation unit at the University of California at Los Angeles Medical Center. “These are things that ED physicians do spectacularly well. But when it gets down to management and reassessment of patients over time, we wanted a dedicated staff of hospitalists who were trained in internal medicine.”

It made sense that many of the early observation units were staffed by ED doctors, says Mark Flitcraft, a nurse and unit director of nursing at UCLA. That’s because the units were originally adjuncts to the ED. These early units were initially seen as a way to take the pressure off overcrowded, overworked EDs, Flitcraft says. “They were a way for hospitals to avoid [diverting patients] as the beds in the ED started filing up,” he adds.

Avoiding such diversions is still one of the main justifications for adding an observation unit, Dr. Ford says. “The observation unit helps increase throughput time.”

Still, he says, if you’re going to create an observation unit staffed by hospitalists, “you need to make sure that the emergency department buys in to the concept. They should be your best friends. Go over and meet with them. If they don’t buy into the idea, then you’re going to have problems.”

Time Is of the Essence

For an observation unit to work well, the staff needs to think about time in a different way, Flitcraft says.

“It’s more of an outpatient designation from a Medicare standpoint,” he explains. “The focus has to be hours rather than days. You really need to know that the clock is ticking and work on rapid turnaround.” Take discharge, for example, Flitcraft says. Normally a hospitalist would wait for morning to send a patient home. “But there are patients we might discharge at 10 p.m.,” he says. “When they are stable they go home.”

In the observation unit, staff members always have the end in sight, agrees Robin J. Trupp, a grad student at Ohio State University, expert on observation units, and president of The American Association of Heart Failure Nurses. “You know what your goal is,” she adds. “There’s a 24-hour clock and it’s always ticking. At the end of 24 hours you have to make a treatment decision: admit the patient or send him home.”

Because observation units are generally limited to treating a select group of medical conditions, they can be more efficient. Some observation units are limited to only one or two diagnoses (e.g., chest pain and heart failure). Others see a slightly broader spectrum of illnesses, including asthma, stomach pain, and pneumonia.

One byproduct of limiting the number of conditions treated in the unit is ending up with a staff that can become specialized in treating those ailments, experts say.

“In the observation unit you’re not looking at urinary tract infections or doing stitches,” Trupp says. “You’re just working on this population. You become an expert on how it’s treated and managed.”

And that offers another advantage: the possibility of doing more patient education.

She points to the example of a unit dedicated to treating heart failure patients.

“You can take advantage of the fact that at this moment, the patient can clearly see cause and effect and maybe you’ll have a chance at getting some behavior changes,” Trupp says. “It’s the case of having put their hand in the fire and feeling and having learned it’s hot; they’ll learn not to do it again. They might learn that the symptoms that landed them in the ED came from excess salt load due to eating Chinese food or chips and salsa.”

Ultimately, for certain conditions, observation units can provide better care. Studies have shown that in the three months following a visit to the hospital, heart failure patients are far less likely to return if they’ve been seen in the observation unit rather than being treated as inpatients.

And if that weren’t enough of an inducement to administrators to create observation units, Dr. Peacock offers one other: The units can do more than pay for themselves.

“We are in an urban environment, and our patient population is not well insured,” he says. “There are years when the ED loses money. The observation unit never loses money. In fact, it’s saved us a few times. That was a pleasant surprise.” TH

Linda Carroll is a medical writer based in New Jersey.

With recent changes in Medicare rules making reimbursement even trickier for patients who aren’t well enough to be sent home quickly but aren’t sick enough to move to an inpatient bed, hospitalists are increasingly being tapped to set up observation units at medical centers around the country.

These patients, experts say, are the ones hospitals are most likely to lose money on. That’s because the Centers for Medicare and Medicaid Services (CMS) won’t pay unless a patient meets stringent guidelines for admission to the hospital. And while recently rewritten rules allow payment for 24 hours of observation, they also can also lead to denial of claims when patients aren’t considered sick enough to have been admitted.

When they’re well run, observation units can even help cover losses from emergency departments (ED) that have trouble collecting on bills because most of their patient population is uninsured or underinsured.

But the drive to create observation units isn’t just about money, says Frank W. Peacock, MD, vice chair of the emergency department at the Cleveland Clinic in Ohio. Studies have shown that death rates drop when hospitals add observation units, Dr. Peacock says.

Despite these clear benefits, experts estimate that a mere 20% of medical centers around the nation have observation units.

This may in part be because creating such a unit—also known as clinical decision unit—takes a lot of planning to start up, says William T. Ford, MD, medical director for Nashville, Tenn.-based Cogent Healthcare and chief of the section of hospital medicine at Temple University in Philadelphia. Without proper planning, observation units can fail to flourish—or just fail.

That’s what happened at Temple, Dr. Ford says. “The original observation unit got bogged down in its own infrastructure,” he explains. “It wasn’t cost effective.”

After that first attempt failed, Temple reached out to Cogent and Dr. Ford for help in developing an observation unit that would be financially viable.

Observation Origins

Classically, Dr. Ford says, observation units were developed and staffed by emergency department physicians. But these days, the units are increasingly being designed and run by hospitalists, he says, adding that this change makes a lot of sense.

“Emergency department physicians don’t have the time or the resources to monitor patients for long periods of time,” Dr. Ford says. “That’s why I think some of the early ones failed—they didn’t work as efficiently and were staffed by the wrong people.”

Hospitalist Jason Napolitano, MD, agrees with the choice to staff observation units with hospitalists. “We want our emergency department physicians to be able to focus on life-or-death issues and on the stabilization of very sick patients,” says Dr. Napolitano, medical director of the observation unit at the University of California at Los Angeles Medical Center. “These are things that ED physicians do spectacularly well. But when it gets down to management and reassessment of patients over time, we wanted a dedicated staff of hospitalists who were trained in internal medicine.”

It made sense that many of the early observation units were staffed by ED doctors, says Mark Flitcraft, a nurse and unit director of nursing at UCLA. That’s because the units were originally adjuncts to the ED. These early units were initially seen as a way to take the pressure off overcrowded, overworked EDs, Flitcraft says. “They were a way for hospitals to avoid [diverting patients] as the beds in the ED started filing up,” he adds.

Avoiding such diversions is still one of the main justifications for adding an observation unit, Dr. Ford says. “The observation unit helps increase throughput time.”

Still, he says, if you’re going to create an observation unit staffed by hospitalists, “you need to make sure that the emergency department buys in to the concept. They should be your best friends. Go over and meet with them. If they don’t buy into the idea, then you’re going to have problems.”

Time Is of the Essence

For an observation unit to work well, the staff needs to think about time in a different way, Flitcraft says.

“It’s more of an outpatient designation from a Medicare standpoint,” he explains. “The focus has to be hours rather than days. You really need to know that the clock is ticking and work on rapid turnaround.” Take discharge, for example, Flitcraft says. Normally a hospitalist would wait for morning to send a patient home. “But there are patients we might discharge at 10 p.m.,” he says. “When they are stable they go home.”

In the observation unit, staff members always have the end in sight, agrees Robin J. Trupp, a grad student at Ohio State University, expert on observation units, and president of The American Association of Heart Failure Nurses. “You know what your goal is,” she adds. “There’s a 24-hour clock and it’s always ticking. At the end of 24 hours you have to make a treatment decision: admit the patient or send him home.”

Because observation units are generally limited to treating a select group of medical conditions, they can be more efficient. Some observation units are limited to only one or two diagnoses (e.g., chest pain and heart failure). Others see a slightly broader spectrum of illnesses, including asthma, stomach pain, and pneumonia.

One byproduct of limiting the number of conditions treated in the unit is ending up with a staff that can become specialized in treating those ailments, experts say.

“In the observation unit you’re not looking at urinary tract infections or doing stitches,” Trupp says. “You’re just working on this population. You become an expert on how it’s treated and managed.”

And that offers another advantage: the possibility of doing more patient education.

She points to the example of a unit dedicated to treating heart failure patients.

“You can take advantage of the fact that at this moment, the patient can clearly see cause and effect and maybe you’ll have a chance at getting some behavior changes,” Trupp says. “It’s the case of having put their hand in the fire and feeling and having learned it’s hot; they’ll learn not to do it again. They might learn that the symptoms that landed them in the ED came from excess salt load due to eating Chinese food or chips and salsa.”

Ultimately, for certain conditions, observation units can provide better care. Studies have shown that in the three months following a visit to the hospital, heart failure patients are far less likely to return if they’ve been seen in the observation unit rather than being treated as inpatients.

And if that weren’t enough of an inducement to administrators to create observation units, Dr. Peacock offers one other: The units can do more than pay for themselves.

“We are in an urban environment, and our patient population is not well insured,” he says. “There are years when the ED loses money. The observation unit never loses money. In fact, it’s saved us a few times. That was a pleasant surprise.” TH

Linda Carroll is a medical writer based in New Jersey.

