General Surgery

SCOTTSDALE, ARIZ. – When it comes to holding or continuing with ACE inhibitors before surgery, all bets are off, a perioperative medicine consultant suggested.

Patients on angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARB) have about a 50% risk of developing hypotension during surgery, and a significant proportion of those episodes could be severe, said Dr. Paul Grant, of the University of Michigan Health System in Ann Arbor.

"I recommend having some sort of standard approach [to perioperative ACE inhibitor use] at your institution if that’s at all possible, either for a certain surgery type or across the board," he said at a meeting on perioperative medicine sponsored by the University of Miami.

Evidence from a small number of randomized trials and observational studies suggests that continuing ACE inhibitors during cardiac surgery may result in less cardiac enzyme release, less kidney injury, and a lower incidence of atrial fibrillation. In vascular surgery, evidence suggests that patients on ACE inhibitors who are undergoing surgery have less of a drop in cardiac output and may have improved creatinine clearance.

On the other hand, patients who remain on ACE inhibitors during surgery can experience a "profound" drop in blood pressure requiring immediate intervention, he said.

Data to support the continue vs. hold debate are sparse, but include a trial of 51 patients randomized to continue ACE inhibitors on the day of surgery or to have the drugs held for 12-24 hours before surgery. In all, 33 of the patients were on captopril (Capoten), and 18 were on enalapril (Vasotec).

The investigators found that among patients randomized to continue ACE inhibitor therapy, 7 of 7 on captopril and 9 of 14 on enalapril developed hypotension, defined as a systolic blood pressure (SBP) less than 90 mm Hg. In contrast, among patients assigned to the ACE-inhibitor hold protocol, only 2 of 11 on captopril and 4 of 19 on enalapril developed hypotension during surgery.

In a second randomized trial, investigators looked at 37 patients on an ARB who were randomly assigned to either discontinue ARB on the day before surgery (18 patients), or to receive their ARB 1 hour before anesthesia induction (19 patients).

The authors defined hypotension for their study as an SBP less than 80 mm Hg for more than 1 minute. They found that all 19 patients who continued on ARB had hypotension during surgery, compared with 12 of 18 who discontinued their ARB the day before. Patients who received their ARB on the day of surgery used significantly more vasoactive drugs. Despite the discontinuation of the ARB, there were no differences in hypertension between the groups in the recovery period. Postoperative cardiac complications occurred in 1 patient in each group.

In the final randomized study that Dr. Grant cited, 40 patients on an ACE inhibitor with good left-ventricular function were scheduled to undergo coronary artery bypass graft (CABG). They were randomly assigned to hold or continue on ACE inhibitors on the day of surgery.

Patients in whom the ACE inhibitors were held before CABG had higher mean blood pressures than patients who continued on the drugs, and they used less vasopressor during the surgery. In contrast, patients who continued on ACE inhibitors needed more vasodilators after CABG and in the recovery period. The authors of this trial did not study other clinical endpoints, Dr. Grant noted.

Evidence from two observational studies was more equivocal, however.

In a retrospective observational study, investigators studied the relationship between the timing of discontinuing ACE inhibitors and angiotensin II receptor subtype 1 antagonists (ARA) and the onset of hypotension in 267 patients scheduled for general surgery.

They found that patients exposed to an ACE inhibitor or ARA within 10 hours of anesthesia had an adjusted odds ratio of 1.74 for moderate hypotension (SBP 85 mm Hg or less; P = .04), but there was no difference in severe hypotension between these patients and those who discontinued the drugs more than 10 hours before surgery. There were no differences in either vasopressor use or postoperative complications, including unplanned intensive care unit stay, myocardial infarction, stroke, renal impairment, or death.

A second, smaller study compared 12 vascular surgery patients on ARB the day of surgery with matched cohorts of patients taking beta-blockers and/or calcium channel blockers the day of surgery, or ACE inhibitors held on the day of surgery.

Hypotension (SBP less than 90 mm Hg in this study) occurred in all of the patients on ARB but in only 60% (27 of 45) patients on the beta-blocker/calcium channel blockers, and in 67% (18 of 27) in the ACE-inhibitor hold cohort. The ARB patients were also less responsive to ephedrine and phenylephrine than other patients, and in some cases responded only to a vasopressin system agonist, Dr. Grant noted.

Finally, the authors of a random-effects meta-analysis of five studies with a total of 434 patients reported that patients receiving an immediate preoperative ACE inhibitor or ARA dose had a relative risk of 1.50 for developing hypotension requiring vasopressors at or shortly after induction of anesthesia, compared with patients who did not receive the drugs.

Dr. Grant noted that the American College of Physicians’ Smart Medicine guidelines on perioperative management of hypertensive patients recommend continuing ACE inhibitors "with caution," and they advise clinicians to avoid hypovolemia in patients maintained on ACE inhibitors during surgery. He said that in certain cases, it may be appropriate to continue surgical patients on ACE inhibitors or ARB, as in patients with hypertension that is difficult to control with multiple medications, or in those with severe heart disease who have adequate blood pressure.

Dr. Grant reported having no financial disclosures.

SCOTTSDALE, ARIZ. – When it comes to holding or continuing with ACE inhibitors before surgery, all bets are off, a perioperative medicine consultant suggested.

Patients on angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARB) have about a 50% risk of developing hypotension during surgery, and a significant proportion of those episodes could be severe, said Dr. Paul Grant, of the University of Michigan Health System in Ann Arbor.

"I recommend having some sort of standard approach [to perioperative ACE inhibitor use] at your institution if that’s at all possible, either for a certain surgery type or across the board," he said at a meeting on perioperative medicine sponsored by the University of Miami.

Evidence from a small number of randomized trials and observational studies suggests that continuing ACE inhibitors during cardiac surgery may result in less cardiac enzyme release, less kidney injury, and a lower incidence of atrial fibrillation. In vascular surgery, evidence suggests that patients on ACE inhibitors who are undergoing surgery have less of a drop in cardiac output and may have improved creatinine clearance.

On the other hand, patients who remain on ACE inhibitors during surgery can experience a "profound" drop in blood pressure requiring immediate intervention, he said.

Data to support the continue vs. hold debate are sparse, but include a trial of 51 patients randomized to continue ACE inhibitors on the day of surgery or to have the drugs held for 12-24 hours before surgery. In all, 33 of the patients were on captopril (Capoten), and 18 were on enalapril (Vasotec).

The investigators found that among patients randomized to continue ACE inhibitor therapy, 7 of 7 on captopril and 9 of 14 on enalapril developed hypotension, defined as a systolic blood pressure (SBP) less than 90 mm Hg. In contrast, among patients assigned to the ACE-inhibitor hold protocol, only 2 of 11 on captopril and 4 of 19 on enalapril developed hypotension during surgery.

In a second randomized trial, investigators looked at 37 patients on an ARB who were randomly assigned to either discontinue ARB on the day before surgery (18 patients), or to receive their ARB 1 hour before anesthesia induction (19 patients).

The authors defined hypotension for their study as an SBP less than 80 mm Hg for more than 1 minute. They found that all 19 patients who continued on ARB had hypotension during surgery, compared with 12 of 18 who discontinued their ARB the day before. Patients who received their ARB on the day of surgery used significantly more vasoactive drugs. Despite the discontinuation of the ARB, there were no differences in hypertension between the groups in the recovery period. Postoperative cardiac complications occurred in 1 patient in each group.

In the final randomized study that Dr. Grant cited, 40 patients on an ACE inhibitor with good left-ventricular function were scheduled to undergo coronary artery bypass graft (CABG). They were randomly assigned to hold or continue on ACE inhibitors on the day of surgery.

Patients in whom the ACE inhibitors were held before CABG had higher mean blood pressures than patients who continued on the drugs, and they used less vasopressor during the surgery. In contrast, patients who continued on ACE inhibitors needed more vasodilators after CABG and in the recovery period. The authors of this trial did not study other clinical endpoints, Dr. Grant noted.

Evidence from two observational studies was more equivocal, however.

In a retrospective observational study, investigators studied the relationship between the timing of discontinuing ACE inhibitors and angiotensin II receptor subtype 1 antagonists (ARA) and the onset of hypotension in 267 patients scheduled for general surgery.

They found that patients exposed to an ACE inhibitor or ARA within 10 hours of anesthesia had an adjusted odds ratio of 1.74 for moderate hypotension (SBP 85 mm Hg or less; P = .04), but there was no difference in severe hypotension between these patients and those who discontinued the drugs more than 10 hours before surgery. There were no differences in either vasopressor use or postoperative complications, including unplanned intensive care unit stay, myocardial infarction, stroke, renal impairment, or death.

A second, smaller study compared 12 vascular surgery patients on ARB the day of surgery with matched cohorts of patients taking beta-blockers and/or calcium channel blockers the day of surgery, or ACE inhibitors held on the day of surgery.

Hypotension (SBP less than 90 mm Hg in this study) occurred in all of the patients on ARB but in only 60% (27 of 45) patients on the beta-blocker/calcium channel blockers, and in 67% (18 of 27) in the ACE-inhibitor hold cohort. The ARB patients were also less responsive to ephedrine and phenylephrine than other patients, and in some cases responded only to a vasopressin system agonist, Dr. Grant noted.

Finally, the authors of a random-effects meta-analysis of five studies with a total of 434 patients reported that patients receiving an immediate preoperative ACE inhibitor or ARA dose had a relative risk of 1.50 for developing hypotension requiring vasopressors at or shortly after induction of anesthesia, compared with patients who did not receive the drugs.

Dr. Grant noted that the American College of Physicians’ Smart Medicine guidelines on perioperative management of hypertensive patients recommend continuing ACE inhibitors "with caution," and they advise clinicians to avoid hypovolemia in patients maintained on ACE inhibitors during surgery. He said that in certain cases, it may be appropriate to continue surgical patients on ACE inhibitors or ARB, as in patients with hypertension that is difficult to control with multiple medications, or in those with severe heart disease who have adequate blood pressure.

Dr. Grant reported having no financial disclosures.

SCOTTSDALE, ARIZ. – When it comes to holding or continuing with ACE inhibitors before surgery, all bets are off, a perioperative medicine consultant suggested.

Patients on angiotensin-converting enzyme (ACE) inhibitors or angiotensin II receptor blockers (ARB) have about a 50% risk of developing hypotension during surgery, and a significant proportion of those episodes could be severe, said Dr. Paul Grant, of the University of Michigan Health System in Ann Arbor.

"I recommend having some sort of standard approach [to perioperative ACE inhibitor use] at your institution if that’s at all possible, either for a certain surgery type or across the board," he said at a meeting on perioperative medicine sponsored by the University of Miami.

Evidence from a small number of randomized trials and observational studies suggests that continuing ACE inhibitors during cardiac surgery may result in less cardiac enzyme release, less kidney injury, and a lower incidence of atrial fibrillation. In vascular surgery, evidence suggests that patients on ACE inhibitors who are undergoing surgery have less of a drop in cardiac output and may have improved creatinine clearance.

On the other hand, patients who remain on ACE inhibitors during surgery can experience a "profound" drop in blood pressure requiring immediate intervention, he said.

Data to support the continue vs. hold debate are sparse, but include a trial of 51 patients randomized to continue ACE inhibitors on the day of surgery or to have the drugs held for 12-24 hours before surgery. In all, 33 of the patients were on captopril (Capoten), and 18 were on enalapril (Vasotec).

The investigators found that among patients randomized to continue ACE inhibitor therapy, 7 of 7 on captopril and 9 of 14 on enalapril developed hypotension, defined as a systolic blood pressure (SBP) less than 90 mm Hg. In contrast, among patients assigned to the ACE-inhibitor hold protocol, only 2 of 11 on captopril and 4 of 19 on enalapril developed hypotension during surgery.

In a second randomized trial, investigators looked at 37 patients on an ARB who were randomly assigned to either discontinue ARB on the day before surgery (18 patients), or to receive their ARB 1 hour before anesthesia induction (19 patients).

The authors defined hypotension for their study as an SBP less than 80 mm Hg for more than 1 minute. They found that all 19 patients who continued on ARB had hypotension during surgery, compared with 12 of 18 who discontinued their ARB the day before. Patients who received their ARB on the day of surgery used significantly more vasoactive drugs. Despite the discontinuation of the ARB, there were no differences in hypertension between the groups in the recovery period. Postoperative cardiac complications occurred in 1 patient in each group.

In the final randomized study that Dr. Grant cited, 40 patients on an ACE inhibitor with good left-ventricular function were scheduled to undergo coronary artery bypass graft (CABG). They were randomly assigned to hold or continue on ACE inhibitors on the day of surgery.

Patients in whom the ACE inhibitors were held before CABG had higher mean blood pressures than patients who continued on the drugs, and they used less vasopressor during the surgery. In contrast, patients who continued on ACE inhibitors needed more vasodilators after CABG and in the recovery period. The authors of this trial did not study other clinical endpoints, Dr. Grant noted.

Evidence from two observational studies was more equivocal, however.

In a retrospective observational study, investigators studied the relationship between the timing of discontinuing ACE inhibitors and angiotensin II receptor subtype 1 antagonists (ARA) and the onset of hypotension in 267 patients scheduled for general surgery.

They found that patients exposed to an ACE inhibitor or ARA within 10 hours of anesthesia had an adjusted odds ratio of 1.74 for moderate hypotension (SBP 85 mm Hg or less; P = .04), but there was no difference in severe hypotension between these patients and those who discontinued the drugs more than 10 hours before surgery. There were no differences in either vasopressor use or postoperative complications, including unplanned intensive care unit stay, myocardial infarction, stroke, renal impairment, or death.

A second, smaller study compared 12 vascular surgery patients on ARB the day of surgery with matched cohorts of patients taking beta-blockers and/or calcium channel blockers the day of surgery, or ACE inhibitors held on the day of surgery.

