Perioperative Medicine

INDIANAPOLIS – Robotic-assisted major pancreatic resection is safe, feasible, reliable, and versatile, according to the findings of the largest reported single-center series of such procedures.

That being said, the next and absolutely critical step needs to be comparative effectiveness studies pitting robotic versus laparoscopic or open pancreatic resections, Dr. Herbert J. Zeh III reported at the annual meeting of the American Surgical Association.

He noted that there was a considerable learning curve with the procedure in this single-center series of 250 consecutive robotic-assisted major pancreatic resections. "If we had compared our first 30, 40, or even 60 cases, we would have been comparing an innovative procedure to one that’s been refined continuously since 1937," noted Dr. Zeh of the University of Pittsburgh.

Discussants praised Dr. Zeh and his coinvestigators as innovators who are taking a rigorously scientific and cautious approach in investigating the applicability of robotic techniques to major pancreatic surgery. But some discussants were concerned that the growing dissemination of robotic surgery is based largely upon what they consider to be marketing hype and competitive pressure.

Dr. Zeh explained that he and his coworkers have undertaken the study of robotic-assisted major pancreatic resections because they believe that a minimally invasive approach will reduce the substantial morbidity traditionally associated with open procedures, and that laparoscopic techniques aren’t the answer in these complex resections, which often require resuturing the pancreas to the GI tract.

"It was our perception as a group of dedicated pancreatic surgeons that we could not utilize the laparoscopic technology to adhere to the standard principles of open surgery that we thought were important for safe performance of pancreatic resections. These include meticulous dissection, safe control of major vascular structures, and precise suturing," he said.

The 250 consecutive robotic-assisted major pancreatic resections in this series included the full range of complex pancreatic operations. The two most common procedures were pancreaticoduodenectomy, also known as the Whipple procedure, in 132 patients and distal pancreatectomy in 83.

Overall 30- and 90-day mortality rates were 0.8% and 2.0%, respectively. All deaths were in pancreaticoduodenectomy patients, with 30- and 90-day mortality rates of 1.5% and 3.8%.

Clinically significant complications occurred in 21% of patients. The most common was intra-abdominal fluid collection requiring drainage via interventional radiology. Morbidity rates were similar to those reported in large series of open and laparoscopic pancreatic resections.

Estimated blood loss in pancreaticoduodenectomy averaged 499 mL in the first one-third of patients who had the robotic procedure; thereafter, the blood loss improved to 401 mL.

Rates of conversion from robotic to open surgery also improved over time, from 18.2% in the first third of the patient series to 3.4% in the latter two-thirds.

Mean operative time was 529 minutes for pancreaticoduodenectomy and 256 minutes for distal pancreatectomy. These times have dropped steadily with experience such that mean operative time in the last 50 pancreaticoduodenectomies was 444 minutes, while in the last 50 distal pancreatectomies it was 222 minutes, which approaches reported times for laparoscopic and open operations, Dr. Zeh noted.

The median length of stay was 10 days for pancreaticoduodenectomy patients and 6 days for those undergoing distal pancreatectomy. As a precautionary measure, surgeons kept patients treated early in the series in the hospital longer than was probably necessary. Length of stay has come down over time, although this trend hasn’t yet reached statistical significance.

The readmission rate was 24% in pancreaticoduodenectomy patients and 28% in distal pancreatectomy patients; 2% of patients required a reoperation.

As experience has grown, the group’s criteria for selecting patients for the robotic approach have loosened considerably. Many recent patients have been obese or superobese.

"Currently the only absolute contraindication is some sort of vascular involvement that would entail resecting a vein and reanastomosing it using a minimally invasive approach. That’s really the only frontier we haven’t crossed," said Dr. Zeh.

The potential advantages of the robotic platform that drew the researchers’ interest include greater range of motion for the robotic needle driver and other tools, compared with what is achievable laparoscopically; enhanced visualization with magnification; computerized smoothing of a surgeon’s tremor; and the ability to see structures in three dimensions, unlike in laparoscopy.

"I think the real advantage is the computer," he added. "Robotic surgery is probably misnamed; it’s really computer-assisted surgery. What this is going to allow us to do is to take the skill sets that we have to the next level. Pilots couldn’t control fighter jets without a computer between them and the plane. In the end, I think the addition of the computer between us and the patient is going to allow us to do things that we haven’t even thought about."

He reported having received an honorarium from Medtronic on a single occasion for participation in a symposium on minimally invasive pancreatic surgery.

INDIANAPOLIS – Robotic-assisted major pancreatic resection is safe, feasible, reliable, and versatile, according to the findings of the largest reported single-center series of such procedures.

That being said, the next and absolutely critical step needs to be comparative effectiveness studies pitting robotic versus laparoscopic or open pancreatic resections, Dr. Herbert J. Zeh III reported at the annual meeting of the American Surgical Association.

He noted that there was a considerable learning curve with the procedure in this single-center series of 250 consecutive robotic-assisted major pancreatic resections. "If we had compared our first 30, 40, or even 60 cases, we would have been comparing an innovative procedure to one that’s been refined continuously since 1937," noted Dr. Zeh of the University of Pittsburgh.

Discussants praised Dr. Zeh and his coinvestigators as innovators who are taking a rigorously scientific and cautious approach in investigating the applicability of robotic techniques to major pancreatic surgery. But some discussants were concerned that the growing dissemination of robotic surgery is based largely upon what they consider to be marketing hype and competitive pressure.

Dr. Zeh explained that he and his coworkers have undertaken the study of robotic-assisted major pancreatic resections because they believe that a minimally invasive approach will reduce the substantial morbidity traditionally associated with open procedures, and that laparoscopic techniques aren’t the answer in these complex resections, which often require resuturing the pancreas to the GI tract.

"It was our perception as a group of dedicated pancreatic surgeons that we could not utilize the laparoscopic technology to adhere to the standard principles of open surgery that we thought were important for safe performance of pancreatic resections. These include meticulous dissection, safe control of major vascular structures, and precise suturing," he said.

The 250 consecutive robotic-assisted major pancreatic resections in this series included the full range of complex pancreatic operations. The two most common procedures were pancreaticoduodenectomy, also known as the Whipple procedure, in 132 patients and distal pancreatectomy in 83.

Overall 30- and 90-day mortality rates were 0.8% and 2.0%, respectively. All deaths were in pancreaticoduodenectomy patients, with 30- and 90-day mortality rates of 1.5% and 3.8%.

Clinically significant complications occurred in 21% of patients. The most common was intra-abdominal fluid collection requiring drainage via interventional radiology. Morbidity rates were similar to those reported in large series of open and laparoscopic pancreatic resections.

Estimated blood loss in pancreaticoduodenectomy averaged 499 mL in the first one-third of patients who had the robotic procedure; thereafter, the blood loss improved to 401 mL.

Rates of conversion from robotic to open surgery also improved over time, from 18.2% in the first third of the patient series to 3.4% in the latter two-thirds.

Mean operative time was 529 minutes for pancreaticoduodenectomy and 256 minutes for distal pancreatectomy. These times have dropped steadily with experience such that mean operative time in the last 50 pancreaticoduodenectomies was 444 minutes, while in the last 50 distal pancreatectomies it was 222 minutes, which approaches reported times for laparoscopic and open operations, Dr. Zeh noted.

The median length of stay was 10 days for pancreaticoduodenectomy patients and 6 days for those undergoing distal pancreatectomy. As a precautionary measure, surgeons kept patients treated early in the series in the hospital longer than was probably necessary. Length of stay has come down over time, although this trend hasn’t yet reached statistical significance.

The readmission rate was 24% in pancreaticoduodenectomy patients and 28% in distal pancreatectomy patients; 2% of patients required a reoperation.

As experience has grown, the group’s criteria for selecting patients for the robotic approach have loosened considerably. Many recent patients have been obese or superobese.

"Currently the only absolute contraindication is some sort of vascular involvement that would entail resecting a vein and reanastomosing it using a minimally invasive approach. That’s really the only frontier we haven’t crossed," said Dr. Zeh.

The potential advantages of the robotic platform that drew the researchers’ interest include greater range of motion for the robotic needle driver and other tools, compared with what is achievable laparoscopically; enhanced visualization with magnification; computerized smoothing of a surgeon’s tremor; and the ability to see structures in three dimensions, unlike in laparoscopy.

"I think the real advantage is the computer," he added. "Robotic surgery is probably misnamed; it’s really computer-assisted surgery. What this is going to allow us to do is to take the skill sets that we have to the next level. Pilots couldn’t control fighter jets without a computer between them and the plane. In the end, I think the addition of the computer between us and the patient is going to allow us to do things that we haven’t even thought about."

He reported having received an honorarium from Medtronic on a single occasion for participation in a symposium on minimally invasive pancreatic surgery.

INDIANAPOLIS – Robotic-assisted major pancreatic resection is safe, feasible, reliable, and versatile, according to the findings of the largest reported single-center series of such procedures.

That being said, the next and absolutely critical step needs to be comparative effectiveness studies pitting robotic versus laparoscopic or open pancreatic resections, Dr. Herbert J. Zeh III reported at the annual meeting of the American Surgical Association.

He noted that there was a considerable learning curve with the procedure in this single-center series of 250 consecutive robotic-assisted major pancreatic resections. "If we had compared our first 30, 40, or even 60 cases, we would have been comparing an innovative procedure to one that’s been refined continuously since 1937," noted Dr. Zeh of the University of Pittsburgh.

Discussants praised Dr. Zeh and his coinvestigators as innovators who are taking a rigorously scientific and cautious approach in investigating the applicability of robotic techniques to major pancreatic surgery. But some discussants were concerned that the growing dissemination of robotic surgery is based largely upon what they consider to be marketing hype and competitive pressure.

Dr. Zeh explained that he and his coworkers have undertaken the study of robotic-assisted major pancreatic resections because they believe that a minimally invasive approach will reduce the substantial morbidity traditionally associated with open procedures, and that laparoscopic techniques aren’t the answer in these complex resections, which often require resuturing the pancreas to the GI tract.

"It was our perception as a group of dedicated pancreatic surgeons that we could not utilize the laparoscopic technology to adhere to the standard principles of open surgery that we thought were important for safe performance of pancreatic resections. These include meticulous dissection, safe control of major vascular structures, and precise suturing," he said.

The 250 consecutive robotic-assisted major pancreatic resections in this series included the full range of complex pancreatic operations. The two most common procedures were pancreaticoduodenectomy, also known as the Whipple procedure, in 132 patients and distal pancreatectomy in 83.

Overall 30- and 90-day mortality rates were 0.8% and 2.0%, respectively. All deaths were in pancreaticoduodenectomy patients, with 30- and 90-day mortality rates of 1.5% and 3.8%.

Clinically significant complications occurred in 21% of patients. The most common was intra-abdominal fluid collection requiring drainage via interventional radiology. Morbidity rates were similar to those reported in large series of open and laparoscopic pancreatic resections.

Estimated blood loss in pancreaticoduodenectomy averaged 499 mL in the first one-third of patients who had the robotic procedure; thereafter, the blood loss improved to 401 mL.

Rates of conversion from robotic to open surgery also improved over time, from 18.2% in the first third of the patient series to 3.4% in the latter two-thirds.

Mean operative time was 529 minutes for pancreaticoduodenectomy and 256 minutes for distal pancreatectomy. These times have dropped steadily with experience such that mean operative time in the last 50 pancreaticoduodenectomies was 444 minutes, while in the last 50 distal pancreatectomies it was 222 minutes, which approaches reported times for laparoscopic and open operations, Dr. Zeh noted.

The median length of stay was 10 days for pancreaticoduodenectomy patients and 6 days for those undergoing distal pancreatectomy. As a precautionary measure, surgeons kept patients treated early in the series in the hospital longer than was probably necessary. Length of stay has come down over time, although this trend hasn’t yet reached statistical significance.

The readmission rate was 24% in pancreaticoduodenectomy patients and 28% in distal pancreatectomy patients; 2% of patients required a reoperation.

As experience has grown, the group’s criteria for selecting patients for the robotic approach have loosened considerably. Many recent patients have been obese or superobese.

"Currently the only absolute contraindication is some sort of vascular involvement that would entail resecting a vein and reanastomosing it using a minimally invasive approach. That’s really the only frontier we haven’t crossed," said Dr. Zeh.

The potential advantages of the robotic platform that drew the researchers’ interest include greater range of motion for the robotic needle driver and other tools, compared with what is achievable laparoscopically; enhanced visualization with magnification; computerized smoothing of a surgeon’s tremor; and the ability to see structures in three dimensions, unlike in laparoscopy.

"I think the real advantage is the computer," he added. "Robotic surgery is probably misnamed; it’s really computer-assisted surgery. What this is going to allow us to do is to take the skill sets that we have to the next level. Pilots couldn’t control fighter jets without a computer between them and the plane. In the end, I think the addition of the computer between us and the patient is going to allow us to do things that we haven’t even thought about."

He reported having received an honorarium from Medtronic on a single occasion for participation in a symposium on minimally invasive pancreatic surgery.

INDIANAPOLIS – Average 30-day readmission rates in a large national study varied widely by surgical specialty, ranging from 5% for general surgery patients to 12% for vascular surgery patients and 16% after hepato-pancreatic-biliary surgery.

This retrospective study was based upon American College of Surgeons National Surgical Quality Improvement Program (NSQIP) 2011 data on 240,125 patients discharged from 316 hospitals after these types of surgery. The results enabled investigators to identify the major risk factors for readmission. They used this information to generate a predictive model to identify patients at greatest risk with an eye toward introducing interventions to keep them out of the hospital, Dr. Timothy M. Pawlik said at the annual meeting of the American Surgical Association.

How effective such interventions will be in a surgical population is as yet unclear, he added.

The importance of this work lies in the growing emphasis health care payers are placing upon 30-day readmission as a quality-of-care indicator. In 2012, Medicare began cutting reimbursement by 1% to hospitals with above-average 30-day readmissions. Next year, this penalty is scheduled to increase to 3% under the Medicare Hospital Readmission Reduction Program. Prior research efforts to identify risk factors for readmission have focused chiefly on medical rather than surgical conditions, noted Dr. Pawlik, professor of surgery and chief of the division of surgical oncology at Johns Hopkins University, Baltimore.

