Impact of epicardial anterior fat pad retention on postcardiothoracic surgery atrial fibrillation incidence: the AFIST-III Study.

OBJECTIVES: We conducted a randomized, blinded, controlled study evaluating the impact of anterior fat pad (AFP) maintenance on postoperative atrial fibrillation (POAF) incidence. BACKGROUND: Drugs with antiadrenergic effects reduce POAF. Because the epicardial AFP is parasympathetically innervated, its routine excision during coronary artery bypass grafting (CABG) might precipitate autonomic imbalance and induce POAF. METHODS: Patients (n = 180, mean age = 66 +/- 10 years, 80% men, 5% with previous atrial fibrillation) undergoing CABG surgery were randomized to either AFP maintenance or AFP removal. Routine prophylaxis against POAF with beta-blockers (85%) and amiodarone (28%) was allowed on the basis of caregivers' discretion. The development of POAF, total hospital costs, and heart rate variability was compared between groups. RESULTS: Anterior fat pad maintenance did not reduce POAF incidence (34.8% vs. 35.2%, p = 0.950) or total hospital costs (data as medians with 25%, 75% percentiles: 22,940 dollars [17,629 dollars, 29,274 dollars] vs. 23,866 dollars [18,602 dollars, 30,370 dollars], p = 0.647) but was associated with higher heart rate variability (SD of normal-to-normal RR intervals [SDNN]: 31.7 +/- 24.6 vs. 22.7 +/- 8.3, p = 0.05 and SD of all 5-min mean RR intervals [SDANN 5]: 17.1 +/- 11.9 vs. 10.1 +/- 5.5, p = 0.003) than AFP removal. CONCLUSIONS: Maintaining the AFP prevents attenuation of parasympathetic tone after CABG but does not reduce POAF or total hospital costs in any appreciable way.

Impact of Hispanic ethnicity on the likelihood of developing postoperative atrial fibrillation.

BACKGROUND: A recent multicenter observational study of 4,657 patients reported a 52% lower risk of postcardiothoracic surgery (CTS) atrial fibrillation (AF) among South American vs United States patients. This study did not evaluate whether the decreased incidence in AF was attributable to differing ethnicity (Hispanic vs Caucasian) or to another cause. METHODS: A cohort study of CTS patients at Hartford Hospital was undertaken to evaluate whether Hispanic patients had a lower incidence of post-CTS AF than Caucasians. First, Hispanic patients were compared to the total Caucasian population. Then differences in important baseline predictors of AF were probed between groups. Finally, Hispanic patients undergoing CTS were matched (1:4 matching) with Caucasian patients based upon known predictors of post-CTS AF including age >70 years, valvular surgery, AF history, previous CTS, peripheral vascular disease, gender, pre-CTS digoxin and beta-blocker intolerance. RESULTS: In the total population [n = 2,739, with 97 (3.5%) Hispanics, 66.6 +/- 11.6 years, 70.9% male, 66.9% valve surgery], Hispanics were 38% less likely to develop AF (15.5% vs 24.8%, P = 0.035). However, the Hispanic patients were 11.9 years younger (P< 0.001) with 14.7% more women (P = 0.002) which reduces the risk of post-CTS AF; they also had a 12.8% higher risk of valvular surgery (P = 0.009) which is known to enhance the risk. When these factors and other important variables were matched for, a total of 485 patients (n = 97 Hispanics, 388 Caucasian) were evaluated (55.8 +/- 13.1 years, 57.3% male, 45.4% valvular surgery). Hispanic and Caucasian patients had a similar incidence of post-CTS AF (15.5% vs 18.3%, P = 0.513). CONCLUSION: Hispanic patients do not have an innately lower risk of post-CTS AF than Caucasians.

The effect of Echinacea on upper respiratory infection symptom severity and quality of life.

We reviewed the current body of evidence supporting the use of Echinacea to reduce URI symptoms and improve QoL. Different Echinacea species have been administered either alone or in combination with other herbals and in various doses and dosage forms. Studies depicting Echinacea's effect on URI symptoms and QoL are contradictory. Despite some positive effects on symptom severity and QoL, given the current data available it would be inappropriate to attribute QoL benefit to Echinacea. The possibility that various facets of QoL may be improved with Echinacea cannot be ruled out. Further research into this compound is warranted.