Hypotension (SBP less than 90 mm Hg in this study) occurred in all of the patients on ARB but in only 60% (27 of 45) patients on the beta-blocker/calcium channel blockers, and in 67% (18 of 27) in the ACE-inhibitor hold cohort. The ARB patients were also less responsive to ephedrine and phenylephrine than other patients, and in some cases responded only to a vasopressin system agonist, Dr. Grant noted.

Finally, the authors of a random-effects meta-analysis of five studies with a total of 434 patients reported that patients receiving an immediate preoperative ACE inhibitor or ARA dose had a relative risk of 1.50 for developing hypotension requiring vasopressors at or shortly after induction of anesthesia, compared with patients who did not receive the drugs.

Dr. Grant noted that the American College of Physicians’ Smart Medicine guidelines on perioperative management of hypertensive patients recommend continuing ACE inhibitors "with caution," and they advise clinicians to avoid hypovolemia in patients maintained on ACE inhibitors during surgery. He said that in certain cases, it may be appropriate to continue surgical patients on ACE inhibitors or ARB, as in patients with hypertension that is difficult to control with multiple medications, or in those with severe heart disease who have adequate blood pressure.

Dr. Grant reported having no financial disclosures.

SILVER SPRING, MD. – A Food and Drug Administration advisory committee voted unanimously to support the approval of the antibacterial drug dalbavancin for the treatment of acute bacterial skin and skin structure infections.

At a March 31 meeting, the FDA Anti-Infective Drugs Advisory Committee voted 12-0 that dalbavancin (Dalvance), manufactured by Durata Therapeutics, is safe and effective for the treatment of acute bacterial skin and skin structure infections (ABSSSI). Because of its long elimination half-life, the firm is proposing a dosing regimen of 1,000 mg on day 1 and 500 mg on day 8, administered intravenously.

Durata is seeking a proposed indication for the lipoglycopeptide antibacterial drug to treat adult patients with ABSSSI caused by the following gram-positive microorganisms: Staphylococcus aureus (including methicillin-resistant isolates [MRSA]), Streptococcus pyogenes, Streptococcus agalactiae, and the Streptococcus anginosus group (including S. anginosus, S. intermedius,and S. constellatus).

The firm’s phase III data was composed of five studies: one uncomplicated skin infection study comparing dalbavancin to cefazolin/cephalexin; two complicated skin infection studies (one comparing skin infection caused by MRSA, dalbavancin to vancomycin/cephalexin; one comparing dalbavancin to linezolid) and two ABSSSI studies (DUR001-301/-302) – both comparing dalbavancin to vancomycin/linezolid.

The DUR001-301 and DUR001-302 studies were identical in design; noninferiority, double-blind, double-dummy, randomized trials comparing two weekly doses of dalbavancin (on day 1 and day 8) to vancomycin IV with the option to switch to oral linezolid in patients with ABSSSI known or suspected to be caused by gram-positive bacteria. Treatment duration lasted 10-14 days.

The primary endpoints for DUR001-301/-302 were early response (defined as cessation of spread of the lesion and absence of fever) at 48-72 hours post initiation of therapy. The noninferiority margin was 10%.

Both studies showed dalbavancin to be noninferior to the regimen of vancomycin/linezolid. Since the lower bound of the 95% confidence interval for the treatment difference was above –10% (–4.6% in DUR001-301 and –7.4% in DUR001-302), both trials met their primary endpoints.

Both studies also met the key secondary endpoint, in which clinical response is defined as a greater than or equal to 20% reduction in lesion area from baseline (no fever component).

The FDA also analyzed the sensitivity studies of additional secondary efficacy outcome measures of clinical status at the end of treatment in the intent-to-treat and clinically evaluable populations. There were inconsistencies between the two trials, with lower success rates for dalbavancin vs. the comparator in DUR001-301 and slightly higher success rates for dalbavancin in DUR001-302.

"Overall, in these sensitivity analyses success rates at [end of treatment/short-term follow-up] tended to be less favorable in both treatment arms in both trials as stricter requirements were placed on the degree of erythema necessary to be evaluated as a success," the FDA wrote in its pre–committee executive summary.

The panel members concluded that the drug was generally both safe and effective, and welcomed it as another treatment option for patients.

"This just gives that clinician who is trying to personalize medicine more tools in their toolbox," said Dr. Alan Magill, a director on malaria policy at the Bill and Melinda Gates Foundation. "I think that’s a very important consideration going forward."

Additionally, panelists suggested that the drug labeling address the major safety finding of possible dalbavancin-associated liver injury, particularly in patients with liver disease.

"I have some issues with liver function tests," said Dr. Paul G. Auwaerter, clinical director of the division of infectious diseases at the Johns Hopkins University, Baltimore. "The labeling might consider something such as preexisting liver disease, or if liver function tests are rising during the hospitalization, there could be consideration whether the second drug administration should be given."

Dr. James M. Steckelberg, professor of medicine in the Mayo Clinic’s division of infectious diseases, Rochester, Minn., noted, "If you’re going to give the second dose on day 8, I’d particularly want to check those [liver function] levels before you do that dose, and probably have the result back, rather than do that later. I would give some thought to that, especially in the labeling, about what should be done about safety monitoring for a drug that’s dosed totally differently from anything we’re doing now."

Furthermore, panelists advised the FDA and the sponsor to develop additional postmarket studies.

"I recommend that the agency work closely with the sponsor to develop some cogent and clear guidelines for follow-up and monitoring for safety before clinicians are using this drug. It’s going to be used a lot, probably in the outpatient setting, and the whole paradigm is very different from what’s currently done," Dr. Steckelberg said.

Dr. Magill also recommended that a postmarket study address pediatric patient populations.

"There are several unanswered questions about other patient populations, like pediatrics, and potential for other indications. I think what happens next is very important, whether it’s a postmarketing surveillance of some kind, required phase IV studies, or the sponsor seeking new indications with new data and a new trial," Dr. Magill said. "I’d be looking forward to see how that evolves."

SILVER SPRING, MD. – A Food and Drug Administration advisory committee voted unanimously to support the approval of the antibacterial drug dalbavancin for the treatment of acute bacterial skin and skin structure infections.

At a March 31 meeting, the FDA Anti-Infective Drugs Advisory Committee voted 12-0 that dalbavancin (Dalvance), manufactured by Durata Therapeutics, is safe and effective for the treatment of acute bacterial skin and skin structure infections (ABSSSI). Because of its long elimination half-life, the firm is proposing a dosing regimen of 1,000 mg on day 1 and 500 mg on day 8, administered intravenously.

Durata is seeking a proposed indication for the lipoglycopeptide antibacterial drug to treat adult patients with ABSSSI caused by the following gram-positive microorganisms: Staphylococcus aureus (including methicillin-resistant isolates [MRSA]), Streptococcus pyogenes, Streptococcus agalactiae, and the Streptococcus anginosus group (including S. anginosus, S. intermedius,and S. constellatus).

The firm’s phase III data was composed of five studies: one uncomplicated skin infection study comparing dalbavancin to cefazolin/cephalexin; two complicated skin infection studies (one comparing skin infection caused by MRSA, dalbavancin to vancomycin/cephalexin; one comparing dalbavancin to linezolid) and two ABSSSI studies (DUR001-301/-302) – both comparing dalbavancin to vancomycin/linezolid.

The DUR001-301 and DUR001-302 studies were identical in design; noninferiority, double-blind, double-dummy, randomized trials comparing two weekly doses of dalbavancin (on day 1 and day 8) to vancomycin IV with the option to switch to oral linezolid in patients with ABSSSI known or suspected to be caused by gram-positive bacteria. Treatment duration lasted 10-14 days.

The primary endpoints for DUR001-301/-302 were early response (defined as cessation of spread of the lesion and absence of fever) at 48-72 hours post initiation of therapy. The noninferiority margin was 10%.

Both studies showed dalbavancin to be noninferior to the regimen of vancomycin/linezolid. Since the lower bound of the 95% confidence interval for the treatment difference was above –10% (–4.6% in DUR001-301 and –7.4% in DUR001-302), both trials met their primary endpoints.

Both studies also met the key secondary endpoint, in which clinical response is defined as a greater than or equal to 20% reduction in lesion area from baseline (no fever component).

The FDA also analyzed the sensitivity studies of additional secondary efficacy outcome measures of clinical status at the end of treatment in the intent-to-treat and clinically evaluable populations. There were inconsistencies between the two trials, with lower success rates for dalbavancin vs. the comparator in DUR001-301 and slightly higher success rates for dalbavancin in DUR001-302.

"Overall, in these sensitivity analyses success rates at [end of treatment/short-term follow-up] tended to be less favorable in both treatment arms in both trials as stricter requirements were placed on the degree of erythema necessary to be evaluated as a success," the FDA wrote in its pre–committee executive summary.

The panel members concluded that the drug was generally both safe and effective, and welcomed it as another treatment option for patients.

"This just gives that clinician who is trying to personalize medicine more tools in their toolbox," said Dr. Alan Magill, a director on malaria policy at the Bill and Melinda Gates Foundation. "I think that’s a very important consideration going forward."

Additionally, panelists suggested that the drug labeling address the major safety finding of possible dalbavancin-associated liver injury, particularly in patients with liver disease.

"I have some issues with liver function tests," said Dr. Paul G. Auwaerter, clinical director of the division of infectious diseases at the Johns Hopkins University, Baltimore. "The labeling might consider something such as preexisting liver disease, or if liver function tests are rising during the hospitalization, there could be consideration whether the second drug administration should be given."

Dr. James M. Steckelberg, professor of medicine in the Mayo Clinic’s division of infectious diseases, Rochester, Minn., noted, "If you’re going to give the second dose on day 8, I’d particularly want to check those [liver function] levels before you do that dose, and probably have the result back, rather than do that later. I would give some thought to that, especially in the labeling, about what should be done about safety monitoring for a drug that’s dosed totally differently from anything we’re doing now."

Furthermore, panelists advised the FDA and the sponsor to develop additional postmarket studies.

"I recommend that the agency work closely with the sponsor to develop some cogent and clear guidelines for follow-up and monitoring for safety before clinicians are using this drug. It’s going to be used a lot, probably in the outpatient setting, and the whole paradigm is very different from what’s currently done," Dr. Steckelberg said.

Dr. Magill also recommended that a postmarket study address pediatric patient populations.

"There are several unanswered questions about other patient populations, like pediatrics, and potential for other indications. I think what happens next is very important, whether it’s a postmarketing surveillance of some kind, required phase IV studies, or the sponsor seeking new indications with new data and a new trial," Dr. Magill said. "I’d be looking forward to see how that evolves."

SILVER SPRING, MD. – A Food and Drug Administration advisory committee voted unanimously to support the approval of the antibacterial drug dalbavancin for the treatment of acute bacterial skin and skin structure infections.

At a March 31 meeting, the FDA Anti-Infective Drugs Advisory Committee voted 12-0 that dalbavancin (Dalvance), manufactured by Durata Therapeutics, is safe and effective for the treatment of acute bacterial skin and skin structure infections (ABSSSI). Because of its long elimination half-life, the firm is proposing a dosing regimen of 1,000 mg on day 1 and 500 mg on day 8, administered intravenously.

Durata is seeking a proposed indication for the lipoglycopeptide antibacterial drug to treat adult patients with ABSSSI caused by the following gram-positive microorganisms: Staphylococcus aureus (including methicillin-resistant isolates [MRSA]), Streptococcus pyogenes, Streptococcus agalactiae, and the Streptococcus anginosus group (including S. anginosus, S. intermedius,and S. constellatus).

The firm’s phase III data was composed of five studies: one uncomplicated skin infection study comparing dalbavancin to cefazolin/cephalexin; two complicated skin infection studies (one comparing skin infection caused by MRSA, dalbavancin to vancomycin/cephalexin; one comparing dalbavancin to linezolid) and two ABSSSI studies (DUR001-301/-302) – both comparing dalbavancin to vancomycin/linezolid.

The DUR001-301 and DUR001-302 studies were identical in design; noninferiority, double-blind, double-dummy, randomized trials comparing two weekly doses of dalbavancin (on day 1 and day 8) to vancomycin IV with the option to switch to oral linezolid in patients with ABSSSI known or suspected to be caused by gram-positive bacteria. Treatment duration lasted 10-14 days.

The primary endpoints for DUR001-301/-302 were early response (defined as cessation of spread of the lesion and absence of fever) at 48-72 hours post initiation of therapy. The noninferiority margin was 10%.

Both studies showed dalbavancin to be noninferior to the regimen of vancomycin/linezolid. Since the lower bound of the 95% confidence interval for the treatment difference was above –10% (–4.6% in DUR001-301 and –7.4% in DUR001-302), both trials met their primary endpoints.

Both studies also met the key secondary endpoint, in which clinical response is defined as a greater than or equal to 20% reduction in lesion area from baseline (no fever component).

The FDA also analyzed the sensitivity studies of additional secondary efficacy outcome measures of clinical status at the end of treatment in the intent-to-treat and clinically evaluable populations. There were inconsistencies between the two trials, with lower success rates for dalbavancin vs. the comparator in DUR001-301 and slightly higher success rates for dalbavancin in DUR001-302.

"Overall, in these sensitivity analyses success rates at [end of treatment/short-term follow-up] tended to be less favorable in both treatment arms in both trials as stricter requirements were placed on the degree of erythema necessary to be evaluated as a success," the FDA wrote in its pre–committee executive summary.

The panel members concluded that the drug was generally both safe and effective, and welcomed it as another treatment option for patients.

"This just gives that clinician who is trying to personalize medicine more tools in their toolbox," said Dr. Alan Magill, a director on malaria policy at the Bill and Melinda Gates Foundation. "I think that’s a very important consideration going forward."

Additionally, panelists suggested that the drug labeling address the major safety finding of possible dalbavancin-associated liver injury, particularly in patients with liver disease.