The readmission risk predictive formula he and his coinvestigators developed is simple: American Society of Anesthesiologists physical status class + (length of stay/2). This number is rounded up to yield a risk score of 1-10. A patient with a readmission score of 1 has a 1% risk of readmission within 30 days of discharge. The risk climbs to 12% with a score of 5, 20% with a score of 8, and 40% with a score of 10.

"A score of 4 had an 8% readmission rate, with 77% sensitivity, 52% specificity, a low positive predictive value of 12%, but a high negative predictive value of 95%," the surgeon observed. "In essence, a score of 4 or higher was able to identify 80% of all readmissions, but it also included about half of all patients."

Because of a quirk in the NSQIP database – it records readmissions within 30 days of surgery instead of starting from discharge – the investigators had to limit the study population to surgery patients with a length of stay of 10 days or less and then apply statistical modeling. However, limiting the data set to patients with a maximum 10-day hospital stay only restricted the study cohort by 6%. Thus, the study results remain highly generalizable to U.S. surgery patients.

The area under the curve (AUC) of the receiver operating characteristic for the readmission risk formula was 0.70. Statisticians consider a test having an AUC of 0.50 to be worthless. An AUC of 1.0 would define a "perfect" test, while a test with an AUC in the 0.70-0.80 range is deemed of only "fair" accuracy.

The AUC for the readmission score varied considerably when applied to the various surgical subspecialties. For example, the AUC was 0.69 for general surgery patients but only 0.51 for thoracic surgery patients, 0.64 for vascular surgery patients, and 0.59 for colorectal surgery patients.

The fact that the predictive formula doesn’t perform any better than barely "fair" is testimony to the difficulty in identifying who will require readmission. That being said, the AUC for the readmission score after surgery compares favorably to published hospital readmission risk formulas developed for medical patients, which have similar and in many cases lower AUCs (JAMA 2011;306:1688-98), Dr. Pawlik observed.

At Johns Hopkins, the plan is to target surgery patients who have high readmission scores with interventions including more frequent follow-up phone calls and earlier scheduled postoperative clinic visits in an effort to keep them out of the hospital, he continued.

Discussant Dr. Keith D. Lillemoe was skeptical that this will result in reduced readmission rates. Indeed, he questioned whether the 30-day readmission rate is a legitimate quality measure for surgeons.

"I can look across the room and predict if a patient is going to come back in to the hospital. But what can we really do to keep such patients from being readmitted other than keeping them indeterminately long until we’ve passed that window? It seems like all the phone calls and early clinic visits in the world can’t stop the progression sometimes," reflected Dr. Lillemoe, professor and chairman of the department of surgery at Massachusetts General Hospital, Boston.

He noted with frustration that he had just stepped out of the lecture hall to arrange for readmission of a patient 1 week after discharge post pancreaticoduodenectomy.

"I made three phone calls myself to that guy trying to nurse him through his nausea and vomiting and other symptoms," the surgeon recalled.

Dr. Pawlik was sympathetic.

"It’s very hard to prevent readmissions. It’s a very complicated metric, and many would argue that it’s an inappropriate quality metric," he said. "Many things are outside our control before we even meet the patient, as are some things that occur in the hospital, and many things are beyond our control after discharge as far as where they live, their family structure, and their financial resources. In my opinion it’s a very problematic quality measure and I am not sure how we are going to tackle it."

He reported having no conflicts of interest.

[email protected]

INDIANAPOLIS – Average 30-day readmission rates in a large national study varied widely by surgical specialty, ranging from 5% for general surgery patients to 12% for vascular surgery patients and 16% after hepato-pancreatic-biliary surgery.

This retrospective study was based upon American College of Surgeons National Surgical Quality Improvement Program (NSQIP) 2011 data on 240,125 patients discharged from 316 hospitals after these types of surgery. The results enabled investigators to identify the major risk factors for readmission. They used this information to generate a predictive model to identify patients at greatest risk with an eye toward introducing interventions to keep them out of the hospital, Dr. Timothy M. Pawlik said at the annual meeting of the American Surgical Association.

How effective such interventions will be in a surgical population is as yet unclear, he added.

The importance of this work lies in the growing emphasis health care payers are placing upon 30-day readmission as a quality-of-care indicator. In 2012, Medicare began cutting reimbursement by 1% to hospitals with above-average 30-day readmissions. Next year, this penalty is scheduled to increase to 3% under the Medicare Hospital Readmission Reduction Program. Prior research efforts to identify risk factors for readmission have focused chiefly on medical rather than surgical conditions, noted Dr. Pawlik, professor of surgery and chief of the division of surgical oncology at Johns Hopkins University, Baltimore.

The readmission risk predictive formula he and his coinvestigators developed is simple: American Society of Anesthesiologists physical status class + (length of stay/2). This number is rounded up to yield a risk score of 1-10. A patient with a readmission score of 1 has a 1% risk of readmission within 30 days of discharge. The risk climbs to 12% with a score of 5, 20% with a score of 8, and 40% with a score of 10.

"A score of 4 had an 8% readmission rate, with 77% sensitivity, 52% specificity, a low positive predictive value of 12%, but a high negative predictive value of 95%," the surgeon observed. "In essence, a score of 4 or higher was able to identify 80% of all readmissions, but it also included about half of all patients."

Because of a quirk in the NSQIP database – it records readmissions within 30 days of surgery instead of starting from discharge – the investigators had to limit the study population to surgery patients with a length of stay of 10 days or less and then apply statistical modeling. However, limiting the data set to patients with a maximum 10-day hospital stay only restricted the study cohort by 6%. Thus, the study results remain highly generalizable to U.S. surgery patients.

The area under the curve (AUC) of the receiver operating characteristic for the readmission risk formula was 0.70. Statisticians consider a test having an AUC of 0.50 to be worthless. An AUC of 1.0 would define a "perfect" test, while a test with an AUC in the 0.70-0.80 range is deemed of only "fair" accuracy.

The AUC for the readmission score varied considerably when applied to the various surgical subspecialties. For example, the AUC was 0.69 for general surgery patients but only 0.51 for thoracic surgery patients, 0.64 for vascular surgery patients, and 0.59 for colorectal surgery patients.

The fact that the predictive formula doesn’t perform any better than barely "fair" is testimony to the difficulty in identifying who will require readmission. That being said, the AUC for the readmission score after surgery compares favorably to published hospital readmission risk formulas developed for medical patients, which have similar and in many cases lower AUCs (JAMA 2011;306:1688-98), Dr. Pawlik observed.

At Johns Hopkins, the plan is to target surgery patients who have high readmission scores with interventions including more frequent follow-up phone calls and earlier scheduled postoperative clinic visits in an effort to keep them out of the hospital, he continued.

Discussant Dr. Keith D. Lillemoe was skeptical that this will result in reduced readmission rates. Indeed, he questioned whether the 30-day readmission rate is a legitimate quality measure for surgeons.

"I can look across the room and predict if a patient is going to come back in to the hospital. But what can we really do to keep such patients from being readmitted other than keeping them indeterminately long until we’ve passed that window? It seems like all the phone calls and early clinic visits in the world can’t stop the progression sometimes," reflected Dr. Lillemoe, professor and chairman of the department of surgery at Massachusetts General Hospital, Boston.

He noted with frustration that he had just stepped out of the lecture hall to arrange for readmission of a patient 1 week after discharge post pancreaticoduodenectomy.

"I made three phone calls myself to that guy trying to nurse him through his nausea and vomiting and other symptoms," the surgeon recalled.

Dr. Pawlik was sympathetic.

"It’s very hard to prevent readmissions. It’s a very complicated metric, and many would argue that it’s an inappropriate quality metric," he said. "Many things are outside our control before we even meet the patient, as are some things that occur in the hospital, and many things are beyond our control after discharge as far as where they live, their family structure, and their financial resources. In my opinion it’s a very problematic quality measure and I am not sure how we are going to tackle it."

He reported having no conflicts of interest.

[email protected]

INDIANAPOLIS – Average 30-day readmission rates in a large national study varied widely by surgical specialty, ranging from 5% for general surgery patients to 12% for vascular surgery patients and 16% after hepato-pancreatic-biliary surgery.

This retrospective study was based upon American College of Surgeons National Surgical Quality Improvement Program (NSQIP) 2011 data on 240,125 patients discharged from 316 hospitals after these types of surgery. The results enabled investigators to identify the major risk factors for readmission. They used this information to generate a predictive model to identify patients at greatest risk with an eye toward introducing interventions to keep them out of the hospital, Dr. Timothy M. Pawlik said at the annual meeting of the American Surgical Association.

How effective such interventions will be in a surgical population is as yet unclear, he added.

The importance of this work lies in the growing emphasis health care payers are placing upon 30-day readmission as a quality-of-care indicator. In 2012, Medicare began cutting reimbursement by 1% to hospitals with above-average 30-day readmissions. Next year, this penalty is scheduled to increase to 3% under the Medicare Hospital Readmission Reduction Program. Prior research efforts to identify risk factors for readmission have focused chiefly on medical rather than surgical conditions, noted Dr. Pawlik, professor of surgery and chief of the division of surgical oncology at Johns Hopkins University, Baltimore.

The readmission risk predictive formula he and his coinvestigators developed is simple: American Society of Anesthesiologists physical status class + (length of stay/2). This number is rounded up to yield a risk score of 1-10. A patient with a readmission score of 1 has a 1% risk of readmission within 30 days of discharge. The risk climbs to 12% with a score of 5, 20% with a score of 8, and 40% with a score of 10.

"A score of 4 had an 8% readmission rate, with 77% sensitivity, 52% specificity, a low positive predictive value of 12%, but a high negative predictive value of 95%," the surgeon observed. "In essence, a score of 4 or higher was able to identify 80% of all readmissions, but it also included about half of all patients."

Because of a quirk in the NSQIP database – it records readmissions within 30 days of surgery instead of starting from discharge – the investigators had to limit the study population to surgery patients with a length of stay of 10 days or less and then apply statistical modeling. However, limiting the data set to patients with a maximum 10-day hospital stay only restricted the study cohort by 6%. Thus, the study results remain highly generalizable to U.S. surgery patients.

The area under the curve (AUC) of the receiver operating characteristic for the readmission risk formula was 0.70. Statisticians consider a test having an AUC of 0.50 to be worthless. An AUC of 1.0 would define a "perfect" test, while a test with an AUC in the 0.70-0.80 range is deemed of only "fair" accuracy.

The AUC for the readmission score varied considerably when applied to the various surgical subspecialties. For example, the AUC was 0.69 for general surgery patients but only 0.51 for thoracic surgery patients, 0.64 for vascular surgery patients, and 0.59 for colorectal surgery patients.

The fact that the predictive formula doesn’t perform any better than barely "fair" is testimony to the difficulty in identifying who will require readmission. That being said, the AUC for the readmission score after surgery compares favorably to published hospital readmission risk formulas developed for medical patients, which have similar and in many cases lower AUCs (JAMA 2011;306:1688-98), Dr. Pawlik observed.

At Johns Hopkins, the plan is to target surgery patients who have high readmission scores with interventions including more frequent follow-up phone calls and earlier scheduled postoperative clinic visits in an effort to keep them out of the hospital, he continued.

Discussant Dr. Keith D. Lillemoe was skeptical that this will result in reduced readmission rates. Indeed, he questioned whether the 30-day readmission rate is a legitimate quality measure for surgeons.

"I can look across the room and predict if a patient is going to come back in to the hospital. But what can we really do to keep such patients from being readmitted other than keeping them indeterminately long until we’ve passed that window? It seems like all the phone calls and early clinic visits in the world can’t stop the progression sometimes," reflected Dr. Lillemoe, professor and chairman of the department of surgery at Massachusetts General Hospital, Boston.

He noted with frustration that he had just stepped out of the lecture hall to arrange for readmission of a patient 1 week after discharge post pancreaticoduodenectomy.

"I made three phone calls myself to that guy trying to nurse him through his nausea and vomiting and other symptoms," the surgeon recalled.

Dr. Pawlik was sympathetic.

"It’s very hard to prevent readmissions. It’s a very complicated metric, and many would argue that it’s an inappropriate quality metric," he said. "Many things are outside our control before we even meet the patient, as are some things that occur in the hospital, and many things are beyond our control after discharge as far as where they live, their family structure, and their financial resources. In my opinion it’s a very problematic quality measure and I am not sure how we are going to tackle it."

He reported having no conflicts of interest.

[email protected]

MINNEAPOLIS – High-risk patients receiving the On-X mechanical aortic valve can be safely managed with less aggressive anticoagulation than currently recommended, interim results of the PROACT trial suggest.*

The lower target international normalized ratio (INR) in the trial resulted in a decline of more than 50% in bleeding events and did not increase the risk of thromboembolism, reported Dr. John Puskas, international principal investigator for PROACT (Prospective Randomized On-X Anticoagulation Clinical Trial) and associate chief of cardiothoracic surgery at Emory University in Atlanta.

©Martin Allred

"This aortic bileaflet mechanical valve may be safely managed in these select patients at an INR of 1.5 to 2.0, with daily low-dose aspirin," he said at the annual meeting of the American Association for Thoracic Surgery.

Current American College of Cardiology and American Heart Association guidelines recommend that warfarin be dosed to achieve an INR of 2.0 to 3.0 after implantation of a bileaflet mechanical valve, and that once-daily aspirin 75-100 mg be added for all patients with mechanical heart valves.

Dr. Puskas and his associates analyzed data from 375 high-risk patients randomly assigned to lower-dose warfarin (INR 1.5-2.0) or to continue standard-dose warfarin (INR 2.0-3.0), 3 months after implantation with the On-X bileaflet mechanical heart valve. All patients received aspirin 81 mg daily. INR was adjusted by rigorous home self-monitoring, with an average of 9 days between readings and at least 96% compliance.

