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Background: Perioperative metoprolol increases postoperative stroke. Animal studies indicate that the mechanism may be related to attenuated β(2)-adrenoreceptor-mediated cerebral vasodilatation. The authors therefore conducted a cohort to study whether the highly β(1)-specific β-blocker (bisoprolol) was associated with a reduced risk of postoperative stroke compared with less selective β-blockers (metoprolol or atenolol)., Methods: The authors conducted a single-center study on 44,092 consecutive patients with age 50 yr or more having noncardiac, nonneurologic surgery. The primary outcome was stroke within 7 days of surgery. The secondary outcome was a composite of all-cause mortality, postoperative myocardial injury, and stroke. A propensity score-matched cohort was created to assess the independent association between bisoprolol and less β(1)-selective agents metoprolol or atenolol. A secondary analysis using logistic regression, based on previously identified confounders, also compared selective β(1)-antagonism., Results: Twenty-four percent (10,756) of patients were exposed to in-hospital β-blockers. A total of 88 patients (0.2%) suffered a stroke within 7 days of surgery. The matched cohort consisted of 2,462 patients, and the pairs were well matched for all variables. Bisoprolol was associated with fewer postoperative strokes than the less selective agents (odds ratio = 0.20; 95% CI, 0.04-0.91). Multivariable risk-adjustment in the β-blockers-exposed patients comparing bisoprolol with the less selective agents was associated with a similarly reduced stroke rate., Conclusions: The use of metoprolol and atenolol is associated with increased risks of postoperative stroke, compared with bisoprolol. These findings warrant confirmation in a pragmatic randomized trial.

Purpose: Cardiac complications following non-cardiac surgery are major causes of morbidity and mortality. The Revised Cardiac Risk Index (RCRI) has become a standard for predicting post-surgical cardiac complications. This study re-examined the original six risk factors to confirm their validity in a large modern prospective database., Methods: Using the definitions in the original risk index, this study included 9,519 patients aged ≥ 50 undergoing elective non-cardiac surgery with an expected length of stay ≥ two days at two major tertiary-care teaching hospitals. The validity of the original predictors was tested in this population using binomial logistic regression modelling, area under the receiver operator curve (ROC) analysis, and the net reclassification index., Results: Rates of major cardiac complications with 0, 1, 2, ≥ 3 of the predictors were 0.5%, 2.6%, 7.2%, and 14.4%, respectively, in our patient cohort compared with 0.4%, 1.1%, 4.6%, and 9.7%, respectively, in the original cohort. Similar to the original report, binary logistic regression analysis showed that both preoperative treatment with insulin (odds ratio [OR] 1.4; 95% confidence interval [CI] 0.7 to 2.6) and preoperative creatinine > 176.8 mmol·L(-1) (OR 1.7; 95% CI 0.8 to 3.6) did not improve the predictive ability of the index. Analysis of the remaining four factors resulted in an area under the curve (AUC) identical to that seen for the reconstructed six-factor RCRI (AUC = 0.79). We found that a glomerular filtration rate (GFR) < 30 mL·min(-1) was a better predictor of major cardiac complications (OR 2.2; 95% CI 1.2 to 4.3) than creatinine > 176.8 mmol·L(-1). The receiver operating characteristic analysis of this resultant 5-Factor model resulted in an AUC of 0.79, with 0, 1, 2, ≥ 3 of the predictors representing 0.5%, 2.9%, 7.4%, and 17.0% risk, respectively, among our patient cohort., Conclusion: Compared with the RCRI, a simplified 5-Factor model using a high-risk type of surgery, a history of ischemic heart disease, congestive heart failure, cerebrovascular disease, and a preoperative GFR < 30 mL·min(-1) results in superior prediction of major cardiac complications following elective non-cardiac surgery.

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.

Purpose of Review: We presume that biomarkers will improve identification of patients at risk, leading to interventions and treatments that reduce perioperative adverse events. Risk stratification is multifactorial, and a biomarker must add information to this process, thereby redistributing patients to either higher or lower risk categories, to improve the allocation of expensive and risky interventions. This review focuses on the utility of three cardiac biomarkers in perioperative management., Recent Findings: Using newly defined epidemiologic criteria, three distinct molecules, brain natriuretic peptide (BNP), troponin (cTn), and glycosylated hemoglobin (HbA1c) emerge as potentially useful in perioperative medicine. A meta-analysis shows, in vascular surgery, BNP improves risk stratification. Four articles highlight the utility of postoperative cTn measurements in cases of myocardial injury. These articles show that most injury is not infarction, and they present preliminary evidence of the populations that will benefit from structured surveillance protocols. HbA1c is shown to improve the prediction of mortality, but there are questions whether this risk is modifiable., Summary: The findings here suggest an expanded role for postoperative cTn surveillance; however, the precise populations that benefit, or the interventions required, are not yet defined. The encouraging data for the other two biomarkers need more investigations before adopting them into routine clinical use.

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.