Supplement Editor:
Amir K. Jaffer, MD

Contents

An overview of venous thromboembolism: Impact, risks, and issues in prophylaxis
A.K. Jaffer

Prevention of venous thromboembolism in the hospitalized medical patient
A.K. Jaffer, A.N. Amin, D.J. Brotman, S.B. Deitelzweig, S.C. McKean, A.C. Spyropoulos

Prevention of venous thromboembolism in the cancer surgery patient
A.C. Spyropoulos, D.J. Brotman, A.N. Amin, S.B. Deitelzweig, A.K. Jaffer, S.C. McKean

Prevention of venous thromboembolism in the orthopedic surgery patient
S.B. Deitelzweig, S.C. McKean, A.N. Amin, D.J. Brotman, A.K. Jaffer, A.C. Spyropoulos

Supplement Editor:
Amir K. Jaffer, MD

Contents

An overview of venous thromboembolism: Impact, risks, and issues in prophylaxis
A.K. Jaffer

Prevention of venous thromboembolism in the hospitalized medical patient
A.K. Jaffer, A.N. Amin, D.J. Brotman, S.B. Deitelzweig, S.C. McKean, A.C. Spyropoulos

Prevention of venous thromboembolism in the cancer surgery patient
A.C. Spyropoulos, D.J. Brotman, A.N. Amin, S.B. Deitelzweig, A.K. Jaffer, S.C. McKean

Prevention of venous thromboembolism in the orthopedic surgery patient
S.B. Deitelzweig, S.C. McKean, A.N. Amin, D.J. Brotman, A.K. Jaffer, A.C. Spyropoulos

Supplement Editor:
Amir K. Jaffer, MD

Contents

An overview of venous thromboembolism: Impact, risks, and issues in prophylaxis
A.K. Jaffer

Prevention of venous thromboembolism in the hospitalized medical patient
A.K. Jaffer, A.N. Amin, D.J. Brotman, S.B. Deitelzweig, S.C. McKean, A.C. Spyropoulos

Prevention of venous thromboembolism in the cancer surgery patient
A.C. Spyropoulos, D.J. Brotman, A.N. Amin, S.B. Deitelzweig, A.K. Jaffer, S.C. McKean

Prevention of venous thromboembolism in the orthopedic surgery patient
S.B. Deitelzweig, S.C. McKean, A.N. Amin, D.J. Brotman, A.K. Jaffer, A.C. Spyropoulos

A 67-year-old retired man presents to his internist with a 3-month history of abdominal discomfort in the right upper quadrant on deep breathing. He has no other abdominal complaints, but he mentions that he underwent laparoscopic cholecystectomy 3 months ago for gallstone pancreatitis.

A biopsy specimen obtained with CT guidance shows chronic inflammation but is sterile on aerobic culture. There is no evidence of malignancy. Because of concern for underlying infection, the infectious disease staff recommends empirical treatment with a 4-week course of ampicillin-sulbactam (Unasyn). At completion of the antibiotic course, the patient’s symptoms have resolved.

LAPAROSCOPY’S DRAWBACKS

Complications of dropped stones, though rare, can include localized or systemic infection, inflammation, fibrosis, adhesion, cutaneous sinus formation, ileus, and abscess.^1,6 Lohan et al¹ estimated that dropped stones produce an intra-abdominal abscess in 0.6% to 2.9% of cases of dropped stones and bile spillage, based on reports by Rice et al⁴ and Morrin et al.⁷ Dropped stones should be recognized as a potential cause of intra-abdominal abscess in any cholecystectomy patient months or even years after the surgery. Also, these abscesses are not necessarily confined to the right upper quadrant: they can occur anywhere in the abdominal cavity.^5,7

Given the ever-increasing popularity of laparoscopic cholecystectomy, the problem of intra-abdominal abscess due to dropped gallstones will only become a more common problem. Early diagnosis is the key to avoiding long and unnecessary treatment.

If dropped gallstones do become infected and eventually cause symptoms, they may require surgical or percutaneous removal in conjunction with antimicrobial therapy.⁸

A 67-year-old retired man presents to his internist with a 3-month history of abdominal discomfort in the right upper quadrant on deep breathing. He has no other abdominal complaints, but he mentions that he underwent laparoscopic cholecystectomy 3 months ago for gallstone pancreatitis.

A biopsy specimen obtained with CT guidance shows chronic inflammation but is sterile on aerobic culture. There is no evidence of malignancy. Because of concern for underlying infection, the infectious disease staff recommends empirical treatment with a 4-week course of ampicillin-sulbactam (Unasyn). At completion of the antibiotic course, the patient’s symptoms have resolved.

LAPAROSCOPY’S DRAWBACKS

Complications of dropped stones, though rare, can include localized or systemic infection, inflammation, fibrosis, adhesion, cutaneous sinus formation, ileus, and abscess.^1,6 Lohan et al¹ estimated that dropped stones produce an intra-abdominal abscess in 0.6% to 2.9% of cases of dropped stones and bile spillage, based on reports by Rice et al⁴ and Morrin et al.⁷ Dropped stones should be recognized as a potential cause of intra-abdominal abscess in any cholecystectomy patient months or even years after the surgery. Also, these abscesses are not necessarily confined to the right upper quadrant: they can occur anywhere in the abdominal cavity.^5,7

Given the ever-increasing popularity of laparoscopic cholecystectomy, the problem of intra-abdominal abscess due to dropped gallstones will only become a more common problem. Early diagnosis is the key to avoiding long and unnecessary treatment.

If dropped gallstones do become infected and eventually cause symptoms, they may require surgical or percutaneous removal in conjunction with antimicrobial therapy.⁸

A 67-year-old retired man presents to his internist with a 3-month history of abdominal discomfort in the right upper quadrant on deep breathing. He has no other abdominal complaints, but he mentions that he underwent laparoscopic cholecystectomy 3 months ago for gallstone pancreatitis.

A biopsy specimen obtained with CT guidance shows chronic inflammation but is sterile on aerobic culture. There is no evidence of malignancy. Because of concern for underlying infection, the infectious disease staff recommends empirical treatment with a 4-week course of ampicillin-sulbactam (Unasyn). At completion of the antibiotic course, the patient’s symptoms have resolved.

LAPAROSCOPY’S DRAWBACKS

Complications of dropped stones, though rare, can include localized or systemic infection, inflammation, fibrosis, adhesion, cutaneous sinus formation, ileus, and abscess.^1,6 Lohan et al¹ estimated that dropped stones produce an intra-abdominal abscess in 0.6% to 2.9% of cases of dropped stones and bile spillage, based on reports by Rice et al⁴ and Morrin et al.⁷ Dropped stones should be recognized as a potential cause of intra-abdominal abscess in any cholecystectomy patient months or even years after the surgery. Also, these abscesses are not necessarily confined to the right upper quadrant: they can occur anywhere in the abdominal cavity.^5,7

Given the ever-increasing popularity of laparoscopic cholecystectomy, the problem of intra-abdominal abscess due to dropped gallstones will only become a more common problem. Early diagnosis is the key to avoiding long and unnecessary treatment.

If dropped gallstones do become infected and eventually cause symptoms, they may require surgical or percutaneous removal in conjunction with antimicrobial therapy.⁸

The “gliptins”—the nickname for dipeptidyl peptidase 4 (DPP-4) inhibitors—are one of the newest classes of drugs for the treatment of type 2 diabetes mellitus.

These drugs work by prolonging the action of gut hormones called incretins, which boost insulin levels. The greatest advantage of the gliptins appears to be their ability to stimulate insulin production with little risk of corresponding hypoglycemia.

Sitagliptin (Januvia), the first commercially available DPP-4 inhibitor, has been approved by the US Food and Drug Administration (FDA) and is currently in clinical use, and vildagliptin (Galvus) awaits FDA approval at the time of this writing. Other drugs of this class are in development.

However, because these drugs are so new, a number of questions remain about their use. In this article, we discuss the rationale behind gliptin drugs, the evidence to date on their use alone or in combination with current oral hypoglycemic drugs (and even with insulin), and when and how to use them in daily practice.

THE NEED FOR MORE EFFECTIVE DIABETES TREATMENT

As the number of patients with type 2 diabetes continues its steep and steady rise,^1,2 much work has gone into studying treatment goals and how to achieve them. Although experts generally agree on glycemic goals,³ we currently fail to achieve those goals in close to two-thirds of patients: only 37% have a hemo-globin A_1c (HbA_1c) value at or below the goal of 7%, and the same number have levels exceeding 8%.⁴

Part of the problem is that treatment regimens are not adjusted in a timely fashion. In a prescribing database of almost 4,000 patients with type 2 diabetes,⁵ the mean time from the first HbA_1c reading above 8% to an actual change in therapy was about 15 months for those taking metformin (Glucophage) alone, and 21 months for those taking a sulfonylurea alone. Another part of the problem is that, on average, patients with an HbA_1c of 8.0% to 8.9% can expect only a 0.6% lowering with the addition of one agent.⁶ Clearly, we need new pharmacologic approaches and new management paradigms. One new approach is the use of gliptins.