High-risk patients included those with chronic atrial fibrillation, left ventricular ejection fraction less than 30%, ventricular aneurysm, left atrium diameter greater than 50 mm, prior neurological events, on estrogen replacement therapy, hypercoagulability, or inadequate platelet response to aspirin or clopidogrel (Plavix). There were 185 patients in the experimental, test arm and 190 in the control arm. After randomization, 11 test patients had a neurological event (5 strokes, 6 transient ischemic attacks) and crossed over to the control group, per protocol.

After an average follow-up of 3.82 years, patients managed with a lower target INR had a significant benefit compared with controls with respect to number of major bleeding events (10 vs. 25, respectively), minor bleeds (8 vs. 25), total bleeds (18 vs. 50), and all bleeding and thrombus (38 vs. 64), Dr. Puskas said. The corresponding rate ratios (RRs) were 0.45, 0.36, 0.40, and 0.66.

There was no difference between groups in the composite primary endpoint of major bleed, stroke, transient ischemic attack, thromboembolic events and thrombosis (30 events vs. 39 events; RR, 0.86; P = .54), he said.

Specifically, hemorrhagic stroke occurred in 1 test patient and 2 controls (RR, 0.56) and ischemic stroke in 5 patients in each group (RR, 1.12), he said.

Valve-related mortality was also similar in the test and control groups (5 deaths vs. 4 deaths), as was total mortality (10 vs. 11), Dr. Puskas said.

Invited discussant Dr. A. Pieter Kappetein, a member of the RE-ALIGN trial steering committee and professor of thoracic surgery at Erasmus Medical Center in Rotterdam, the Netherlands, said the number of patients in the analysis was extremely low and questioned the validity of combining bleeding and thromboembolic events in the primary endpoint.

"In this study, you mix the efficacy endpoint with the safety endpoints," he said, observing that they move in opposite directions.

In light of such large-scale trials as ARISTOTLE and RELY, he asked whether PROACT should be considered a pilot trial and whether a new trial, designed with roughly 8,000 patients, should be performed that would also include newer anticoagulation agents to adequately evaluate reduced anticoagulation in mechanical valves.

"Is it not potentially dangerous if we do not know what the increase is for thrombosis and follow your conclusions?" he added.

Dr. Puskas said he shared Dr. Kappetein’s concern about the noninferiority design of the trial and that it was a topic of great discussion with the Food and Drug Administration (FDA). He also agreed that thrombotic events and bleeding events move in the opposite direction.

"What we are really looking for is to determine the sweet spot where those two curves intersect," he said. "While it is theoretically and intellectually correct to say that thrombosis is the efficacy issue and hemorrhage is the safety issue, we are obliged to combine those for two reasons.

"The first is practical; no company will sponsor an 8,000-patient trial, and second, this is, in fact, a trade-off in the minds of patients and clinicians. So, it is a relevant clinical endpoint – the unholy composite, if you will – of thrombosis and hemorrhage."

Finally, a member of the audience asked whether the results would hold up with standard management because universal point-of-care home testing is not the "real world" in the United States.

Dr. Puskas replied that it is in Scandinavia and other parts of the world, and admonished American clinicians, including himself, "to catch up to what should be standard of care." He noted that, based on the roughly 53,000 INR readings in PROACT, controlling INR within your range was more important in terms of adverse events, particularly hemorrhagic events, than what arm patients were assigned to.

"Home monitoring is available, it’s not high tech and it’s much easier for patients," he said. "To be perfectly blunt, there’s really no excuse for us not using it uniformly in America. Quite frankly, it is a conflict of interest between local caregivers and their patients’ well-being.

"There is a small revenue stream to cardiology offices and primary care doctors running Coumadin clinics, and that is keeping us in the system that we have now rather than home monitoring through bigger, centralized Coumadin clinics."

Dr. Puskas did not report data on PROACT’s low-risk arm managed with clopidogrel 75 mg/day plus aspirin 325 mg/day, or a third arm managed on warfarin at an INR of 2.0-2.5 plus aspirin 81 mg/day. The low-risk data will not be available for at least one more year, although the investigators are in discussion with the FDA about a possible interim analysis, he said in an interview.

The evaluable high-risk patients were 79% male, 93% were in sinus rhythm preoperatively, and concomitant procedures included coronary artery bypass grafting in 27%, aortic aneurysm repair in 14%, and other procedures in 25%. Their average age was 55 years.

Life Technologies sponsored the study. Dr. Puskas reported having no financial relationship with Life Technologies.

Correction, 6/18/2013: An earlier version of this article stated that the On-X aortic valve is investigational. This was a misstatement. The valve itself has been approved in the United States since 2001. The PROACT trial applications of lowered INR and an aspirin/Plavix regimen are not approved.

[email protected]

MINNEAPOLIS – High-risk patients receiving the On-X mechanical aortic valve can be safely managed with less aggressive anticoagulation than currently recommended, interim results of the PROACT trial suggest.*

The lower target international normalized ratio (INR) in the trial resulted in a decline of more than 50% in bleeding events and did not increase the risk of thromboembolism, reported Dr. John Puskas, international principal investigator for PROACT (Prospective Randomized On-X Anticoagulation Clinical Trial) and associate chief of cardiothoracic surgery at Emory University in Atlanta.

©Martin Allred

"This aortic bileaflet mechanical valve may be safely managed in these select patients at an INR of 1.5 to 2.0, with daily low-dose aspirin," he said at the annual meeting of the American Association for Thoracic Surgery.

Current American College of Cardiology and American Heart Association guidelines recommend that warfarin be dosed to achieve an INR of 2.0 to 3.0 after implantation of a bileaflet mechanical valve, and that once-daily aspirin 75-100 mg be added for all patients with mechanical heart valves.

Dr. Puskas and his associates analyzed data from 375 high-risk patients randomly assigned to lower-dose warfarin (INR 1.5-2.0) or to continue standard-dose warfarin (INR 2.0-3.0), 3 months after implantation with the On-X bileaflet mechanical heart valve. All patients received aspirin 81 mg daily. INR was adjusted by rigorous home self-monitoring, with an average of 9 days between readings and at least 96% compliance.

High-risk patients included those with chronic atrial fibrillation, left ventricular ejection fraction less than 30%, ventricular aneurysm, left atrium diameter greater than 50 mm, prior neurological events, on estrogen replacement therapy, hypercoagulability, or inadequate platelet response to aspirin or clopidogrel (Plavix). There were 185 patients in the experimental, test arm and 190 in the control arm. After randomization, 11 test patients had a neurological event (5 strokes, 6 transient ischemic attacks) and crossed over to the control group, per protocol.

After an average follow-up of 3.82 years, patients managed with a lower target INR had a significant benefit compared with controls with respect to number of major bleeding events (10 vs. 25, respectively), minor bleeds (8 vs. 25), total bleeds (18 vs. 50), and all bleeding and thrombus (38 vs. 64), Dr. Puskas said. The corresponding rate ratios (RRs) were 0.45, 0.36, 0.40, and 0.66.

There was no difference between groups in the composite primary endpoint of major bleed, stroke, transient ischemic attack, thromboembolic events and thrombosis (30 events vs. 39 events; RR, 0.86; P = .54), he said.

Specifically, hemorrhagic stroke occurred in 1 test patient and 2 controls (RR, 0.56) and ischemic stroke in 5 patients in each group (RR, 1.12), he said.

Valve-related mortality was also similar in the test and control groups (5 deaths vs. 4 deaths), as was total mortality (10 vs. 11), Dr. Puskas said.

Invited discussant Dr. A. Pieter Kappetein, a member of the RE-ALIGN trial steering committee and professor of thoracic surgery at Erasmus Medical Center in Rotterdam, the Netherlands, said the number of patients in the analysis was extremely low and questioned the validity of combining bleeding and thromboembolic events in the primary endpoint.

"In this study, you mix the efficacy endpoint with the safety endpoints," he said, observing that they move in opposite directions.

In light of such large-scale trials as ARISTOTLE and RELY, he asked whether PROACT should be considered a pilot trial and whether a new trial, designed with roughly 8,000 patients, should be performed that would also include newer anticoagulation agents to adequately evaluate reduced anticoagulation in mechanical valves.

"Is it not potentially dangerous if we do not know what the increase is for thrombosis and follow your conclusions?" he added.

Dr. Puskas said he shared Dr. Kappetein’s concern about the noninferiority design of the trial and that it was a topic of great discussion with the Food and Drug Administration (FDA). He also agreed that thrombotic events and bleeding events move in the opposite direction.

"What we are really looking for is to determine the sweet spot where those two curves intersect," he said. "While it is theoretically and intellectually correct to say that thrombosis is the efficacy issue and hemorrhage is the safety issue, we are obliged to combine those for two reasons.

"The first is practical; no company will sponsor an 8,000-patient trial, and second, this is, in fact, a trade-off in the minds of patients and clinicians. So, it is a relevant clinical endpoint – the unholy composite, if you will – of thrombosis and hemorrhage."

Finally, a member of the audience asked whether the results would hold up with standard management because universal point-of-care home testing is not the "real world" in the United States.

Dr. Puskas replied that it is in Scandinavia and other parts of the world, and admonished American clinicians, including himself, "to catch up to what should be standard of care." He noted that, based on the roughly 53,000 INR readings in PROACT, controlling INR within your range was more important in terms of adverse events, particularly hemorrhagic events, than what arm patients were assigned to.

"Home monitoring is available, it’s not high tech and it’s much easier for patients," he said. "To be perfectly blunt, there’s really no excuse for us not using it uniformly in America. Quite frankly, it is a conflict of interest between local caregivers and their patients’ well-being.

"There is a small revenue stream to cardiology offices and primary care doctors running Coumadin clinics, and that is keeping us in the system that we have now rather than home monitoring through bigger, centralized Coumadin clinics."

Dr. Puskas did not report data on PROACT’s low-risk arm managed with clopidogrel 75 mg/day plus aspirin 325 mg/day, or a third arm managed on warfarin at an INR of 2.0-2.5 plus aspirin 81 mg/day. The low-risk data will not be available for at least one more year, although the investigators are in discussion with the FDA about a possible interim analysis, he said in an interview.

The evaluable high-risk patients were 79% male, 93% were in sinus rhythm preoperatively, and concomitant procedures included coronary artery bypass grafting in 27%, aortic aneurysm repair in 14%, and other procedures in 25%. Their average age was 55 years.

Life Technologies sponsored the study. Dr. Puskas reported having no financial relationship with Life Technologies.

Correction, 6/18/2013: An earlier version of this article stated that the On-X aortic valve is investigational. This was a misstatement. The valve itself has been approved in the United States since 2001. The PROACT trial applications of lowered INR and an aspirin/Plavix regimen are not approved.

[email protected]

MINNEAPOLIS – High-risk patients receiving the On-X mechanical aortic valve can be safely managed with less aggressive anticoagulation than currently recommended, interim results of the PROACT trial suggest.*

The lower target international normalized ratio (INR) in the trial resulted in a decline of more than 50% in bleeding events and did not increase the risk of thromboembolism, reported Dr. John Puskas, international principal investigator for PROACT (Prospective Randomized On-X Anticoagulation Clinical Trial) and associate chief of cardiothoracic surgery at Emory University in Atlanta.

©Martin Allred

"This aortic bileaflet mechanical valve may be safely managed in these select patients at an INR of 1.5 to 2.0, with daily low-dose aspirin," he said at the annual meeting of the American Association for Thoracic Surgery.

Current American College of Cardiology and American Heart Association guidelines recommend that warfarin be dosed to achieve an INR of 2.0 to 3.0 after implantation of a bileaflet mechanical valve, and that once-daily aspirin 75-100 mg be added for all patients with mechanical heart valves.

Dr. Puskas and his associates analyzed data from 375 high-risk patients randomly assigned to lower-dose warfarin (INR 1.5-2.0) or to continue standard-dose warfarin (INR 2.0-3.0), 3 months after implantation with the On-X bileaflet mechanical heart valve. All patients received aspirin 81 mg daily. INR was adjusted by rigorous home self-monitoring, with an average of 9 days between readings and at least 96% compliance.

High-risk patients included those with chronic atrial fibrillation, left ventricular ejection fraction less than 30%, ventricular aneurysm, left atrium diameter greater than 50 mm, prior neurological events, on estrogen replacement therapy, hypercoagulability, or inadequate platelet response to aspirin or clopidogrel (Plavix). There were 185 patients in the experimental, test arm and 190 in the control arm. After randomization, 11 test patients had a neurological event (5 strokes, 6 transient ischemic attacks) and crossed over to the control group, per protocol.

After an average follow-up of 3.82 years, patients managed with a lower target INR had a significant benefit compared with controls with respect to number of major bleeding events (10 vs. 25, respectively), minor bleeds (8 vs. 25), total bleeds (18 vs. 50), and all bleeding and thrombus (38 vs. 64), Dr. Puskas said. The corresponding rate ratios (RRs) were 0.45, 0.36, 0.40, and 0.66.

There was no difference between groups in the composite primary endpoint of major bleed, stroke, transient ischemic attack, thromboembolic events and thrombosis (30 events vs. 39 events; RR, 0.86; P = .54), he said.

Specifically, hemorrhagic stroke occurred in 1 test patient and 2 controls (RR, 0.56) and ischemic stroke in 5 patients in each group (RR, 1.12), he said.

Valve-related mortality was also similar in the test and control groups (5 deaths vs. 4 deaths), as was total mortality (10 vs. 11), Dr. Puskas said.

Invited discussant Dr. A. Pieter Kappetein, a member of the RE-ALIGN trial steering committee and professor of thoracic surgery at Erasmus Medical Center in Rotterdam, the Netherlands, said the number of patients in the analysis was extremely low and questioned the validity of combining bleeding and thromboembolic events in the primary endpoint.

"In this study, you mix the efficacy endpoint with the safety endpoints," he said, observing that they move in opposite directions.

In light of such large-scale trials as ARISTOTLE and RELY, he asked whether PROACT should be considered a pilot trial and whether a new trial, designed with roughly 8,000 patients, should be performed that would also include newer anticoagulation agents to adequately evaluate reduced anticoagulation in mechanical valves.