Purpose: Postoperative myocardial infarction causes hundreds of thousands of deaths annually, and "failure to rescue" is a leading cause of hospital mortality. Strategies to recognize cardiac injury are important to reduce the burden of cardiac-related morbidity. For these reasons, we chose to assess the association between postoperative troponin I elevations and 30-day in-hospital mortality and, secondarily, to compare the predictive value of regularly scheduled troponin estimates with troponin ordered in response to clinical indications., Methods: We carried out a retrospective cohort analysis of 51,701 consecutive patients throughout 2003 to 2009. All patients were from a single university referral hospital and included all non-cardiac non-transplant surgery patients requiring overnight admission. Logistic regression was used to assess the risk-adjusted associations between troponin I and 30-day in-hospital mortality., Results: The multivariable predictive model for death improved after troponin I was included. The receiver operating characteristic was 0.902 before troponin I vs 0.934 after troponin I (P<0.0001). The likelihood ratio for troponin was 3.0 (95% confidence interval 2.8 to 3.2) and evident in each surgical service. Increasing troponin I showed a dose-response associated with increased mortality, and compared with clinically based measurements, a regularly scheduled postoperative troponin protocol showed a threefold increase in the probability of detecting myocardial injury. However, troponin I was not found to improve the risk prediction model in the lowest risk patients (n=18,953; probability of death<0.02%) with one cardiac death., Conclusions: Postoperatively elevated troponin I is associated with 30-day in-hospital mortality in a dose-dependent manner. A postoperative measurement protocol provides a threefold increase in the ability to detect myocardial injury. Conversely, in patients with a low mortality risk, cardiac injury is low; there is minimal improvement in the ability to detect cardiac injury, and the rescue rates from cardiac injury are excellent. These findings suggest that a surveillance protocol of troponin I would be optimal when limited to moderate to high-risk patients.

Background: Guidelines recommend that noncardiac surgery be delayed until 30 to 45 days after bare-metal stent implantation and 1 year after drug-eluting stent implantation., Methods and Results: We used linked registry data and population-based administrative health care databases to conduct a cohort study of 8116 patients (≥40 years of age) who underwent major elective noncardiac surgery in Ontario, Canada between 2003 and 2009, and received coronary stents within 10 years before surgery. Approximately 34% (n=2725) underwent stent insertion within 2 years before surgery, of whom 905 (33%) received drug-eluting stents. For comparison, we assembled a separate cohort of 341 350 surgical patients who had not undergone coronary revascularization. The primary outcome was 30-day major adverse cardiac events (mortality, readmission for acute coronary syndrome, or repeat coronary revascularization). The overall rate of 30-day events in patients with coronary stents was 2.1% (n=170). When the interval between stent insertion and surgery was <45 days, event rates were high for bare-metal (6.7%) and drug-eluting (20.0%) stents. When the interval was 45 to 180 days, the event rate for bare-metal stents was 2.6%, approaching that of intermediate-risk nonrevascularized individuals. Adjusted analyses suggested that event rates were increased if this interval exceeded 180 days. For drug-eluting stents, the event rate was 1.2% once the interval exceeded 180 days, approaching that of intermediate-risk nonrevascularized individuals., Conclusions: The earliest optimal time for elective surgery is 46 to 180 days after bare-metal stent implantation or >180 days after drug-eluting stent implantation.

Background: Largely on the basis of 2 randomized trials published in the 1990s, β-blockers were initially promoted as an evidence-based intervention for preventing cardiac complications of noncardiac surgery. However, subsequent studies raised concerns about a widespread use of perioperative β-blockade. Little is known regarding how this changing evidence influenced the use of perioperative β-blockers in clinical practice., Methods and Results: We conducted a population-based, time-series analysis (April 1999 to March 2010) among residents of Ontario, Canada (age 66 years and older), to evaluate the influence of research publications and practice guidelines on rates of new β-blocker prescriptions before major elective noncardiac surgery. In an analysis of 249 828 procedures, the rate of new β-blocker prescriptions increased from 26.3 per 1000 procedures in April 1999 to 62.7 per 1000 procedures in the first quarter of 2005, after which it decreased to 19.7 per 1000 procedures by March 2010. We observed a marked decrease in prescriptions (P=0.004) during early 2005, without any preceding publications that raised concerns about perioperative β-blockade. There was no change (P=0.98) in prescription rates after the May 2008 publication of a multicenter, randomized trial that showed increased mortality from perioperative β-blockade. Prescribing trends remain unchanged after revisions of related practice guidelines in 2002 (P=0.28) and 2006 (P=0.53)., Conclusions: After a period characterized by increasing adoption of preoperative β-blockade between 1999 and 2005, prescriptions rates subsequently fell from 2005 to 2010. Further research is needed to understand the basis for these changes, which are only partially explained by evidence of potential harm.