HOW GLIPTINS WORK

Incretins promote insulin secretion

We have known for more than 20 years that insulin levels rise considerably higher in response to an oral glucose load than to an intravenous glucose infusion, even though the plasma glucose concentrations may be similar.⁷ This phenomenon involves a myriad of neural and nutritional factors, but the gut hormones glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) appear to be key.

These peptides—called incretins—have a high degree of homology, and both promote insulin secretion. However, GLP-1, produced by the L cells of the ileum and colon, inhibits glucagon secretion and slows gastric emptying, whereas GIP, secreted from the K cells of the duodenum, has no effect on glucagon and little effect on gastric emptying. Both peptides appear to promote pancreatic beta cell growth and survival,^8,9 an effect that in theory might allow us to slow the progressive loss of insulin secretory capacity in type 2 diabetes.

Furthermore, the effect of GLP-1 on insulin secretion depends on the plasma glucose concentration, with a greater insulin secretory effect at higher glucose levels and minimal effect at euglycemic levels.¹⁰ This phenomenon suggests that drugs that boost GLP-1 activity should not cause the troublesome hypoglycemia typically seen in patients taking insulin, insulin secretagogues, sulfonyl-ureas, or the meglitinides repaglinide (Prandin) or nateglinide (Starlix). Studies of combination treatment with metformin and the GLP-1 receptor agonist exenatide (Byetta) have shown little risk of hypoglycemia,¹¹ offering evidence favoring this conjecture.

Inhibition of DPP-4 boosts incretin action

The challenge for creating treatments that take advantage of the beneficial effects of GLP-1 and GIP is that they have very short physiologic half-lives, ie, less than 10 minutes. GLP-1 and GIP both have two N-terminal amino acids that are quickly cleaved by DPP-4,¹² an enzyme present in the circulation¹³ and on endothelial cells.¹⁴

Currently, there are two classes of drugs based on incretins. One class, the incretin mimetics or GLP-1 receptor agonists, includes drugs that mimic the effect of GLP-1 but are not so quickly degraded by DPP-4. Examples of these drugs are exenatide, which is currently FDA-approved, and liraglutide, which is not yet approved.

On the other hand, by inhibiting the cleaving action of DPP-4, the gliptins can prolong the half-life of endogenous GLP-1, increasing its physiologic effects.

Studies comparing gliptins with GLP-1 receptor agonists are only at the preclinical phase. Liraglutide showed an antiglycemic effect similar to that of vildagliptin in an animal model of glucose intolerance.¹⁵ This and other^16,17 preclinical studies have shown evidence of improved beta cell growth and survival with DPP-4 inhibitor treatment, to an extent similar to that reported with thiazo-lidinediones, whereas sulfonylureas show no evidence either of increase in beta cells or of improved intrinsic beta cell secretory function in these models. Of course, animal studies can only be cautiously extrapolated to potential effects in humans, and it is uncertain whether such benefits will occur with the therapeutic use of DPP-4 inhibitors.

RANDOMIZED CLINICAL TRIALS OF SITAGLIPTIN

Sitagliptin is effective when used by itself,reducing a baseline HbA1c level of about 8% by 0.6% to 0.8%,^19,20,24 and is similarly effective when combined with metformin^21,22,25 or pioglitazone (Actos, a thiazolidinedione).²³ It also decreases fasting blood glucose levels and improves other measures of glucose control.

A study comparing sitagliptin and the sul-fonylurea glipizide (Glucotrol) showed identical glucose-lowering over a 1-year period, with less hypoglycemia and weight gain with sitagliptin.²⁵ Hypoglycemic episodes occurred in 32% of patients taking glipizide but in only 5% of those taking sitagliptin.

Studies noted several trends in laboratory values, though none was associated with clinical evidence of adverse outcome:

• White blood cell counts were noted to increase in three of the studies by 4.7% to 10%, owing to increases in neutro-phils^19,20,22
• Alkaline phosphatase concentrations decreased in four studies^19,20,22,23
• Uric acid levels increased in four studies.^19,20,22,23

RENAL INSUFFICIENCY SLOWS SITAGLIPTIN CLEARANCE

Lower doses and periodic monitoring of renal function are recommended in patients taking sitagliptin who have some degree of renal insufficiency. Clearance of sitagliptin is delayed in patients with renal insufficiency (creatinine clearance < 50 mL/minute).

In a placebo-controlled study of sitagliptin safety, Scott et al²⁶ found that the area under the sitagliptin concentration-time curve was 2.3 times greater in patients with moderate renal insufficiency (creatinine clearance rate 30–49.9 mL/minute), 3.8 times greater in those with severe renal insufficiency (15–29.9 mL/minute), and 4.5 times greater in those with end-stage renal disease (< 15 mL/minute).

The Januvia package insert²⁷ recommends that the daily dose be decreased to 50 mg in patients with creatinine clearance rates of 30 to 49.9 mL/minute (serum creatinine > 1.7 mg/dL in men, > 1.5 mg/dL in women), and that the dose be decreased to 25 mg per day in those with creatinine clearance rates below 30 mL/minute (creatinine > 3.0/2.5 mg/dL).

CLINICAL TRIALS OF VILDAGLIPTIN BEGIN

A study comparing vildagliptin against metformin³⁴ showed less glucose-lowering over a 1-year period with vildagliptin, albeit with fewer gastrointestinal side effects, while comparisons with rosiglitazone (Avandia)³⁵ and with pioglitazone³⁶ showed similar glucose-lowering ability.

In a 24-week study,³³ 256 patients with type 2 diabetes who had a mean body mass index of 33 kg/m² and who were taking more than 30 units of insulin daily (an average of 82 units) were randomized to additionally receive either vildagliptin 50 mg twice daily or placebo. The HbA_1c decreased by 0.5% with vildagliptin and by 0.2% with placebo, from a baseline level of 8.5%. Of interest, 33 patients receiving vildagliptin had a hypo-glycemic episode (a total of 113 events), compared with 45 patients in the placebo group (185 events). None of the episodes in the vildagliptin group was classified as severe, whereas six episodes in the placebo group were classified as severe. This suggests that adding vildagliptin in patients taking insulin can improve glycemia without causing excessive hypoglycemia.

A weakness of the design of this study is that it did not include patients who were receiving an insulin sensitizer, an approach that is typically taken. Given this, it is understandable that overall glycemic control was relatively poor. More effort is needed to explore the use of gliptins with insulin.

WHAT ROLE FOR GLIPTINS?

The evidence from the studies reviewed in this article suggests that gliptins can play an important role in the treatment of type 2 diabetes. In certain patient groups such as the elderly, who cannot take either metformin or a thiazolidinedione and in whom concerns about hypoglycemia are greatest, thus precluding sulfonylurea therapy, gliptins may be the agents of choice. The trials reviewed here suggest that gliptins have glucose-lowering efficacy similar to that of these classes of agents. Gliptins are also effective when combined with metformin or a thiazolidinedione and, as discussed above, may prove to be useful in combination with insulin.

The eventual role of gliptins in the treatment of type 2 diabetes will depend on the answers to several questions. For example, do they preserve beta cell function and reverse the progression of diabetes? Do they affect insulin resistance? Do they have cardiovascular benefits beyond glucose-lowering? Also, since DPP-4 is widely distributed in the body, and since we do not yet know the effects of all the proteins cleaved by this enzyme, will this affect the long-term safety of these drugs?

For now, we can state with reasonable certainty that gliptins lower blood sugar levels to a degree similar to that of other oral hypo-glycemic therapies, with minimal risk of hypo-glycemia, with few immediate adverse effects, and without requiring dose titration. These characteristics suggest that gliptins should be considered useful agents in monotherapy and combination therapy for the treatment of type 2 diabetes.

The “gliptins”—the nickname for dipeptidyl peptidase 4 (DPP-4) inhibitors—are one of the newest classes of drugs for the treatment of type 2 diabetes mellitus.

These drugs work by prolonging the action of gut hormones called incretins, which boost insulin levels. The greatest advantage of the gliptins appears to be their ability to stimulate insulin production with little risk of corresponding hypoglycemia.

Sitagliptin (Januvia), the first commercially available DPP-4 inhibitor, has been approved by the US Food and Drug Administration (FDA) and is currently in clinical use, and vildagliptin (Galvus) awaits FDA approval at the time of this writing. Other drugs of this class are in development.

However, because these drugs are so new, a number of questions remain about their use. In this article, we discuss the rationale behind gliptin drugs, the evidence to date on their use alone or in combination with current oral hypoglycemic drugs (and even with insulin), and when and how to use them in daily practice.