"Is it not potentially dangerous if we do not know what the increase is for thrombosis and follow your conclusions?" he added.

Dr. Puskas said he shared Dr. Kappetein’s concern about the noninferiority design of the trial and that it was a topic of great discussion with the Food and Drug Administration (FDA). He also agreed that thrombotic events and bleeding events move in the opposite direction.

"What we are really looking for is to determine the sweet spot where those two curves intersect," he said. "While it is theoretically and intellectually correct to say that thrombosis is the efficacy issue and hemorrhage is the safety issue, we are obliged to combine those for two reasons.

"The first is practical; no company will sponsor an 8,000-patient trial, and second, this is, in fact, a trade-off in the minds of patients and clinicians. So, it is a relevant clinical endpoint – the unholy composite, if you will – of thrombosis and hemorrhage."

Finally, a member of the audience asked whether the results would hold up with standard management because universal point-of-care home testing is not the "real world" in the United States.

Dr. Puskas replied that it is in Scandinavia and other parts of the world, and admonished American clinicians, including himself, "to catch up to what should be standard of care." He noted that, based on the roughly 53,000 INR readings in PROACT, controlling INR within your range was more important in terms of adverse events, particularly hemorrhagic events, than what arm patients were assigned to.

"Home monitoring is available, it’s not high tech and it’s much easier for patients," he said. "To be perfectly blunt, there’s really no excuse for us not using it uniformly in America. Quite frankly, it is a conflict of interest between local caregivers and their patients’ well-being.

"There is a small revenue stream to cardiology offices and primary care doctors running Coumadin clinics, and that is keeping us in the system that we have now rather than home monitoring through bigger, centralized Coumadin clinics."

Dr. Puskas did not report data on PROACT’s low-risk arm managed with clopidogrel 75 mg/day plus aspirin 325 mg/day, or a third arm managed on warfarin at an INR of 2.0-2.5 plus aspirin 81 mg/day. The low-risk data will not be available for at least one more year, although the investigators are in discussion with the FDA about a possible interim analysis, he said in an interview.

The evaluable high-risk patients were 79% male, 93% were in sinus rhythm preoperatively, and concomitant procedures included coronary artery bypass grafting in 27%, aortic aneurysm repair in 14%, and other procedures in 25%. Their average age was 55 years.

Life Technologies sponsored the study. Dr. Puskas reported having no financial relationship with Life Technologies.

Correction, 6/18/2013: An earlier version of this article stated that the On-X aortic valve is investigational. This was a misstatement. The valve itself has been approved in the United States since 2001. The PROACT trial applications of lowered INR and an aspirin/Plavix regimen are not approved.

[email protected]

LAS VEGAS – The development of euglycemic insulin resistance soon after intubation may herald the onset of ventilator-associated pneumonia, a study by investigators at Vanderbilt University in Nashville, Tenn., has shown.

Researchers compared 92 critically injured trauma patients who developed VAP (ventilator-associated pneumonia) 3-4 days after intubation with 2,162 who did not. All the subjects had their blood glucose levels kept mostly between 80 and 150 mg/dL with the help of a computer-assisted protocol that adjusted insulin drip rates as necessary, lead investigator Dr. Kaushik Mukherjee reported at the annual meeting of the Surgical Infection Society.

There were no differences in baseline demographics between the two groups, but compared with controls, patients who developed VAP needed significantly higher insulin drip rates to stay in that range the day before and the first and third days after they met clinical criteria for VAP diagnosis (maximum difference, 1.1 U/hr [95% CI, 0.8-1.5; P less than .001]).

The M multiplier, a surrogate for insulin resistance calculated from blood glucose levels and insulin drip rates, was significantly higher 2 days before VAP was diagnosed, and remained so for 10 days afterward.

If the findings hold up with further investigation, the Vanderbilt team believes they may one day help predict who’s at risk for VAP so that preventative measures can be taken. Among other things, the model will need to incorporate body mass index, steroid use, tube-feeding schedule, and other confounders that impact insulin requirements, and be put through a prospective trial.

Even so, "these data indicate euglycemic insulin resistance may be an important new indicator for VAP in the era of strict glycemic control. [This] may be valuable moving forward," said Dr. Mukherjee of Vanderbilt’s division of trauma and surgical critical care.

"We believe that critically injured patients with VAP show euglycemic insulin resistance as measured by the multiplier, and we think [that] could be predictive of infection. We are hoping to turn this into an insulin resistance–based screening tool for VAP that would help us decide when we should obtain a [bronchoalveolar lavage]. Earlier detection of pneumonias could result in earlier antibiotic therapy and survival," he said.

Patients in the study were at least 16 years old, and had been ventilated for at least 48 hours.

Both VAP and control patients needed increasing amounts of insulin in the 10 days following intubation, probably "due to added nutrition, but [the VAP group required] a more rapid increase in their insulin infusion rates" starting about 3 days before VAP was diagnosed.

Overall, VAP patients had lower blood glucose levels both before and after diagnosis and were less likely to exceed the target range. "We think it’s because their innate ability to control glucose [was more] impaired, [so] there was less variability from the patient’s own system," Dr. Mukherjee said.

He said he had no relevant financial disclosures.

[email protected]

LAS VEGAS – The development of euglycemic insulin resistance soon after intubation may herald the onset of ventilator-associated pneumonia, a study by investigators at Vanderbilt University in Nashville, Tenn., has shown.

Researchers compared 92 critically injured trauma patients who developed VAP (ventilator-associated pneumonia) 3-4 days after intubation with 2,162 who did not. All the subjects had their blood glucose levels kept mostly between 80 and 150 mg/dL with the help of a computer-assisted protocol that adjusted insulin drip rates as necessary, lead investigator Dr. Kaushik Mukherjee reported at the annual meeting of the Surgical Infection Society.

There were no differences in baseline demographics between the two groups, but compared with controls, patients who developed VAP needed significantly higher insulin drip rates to stay in that range the day before and the first and third days after they met clinical criteria for VAP diagnosis (maximum difference, 1.1 U/hr [95% CI, 0.8-1.5; P less than .001]).

The M multiplier, a surrogate for insulin resistance calculated from blood glucose levels and insulin drip rates, was significantly higher 2 days before VAP was diagnosed, and remained so for 10 days afterward.

If the findings hold up with further investigation, the Vanderbilt team believes they may one day help predict who’s at risk for VAP so that preventative measures can be taken. Among other things, the model will need to incorporate body mass index, steroid use, tube-feeding schedule, and other confounders that impact insulin requirements, and be put through a prospective trial.

Even so, "these data indicate euglycemic insulin resistance may be an important new indicator for VAP in the era of strict glycemic control. [This] may be valuable moving forward," said Dr. Mukherjee of Vanderbilt’s division of trauma and surgical critical care.

"We believe that critically injured patients with VAP show euglycemic insulin resistance as measured by the multiplier, and we think [that] could be predictive of infection. We are hoping to turn this into an insulin resistance–based screening tool for VAP that would help us decide when we should obtain a [bronchoalveolar lavage]. Earlier detection of pneumonias could result in earlier antibiotic therapy and survival," he said.

Patients in the study were at least 16 years old, and had been ventilated for at least 48 hours.

Both VAP and control patients needed increasing amounts of insulin in the 10 days following intubation, probably "due to added nutrition, but [the VAP group required] a more rapid increase in their insulin infusion rates" starting about 3 days before VAP was diagnosed.

Overall, VAP patients had lower blood glucose levels both before and after diagnosis and were less likely to exceed the target range. "We think it’s because their innate ability to control glucose [was more] impaired, [so] there was less variability from the patient’s own system," Dr. Mukherjee said.

He said he had no relevant financial disclosures.

[email protected]

LAS VEGAS – The development of euglycemic insulin resistance soon after intubation may herald the onset of ventilator-associated pneumonia, a study by investigators at Vanderbilt University in Nashville, Tenn., has shown.

Researchers compared 92 critically injured trauma patients who developed VAP (ventilator-associated pneumonia) 3-4 days after intubation with 2,162 who did not. All the subjects had their blood glucose levels kept mostly between 80 and 150 mg/dL with the help of a computer-assisted protocol that adjusted insulin drip rates as necessary, lead investigator Dr. Kaushik Mukherjee reported at the annual meeting of the Surgical Infection Society.

There were no differences in baseline demographics between the two groups, but compared with controls, patients who developed VAP needed significantly higher insulin drip rates to stay in that range the day before and the first and third days after they met clinical criteria for VAP diagnosis (maximum difference, 1.1 U/hr [95% CI, 0.8-1.5; P less than .001]).

The M multiplier, a surrogate for insulin resistance calculated from blood glucose levels and insulin drip rates, was significantly higher 2 days before VAP was diagnosed, and remained so for 10 days afterward.

If the findings hold up with further investigation, the Vanderbilt team believes they may one day help predict who’s at risk for VAP so that preventative measures can be taken. Among other things, the model will need to incorporate body mass index, steroid use, tube-feeding schedule, and other confounders that impact insulin requirements, and be put through a prospective trial.

Even so, "these data indicate euglycemic insulin resistance may be an important new indicator for VAP in the era of strict glycemic control. [This] may be valuable moving forward," said Dr. Mukherjee of Vanderbilt’s division of trauma and surgical critical care.

"We believe that critically injured patients with VAP show euglycemic insulin resistance as measured by the multiplier, and we think [that] could be predictive of infection. We are hoping to turn this into an insulin resistance–based screening tool for VAP that would help us decide when we should obtain a [bronchoalveolar lavage]. Earlier detection of pneumonias could result in earlier antibiotic therapy and survival," he said.

Patients in the study were at least 16 years old, and had been ventilated for at least 48 hours.

Both VAP and control patients needed increasing amounts of insulin in the 10 days following intubation, probably "due to added nutrition, but [the VAP group required] a more rapid increase in their insulin infusion rates" starting about 3 days before VAP was diagnosed.

Overall, VAP patients had lower blood glucose levels both before and after diagnosis and were less likely to exceed the target range. "We think it’s because their innate ability to control glucose [was more] impaired, [so] there was less variability from the patient’s own system," Dr. Mukherjee said.

He said he had no relevant financial disclosures.

[email protected]

INDIANAPOLIS – A major hidden cost of the obesity epidemic is the physical toll it takes on hospital nurses and other employees in helping to move heavy patients. The cost of these workplace injuries is skyrocketing, not only in terms of direct medical care bills, but also in terms of work absenteeism, activity restrictions, retraining, and employee dissatisfaction and fear.

The solution at one large tertiary academic medical center in eastern North Carolina has been to create specially trained two-person lift teams available 24/7. The results of a pilot study have been impressive, particularly in light of the fact that nothing else hospital officials tried earlier – including spending more than $1.5 million for motorized patient ceiling lifts – had any significant impact, Dr. Walter J. Pories said at the annual meeting of the American Surgical Association.

Hospital employee injuries incurred in handling obese patients are an issue that has until now been largely beneath physicians’ radar.

"I don’t think anybody here would ask two nurses to pick up a washing machine, or a 400-lb calf, or an 800-lb lathe, and yet whether we like it or not we ask our staff to move patients with such weights daily," observed Dr. Pories, professor of surgery at East Carolina University in Greenville, N.C.

He practices at Vidant Medical Center, a 909-bed hospital where administrators noticed back in 2005 that employee workplace compensation claims for injuries during patient transport were rapidly escalating. In that year, 98 staff experienced patient-handling injuries, resulting in 670 lost workdays and 3,022 restricted workdays.

Hospital officials tried several interventions. First came an intensive education program on safe lifting and patient mobilization conducted by an ergonomist.

"It didn’t make a bit of difference," Dr. Pories recalled.

Indeed, during 2008 there were 2,141 lost workdays due to these types of injuries, more than triple the number in 2005.

Next came a big investment in ceiling-mounted motorized lifts. The impact was minimal: roughly a 10% reduction in staff injuries. Problems with the lifts abounded. They broke. Some staff had difficulty operating them. But the biggest issue was that the rooms with the lifts weren’t always available because the hospital is always fully occupied.

Dr. Pories credited the nursing staff with providing the leadership in developing what he calls the Vidant Medical Center lift team model. Coverage is available 24/7. There are three teams of two individuals on duty during the day and two teams of two at night. They work 12-hour shifts. There is one supervisor for 23 lift team technicians, including three women. They are paid an average of $10 per hour, which the surgeon called "a pretty good wage in eastern North Carolina."

Individuals must pass a rigorous physical assessment before they can join the lift team. Members take a 3-week orientation program in which they learn safe lift techniques, skin and wound care, and infection control. They have their own uniforms to foster esprit de corps.

Many other organizations had tried using lift teams, with disappointing results. That’s because they limited the teams to the day shift or scheduled transfers, according to Dr. Pories.

"The real problems happen late at night," he said.

Dr. Pories and his coinvestigators conducted a pilot study in which they utilized the lift teams in the five hospital units having the highest staff injury rates due to patient-handling mishaps. The lift team was called to those units for moving patients who weighed more than 200 lb, had pressure ulcers, or who were at risk for pressure ulcers by virtue of a Braden scale score of 18 or less.

During the pilot study, 8 employee injuries resulted from patient handling in the five test units, for a rate of 0.134 injuries per 1,000 patient-days, compared with 71 injuries and a rate of 0.319 injuries per 1,000 patient-days in control units.

Once use of the lift teams expanded hospital-wide, the result was a 39% drop in employee injuries due to patient handling, as well as a 43% reduction in hospital-acquired pressure ulcers. Multiple staff surveys have shown 90%-99% satisfaction rates with the lift teams as having improved the workplace while demonstrating that the hospital cares about employee safety.

The total direct and indirect cost of staff injuries due to patient handling was approximately $2.76 million per year prior to introduction of the lift teams. The lift teams provided an estimated $423,152 in savings due to fewer staff injuries and hospital-acquired pressure ulcers, even after factoring in team salaries and equipment, Dr. Pories reported.

The next step in this project will be to document whether the presence of the lift teams also has resulted in fewer patient injuries, he added.