"I have some issues with liver function tests," said Dr. Paul G. Auwaerter, clinical director of the division of infectious diseases at the Johns Hopkins University, Baltimore. "The labeling might consider something such as preexisting liver disease, or if liver function tests are rising during the hospitalization, there could be consideration whether the second drug administration should be given."

Dr. James M. Steckelberg, professor of medicine in the Mayo Clinic’s division of infectious diseases, Rochester, Minn., noted, "If you’re going to give the second dose on day 8, I’d particularly want to check those [liver function] levels before you do that dose, and probably have the result back, rather than do that later. I would give some thought to that, especially in the labeling, about what should be done about safety monitoring for a drug that’s dosed totally differently from anything we’re doing now."

Furthermore, panelists advised the FDA and the sponsor to develop additional postmarket studies.

"I recommend that the agency work closely with the sponsor to develop some cogent and clear guidelines for follow-up and monitoring for safety before clinicians are using this drug. It’s going to be used a lot, probably in the outpatient setting, and the whole paradigm is very different from what’s currently done," Dr. Steckelberg said.

Dr. Magill also recommended that a postmarket study address pediatric patient populations.

"There are several unanswered questions about other patient populations, like pediatrics, and potential for other indications. I think what happens next is very important, whether it’s a postmarketing surveillance of some kind, required phase IV studies, or the sponsor seeking new indications with new data and a new trial," Dr. Magill said. "I’d be looking forward to see how that evolves."

LAS VEGAS – Lengths of hospital stay were nearly halved in elderly hip fracture patients started on enteral nutrition within 24 hours of surgery, according to a retrospective cohort study of 100 sequential hip fracture patients at Salem (Ore.) Hospital.

The 89 patients fed by nasogastric tube within 24 hours stayed in the hospital an average of 4.43 days. The 11 fed an average of 4.36 days later stayed an average of 7.80 days.

The risk of hospital stays 5 days or longer quadrupled when enteral nutrition was delayed (RR, 4.14). Two patients (18%) died in the delayed-feeding group; eight (9%) died in the early-feeding group.

The average age in the study was 83 years old. Patients who went for more than a day without being fed – the range was 2-7 days – were a bit older with an average age of 86 years, "meaning that they were unlikely to have much in the way of reserves and were very likely to have some malnutrition at baseline," said Dr. Cynthia Wallace, medical director of Vibra Specialty Hospital in Portland, Ore., as well as a palliative care consultant at Salem Hospital.

"Association doesn’t prove causality," she said. It’s possible that those who went longer without nutrition were sicker and more confused.

Alex Otto/Frontline Medical News

Even so, "the correlation was pretty compelling." The findings argue strongly for early nutrition "whether or not it’s known absolutely" that it improves outcomes. Nutrition is essential for recovery: "If you are going to treat a patient aggressively, you need to give them nutrition. It’s just the right thing to do." It may also save a lot of money. A day in the hospital costs more than $4,000, while feedings cost about $35 a day, Dr. Wallace said at the Society of Hospital Medicine annual meeting.

"Given an ALOS [average length of stay] of 7 days without intervention, an early 3-day trial of enteral nutrition could save the hospital between $2,939 and $12,065 for an ALOS reduction of 1-4 days, respectively," she reported in the accompanying abstract. "Assuming a utility of 100%, the cost per outpatient day gained for the patient varies from $25 to $100 for a range of 4 to 1 days gained. If early enteral nutrition is responsible for the reduction in ALOS, less than 10% of 1 cent is spent to garner $1 in reduced inpatient costs."

Days go by

It’s not uncommon for elderly patients to go days without being fed. One of the reasons, Dr. Wallace said, is because there’s been an overextrapolation from studies showing that percutaneous gastrostomy tubes don’t improve quality of life or survival in end-stage dementia.

Those findings "have unintentionally influenced use of temporary feeding tubes in patients with acute issues who are otherwise receiving full medical treatment" and have resulted "in inappropriate withholding of enteral nutrition" in the elderly, she said.

"We’ve morphed the data into saying, ‘Oh, if I’ve got a patient who has some underlying dementia, I shouldn’t give them tube feeds. But the data about not doing [gastrostomy] tubes in advanced dementia has to do with people who are not undergoing acute medical treatment. That’s a very different situation from hip fractures and other acute problems in the elderly. Unfortunately, the evidence for one situation has been transposed onto a different situation, so a lot of hospitalists hesitate to initiate tube feeds," she said.

In patients who waited more than a day to get fed, "there was a lag time to even getting a nutrition consult. Nobody really quite noticed that they weren’t getting nutrition." That’s consistent "with what I’ve seen throughout my hospitalist career, and not just in hip fractures. As hospitalist doctors, we get very worked up about the medical issues, and we simply don’t attend to nutrition. We sometimes think somebody else is taking care of it," she said.

"The ages were [statistically] the same between the two groups, and there was a pretty [even] distribution of comorbidities," she noted.

Dr. Wallace said she had no relevant financial disclosures. The work received no outside funding.

[email protected]

LAS VEGAS – Lengths of hospital stay were nearly halved in elderly hip fracture patients started on enteral nutrition within 24 hours of surgery, according to a retrospective cohort study of 100 sequential hip fracture patients at Salem (Ore.) Hospital.

The 89 patients fed by nasogastric tube within 24 hours stayed in the hospital an average of 4.43 days. The 11 fed an average of 4.36 days later stayed an average of 7.80 days.

The risk of hospital stays 5 days or longer quadrupled when enteral nutrition was delayed (RR, 4.14). Two patients (18%) died in the delayed-feeding group; eight (9%) died in the early-feeding group.

The average age in the study was 83 years old. Patients who went for more than a day without being fed – the range was 2-7 days – were a bit older with an average age of 86 years, "meaning that they were unlikely to have much in the way of reserves and were very likely to have some malnutrition at baseline," said Dr. Cynthia Wallace, medical director of Vibra Specialty Hospital in Portland, Ore., as well as a palliative care consultant at Salem Hospital.

"Association doesn’t prove causality," she said. It’s possible that those who went longer without nutrition were sicker and more confused.

Alex Otto/Frontline Medical News

Even so, "the correlation was pretty compelling." The findings argue strongly for early nutrition "whether or not it’s known absolutely" that it improves outcomes. Nutrition is essential for recovery: "If you are going to treat a patient aggressively, you need to give them nutrition. It’s just the right thing to do." It may also save a lot of money. A day in the hospital costs more than $4,000, while feedings cost about $35 a day, Dr. Wallace said at the Society of Hospital Medicine annual meeting.

"Given an ALOS [average length of stay] of 7 days without intervention, an early 3-day trial of enteral nutrition could save the hospital between $2,939 and $12,065 for an ALOS reduction of 1-4 days, respectively," she reported in the accompanying abstract. "Assuming a utility of 100%, the cost per outpatient day gained for the patient varies from $25 to $100 for a range of 4 to 1 days gained. If early enteral nutrition is responsible for the reduction in ALOS, less than 10% of 1 cent is spent to garner $1 in reduced inpatient costs."

Days go by

It’s not uncommon for elderly patients to go days without being fed. One of the reasons, Dr. Wallace said, is because there’s been an overextrapolation from studies showing that percutaneous gastrostomy tubes don’t improve quality of life or survival in end-stage dementia.

Those findings "have unintentionally influenced use of temporary feeding tubes in patients with acute issues who are otherwise receiving full medical treatment" and have resulted "in inappropriate withholding of enteral nutrition" in the elderly, she said.

"We’ve morphed the data into saying, ‘Oh, if I’ve got a patient who has some underlying dementia, I shouldn’t give them tube feeds. But the data about not doing [gastrostomy] tubes in advanced dementia has to do with people who are not undergoing acute medical treatment. That’s a very different situation from hip fractures and other acute problems in the elderly. Unfortunately, the evidence for one situation has been transposed onto a different situation, so a lot of hospitalists hesitate to initiate tube feeds," she said.

In patients who waited more than a day to get fed, "there was a lag time to even getting a nutrition consult. Nobody really quite noticed that they weren’t getting nutrition." That’s consistent "with what I’ve seen throughout my hospitalist career, and not just in hip fractures. As hospitalist doctors, we get very worked up about the medical issues, and we simply don’t attend to nutrition. We sometimes think somebody else is taking care of it," she said.

"The ages were [statistically] the same between the two groups, and there was a pretty [even] distribution of comorbidities," she noted.

Dr. Wallace said she had no relevant financial disclosures. The work received no outside funding.

[email protected]

LAS VEGAS – Lengths of hospital stay were nearly halved in elderly hip fracture patients started on enteral nutrition within 24 hours of surgery, according to a retrospective cohort study of 100 sequential hip fracture patients at Salem (Ore.) Hospital.

The 89 patients fed by nasogastric tube within 24 hours stayed in the hospital an average of 4.43 days. The 11 fed an average of 4.36 days later stayed an average of 7.80 days.

The risk of hospital stays 5 days or longer quadrupled when enteral nutrition was delayed (RR, 4.14). Two patients (18%) died in the delayed-feeding group; eight (9%) died in the early-feeding group.

The average age in the study was 83 years old. Patients who went for more than a day without being fed – the range was 2-7 days – were a bit older with an average age of 86 years, "meaning that they were unlikely to have much in the way of reserves and were very likely to have some malnutrition at baseline," said Dr. Cynthia Wallace, medical director of Vibra Specialty Hospital in Portland, Ore., as well as a palliative care consultant at Salem Hospital.

"Association doesn’t prove causality," she said. It’s possible that those who went longer without nutrition were sicker and more confused.

Alex Otto/Frontline Medical News

Even so, "the correlation was pretty compelling." The findings argue strongly for early nutrition "whether or not it’s known absolutely" that it improves outcomes. Nutrition is essential for recovery: "If you are going to treat a patient aggressively, you need to give them nutrition. It’s just the right thing to do." It may also save a lot of money. A day in the hospital costs more than $4,000, while feedings cost about $35 a day, Dr. Wallace said at the Society of Hospital Medicine annual meeting.

"Given an ALOS [average length of stay] of 7 days without intervention, an early 3-day trial of enteral nutrition could save the hospital between $2,939 and $12,065 for an ALOS reduction of 1-4 days, respectively," she reported in the accompanying abstract. "Assuming a utility of 100%, the cost per outpatient day gained for the patient varies from $25 to $100 for a range of 4 to 1 days gained. If early enteral nutrition is responsible for the reduction in ALOS, less than 10% of 1 cent is spent to garner $1 in reduced inpatient costs."

Days go by

It’s not uncommon for elderly patients to go days without being fed. One of the reasons, Dr. Wallace said, is because there’s been an overextrapolation from studies showing that percutaneous gastrostomy tubes don’t improve quality of life or survival in end-stage dementia.

Those findings "have unintentionally influenced use of temporary feeding tubes in patients with acute issues who are otherwise receiving full medical treatment" and have resulted "in inappropriate withholding of enteral nutrition" in the elderly, she said.

"We’ve morphed the data into saying, ‘Oh, if I’ve got a patient who has some underlying dementia, I shouldn’t give them tube feeds. But the data about not doing [gastrostomy] tubes in advanced dementia has to do with people who are not undergoing acute medical treatment. That’s a very different situation from hip fractures and other acute problems in the elderly. Unfortunately, the evidence for one situation has been transposed onto a different situation, so a lot of hospitalists hesitate to initiate tube feeds," she said.

In patients who waited more than a day to get fed, "there was a lag time to even getting a nutrition consult. Nobody really quite noticed that they weren’t getting nutrition." That’s consistent "with what I’ve seen throughout my hospitalist career, and not just in hip fractures. As hospitalist doctors, we get very worked up about the medical issues, and we simply don’t attend to nutrition. We sometimes think somebody else is taking care of it," she said.

"The ages were [statistically] the same between the two groups, and there was a pretty [even] distribution of comorbidities," she noted.

Dr. Wallace said she had no relevant financial disclosures. The work received no outside funding.

[email protected]

Neither perioperative aspirin therapy nor perioperative clonidine prevented death or MI in patients undergoing noncardiac surgery who were at risk for major vascular complications, according to data reported at the annual meeting of the American College of Cardiology.

Far from being protective, both preventive strategies exerted harmful effects: Aspirin raised the risk of major bleeding, and clonidine increased the risks of clinically important hypotension, bradycardia, and nonfatal MI, said Dr. P. J. Devereaux of the Population Health Research Institute, David Braley Cardiac, Vascular, and Stroke Research Institute, Hamilton (Ont.) General Hospital, and his associates in the POISE-2 (Perioperative Ischemic Evaluation 2) clinical trial.

The POISE-2 findings were simultaneously reported online in the New England Journal of Medicine 2014 March 31 [doi:10/1056.
NEJMoa1401105] and [doi:10/1056.
NEJMoa1401106]).

© Darren Hester/Fotolia.com

MI is the most common major vascular complication related to noncardiac surgery, and perioperative aspirin is thought to prevent it by inhibiting thrombus formation. At present, one-third of patients at risk for vascular complications receive perioperative aspirin even though the risks and benefits of this preventive strategy are uncertain.

Similarly, small trials have indicated that the antihypertensive agent clonidine, an alpha₂ adrenergic agonist, reduces the risk of myocardial ischemia without inducing hemodynamic instability when given to at-risk patients undergoing noncardiac surgery, which in turn may prevent MI and death. Clonidine has additional analgesic, anxiolytic, antishivering, and anti-inflammatory effects that may be helpful.

The POISE-2 trial was designed to determine whether either of these approaches was more effective than placebo at preventing the composite endpoint of MI or death within 30 days of surgery.

A total of 10,010 patients were enrolled at 135 hospitals in 23 countries, stratified by whether they were already taking daily aspirin prophylaxis, and randomly assigned in a double-blind fashion to receive either perioperative aspirin (4,998 subjects) or placebo (5,012 subjects), and to receive either perioperative clonidine (5,009 subjects) or placebo (5,001 subjects). The mean age of these participants was 68.6 years, and 52.8% were men. Most were at risk because of their history of vascular disease; advanced age; need for dialysis; smoking status; or comorbid diabetes, heart failure, transient ischemic attack, or hypertension.