THE NEED FOR MORE EFFECTIVE DIABETES TREATMENT

As the number of patients with type 2 diabetes continues its steep and steady rise,^1,2 much work has gone into studying treatment goals and how to achieve them. Although experts generally agree on glycemic goals,³ we currently fail to achieve those goals in close to two-thirds of patients: only 37% have a hemo-globin A_1c (HbA_1c) value at or below the goal of 7%, and the same number have levels exceeding 8%.⁴

Part of the problem is that treatment regimens are not adjusted in a timely fashion. In a prescribing database of almost 4,000 patients with type 2 diabetes,⁵ the mean time from the first HbA_1c reading above 8% to an actual change in therapy was about 15 months for those taking metformin (Glucophage) alone, and 21 months for those taking a sulfonylurea alone. Another part of the problem is that, on average, patients with an HbA_1c of 8.0% to 8.9% can expect only a 0.6% lowering with the addition of one agent.⁶ Clearly, we need new pharmacologic approaches and new management paradigms. One new approach is the use of gliptins.

HOW GLIPTINS WORK

Incretins promote insulin secretion

We have known for more than 20 years that insulin levels rise considerably higher in response to an oral glucose load than to an intravenous glucose infusion, even though the plasma glucose concentrations may be similar.⁷ This phenomenon involves a myriad of neural and nutritional factors, but the gut hormones glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) appear to be key.

These peptides—called incretins—have a high degree of homology, and both promote insulin secretion. However, GLP-1, produced by the L cells of the ileum and colon, inhibits glucagon secretion and slows gastric emptying, whereas GIP, secreted from the K cells of the duodenum, has no effect on glucagon and little effect on gastric emptying. Both peptides appear to promote pancreatic beta cell growth and survival,^8,9 an effect that in theory might allow us to slow the progressive loss of insulin secretory capacity in type 2 diabetes.

Furthermore, the effect of GLP-1 on insulin secretion depends on the plasma glucose concentration, with a greater insulin secretory effect at higher glucose levels and minimal effect at euglycemic levels.¹⁰ This phenomenon suggests that drugs that boost GLP-1 activity should not cause the troublesome hypoglycemia typically seen in patients taking insulin, insulin secretagogues, sulfonyl-ureas, or the meglitinides repaglinide (Prandin) or nateglinide (Starlix). Studies of combination treatment with metformin and the GLP-1 receptor agonist exenatide (Byetta) have shown little risk of hypoglycemia,¹¹ offering evidence favoring this conjecture.

Inhibition of DPP-4 boosts incretin action

The challenge for creating treatments that take advantage of the beneficial effects of GLP-1 and GIP is that they have very short physiologic half-lives, ie, less than 10 minutes. GLP-1 and GIP both have two N-terminal amino acids that are quickly cleaved by DPP-4,¹² an enzyme present in the circulation¹³ and on endothelial cells.¹⁴

Currently, there are two classes of drugs based on incretins. One class, the incretin mimetics or GLP-1 receptor agonists, includes drugs that mimic the effect of GLP-1 but are not so quickly degraded by DPP-4. Examples of these drugs are exenatide, which is currently FDA-approved, and liraglutide, which is not yet approved.

On the other hand, by inhibiting the cleaving action of DPP-4, the gliptins can prolong the half-life of endogenous GLP-1, increasing its physiologic effects.

Studies comparing gliptins with GLP-1 receptor agonists are only at the preclinical phase. Liraglutide showed an antiglycemic effect similar to that of vildagliptin in an animal model of glucose intolerance.¹⁵ This and other^16,17 preclinical studies have shown evidence of improved beta cell growth and survival with DPP-4 inhibitor treatment, to an extent similar to that reported with thiazo-lidinediones, whereas sulfonylureas show no evidence either of increase in beta cells or of improved intrinsic beta cell secretory function in these models. Of course, animal studies can only be cautiously extrapolated to potential effects in humans, and it is uncertain whether such benefits will occur with the therapeutic use of DPP-4 inhibitors.

RANDOMIZED CLINICAL TRIALS OF SITAGLIPTIN

Sitagliptin is effective when used by itself,reducing a baseline HbA1c level of about 8% by 0.6% to 0.8%,^19,20,24 and is similarly effective when combined with metformin^21,22,25 or pioglitazone (Actos, a thiazolidinedione).²³ It also decreases fasting blood glucose levels and improves other measures of glucose control.

A study comparing sitagliptin and the sul-fonylurea glipizide (Glucotrol) showed identical glucose-lowering over a 1-year period, with less hypoglycemia and weight gain with sitagliptin.²⁵ Hypoglycemic episodes occurred in 32% of patients taking glipizide but in only 5% of those taking sitagliptin.

Studies noted several trends in laboratory values, though none was associated with clinical evidence of adverse outcome:

• White blood cell counts were noted to increase in three of the studies by 4.7% to 10%, owing to increases in neutro-phils^19,20,22
• Alkaline phosphatase concentrations decreased in four studies^19,20,22,23
• Uric acid levels increased in four studies.^19,20,22,23

RENAL INSUFFICIENCY SLOWS SITAGLIPTIN CLEARANCE

Lower doses and periodic monitoring of renal function are recommended in patients taking sitagliptin who have some degree of renal insufficiency. Clearance of sitagliptin is delayed in patients with renal insufficiency (creatinine clearance < 50 mL/minute).

In a placebo-controlled study of sitagliptin safety, Scott et al²⁶ found that the area under the sitagliptin concentration-time curve was 2.3 times greater in patients with moderate renal insufficiency (creatinine clearance rate 30–49.9 mL/minute), 3.8 times greater in those with severe renal insufficiency (15–29.9 mL/minute), and 4.5 times greater in those with end-stage renal disease (< 15 mL/minute).

The Januvia package insert²⁷ recommends that the daily dose be decreased to 50 mg in patients with creatinine clearance rates of 30 to 49.9 mL/minute (serum creatinine > 1.7 mg/dL in men, > 1.5 mg/dL in women), and that the dose be decreased to 25 mg per day in those with creatinine clearance rates below 30 mL/minute (creatinine > 3.0/2.5 mg/dL).

CLINICAL TRIALS OF VILDAGLIPTIN BEGIN

A study comparing vildagliptin against metformin³⁴ showed less glucose-lowering over a 1-year period with vildagliptin, albeit with fewer gastrointestinal side effects, while comparisons with rosiglitazone (Avandia)³⁵ and with pioglitazone³⁶ showed similar glucose-lowering ability.

In a 24-week study,³³ 256 patients with type 2 diabetes who had a mean body mass index of 33 kg/m² and who were taking more than 30 units of insulin daily (an average of 82 units) were randomized to additionally receive either vildagliptin 50 mg twice daily or placebo. The HbA_1c decreased by 0.5% with vildagliptin and by 0.2% with placebo, from a baseline level of 8.5%. Of interest, 33 patients receiving vildagliptin had a hypo-glycemic episode (a total of 113 events), compared with 45 patients in the placebo group (185 events). None of the episodes in the vildagliptin group was classified as severe, whereas six episodes in the placebo group were classified as severe. This suggests that adding vildagliptin in patients taking insulin can improve glycemia without causing excessive hypoglycemia.

A weakness of the design of this study is that it did not include patients who were receiving an insulin sensitizer, an approach that is typically taken. Given this, it is understandable that overall glycemic control was relatively poor. More effort is needed to explore the use of gliptins with insulin.

WHAT ROLE FOR GLIPTINS?

The evidence from the studies reviewed in this article suggests that gliptins can play an important role in the treatment of type 2 diabetes. In certain patient groups such as the elderly, who cannot take either metformin or a thiazolidinedione and in whom concerns about hypoglycemia are greatest, thus precluding sulfonylurea therapy, gliptins may be the agents of choice. The trials reviewed here suggest that gliptins have glucose-lowering efficacy similar to that of these classes of agents. Gliptins are also effective when combined with metformin or a thiazolidinedione and, as discussed above, may prove to be useful in combination with insulin.

The eventual role of gliptins in the treatment of type 2 diabetes will depend on the answers to several questions. For example, do they preserve beta cell function and reverse the progression of diabetes? Do they affect insulin resistance? Do they have cardiovascular benefits beyond glucose-lowering? Also, since DPP-4 is widely distributed in the body, and since we do not yet know the effects of all the proteins cleaved by this enzyme, will this affect the long-term safety of these drugs?

For now, we can state with reasonable certainty that gliptins lower blood sugar levels to a degree similar to that of other oral hypo-glycemic therapies, with minimal risk of hypo-glycemia, with few immediate adverse effects, and without requiring dose titration. These characteristics suggest that gliptins should be considered useful agents in monotherapy and combination therapy for the treatment of type 2 diabetes.

The “gliptins”—the nickname for dipeptidyl peptidase 4 (DPP-4) inhibitors—are one of the newest classes of drugs for the treatment of type 2 diabetes mellitus.

These drugs work by prolonging the action of gut hormones called incretins, which boost insulin levels. The greatest advantage of the gliptins appears to be their ability to stimulate insulin production with little risk of corresponding hypoglycemia.

Sitagliptin (Januvia), the first commercially available DPP-4 inhibitor, has been approved by the US Food and Drug Administration (FDA) and is currently in clinical use, and vildagliptin (Galvus) awaits FDA approval at the time of this writing. Other drugs of this class are in development.