Safety of amiodarone in the prevention of postoperative atrial fibrillation: a meta-analysis.

PURPOSE: A meta-analysis was conducted to assess the safety of amiodarone in the prevention of postoperative atrial fibrillation. METHODS: A search of the medical literature was conducted to identify randomized controlled trials of prophylactic amiodarone use in cardiothoracic surgery. Studies were independently reviewed by three investigators and selected for inclusion if they met the following three criteria: (1) randomized controlled trial of amiodarone versus placebo or routine treatment, (2) patients underwent coronary artery bypass graft or valvular surgery, and (3) reported data on the frequency of at least one of the following safety endpoints: bradycardia, hypotension, heart block, nausea, cerebral vascular accident, myocardial infarction, and death. Both random- and fixed-effects models were used to determine any significant associations between amiodarone and safety endpoints. RESULTS: Eighteen trials were analyzed. A total of 3408 patients were enrolled in these trials (1736 received amiodarone and 1672 received placebo). Amiodarone increased the odds of developing bradycardia (odds ratio [OR], 1.70; 95% confidence interval [CI], 1.05-2.74) and hypotension (OR, 1.62; 95% CI, 1.04-2.54). The administration of i.v. amiodarone, an average daily dose exceeding 1 g, and postoperative amiodarone administration were each associated with a greater likelihood of hemodynamic adverse effects. Amiodarone did not appear to affect other safety endpoints. CONCLUSION: Meta-analysis showed amiodarone to be associated with an increased risk of developing bradycardia and hypotension when used for the prophylaxis of postoperative atrial fibrillation. The greatest risk in the occurrence of these adverse events arose when using regimens containing i.v. amiodarone, initiating prophylaxis during the postoperative period, and using regimens with average daily doses exceeding 1 g.

Cost-effectiveness of amiodarone for prophylaxis of atrial fibrillation after cardiothoracic surgery.

STUDY OBJECTIVE: To determine whether prophylactic amiodarone, dosed according to Atrial Fibrillation Suppression Trial (AFIST) I and II regimens, is a cost-effective strategy for prevention of postoperative atrial fibrillation. DESIGN: Cost-effectiveness analysis of retrospective cohort study. SETTING: Urban, academic hospital. PATIENTS: A total of 2046 patients who underwent cardiothoracic surgery between February 1, 1998, and October 31, 2003. Of these patients, 186 received amiodarone and 1860 served as controls. MEASUREMENTS AND MAIN RESULTS: Each patient who received prophylactic amiodarone using the AFIST I or II dosing strategies was matched for age, sex, history of valvular surgery, history of atrial fibrillation, beta-blocker intolerance, and receipt of preoperative digoxin therapy with 10 patients who did not receive prophylactic amiodarone. Occurrence of postoperative atrial fibrillation, total hospital costs, and both intensive care unit (ICU) and total hospital length of stay (LOS) were compared between groups. Nonparametric bootstrapping was conducted to examine study results as part of a quadrant analysis and to calculate confidence intervals for the incremental cost-effectiveness ratio. The ICU and total hospital LOS, and total costs for patients with and without postoperative atrial fibrillation were also compared. Fewer patients receiving prophylactic amiodarone developed postoperative atrial fibrillation compared with controls (23.1% vs 29.9%, p=0.05). Total hospital costs for the amiodarone group were 28% less than those for the control group (24,131 US dollars +/- 26,539 vs 33,518 US dollars +/- 40,892, p=0.002). Approximately 98% of the time, patients receiving amiodarone prophylaxis fell into the quadrant that showed superior efficacy and lower total costs. Patients who developed postoperative atrial fibrillation, compared with those who did not, regardless of amiodarone prophylaxis, had a longer mean +/- SD stay in the ICU (6.9 +/- 17.1 vs 3.7 +/- 7.9 days, p<0.001), a longer mean total hospital LOS (14.8 +/- 18.8 vs 10.2 +/- 10.4 days, p+/-0.001), and higher mean total hospital costs (41,574 US dollars +/- 54,721 vs 28,968 US dollars +/- 31,046, p<0.001). CONCLUSION: Prophylactic amiodarone was shown to reduce the occurrence of postoperative atrial fibrillation as well as total hospital costs in patients undergoing cardiothoracic surgery. In patients who developed postoperative atrial fibrillation, both ICU and total hospital LOS as well as total hospital costs were increased.