Unlabelled: BACKGROUND⁄, Objectives: Pain-related misbeliefs among health care professionals (HCPs) are common and contribute to ineffective postoperative pain assessment. While standardized patients (SPs) have been effectively used to improve HCPs' assessment skills, not all centres have SP programs. The present equivalence randomized controlled pilot trial examined the efficacy of an alternative simulation method - deteriorating patient-based simulation (DPS) - versus SPs for improving HCPs' pain knowledge and assessment skills., Methods: Seventy-two HCPs were randomly assigned to a 3 h SP or DPS simulation intervention. Measures were recorded at baseline, immediate postintervention and two months postintervention. The primary outcome was HCPs' pain assessment performance as measured by the postoperative Pain Assessment Skills Tool (PAST). Secondary outcomes included HCPs knowledge of pain-related misbeliefs, and perceived satisfaction and quality of the simulation. These outcomes were measured by the Pain Beliefs Scale (PBS), the Satisfaction with Simulated Learning Scale (SSLS) and the Simulation Design Scale (SDS), respectively. Student's t tests were used to test for overall group differences in postintervention PAST, SSLS and SDS scores. One-way analysis of covariance tested for overall group differences in PBS scores., Results: DPS and SP groups did not differ on post-test PAST, SSLS or SDS scores. Knowledge of pain-related misbeliefs was also similar between groups., Conclusions: These pilot data suggest that DPS is an effective simulation alternative for HCPs' education on postoperative pain assessment, with improvements in performance and knowledge comparable with SP-based simulation. An equivalence trial to examine the effectiveness of deteriorating patient-based simulation versus standardized patients is warranted.

Acute β-blockade with metoprolol has been associated with increased mortality by undefined mechanisms. Since metoprolol is a relatively high affinity blocker of β(2)-adrenoreceptors, we hypothesized that some of the increased mortality associated with its use may be due to its abrogation of β(2)-adrenoreceptor-mediated vasodilation of microvessels in different vascular beds. Cardiac output (CO; pressure volume loops), mean arterial pressure (MAP), relative cerebral blood flow (rCBF; laser Doppler), and microvascular brain tissue Po(2) (G2 oxyphor) were measured in anesthetized mice before and after acute treatment with metoprolol (3 mg/kg iv). The vasodilatory dose responses to β-adrenergic agonists (isoproterenol and clenbuterol), and the myogenic response, were assessed in isolated mesenteric resistance arteries (MRAs; ∼200-μm diameter) and posterior cerebral arteries (PCAs ∼150-μm diameter). Data are presented as means ± SE with statistical significance applied at P < 0.05. Metoprolol treatment did not effect MAP but reduced heart rate and stroke volume, CO, rCBF, and brain microvascular Po(2), while concurrently increasing systemic vascular resistance (P < 0.05 for all). In isolated MRAs, metoprolol did not affect basal artery tone or the myogenic response, but it did cause a dose-dependent impairment of isoproterenol- and clenbuterol-induced vasodilation. In isolated PCAs, metoprolol (50 μM) impaired maximal vasodilation in response to isoproterenol. These data support the hypothesis that acute administration of metoprolol can reduce tissue oxygen delivery by impairing the vasodilatory response to β(2)-adrenergic agonists. This mechanism may contribute to the observed increase in mortality associated with acute administration of metoprolol in perioperative patients.

Purpose: Peripherally inserted central venous catheters (PICCs) do not interfere with surgical access during neck dissection and are used in patients undergoing head and neck surgery. However, severe complications associated with malpositioning of PICCs have been reported in these patients. We conducted a retrospective study to determine the incidence of aberrant positioning of PICCs in patients undergoing free flap reconstructive (FFR) surgery for head and neck malignancies., Methods: We analyzed a database of 269 patients undergoing FFR surgery. After induction of general anesthesia, a PICC was inserted successfully in 130 patients (48%) at bedside without image guidance. A PICC was not used in 139 patients (52%). A chest x-ray was performed at admission to the postanesthetic care unit, stored digitally, and reviewed retrospectively by two independent observers. Based on the chest x-ray findings, the PICC position was classified as proper, suboptimal, or aberrant and defined according to the position of the PICC tip, i.e., proper, if situated in the ipsilateral innominate vein or in the superior vena cava; suboptimal, if situated in the subclavian vein; and aberrant, if situated in any other location., Results: Proper, suboptimal, and aberrant PICC positions were found in 68 (52%), 17 (13%), and 45 (35%) patients, respectively. The proper position was confirmed more frequently with a left- than with a right-sided approach: 23/29 (79%) vs 45/101 (44%) patients, respectively (P < 0.001)., Conclusions: There is a high incidence of aberrant positioning when PICCs are inserted without image guidance. The left-sided approach might be preferable due to a lower incidence of malpositions. The risk-benefit ratio should be estimated carefully before using a PICC in patients undergoing FFR procedures.