Discussant Dr. Philip R. Schauer commented that if the favorable Vidant experience with dedicated lift teams can be confirmed elsewhere, this is the type of program that should be widely instituted all across the country.

"It’s quite extraordinary to improve patient care and employee health while at the same time reducing overall cost," noted Dr. Schauer, professor of surgery and director of the Bariatric and Metabolic Institute at the Cleveland Clinic.

Discussant Dr. William B. Inabnet III said many malpractice insurance carriers are now offering hospitals incentives for reduced premiums for implementation of best-practices clinical pathways for management of obese patients.

"I think your work will support that type of mission. It’s a win-win for all parties involved," said Dr. Inabnet, professor of surgery at Mt. Sinai Hospital in New York.

Dr. Pories reported having no conflicts of interest.

[email protected]

INDIANAPOLIS – A major hidden cost of the obesity epidemic is the physical toll it takes on hospital nurses and other employees in helping to move heavy patients. The cost of these workplace injuries is skyrocketing, not only in terms of direct medical care bills, but also in terms of work absenteeism, activity restrictions, retraining, and employee dissatisfaction and fear.

The solution at one large tertiary academic medical center in eastern North Carolina has been to create specially trained two-person lift teams available 24/7. The results of a pilot study have been impressive, particularly in light of the fact that nothing else hospital officials tried earlier – including spending more than $1.5 million for motorized patient ceiling lifts – had any significant impact, Dr. Walter J. Pories said at the annual meeting of the American Surgical Association.

Hospital employee injuries incurred in handling obese patients are an issue that has until now been largely beneath physicians’ radar.

"I don’t think anybody here would ask two nurses to pick up a washing machine, or a 400-lb calf, or an 800-lb lathe, and yet whether we like it or not we ask our staff to move patients with such weights daily," observed Dr. Pories, professor of surgery at East Carolina University in Greenville, N.C.

He practices at Vidant Medical Center, a 909-bed hospital where administrators noticed back in 2005 that employee workplace compensation claims for injuries during patient transport were rapidly escalating. In that year, 98 staff experienced patient-handling injuries, resulting in 670 lost workdays and 3,022 restricted workdays.

Hospital officials tried several interventions. First came an intensive education program on safe lifting and patient mobilization conducted by an ergonomist.

"It didn’t make a bit of difference," Dr. Pories recalled.

Indeed, during 2008 there were 2,141 lost workdays due to these types of injuries, more than triple the number in 2005.

Next came a big investment in ceiling-mounted motorized lifts. The impact was minimal: roughly a 10% reduction in staff injuries. Problems with the lifts abounded. They broke. Some staff had difficulty operating them. But the biggest issue was that the rooms with the lifts weren’t always available because the hospital is always fully occupied.

Dr. Pories credited the nursing staff with providing the leadership in developing what he calls the Vidant Medical Center lift team model. Coverage is available 24/7. There are three teams of two individuals on duty during the day and two teams of two at night. They work 12-hour shifts. There is one supervisor for 23 lift team technicians, including three women. They are paid an average of $10 per hour, which the surgeon called "a pretty good wage in eastern North Carolina."

Individuals must pass a rigorous physical assessment before they can join the lift team. Members take a 3-week orientation program in which they learn safe lift techniques, skin and wound care, and infection control. They have their own uniforms to foster esprit de corps.

Many other organizations had tried using lift teams, with disappointing results. That’s because they limited the teams to the day shift or scheduled transfers, according to Dr. Pories.

"The real problems happen late at night," he said.

Dr. Pories and his coinvestigators conducted a pilot study in which they utilized the lift teams in the five hospital units having the highest staff injury rates due to patient-handling mishaps. The lift team was called to those units for moving patients who weighed more than 200 lb, had pressure ulcers, or who were at risk for pressure ulcers by virtue of a Braden scale score of 18 or less.

During the pilot study, 8 employee injuries resulted from patient handling in the five test units, for a rate of 0.134 injuries per 1,000 patient-days, compared with 71 injuries and a rate of 0.319 injuries per 1,000 patient-days in control units.

Once use of the lift teams expanded hospital-wide, the result was a 39% drop in employee injuries due to patient handling, as well as a 43% reduction in hospital-acquired pressure ulcers. Multiple staff surveys have shown 90%-99% satisfaction rates with the lift teams as having improved the workplace while demonstrating that the hospital cares about employee safety.

The total direct and indirect cost of staff injuries due to patient handling was approximately $2.76 million per year prior to introduction of the lift teams. The lift teams provided an estimated $423,152 in savings due to fewer staff injuries and hospital-acquired pressure ulcers, even after factoring in team salaries and equipment, Dr. Pories reported.

The next step in this project will be to document whether the presence of the lift teams also has resulted in fewer patient injuries, he added.

Discussant Dr. Philip R. Schauer commented that if the favorable Vidant experience with dedicated lift teams can be confirmed elsewhere, this is the type of program that should be widely instituted all across the country.

"It’s quite extraordinary to improve patient care and employee health while at the same time reducing overall cost," noted Dr. Schauer, professor of surgery and director of the Bariatric and Metabolic Institute at the Cleveland Clinic.

Discussant Dr. William B. Inabnet III said many malpractice insurance carriers are now offering hospitals incentives for reduced premiums for implementation of best-practices clinical pathways for management of obese patients.

"I think your work will support that type of mission. It’s a win-win for all parties involved," said Dr. Inabnet, professor of surgery at Mt. Sinai Hospital in New York.

Dr. Pories reported having no conflicts of interest.

[email protected]

INDIANAPOLIS – A major hidden cost of the obesity epidemic is the physical toll it takes on hospital nurses and other employees in helping to move heavy patients. The cost of these workplace injuries is skyrocketing, not only in terms of direct medical care bills, but also in terms of work absenteeism, activity restrictions, retraining, and employee dissatisfaction and fear.

The solution at one large tertiary academic medical center in eastern North Carolina has been to create specially trained two-person lift teams available 24/7. The results of a pilot study have been impressive, particularly in light of the fact that nothing else hospital officials tried earlier – including spending more than $1.5 million for motorized patient ceiling lifts – had any significant impact, Dr. Walter J. Pories said at the annual meeting of the American Surgical Association.

Hospital employee injuries incurred in handling obese patients are an issue that has until now been largely beneath physicians’ radar.

"I don’t think anybody here would ask two nurses to pick up a washing machine, or a 400-lb calf, or an 800-lb lathe, and yet whether we like it or not we ask our staff to move patients with such weights daily," observed Dr. Pories, professor of surgery at East Carolina University in Greenville, N.C.

He practices at Vidant Medical Center, a 909-bed hospital where administrators noticed back in 2005 that employee workplace compensation claims for injuries during patient transport were rapidly escalating. In that year, 98 staff experienced patient-handling injuries, resulting in 670 lost workdays and 3,022 restricted workdays.

Hospital officials tried several interventions. First came an intensive education program on safe lifting and patient mobilization conducted by an ergonomist.

"It didn’t make a bit of difference," Dr. Pories recalled.

Indeed, during 2008 there were 2,141 lost workdays due to these types of injuries, more than triple the number in 2005.

Next came a big investment in ceiling-mounted motorized lifts. The impact was minimal: roughly a 10% reduction in staff injuries. Problems with the lifts abounded. They broke. Some staff had difficulty operating them. But the biggest issue was that the rooms with the lifts weren’t always available because the hospital is always fully occupied.

Dr. Pories credited the nursing staff with providing the leadership in developing what he calls the Vidant Medical Center lift team model. Coverage is available 24/7. There are three teams of two individuals on duty during the day and two teams of two at night. They work 12-hour shifts. There is one supervisor for 23 lift team technicians, including three women. They are paid an average of $10 per hour, which the surgeon called "a pretty good wage in eastern North Carolina."

Individuals must pass a rigorous physical assessment before they can join the lift team. Members take a 3-week orientation program in which they learn safe lift techniques, skin and wound care, and infection control. They have their own uniforms to foster esprit de corps.

Many other organizations had tried using lift teams, with disappointing results. That’s because they limited the teams to the day shift or scheduled transfers, according to Dr. Pories.

"The real problems happen late at night," he said.

Dr. Pories and his coinvestigators conducted a pilot study in which they utilized the lift teams in the five hospital units having the highest staff injury rates due to patient-handling mishaps. The lift team was called to those units for moving patients who weighed more than 200 lb, had pressure ulcers, or who were at risk for pressure ulcers by virtue of a Braden scale score of 18 or less.

During the pilot study, 8 employee injuries resulted from patient handling in the five test units, for a rate of 0.134 injuries per 1,000 patient-days, compared with 71 injuries and a rate of 0.319 injuries per 1,000 patient-days in control units.

Once use of the lift teams expanded hospital-wide, the result was a 39% drop in employee injuries due to patient handling, as well as a 43% reduction in hospital-acquired pressure ulcers. Multiple staff surveys have shown 90%-99% satisfaction rates with the lift teams as having improved the workplace while demonstrating that the hospital cares about employee safety.

The total direct and indirect cost of staff injuries due to patient handling was approximately $2.76 million per year prior to introduction of the lift teams. The lift teams provided an estimated $423,152 in savings due to fewer staff injuries and hospital-acquired pressure ulcers, even after factoring in team salaries and equipment, Dr. Pories reported.

The next step in this project will be to document whether the presence of the lift teams also has resulted in fewer patient injuries, he added.

Discussant Dr. Philip R. Schauer commented that if the favorable Vidant experience with dedicated lift teams can be confirmed elsewhere, this is the type of program that should be widely instituted all across the country.

"It’s quite extraordinary to improve patient care and employee health while at the same time reducing overall cost," noted Dr. Schauer, professor of surgery and director of the Bariatric and Metabolic Institute at the Cleveland Clinic.

Discussant Dr. William B. Inabnet III said many malpractice insurance carriers are now offering hospitals incentives for reduced premiums for implementation of best-practices clinical pathways for management of obese patients.

"I think your work will support that type of mission. It’s a win-win for all parties involved," said Dr. Inabnet, professor of surgery at Mt. Sinai Hospital in New York.

Dr. Pories reported having no conflicts of interest.

[email protected]

FORT LAUDERDALE, FLA. – Opioids aren’t always appropriate for treating pain, and if they have to be prescribed, they must be used cautiously and at the lowest effective dosage, Dr. Lynn R. Webster advised.

Misuse and abuse of pharmaceuticals including opioids rank high among the nation’s public health concerns. Emergency department visits involving these drugs increased from 627,000 in 2004 to nearly 1,430,000 in 2011, according to the latest data from the Substance Abuse and Mental Health Services Administration. Narcotic pain relievers were among the most commonly misused or abused drug (134.8 ED visits per 100,000 population).

And while the majority of overdose deaths due to opioids occur in people who obtain them illegally, "there’s a subset that physicians are responsible for," Dr. Webster, president of the American Academy of Pain Medicine, said at the academy’s annual meeting.

For the past 8 years, since Utah’s medical examiner was quoted on the front page of a local newspaper saying that there was an epidemic of overdose deaths from prescription drugs, Dr. Webster has been on a mission to establish easy-to-follow, evidence-based principles for safe opioid prescribing in outpatient settings.

Various guidelines on safe opioid prescribing are currently available, "and they are all useful and helpful, but, in my view, not specific-enough to have an immediate impact," Dr. Webster said in an interview. "They address grander, larger problems. But these eight principles are specifically targeted to prevent deaths."

For easy recall, the principles are summed up in the trademarked acronym: RELIABLE – Respiratory, Experience, Long term, Initiating methadone, Apnea, Benzodiazepine, Look for comorbidities, and Exercise caution with switching. They’re now part of the AAPM’s Safe Opioid Prescribing Initiative:

• Respiratory: If you have a patient who is on long-term opioids and develops a respiratory condition (asthma, pneumonia, flu), reduce the opioid dose by 20%-30%.

• Experience: Assess the patient before prescribing opioids. Find out what the biologic, social, and psychiatric risk factors are.

• Long term: Extended-release opioids should not be used for acute pain. "And that’s the bottom line," said Dr. Webster.

• Initiating methadone: "Never start anybody on more than 15 mg a day," Dr. Webster advised, adding that the wrong starting dose for methadone can be lethal. "There are reported deaths of people on 30 mg a day."

• Apnea: Screen for obstructive and central sleep apnea. Screen for hypoxemia. "Patients that are on 150 mg morphine-equivalent, people who are very overweight, people who are infirm and elderly people, we need to make sure that opioids are safe for them, and we need to do sleep studies."

• Benzodiazepines: "Should be avoided if at all possible when you are prescribing opioids," because in the face of benzodiazepines, the toxicity of opioids is significantly enhanced. "If a benzo is used, reduce the dose of opioids. And look for an alternative (to benzodiazepines) if you have to prescribe an opioid."

• Look for comorbidities: Find out if patients have a history of bipolar disorder, posttraumatic stress disorder, depression, stress, "and particularly general anxiety disorder." Patients will often misuse the medications for their mental health disorder instead of their pain.

• Exercise caution with rotation: "Conversion tables and equal analgesic tables should not be used to determine the starting dose of opioids. You have to assume that everybody is opioid naive, and start on a low dose, and titrate slowly to a level that you think is the maximum dose you think you can safely prescribe.

"Physicians can have an impact in reducing the number of overdose deaths, but it’s going to require a little bit of effort to learn these eight principles, and if we all do this, I think we’ll see a dramatic reduction in overdose deaths," Dr. Webster said.

The principles are likely to be published soon, he said, and they will be available on the AAPM’s website in the near future.

Dr. Webster said he had received honoraria/travel support from AstraZeneca, Covidien Mallinckrodt, Jazz Pharmaceuticals, Medtronic, Nektar Therapeutics, Pfizer, and Salix.

[email protected]

On Twitter @NaseemSMiller

FORT LAUDERDALE, FLA. – Opioids aren’t always appropriate for treating pain, and if they have to be prescribed, they must be used cautiously and at the lowest effective dosage, Dr. Lynn R. Webster advised.