Impact of intravenous magnesium on post-cardiothoracic surgery atrial fibrillation and length of hospital stay: a meta-analysis.

Postoperative atrial fibrillation can occur in 25% to 40% of patients undergoing cardiothoracic surgery. Although the majority of postoperative atrial fibrillation is benign, it has been associated with prolonged hospital length of stay. Magnesium prophylaxis against postoperative atrial fibrillation has been evaluated in several clinical trials; however these trials were small in size and therefore conveyed mixed or inconclusive results. In an attempt to better understand magnesium's role in this setting, we conducted a meta-analysis. A systematic literature search was conducted from January 1999 through August 2004 to identify trials of prophylactic magnesium in the setting of cardiothoracic surgery. The primary outcome measure was the incidence of postoperative atrial fibrillation. Trials were further analyzed based on cumulative doses of magnesium and perioperative time of initiation of prophylaxis, as well as length of stay. Seven randomized trials were identified. Upon meta-analysis, magnesium was found to prevent postoperative atrial fibrillation with an odds ratio of 0.66 and 95% confidence interval of 0.51 to 0.87. The incidence of postoperative atrial fibrillation was also significantly reduced in the low dose with an odds ratio of 0.36 and 95% confidence interval of 0.23 to 0.56, and in the preoperative groups with an odds ratio of 0.46 and 95% confidence interval of 0.31 to 0.67. Prophylactic magnesium reduced length of stay (n = 6 studies) by a weighted mean difference of 0.29 days, with a 95% confidence interval 0.54 to 0.05. Prophylactic magnesium reduced cardiothoracic surgery patients' risk of postoperative atrial fibrillation and length of stay. Administering lower doses and initiating prophylaxis in the preoperative period achieved the greatest reduction in postoperative atrial fibrillation.

The impact of ACE inhibitors or angiotensin II type 1 receptor blockers on the development of new-onset type 2 diabetes.

OBJECTIVE: Angiotensin II has been shown to increase hepatic glucose production and decrease insulin sensitivity. Patients who utilize either an ACE inhibitor (ACEI) or angiotensin receptor blocker (ARB) may experience a decreased incidence of new-onset type 2 diabetes. RESEARCH DESIGN AND METHODS: Three reviewers conducted a systematic literature search of Medline, EMBASE, CINAHL, and the Cochrane Library (1966 to present) to extract a consensus of trial data involving an ACEI or ARB with an end point of new-onset type 2 diabetes. Studies were included if they were randomized controlled trials verses placebo/routine therapy. A random-effects model was utilized. Subgroup and sensitivity analyses were conducted. RESULTS: Eleven trials were identified, including 66,608 patients. An ACEI or ARB prevented new-onset type 2 diabetes (odds ratio 0.78 [95% CI 0.73-0.83]). The influence of either an ACEI (six trials) or an ARB (five trials) alone on new-onset type 2 diabetes was similar (0.79 [0.71-0.89] and 0.76 [0.70-0.82], respectively). Regardless of indication for use, hypertension (seven trials), coronary artery disease (two trials), or heart failure (two trials), reductions in new-onset type 2 diabetes were maintained (0.79 [0.72-0.85], 0.76 [0.60-0.95], and 0.70 [0.50-0.96], respectively). No statistical heterogeneity was observed for any evaluation (P > 0.1 for all comparisons). ACEIs and ARBs did not reduce the odds of mortality, cardiovascular, or cerebrovascular events versus control therapy among all of these studies combined or the hypertension trials. ACEIs and ARBs did reduce the odds of these outcomes among the coronary artery disease studies versus control therapy. CONCLUSIONS: ACEIs or ARBs may decrease patients' odds of developing new-onset type 2 diabetes but does not reduce the odds of mortality, cardiovascular, or cerebrovascular outcomes over the study follow-up periods among patients with hypertension.

When "S" does not mean success: the importance of choice of antibiotic and dose on clinical and economic outcomes of severe infection.