Objective: To determine the association of resting echocardiography before elective intermediate to high risk non-cardiac surgery with survival and length of hospital stay., Design: Population based retrospective cohort study., Setting: Acute care hospitals in Ontario, Canada, between 1 April 1999 and 31 March 2008., Participants: Patients aged over 40 years who had elective intermediate to high risk non-cardiac surgery., Intervention: Resting echocardiography within 6 months before surgery., Main Outcome Measures: Postoperative survival (30 days and 1 year) and length of hospital stay; postoperative surgical site infection as an outcome for which no association with echocardiography would be expected., Results: Of the 264,823 patients in the entire cohort, 15.1% (n = 40,084) had echocardiography. After use of propensity score methods to assemble a matched cohort (n = 70,996) that reduced differences between patients who had or had not had echocardiography, echocardiography was associated with increases in 30 day mortality (relative risk 1.14, 95% confidence interval 1.02 to 1.27), 1 year mortality (1.07, 1.01 to 1.12), and length of hospital stay but no difference in surgical site infections (1.03, 0.98 to 1.06). The association with mortality was influenced (P = 0.02) by whether patients had had stress testing or had risk factors for cardiac complications. No association existed between echocardiography and mortality among patients who had stress testing (relative risk 1.01, 0.92 to 1.11) or among patients at high risk who had not had stress testing (1.00, 0.87 to 1.13). However, echocardiography was associated with mortality in patients at low risk (relative risk 1.44, 1.14 to 1.82) and intermediate risk (1.10, 1.02 to 1.18) who had not had stress testing., Conclusions: Preoperative echocardiography was not associated with improved survival or shorter hospital stay after major non-cardiac surgery. These findings highlight the need for further research to guide better use of this common preoperative test.

Background: Current guidelines on perioperative care recommend the prophylactic use of β blockers in high-risk patients undergoing noncardiac surgery. However, recent studies show that, in some instances, perioperative β blockade can cause harm. Furthermore, chronic β blockade, titrated to effect before surgery, may be superior to acute perioperative β blockade. The primary objective of this study was to compare major acute cardiac outcomes in patients who underwent surgery with chronic β blocker therapy with those in patients with acute β-blocker therapy., Methods: Data were collected for 10,691 consecutive patients undergoing elective noncardiac surgery between April 1, 2008, and April 30, 2010. Propensity scores, estimating the probability of receiving a preoperative β blocker, were calculated to match (1:1) the patients with acute and chronic β-blocker therapy. The primary outcome was a composite of myocardial infarction, nonfatal cardiac arrest, and perioperative mortality. The rate of cardiac events was compared in the matched cohorts., Results: A total of 962 patients were chronically treated with a β blocker before surgery; in 436 patients, the β blocker was administrated acutely. Propensity score matching created 301 patient pairs who were well-balanced for major comorbidities, concomitant drug use, and type of surgery. The primary outcome was observed in 9 (3.0%) chronic versus 24 (8.0%) acute β-blocked patients (relative risk, 2.67; 95% CI, 1.27-5.60; P = 0.011)., Conclusions: Acute β blockade, initiated within the first 2 days after surgery, was associated with worse cardiac outcome compared with a matched cohort of patients who underwent surgery on chronic β blockade. These results should be validated in a larger prospective trial.

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.

Purpose: Administrative electronic databases are highly specific for postoperative complications, but they lack sensitivity. The objective of this study was to determine the incidence of delirium after cardiac surgery using a targeted prospectively collected dataset and to compare the findings with the incidence of delirium in the same cohort of patients identified in a hospital administrative database., Methods: Following Research Ethics Board approval, we compared delirium rates in a prospectively collected data research database with delirium rates in the same cohort of patients in an administrative hospital database where delirium was identified from codes entered by coding and abstracting staff. Every 12 hr postoperatively, delirium was assessed with a Confusion Assessment Method in the Intensive Care Unit. The administrative database contained the International Classification of Diseases version 10 (ICD-10) codes for patient diagnoses. The ICD-10 codes were extracted from the administrative database for each patient in the research database and were checked for the presence of the ICD-10 code for delirium., Results: Data from a cohort of 1,528 patients were analyzed. Postoperative delirium was identified in 182 (11.9%) patients (95% confidence interval [CI], 10.3-13.5%) in the research dataset and 46 (3%) patients (95% CI, 2.2-3.8%) in the administrative dataset (P < 0.001). Thirteen (0.85%) patients who were coded for delirium in the administrative database were not identified in the research dataset. The median onset of postoperative delirium in these patients was significantly delayed (4 [3-9] days) compared with patients identified by both datasets (2 [1-9] days) and compared with patients from the research database only (1 [1-14] days) (P = 0.007)., Conclusion: Postoperative delirium rates after cardiac surgery are underestimated by the hospital administrative database.

