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Background: Tranexamic acid (TXA) is a common antifibrinolytic agent used to minimize bleeding in cardiac surgery. Up to 50% cardiac surgical patients have chronic renal dysfunction (CRD). Optimal dosing of TXA in CRD remains poorly investigated. This is important as TXA is renally eliminated with accumulation in CRD. High TXA doses are associated with postoperative seizures. This study measures plasma TXA concentrations in CRD cardiac surgical patients for pharmacokinetic modeling and dose adjustment recommendations., Methods: This prospective cohort study enrolled 48 patients with stages 1-5 CRD, classified by Kidney Disease Outcome Quality Initiative. Patients were separated into 2 treatment groups. A "low-risk" group underwent simple aortocoronary bypass or single-valve repair/replacement and received a 50 mg/kg TXA bolus. A "high-risk" group underwent redo, aortic, multiple valve or combination surgery and received the Blood Conservation Using Anti-fibrinolytics Trial dosing regimen (loading dose 30 mg/kg, infusion 16 mg/kg/h with 2 mg/kg in pump prime). Primary outcome identified changes in TXA clearance and distribution volume, which provided the rationale for dose adjustment. Descriptive clinical outcomes assessed postoperative seizures, blood loss, ischemic-thrombotic complications, in-hospital mortality, and length of hospital stay., Results: TXA concentrations were elevated and sustained above the therapeutic threshold for approximately 12 hours in high-risk stages 3-5 groups, in accordance to CRD severity., Conclusions: Using a pharmacokinetic model, we propose a simple new TXA dosing regimen that optimizes maximal antifibrinolysis and avoids excessive drug dosing.

Background: Globally, >300 million patients have surgery annually, and ≤20% experience adverse postoperative events. We studied the impact of both cardiac and noncardiac adverse events on 1-year disability-free survival after noncardiac surgery., Methods: We used the study cohort from the Evaluation of Nitrous oxide in Gas Mixture of Anesthesia (ENIGMA-II) trial, an international randomized trial of 6992 noncardiac surgical patients. All were ≥45 years of age and had moderate to high cardiac risk. The primary outcome was mortality within 1 postoperative year. We defined 4 separate types of postoperative adverse events. Major adverse cardiac events (MACEs) included myocardial infarction (MI), cardiac arrest, and myocardial revascularization with or without troponin elevation. MI was defined using the third Universal Definition and was blindly adjudicated. A second cohort consisted of patients with isolated troponin increases who did not meet the definition for MI. We also considered a cohort of patients who experienced major adverse postoperative events (MAPEs), including unplanned admission to intensive care, prolonged mechanical ventilation, wound infection, pulmonary embolism, and stroke. From this cohort, we identified a group without troponin elevation and another with troponin elevation that was not judged to be an MI. Multivariable Cox proportional hazard models for death at 1 year and assessments of proportionality of hazard functions were performed and expressed as an adjusted hazard ratio (aHR) and 95% confidence intervals (CIs)., Results: MACEs were observed in 469 patients, and another 754 patients had isolated troponin increases. MAPEs were observed in 631 patients. Compared with control patients, patients with a MACE were at increased risk of mortality (aHR, 3.36 [95% CI, 2.55-4.46]), similar to patients who suffered a MAPE without troponin elevation (n = 501) (aHR, 2.98 [95% CI, 2.26-3.92]). Patients who suffered a MAPE with troponin elevation but without MI had the highest risk of death (n = 116) (aHR, 4.29 [95% CI, 2.89-6.36]). These 4 types of adverse events similarly affected 1-year disability-free survival., Conclusions: MACEs and MAPEs occur at similar frequencies and affect survival to a similar degree. All 3 types of postoperative troponin elevation in this analysis were associated, to varying degrees, with increased risk of death and disability.