Antimicrobial resistance among bacterial pathogens continues to challenge clinicians. It is the main reason for antibiotic therapy to be deemed inappropriate and leads to unfavorable outcomes and increased costs. Knowledge of local susceptibility patterns can help clinicians empirically choose the appropriate antibiotic. In addition, the proper dosage regimen, based on pharmacodynamics, is essential to maximize the likelihood of achieving optimal therapy. Pharmacodynamic surveillance studies have demonstrated that percent susceptibility provides an accurate estimate of bactericidal exposure at standard dosage regimens for carbapenems, ceftazidime, and cefepime, whereas percent susceptibility overestimates actual bactericidal exposure for piperacillin/tazobactam and ciprofloxacin. The empiric use of appropriate broad-spectrum antimicrobial therapy at the correct dosages for severe infections should improve clinical outcomes and result in economic benefit. Initial therapy should have a high likelihood of covering resistant pathogens.

Effect of aprotinin on the frequency of postoperative atrial fibrillation or flutter.

PURPOSE: The relationship between adding aprotinin to standard care and the frequency of postoperative atrial fibrillation or flutter (POAF) in patients undergoing cardiothoracic surgery (CTS) with cardiopulmonary bypass (CPB) was studied. METHODS: This was a retrospective cohort evaluation. All patients at a hospital who underwent CTS with CPB between October 1999 and October 2003 and who received aprotinin during surgery were included in the treatment group. Control patients were those who did not receive aprotinin; they were matched with treatment group patients for age, valvular surgery, history of atrial fibrillation or flutter, renal dysfunction, peripheral artery disease, smoking, angina, diabetes mellitus, congestive heart failure, previous CTS, sex, beta-blocker intolerance, and use of preoperative digoxin. The primary endpoint was POAF; secondary endpoints were perioperative transfusion use, length of stay (LOS), stroke, myocardial infarction, renal failure, graft occlusion, and death. RESULTS: A total of 438 patients (219 per group) were evaluated. The patients' mean age was 68 years, 67% were men, and 74% had had valvular surgery. Patients who received aprotinin (mean +/- S.D. dose, 2.75 million +/- 1.24 million kallikrein-inhibiting units) did not have a significantly lower frequency of POAF than control patients (28% versus 27%, respectively [p = 0.92]), nor was there a significant difference in secondary endpoints. CONCLUSION: Aprotinin therapy was not associated with a significant reduction in POAF in patients undergoing CTS with CPB. Perioperative transfusion use, LOS, stroke, myocardial infarction, renal failure, graft occlusion, and mortality also did not differ significantly between aprotinin and control groups.

Effect of prophylactic amiodarone on clinical and economic outcomes after cardiothoracic surgery: a meta-analysis.

BACKGROUND: Two previous meta-analyses of amiodarone for prevention of postoperative atrial fibrillation (POAF) after cardiothoracic surgery did not evaluate total hospital cost, concluded that data on stroke are incomplete, and did not evaluate the effect of clinical heterogeneity between trials. OBJECTIVE: To conduct a meta-analysis examining amiodarone's prophylactic impact on cardiothoracic surgery POAF, length of stay (LOS), stroke, and total costs. METHODS: Three reviewers conducted a systematic literature search of MEDLINE, EMBASE, CINAHL, and the Cochrane Library (1966-SEPTEMBER 2004). Studies were included if they met the following criteria: (1) randomized controlled trial versus placebo/routine treatment, (2) coronary artery bypass graft and/or valvular surgery, (3) Jadad score > or = 3, (4) reported data on incidence of POAF or stroke, LOS, or total costs, (5) used electrocardiographic/Holter monitoring, and (6) monitored subjects for > or = 2 days. A random-effects model was utilized. Subgroup and sensitivity analyses were conducted. RESULTS: Fifteen trials were identified, including 1512 and 1429 patients in the amiodarone and control groups, respectively. Amiodarone reduced POAF (OR 0.50; 95% CI 0.42 to 0.60) and decreased stroke (n = 8 studies), LOS (n = 10), and total costs (n = 6) (OR 0.47; 95% CI 0.23 to 0.96; -0.73 days, 95% CI -0.95 to -0.51; and -dollar 1619, 95% CI -3395 to 156, respectively). Surgery type, beta-blocker use, route of administration, use of a fixed-effects model, or exclusion of unblinded/unpublished studies did not affect the overall results. No statistical heterogeneity was observed for any endpoint evaluated (p > 0.22 for all comparisons). CONCLUSIONS: Prophylactic treatment with amiodarone decreases patients' risk of POAF and stroke while reducing LOS.