However, because these drugs are so new, a number of questions remain about their use. In this article, we discuss the rationale behind gliptin drugs, the evidence to date on their use alone or in combination with current oral hypoglycemic drugs (and even with insulin), and when and how to use them in daily practice.

THE NEED FOR MORE EFFECTIVE DIABETES TREATMENT

As the number of patients with type 2 diabetes continues its steep and steady rise,^1,2 much work has gone into studying treatment goals and how to achieve them. Although experts generally agree on glycemic goals,³ we currently fail to achieve those goals in close to two-thirds of patients: only 37% have a hemo-globin A_1c (HbA_1c) value at or below the goal of 7%, and the same number have levels exceeding 8%.⁴

Part of the problem is that treatment regimens are not adjusted in a timely fashion. In a prescribing database of almost 4,000 patients with type 2 diabetes,⁵ the mean time from the first HbA_1c reading above 8% to an actual change in therapy was about 15 months for those taking metformin (Glucophage) alone, and 21 months for those taking a sulfonylurea alone. Another part of the problem is that, on average, patients with an HbA_1c of 8.0% to 8.9% can expect only a 0.6% lowering with the addition of one agent.⁶ Clearly, we need new pharmacologic approaches and new management paradigms. One new approach is the use of gliptins.

HOW GLIPTINS WORK

Incretins promote insulin secretion

We have known for more than 20 years that insulin levels rise considerably higher in response to an oral glucose load than to an intravenous glucose infusion, even though the plasma glucose concentrations may be similar.⁷ This phenomenon involves a myriad of neural and nutritional factors, but the gut hormones glucagon-like peptide 1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP) appear to be key.

These peptides—called incretins—have a high degree of homology, and both promote insulin secretion. However, GLP-1, produced by the L cells of the ileum and colon, inhibits glucagon secretion and slows gastric emptying, whereas GIP, secreted from the K cells of the duodenum, has no effect on glucagon and little effect on gastric emptying. Both peptides appear to promote pancreatic beta cell growth and survival,^8,9 an effect that in theory might allow us to slow the progressive loss of insulin secretory capacity in type 2 diabetes.

Furthermore, the effect of GLP-1 on insulin secretion depends on the plasma glucose concentration, with a greater insulin secretory effect at higher glucose levels and minimal effect at euglycemic levels.¹⁰ This phenomenon suggests that drugs that boost GLP-1 activity should not cause the troublesome hypoglycemia typically seen in patients taking insulin, insulin secretagogues, sulfonyl-ureas, or the meglitinides repaglinide (Prandin) or nateglinide (Starlix). Studies of combination treatment with metformin and the GLP-1 receptor agonist exenatide (Byetta) have shown little risk of hypoglycemia,¹¹ offering evidence favoring this conjecture.

Inhibition of DPP-4 boosts incretin action

The challenge for creating treatments that take advantage of the beneficial effects of GLP-1 and GIP is that they have very short physiologic half-lives, ie, less than 10 minutes. GLP-1 and GIP both have two N-terminal amino acids that are quickly cleaved by DPP-4,¹² an enzyme present in the circulation¹³ and on endothelial cells.¹⁴

Currently, there are two classes of drugs based on incretins. One class, the incretin mimetics or GLP-1 receptor agonists, includes drugs that mimic the effect of GLP-1 but are not so quickly degraded by DPP-4. Examples of these drugs are exenatide, which is currently FDA-approved, and liraglutide, which is not yet approved.

On the other hand, by inhibiting the cleaving action of DPP-4, the gliptins can prolong the half-life of endogenous GLP-1, increasing its physiologic effects.

Studies comparing gliptins with GLP-1 receptor agonists are only at the preclinical phase. Liraglutide showed an antiglycemic effect similar to that of vildagliptin in an animal model of glucose intolerance.¹⁵ This and other^16,17 preclinical studies have shown evidence of improved beta cell growth and survival with DPP-4 inhibitor treatment, to an extent similar to that reported with thiazo-lidinediones, whereas sulfonylureas show no evidence either of increase in beta cells or of improved intrinsic beta cell secretory function in these models. Of course, animal studies can only be cautiously extrapolated to potential effects in humans, and it is uncertain whether such benefits will occur with the therapeutic use of DPP-4 inhibitors.

RANDOMIZED CLINICAL TRIALS OF SITAGLIPTIN

Sitagliptin is effective when used by itself,reducing a baseline HbA1c level of about 8% by 0.6% to 0.8%,^19,20,24 and is similarly effective when combined with metformin^21,22,25 or pioglitazone (Actos, a thiazolidinedione).²³ It also decreases fasting blood glucose levels and improves other measures of glucose control.

A study comparing sitagliptin and the sul-fonylurea glipizide (Glucotrol) showed identical glucose-lowering over a 1-year period, with less hypoglycemia and weight gain with sitagliptin.²⁵ Hypoglycemic episodes occurred in 32% of patients taking glipizide but in only 5% of those taking sitagliptin.

Studies noted several trends in laboratory values, though none was associated with clinical evidence of adverse outcome:

• White blood cell counts were noted to increase in three of the studies by 4.7% to 10%, owing to increases in neutro-phils^19,20,22
• Alkaline phosphatase concentrations decreased in four studies^19,20,22,23
• Uric acid levels increased in four studies.^19,20,22,23

RENAL INSUFFICIENCY SLOWS SITAGLIPTIN CLEARANCE

Lower doses and periodic monitoring of renal function are recommended in patients taking sitagliptin who have some degree of renal insufficiency. Clearance of sitagliptin is delayed in patients with renal insufficiency (creatinine clearance < 50 mL/minute).

In a placebo-controlled study of sitagliptin safety, Scott et al²⁶ found that the area under the sitagliptin concentration-time curve was 2.3 times greater in patients with moderate renal insufficiency (creatinine clearance rate 30–49.9 mL/minute), 3.8 times greater in those with severe renal insufficiency (15–29.9 mL/minute), and 4.5 times greater in those with end-stage renal disease (< 15 mL/minute).

The Januvia package insert²⁷ recommends that the daily dose be decreased to 50 mg in patients with creatinine clearance rates of 30 to 49.9 mL/minute (serum creatinine > 1.7 mg/dL in men, > 1.5 mg/dL in women), and that the dose be decreased to 25 mg per day in those with creatinine clearance rates below 30 mL/minute (creatinine > 3.0/2.5 mg/dL).

CLINICAL TRIALS OF VILDAGLIPTIN BEGIN

A study comparing vildagliptin against metformin³⁴ showed less glucose-lowering over a 1-year period with vildagliptin, albeit with fewer gastrointestinal side effects, while comparisons with rosiglitazone (Avandia)³⁵ and with pioglitazone³⁶ showed similar glucose-lowering ability.

In a 24-week study,³³ 256 patients with type 2 diabetes who had a mean body mass index of 33 kg/m² and who were taking more than 30 units of insulin daily (an average of 82 units) were randomized to additionally receive either vildagliptin 50 mg twice daily or placebo. The HbA_1c decreased by 0.5% with vildagliptin and by 0.2% with placebo, from a baseline level of 8.5%. Of interest, 33 patients receiving vildagliptin had a hypo-glycemic episode (a total of 113 events), compared with 45 patients in the placebo group (185 events). None of the episodes in the vildagliptin group was classified as severe, whereas six episodes in the placebo group were classified as severe. This suggests that adding vildagliptin in patients taking insulin can improve glycemia without causing excessive hypoglycemia.

A weakness of the design of this study is that it did not include patients who were receiving an insulin sensitizer, an approach that is typically taken. Given this, it is understandable that overall glycemic control was relatively poor. More effort is needed to explore the use of gliptins with insulin.

WHAT ROLE FOR GLIPTINS?

The evidence from the studies reviewed in this article suggests that gliptins can play an important role in the treatment of type 2 diabetes. In certain patient groups such as the elderly, who cannot take either metformin or a thiazolidinedione and in whom concerns about hypoglycemia are greatest, thus precluding sulfonylurea therapy, gliptins may be the agents of choice. The trials reviewed here suggest that gliptins have glucose-lowering efficacy similar to that of these classes of agents. Gliptins are also effective when combined with metformin or a thiazolidinedione and, as discussed above, may prove to be useful in combination with insulin.

The eventual role of gliptins in the treatment of type 2 diabetes will depend on the answers to several questions. For example, do they preserve beta cell function and reverse the progression of diabetes? Do they affect insulin resistance? Do they have cardiovascular benefits beyond glucose-lowering? Also, since DPP-4 is widely distributed in the body, and since we do not yet know the effects of all the proteins cleaved by this enzyme, will this affect the long-term safety of these drugs?

For now, we can state with reasonable certainty that gliptins lower blood sugar levels to a degree similar to that of other oral hypo-glycemic therapies, with minimal risk of hypo-glycemia, with few immediate adverse effects, and without requiring dose titration. These characteristics suggest that gliptins should be considered useful agents in monotherapy and combination therapy for the treatment of type 2 diabetes.