Misuse and abuse of pharmaceuticals including opioids rank high among the nation’s public health concerns. Emergency department visits involving these drugs increased from 627,000 in 2004 to nearly 1,430,000 in 2011, according to the latest data from the Substance Abuse and Mental Health Services Administration. Narcotic pain relievers were among the most commonly misused or abused drug (134.8 ED visits per 100,000 population).

And while the majority of overdose deaths due to opioids occur in people who obtain them illegally, "there’s a subset that physicians are responsible for," Dr. Webster, president of the American Academy of Pain Medicine, said at the academy’s annual meeting.

For the past 8 years, since Utah’s medical examiner was quoted on the front page of a local newspaper saying that there was an epidemic of overdose deaths from prescription drugs, Dr. Webster has been on a mission to establish easy-to-follow, evidence-based principles for safe opioid prescribing in outpatient settings.

Various guidelines on safe opioid prescribing are currently available, "and they are all useful and helpful, but, in my view, not specific-enough to have an immediate impact," Dr. Webster said in an interview. "They address grander, larger problems. But these eight principles are specifically targeted to prevent deaths."

For easy recall, the principles are summed up in the trademarked acronym: RELIABLE – Respiratory, Experience, Long term, Initiating methadone, Apnea, Benzodiazepine, Look for comorbidities, and Exercise caution with switching. They’re now part of the AAPM’s Safe Opioid Prescribing Initiative:

• Respiratory: If you have a patient who is on long-term opioids and develops a respiratory condition (asthma, pneumonia, flu), reduce the opioid dose by 20%-30%.

• Experience: Assess the patient before prescribing opioids. Find out what the biologic, social, and psychiatric risk factors are.

• Long term: Extended-release opioids should not be used for acute pain. "And that’s the bottom line," said Dr. Webster.

• Initiating methadone: "Never start anybody on more than 15 mg a day," Dr. Webster advised, adding that the wrong starting dose for methadone can be lethal. "There are reported deaths of people on 30 mg a day."

• Apnea: Screen for obstructive and central sleep apnea. Screen for hypoxemia. "Patients that are on 150 mg morphine-equivalent, people who are very overweight, people who are infirm and elderly people, we need to make sure that opioids are safe for them, and we need to do sleep studies."

• Benzodiazepines: "Should be avoided if at all possible when you are prescribing opioids," because in the face of benzodiazepines, the toxicity of opioids is significantly enhanced. "If a benzo is used, reduce the dose of opioids. And look for an alternative (to benzodiazepines) if you have to prescribe an opioid."

• Look for comorbidities: Find out if patients have a history of bipolar disorder, posttraumatic stress disorder, depression, stress, "and particularly general anxiety disorder." Patients will often misuse the medications for their mental health disorder instead of their pain.

• Exercise caution with rotation: "Conversion tables and equal analgesic tables should not be used to determine the starting dose of opioids. You have to assume that everybody is opioid naive, and start on a low dose, and titrate slowly to a level that you think is the maximum dose you think you can safely prescribe.

"Physicians can have an impact in reducing the number of overdose deaths, but it’s going to require a little bit of effort to learn these eight principles, and if we all do this, I think we’ll see a dramatic reduction in overdose deaths," Dr. Webster said.

The principles are likely to be published soon, he said, and they will be available on the AAPM’s website in the near future.

Dr. Webster said he had received honoraria/travel support from AstraZeneca, Covidien Mallinckrodt, Jazz Pharmaceuticals, Medtronic, Nektar Therapeutics, Pfizer, and Salix.

[email protected]

On Twitter @NaseemSMiller

FORT LAUDERDALE, FLA. – Opioids aren’t always appropriate for treating pain, and if they have to be prescribed, they must be used cautiously and at the lowest effective dosage, Dr. Lynn R. Webster advised.

Misuse and abuse of pharmaceuticals including opioids rank high among the nation’s public health concerns. Emergency department visits involving these drugs increased from 627,000 in 2004 to nearly 1,430,000 in 2011, according to the latest data from the Substance Abuse and Mental Health Services Administration. Narcotic pain relievers were among the most commonly misused or abused drug (134.8 ED visits per 100,000 population).

And while the majority of overdose deaths due to opioids occur in people who obtain them illegally, "there’s a subset that physicians are responsible for," Dr. Webster, president of the American Academy of Pain Medicine, said at the academy’s annual meeting.

For the past 8 years, since Utah’s medical examiner was quoted on the front page of a local newspaper saying that there was an epidemic of overdose deaths from prescription drugs, Dr. Webster has been on a mission to establish easy-to-follow, evidence-based principles for safe opioid prescribing in outpatient settings.

Various guidelines on safe opioid prescribing are currently available, "and they are all useful and helpful, but, in my view, not specific-enough to have an immediate impact," Dr. Webster said in an interview. "They address grander, larger problems. But these eight principles are specifically targeted to prevent deaths."

For easy recall, the principles are summed up in the trademarked acronym: RELIABLE – Respiratory, Experience, Long term, Initiating methadone, Apnea, Benzodiazepine, Look for comorbidities, and Exercise caution with switching. They’re now part of the AAPM’s Safe Opioid Prescribing Initiative:

• Respiratory: If you have a patient who is on long-term opioids and develops a respiratory condition (asthma, pneumonia, flu), reduce the opioid dose by 20%-30%.

• Experience: Assess the patient before prescribing opioids. Find out what the biologic, social, and psychiatric risk factors are.

• Long term: Extended-release opioids should not be used for acute pain. "And that’s the bottom line," said Dr. Webster.

• Initiating methadone: "Never start anybody on more than 15 mg a day," Dr. Webster advised, adding that the wrong starting dose for methadone can be lethal. "There are reported deaths of people on 30 mg a day."

• Apnea: Screen for obstructive and central sleep apnea. Screen for hypoxemia. "Patients that are on 150 mg morphine-equivalent, people who are very overweight, people who are infirm and elderly people, we need to make sure that opioids are safe for them, and we need to do sleep studies."

• Benzodiazepines: "Should be avoided if at all possible when you are prescribing opioids," because in the face of benzodiazepines, the toxicity of opioids is significantly enhanced. "If a benzo is used, reduce the dose of opioids. And look for an alternative (to benzodiazepines) if you have to prescribe an opioid."

• Look for comorbidities: Find out if patients have a history of bipolar disorder, posttraumatic stress disorder, depression, stress, "and particularly general anxiety disorder." Patients will often misuse the medications for their mental health disorder instead of their pain.

• Exercise caution with rotation: "Conversion tables and equal analgesic tables should not be used to determine the starting dose of opioids. You have to assume that everybody is opioid naive, and start on a low dose, and titrate slowly to a level that you think is the maximum dose you think you can safely prescribe.

"Physicians can have an impact in reducing the number of overdose deaths, but it’s going to require a little bit of effort to learn these eight principles, and if we all do this, I think we’ll see a dramatic reduction in overdose deaths," Dr. Webster said.

The principles are likely to be published soon, he said, and they will be available on the AAPM’s website in the near future.

Dr. Webster said he had received honoraria/travel support from AstraZeneca, Covidien Mallinckrodt, Jazz Pharmaceuticals, Medtronic, Nektar Therapeutics, Pfizer, and Salix.

[email protected]

On Twitter @NaseemSMiller

For patients at elevated cardiac risk who are undergoing major noncardiac surgery, early perioperative use of beta-blockers is associated with significantly lower 30-day all-cause mortality and cardiac morbidity, according to a report in the April 24 issue of JAMA.

In a retrospective cohort study, this association was strongest in the patients at highest cardiac risk – those with two or more factors on the six-item Cardiac Risk Index, said Dr. Martin J. London of the department of anesthesia and perioperative care, U.S. Department of Veterans Affairs Medical Center, San Francisco, and his associates.

Beta-blocker use in this setting remains controversial, and the use of perioperative beta-blockers has been declining, because of safety concerns. To examine whether high-risk patients are helped or harmed by the treatment, Dr. London and his colleagues analyzed data from the VA Surgical Quality Improvement Program database, a VA pharmacy database, and a VA administrative database.

They assessed the records of 136,745 patients who had vascular, general, neurologic, orthopedic, thoracic, urologic, or otolaryngologic surgery at 104 VA medical centers in 2005-2010.

A total of 40.3% of these subjects had received beta-blockers on the day of or the day after surgery, and 33.2% were given outpatient prescriptions for beta-blockers within 7 days of surgery.

There was a modest but significant decline in beta-blocker use during the 5-year study period, from 43.5% in the first year to 36.2% in the last. A similar national trend has been reported in previous studies. "This may be related to the findings of the POISE trial of increased stroke and death in treated patients, leading to more conservative guideline recommendations within this period," the investigators said.

They performed 1:1 propensity matching and identified 37,805 matched pairs of exposed and nonexposed patients for the primary outcome analysis. The primary outcome measure – all-cause mortality at 30 days – was significantly lower (relative risk 0.73) among patients who used beta-blockers than among those who did not, with a number needed to treat of 241 (JAMA 2013;309:1704-13).

The study subjects were categorized according to their scores on the revised Cardiac Risk Index, which includes six variables: high-risk surgery, cerebrovascular disease, ischemic heart disease, heart failure, diabetes, and renal insufficiency. Patients who had two or more of these CRI risk factors showed the greatest mortality benefit from perioperative beta-blocker therapy, with an relative risk of 0.63.

When the data were broken down by type of surgery, mortality remained significantly lower in beta-blocker users, compared with nonusers for every category except vascular surgery. In previous studies, beta-blockers have shown equivocal benefit in this same subgroup of surgery patients, Dr. London and his associates noted.

The secondary outcome measure of the study was a composite of Q-wave myocardial infarction or nonfatal cardiac arrest at 30 days. These may be rare complications but they are highly predictive of subsequent mortality, the researchers said.

Again, patients who took beta-blockers showed significantly less cardiac morbidity than those who did not, with a relative risk of 0.67 and a number needed to treat of 339.

The study results remained robust in a sensitivity analysis that categorized patients according to whether they had been taking beta-blockers before hospitalization, as well as in a sensitivity analysis that categorized patients as either acute or chronic users of beta-blockers.

This study confirmed the previous finding that withdrawal of beta-blockers within 30 days of surgery is associated with increased mortality. In this study, the risk of death was approximately doubled if beta-blockers were withdrawn perioperatively.

In a post hoc analysis, "we were unable to demonstrate significant associations of perioperative beta-blockade with the risk of postoperative stroke." There was no significant difference in stroke rates between patients who received beta-blockers and those who did not, Dr. London and his colleagues said.

This study was supported by a grant from the Anesthesia Patient Safety Foundation. Dr. London reported no financial conflicts of interest. An associate reported ties to Roche, Resverlogie, Anthera, and Sanofi.

For patients at elevated cardiac risk who are undergoing major noncardiac surgery, early perioperative use of beta-blockers is associated with significantly lower 30-day all-cause mortality and cardiac morbidity, according to a report in the April 24 issue of JAMA.

In a retrospective cohort study, this association was strongest in the patients at highest cardiac risk – those with two or more factors on the six-item Cardiac Risk Index, said Dr. Martin J. London of the department of anesthesia and perioperative care, U.S. Department of Veterans Affairs Medical Center, San Francisco, and his associates.

Beta-blocker use in this setting remains controversial, and the use of perioperative beta-blockers has been declining, because of safety concerns. To examine whether high-risk patients are helped or harmed by the treatment, Dr. London and his colleagues analyzed data from the VA Surgical Quality Improvement Program database, a VA pharmacy database, and a VA administrative database.

They assessed the records of 136,745 patients who had vascular, general, neurologic, orthopedic, thoracic, urologic, or otolaryngologic surgery at 104 VA medical centers in 2005-2010.

A total of 40.3% of these subjects had received beta-blockers on the day of or the day after surgery, and 33.2% were given outpatient prescriptions for beta-blockers within 7 days of surgery.

There was a modest but significant decline in beta-blocker use during the 5-year study period, from 43.5% in the first year to 36.2% in the last. A similar national trend has been reported in previous studies. "This may be related to the findings of the POISE trial of increased stroke and death in treated patients, leading to more conservative guideline recommendations within this period," the investigators said.

They performed 1:1 propensity matching and identified 37,805 matched pairs of exposed and nonexposed patients for the primary outcome analysis. The primary outcome measure – all-cause mortality at 30 days – was significantly lower (relative risk 0.73) among patients who used beta-blockers than among those who did not, with a number needed to treat of 241 (JAMA 2013;309:1704-13).

The study subjects were categorized according to their scores on the revised Cardiac Risk Index, which includes six variables: high-risk surgery, cerebrovascular disease, ischemic heart disease, heart failure, diabetes, and renal insufficiency. Patients who had two or more of these CRI risk factors showed the greatest mortality benefit from perioperative beta-blocker therapy, with an relative risk of 0.63.

When the data were broken down by type of surgery, mortality remained significantly lower in beta-blocker users, compared with nonusers for every category except vascular surgery. In previous studies, beta-blockers have shown equivocal benefit in this same subgroup of surgery patients, Dr. London and his associates noted.

The secondary outcome measure of the study was a composite of Q-wave myocardial infarction or nonfatal cardiac arrest at 30 days. These may be rare complications but they are highly predictive of subsequent mortality, the researchers said.

Again, patients who took beta-blockers showed significantly less cardiac morbidity than those who did not, with a relative risk of 0.67 and a number needed to treat of 339.

The study results remained robust in a sensitivity analysis that categorized patients according to whether they had been taking beta-blockers before hospitalization, as well as in a sensitivity analysis that categorized patients as either acute or chronic users of beta-blockers.

This study confirmed the previous finding that withdrawal of beta-blockers within 30 days of surgery is associated with increased mortality. In this study, the risk of death was approximately doubled if beta-blockers were withdrawn perioperatively.

In a post hoc analysis, "we were unable to demonstrate significant associations of perioperative beta-blockade with the risk of postoperative stroke." There was no significant difference in stroke rates between patients who received beta-blockers and those who did not, Dr. London and his colleagues said.

This study was supported by a grant from the Anesthesia Patient Safety Foundation. Dr. London reported no financial conflicts of interest. An associate reported ties to Roche, Resverlogie, Anthera, and Sanofi.