Impact of prophylactic amiodarone on length of hospital stay, stroke, and atrial fibrillation after cardiothoracic surgery.

STUDY OBJECTIVE: To evaluate the effect of prophylactic amiodarone on length of stay (LOS), postoperative stroke, and postoperative atrial fibrillation (POAF). DESIGN: Retrospective cohort study. SETTING: Hartford Hospital, Hartford, Connecticut. PATIENTS: Two thousand forty-six patients who underwent cardiothoracic surgery from February 1998-October 2003 (186 received amiodarone, 1860 were controls). MEASUREMENTS AND MAIN RESULTS: Patients receiving any of the prophylactic amiodarone regimens used in the Atrial Fibrillation Suppression Trials (AFIST) I and II were matched (1:10 matching) for age, valvular surgery, history of atrial fibrillation, sex, beta-blocker intolerance, and preoperative digoxin therapy with patients not receiving amiodarone prophylaxis. The AFIST regimens consisted of oral amiodarone 6 g over 6 days and 7 g over 10 days, beginning on preoperative days 1 and 5, respectively, or a hybrid intravenous and oral loading regimen delivering amiodarone 7 g over 5 days. Mean+/-SD age of the patients was 68.9+/-9.8 years, 75% were men, and 21% had undergone valvular surgery. Patients receiving prophylactic amiodarone had a shorter LOS (8.6+/-6.0 days) than controls (11.6+/-14.0 days, p=0.003) and a reduced frequency of POAF (23.1% vs 29.9%, p=0.05). Frequency of stroke was not significantly affected (2.2% vs 2.7% in the amiodarone vs control groups, p=0.61). CONCLUSION: Use of the prophylactic amiodarone regimens from the AFIST trials reduced LOS by 3.0 days and frequency of POAF by 22.7%.

Probable topical permethrin-induced neck dystonia.

A 28-year-old Caucasian man who applied topical 5% permethrin cream once for the treatment of scabies infestation experienced a severe dystonic reaction on the left side of his neck. Assessment of causality using the Naranjo algorithm revealed a probable relationship between this adverse drug event and application of topical permethrin. Dystonic or musculoskeletal adverse reactions, including muscle spasms, have been reported with pyrethroid insecticides only after inappropriate occupational dermal exposure. These reported reactions occurred 4-48 hours after exposure and lasted from a few days to a few weeks. The mechanism behind these adverse effects may be related to permethrin's ability to delay sodium channel closure within nerve cells. This may result in a lowered threshold of nerve fibers to activation of further action potentials, leading to repetitive firing and hyperexcitation of the nervous system. Clinicians should be aware of this rare but potential adverse effect of permethrin.

Pharmacodynamics of antimicrobials: treatment optimisation.

As bacterial resistance continues to increase, optimising the potential for successful clinical outcomes with antimicrobial therapy requires consideration of pharmacodynamic concepts in order to maximise bacterial eradication and minimise the potential for further resistance. Based on the pharmacodynamic characteristics of specific antibiotics, dosage modifications can be implemented to improve the likelihood of bactericidal exposure. Considering their concentration-dependent bactericidal activity, aminoglycosides benefit from increased dosages and infrequent administration, so as to achieve a maximum concentration/minimum inhibitory concentration (MIC) of 10-12. In contrast, beta-lactams are concentration-independent killers and benefit greatest by increasing the time above the MIC (T > MIC). This can be accomplished with the use of prolonged or continuous infusion. By optimising pharmacodynamic parameters with these methodologies, successful treatment of pathogens may be possible in patient populations for whom standard dosing regimens are not effective.

A hospital perspective on the cost-effectiveness of beta-blockade for prophylaxis of atrial fibrillation after cardiothoracic surgery.