Background: Inhalation agents are being used in place of intravenous agents to provide sedation in some intensive care units. We performed a systematic review and meta-analysis of prospective randomized controlled trials, which compared the use of volatile agents versus intravenous midazolam or propofol in critical care units., Methods: A search was conducted using MEDLINE (1946-2015), EMBASE (1947-2015), Web of Science index (1900-2015), and Cochrane Central Register of Controlled Trials. Eligible studies included randomized controlled trials comparing inhaled volatile (desflurane, sevoflurane, and isoflurane) sedation to intravenous midazolam or propofol. Primary outcome assessed the effect of volatile-based sedation on extubation times (time between discontinuing sedation and tracheal extubation). Secondary outcomes included time to obey verbal commands, proportion of time spent in target sedation, nausea and vomiting, mortality, length of intensive care unit, and length of hospital stay. Heterogeneity was assessed using the I statistic. Outcomes were assessed using a random or fixed-effects model depending on heterogeneity., Results: Eight trials with 523 patients comparing all volatile agents with intravenous midazolam or propofol showed a reduction in extubation times using volatile agents (difference in means, -52.7 minutes; 95% confidence interval [CI], -75.1 to -30.3; P < .00001). Reductions in extubation time were greater when comparing volatiles with midazolam (difference in means, -292.2 minutes; 95% CI, -384.4 to -200.1; P < .00001) than propofol (difference in means, -29.1 minutes; 95% CI, -46.7 to -11.4; P = .001). There was no significant difference in time to obey verbal commands, proportion of time spent in target sedation, adverse events, death, or length of hospital stay., Conclusions: Volatile-based sedation demonstrates a reduction in time to extubation, with no increase in short-term adverse outcomes. Marked study heterogeneity was present, and the results show marked positive publication bias. However, a reduction in extubation time was still evident after statistical correction of publication bias. Larger clinical trials are needed to further evaluate the role of these agents as sedatives for critically ill patients.

Background: The use of normal saline is associated with hyperchloremic metabolic acidosis. In this study, we sought to determine the incidence of acute postoperative hyperchloremia (serum chloride >110 mEq/L) and whether this electrolyte disturbance is associated with an increase in length of hospital stay, morbidity, or 30-day postoperative mortality., Methods: Data were retrospectively collected on consecutive adult patients (>18 years of age) who underwent inpatient, noncardiac, nontransplant surgery between January 1, 2003 and December 31, 2008. The impact of postoperative hyperchloremia on patient morbidity and length of hospital stay was examined using propensity-matched and logistic multivariable analysis., Results: The dataset consisted of 22,851 surgical patients with normal preoperative serum chloride concentration and renal function. Acute postoperative hyperchloremia (serum chloride >110 mmol/L) is quite common, with an incidence of 22%. Patients were propensity-matched based on their likelihood to develop acute postoperative hyperchloremia. Of the 4955 patients with hyperchloremia after surgery, 4266 (85%) patients were matched to patients who had normal serum chloride levels after surgery. These 2 groups were well balanced with respect to all variables collected. The hyperchloremic group was at increased risk of mortality at 30 days postoperatively (3.0% vs 1.9%; odds ratio = 1.58; 95% confidence interval, 1.25-1.98) (relative risk 1.6 or risk increase of 1.1%) and had a longer hospital stay (7.0 days [interquartile range 4.1-12.3] compared with 6.3 [interquartile range 4.0-11.3]) than patients with normal postoperative serum chloride levels. Patients with postoperative hyperchloremia were more likely to have postoperative renal dysfunction. Using all preoperative variables and measured outcome variables in a logistic regression analysis, hyperchloremia remained an independent predictor of 30-day mortality with an odds ratio of 2.05 (95% confidence interval, 1.62-2.59)., Conclusion: This retrospective cohort trial demonstrates an association between hyperchloremia and poor postoperative outcome. Additional studies are required to demonstrate a causal relationship between these variables.

Background: Coagulopathy leading to excessive blood loss and large volume red cell transfusion is a frequent complication of cardiac surgery with cardiopulmonary bypass (CPB) that may be caused by low perioperative fibrinogen levels. We explored the relationship between post-CPB fibrinogen levels and large volume red cell transfusion., Methods: Patients who underwent cardiac surgery with CPB from 2005 to 2011 at a single institution and had a fibrinogen level measured after CPB were included in this retrospective observational study. The relationship between post-CPB fibrinogen levels and large volume red cell transfusion (defined as ≥5 units transfused on the day of or the day after surgery) was assessed by cubic spline function and receiver operating characteristic analyses. The independent relationship between fibrinogen levels and large volume transfusion was assessed by multivariable logistic regression and propensity score analyses., Results: In the 4606 patients included, the probability of large volume transfusion increased when fibrinogen levels decreased below approximately 2.0 g/L. Using <2.0 g/L as the threshold for low fibrinogen, 1918 (42%) were categorized into the low fibrinogen group, of whom 363 (18.9%) had large volume transfusion compared with 164 (13.5%) of the 2688 patients whose fibrinogen level was ≥2.0 g/L (P < 0.0001). In the low fibrinogen group, the unadjusted odds ratio (95% confidence interval) for large volume transfusion was 1.5 (1.3-1.7). The risk-adjusted odds ratio obtained by logistic regression was 1.8 (1.4-2.2) and by propensity score methods was 1.5 (1.2-2.0)., Conclusions: While this study was not equipped to detect the critical fibrinogen level in bleeding patients, its results suggest that current recommendations that fibrinogen replacement not be initiated in bleeding patients unless fibrinogen levels decrease below 0.8 to 1.0 g/L may be too conservative. Randomized trials are needed to determine whether maintaining higher fibrinogen levels in bleeding patients can reduce blood loss and transfusions and by that means improve clinical outcomes in cardiac surgery.