The types of surgery they underwent included general, orthopedic, urologic, gynecologic, vascular, and thoracic procedures.

The primary outcome of death or MI occurred in 7% of the aspirin group and 7.1% of the placebo group, a nonsignificant difference. The risks of other adverse outcomes, including stroke, cardiac revascularization, pulmonary embolism, acute kidney injury, and deep vein thrombosis, also were not significantly different between the two groups.

Median length of hospital stay and length of ICU and CCU stays also were not significantly different between patients who received aspirin and those who received placebo. However, aspirin raised the risk of major bleeding (4.6%), compared with placebo (3.8%), for a hazard ratio of 1.23. The most common sites of bleeding were the surgical site and the GI tract.

These effects were consistent across all subgroups of patients. In particular, they were the same whether the patients were already taking daily prophylactic aspirin therapy.

Clonidine also did not prevent death or MI within 30 days, compared with placebo; the rates were 7.3% and 6.8%, respectively. The risks of other adverse outcomes also were not significantly different between the two groups, nor were lengths of hospital, ICU, or CCU stays. However, clonidine raised the risk of clinically important hypotension (47.6% vs. 37.1%), clinically important bradycardia (12% vs. 8.1%), and nonfatal cardiac arrest (0.3% vs. 0.1%).

These effects were consistent across all subgroups of patients. In particular, clonidine was no more beneficial than was placebo in patients who underwent vascular surgery, a subgroup in whom previous, smaller studies found the drug to protect against both MI and mortality.

POISE-2 was not designed to determine why aspirin wasn’t effective at preventing perioperative MI, but Dr. Devereaux and his associates offered three possible explanations. First, MI was associated with major bleeding, and aspirin raises the risk of this complication. "It is possible that aspirin prevented some perioperative MI through thrombus inhibition [but] caused some MIs through bleeding and the subsequent mismatch between the supply of and the demand for myocardial oxygen, thus resulting in the overall neutral effect in our study," they said.

Second, the heart rate findings couldn’t statistically rule out a possible moderate beneficial effect of aspirin therapy. And third, it is possible that coronary-artery thrombus isn’t the dominant mechanism of perioperative MI, and aspirin’s antithrombotic effect didn’t address this unknown dominant mechanism.

Similarly, it is not known why clonidine failed to be protective, but the investigators offered two possible reasons. First, the drug induced hypotension, which raises the risk of perioperative MI. And second, it also induced bradycardia, which may be a proxy for an overall adverse effect on heart rate control; this also can increase the risk of perioperative MI, they said.

The POISE-2 trial was supported by the Canadian Institutes of Health Research, the National Health and Medical Research Council of Australia, and the Spanish Ministry of Health and Social Policy. Bayer Pharma provided the aspirin used in the study, and Boehringer Ingelheim provided the clonidine and some funding. Dr. Devereaux reported ties to Abbott, Bayer Pharma, Boehringer Ingelheim, Covidien, Roche, and Stryker and; some of his associates reported ties to several industry sources.

Neither perioperative aspirin therapy nor perioperative clonidine prevented death or MI in patients undergoing noncardiac surgery who were at risk for major vascular complications, according to data reported at the annual meeting of the American College of Cardiology.

Far from being protective, both preventive strategies exerted harmful effects: Aspirin raised the risk of major bleeding, and clonidine increased the risks of clinically important hypotension, bradycardia, and nonfatal MI, said Dr. P. J. Devereaux of the Population Health Research Institute, David Braley Cardiac, Vascular, and Stroke Research Institute, Hamilton (Ont.) General Hospital, and his associates in the POISE-2 (Perioperative Ischemic Evaluation 2) clinical trial.

The POISE-2 findings were simultaneously reported online in the New England Journal of Medicine 2014 March 31 [doi:10/1056.
NEJMoa1401105] and [doi:10/1056.
NEJMoa1401106]).

© Darren Hester/Fotolia.com

MI is the most common major vascular complication related to noncardiac surgery, and perioperative aspirin is thought to prevent it by inhibiting thrombus formation. At present, one-third of patients at risk for vascular complications receive perioperative aspirin even though the risks and benefits of this preventive strategy are uncertain.

Similarly, small trials have indicated that the antihypertensive agent clonidine, an alpha₂ adrenergic agonist, reduces the risk of myocardial ischemia without inducing hemodynamic instability when given to at-risk patients undergoing noncardiac surgery, which in turn may prevent MI and death. Clonidine has additional analgesic, anxiolytic, antishivering, and anti-inflammatory effects that may be helpful.

The POISE-2 trial was designed to determine whether either of these approaches was more effective than placebo at preventing the composite endpoint of MI or death within 30 days of surgery.

A total of 10,010 patients were enrolled at 135 hospitals in 23 countries, stratified by whether they were already taking daily aspirin prophylaxis, and randomly assigned in a double-blind fashion to receive either perioperative aspirin (4,998 subjects) or placebo (5,012 subjects), and to receive either perioperative clonidine (5,009 subjects) or placebo (5,001 subjects). The mean age of these participants was 68.6 years, and 52.8% were men. Most were at risk because of their history of vascular disease; advanced age; need for dialysis; smoking status; or comorbid diabetes, heart failure, transient ischemic attack, or hypertension.

The types of surgery they underwent included general, orthopedic, urologic, gynecologic, vascular, and thoracic procedures.

The primary outcome of death or MI occurred in 7% of the aspirin group and 7.1% of the placebo group, a nonsignificant difference. The risks of other adverse outcomes, including stroke, cardiac revascularization, pulmonary embolism, acute kidney injury, and deep vein thrombosis, also were not significantly different between the two groups.

Median length of hospital stay and length of ICU and CCU stays also were not significantly different between patients who received aspirin and those who received placebo. However, aspirin raised the risk of major bleeding (4.6%), compared with placebo (3.8%), for a hazard ratio of 1.23. The most common sites of bleeding were the surgical site and the GI tract.

These effects were consistent across all subgroups of patients. In particular, they were the same whether the patients were already taking daily prophylactic aspirin therapy.

Clonidine also did not prevent death or MI within 30 days, compared with placebo; the rates were 7.3% and 6.8%, respectively. The risks of other adverse outcomes also were not significantly different between the two groups, nor were lengths of hospital, ICU, or CCU stays. However, clonidine raised the risk of clinically important hypotension (47.6% vs. 37.1%), clinically important bradycardia (12% vs. 8.1%), and nonfatal cardiac arrest (0.3% vs. 0.1%).

These effects were consistent across all subgroups of patients. In particular, clonidine was no more beneficial than was placebo in patients who underwent vascular surgery, a subgroup in whom previous, smaller studies found the drug to protect against both MI and mortality.

POISE-2 was not designed to determine why aspirin wasn’t effective at preventing perioperative MI, but Dr. Devereaux and his associates offered three possible explanations. First, MI was associated with major bleeding, and aspirin raises the risk of this complication. "It is possible that aspirin prevented some perioperative MI through thrombus inhibition [but] caused some MIs through bleeding and the subsequent mismatch between the supply of and the demand for myocardial oxygen, thus resulting in the overall neutral effect in our study," they said.

Second, the heart rate findings couldn’t statistically rule out a possible moderate beneficial effect of aspirin therapy. And third, it is possible that coronary-artery thrombus isn’t the dominant mechanism of perioperative MI, and aspirin’s antithrombotic effect didn’t address this unknown dominant mechanism.

Similarly, it is not known why clonidine failed to be protective, but the investigators offered two possible reasons. First, the drug induced hypotension, which raises the risk of perioperative MI. And second, it also induced bradycardia, which may be a proxy for an overall adverse effect on heart rate control; this also can increase the risk of perioperative MI, they said.

The POISE-2 trial was supported by the Canadian Institutes of Health Research, the National Health and Medical Research Council of Australia, and the Spanish Ministry of Health and Social Policy. Bayer Pharma provided the aspirin used in the study, and Boehringer Ingelheim provided the clonidine and some funding. Dr. Devereaux reported ties to Abbott, Bayer Pharma, Boehringer Ingelheim, Covidien, Roche, and Stryker and; some of his associates reported ties to several industry sources.

Neither perioperative aspirin therapy nor perioperative clonidine prevented death or MI in patients undergoing noncardiac surgery who were at risk for major vascular complications, according to data reported at the annual meeting of the American College of Cardiology.

Far from being protective, both preventive strategies exerted harmful effects: Aspirin raised the risk of major bleeding, and clonidine increased the risks of clinically important hypotension, bradycardia, and nonfatal MI, said Dr. P. J. Devereaux of the Population Health Research Institute, David Braley Cardiac, Vascular, and Stroke Research Institute, Hamilton (Ont.) General Hospital, and his associates in the POISE-2 (Perioperative Ischemic Evaluation 2) clinical trial.

The POISE-2 findings were simultaneously reported online in the New England Journal of Medicine 2014 March 31 [doi:10/1056.
NEJMoa1401105] and [doi:10/1056.
NEJMoa1401106]).

© Darren Hester/Fotolia.com

MI is the most common major vascular complication related to noncardiac surgery, and perioperative aspirin is thought to prevent it by inhibiting thrombus formation. At present, one-third of patients at risk for vascular complications receive perioperative aspirin even though the risks and benefits of this preventive strategy are uncertain.

Similarly, small trials have indicated that the antihypertensive agent clonidine, an alpha₂ adrenergic agonist, reduces the risk of myocardial ischemia without inducing hemodynamic instability when given to at-risk patients undergoing noncardiac surgery, which in turn may prevent MI and death. Clonidine has additional analgesic, anxiolytic, antishivering, and anti-inflammatory effects that may be helpful.

The POISE-2 trial was designed to determine whether either of these approaches was more effective than placebo at preventing the composite endpoint of MI or death within 30 days of surgery.

A total of 10,010 patients were enrolled at 135 hospitals in 23 countries, stratified by whether they were already taking daily aspirin prophylaxis, and randomly assigned in a double-blind fashion to receive either perioperative aspirin (4,998 subjects) or placebo (5,012 subjects), and to receive either perioperative clonidine (5,009 subjects) or placebo (5,001 subjects). The mean age of these participants was 68.6 years, and 52.8% were men. Most were at risk because of their history of vascular disease; advanced age; need for dialysis; smoking status; or comorbid diabetes, heart failure, transient ischemic attack, or hypertension.

The types of surgery they underwent included general, orthopedic, urologic, gynecologic, vascular, and thoracic procedures.

The primary outcome of death or MI occurred in 7% of the aspirin group and 7.1% of the placebo group, a nonsignificant difference. The risks of other adverse outcomes, including stroke, cardiac revascularization, pulmonary embolism, acute kidney injury, and deep vein thrombosis, also were not significantly different between the two groups.

Median length of hospital stay and length of ICU and CCU stays also were not significantly different between patients who received aspirin and those who received placebo. However, aspirin raised the risk of major bleeding (4.6%), compared with placebo (3.8%), for a hazard ratio of 1.23. The most common sites of bleeding were the surgical site and the GI tract.

These effects were consistent across all subgroups of patients. In particular, they were the same whether the patients were already taking daily prophylactic aspirin therapy.

Clonidine also did not prevent death or MI within 30 days, compared with placebo; the rates were 7.3% and 6.8%, respectively. The risks of other adverse outcomes also were not significantly different between the two groups, nor were lengths of hospital, ICU, or CCU stays. However, clonidine raised the risk of clinically important hypotension (47.6% vs. 37.1%), clinically important bradycardia (12% vs. 8.1%), and nonfatal cardiac arrest (0.3% vs. 0.1%).

These effects were consistent across all subgroups of patients. In particular, clonidine was no more beneficial than was placebo in patients who underwent vascular surgery, a subgroup in whom previous, smaller studies found the drug to protect against both MI and mortality.

POISE-2 was not designed to determine why aspirin wasn’t effective at preventing perioperative MI, but Dr. Devereaux and his associates offered three possible explanations. First, MI was associated with major bleeding, and aspirin raises the risk of this complication. "It is possible that aspirin prevented some perioperative MI through thrombus inhibition [but] caused some MIs through bleeding and the subsequent mismatch between the supply of and the demand for myocardial oxygen, thus resulting in the overall neutral effect in our study," they said.

Second, the heart rate findings couldn’t statistically rule out a possible moderate beneficial effect of aspirin therapy. And third, it is possible that coronary-artery thrombus isn’t the dominant mechanism of perioperative MI, and aspirin’s antithrombotic effect didn’t address this unknown dominant mechanism.

Similarly, it is not known why clonidine failed to be protective, but the investigators offered two possible reasons. First, the drug induced hypotension, which raises the risk of perioperative MI. And second, it also induced bradycardia, which may be a proxy for an overall adverse effect on heart rate control; this also can increase the risk of perioperative MI, they said.

The POISE-2 trial was supported by the Canadian Institutes of Health Research, the National Health and Medical Research Council of Australia, and the Spanish Ministry of Health and Social Policy. Bayer Pharma provided the aspirin used in the study, and Boehringer Ingelheim provided the clonidine and some funding. Dr. Devereaux reported ties to Abbott, Bayer Pharma, Boehringer Ingelheim, Covidien, Roche, and Stryker and; some of his associates reported ties to several industry sources.

One in 25 hospitalized patients on any given day has an infection acquired from health care, and as many as 1 in 9 of those will die.

At a press briefing, Dr. Michael Bell discussed new data from a prevalence study conducted by the Centers for Disease Control and Prevention, where he is the deputy director for the division of health care quality promotion. Hospitals, doctors, and patients all have a role to play in decreasing the risks of these infections, he said.

[email protected]

On Twitter @sherryboschert

This article was updated 3/28/2014.

One in 25 hospitalized patients on any given day has an infection acquired from health care, and as many as 1 in 9 of those will die.