In patients at risk of myocardial infarction or stroke, two antiplatelet drugs are not always better than one. In a large recent trial,^1,2 adding clopidogrel (Plavix) to aspirin therapy did not offer much benefit to a cohort of patients at risk of cardiovascular events, although a subgroup did appear to benefit: those at even higher risk because they already had a history of myocardial infarction, ischemic stroke, or peripheral arterial disease.

These were the principal findings in the Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance (CHARISMA) study,^1,2 in which one of us (D.L.B.) was principal investigator.

These findings further our understanding of who should receive dual antiplatelet therapy, and who would be better served with aspirin therapy alone. In this article, we discuss important studies that led up to the CHARISMA trial, review CHARISMA’s purpose and study design, and interpret its results.

PREVENTING ATHEROTHROMBOSIS BY BLOCKING PLATELETS

Platelets are key players in the atherothrom-botic process.^3–5 The Antiplatelet Trialists’ Collaboration,⁶ in a meta-analysis of trials performed up to 1997, calculated that antiplatelet therapy (mostly with aspirin) reduced the vascular mortality rate by 15% in patients with acute or previous vascular disease or some other predisposing condition. Thus, aspirin has already been shown to be effective as primary prevention (ie, in patients at risk but without established vascular disease) and as secondary prevention (ie, in those with established disease).^7,8

Yet many patients have significant vascular events in spite of taking aspirin.⁶ Aspirin failure is thought to be multifactorial, with causes that include weak platelet inhibition, noncompliance, discontinuation due to adverse effects (including severe bleeding), and drug interactions. In addition, aspirin resistance has been linked to worse prognosis and may prove to be another cause of aspirin failure.^9–11

Clopidogrel, an adenosine diphosphate (ADP) receptor antagonist, has also been studied extensively as an antiplatelet agent.^5,12 Several studies have indicated that clopidogrel and ticlopidine (Ticlid, a related drug) may be more potent than aspirin, both in the test tube and in real patients.^13–15

KEY TRIALS LEADING TO CHARISMA

• Clopidogrel is more effective and slightly safer than aspirin as secondary prevention, as shown in the Clopidogrel Versus Aspirin in Patients at Risk of Ischemic Events (CAPRIE) trial.^16–21
• The combination of clopidogrel plus aspirin is more beneficial than placebo plus aspirin in patients with acute coronary syndromes, as shown in the Clopidogrel in Unstable Angina to Prevent Recurrent Ischemic Events (CURE) trial,^22–24 the Clopidogrel as Adjunctive Reperfusion Therapy-Thrombolysis in Myo-car-dial Infarction (CLARITY-TIMI 28) trial,²⁵ and the Clopidogrel and Metoprolol in Myocardial Infarction Trial (COMMIT).²⁶
• The combination of clopidogrel plus aspirin is beneficial in patients undergoing percutaneous coronary interventions, with or without drug-eluting stent placement,^27–30 as shown in the Clopidogrel for the Reduction of Events During Observation (CREDO) trial,²⁸ the Effect of Clopidogrel Pretreatment Before Percutaneous Coronary Intervention in Patients With ST-Elevation Myocardial Infarction With Fibrinolytics (PCI-CLARITY) study,²⁹ and the Effects of Pre-treatment With Clopidogrel and Aspirin Followed by Long-term Therapy in Patients Undergoing Percutaneous Coronary Intervention (PCI-CURE) study.³⁰ In fact, most patients undergoing percutaneous interventions now receive a loading dose of clopidogrel before the procedure and continue to take it for up to 1 year afterward. However, the ideal long-term duration of clopidogrel treatment is still under debate.

In view of these previous studies, we wanted to test dual antiplatelet therapy in a broader population at high risk of atherothrombosis, ie, in patients with either established vascular disease or with multiple risk factors for it.

CHARISMA STUDY DESIGN

CHARISMA was a prospective, randomized, double-blind, placebo-controlled study of the efficacy and safety of clopidogrel plus aspirin vs placebo plus aspirin in patients at high risk of cardiovascular events.

A total of 15,603 patients, all older than 45 years, were randomly assigned to receive clopidogrel 75 mg/day plus aspirin 75 to 162 mg/day or placebo plus aspirin, in addition to standard therapy as directed by individual clinicians (eg, statins, beta-blockers). Patients were followed up at 1, 3, and 6 months and every 6 months thereafter until study completion, which occurred after 1,040 primary efficacy end points. The median duration of follow-up was 28 months.¹

Patients had to have one of the following to be included: multiple atherothrombotic risk factors, documented coronary disease, documented cerebrovascular disease, or documented peripheral arterial disease (Table 2). Specific exclusion criteria included the use of oral antithrombotic or chronic nonsteroidal anti-inflammatory medications.¹

End points

The primary end point was the combined incidence of the first episode of myocardial infarction or stroke, or death from cardiovascular causes.

The secondary end point was the combined incidence of myocardial infarction, stroke, death from cardiovascular causes, or hospitalization for unstable angina, a transient ischemic attack, or revascularization procedure.

The primary safety end point was severe bleeding, as defined in the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO) study³¹ as intracranial hemorrhage, fatal bleeding, or bleeding leading to hemody-namic compromise. Moderate bleeding was defined as bleeding that required transfusion but did not meet the GUSTO definition of severe bleeding.

OVERALL, NO BENEFIT

The rates of the secondary end point were 16.7% vs 17.9% (absolute risk reduction 1.2%; relative risk reduction 8%; P = .04).

Possible benefit in symptomatic patients

In a prespecified analysis, patients were classified as being “symptomatic” (having documented cardiovascular disease, ie, coronary, cerebrovascular, or symptomatic peripheral arterial disease) or “asymptomatic” (having multiple risk factors without established cardiovascular disease).¹

In the symptomatic group (n = 12,153), the primary end point was reached in 6.9% of patients treated with clopidogrel vs 7.9% with placebo (absolute risk reduction 1.0%; relative risk reduction 13%; P = .046). The 3,284 asymptomatic patients showed no benefit; the rate of the primary end point for the clopido-grel group was 6.6% vs 5.5% in the placebo group (P = .20).

In a post hoc analysis, we examined the data from 9,478 patients who were similar to those in the CAPRIE study (ie, with documented prior myocardial infarction, prior ischemic stroke, or symptomatic peripheral arterial disease). The rate of cardiovascular death, myocardial infarction, or stroke was 8.8% in the placebo-plus-aspirin group and 7.3% in the clopidogrel-plus-aspirin group (absolute risk reduction 1.5%; relative risk reduction 17%; P = .01; Figure 1).²

HOW SHOULD WE INTERPRET THESE FINDINGS?

CHARISMA was the first trial to evaluate whether adding clopidogrel to aspirin therapy would reduce the rates of vascular events and death from cardiovascular causes in stable patients at risk of ischemic events. As in other trials, the benefit of clopidogrel-plus-aspirin therapy was weighed against the risk of bleeding with this regimen. How are we to interpret the findings?

• In the group with multiple risk factors but without clearly documented cardiovascular disease, there was no benefit—and there was an increase in moderate bleeding. Given these findings, physicians should not prescribe dual antiplatelet therapy for primary prevention in patients without known vascular disease.
• A potential benefit was seen in a prespecified subgroup who had documented cardiovascular disease. Given the limitations of subgroup analysis, however, and given the increased risk of moderate bleeding, this positive result should be interpreted with some degree of caution.
• CHARISMA suggests that there may be benefit of protracted dual antiplatelet therapy in stable patients with documented prior ischemic events.

A possible reason for the observed lack of benefit in the overall cohort but the positive results in the subgroups with established vascular disease is that plaque rupture and thrombosis may be a precondition for dual antiplatelet therapy to work.

Another possibility is that, although we have been saying that diabetes mellitus (one of the possible entry criteria in CHARISMA) is a “coronary risk equivalent,” this may not be absolutely true. Although it had been demonstrated that patients with certain risk factors, such as diabetes, have an incidence of ischemic events similar to that in patients with prior MI and should be considered for antiplatelet therapy to prevent vascular events,³² more recent data have shown that patients with prior ischemic events are at much higher risk than patients without ischemic events, even if the latter have diabetes.^33,34

• The observation in CHARISMA that the incremental bleeding risk of dual antiplatelet therapy vs aspirin does not persist beyond a year in patients who have tolerated therapy for a year without a bleeding event may affect the decision to continue clopidogrel beyond 1 year, such as in patients with acute coronary syndromes or patients who have received drug-eluting stents.^35,36
• Another important consideration is cost-effectiveness. Several studies have analyzed the impact of cost and found clopidogrel to be cost-effective by preventing ischemic events and adding years of life.^37,38 A recent analysis from CHARISMA also shows cost-effectiveness in the subgroup of patients enrolled with established cardiovascular disease.³⁹ Once clopidogrel becomes generic, the cost-effectiveness will become even better.