Background: Acute β-blockade has been associated with a dose-dependent increase in adverse outcomes, including stroke and mortality. Acute blood loss contributes to the incidence of these adverse events. In an attempt to link the risks of acute blood loss and β-blockade, animal studies have demonstrated that acute β-blockade impairs cerebral perfusion after hemodilution. We expanded on these findings by testing the hypothesis that acute β-blockade with a highly β(1)-specific antagonist (nebivolol) causes dose-dependent cerebral hypoxia during hemodilution., Methods: Anesthetized rats and mice were randomized to receive vehicle or nebivolol (1.25 or 2.5 mg/kg) IV before hemodilution to a hemoglobin concentration near 60 g/L. Drug levels, heart rate (HR), cardiac output (CO), regional cerebral blood flow (rCBF, laser Doppler), and microvascular brain Po(2) (P(Br)O(2), G2 Oxyphor) were measured before and after hemodilution. Endothelial nitric oxide synthase (NOS), neuronal NOS (nNOS), inducible NOS, and hypoxia inducible factor (HIF)-1α were assessed by Western blot. HIF-α expression was also assessed using an HIF-(ODD)-luciferase mouse model. Data were analyzed using analysis of variance with significance assigned at P < 0.05, and corrected P values are reported for all post hoc analyses., Results: Nebivolol treatment resulted in dose-specific plasma drug levels. In vehicle-treated rats, hemodilution increased CO and rCBF (P < 0.010) whereas P(Br)O(2) decreased to 45.8 ± 18.7 mm Hg (corrected P < 0.001; 95% CI 29.4-69.7). Both nebivolol doses comparably reduced HR and attenuated the CO response to hemodilution (P < 0.012). Low-dose nebivolol did not impair rCBF or further reduce P(Br)O(2) after hemodilution. High-dose nebivolol attenuated the rCBF response to hemodilution and caused a further reduction in P(Br)O(2) to 28.4 ± 9.6 mm Hg (corrected P = 0.019; 95% CI 17.4-42.7). Both nebivolol doses increased brain endothelial NOS protein levels. Brain HIF-1α, inducible NOS, and nNOS protein levels and brain HIF-luciferase activity were increased in the high-dose nebivolol group after hemodilution (P < 0.032)., Conclusions: Our data demonstrate that nebivolol resulted in a dose-dependent decrease in cerebral oxygen delivery after hemodilution as reflected by a decrease in brain tissue Po(2) and an increase in hypoxic protein responses (HIF-1α and nNOS). Low-dose nebivolol treatment did not result in worsened tissue hypoxia after hemodilution, despite comparable effects on HR and CO. These data support the hypothesis that acute β-blockade with a highly β(1)-specific antagonist causes a dose-dependent impairment in cerebral perfusion during hemodilution.