For patients at elevated cardiac risk who are undergoing major noncardiac surgery, early perioperative use of beta-blockers is associated with significantly lower 30-day all-cause mortality and cardiac morbidity, according to a report in the April 24 issue of JAMA.

In a retrospective cohort study, this association was strongest in the patients at highest cardiac risk – those with two or more factors on the six-item Cardiac Risk Index, said Dr. Martin J. London of the department of anesthesia and perioperative care, U.S. Department of Veterans Affairs Medical Center, San Francisco, and his associates.

Beta-blocker use in this setting remains controversial, and the use of perioperative beta-blockers has been declining, because of safety concerns. To examine whether high-risk patients are helped or harmed by the treatment, Dr. London and his colleagues analyzed data from the VA Surgical Quality Improvement Program database, a VA pharmacy database, and a VA administrative database.

They assessed the records of 136,745 patients who had vascular, general, neurologic, orthopedic, thoracic, urologic, or otolaryngologic surgery at 104 VA medical centers in 2005-2010.

A total of 40.3% of these subjects had received beta-blockers on the day of or the day after surgery, and 33.2% were given outpatient prescriptions for beta-blockers within 7 days of surgery.

There was a modest but significant decline in beta-blocker use during the 5-year study period, from 43.5% in the first year to 36.2% in the last. A similar national trend has been reported in previous studies. "This may be related to the findings of the POISE trial of increased stroke and death in treated patients, leading to more conservative guideline recommendations within this period," the investigators said.

They performed 1:1 propensity matching and identified 37,805 matched pairs of exposed and nonexposed patients for the primary outcome analysis. The primary outcome measure – all-cause mortality at 30 days – was significantly lower (relative risk 0.73) among patients who used beta-blockers than among those who did not, with a number needed to treat of 241 (JAMA 2013;309:1704-13).

The study subjects were categorized according to their scores on the revised Cardiac Risk Index, which includes six variables: high-risk surgery, cerebrovascular disease, ischemic heart disease, heart failure, diabetes, and renal insufficiency. Patients who had two or more of these CRI risk factors showed the greatest mortality benefit from perioperative beta-blocker therapy, with an relative risk of 0.63.

When the data were broken down by type of surgery, mortality remained significantly lower in beta-blocker users, compared with nonusers for every category except vascular surgery. In previous studies, beta-blockers have shown equivocal benefit in this same subgroup of surgery patients, Dr. London and his associates noted.

The secondary outcome measure of the study was a composite of Q-wave myocardial infarction or nonfatal cardiac arrest at 30 days. These may be rare complications but they are highly predictive of subsequent mortality, the researchers said.

Again, patients who took beta-blockers showed significantly less cardiac morbidity than those who did not, with a relative risk of 0.67 and a number needed to treat of 339.

The study results remained robust in a sensitivity analysis that categorized patients according to whether they had been taking beta-blockers before hospitalization, as well as in a sensitivity analysis that categorized patients as either acute or chronic users of beta-blockers.

This study confirmed the previous finding that withdrawal of beta-blockers within 30 days of surgery is associated with increased mortality. In this study, the risk of death was approximately doubled if beta-blockers were withdrawn perioperatively.

In a post hoc analysis, "we were unable to demonstrate significant associations of perioperative beta-blockade with the risk of postoperative stroke." There was no significant difference in stroke rates between patients who received beta-blockers and those who did not, Dr. London and his colleagues said.

This study was supported by a grant from the Anesthesia Patient Safety Foundation. Dr. London reported no financial conflicts of interest. An associate reported ties to Roche, Resverlogie, Anthera, and Sanofi.

Fifty-one runners and spectators remained hospitalized April 23 with injuries from the Boston Marathon bombings, according to the Boston Public Health Commission.

With a total of 264 patients treated at Boston area hospitals, "the team approach [was] vital," said Dr. Jeffrey Kalish, director of endovascular surgery at Boston Medical Center. "These types of injuries require multiple teams talking together and working together. It taught us really how to work together across multiple disciplines in a really acute time frame."

At BMC, "the initial approach was gathering every single surgeon available and figuring out who could do which specific operations," Dr. Kalish said.

"On the first day, the goal was to get the patients in and out of the operating room and stop the bleeding," he said. The next day [Tuesday], "we got together as a big group and talked about every patient and decided who was going to take over their care."

Teams met twice a day and while the surgeons focused on the patients, the hospital leadership made sure that adequate staff and infrastructure were available.

"This [experience] really taught me the importance of practicing for the unthinkable and practicing for the unknown, so when these things happen, it’s not as much of a surprise," said Dr. Kalish. "Talking about command structure and incident reporting and how to deploy the resources to the best of hospital’s knowledge is a very worthwhile thing."

Five patients at BMC have had above- or below-the-knee amputations and have averaged at least two surgical procedures each. One patient has had five.

For those with amputations, wound healing and pain control are now the most important factors, according to Dr. Simona Manasian, a rehabilitation medicine physician at BMC. Once the wounds are healed, the focus turns to shaping the stumps for prostheses.

Patients have begun early rehabilitation and physical therapy to strengthen the lower limbs and their upper bodies for mobility and support.

Patients also have been receiving psychological support, Dr. Manasian said. She added that they have been visited by several veterans who were similarly injured in Iraq or Afghanistan and who are farther along in adapting to amputations and prostheses. "That was very helpful."

Dr. Kalish added, "We’ve seen a full range of emotions over the past week. But now that we’re a week into this, everyone’s emotionally doing much better. [The patients are] optimistic, and they know that life will be a little different, but life is not over."

[email protected]

On Twitter @NaseemSMiller

Fifty-one runners and spectators remained hospitalized April 23 with injuries from the Boston Marathon bombings, according to the Boston Public Health Commission.

With a total of 264 patients treated at Boston area hospitals, "the team approach [was] vital," said Dr. Jeffrey Kalish, director of endovascular surgery at Boston Medical Center. "These types of injuries require multiple teams talking together and working together. It taught us really how to work together across multiple disciplines in a really acute time frame."

At BMC, "the initial approach was gathering every single surgeon available and figuring out who could do which specific operations," Dr. Kalish said.

"On the first day, the goal was to get the patients in and out of the operating room and stop the bleeding," he said. The next day [Tuesday], "we got together as a big group and talked about every patient and decided who was going to take over their care."

Teams met twice a day and while the surgeons focused on the patients, the hospital leadership made sure that adequate staff and infrastructure were available.

"This [experience] really taught me the importance of practicing for the unthinkable and practicing for the unknown, so when these things happen, it’s not as much of a surprise," said Dr. Kalish. "Talking about command structure and incident reporting and how to deploy the resources to the best of hospital’s knowledge is a very worthwhile thing."

Five patients at BMC have had above- or below-the-knee amputations and have averaged at least two surgical procedures each. One patient has had five.

For those with amputations, wound healing and pain control are now the most important factors, according to Dr. Simona Manasian, a rehabilitation medicine physician at BMC. Once the wounds are healed, the focus turns to shaping the stumps for prostheses.

Patients have begun early rehabilitation and physical therapy to strengthen the lower limbs and their upper bodies for mobility and support.

Patients also have been receiving psychological support, Dr. Manasian said. She added that they have been visited by several veterans who were similarly injured in Iraq or Afghanistan and who are farther along in adapting to amputations and prostheses. "That was very helpful."

Dr. Kalish added, "We’ve seen a full range of emotions over the past week. But now that we’re a week into this, everyone’s emotionally doing much better. [The patients are] optimistic, and they know that life will be a little different, but life is not over."

[email protected]

On Twitter @NaseemSMiller

Fifty-one runners and spectators remained hospitalized April 23 with injuries from the Boston Marathon bombings, according to the Boston Public Health Commission.

With a total of 264 patients treated at Boston area hospitals, "the team approach [was] vital," said Dr. Jeffrey Kalish, director of endovascular surgery at Boston Medical Center. "These types of injuries require multiple teams talking together and working together. It taught us really how to work together across multiple disciplines in a really acute time frame."

At BMC, "the initial approach was gathering every single surgeon available and figuring out who could do which specific operations," Dr. Kalish said.

"On the first day, the goal was to get the patients in and out of the operating room and stop the bleeding," he said. The next day [Tuesday], "we got together as a big group and talked about every patient and decided who was going to take over their care."

Teams met twice a day and while the surgeons focused on the patients, the hospital leadership made sure that adequate staff and infrastructure were available.

"This [experience] really taught me the importance of practicing for the unthinkable and practicing for the unknown, so when these things happen, it’s not as much of a surprise," said Dr. Kalish. "Talking about command structure and incident reporting and how to deploy the resources to the best of hospital’s knowledge is a very worthwhile thing."

Five patients at BMC have had above- or below-the-knee amputations and have averaged at least two surgical procedures each. One patient has had five.

For those with amputations, wound healing and pain control are now the most important factors, according to Dr. Simona Manasian, a rehabilitation medicine physician at BMC. Once the wounds are healed, the focus turns to shaping the stumps for prostheses.

Patients have begun early rehabilitation and physical therapy to strengthen the lower limbs and their upper bodies for mobility and support.

Patients also have been receiving psychological support, Dr. Manasian said. She added that they have been visited by several veterans who were similarly injured in Iraq or Afghanistan and who are farther along in adapting to amputations and prostheses. "That was very helpful."

Dr. Kalish added, "We’ve seen a full range of emotions over the past week. But now that we’re a week into this, everyone’s emotionally doing much better. [The patients are] optimistic, and they know that life will be a little different, but life is not over."

[email protected]

On Twitter @NaseemSMiller

In an eleventh-hour action that derailed the possibility of generic formulations of controlled-release oxycodone (OxyContin) from appearing on the U.S. market anytime soon, the Food and Drug Administration announced April 16 that it withdrew its approval of the original, conventional formulation of OxyContin.

Acting on the very day that the patent on the original formulation of OxyContin, held by Purdue Pharma, was set to expire, the FDA took an additional step to support the newer formulation of OxyContin that Purdue has marketed exclusively since August 2010. The newer version includes a polymer so that, when a pill is crushed and then mixed with water it turns into a gel rather than remaining a more easily manipulated powder. The FDA approved updated labeling for OxyContin that highlights the abuse-deterring features of the newer formulation, which means that Purdue can now cite these attributes when marketing the drug.

The FDA "approved labeling for reformulated OxyContin stating that it possesses physiochemical properties that are expected to: (1) make abuse via injection difficult, and (2) reduce abuse via the intranasal route. This is the first opioid product for which FDA has approved labeling that includes statements regarding abuse-deterrence," according to a letter from FDA Commissioner Margaret A. Hamburg sent April 16 to Rep. Fred Upton (R-Mich.) and Sen. Tom Coburn (R-Okla).

"We applaud FDA Commissioner Hamburg’s announcement that the FDA will not approve any abbreviated new drug applications that rely upon the approval of original OxyContin which did not have abuse-deterrent properties," the lawmakers said in a statement. "With more than 16,000 Americans dying from opioid drug overdoses each year, Commissioner Hamburg’s announcement is a significant step forward in the federal government’s effort to reduce opioid drug abuse and protect consumers. For too long, drug abusers have been able to crush or dissolve opioid drug products in order to defeat their time-release mechanisms for snorting or injecting the drugs."

For patients, the major downside of the FDA’s action is economic. OxyContin retails for about $7.50 per tablet and had roughly $2.7 billion in U.S. sales in 2012. The patent on the abuse-deterring formulation of the drug lasts until 2025.

[email protected]

On Twitter @mitchelzoler

In an eleventh-hour action that derailed the possibility of generic formulations of controlled-release oxycodone (OxyContin) from appearing on the U.S. market anytime soon, the Food and Drug Administration announced April 16 that it withdrew its approval of the original, conventional formulation of OxyContin.

Acting on the very day that the patent on the original formulation of OxyContin, held by Purdue Pharma, was set to expire, the FDA took an additional step to support the newer formulation of OxyContin that Purdue has marketed exclusively since August 2010. The newer version includes a polymer so that, when a pill is crushed and then mixed with water it turns into a gel rather than remaining a more easily manipulated powder. The FDA approved updated labeling for OxyContin that highlights the abuse-deterring features of the newer formulation, which means that Purdue can now cite these attributes when marketing the drug.

The FDA "approved labeling for reformulated OxyContin stating that it possesses physiochemical properties that are expected to: (1) make abuse via injection difficult, and (2) reduce abuse via the intranasal route. This is the first opioid product for which FDA has approved labeling that includes statements regarding abuse-deterrence," according to a letter from FDA Commissioner Margaret A. Hamburg sent April 16 to Rep. Fred Upton (R-Mich.) and Sen. Tom Coburn (R-Okla).

"We applaud FDA Commissioner Hamburg’s announcement that the FDA will not approve any abbreviated new drug applications that rely upon the approval of original OxyContin which did not have abuse-deterrent properties," the lawmakers said in a statement. "With more than 16,000 Americans dying from opioid drug overdoses each year, Commissioner Hamburg’s announcement is a significant step forward in the federal government’s effort to reduce opioid drug abuse and protect consumers. For too long, drug abusers have been able to crush or dissolve opioid drug products in order to defeat their time-release mechanisms for snorting or injecting the drugs."

For patients, the major downside of the FDA’s action is economic. OxyContin retails for about $7.50 per tablet and had roughly $2.7 billion in U.S. sales in 2012. The patent on the abuse-deterring formulation of the drug lasts until 2025.

[email protected]

On Twitter @mitchelzoler

In an eleventh-hour action that derailed the possibility of generic formulations of controlled-release oxycodone (OxyContin) from appearing on the U.S. market anytime soon, the Food and Drug Administration announced April 16 that it withdrew its approval of the original, conventional formulation of OxyContin.

Acting on the very day that the patent on the original formulation of OxyContin, held by Purdue Pharma, was set to expire, the FDA took an additional step to support the newer formulation of OxyContin that Purdue has marketed exclusively since August 2010. The newer version includes a polymer so that, when a pill is crushed and then mixed with water it turns into a gel rather than remaining a more easily manipulated powder. The FDA approved updated labeling for OxyContin that highlights the abuse-deterring features of the newer formulation, which means that Purdue can now cite these attributes when marketing the drug.