At a press briefing, Dr. Michael Bell discussed new data from a prevalence study conducted by the Centers for Disease Control and Prevention, where he is the deputy director for the division of health care quality promotion. Hospitals, doctors, and patients all have a role to play in decreasing the risks of these infections, he said.

[email protected]

On Twitter @sherryboschert

This article was updated 3/28/2014.

One in 25 hospitalized patients on any given day has an infection acquired from health care, and as many as 1 in 9 of those will die.

At a press briefing, Dr. Michael Bell discussed new data from a prevalence study conducted by the Centers for Disease Control and Prevention, where he is the deputy director for the division of health care quality promotion. Hospitals, doctors, and patients all have a role to play in decreasing the risks of these infections, he said.

[email protected]

On Twitter @sherryboschert

This article was updated 3/28/2014.

LAS VEGAS – Hospital quality and safety are improving across the board, with readmissions and health care–acquired infections falling fast, according to the Centers for Medicare & Medicaid Services.

The official data will be released in April, but Dr. Patrick Conway, chief medical officer and director of the Center for Clinical Standards and Quality at CMS in Baltimore, told attendees at the annual meeting of the Society of Hospital Medicine that the preliminary numbers show "dramatic progress."

Over the last 2 years, U.S. hospitals have reduced harm for hospitalized patients by almost 10% nationally, saving 15,000 lives and more than $4 billion, he said. The estimate comes from chart reviews of all-cause patient harm measures such as central line–associated bloodstream infections, adverse drug events, pressure ulcers, catheter-associated urinary tract infections, and others.

Other quality improvements include:

• Central line–associated bloodstream infections down 40%.

• Surgical site infections down 22%.

• Early elective deliveries down more than 50%.

"You are improving so fast on quality process of care measures for CMS that we actually have to pull them out of the program," Dr. Conway told the audience of hospitalists. "We’ve removed almost half of the measures that were in hospital value-based purchasing in the inpatient quality reporting program over the last 3 years and that’s because the performance has increased so much."

Hospital readmissions – a measure that is getting increasing attention from hospitals now that CMS is tying it to payments – are also dropping. Medicare’s 30-day all-cause hospital readmission rate had been hovering around 19% or 20% nationally through 2011, but it has now dropped below 17.5%, Dr. Conway said.

"This is over 150,000 beneficiaries every year staying home and healthy," he said.

[email protected]

On Twitter @maryellenny

LAS VEGAS – Hospital quality and safety are improving across the board, with readmissions and health care–acquired infections falling fast, according to the Centers for Medicare & Medicaid Services.

The official data will be released in April, but Dr. Patrick Conway, chief medical officer and director of the Center for Clinical Standards and Quality at CMS in Baltimore, told attendees at the annual meeting of the Society of Hospital Medicine that the preliminary numbers show "dramatic progress."

Over the last 2 years, U.S. hospitals have reduced harm for hospitalized patients by almost 10% nationally, saving 15,000 lives and more than $4 billion, he said. The estimate comes from chart reviews of all-cause patient harm measures such as central line–associated bloodstream infections, adverse drug events, pressure ulcers, catheter-associated urinary tract infections, and others.

Other quality improvements include:

• Central line–associated bloodstream infections down 40%.

• Surgical site infections down 22%.

• Early elective deliveries down more than 50%.

"You are improving so fast on quality process of care measures for CMS that we actually have to pull them out of the program," Dr. Conway told the audience of hospitalists. "We’ve removed almost half of the measures that were in hospital value-based purchasing in the inpatient quality reporting program over the last 3 years and that’s because the performance has increased so much."

Hospital readmissions – a measure that is getting increasing attention from hospitals now that CMS is tying it to payments – are also dropping. Medicare’s 30-day all-cause hospital readmission rate had been hovering around 19% or 20% nationally through 2011, but it has now dropped below 17.5%, Dr. Conway said.

"This is over 150,000 beneficiaries every year staying home and healthy," he said.

[email protected]

On Twitter @maryellenny

LAS VEGAS – Hospital quality and safety are improving across the board, with readmissions and health care–acquired infections falling fast, according to the Centers for Medicare & Medicaid Services.

The official data will be released in April, but Dr. Patrick Conway, chief medical officer and director of the Center for Clinical Standards and Quality at CMS in Baltimore, told attendees at the annual meeting of the Society of Hospital Medicine that the preliminary numbers show "dramatic progress."

Over the last 2 years, U.S. hospitals have reduced harm for hospitalized patients by almost 10% nationally, saving 15,000 lives and more than $4 billion, he said. The estimate comes from chart reviews of all-cause patient harm measures such as central line–associated bloodstream infections, adverse drug events, pressure ulcers, catheter-associated urinary tract infections, and others.

Other quality improvements include:

• Central line–associated bloodstream infections down 40%.

• Surgical site infections down 22%.

• Early elective deliveries down more than 50%.

"You are improving so fast on quality process of care measures for CMS that we actually have to pull them out of the program," Dr. Conway told the audience of hospitalists. "We’ve removed almost half of the measures that were in hospital value-based purchasing in the inpatient quality reporting program over the last 3 years and that’s because the performance has increased so much."

Hospital readmissions – a measure that is getting increasing attention from hospitals now that CMS is tying it to payments – are also dropping. Medicare’s 30-day all-cause hospital readmission rate had been hovering around 19% or 20% nationally through 2011, but it has now dropped below 17.5%, Dr. Conway said.

"This is over 150,000 beneficiaries every year staying home and healthy," he said.

[email protected]

On Twitter @maryellenny

An estimated 4% of inpatients at U.S. acute care hospitals have at least one health care–associated infection on any given day, according to a report published online March 26 in the New England Journal of Medicine.

Moreover, in a prevalence survey involving 183 acute care hospitals across 10 geographically diverse states, device-associated infections, "which have been a major focus of infection prevention in recent decades," accounted for only 25.6% of all health care–associated infections, said Dr. Shelley S. Magill of the division of health care quality promotion, Centers for Disease Control and Prevention, and her associates (N. Engl. J. Med. 2014;370:1198-1208).

In contrast, Clostridium difficile and other gastrointestinal infections, as well as non–ventilator-associated pneumonia, accounted for approximately half of all health care–associated infections in the survey. Surgical site infections also are still very common, accounting for 21.8%.

Because it appears that ventilator-associated pneumonia, catheter-associated UTIs, and central catheter–associated bloodstream infections are no longer the primary threat that they used to be, the study findings should prompt experts to "expand the public health focus to include these other types of infections, identifying patients at risk and developing effective countermeasures," the report’s authors noted.

The report shows that as a nation, we’re moving in the right direction; but there’s a great deal of work still to be done," Dr. Michael Bell said in a media briefing. "On any given day, 1 out of 25 hospitalized patients has an infection. And of those people, as many as one out of nine go on to die. This is not a minor issue," said Dr. Bell, deputy director of the CDC’s division of health care quality promotion.

The investigators developed and conducted the survey in 2011 to address a serious knowledge gap: No single surveillance system can provide estimates of "the burden of all types of such infections across acute care patient populations." So, Dr. Magill and her colleagues studied health care–associated infections among inpatients of all ages at 93 small, 68 medium-sized, and 22 large hospitals.

They found 504 such infections in 452 patients out of 11,282 patients covered in the survey, for an overall incidence of 4%. Using a statistical modeling process that accounted for predictors of infection prevalence and then applying those results to a nationally representative sample of U.S. community hospital stays, the investigators estimated that 648,000 inpatients nationwide had approximately 721,800 health care–associated infections in 2011.

Those estimates are lower than previous ones, such as those derived from the Study on the Efficacy of Nosocomial Infection Control in the 1970s , which postulated 2.1 million health care–associated infections each year, and those derived from National Nosocomial Infections Surveillance system data from 1990 to 2002, which estimated 1.7 million each year.

However, "it is difficult to draw conclusions from these comparisons because of the differences in patient populations, surveillance definitions of health care–associated infections, and data collection and analytical methods among these CDC methods," Dr. Magill and her associates said.

The current survey showed that 42.9% of health care–associated infections developed during a stay in a critical care unit or within 48 hours after; another 42.4% developed after a stay in a nonnursery ward.

Most of the surgical site infections were related to colon surgeries (14.5%), hip arthroplasty (10.0%), and small-bowel procedures (6.4%).

The median length of time between hospital admission and the onset of infection symptoms was 6 days.

C. difficile was the most frequently identified pathogen, accounting for 70.9% of all nosocomial GI infections and 12.1% of all health care–associated infections. Other common pathogens included Staphylococcus aureus (10.7% of all health care–associated infections), Klebsiella pneumoniae and Klebsiella oxytoca (9.9%), and Escherichia coli (9.3%).

The report’s investigators noted that their estimates "are remarkably similar to estimates from other data sources," such as the National Healthcare Safety Network and the Emerging Infections Program. That "bolsters our confidence in the overall estimates of health care–associated infections that we have generated," they said.

Sounding the alarm

The report "sounds the alarm" about infectious threats to hospitalized patients that need addressing, especially lung and gut infections and infections related to surgery or urinary catheters, Dr. Bell said. It also sheds light on several important pathogens, especially C. difficile, Staphylococci, and the family of Enterobacter organisms.

Those pathogens are at the center of President Barack Obama’s request for $30 million as part of his proposed $6.6 billion budget for 2015 for a new initiative to halve infections by those organisms within 5 years, Dr. Bell said.

The $30 million would be used to improve tracking of infections, the nation’s capacity for lab testing to determine which pathogens are most problematic, and "boots on the ground" to help hospitals implement best practices, Dr. Bell said.

The CDC would like to see every hospital in the country develop a strong antibiotic stewardship program, because "the challenge with antibiotic resistance can’t be overstated," he cautioned.

A patient advocate echoed that concern at the media briefing.

"While inwardly I breathe a small sigh of relief that annual infections and mortalities are diminishing, I remain extremely cautious regarding the growing threat of antibiotic resistance and the dire impact of this potential danger to American health care," said Victoria Nahum, executive director of the Safe Care Campaign. Ms. Nahum and her husband, Armando Nahum, founded the nonprofit organization after their son died of a health care–associated infection and two other family members developed complications from health care–associated infections.

Health care providers "have the power to prevent health care–associated infections" through compulsive hand hygiene and other best practices, Ms. Nahum said. Patients need to be more assertive, she added. "You just don’t flop down and say, ‘Take care of me.’ You have to kind of navigate what’s going to happen to you. In doing so, that can save your own life."

Dr. Bell suggested that hospitalized patients have a friend or family member be the "bad cop" and repeatedly ask caregivers if they have washed their hands, when urinary catheters can come out, and whether testing is being done to ensure that the right antibiotic is being used.

He said he knows that can be difficult for patients who may feel intimidated. "When my own mother was in the intensive care unit, I found it hard to pipe up," Dr. Bell said. "If I find it hard, I can’t imagine what it’s like for everybody else."

Dr. Magill reported no potential financial conflicts of interest; two of her associates reported ties to the Infectious Disease Consulting Corp. and Parexel.

An estimated 4% of inpatients at U.S. acute care hospitals have at least one health care–associated infection on any given day, according to a report published online March 26 in the New England Journal of Medicine.

Moreover, in a prevalence survey involving 183 acute care hospitals across 10 geographically diverse states, device-associated infections, "which have been a major focus of infection prevention in recent decades," accounted for only 25.6% of all health care–associated infections, said Dr. Shelley S. Magill of the division of health care quality promotion, Centers for Disease Control and Prevention, and her associates (N. Engl. J. Med. 2014;370:1198-1208).

In contrast, Clostridium difficile and other gastrointestinal infections, as well as non–ventilator-associated pneumonia, accounted for approximately half of all health care–associated infections in the survey. Surgical site infections also are still very common, accounting for 21.8%.

Because it appears that ventilator-associated pneumonia, catheter-associated UTIs, and central catheter–associated bloodstream infections are no longer the primary threat that they used to be, the study findings should prompt experts to "expand the public health focus to include these other types of infections, identifying patients at risk and developing effective countermeasures," the report’s authors noted.

The report shows that as a nation, we’re moving in the right direction; but there’s a great deal of work still to be done," Dr. Michael Bell said in a media briefing. "On any given day, 1 out of 25 hospitalized patients has an infection. And of those people, as many as one out of nine go on to die. This is not a minor issue," said Dr. Bell, deputy director of the CDC’s division of health care quality promotion.

The investigators developed and conducted the survey in 2011 to address a serious knowledge gap: No single surveillance system can provide estimates of "the burden of all types of such infections across acute care patient populations." So, Dr. Magill and her colleagues studied health care–associated infections among inpatients of all ages at 93 small, 68 medium-sized, and 22 large hospitals.

They found 504 such infections in 452 patients out of 11,282 patients covered in the survey, for an overall incidence of 4%. Using a statistical modeling process that accounted for predictors of infection prevalence and then applying those results to a nationally representative sample of U.S. community hospital stays, the investigators estimated that 648,000 inpatients nationwide had approximately 721,800 health care–associated infections in 2011.

Those estimates are lower than previous ones, such as those derived from the Study on the Efficacy of Nosocomial Infection Control in the 1970s , which postulated 2.1 million health care–associated infections each year, and those derived from National Nosocomial Infections Surveillance system data from 1990 to 2002, which estimated 1.7 million each year.

However, "it is difficult to draw conclusions from these comparisons because of the differences in patient populations, surveillance definitions of health care–associated infections, and data collection and analytical methods among these CDC methods," Dr. Magill and her associates said.

The current survey showed that 42.9% of health care–associated infections developed during a stay in a critical care unit or within 48 hours after; another 42.4% developed after a stay in a nonnursery ward.

Most of the surgical site infections were related to colon surgeries (14.5%), hip arthroplasty (10.0%), and small-bowel procedures (6.4%).

The median length of time between hospital admission and the onset of infection symptoms was 6 days.