Background: Preoperative consultations by internal medicine physicians facilitate documentation of comorbid disease, optimization of medical conditions, risk stratification, and initiation of interventions intended to reduce risk. Nonetheless, the impact of these consultations, which may be performed by general internists or specialists, on outcomes is unclear., Methods: We used population-based administrative databases to conduct a cohort study of patients 40 years or older who underwent major elective noncardiac surgery in Ontario, Canada, between 1994 and 2004. Propensity scores were used to assemble a matched-pairs cohort that reduced differences between patients who did and did not undergo preoperative consultation by general internists or specialists. The association of consultation with mortality and hospital stay was determined within this matched cohort. As a sensitivity analysis, we evaluated the association of consultation with an outcome for which no difference would be expected: postoperative wound infection., Results: Of 269,866 patients in the cohort, 38.8% (n=104,695) underwent consultation. Within the matched cohort (n=191,852), consultation was associated with increased 30-day mortality (relative risk [RR], 1.16; 95% confidence interval [CI], 1.07-1.25; number needed to harm, 516), 1-year mortality (1.08; 1.04-1.12; number needed to harm, 227), mean hospital stay (difference, 0.67 days; 0.59-0.76), preoperative testing, and preoperative pharmacologic interventions. Notably, consultation was not associated with any difference in postoperative wound infections (RR, 0.98; 95% CI, 0.95-1.02). These findings were stable across subgroups as well as sensitivity analyses that tested for unmeasured confounding., Conclusions: Medical consultation before major elective noncardiac surgery is associated with increased mortality and hospital stay, as well as increases in preoperative pharmacologic interventions and testing. These findings highlight the need to better understand mechanisms by which consultation influences outcomes and to identify efficacious interventions to decrease perioperative risk.

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.

Purpose: To report the identification of a novel mutation in the CACNA1S gene that encodes the alpha-1-subunit (Cav1.1) of the voltage-gated skeletal muscle L-type calcium channel in a patient with malignant hyperthermia., Clinical Findings: An otherwise healthy 34-yr-old female developed fulminant malignant hyperthermia (MH) under sevoflurane anesthesia during laparoscopic donor nephrectomy. The first sign was an increase in end-tidal CO(2). Malignant hyperthermia was suspected early, and resuscitative measures, including supportive and specific treatment, were successfully implemented. The patient rejected the open muscle biopsy for the Caffeine-Halothane Contracture Test (CHCT); therefore, only molecular genetic testing was performed. Sequencing of the entire ryanodine receptor type 1 transcript did not reveal any MH causative mutations. However, a novel homozygous mutation, p.Arg1086Ser, was identified in the CACNA1S gene that encoded for the alpha-1-subunit of the skeletal muscle L-type calcium channel (Cav1.1). A CACNA1S mutation, p.Arg1086His, involving the same Arg1086 residue that is mutated in our patient has previously been reported in association with MH in three independent families., Conclusion: The homozygous p.Arg1086Ser mutation of CACNA1S, the gene that encodes the alpha-1-subunit of the voltage-gated skeletal muscle L-type calcium channel, is a novel mutation associated with malignant hyperthermia.

Objective: To determine the association of non-invasive cardiac stress testing before elective intermediate to high risk non-cardiac surgery with survival and hospital stay., Design: Population based retrospective cohort study., Setting: Acute care hospitals in Ontario, Canada, between 1 April 1994 and 31 March 2004., Participants: Patients aged 40 years or older who underwent specific elective intermediate to high risk non-cardiac surgical procedures., Interventions: Non-invasive cardiac stress testing performed within six months before surgery., Main Outcome Measures: Postoperative one year survival and length of stay in hospital., Results: Of the 271 082 patients in the entire cohort, 23 991 (8.9%) underwent stress testing. After propensity score methods were used to reduce important differences between patients who did or did not undergo preoperative stress testing and assemble a matched cohort (n=46 120), testing was associated with improved one year survival (hazard ratio (HR) 0.92, 95% CI 0.86 to 0.99; P=0.03) and reduced mean hospital stay (difference -0.24 days, 95% CI -0.07 to -0.43; P<0.001). In an analysis of subgroups defined by Revised Cardiac Risk Index (RCRI) class, testing was associated with harm in low risk patients (RCRI 0 points: HR 1.35, 95% CI 1.05 to 1.74), but with benefit in patients who were at intermediate risk (RCRI 1-2 points: 0.92, 95% CI 0.85 to 0.99) or high risk (RCRI 3-6 points: 0.80, 95% CI 0.67 to 0.97)., Conclusions: Preoperative non-invasive cardiac stress testing is associated with improved one year survival and length of hospital stay in patients undergoing elective intermediate to high risk non-cardiac surgery. These benefits principally apply to patients with risk factors for perioperative cardiac complications.