Background: Although β blockers have been found to decrease perioperative myocardial infarction (MI), β-blocker-mediated hypotension is associated with postoperative stroke and mortality. In this systematic review we assessed the safety and efficacy of the β1-specific, adrenergic receptor antagonist esmolol in noncardiac surgery. Safety was assessed by analyzing the incidence of postoperative hypotension and bradycardia, and efficacy was assessed by analyzing the incidence of myocardial ischemia., Methods: We searched electronic databases for randomized placebo-controlled trials of the perioperative use of esmolol in noncardiac surgery. We abstracted data on design, demographics, hemodynamic changes (planned or unplanned), myocardial ischemia, and MI. Heterogeneity was assessed via meta-regression., Results: Our search identified 67 trials, which were well matched for study characteristics. The quality of the studies was limited by small sample size and poorly defined allocation concealment. Overall, the analysis demonstrates an increased incidence of unplanned hypotension (OR 2.13; 95% confidence interval [CI], 1.48 to 3.04), which was found to be dose related (R(2) = 0.408). An increased incidence of significant bradycardia was not demonstrated (OR 1.18; 95% CI, 0.69 to 2.02). Dose titration was shown to influence both the change in arterial blood pressure and heart rate. In comparison with placebo, esmolol decreased the frequency of myocardial ischemia in the 7 evaluating studies (OR 0.17; 95% CI, 0.02 to 0.45). We did not assess the effects of esmolol on the incidence of MI or stroke because the incidence of these events was too infrequent in the retrieved studies., Conclusion: This review suggests that titration of esmolol to a hemodynamic end point can be safe and effective. Safety data from studies in higher-risk patients are needed to establish a perioperative safety and efficacy profile of esmolol.

Background: Accurate risk stratification may help reduce the burden of excessive blood loss after cardiac surgery. We measured the incremental value of thrombelastography to an existing risk prediction model for excessive blood loss in cardiac surgery., Methods: This observational study included 434 patients who underwent cardiac surgery with cardiopulmonary bypass (CPB) and had thrombelastographic measures before and during CPB, their risk of excessive blood loss could be calculated with an existing risk prediction model and they had not received clopidogrel or warfarin within 5 days of surgery. Excessive blood loss was defined as transfusion of > or = 5 U of red blood cells from termination of CPB to 1 day after surgery. Logistic regression models including an existing risk prediction model without and with thrombelastographic measures were constructed. Improvement in risk prediction was measured by the area under the curve and net reclassification improvement., Results: Excessive blood loss occurred in 59 of 434 patients (13.6%). The only thrombelastographic measure that improved risk stratification was maximum amplitude during CPB, which reflects maximum clot strength. Although the addition of this variable to the existing prediction model did not have a material effect on the area under the curve (increased from 0.780 to 0.784; P = 0.8), it did improve the net reclassification improvement by 12% (P = 0.05), primarily by improving the detection of high-risk cases., Conclusions: Risk stratification for excessive blood loss after cardiac surgery is improved when on-CPB thrombelastography is added to an existing risk prediction model that incorporates readily available patient- and surgery-related variables, but large, multicenter trials are needed to verify this finding and create a new risk prediction model.

Background: Aprotinin is superior to other antifibrinolytic drugs for preventing major blood loss after cardiac surgery but may also increase perioperative mortality. It remains unclear whether its risk-benefit profile differs among low-, moderate-, and high-risk cardiac surgical patients., Methods: In this retrospective single-center cohort study, we included 15,365 patients who underwent cardiac surgery with cardiopulmonary bypass from 2000 to 2008. Of these, 1017 received aprotinin (6 x 10(6) U) and 14,358 received tranexamic acid (50-100 mg/kg). Propensity score methods were used to create a matched-pairs cohort (n = 1544) that adjusted for important between-group differences. The influence of patients' risk status on aprotinin's association with in-hospital mortality, morbidity, and blood loss was measured., Results: In the matched set, aprotinin was only associated with increased acute kidney injury (> 50% decrease in estimated glomerular filtration or dialysis; odds ratio 1.5; 95% confidence interval [CI] 1.1-2.1). Patients' risk status significantly influenced the associations of aprotinin with mortality, acute kidney injury, and massive blood loss (transfusion of > or = 10 U of red blood cells or need for surgical reexploration). Among high-risk patients, the respective odds ratios were 0.6 (CI 0.3-1.0), 1.1 (CI 0.7-1.7), and 0.7 (CI 0.4-1.04), and among low- to moderate-risk patients, they were 1.5 (CI 0.9-2.7), 2.2 (CI 1.4-3.5), and 1.2 (CI 0.9-1.07) (Breslow-Day test for homogeneity of odds ratios between high-risk versus low- to moderate-risk patients: P < 0.05 for all 3 outcomes)., Conclusions: Aprotinin tends to have a better risk-benefit profile than tranexamic acid in high-risk, but not low- to moderate-risk, patients. Its use in high-risk cases may therefore be warranted.