C. difficile was the most frequently identified pathogen, accounting for 70.9% of all nosocomial GI infections and 12.1% of all health care–associated infections. Other common pathogens included Staphylococcus aureus (10.7% of all health care–associated infections), Klebsiella pneumoniae and Klebsiella oxytoca (9.9%), and Escherichia coli (9.3%).

The report’s investigators noted that their estimates "are remarkably similar to estimates from other data sources," such as the National Healthcare Safety Network and the Emerging Infections Program. That "bolsters our confidence in the overall estimates of health care–associated infections that we have generated," they said.

Sounding the alarm

The report "sounds the alarm" about infectious threats to hospitalized patients that need addressing, especially lung and gut infections and infections related to surgery or urinary catheters, Dr. Bell said. It also sheds light on several important pathogens, especially C. difficile, Staphylococci, and the family of Enterobacter organisms.

Those pathogens are at the center of President Barack Obama’s request for $30 million as part of his proposed $6.6 billion budget for 2015 for a new initiative to halve infections by those organisms within 5 years, Dr. Bell said.

The $30 million would be used to improve tracking of infections, the nation’s capacity for lab testing to determine which pathogens are most problematic, and "boots on the ground" to help hospitals implement best practices, Dr. Bell said.

The CDC would like to see every hospital in the country develop a strong antibiotic stewardship program, because "the challenge with antibiotic resistance can’t be overstated," he cautioned.

A patient advocate echoed that concern at the media briefing.

"While inwardly I breathe a small sigh of relief that annual infections and mortalities are diminishing, I remain extremely cautious regarding the growing threat of antibiotic resistance and the dire impact of this potential danger to American health care," said Victoria Nahum, executive director of the Safe Care Campaign. Ms. Nahum and her husband, Armando Nahum, founded the nonprofit organization after their son died of a health care–associated infection and two other family members developed complications from health care–associated infections.

Health care providers "have the power to prevent health care–associated infections" through compulsive hand hygiene and other best practices, Ms. Nahum said. Patients need to be more assertive, she added. "You just don’t flop down and say, ‘Take care of me.’ You have to kind of navigate what’s going to happen to you. In doing so, that can save your own life."

Dr. Bell suggested that hospitalized patients have a friend or family member be the "bad cop" and repeatedly ask caregivers if they have washed their hands, when urinary catheters can come out, and whether testing is being done to ensure that the right antibiotic is being used.

He said he knows that can be difficult for patients who may feel intimidated. "When my own mother was in the intensive care unit, I found it hard to pipe up," Dr. Bell said. "If I find it hard, I can’t imagine what it’s like for everybody else."

Dr. Magill reported no potential financial conflicts of interest; two of her associates reported ties to the Infectious Disease Consulting Corp. and Parexel.

An estimated 4% of inpatients at U.S. acute care hospitals have at least one health care–associated infection on any given day, according to a report published online March 26 in the New England Journal of Medicine.

Moreover, in a prevalence survey involving 183 acute care hospitals across 10 geographically diverse states, device-associated infections, "which have been a major focus of infection prevention in recent decades," accounted for only 25.6% of all health care–associated infections, said Dr. Shelley S. Magill of the division of health care quality promotion, Centers for Disease Control and Prevention, and her associates (N. Engl. J. Med. 2014;370:1198-1208).

In contrast, Clostridium difficile and other gastrointestinal infections, as well as non–ventilator-associated pneumonia, accounted for approximately half of all health care–associated infections in the survey. Surgical site infections also are still very common, accounting for 21.8%.

Because it appears that ventilator-associated pneumonia, catheter-associated UTIs, and central catheter–associated bloodstream infections are no longer the primary threat that they used to be, the study findings should prompt experts to "expand the public health focus to include these other types of infections, identifying patients at risk and developing effective countermeasures," the report’s authors noted.

The report shows that as a nation, we’re moving in the right direction; but there’s a great deal of work still to be done," Dr. Michael Bell said in a media briefing. "On any given day, 1 out of 25 hospitalized patients has an infection. And of those people, as many as one out of nine go on to die. This is not a minor issue," said Dr. Bell, deputy director of the CDC’s division of health care quality promotion.

The investigators developed and conducted the survey in 2011 to address a serious knowledge gap: No single surveillance system can provide estimates of "the burden of all types of such infections across acute care patient populations." So, Dr. Magill and her colleagues studied health care–associated infections among inpatients of all ages at 93 small, 68 medium-sized, and 22 large hospitals.

They found 504 such infections in 452 patients out of 11,282 patients covered in the survey, for an overall incidence of 4%. Using a statistical modeling process that accounted for predictors of infection prevalence and then applying those results to a nationally representative sample of U.S. community hospital stays, the investigators estimated that 648,000 inpatients nationwide had approximately 721,800 health care–associated infections in 2011.

Those estimates are lower than previous ones, such as those derived from the Study on the Efficacy of Nosocomial Infection Control in the 1970s , which postulated 2.1 million health care–associated infections each year, and those derived from National Nosocomial Infections Surveillance system data from 1990 to 2002, which estimated 1.7 million each year.

However, "it is difficult to draw conclusions from these comparisons because of the differences in patient populations, surveillance definitions of health care–associated infections, and data collection and analytical methods among these CDC methods," Dr. Magill and her associates said.

The current survey showed that 42.9% of health care–associated infections developed during a stay in a critical care unit or within 48 hours after; another 42.4% developed after a stay in a nonnursery ward.

Most of the surgical site infections were related to colon surgeries (14.5%), hip arthroplasty (10.0%), and small-bowel procedures (6.4%).

The median length of time between hospital admission and the onset of infection symptoms was 6 days.

C. difficile was the most frequently identified pathogen, accounting for 70.9% of all nosocomial GI infections and 12.1% of all health care–associated infections. Other common pathogens included Staphylococcus aureus (10.7% of all health care–associated infections), Klebsiella pneumoniae and Klebsiella oxytoca (9.9%), and Escherichia coli (9.3%).

The report’s investigators noted that their estimates "are remarkably similar to estimates from other data sources," such as the National Healthcare Safety Network and the Emerging Infections Program. That "bolsters our confidence in the overall estimates of health care–associated infections that we have generated," they said.

Sounding the alarm

The report "sounds the alarm" about infectious threats to hospitalized patients that need addressing, especially lung and gut infections and infections related to surgery or urinary catheters, Dr. Bell said. It also sheds light on several important pathogens, especially C. difficile, Staphylococci, and the family of Enterobacter organisms.

Those pathogens are at the center of President Barack Obama’s request for $30 million as part of his proposed $6.6 billion budget for 2015 for a new initiative to halve infections by those organisms within 5 years, Dr. Bell said.

The $30 million would be used to improve tracking of infections, the nation’s capacity for lab testing to determine which pathogens are most problematic, and "boots on the ground" to help hospitals implement best practices, Dr. Bell said.

The CDC would like to see every hospital in the country develop a strong antibiotic stewardship program, because "the challenge with antibiotic resistance can’t be overstated," he cautioned.

A patient advocate echoed that concern at the media briefing.

"While inwardly I breathe a small sigh of relief that annual infections and mortalities are diminishing, I remain extremely cautious regarding the growing threat of antibiotic resistance and the dire impact of this potential danger to American health care," said Victoria Nahum, executive director of the Safe Care Campaign. Ms. Nahum and her husband, Armando Nahum, founded the nonprofit organization after their son died of a health care–associated infection and two other family members developed complications from health care–associated infections.

Health care providers "have the power to prevent health care–associated infections" through compulsive hand hygiene and other best practices, Ms. Nahum said. Patients need to be more assertive, she added. "You just don’t flop down and say, ‘Take care of me.’ You have to kind of navigate what’s going to happen to you. In doing so, that can save your own life."

Dr. Bell suggested that hospitalized patients have a friend or family member be the "bad cop" and repeatedly ask caregivers if they have washed their hands, when urinary catheters can come out, and whether testing is being done to ensure that the right antibiotic is being used.

He said he knows that can be difficult for patients who may feel intimidated. "When my own mother was in the intensive care unit, I found it hard to pipe up," Dr. Bell said. "If I find it hard, I can’t imagine what it’s like for everybody else."

Dr. Magill reported no potential financial conflicts of interest; two of her associates reported ties to the Infectious Disease Consulting Corp. and Parexel.

TAMPA – Women who undergo bariatric surgery to lose weight are about 70% less likely to develop uterine cancer than are obese women who do not undergo such surgery, according to findings from a large retrospective cohort study.

The risk reduction was even greater (81%) among those who maintained their weight loss after surgery. The findings suggest that obesity may be a modifiable risk factor for uterine cancer, reported Dr. Kristy Kay Ward of the Moores Cancer Center at the University of California, San Diego.

Of more than 7.4 million inpatient admissions among women aged 18 years or older who were registered in the University Health System Consortium dataset from Jan. 1, 2009, to June 1, 2013, 103,797 had a history of bariatric surgery, and 44,345 had a diagnosis of uterine malignancy. The overall rate of uterine malignancy was 599/100,000 patients among those without a history of bariatric surgery, and which was 2.8 times higher among obese vs. nonobese patients within this group (1,409 vs. 496 per 100,000).

The overall rate of uterine cancer among those with a history of bariatric surgery was 408/100,000, but the rate was 2.5 times higher among those with persistent obesity after surgery, compared with those who maintained weight loss after surgery (682/100,000 vs. 270/100,000), Dr. Ward said at the annual meeting of the Society of Gynecologic Oncology.

Compared with obese women without a history of bariatric surgery, the relative risk of uterine cancer was 0.29 for women with prior bariatric surgery, 0.19 for women with normal weight after surgery, and 0.48 for women who remained obese after surgery, so the overall risk reduction with surgery was 70%, the maximum risk reduction (for those with normal weight after surgery) was 81%, and the lowest reduction in risk (for those who had surgery but remained obese) was 52%, Dr. Ward said.

Though limited by the retrospective nature of the study and the fact that the data didn’t differentiate between types of bariatric surgery, the findings are notable, because about 50,000 women were diagnosed with uterine cancer in 2013, making it the most common cancer affecting female reproductive organs. Furthermore, endometrial cancer, which accounts for 95% of uterine cancers, is associated with obesity in about 50% of cases, she explained.

In fact, obese women are two- to fourfold more likely to develop endometrial cancer than are women of normal weight, she said.

The current findings suggest that "a history of bariatric surgery is associated with substantial and clinically significantly reduced risk of uterine malignancy," she said, adding: "Our previous work, in agreement with the findings of others, had indicated that the risk of uterine malignancy increases linearly with BMI [body mass index]. Along with the findings of the current study, this supports that obesity may be a modifiable risk factor related to the development of endometrial cancer."

The mechanism for the link between bariatric surgery and reduced uterine cancer risk remains unclear, but fat loss likely plays a role, as adiposity is known to increase endogenous estrogen circulation. The bariatric surgery itself may also "somehow be influencing the immune system and decreasing inflammation," thereby contributing to decreased cancer risk, Dr. Ward noted.

The findings suggest that weight reduction measures, including bariatric surgery in appropriate candidates, are vitally important in obese women, she said.

"Screening of patients, counseling patients about the dangers of obesity, and appropriate referral for bariatric surgery may have great impact on the overall health of this population," she concluded, adding that future research should examine the benefits of bariatric surgery for the reduction of cancer, including endometrial cancer.

Dr. Ward reported having no disclosures.

TAMPA – Women who undergo bariatric surgery to lose weight are about 70% less likely to develop uterine cancer than are obese women who do not undergo such surgery, according to findings from a large retrospective cohort study.

The risk reduction was even greater (81%) among those who maintained their weight loss after surgery. The findings suggest that obesity may be a modifiable risk factor for uterine cancer, reported Dr. Kristy Kay Ward of the Moores Cancer Center at the University of California, San Diego.

Of more than 7.4 million inpatient admissions among women aged 18 years or older who were registered in the University Health System Consortium dataset from Jan. 1, 2009, to June 1, 2013, 103,797 had a history of bariatric surgery, and 44,345 had a diagnosis of uterine malignancy. The overall rate of uterine malignancy was 599/100,000 patients among those without a history of bariatric surgery, and which was 2.8 times higher among obese vs. nonobese patients within this group (1,409 vs. 496 per 100,000).

The overall rate of uterine cancer among those with a history of bariatric surgery was 408/100,000, but the rate was 2.5 times higher among those with persistent obesity after surgery, compared with those who maintained weight loss after surgery (682/100,000 vs. 270/100,000), Dr. Ward said at the annual meeting of the Society of Gynecologic Oncology.

Compared with obese women without a history of bariatric surgery, the relative risk of uterine cancer was 0.29 for women with prior bariatric surgery, 0.19 for women with normal weight after surgery, and 0.48 for women who remained obese after surgery, so the overall risk reduction with surgery was 70%, the maximum risk reduction (for those with normal weight after surgery) was 81%, and the lowest reduction in risk (for those who had surgery but remained obese) was 52%, Dr. Ward said.

Though limited by the retrospective nature of the study and the fact that the data didn’t differentiate between types of bariatric surgery, the findings are notable, because about 50,000 women were diagnosed with uterine cancer in 2013, making it the most common cancer affecting female reproductive organs. Furthermore, endometrial cancer, which accounts for 95% of uterine cancers, is associated with obesity in about 50% of cases, she explained.

In fact, obese women are two- to fourfold more likely to develop endometrial cancer than are women of normal weight, she said.

The current findings suggest that "a history of bariatric surgery is associated with substantial and clinically significantly reduced risk of uterine malignancy," she said, adding: "Our previous work, in agreement with the findings of others, had indicated that the risk of uterine malignancy increases linearly with BMI [body mass index]. Along with the findings of the current study, this supports that obesity may be a modifiable risk factor related to the development of endometrial cancer."