Further studies should better define which stable patients with cardiovascular disease should be on more than aspirin alone.

In patients at risk of myocardial infarction or stroke, two antiplatelet drugs are not always better than one. In a large recent trial,^1,2 adding clopidogrel (Plavix) to aspirin therapy did not offer much benefit to a cohort of patients at risk of cardiovascular events, although a subgroup did appear to benefit: those at even higher risk because they already had a history of myocardial infarction, ischemic stroke, or peripheral arterial disease.

These were the principal findings in the Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance (CHARISMA) study,^1,2 in which one of us (D.L.B.) was principal investigator.

These findings further our understanding of who should receive dual antiplatelet therapy, and who would be better served with aspirin therapy alone. In this article, we discuss important studies that led up to the CHARISMA trial, review CHARISMA’s purpose and study design, and interpret its results.

PREVENTING ATHEROTHROMBOSIS BY BLOCKING PLATELETS

Platelets are key players in the atherothrom-botic process.^3–5 The Antiplatelet Trialists’ Collaboration,⁶ in a meta-analysis of trials performed up to 1997, calculated that antiplatelet therapy (mostly with aspirin) reduced the vascular mortality rate by 15% in patients with acute or previous vascular disease or some other predisposing condition. Thus, aspirin has already been shown to be effective as primary prevention (ie, in patients at risk but without established vascular disease) and as secondary prevention (ie, in those with established disease).^7,8

Yet many patients have significant vascular events in spite of taking aspirin.⁶ Aspirin failure is thought to be multifactorial, with causes that include weak platelet inhibition, noncompliance, discontinuation due to adverse effects (including severe bleeding), and drug interactions. In addition, aspirin resistance has been linked to worse prognosis and may prove to be another cause of aspirin failure.^9–11

Clopidogrel, an adenosine diphosphate (ADP) receptor antagonist, has also been studied extensively as an antiplatelet agent.^5,12 Several studies have indicated that clopidogrel and ticlopidine (Ticlid, a related drug) may be more potent than aspirin, both in the test tube and in real patients.^13–15

KEY TRIALS LEADING TO CHARISMA

• Clopidogrel is more effective and slightly safer than aspirin as secondary prevention, as shown in the Clopidogrel Versus Aspirin in Patients at Risk of Ischemic Events (CAPRIE) trial.^16–21
• The combination of clopidogrel plus aspirin is more beneficial than placebo plus aspirin in patients with acute coronary syndromes, as shown in the Clopidogrel in Unstable Angina to Prevent Recurrent Ischemic Events (CURE) trial,^22–24 the Clopidogrel as Adjunctive Reperfusion Therapy-Thrombolysis in Myo-car-dial Infarction (CLARITY-TIMI 28) trial,²⁵ and the Clopidogrel and Metoprolol in Myocardial Infarction Trial (COMMIT).²⁶
• The combination of clopidogrel plus aspirin is beneficial in patients undergoing percutaneous coronary interventions, with or without drug-eluting stent placement,^27–30 as shown in the Clopidogrel for the Reduction of Events During Observation (CREDO) trial,²⁸ the Effect of Clopidogrel Pretreatment Before Percutaneous Coronary Intervention in Patients With ST-Elevation Myocardial Infarction With Fibrinolytics (PCI-CLARITY) study,²⁹ and the Effects of Pre-treatment With Clopidogrel and Aspirin Followed by Long-term Therapy in Patients Undergoing Percutaneous Coronary Intervention (PCI-CURE) study.³⁰ In fact, most patients undergoing percutaneous interventions now receive a loading dose of clopidogrel before the procedure and continue to take it for up to 1 year afterward. However, the ideal long-term duration of clopidogrel treatment is still under debate.

In view of these previous studies, we wanted to test dual antiplatelet therapy in a broader population at high risk of atherothrombosis, ie, in patients with either established vascular disease or with multiple risk factors for it.

CHARISMA STUDY DESIGN

CHARISMA was a prospective, randomized, double-blind, placebo-controlled study of the efficacy and safety of clopidogrel plus aspirin vs placebo plus aspirin in patients at high risk of cardiovascular events.

A total of 15,603 patients, all older than 45 years, were randomly assigned to receive clopidogrel 75 mg/day plus aspirin 75 to 162 mg/day or placebo plus aspirin, in addition to standard therapy as directed by individual clinicians (eg, statins, beta-blockers). Patients were followed up at 1, 3, and 6 months and every 6 months thereafter until study completion, which occurred after 1,040 primary efficacy end points. The median duration of follow-up was 28 months.¹

Patients had to have one of the following to be included: multiple atherothrombotic risk factors, documented coronary disease, documented cerebrovascular disease, or documented peripheral arterial disease (Table 2). Specific exclusion criteria included the use of oral antithrombotic or chronic nonsteroidal anti-inflammatory medications.¹

End points

The primary end point was the combined incidence of the first episode of myocardial infarction or stroke, or death from cardiovascular causes.

The secondary end point was the combined incidence of myocardial infarction, stroke, death from cardiovascular causes, or hospitalization for unstable angina, a transient ischemic attack, or revascularization procedure.

The primary safety end point was severe bleeding, as defined in the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO) study³¹ as intracranial hemorrhage, fatal bleeding, or bleeding leading to hemody-namic compromise. Moderate bleeding was defined as bleeding that required transfusion but did not meet the GUSTO definition of severe bleeding.

OVERALL, NO BENEFIT

The rates of the secondary end point were 16.7% vs 17.9% (absolute risk reduction 1.2%; relative risk reduction 8%; P = .04).

Possible benefit in symptomatic patients

In a prespecified analysis, patients were classified as being “symptomatic” (having documented cardiovascular disease, ie, coronary, cerebrovascular, or symptomatic peripheral arterial disease) or “asymptomatic” (having multiple risk factors without established cardiovascular disease).¹

In the symptomatic group (n = 12,153), the primary end point was reached in 6.9% of patients treated with clopidogrel vs 7.9% with placebo (absolute risk reduction 1.0%; relative risk reduction 13%; P = .046). The 3,284 asymptomatic patients showed no benefit; the rate of the primary end point for the clopido-grel group was 6.6% vs 5.5% in the placebo group (P = .20).

In a post hoc analysis, we examined the data from 9,478 patients who were similar to those in the CAPRIE study (ie, with documented prior myocardial infarction, prior ischemic stroke, or symptomatic peripheral arterial disease). The rate of cardiovascular death, myocardial infarction, or stroke was 8.8% in the placebo-plus-aspirin group and 7.3% in the clopidogrel-plus-aspirin group (absolute risk reduction 1.5%; relative risk reduction 17%; P = .01; Figure 1).²

HOW SHOULD WE INTERPRET THESE FINDINGS?

CHARISMA was the first trial to evaluate whether adding clopidogrel to aspirin therapy would reduce the rates of vascular events and death from cardiovascular causes in stable patients at risk of ischemic events. As in other trials, the benefit of clopidogrel-plus-aspirin therapy was weighed against the risk of bleeding with this regimen. How are we to interpret the findings?

• In the group with multiple risk factors but without clearly documented cardiovascular disease, there was no benefit—and there was an increase in moderate bleeding. Given these findings, physicians should not prescribe dual antiplatelet therapy for primary prevention in patients without known vascular disease.
• A potential benefit was seen in a prespecified subgroup who had documented cardiovascular disease. Given the limitations of subgroup analysis, however, and given the increased risk of moderate bleeding, this positive result should be interpreted with some degree of caution.
• CHARISMA suggests that there may be benefit of protracted dual antiplatelet therapy in stable patients with documented prior ischemic events.

A possible reason for the observed lack of benefit in the overall cohort but the positive results in the subgroups with established vascular disease is that plaque rupture and thrombosis may be a precondition for dual antiplatelet therapy to work.

Another possibility is that, although we have been saying that diabetes mellitus (one of the possible entry criteria in CHARISMA) is a “coronary risk equivalent,” this may not be absolutely true. Although it had been demonstrated that patients with certain risk factors, such as diabetes, have an incidence of ischemic events similar to that in patients with prior MI and should be considered for antiplatelet therapy to prevent vascular events,³² more recent data have shown that patients with prior ischemic events are at much higher risk than patients without ischemic events, even if the latter have diabetes.^33,34

• The observation in CHARISMA that the incremental bleeding risk of dual antiplatelet therapy vs aspirin does not persist beyond a year in patients who have tolerated therapy for a year without a bleeding event may affect the decision to continue clopidogrel beyond 1 year, such as in patients with acute coronary syndromes or patients who have received drug-eluting stents.^35,36
• Another important consideration is cost-effectiveness. Several studies have analyzed the impact of cost and found clopidogrel to be cost-effective by preventing ischemic events and adding years of life.^37,38 A recent analysis from CHARISMA also shows cost-effectiveness in the subgroup of patients enrolled with established cardiovascular disease.³⁹ Once clopidogrel becomes generic, the cost-effectiveness will become even better.

Further studies should better define which stable patients with cardiovascular disease should be on more than aspirin alone.