The FDA "approved labeling for reformulated OxyContin stating that it possesses physiochemical properties that are expected to: (1) make abuse via injection difficult, and (2) reduce abuse via the intranasal route. This is the first opioid product for which FDA has approved labeling that includes statements regarding abuse-deterrence," according to a letter from FDA Commissioner Margaret A. Hamburg sent April 16 to Rep. Fred Upton (R-Mich.) and Sen. Tom Coburn (R-Okla).

"We applaud FDA Commissioner Hamburg’s announcement that the FDA will not approve any abbreviated new drug applications that rely upon the approval of original OxyContin which did not have abuse-deterrent properties," the lawmakers said in a statement. "With more than 16,000 Americans dying from opioid drug overdoses each year, Commissioner Hamburg’s announcement is a significant step forward in the federal government’s effort to reduce opioid drug abuse and protect consumers. For too long, drug abusers have been able to crush or dissolve opioid drug products in order to defeat their time-release mechanisms for snorting or injecting the drugs."

For patients, the major downside of the FDA’s action is economic. OxyContin retails for about $7.50 per tablet and had roughly $2.7 billion in U.S. sales in 2012. The patent on the abuse-deterring formulation of the drug lasts until 2025.

[email protected]

On Twitter @mitchelzoler

Early supplemental glutamine appears to harm rather than benefit critically ill patients who have multiorgan failure, according to a report published online April 18 in the New England Journal of Medicine.

In an international randomized controlled trial, in-hospital mortality and 6-month mortality were significantly increased in patients given intravenous glutamine within 24 hours of presentation to the ICU, compared with those given placebo, said Dr. Daren Heyland of Kingston (Ont.) General Hospital and his associates. A nonsignificant increase was seen in 28-day mortality.

Most of the patients in this study showed no glutamine deficiency at study entry. This observation, together with the primary finding that glutamine therapy may actually be harmful in this setting, "challenges the prevailing concept that glutamine is an essential nutrient that is deficient in critically ill patients and requires immediate supplementation," Dr. Heyland and his colleagues said.

The researchers also assessed whether supplemental antioxidants improved mortality or other outcomes in this study population and found that they did not.

Dr. Heyland and his associates performed this study because glutamine is thought to be rapidly depleted in critical illness and low levels of glutamine have been linked to increased mortality in ICU patients. Metaanalyses of small randomized trials suggested that both glutamine and antioxidant supplementation might improve survival in critically ill patients, but more recent and larger studies failed to confirm such a benefit.

This study included 1,223 consecutive adults who presented to 40 ICUs in the United States, Canada, and Europe during a 6-year period and required mechanical ventilation and had two or more organ failures related to their acute illness. The average patient age was 63 years. Primary diagnoses included cardiovascular, respiratory, gastrointestinal, neurologic, metabolic, and gynecologic disorders as well as sepsis and trauma.

The patients were randomly assigned in a double-blind fashion to receive daily intravenous glutamine, intravenous plus enteral antioxidants, glutamine plus antioxidants, or placebo fluids. The antioxidants included selenium, zinc, beta carotene, vitamin E, and vitamin C.

The primary outcome measure was 28-day mortality. There was a nonsignificant trend toward higher mortality in the patients given glutamine (32.4%) compared with those not given glutamine (27.2%). However, two secondary outcomes – in-hospital mortality and 6-month mortality – both were significantly higher in patients given glutamine than in those not given glutamine. In hospital mortality was 37.2% vs. 31%, respectively; 6-month mortality was 43.7% vs. 37.2%, respectively.

Other secondary outcomes – median time from randomization to ICU discharge and median time to hospital discharge – also were significantly longer for patients who received glutamine (17.1 vs. 13.1 days and 51.1 vs. 40.1 days, respectively), the investigators said (N. Engl. J. Med. 2013 April 18 [doi:10.1056/NEJMoa1212722]).

These results were confirmed in a sensitivity analysis that included only patients who received their assigned intervention for a minimum of 5 days. They also remained the same in several subgroup analyses and in an intention-to-treat analysis.

Glutamine showed no effect on the secondary outcomes of organ failure or infections.

Antioxidants had no significant effect on any outcome, either in the study population as a whole or in any subgroups of patients. "This finding may reflect the true lack of usefulness of antioxidants; alternatively, it may be due to the characteristics of the study population or to the dose and method of administration in this trial," Dr. Heyland and his associates said.

Rates of serious adverse events were similar across all the study groups, but the frequency of excessively high urea levels was greater in patients who received glutamine (13.4%) than in those who did not (4.0%).

There may be several reasons why the findings of this clinical trial are so different from those of previous trials.

The earlier trials were smaller and less methodologically robust, and their results had to be pooled in metaanalyses. Patients in this trial received the highest dose of glutamine currently prescribed for critically ill patients, which is higher than the maximal doses used in previous studies. The agents were administered through both intravenous and enteral routes in this study, while in previous studies the subjects received either exclusively intravenous or exclusively enteral administration.

In addition, "we targeted critically ill patients with multiorgan failure, the majority of whom were in shock, whereas previous studies typically excluded such patients," Dr. Heyland and his colleagues said.

Treatment was initiated within 24 hours of admission to the ICU in this study, but in earlier studies it was given later in the course of critical illness. And finally, most of the patients in this study received enteral nutrition, while those in previous trials received parenteral nutrition.

This study was supported by the Canadian Institutes of Health Research. Fresenius Kabi provided the glutamine supplements and Biosyn provided the selenium to the participating European sites. Dr. Heyland and his associates reported ties to numerous industry sources.

Early supplemental glutamine appears to harm rather than benefit critically ill patients who have multiorgan failure, according to a report published online April 18 in the New England Journal of Medicine.

In an international randomized controlled trial, in-hospital mortality and 6-month mortality were significantly increased in patients given intravenous glutamine within 24 hours of presentation to the ICU, compared with those given placebo, said Dr. Daren Heyland of Kingston (Ont.) General Hospital and his associates. A nonsignificant increase was seen in 28-day mortality.

Most of the patients in this study showed no glutamine deficiency at study entry. This observation, together with the primary finding that glutamine therapy may actually be harmful in this setting, "challenges the prevailing concept that glutamine is an essential nutrient that is deficient in critically ill patients and requires immediate supplementation," Dr. Heyland and his colleagues said.

The researchers also assessed whether supplemental antioxidants improved mortality or other outcomes in this study population and found that they did not.

Dr. Heyland and his associates performed this study because glutamine is thought to be rapidly depleted in critical illness and low levels of glutamine have been linked to increased mortality in ICU patients. Metaanalyses of small randomized trials suggested that both glutamine and antioxidant supplementation might improve survival in critically ill patients, but more recent and larger studies failed to confirm such a benefit.

This study included 1,223 consecutive adults who presented to 40 ICUs in the United States, Canada, and Europe during a 6-year period and required mechanical ventilation and had two or more organ failures related to their acute illness. The average patient age was 63 years. Primary diagnoses included cardiovascular, respiratory, gastrointestinal, neurologic, metabolic, and gynecologic disorders as well as sepsis and trauma.

The patients were randomly assigned in a double-blind fashion to receive daily intravenous glutamine, intravenous plus enteral antioxidants, glutamine plus antioxidants, or placebo fluids. The antioxidants included selenium, zinc, beta carotene, vitamin E, and vitamin C.

The primary outcome measure was 28-day mortality. There was a nonsignificant trend toward higher mortality in the patients given glutamine (32.4%) compared with those not given glutamine (27.2%). However, two secondary outcomes – in-hospital mortality and 6-month mortality – both were significantly higher in patients given glutamine than in those not given glutamine. In hospital mortality was 37.2% vs. 31%, respectively; 6-month mortality was 43.7% vs. 37.2%, respectively.

Other secondary outcomes – median time from randomization to ICU discharge and median time to hospital discharge – also were significantly longer for patients who received glutamine (17.1 vs. 13.1 days and 51.1 vs. 40.1 days, respectively), the investigators said (N. Engl. J. Med. 2013 April 18 [doi:10.1056/NEJMoa1212722]).

These results were confirmed in a sensitivity analysis that included only patients who received their assigned intervention for a minimum of 5 days. They also remained the same in several subgroup analyses and in an intention-to-treat analysis.

Glutamine showed no effect on the secondary outcomes of organ failure or infections.

Antioxidants had no significant effect on any outcome, either in the study population as a whole or in any subgroups of patients. "This finding may reflect the true lack of usefulness of antioxidants; alternatively, it may be due to the characteristics of the study population or to the dose and method of administration in this trial," Dr. Heyland and his associates said.

Rates of serious adverse events were similar across all the study groups, but the frequency of excessively high urea levels was greater in patients who received glutamine (13.4%) than in those who did not (4.0%).

There may be several reasons why the findings of this clinical trial are so different from those of previous trials.

The earlier trials were smaller and less methodologically robust, and their results had to be pooled in metaanalyses. Patients in this trial received the highest dose of glutamine currently prescribed for critically ill patients, which is higher than the maximal doses used in previous studies. The agents were administered through both intravenous and enteral routes in this study, while in previous studies the subjects received either exclusively intravenous or exclusively enteral administration.

In addition, "we targeted critically ill patients with multiorgan failure, the majority of whom were in shock, whereas previous studies typically excluded such patients," Dr. Heyland and his colleagues said.

Treatment was initiated within 24 hours of admission to the ICU in this study, but in earlier studies it was given later in the course of critical illness. And finally, most of the patients in this study received enteral nutrition, while those in previous trials received parenteral nutrition.

This study was supported by the Canadian Institutes of Health Research. Fresenius Kabi provided the glutamine supplements and Biosyn provided the selenium to the participating European sites. Dr. Heyland and his associates reported ties to numerous industry sources.

Early supplemental glutamine appears to harm rather than benefit critically ill patients who have multiorgan failure, according to a report published online April 18 in the New England Journal of Medicine.

In an international randomized controlled trial, in-hospital mortality and 6-month mortality were significantly increased in patients given intravenous glutamine within 24 hours of presentation to the ICU, compared with those given placebo, said Dr. Daren Heyland of Kingston (Ont.) General Hospital and his associates. A nonsignificant increase was seen in 28-day mortality.

Most of the patients in this study showed no glutamine deficiency at study entry. This observation, together with the primary finding that glutamine therapy may actually be harmful in this setting, "challenges the prevailing concept that glutamine is an essential nutrient that is deficient in critically ill patients and requires immediate supplementation," Dr. Heyland and his colleagues said.

The researchers also assessed whether supplemental antioxidants improved mortality or other outcomes in this study population and found that they did not.

Dr. Heyland and his associates performed this study because glutamine is thought to be rapidly depleted in critical illness and low levels of glutamine have been linked to increased mortality in ICU patients. Metaanalyses of small randomized trials suggested that both glutamine and antioxidant supplementation might improve survival in critically ill patients, but more recent and larger studies failed to confirm such a benefit.

This study included 1,223 consecutive adults who presented to 40 ICUs in the United States, Canada, and Europe during a 6-year period and required mechanical ventilation and had two or more organ failures related to their acute illness. The average patient age was 63 years. Primary diagnoses included cardiovascular, respiratory, gastrointestinal, neurologic, metabolic, and gynecologic disorders as well as sepsis and trauma.

The patients were randomly assigned in a double-blind fashion to receive daily intravenous glutamine, intravenous plus enteral antioxidants, glutamine plus antioxidants, or placebo fluids. The antioxidants included selenium, zinc, beta carotene, vitamin E, and vitamin C.

The primary outcome measure was 28-day mortality. There was a nonsignificant trend toward higher mortality in the patients given glutamine (32.4%) compared with those not given glutamine (27.2%). However, two secondary outcomes – in-hospital mortality and 6-month mortality – both were significantly higher in patients given glutamine than in those not given glutamine. In hospital mortality was 37.2% vs. 31%, respectively; 6-month mortality was 43.7% vs. 37.2%, respectively.

Other secondary outcomes – median time from randomization to ICU discharge and median time to hospital discharge – also were significantly longer for patients who received glutamine (17.1 vs. 13.1 days and 51.1 vs. 40.1 days, respectively), the investigators said (N. Engl. J. Med. 2013 April 18 [doi:10.1056/NEJMoa1212722]).

These results were confirmed in a sensitivity analysis that included only patients who received their assigned intervention for a minimum of 5 days. They also remained the same in several subgroup analyses and in an intention-to-treat analysis.

Glutamine showed no effect on the secondary outcomes of organ failure or infections.

Antioxidants had no significant effect on any outcome, either in the study population as a whole or in any subgroups of patients. "This finding may reflect the true lack of usefulness of antioxidants; alternatively, it may be due to the characteristics of the study population or to the dose and method of administration in this trial," Dr. Heyland and his associates said.

Rates of serious adverse events were similar across all the study groups, but the frequency of excessively high urea levels was greater in patients who received glutamine (13.4%) than in those who did not (4.0%).

There may be several reasons why the findings of this clinical trial are so different from those of previous trials.

The earlier trials were smaller and less methodologically robust, and their results had to be pooled in metaanalyses. Patients in this trial received the highest dose of glutamine currently prescribed for critically ill patients, which is higher than the maximal doses used in previous studies. The agents were administered through both intravenous and enteral routes in this study, while in previous studies the subjects received either exclusively intravenous or exclusively enteral administration.

In addition, "we targeted critically ill patients with multiorgan failure, the majority of whom were in shock, whereas previous studies typically excluded such patients," Dr. Heyland and his colleagues said.

Treatment was initiated within 24 hours of admission to the ICU in this study, but in earlier studies it was given later in the course of critical illness. And finally, most of the patients in this study received enteral nutrition, while those in previous trials received parenteral nutrition.

This study was supported by the Canadian Institutes of Health Research. Fresenius Kabi provided the glutamine supplements and Biosyn provided the selenium to the participating European sites. Dr. Heyland and his associates reported ties to numerous industry sources.