The mechanism for the link between bariatric surgery and reduced uterine cancer risk remains unclear, but fat loss likely plays a role, as adiposity is known to increase endogenous estrogen circulation. The bariatric surgery itself may also "somehow be influencing the immune system and decreasing inflammation," thereby contributing to decreased cancer risk, Dr. Ward noted.

The findings suggest that weight reduction measures, including bariatric surgery in appropriate candidates, are vitally important in obese women, she said.

"Screening of patients, counseling patients about the dangers of obesity, and appropriate referral for bariatric surgery may have great impact on the overall health of this population," she concluded, adding that future research should examine the benefits of bariatric surgery for the reduction of cancer, including endometrial cancer.

Dr. Ward reported having no disclosures.

TAMPA – Women who undergo bariatric surgery to lose weight are about 70% less likely to develop uterine cancer than are obese women who do not undergo such surgery, according to findings from a large retrospective cohort study.

The risk reduction was even greater (81%) among those who maintained their weight loss after surgery. The findings suggest that obesity may be a modifiable risk factor for uterine cancer, reported Dr. Kristy Kay Ward of the Moores Cancer Center at the University of California, San Diego.

Of more than 7.4 million inpatient admissions among women aged 18 years or older who were registered in the University Health System Consortium dataset from Jan. 1, 2009, to June 1, 2013, 103,797 had a history of bariatric surgery, and 44,345 had a diagnosis of uterine malignancy. The overall rate of uterine malignancy was 599/100,000 patients among those without a history of bariatric surgery, and which was 2.8 times higher among obese vs. nonobese patients within this group (1,409 vs. 496 per 100,000).

The overall rate of uterine cancer among those with a history of bariatric surgery was 408/100,000, but the rate was 2.5 times higher among those with persistent obesity after surgery, compared with those who maintained weight loss after surgery (682/100,000 vs. 270/100,000), Dr. Ward said at the annual meeting of the Society of Gynecologic Oncology.

Compared with obese women without a history of bariatric surgery, the relative risk of uterine cancer was 0.29 for women with prior bariatric surgery, 0.19 for women with normal weight after surgery, and 0.48 for women who remained obese after surgery, so the overall risk reduction with surgery was 70%, the maximum risk reduction (for those with normal weight after surgery) was 81%, and the lowest reduction in risk (for those who had surgery but remained obese) was 52%, Dr. Ward said.

Though limited by the retrospective nature of the study and the fact that the data didn’t differentiate between types of bariatric surgery, the findings are notable, because about 50,000 women were diagnosed with uterine cancer in 2013, making it the most common cancer affecting female reproductive organs. Furthermore, endometrial cancer, which accounts for 95% of uterine cancers, is associated with obesity in about 50% of cases, she explained.

In fact, obese women are two- to fourfold more likely to develop endometrial cancer than are women of normal weight, she said.

The current findings suggest that "a history of bariatric surgery is associated with substantial and clinically significantly reduced risk of uterine malignancy," she said, adding: "Our previous work, in agreement with the findings of others, had indicated that the risk of uterine malignancy increases linearly with BMI [body mass index]. Along with the findings of the current study, this supports that obesity may be a modifiable risk factor related to the development of endometrial cancer."

The mechanism for the link between bariatric surgery and reduced uterine cancer risk remains unclear, but fat loss likely plays a role, as adiposity is known to increase endogenous estrogen circulation. The bariatric surgery itself may also "somehow be influencing the immune system and decreasing inflammation," thereby contributing to decreased cancer risk, Dr. Ward noted.

The findings suggest that weight reduction measures, including bariatric surgery in appropriate candidates, are vitally important in obese women, she said.

"Screening of patients, counseling patients about the dangers of obesity, and appropriate referral for bariatric surgery may have great impact on the overall health of this population," she concluded, adding that future research should examine the benefits of bariatric surgery for the reduction of cancer, including endometrial cancer.

Dr. Ward reported having no disclosures.

MIAMI BEACH – A failure to develop hypophosphatemia during the first few days after major hepatectomy was associated with up to a threefold increase in the risk of major complications, hepatic insufficiency, and 30-day mortality.

Contrary to a widely held belief, hypophosphatemia may not be a problem requiring treatment, but rather a normal physiologic response to liver resection – a sign that hepatocytes are working hard to regenerate and recover their function, Dr. Malcolm Squires said at the annual meeting of the Americas Hepato-Pancreato-Biliary Association.

"The process of liver regeneration is metabolically demanding," said Dr. Squires of Emory University, Atlanta. "Immediately after hepatectomy, the [adenosine triphosphate] content decreases by 35%. The level starts to recover by day 6, to about preoperative levels by day 14. But during that process, the hepatocytes are rapidly consuming ATP; there is a significant concurrent phosphate uptake by the liver remnant, and we see that decrease in serum phosphorus."

These are all signs of normal liver remnant recovery, Dr. Squires said. Consequently, the failure to follow this pathway suggests that the remnant is not on a good recovery trajectory, but instead, a path that could lead to big problems.

To examine this idea, he and his colleagues looked at 719 patients who had undergone major hepatectomy from 2000 to 2012 and who had serum phosphorus evaluated after surgery.

Measures included daily phosphorus levels for the first week after surgery, as well as the day of the phosphorus nadir. Mean age of the patients was 57 years. The most common type of resection was a right hepatectomy (39%), followed by a left (23%), extended right (20%), and extended left (6%). Ten percent of patients had a nonanatomic resection, and 20% a concurrent bile duct resection.

The most common pathology was metastatic colorectal cancer (32%), followed by cholangiocarcinoma (12%), hepatocellular carcinoma (9%), and metastatic neuroendocrine tumor (5%). Other pathologies made up the remainder.

Most patients (69%) got phosphorus repletion in the first 72 hours after surgery, although this intervention was not protocol driven, Dr. Squires noted.

Postoperative hepatic insufficiency developed in 63 patients (9%). About a fourth (169) had major complications. Mortality was 4% within 30 days and 5% within 90 days.

The median preoperative serum phosphorus level was 3.7 mg/dL. This fell precipitously to a median nadir of 2.4 mg/dL (the lower limit of normal), which occurred on postoperative day 2 or 3 for the majority of patients. Recovery was linear, with a near-complete postoperative recovery by day 14. Patients followed the same trajectory regardless of the type of hepatectomy.

The researchers dichotomized the patients into those with a postoperative day 2 phosphorus of 2.4 mg/dL or higher (72%), or below 2.4 mg/dL (28%).

Patients with the higher levels were significantly more likely to develop hepatic insufficiency (12% vs. 7%) and major complications (27% vs. 20%), and to die within 30 days (4% vs. 2%) and 90 days (8% vs. 4%).

A multivariate analysis found that phosphorus of more than 2.4 mg/dL increased the risk of hepatic insufficiency by 78% and major complications by 60%. It nearly tripled the risk of 30-day mortality (HR 2.7) and more than doubled the risk of 90-day mortality (HR 2.5).

The team also looked at the timing of phosphorus nadir. Most patients (80%) achieved this by postoperative day 3, so the researchers divided the group into those who had that level within 3 days and those who had it later. Patients with the delayed nadir were twice as likely to have hepatic insufficiency and major complications, and to die within 30 days. The trend was to increased death within 90 days as well, but Dr. Squires said the difference was not statistically significant.

Early postoperative phosphorus administration did not affect these findings, he added.

Dr. Squires reported having no financial disclosures.

[email protected]

MIAMI BEACH – A failure to develop hypophosphatemia during the first few days after major hepatectomy was associated with up to a threefold increase in the risk of major complications, hepatic insufficiency, and 30-day mortality.

Contrary to a widely held belief, hypophosphatemia may not be a problem requiring treatment, but rather a normal physiologic response to liver resection – a sign that hepatocytes are working hard to regenerate and recover their function, Dr. Malcolm Squires said at the annual meeting of the Americas Hepato-Pancreato-Biliary Association.

"The process of liver regeneration is metabolically demanding," said Dr. Squires of Emory University, Atlanta. "Immediately after hepatectomy, the [adenosine triphosphate] content decreases by 35%. The level starts to recover by day 6, to about preoperative levels by day 14. But during that process, the hepatocytes are rapidly consuming ATP; there is a significant concurrent phosphate uptake by the liver remnant, and we see that decrease in serum phosphorus."

These are all signs of normal liver remnant recovery, Dr. Squires said. Consequently, the failure to follow this pathway suggests that the remnant is not on a good recovery trajectory, but instead, a path that could lead to big problems.

To examine this idea, he and his colleagues looked at 719 patients who had undergone major hepatectomy from 2000 to 2012 and who had serum phosphorus evaluated after surgery.

Measures included daily phosphorus levels for the first week after surgery, as well as the day of the phosphorus nadir. Mean age of the patients was 57 years. The most common type of resection was a right hepatectomy (39%), followed by a left (23%), extended right (20%), and extended left (6%). Ten percent of patients had a nonanatomic resection, and 20% a concurrent bile duct resection.

The most common pathology was metastatic colorectal cancer (32%), followed by cholangiocarcinoma (12%), hepatocellular carcinoma (9%), and metastatic neuroendocrine tumor (5%). Other pathologies made up the remainder.

Most patients (69%) got phosphorus repletion in the first 72 hours after surgery, although this intervention was not protocol driven, Dr. Squires noted.

Postoperative hepatic insufficiency developed in 63 patients (9%). About a fourth (169) had major complications. Mortality was 4% within 30 days and 5% within 90 days.

The median preoperative serum phosphorus level was 3.7 mg/dL. This fell precipitously to a median nadir of 2.4 mg/dL (the lower limit of normal), which occurred on postoperative day 2 or 3 for the majority of patients. Recovery was linear, with a near-complete postoperative recovery by day 14. Patients followed the same trajectory regardless of the type of hepatectomy.

The researchers dichotomized the patients into those with a postoperative day 2 phosphorus of 2.4 mg/dL or higher (72%), or below 2.4 mg/dL (28%).

Patients with the higher levels were significantly more likely to develop hepatic insufficiency (12% vs. 7%) and major complications (27% vs. 20%), and to die within 30 days (4% vs. 2%) and 90 days (8% vs. 4%).

A multivariate analysis found that phosphorus of more than 2.4 mg/dL increased the risk of hepatic insufficiency by 78% and major complications by 60%. It nearly tripled the risk of 30-day mortality (HR 2.7) and more than doubled the risk of 90-day mortality (HR 2.5).

The team also looked at the timing of phosphorus nadir. Most patients (80%) achieved this by postoperative day 3, so the researchers divided the group into those who had that level within 3 days and those who had it later. Patients with the delayed nadir were twice as likely to have hepatic insufficiency and major complications, and to die within 30 days. The trend was to increased death within 90 days as well, but Dr. Squires said the difference was not statistically significant.

Early postoperative phosphorus administration did not affect these findings, he added.

Dr. Squires reported having no financial disclosures.

[email protected]

MIAMI BEACH – A failure to develop hypophosphatemia during the first few days after major hepatectomy was associated with up to a threefold increase in the risk of major complications, hepatic insufficiency, and 30-day mortality.

Contrary to a widely held belief, hypophosphatemia may not be a problem requiring treatment, but rather a normal physiologic response to liver resection – a sign that hepatocytes are working hard to regenerate and recover their function, Dr. Malcolm Squires said at the annual meeting of the Americas Hepato-Pancreato-Biliary Association.

"The process of liver regeneration is metabolically demanding," said Dr. Squires of Emory University, Atlanta. "Immediately after hepatectomy, the [adenosine triphosphate] content decreases by 35%. The level starts to recover by day 6, to about preoperative levels by day 14. But during that process, the hepatocytes are rapidly consuming ATP; there is a significant concurrent phosphate uptake by the liver remnant, and we see that decrease in serum phosphorus."

These are all signs of normal liver remnant recovery, Dr. Squires said. Consequently, the failure to follow this pathway suggests that the remnant is not on a good recovery trajectory, but instead, a path that could lead to big problems.

To examine this idea, he and his colleagues looked at 719 patients who had undergone major hepatectomy from 2000 to 2012 and who had serum phosphorus evaluated after surgery.

Measures included daily phosphorus levels for the first week after surgery, as well as the day of the phosphorus nadir. Mean age of the patients was 57 years. The most common type of resection was a right hepatectomy (39%), followed by a left (23%), extended right (20%), and extended left (6%). Ten percent of patients had a nonanatomic resection, and 20% a concurrent bile duct resection.

The most common pathology was metastatic colorectal cancer (32%), followed by cholangiocarcinoma (12%), hepatocellular carcinoma (9%), and metastatic neuroendocrine tumor (5%). Other pathologies made up the remainder.

Most patients (69%) got phosphorus repletion in the first 72 hours after surgery, although this intervention was not protocol driven, Dr. Squires noted.

Postoperative hepatic insufficiency developed in 63 patients (9%). About a fourth (169) had major complications. Mortality was 4% within 30 days and 5% within 90 days.

The median preoperative serum phosphorus level was 3.7 mg/dL. This fell precipitously to a median nadir of 2.4 mg/dL (the lower limit of normal), which occurred on postoperative day 2 or 3 for the majority of patients. Recovery was linear, with a near-complete postoperative recovery by day 14. Patients followed the same trajectory regardless of the type of hepatectomy.

The researchers dichotomized the patients into those with a postoperative day 2 phosphorus of 2.4 mg/dL or higher (72%), or below 2.4 mg/dL (28%).

Patients with the higher levels were significantly more likely to develop hepatic insufficiency (12% vs. 7%) and major complications (27% vs. 20%), and to die within 30 days (4% vs. 2%) and 90 days (8% vs. 4%).

A multivariate analysis found that phosphorus of more than 2.4 mg/dL increased the risk of hepatic insufficiency by 78% and major complications by 60%. It nearly tripled the risk of 30-day mortality (HR 2.7) and more than doubled the risk of 90-day mortality (HR 2.5).