Background: The Revised Cardiac Risk Index (RCRI) is widely used to predict perioperative cardiac complications., Purpose: To evaluate the ability of the RCRI to predict cardiac complications and death after noncardiac surgery., Data Sources: MEDLINE, EMBASE, and ISI Web of Science (1966 to 31 December 2008)., Study Selection: Cohort studies that reported the association of the RCRI with major cardiac complications (cardiac death, myocardial infarction, and nonfatal cardiac arrest) or death in the hospital or within 30 days of surgery., Data Extraction: Two reviewers independently extracted study characteristics, documented outcome data, and evaluated study quality., Data Synthesis: Of 24 studies (792 740 patients), 18 reported cardiac complications; 6 of the 18 studies were prospective and had uniform outcome surveillance and blinded outcome adjudication. The RCRI discriminated moderately well between patients at low versus high risk for cardiac events after mixed noncardiac surgery (area under the receiver-operating characteristic curve [AUC], 0.75 [95% CI, 0.72 to 0.79]); sensitivity, 0.65 [CI, 0.46 to 0.81]; specificity, 0.76 [CI, 0.58 to 0.88]; positive likelihood ratio, 2.78 [CI, 1.74 to 4.45]; negative likelihood ratio, 0.45 [CI, 0.31 to 0.67]). Prediction of cardiac events after vascular noncardiac surgery was less accurate (AUC, 0.64 [CI, 0.61 to 0.66]; sensitivity, 0.70 [CI, 0.53 to 0.82]; specificity, 0.55 [CI, 0.45 to 0.66]; positive likelihood ratio, 1.56 [CI, 1.42 to 1.73]; negative likelihood ratio, 0.55 [CI, 0.40 to 0.76]). Six studies reported death, with a median AUC of 0.62 (range, 0.54 to 0.78). A pooled AUC for predicting death could not be calculated because of very high heterogeneity (I(2) = 95%)., Limitation: Studies generally were of low methodological quality, had varied definitions of cardiac events, and were statistically and clinically heterogeneous., Conclusion: The RCRI discriminated moderately well between patients at low versus high risk for cardiac events after mixed noncardiac surgery. It did not perform well at predicting cardiac events after vascular noncardiac surgery or at predicting death. High-quality research is needed in this area of perioperative medicine.

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: Perioperative beta-blockade and anemia are independent predictors of increased stroke and mortality by undefined mechanisms. This study investigated the effect of beta-blockade on cerebral tissue oxygen delivery in an experimental model of blood loss and fluid resuscitation (hemodilution)., Methods: Anesthetized rats were treated with metoprolol (3 mg x kg) or saline before undergoing hemodilution with pentastarch (1:1 blood volume exchange, 30 ml x kg). Outcomes included cardiac output, cerebral blood flow, and brain (PBrO2) and kidney (PKO2) tissue oxygen tension. Hypoxia inducible factor-1alpha (HIF-1alpha) protein levels were assessed by Western blot. Systemic catecholamines, erythropoietin, and angiotensin II levels were measured., Results: Hemodilution increased heart rate, stroke volume, cardiac output (60%), and cerebral blood flow (50%), thereby maintaining PBrO2 despite an approximately 50% reduction in blood oxygen content (P < 0.05 for all). By contrast, PKO2 decreased (50%) under the same conditions (P < 0.05). Beta-blockade reduced baseline heart rate (20%) and abolished the compensatory increase in cardiac output after hemodilution (P < 0.05). This attenuated the cerebral blood flow response and reduced PBrO2 (50%), without further decreasing PKO2. Cerebral HIF-1alpha protein levels were increased in beta-blocked hemodiluted rats relative to hemodiluted controls (P < 0.05). Systemic catecholamine and erythropoietin levels increased comparably after hemodilution in both groups, whereas angiotensin II levels increased only after beta-blockade and hemodilution., Conclusions: Cerebral tissue oxygen tension is preferentially maintained during hemodilution, relative to the kidney, despite elevated systemic catecholamines. Acute beta-blockade impaired the compensatory cardiac output response to hemodilution, resulting in a reduction in cerebral tissue oxygen tension and increased expression of HIF-1alpha.

Background: The surgical stress response plays an important role on the pathogenesis of perioperative cardiac complications. Alpha-2 adrenergic agonists attenuate this response and may thereby prevent cardiac complications., Objectives: This review assessed the efficacy and safety of preoperative (within 24 hours), intraoperative, and postoperative (first 48 hours) alpha-2 adrenergic agonists for preventing mortality and cardiac complications after surgery performed under either general or neuraxial anaesthesia, or both., Search Strategy: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2008, Issue 3), MEDLINE (1950 to August week 4 2008), EMBASE (1980 to week 36 2008), the Science Citation Index, and reference lists of articles., Selection Criteria: We included randomized controlled trials that compared alpha-2 adrenergic agonists (clonidine, dexmedetomidine, or mivazerol) against placebo or non-alpha-2 adrenergic agonists. Included studies had to report on mortality, myocardial infarction, myocardial ischaemia, or supraventricular tachyarrhythmia., Data Collection and Analysis: Three authors independently assessed trial quality and extracted data. Two authors independently performed computer entry of abstracted data. We contacted study authors for additional information. Adverse event data were gathered from the trials., Main Results: We included 31 studies (4578 participants). Study quality was generally inadequate, with only six studies clearly reporting methods for blinding and allocation concealment. Overall, alpha-2 adrenergic agonists reduced mortality (relative risk (RR) 0.66; 95% CI 0.44 to 0.98; P = 0.04) and myocardial ischaemia (RR 0.68; 95% CI 0.57 to 0.81; P < 0.0001). However, their effects appeared to vary with the surgical procedure. The most encouraging data pertained to vascular surgery, where they reduced mortality (RR 0.47; 95% CI 0.25 to 0.90; P = 0.02), cardiac mortality (RR 0.36; 95% CI 0.16 to 0.79; P = 0.01), and myocardial infarction (RR 0.66; 95% CI 0.46 to 0.94; P = 0.02). With regard to adverse effects, alpha-2 adrenergic agonists significantly increased perioperative hypotension (RR 1.32; 95% CI 1.07 to 1.62; P = 0.009) and bradycardia (RR 1.66; 95% CI 1.14 to 2.41; P = 0.008)., Authors' Conclusions: Our study provides encouraging evidence that alpha-2 adrenergic agonists may reduce cardiac risk, especially during vascular surgery. Nonetheless, these data remain insufficient to make firm conclusions about their efficacy and safety. A large randomized trial of alpha-2 adrenergic agonists is therefore warranted. Additionally, future research must determine which specific alpha-2 adrenergic agonist should be used, and whether it is safe to combine them with other perioperative interventions (for example beta-adrenergic blockade).