Background: Recent meta-analyses assessing the efficacy of perioperative beta-blockade trials have failed to show a reduction in postoperative morbidity and mortality. Tight control of heart rate (HR) has been suggested to improve these outcomes. Meta-analyses have not considered the influence of tight HR control on the efficacy of perioperative beta-blockade., Methods: Using previously published search strategies, we identified all randomized trials evaluating perioperative beta-blockers after noncardiac surgery. This search yielded 10 trials with 2176 patients. We used the data from these studies to correlate measures of HR control with major postoperative outcomes, primarily in-hospital myocardial infarction (MI). Odds ratio (OR) and 95% confidence intervals (CI) were calculated, and metaregression was performed correlating measures of HR control with MI., Results: The combined results of all studies did not show a significant cardioprotective effect of beta-blockers, with considerable heterogeneity among the studies (OR = 0.76; 95% CI = 0.4-1.4; P = 0.38 heterogeneity: I(2) = 34%). However, grouping the trials on the basis of maximal HR showed that trials where the estimated maximal HR was <100 bpm were associated with cardioprotection (OR = 0.23; 95% CI = 0.08-0.65; P = 0.005) whereas trials where the estimated maximal HR was >100 bpm did not demonstrate cardioprotection (OR = 1.17; 95% CI = 0.79-1.80; P = 0.43) with no heterogeneity. Moreover, metaregression of the HR response to beta-blockade against the log OR of postoperative MI demonstrated a linear association between the effect of beta-blockade on the mean, maximal, and variation in HR and the OR of an MI (r(2) = 0.63; P < 0.001) where a larger effect of beta-blockers on HR was associated with a decreased incidence of postoperative MI. Across all studies, beta-blockade resulted in a reduction in postoperative HR (weighted mean difference: 8.6 bpm; 95% CI = -9.6 to -7.6; I(2) = 85.3%) with considerable heterogeneity. This large heterogeneity in HR response to beta-blockade was found to be related, in part, to the type of beta-blocker, specifically, metoprolol, and the concomitant use of calcium channel blockers. Calcium channel blocker use and beta-blockers other than metoprolol resulted in more effective control of HR. There was wide variability in the HR response to beta-blockade. Twenty-five percent of patients receiving beta-blockers had episodes when the HRs were more than 100 bpm, although 15% of placebo patients also had bradycardia, which would have required a dose reduction had they been administered beta-blockers. Finally, this analysis found that perioperative beta-blockade was associated with an increased incidence of bradycardia (OR = 3.49; 95% CI = 2.4-5.9) and congestive heart failure (OR = 1.68; 95% CI = 1.00-2.8)., Conclusions: The trials that achieve the most effective control of HR are associated with a reduced incidence of postoperative MI, suggesting that effective control of HR is important for achieving cardioprotection. Second, this analysis demonstrates that administration of beta-blockers does not reliably decrease HRs in all patients, and may be associated with increased side effects. Judicious use of combination therapy with other drugs may be necessary to achieve effective postoperative control of HR.

Background: Isocapnic hyperpnoea (IH) reduces recovery time from isoflurane anesthesia in animals and humans. We studied the effect of IH on the emergence profile of sevoflurane-anesthetized patients by comparing postoperative recovery variables in patients administered IH (IH group) to those recovered in the customary fashion (control group)., Methods: We enrolled 30 ASA I-III patients undergoing elective gynecological surgery. Induction and maintenance of anesthesia were standardized with a protocol consisting of fentanyl, propofol, rocuronium, and sevoflurane in air/O2. Patients were randomly assigned to control (C) or IH groups at the end of the surgery. We recorded time intervals from discontinuing sevoflurane to recovery milestones., Results: Time to tracheal extubation was much shorter in the IH group compared with group C (6.2 +/- 2.1 vs 12.3 +/- 3.8 min, respectively, P < 0.01). The IH group also had shorter times to initiation of spontaneous ventilation (4.2 +/- 1.7 vs 6.5 +/- 3.8 min, P = 0.047), eye opening (5.5 +/- 1.4 vs 13.3 +/- 4.4 min, P < 0.01), bispectral index value >75 (3.9 +/- 1.1 vs 8.8 +/- 3.7 min, P < 0.01), leaving operating room (7.7 +/- 2.0 vs 15.3 +/- 3.4 min, P < 0.01), and eligibility for postanesthetic care unit discharge (67.2 +/- 19.3 vs 90.6 +/- 20.0 min, P < 0.01)., Conclusion: IH accelerates recovery from sevoflurane anesthesia and shortens operating room and postanesthetic care unit stay.