BACKGROUND: Prophylactic beta-blockade is the recommended strategy for suppressing atrial fibrillation after cardiothoracic surgery (CTS). However, beta-blockade's impact on the hospital length of stay (LOS) and other economic end points has not been adequately assessed. OBJECTIVE: The present evaluation sought to determine whether beta-blocker use after CTS is a cost-effective strategy for the prevention of postoperative atrial fibrillation (POAF). METHODS: This was a piggyback cost-effectiveness analysis of a prospective cohort evaluation comprising 1660 patients undergoing CTS at an urban academic hospital from October 1999 to October 2003. Patients receiving beta-blocker prophylaxis were matched 1:1 with control patients not receiving prophylaxis based on age >70 years, valvular surgery, history of atrial fibrillation, male sex, and use of preoperative digoxin or beta-blockers. The incidence of POAF, total hospital costs, and LOS were compared in each group. Nonparametric bootstrapping analysis was performed to examine the study results as part of a quadrant analysis and to calculate CIs for the incremental cost-effectiveness ratio. LOS and total costs were also compared in patients with and without POAF, regardless of beta-blocker use. RESULTS: Use of prophylactic beta-blockade was associated with a 17.3 % reduction in the incidence of POAF (P = 0.02) and a 2.2-day reduction in LOS (P = 0.001) compared with nonuse. It also was associated with a 25.7% reduction in total hospital costs compared with nonuse (mean [SD], $30,978 [$33,108] vs $41,700 [$67,369], respectively; P < 0.001), possibly due to a 27.6% reduction in room and board costs ($11,144 [$15,398] vs $14,920 [$22,132]; P < 0.001). In the bootstrapping analysis, 99.0% of the time prophylactic beta-blockade fell into quadrant IV, which indicated superior effectiveness and lower total costs. Regardless of beta-blocker use, patients who developed POAF had a significantly longer LOS compared with those who did not develop POAF (14.7 [19.1] days vs 10.1 [11.1] days, respectively; P < 0.001) and higher total costs ($47,240 [$85,941] vs $32,516 [$34,644]; P < 0.001). CONCLUSIONS: At the institution studied, beta-blocker prophylaxis against POAF after CTS was associated with significantly reduced total costs compared with nonuse of beta-blocker prophylaxis. Patients who developed POAF had significantly increased LOS and total costs compared with those who did not develop POAE An adequately powered prospective, randomized, placebo-controlled trial is necessary to confirm the results of this evaluation.

Impact of prophylactic postoperative beta-blockade on post-cardiothoracic surgery length of stay and atrial fibrillation.

BACKGROUND: Previous studies have shown that post-cardiothoracic surgery atrial fibrillation (AF) increases the risk of hospital length of stay (LOS), overall mortality, pulmonary edema, and need for a balloon pump. A meta-analysis of 2 previous trials showed a nonsignificant reduction in LOS with postoperative beta-blockers but only encompassed 1200 patients, with few valve surgery patients, and neither study used a hospital within the US. OBJECTIVE: To evaluate the impact of postoperative beta-blockers on LOS and AF. Secondary endpoints of overall mortality, pulmonary edema, and need for an intra-aortic balloon pump (IABP) were also evaluated between groups. METHODS: This was a prospective cohort evaluation of all patients undergoing cardiothoracic surgery at our institution between October 1999 and October 2003. Patients receiving prophylactic postoperative beta-blockers were matched (1:1) with patients not receiving prophylaxis for age >70 years, valvular surgery, history of AF, gender, and use of preoperative digoxin and beta-blockers. RESULTS: Patients (n = 1660) receiving postoperative beta-blockade had a reduction in LOS (mean +/- SD 10.22 +/- 11.38 vs 12.40 +/- 15.67; p = 0.001) and AF (23.5% vs 28.4%; p = 0.02). Mortality, pulmonary edema, and need for IABP were reduced by >50% (p < 0.001; p = 0.001; p < 0.001, respectively), while myocardial infarction and stroke were not significantly impacted. CONCLUSIONS: In this observational cohort study, prophylactic postoperative beta-blocker use was associated with shorter hospital LOS by an average of 2.2 days and a 17.3% lower incidence of AF. It may also be associated with reductions in overall mortality, pulmonary edema, and need for an IABP.