Background: In single-center studies, consultation by an anesthesiologist days to weeks before surgery was associated with reduced patient anxiety, case cancellations on the day of surgery, and duration of hospitalization. Nonetheless, the impact of anesthesia consultation on outcomes in the population remains unclear., Methods: We used population-based, linked, administrative databases to conduct a cohort study of patients, aged 40 years and older, who underwent selected elective intermediate- to high-risk noncardiac surgical procedures in Ontario, Canada, between April 1, 1994, and March 31, 2004. Propensity-score methods were used to construct a matched-pairs cohort that resolved important differences between patients who underwent consultation and those who did not. We then determined the association of consultation (within 60 days before surgery) with hospital length of stay and postoperative mortality (30-day and 1-year) rates within the matched pairs., Results: Of the 271 082 patients in the entire cohort, 39% (n = 104 716) underwent anesthesia consultation. The proportion of patients who underwent consultation increased from 19% in 1994 to 53% in 2003. Within the matched-pairs (n = 180 254), consultation was associated with reduced mean hospital length of stay (8.17 days vs 8.52 days; difference, -0.35 days; 95% confidence interval [CI], -0.27 to -0.43; P < .001). Consultation was not associated with reduced mortality at 30 days (relative risk, 1.04; 95% CI, 0.96 to 1.13; P = .36) or 1 year (relative risk, 0.98; 95% CI, 0.95 to 1.02; P = .20)., Conclusions: Preoperative anesthesia consultation is associated with reduced length of stay but not with reduced mortality. Future research should evaluate the cost-effectiveness of the increasing use of anesthesia consultation.

Objective: Randomized trials generally use "frequentist" statistics based on P-values and 95% confidence intervals. Frequentist methods have limitations that might be overcome, in part, by Bayesian inference. To illustrate these advantages, we re-analyzed randomized trials published in four general medical journals during 2004., Study Design and Setting: We used Medline to identify randomized superiority trials with two parallel arms, individual-level randomization and dichotomous or time-to-event primary outcomes. Studies with P<0.05 in favor of the intervention were deemed "positive"; otherwise, they were "negative." We used several prior distributions and exact conjugate analyses to calculate Bayesian posterior probabilities for clinically relevant effects., Results: Of 88 included studies, 39 were positive using a frequentist analysis. Although the Bayesian posterior probabilities of any benefit (relative risk or hazard ratio<1) were high in positive studies, these probabilities were lower and variable for larger benefits. The positive studies had only moderate probabilities for exceeding the effects that were assumed for calculating the sample size. By comparison, there were moderate probabilities of any benefit in negative studies., Conclusion: Bayesian and frequentist analyses complement each other when interpreting the results of randomized trials. Future reports of randomized trials should include both.

Background: Early randomized controlled trials have suggested that neuraxial blockade may reduce cardiorespiratory complications after non-cardiothoracic surgery, but recent larger trials have been inconclusive. We conducted a pilot study to assess the feasibility of conducting a large multicentre randomized controlled trial in Canada., Methodology/principal Findings: After Research Ethics Board approvals from the participating institutions, subjects were recruited if they were > or = 45 years old, had an expected hospital stay > or = 48 hours, were undergoing a noncardiothoracic procedure amenable to epidural analgesia, met one of six risk criteria, and did not have contraindications to neuraxial blockade. After informed consent, subjects were randomly allocated to combined epidural analgesia (epidural group) and neuraxial anesthesia, with or without general anesthesia, or intravenous opioid analgesia (IV group) and general anesthesia. The primary outcomes were the rate of recruitment and the percents of eligible patients recruited, crossed over, and followed completely. Feasibility targets were defined a priori. A blinded, independent committee adjudicated the secondary clinical outcomes. Subjects were followed daily while in hospital and then at 30 days after surgery. Analysis was intention-to-treat. Over a 15-month period, the recruitment rate was 0.5+/-0.3 (mean+/-SEM) subjects per week per centre; 112/494 (22.7%) eligible subjects were recruited at four tertiary-care teaching hospitals in Canada. Thirteen (26.5%) of 49 subjects in the epidural group crossed over to the IV group; seven (14.3%) were due to failed or inadequate analgesia or complications from epidural analgesia. Five (9.8%) of 51 subjects in the IV group crossed over to the epidural group but none were due to inadequate analgesia or complications. Ninety-eight (97.0%) of 101 subjects were successfully followed up until 30 days after their surgery., Conclusion/significance: Of the criteria we defined for the feasibility of a full-scale trial, only the follow-up target was met. The other feasibility outcomes did not meet our preset criteria for success. The results suggest that a large multicentre trial may not be a feasible design to study the perioperative effects of neuraxial blockade., Trial Registration: ClinicalTrials.gov NCT 0221260 Controlled-Trials.com ISRCTN 35629817.