In this meta-analysis we compared thallium imaging (TI) and stress echocardiography (SE) in patients at risk for myocardial infarction (MI) scheduled for elective noncardiac surgery. Two searches of published articles were used to identify relevant articles. We included all studies that stated the criteria for a positive test and detailed the frequency of postoperative MI and in-hospital death. Data were abstracted by two authors and captured preoperative patient characteristics, study design, blinding, and outcome adjudication. We defined a positive test as a test with a reversible defect and, where possible, quantified the size of the defects in each study. MI and/or death were the only postoperative outcomes of interest. We calculated the sensitivity, specificity, and likelihood ratio (LR) and, where possible, the Receiver Operating Characteristic (ROC) curve of a cardiac event in each study. The LR and ROC were combined by meta-analyses using the random effects model. Heterogeneity was assessed using the I2 test. The search revealed 68 studies of 10,049 patients. There were 25 SE studies and 50 TI studies. There were 7 studies with a direct comparison of the two methodologies. The quality of studies differed; routine screening for MI was used more frequently in SE studies (47.8% versus 21.2%; P = 0.008) and screening dictated treatment more often after TI (72.1%) than after SE (46.3%) (P = 0.027). The LR for SE was more indicative of a postoperative cardiac event than TI (LR, 4.09; 95% CI, 3.21-6.56 versus 1.83; 1.59-2.10; P = 0.001). This difference was attributable to fewer false-negative SEs. There was no difference in the cumulative ROC curves from qualitative studies (SE, 0.80; 95% CI, 0.76-.84 versus TI, 0.75; 95% CI, 0.70-081). Again, the LR for a negative SE was less (0.23; 95% CI, 0.17-0.32 versus 0.44; 95% CI, 0.36-0.54). A moderate-to-large defect, seen in 14% of patients, by either method predicts a postoperative cardiac event (LR, 8.35; 95% CI, 5.6-12.45). This meta-analysis possesses the statistical power to demonstrate that SE has better negative predicative characteristics than TI. A moderate-to-large perfusion defect by either SE or TI predicts postoperative MI and death. We conclude the SE is superior to TI in predicting postoperative cardiac events.

Cardiac complications are the leading cause of death after noncardiac surgery. Despite theoretical benefits, calcium channel blockers (CCB) are not widely used in the perioperative setting. This systematic review assessed the efficacy of CCBs during noncardiac surgery. MEDLINE, EMBASE, Science Citation Index, PubMed, and reference lists were searched without language restriction for randomized controlled trials (RCT) evaluating CCBs during noncardiac surgery. Two reviewers independently abstracted data on death, myocardial infarction (MI), ischemia, supraventricular tachyarrhythmia (SVT), and congestive heart failure (CHF). Treatment effects were calculated as relative risks (RR) with 95% confidence intervals (CI). Eleven studies (1007 patients) were included. CCBs significantly reduced ischemia (RR, 0.49; 95% CI, 0.30-0.80; P = 0.004) and SVT (RR, 0.52; 95% CI, 0.37-0.72; P < 0.0001). CCBs were associated with trends towards reduced death and MI. In post hoc analyses, CCBs significantly reduced death/MI (RR, 0.35; 95% CI, 0.15-0.86; P = 0.02) and major morbid events (MME), defined as death, MI, or CHF (RR, 0.39; 95% CI, 0.17-0.89; P = 0.02). In subgroup analyses, diltiazem significantly reduced ischemia, SVT, death/MI, and MMEs. This meta-analysis shows CCBs significantly reduced ischemia, SVT, and combined end-points in the setting of noncardiac surgery. The majority of these benefits are attributable to diltiazem, suggesting the need for further evaluation of this drug in a large RCT.