The team also looked at the timing of phosphorus nadir. Most patients (80%) achieved this by postoperative day 3, so the researchers divided the group into those who had that level within 3 days and those who had it later. Patients with the delayed nadir were twice as likely to have hepatic insufficiency and major complications, and to die within 30 days. The trend was to increased death within 90 days as well, but Dr. Squires said the difference was not statistically significant.

Early postoperative phosphorus administration did not affect these findings, he added.

Dr. Squires reported having no financial disclosures.

[email protected]

SCOTTSDALE, ARIZ. – The presence of a coronary artery stent is not a barrier to noncardiac surgery, but it may change the timing of surgery and perioperative management of the patient, a hospitalist cautions.

Patients who receive bare-metal stents should delay having elective surgery for at least 6 weeks after stent placement, and those who receive a drug-eluting stent should put off elective procedures for at least a year, said Dr. Amir K. Jaffer, professor of medicine and chief of the division of hospital medicine at Rush University Medical Center in Chicago.

© Darren Hester/Fotolia.com

The type of stent, its placement, and the time since placement are just some of the key pieces of information that clinicians need to manage patients, Dr. Jaffer said at a meeting on perioperative medicine sponsored by the University of Miami.

"You want to try to get that [information] card if you can from the patient, about where the stents were placed, and if they don’t have the card handy, you really need to go to the procedure note, because the patient may or may not know if it was a drug-eluting stent," he said.

Other vital pieces of the perioperative puzzle are which coronary vessel the stent was implanted in; when the stent was implanted; what drug, if any (sirolimus or paclitaxel) is eluted by the stent; whether there were surgical or postoperative complications; prior history of stent thrombosis; the patient’s comorbidities; duration of dual-antiplatelet therapy; and how the patient has fared on therapy.

Prior to an elective noncardiac procedure, clinicians must consider patient risk factors, including indication for antithrombotic therapy, risk factors for thrombosis or thromboembolism, and type of antithrombotic agent; and surgical risk factors, including type of procedure, bleeding risk, thromboembolism risk, and time off antithrombotic therapy.

When to stop antithrombotic agents

Dr. Jaffer noted that because aspirin is an irreversible inhibitor of platelet cyclooxygenase and the circulating platelet pool is replaced every 7 to 10 days, patients on aspirin as part of their dual-antiplatelet therapy should stop taking the drug from 7 to 10 days before scheduled surgery.

Thienopyridines/P2Y12 receptor antagonists such as clopidogrel (Plavix) and ticagrelor (Brilinta) work by inhibiting adenosine diphosphate (ADP) receptor-mediated platelet activation and aggregation. Dr. Jaffer said that although guidelines recommend stopping these agents 7 days before surgery, there is evidence to suggest that 5 days may be a sufficient window of safety.

It is also important to take into consideration the pharmacokinetic profiles of the specific antiplatelet agents. For example, ticagrelor has a more rapid onset and greater degree of platelet-aggregation inhibition than clopidogrel, although the time from stopping each agent until the return to near-baseline platelet aggregation is similar, on the order of about 120 hours (5 days) or longer, he said.

Risk varies by surgery type

The type of surgery is also important, as certain procedures – such as neurocranial surgery, spinal canal surgery, and procedures performed in the posterior chamber of the eye – carry a high risk for hemorrhage and are likely to require blood transfusions.

Dr. Jaffer noted that in 2007, the American College of Cardiology and American Heart Association issued a joint advisory on antiplatelet therapy and noncardiac surgery, which warned health care providers about the potentially catastrophic risks of stopping thienopyridines prematurely, which could result in acute stent thrombosis, myocardial infarction, and death. The guidelines recommend waiting a minimum of 6 weeks for noncardiac surgery following implantation of a bare-metal stent, and 1 year after a drug-eluting stent.

He pointed to two studies from the Mayo Clinic published in 2008. The first study showed that the risk of major cardiac adverse events among patients with a bare-metal stent undergoing noncardiac surgery within 30 days of stent placement was approximately 10%, but diminished to 2.7% at 91 days after placement (Anesthesiology 2008;109:588-95). The second study showed that the risk of major cardiac adverse events was 6.1% within 90 days after implantation of a drug-eluting stent, with the risk dwindling to 3.1% after 1 year (Anesthesiology 2008;109:596-604).

If urgent surgery such as a hemicolectomy for colon cancer is required within 6 months of drug-eluting stent implantation, the patient should continue on dual-antiplatelet therapy, Dr. Jaffer said. If the surgery is from 6 months to 1 year after implantation in these patients, the patient should be continued on at least 81 mg aspirin, but if the patient is taking clopidogrel, he or she should have the thienopyridine discontinued 5 days before surgery and the drug resumed as soon as possible after surgery with a 300-mg loading dose, followed by 75 mg daily. If the patient is not yet able to eat, the dual-antiplatelet therapy should be delivered via nasogastric tube, he said.

Dr. Jaffer reported serving as a consultant to Boehringer Ingelheim, Janssen Pharmaceuticals, and other companies. Dr. Jaffer also serves on the editorial advisory board of Hospitalist News.

SCOTTSDALE, ARIZ. – The presence of a coronary artery stent is not a barrier to noncardiac surgery, but it may change the timing of surgery and perioperative management of the patient, a hospitalist cautions.

Patients who receive bare-metal stents should delay having elective surgery for at least 6 weeks after stent placement, and those who receive a drug-eluting stent should put off elective procedures for at least a year, said Dr. Amir K. Jaffer, professor of medicine and chief of the division of hospital medicine at Rush University Medical Center in Chicago.

© Darren Hester/Fotolia.com

The type of stent, its placement, and the time since placement are just some of the key pieces of information that clinicians need to manage patients, Dr. Jaffer said at a meeting on perioperative medicine sponsored by the University of Miami.

"You want to try to get that [information] card if you can from the patient, about where the stents were placed, and if they don’t have the card handy, you really need to go to the procedure note, because the patient may or may not know if it was a drug-eluting stent," he said.

Other vital pieces of the perioperative puzzle are which coronary vessel the stent was implanted in; when the stent was implanted; what drug, if any (sirolimus or paclitaxel) is eluted by the stent; whether there were surgical or postoperative complications; prior history of stent thrombosis; the patient’s comorbidities; duration of dual-antiplatelet therapy; and how the patient has fared on therapy.

Prior to an elective noncardiac procedure, clinicians must consider patient risk factors, including indication for antithrombotic therapy, risk factors for thrombosis or thromboembolism, and type of antithrombotic agent; and surgical risk factors, including type of procedure, bleeding risk, thromboembolism risk, and time off antithrombotic therapy.

When to stop antithrombotic agents

Dr. Jaffer noted that because aspirin is an irreversible inhibitor of platelet cyclooxygenase and the circulating platelet pool is replaced every 7 to 10 days, patients on aspirin as part of their dual-antiplatelet therapy should stop taking the drug from 7 to 10 days before scheduled surgery.

Thienopyridines/P2Y12 receptor antagonists such as clopidogrel (Plavix) and ticagrelor (Brilinta) work by inhibiting adenosine diphosphate (ADP) receptor-mediated platelet activation and aggregation. Dr. Jaffer said that although guidelines recommend stopping these agents 7 days before surgery, there is evidence to suggest that 5 days may be a sufficient window of safety.

It is also important to take into consideration the pharmacokinetic profiles of the specific antiplatelet agents. For example, ticagrelor has a more rapid onset and greater degree of platelet-aggregation inhibition than clopidogrel, although the time from stopping each agent until the return to near-baseline platelet aggregation is similar, on the order of about 120 hours (5 days) or longer, he said.

Risk varies by surgery type

The type of surgery is also important, as certain procedures – such as neurocranial surgery, spinal canal surgery, and procedures performed in the posterior chamber of the eye – carry a high risk for hemorrhage and are likely to require blood transfusions.

Dr. Jaffer noted that in 2007, the American College of Cardiology and American Heart Association issued a joint advisory on antiplatelet therapy and noncardiac surgery, which warned health care providers about the potentially catastrophic risks of stopping thienopyridines prematurely, which could result in acute stent thrombosis, myocardial infarction, and death. The guidelines recommend waiting a minimum of 6 weeks for noncardiac surgery following implantation of a bare-metal stent, and 1 year after a drug-eluting stent.

He pointed to two studies from the Mayo Clinic published in 2008. The first study showed that the risk of major cardiac adverse events among patients with a bare-metal stent undergoing noncardiac surgery within 30 days of stent placement was approximately 10%, but diminished to 2.7% at 91 days after placement (Anesthesiology 2008;109:588-95). The second study showed that the risk of major cardiac adverse events was 6.1% within 90 days after implantation of a drug-eluting stent, with the risk dwindling to 3.1% after 1 year (Anesthesiology 2008;109:596-604).

If urgent surgery such as a hemicolectomy for colon cancer is required within 6 months of drug-eluting stent implantation, the patient should continue on dual-antiplatelet therapy, Dr. Jaffer said. If the surgery is from 6 months to 1 year after implantation in these patients, the patient should be continued on at least 81 mg aspirin, but if the patient is taking clopidogrel, he or she should have the thienopyridine discontinued 5 days before surgery and the drug resumed as soon as possible after surgery with a 300-mg loading dose, followed by 75 mg daily. If the patient is not yet able to eat, the dual-antiplatelet therapy should be delivered via nasogastric tube, he said.

Dr. Jaffer reported serving as a consultant to Boehringer Ingelheim, Janssen Pharmaceuticals, and other companies. Dr. Jaffer also serves on the editorial advisory board of Hospitalist News.

SCOTTSDALE, ARIZ. – The presence of a coronary artery stent is not a barrier to noncardiac surgery, but it may change the timing of surgery and perioperative management of the patient, a hospitalist cautions.

Patients who receive bare-metal stents should delay having elective surgery for at least 6 weeks after stent placement, and those who receive a drug-eluting stent should put off elective procedures for at least a year, said Dr. Amir K. Jaffer, professor of medicine and chief of the division of hospital medicine at Rush University Medical Center in Chicago.

© Darren Hester/Fotolia.com

The type of stent, its placement, and the time since placement are just some of the key pieces of information that clinicians need to manage patients, Dr. Jaffer said at a meeting on perioperative medicine sponsored by the University of Miami.

"You want to try to get that [information] card if you can from the patient, about where the stents were placed, and if they don’t have the card handy, you really need to go to the procedure note, because the patient may or may not know if it was a drug-eluting stent," he said.

Other vital pieces of the perioperative puzzle are which coronary vessel the stent was implanted in; when the stent was implanted; what drug, if any (sirolimus or paclitaxel) is eluted by the stent; whether there were surgical or postoperative complications; prior history of stent thrombosis; the patient’s comorbidities; duration of dual-antiplatelet therapy; and how the patient has fared on therapy.

Prior to an elective noncardiac procedure, clinicians must consider patient risk factors, including indication for antithrombotic therapy, risk factors for thrombosis or thromboembolism, and type of antithrombotic agent; and surgical risk factors, including type of procedure, bleeding risk, thromboembolism risk, and time off antithrombotic therapy.

When to stop antithrombotic agents

Dr. Jaffer noted that because aspirin is an irreversible inhibitor of platelet cyclooxygenase and the circulating platelet pool is replaced every 7 to 10 days, patients on aspirin as part of their dual-antiplatelet therapy should stop taking the drug from 7 to 10 days before scheduled surgery.

Thienopyridines/P2Y12 receptor antagonists such as clopidogrel (Plavix) and ticagrelor (Brilinta) work by inhibiting adenosine diphosphate (ADP) receptor-mediated platelet activation and aggregation. Dr. Jaffer said that although guidelines recommend stopping these agents 7 days before surgery, there is evidence to suggest that 5 days may be a sufficient window of safety.

It is also important to take into consideration the pharmacokinetic profiles of the specific antiplatelet agents. For example, ticagrelor has a more rapid onset and greater degree of platelet-aggregation inhibition than clopidogrel, although the time from stopping each agent until the return to near-baseline platelet aggregation is similar, on the order of about 120 hours (5 days) or longer, he said.

Risk varies by surgery type

The type of surgery is also important, as certain procedures – such as neurocranial surgery, spinal canal surgery, and procedures performed in the posterior chamber of the eye – carry a high risk for hemorrhage and are likely to require blood transfusions.

Dr. Jaffer noted that in 2007, the American College of Cardiology and American Heart Association issued a joint advisory on antiplatelet therapy and noncardiac surgery, which warned health care providers about the potentially catastrophic risks of stopping thienopyridines prematurely, which could result in acute stent thrombosis, myocardial infarction, and death. The guidelines recommend waiting a minimum of 6 weeks for noncardiac surgery following implantation of a bare-metal stent, and 1 year after a drug-eluting stent.

He pointed to two studies from the Mayo Clinic published in 2008. The first study showed that the risk of major cardiac adverse events among patients with a bare-metal stent undergoing noncardiac surgery within 30 days of stent placement was approximately 10%, but diminished to 2.7% at 91 days after placement (Anesthesiology 2008;109:588-95). The second study showed that the risk of major cardiac adverse events was 6.1% within 90 days after implantation of a drug-eluting stent, with the risk dwindling to 3.1% after 1 year (Anesthesiology 2008;109:596-604).

If urgent surgery such as a hemicolectomy for colon cancer is required within 6 months of drug-eluting stent implantation, the patient should continue on dual-antiplatelet therapy, Dr. Jaffer said. If the surgery is from 6 months to 1 year after implantation in these patients, the patient should be continued on at least 81 mg aspirin, but if the patient is taking clopidogrel, he or she should have the thienopyridine discontinued 5 days before surgery and the drug resumed as soon as possible after surgery with a 300-mg loading dose, followed by 75 mg daily. If the patient is not yet able to eat, the dual-antiplatelet therapy should be delivered via nasogastric tube, he said.

Dr. Jaffer reported serving as a consultant to Boehringer Ingelheim, Janssen Pharmaceuticals, and other companies. Dr. Jaffer also serves on the editorial advisory board of Hospitalist News.