In patients at risk of myocardial infarction or stroke, two antiplatelet drugs are not always better than one. In a large recent trial,^1,2 adding clopidogrel (Plavix) to aspirin therapy did not offer much benefit to a cohort of patients at risk of cardiovascular events, although a subgroup did appear to benefit: those at even higher risk because they already had a history of myocardial infarction, ischemic stroke, or peripheral arterial disease.

These were the principal findings in the Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance (CHARISMA) study,^1,2 in which one of us (D.L.B.) was principal investigator.

These findings further our understanding of who should receive dual antiplatelet therapy, and who would be better served with aspirin therapy alone. In this article, we discuss important studies that led up to the CHARISMA trial, review CHARISMA’s purpose and study design, and interpret its results.

PREVENTING ATHEROTHROMBOSIS BY BLOCKING PLATELETS

Platelets are key players in the atherothrom-botic process.^3–5 The Antiplatelet Trialists’ Collaboration,⁶ in a meta-analysis of trials performed up to 1997, calculated that antiplatelet therapy (mostly with aspirin) reduced the vascular mortality rate by 15% in patients with acute or previous vascular disease or some other predisposing condition. Thus, aspirin has already been shown to be effective as primary prevention (ie, in patients at risk but without established vascular disease) and as secondary prevention (ie, in those with established disease).^7,8

Yet many patients have significant vascular events in spite of taking aspirin.⁶ Aspirin failure is thought to be multifactorial, with causes that include weak platelet inhibition, noncompliance, discontinuation due to adverse effects (including severe bleeding), and drug interactions. In addition, aspirin resistance has been linked to worse prognosis and may prove to be another cause of aspirin failure.^9–11

Clopidogrel, an adenosine diphosphate (ADP) receptor antagonist, has also been studied extensively as an antiplatelet agent.^5,12 Several studies have indicated that clopidogrel and ticlopidine (Ticlid, a related drug) may be more potent than aspirin, both in the test tube and in real patients.^13–15

KEY TRIALS LEADING TO CHARISMA

• Clopidogrel is more effective and slightly safer than aspirin as secondary prevention, as shown in the Clopidogrel Versus Aspirin in Patients at Risk of Ischemic Events (CAPRIE) trial.^16–21
• The combination of clopidogrel plus aspirin is more beneficial than placebo plus aspirin in patients with acute coronary syndromes, as shown in the Clopidogrel in Unstable Angina to Prevent Recurrent Ischemic Events (CURE) trial,^22–24 the Clopidogrel as Adjunctive Reperfusion Therapy-Thrombolysis in Myo-car-dial Infarction (CLARITY-TIMI 28) trial,²⁵ and the Clopidogrel and Metoprolol in Myocardial Infarction Trial (COMMIT).²⁶
• The combination of clopidogrel plus aspirin is beneficial in patients undergoing percutaneous coronary interventions, with or without drug-eluting stent placement,^27–30 as shown in the Clopidogrel for the Reduction of Events During Observation (CREDO) trial,²⁸ the Effect of Clopidogrel Pretreatment Before Percutaneous Coronary Intervention in Patients With ST-Elevation Myocardial Infarction With Fibrinolytics (PCI-CLARITY) study,²⁹ and the Effects of Pre-treatment With Clopidogrel and Aspirin Followed by Long-term Therapy in Patients Undergoing Percutaneous Coronary Intervention (PCI-CURE) study.³⁰ In fact, most patients undergoing percutaneous interventions now receive a loading dose of clopidogrel before the procedure and continue to take it for up to 1 year afterward. However, the ideal long-term duration of clopidogrel treatment is still under debate.

In view of these previous studies, we wanted to test dual antiplatelet therapy in a broader population at high risk of atherothrombosis, ie, in patients with either established vascular disease or with multiple risk factors for it.

CHARISMA STUDY DESIGN

CHARISMA was a prospective, randomized, double-blind, placebo-controlled study of the efficacy and safety of clopidogrel plus aspirin vs placebo plus aspirin in patients at high risk of cardiovascular events.

A total of 15,603 patients, all older than 45 years, were randomly assigned to receive clopidogrel 75 mg/day plus aspirin 75 to 162 mg/day or placebo plus aspirin, in addition to standard therapy as directed by individual clinicians (eg, statins, beta-blockers). Patients were followed up at 1, 3, and 6 months and every 6 months thereafter until study completion, which occurred after 1,040 primary efficacy end points. The median duration of follow-up was 28 months.¹

Patients had to have one of the following to be included: multiple atherothrombotic risk factors, documented coronary disease, documented cerebrovascular disease, or documented peripheral arterial disease (Table 2). Specific exclusion criteria included the use of oral antithrombotic or chronic nonsteroidal anti-inflammatory medications.¹

End points

The primary end point was the combined incidence of the first episode of myocardial infarction or stroke, or death from cardiovascular causes.

The secondary end point was the combined incidence of myocardial infarction, stroke, death from cardiovascular causes, or hospitalization for unstable angina, a transient ischemic attack, or revascularization procedure.

The primary safety end point was severe bleeding, as defined in the Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO) study³¹ as intracranial hemorrhage, fatal bleeding, or bleeding leading to hemody-namic compromise. Moderate bleeding was defined as bleeding that required transfusion but did not meet the GUSTO definition of severe bleeding.

OVERALL, NO BENEFIT

The rates of the secondary end point were 16.7% vs 17.9% (absolute risk reduction 1.2%; relative risk reduction 8%; P = .04).

Possible benefit in symptomatic patients

In a prespecified analysis, patients were classified as being “symptomatic” (having documented cardiovascular disease, ie, coronary, cerebrovascular, or symptomatic peripheral arterial disease) or “asymptomatic” (having multiple risk factors without established cardiovascular disease).¹

In the symptomatic group (n = 12,153), the primary end point was reached in 6.9% of patients treated with clopidogrel vs 7.9% with placebo (absolute risk reduction 1.0%; relative risk reduction 13%; P = .046). The 3,284 asymptomatic patients showed no benefit; the rate of the primary end point for the clopido-grel group was 6.6% vs 5.5% in the placebo group (P = .20).

In a post hoc analysis, we examined the data from 9,478 patients who were similar to those in the CAPRIE study (ie, with documented prior myocardial infarction, prior ischemic stroke, or symptomatic peripheral arterial disease). The rate of cardiovascular death, myocardial infarction, or stroke was 8.8% in the placebo-plus-aspirin group and 7.3% in the clopidogrel-plus-aspirin group (absolute risk reduction 1.5%; relative risk reduction 17%; P = .01; Figure 1).²

HOW SHOULD WE INTERPRET THESE FINDINGS?

CHARISMA was the first trial to evaluate whether adding clopidogrel to aspirin therapy would reduce the rates of vascular events and death from cardiovascular causes in stable patients at risk of ischemic events. As in other trials, the benefit of clopidogrel-plus-aspirin therapy was weighed against the risk of bleeding with this regimen. How are we to interpret the findings?

• In the group with multiple risk factors but without clearly documented cardiovascular disease, there was no benefit—and there was an increase in moderate bleeding. Given these findings, physicians should not prescribe dual antiplatelet therapy for primary prevention in patients without known vascular disease.
• A potential benefit was seen in a prespecified subgroup who had documented cardiovascular disease. Given the limitations of subgroup analysis, however, and given the increased risk of moderate bleeding, this positive result should be interpreted with some degree of caution.
• CHARISMA suggests that there may be benefit of protracted dual antiplatelet therapy in stable patients with documented prior ischemic events.

A possible reason for the observed lack of benefit in the overall cohort but the positive results in the subgroups with established vascular disease is that plaque rupture and thrombosis may be a precondition for dual antiplatelet therapy to work.

Another possibility is that, although we have been saying that diabetes mellitus (one of the possible entry criteria in CHARISMA) is a “coronary risk equivalent,” this may not be absolutely true. Although it had been demonstrated that patients with certain risk factors, such as diabetes, have an incidence of ischemic events similar to that in patients with prior MI and should be considered for antiplatelet therapy to prevent vascular events,³² more recent data have shown that patients with prior ischemic events are at much higher risk than patients without ischemic events, even if the latter have diabetes.^33,34

• The observation in CHARISMA that the incremental bleeding risk of dual antiplatelet therapy vs aspirin does not persist beyond a year in patients who have tolerated therapy for a year without a bleeding event may affect the decision to continue clopidogrel beyond 1 year, such as in patients with acute coronary syndromes or patients who have received drug-eluting stents.^35,36
• Another important consideration is cost-effectiveness. Several studies have analyzed the impact of cost and found clopidogrel to be cost-effective by preventing ischemic events and adding years of life.^37,38 A recent analysis from CHARISMA also shows cost-effectiveness in the subgroup of patients enrolled with established cardiovascular disease.³⁹ Once clopidogrel becomes generic, the cost-effectiveness will become even better.

Further studies should better define which stable patients with cardiovascular disease should be on more than aspirin alone.