Unlabelled: Renal insufficiency after cardiac surgery is associated with increased mortality, morbidity, and length of intensive care unit stay. A convenient surrogate measure would facilitate the evaluation of renal-protective therapies. We evaluated two measures: the 72-h change in serum creatinine (Cr) (DeltaCr(72h)) and the percentage 72-h change in calculated (Cockcroft-Gault equation) Cr clearance (%DeltaCrCl(72h)). We randomly selected 2000 individuals who underwent aortocoronary bypass, valve surgery, or both at the Toronto General Hospital between May 1999 and August 2000. The variables were analyzed with frequency histograms and normal probability plots. Their association with dialysis, mortality, and prolonged intensive care unit stay was determined by using receiver operating characteristic (ROC) curves. DeltaCr(72h) was skewed to the right, whereas %DeltaCrCl(72h) was normally distributed. ROC curve areas showed DeltaCr(72h) to be a good predictor of dialysis (0.98), death (0.83), and prolonged hospitalization (0.74). %DeltaCrCl(72h) had similar ROC curve areas for predicting dialysis (0.97), death (0.82), and prolonged hospitalization (0.74). ROC curve areas did not differ significantly with respect to mortality (P = 0.89), dialysis (P = 0.49), or prolonged hospitalization (P = 0.85). Both variables were correlated with patient-relevant outcomes. Mathematical transformation of DeltaCr(72h) to %DeltaCrCl(72h) results in a normal distribution that is amenable to parametric statistical tests. DeltaCr(72h) and %DeltaCrCl(72h) may be used as surrogate outcomes in future trials., Implications: A convenient surrogate measure of renal function is needed for evaluating renal-protective therapies in cardiac surgery. We evaluated the performance of serum creatinine concentration and calculated creatinine clearance for predicting dialysis, mortality, and prolonged hospitalization. Both measures were correlated with clinical outcomes. Creatinine clearance had the advantage of a distribution suitable for parametric statistical tests.

Unlabelled: Postoperative cardiac morbidity and mortality continue to pose considerable risks to surgical patients. Postoperative epidural analgesia is considered to have beneficial effects on cardiac outcomes. The use in high-risk cardiac patients remains controversial. No study has shown that postoperative epidural analgesia decreases postoperative myocardial infarction (PMI) or death. All studies are underpowered to show such a result, and the cost of conducting a large trial is prohibitive. We performed a metaanalysis to determine whether postoperative epidural analgesia continued for more than 24 h after surgery reduces PMI or in-hospital death. The available databases were searched for randomized controlled trials of epidural analgesia that was extended at least 24 h into the postoperative period. The search yielded 17 studies, of which 11 were randomized controlled trials comprising 1173 patients. Metaanalysis was conducted by using the fixed-effects model, calculating both an odds ratio and a rate difference. Postoperative epidural analgesia resulted in better analgesia for the first 24 h after surgery. The rate of PMI was 6.3%, with lower rates in the Epidural group (rate difference, -3.8%; 95% confidence interval [CI] -7.4%, -0.2%; P = 0.049). The frequency of in-hospital death was 3.3%, with no significant difference between Epidural and Nonepidural groups (rate difference, -1.3%; 95% CI, -3.8%, 1.2%, P = 0.091). Subgroup analysis of postoperative thoracic epidural analgesia showed a significant reduction in PMI in the Epidural group (rate difference, -5.3%; 95% CI, -9.9%, -0.7%; P = 0.04)., Implications: Postoperative epidural analgesia, especially thoracic epidural analgesia, continued for more than 24 h reduces postoperative myocardial infarctions.

Unlabelled: Nitrous oxide anesthesia causes increased postoperative plasma homocysteine levels. Acute increases in plasma homocysteine are associated with impaired endothelial function and procoagulant effects. This nitrous oxide-induced plasma homocysteine increase may therefore affect the risk of perioperative cardiovascular events. This prospective, randomized study was therefore designed to evaluate the effect of nitrous oxide anesthesia and postoperative plasma homocysteine levels on myocardial ischemia in patients undergoing carotid endarterectomy. After institutional review board approval and written informed consent, 90 ASA Class I-III patients presenting for elective carotid endarterectomy were randomized to receive general anesthesia with or without nitrous oxide. Prior to induction, on arrival in the postanesthesia care unit, and after 48 h, blood samples were obtained for homocysteine analysis. Three hours prior to induction and for 48 h postoperatively patients were monitored by a three-channel, seven-lead Holter monitor. Postoperatively in the postanesthesia care unit and at 48 h the nitrous oxide group had increased mean plasma homocysteine concentrations of 15.5 +/- 5.9 and 18.8 +/- 14.7 when compared with the nonnitrous group of 11.4 +/- 5.2 and 11.3 +/- 4.0 micromol/L, P: < 0.001. The nitrous oxide group had an increased incidence of ischemia (46% vs. 25%, P: < 0.05), significantly more ischemia (63 +/- 71 vs. 40 +/- 68 min, P: < 0.05), had more ischemic events (82 vs. 53, P: < 0.02), and had more ischemic events lasting 30 min (23 vs. 14, P: < 0.05) than the nonnitrous group. This study reconfirmed that intraoperative nitrous oxide is associated with postoperative increases in plasma homocysteine concentration. This was associated with an increase in postoperative myocardial ischemia., Implications: Use of nitrous oxide during carotid artery surgery induces increases in postoperative plasma homocysteine concentration and is associated with increases in postoperative myocardial ischemia.

The purpose of this study was to determine whether a lumbar epidural infusion of ropivacaine 0.2% would provide effective analgesia with an acceptably low incidence of motor blockade and side effects after lower abdominal surgery. After combined general and epidural anesthesia and surgery, 125 patients were randomly assigned to receive either saline or ropivacaine 0.2% at a rate of 6, 8, 10, 12, or 14 mL/h (Groups R6, R8, R10, R12, and R14, respectively) for 21 h. Supplemental analgesia, if required, was provided with intravenous patient-controlled analgesia with morphine. Data were collected at 4, 8, and 21 h, and included morphine consumption, pain scores at rest and with coughing, motor and sensory block, and adverse events. Cumulative morphine consumption was less in Groups R10, R12, and R14 compared with the saline group. At 4 h analgesia was better among patients receiving ropivacaine, but at 21 h pain scores were identical. Sensory blockade at 8 and 21 h was greater in the ropivacaine groups compared with the saline group. Approximately 30% of R8, R10, and R12 patients, and 63% of R14 patients had demonstrable motor block of the lower limbs at 21 hours. We conclude that lumbar epidural ropivacaine 0.2% reduces parenteral morphine requirements but has little effect on pain scores and may be associated with motor blockade.

This double-blind randomized trial assessed the effect of adding an intravenous continuous infusion of ketorolac to a patient-controlled analgesia (PCA) morphine regimen on analgesia, heart rate, arterial blood pressure, and postoperative myocardial ischemia. Patients having elective total hip or knee replacement were randomized to receive ketorolac 30 mg bolus, followed by an infusion of 5 mg/h for 24 h or placebo. All patients had access to PCA morphine (20 microg/kg bolus, with a lockout of 6 min). Patients were monitored for pain visual analog scale, blood pressure, heart rate, and ST segment depression via a continuous Holter monitor. ST depression of 1 mm 60 ms after the J point was considered significant if it lasted more than 1 min. There was no difference in demographics, risk factors, or cardiac medications between the groups. Ketorolac-treated patients had significantly better pain control at 2, 6, and 24 h. There was significant morphine sparing at all times after 3 h. There was no difference in the number of ischemic events between the groups. The ischemic episodes of the patients who received ketorolac occurred at slower heart rates (97 +/- 15 vs 114 +/- 16 bpm, P = 0.001) than those of patients in the placebo group. The duration of ST depression was shorter in ketorolac-treated patients (24 +/- 35 vs 76 +/- 95 min, P < 0.05). All ST depressions were clinically silent. Logistic regression of factors predicting ischemia included the use of calcium channel blockers and low pain score. These results suggest that analgesia with ketorolac reduces the duration of ischemic episodes in the first 24 h postoperatively.

The purpose of this study was to determine the analgesic efficacy, opioid-sparing effect, and tolerability of ketorolac administered as an intravenous (i.v.) bolus followed by a continuous infusion after total hip or knee arthroplasty. After general anesthesia, patients received either placebo or ketorolac 30 mg i.v. as a bolus over 15-30 s followed by a continuous i.v. infusion of ketorolac 5 mg/h for 24 h. All patients received patient-controlled i.v. morphine with no background infusion. Patients were assessed at 2, 4, 6, and 24 postoperatively with respect to analgesia, morphine consumption, side effects, and blood loss. Patients receiving ketorolac reported were less sedated and required fewer antiemetics. There was no difference in blood loss. Patients receiving ketorolac reported better analgesia and used less morphine (35% for hips and 44% for knees) than those receiving placebo.