Background: Delirium is an acute deterioration of brain function characterized by fluctuating consciousness and an inability to maintain attention. Use of statins has been shown to decrease morbidity and mortality after major surgical procedures. The objective of this study was to determine an association between preoperative administration of statins and postoperative delirium in a large prospective cohort of patients undergoing cardiac surgery with cardiopulmonary bypass., Methods: After Institutional Review Board approval, data were prospectively collected on consecutive patients undergoing cardiac surgery with cardiopulmonary bypass from April 2005 to June 2006 in an academic hospital. All patients were screened for delirium during their hospitalization using the Confusion Assessment Method in the intensive care unit. Multivariable logistic regression analysis was used to identify independent perioperative predictors of delirium after cardiac surgery. Statins were tested for a potential protective effect., Results: Of the 1,059 patients analyzed, 122 patients (11.5%) had delirium at any time during their cardiovascular intensive care unit stay. Administration of statins had a protective effect, reducing the odds of delirium by 46%. Independent predictors of postoperative delirium included older age, preoperative depression, preoperative renal dysfunction, complex cardiac surgery, perioperative intraaortic balloon pump support, and massive blood transfusion. The model was reliable (Hosmer-Lemeshow test, P = 0.3) and discriminative (area under receiver operating characteristic curve = 0.77)., Conclusions: Preoperative administration of statins is associated with the reduced risk of postoperative delirium after cardiac surgery with cardiopulmonary bypass.

Purpose: To assess the effect of N-acetylcysteine (NAC) on acute renal failure and important clinical outcomes after cardiac surgery., Methods: Two reviewers performed literature searches, using EMBASE and PubMed, of randomized controlled trials investigating the renoprotective effect of N-acetylcysteine in cardiac surgery. Treatment effects were calculated as relative risks (RR) with 95% confidence intervals (CI). Heterogeneity and publication bias were assessed using the I(2) test and funnel plots, respectively. Meta regression was performed to assess the effect of baseline renal function and the use of aprotinin on renal function., Results: Seven randomized controlled trials (RCTs) (n = 1000) were identified. No study could demonstrate, either independently or meta-analytically, an improvement in the postoperative increase in creatinine, mortality (RR 0.93, 95% CI 0.4 to 2.07), renal failure requiring renal replacement therapy (RR 1.01, 95% CI 0.49 to 2.12), myocardial infarction (RR 0.88, 95% CI 0.36 to 1.88), atrial fibrillation (RR 0.88, 95% CI 0.70 to 1.10), or stroke (RR 0.69, 95% CI 0.27 to 1.69). There was a small, though significant increase in postoperative blood loss among patients treated with NAC (weighted mean difference 119 mL 95% CI 51, 187). After meta regression neither increase in postoperative creatinine (r(2) = 0.33) nor renal replacement therapy (r(2) = 0.04) was associated with the baseline creatinine or with NAC dose (r(2) =0.04)., Conclusion: This analysis did not find that treatment with NAC was associated with clinical renal protection during cardiac surgery, or improvement in other clinical outcomes.

Background: Current red blood cell (RBC) transfusion guidelines assume that most acutely anemic patients can tolerate hemoglobin (Hb) concentrations as low as 6.0 to 7.0 g per dL and recommend that range as the transfusion threshold in patients who have no overt signs of organ dysfunction. Nonetheless, "normal" Hb concentrations vary widely in the population, and this variability may influence patients' tolerance of acute anemia. This retrospective cohort study was carried out to test this hypothesis., Study Design and Methods: Data were analyzed on 10,179 consecutive patients who had normal Hb concentrations (12.0-16.0 g/dL in women and 13.0-18.0 g/dL in men) and underwent on-pump cardiac surgery from 1999 to 2006 at an academic hospital. The relationships of lowest intraoperative Hb concentration and maximum decrease in Hb concentration (from baseline) with the composite outcome of in-hospital death, stroke, or kidney failure were determined in various patient subgroups., Results: The relationship between lowest Hb concentration and adverse outcomes was not independently associated with increased risk. In contrast, the relationship between maximum decrease in Hb concentration and adverse outcomes was independently associated with increased risk, with a 50 percent decrease being the threshold beyond which risk was increased (adjusted odds ratio, 1.53; 95% confidence interval, 1.12-2.08; p = 0.007)., Conclusion: The degree of acute anemia that patients can safely tolerate during cardiac surgery is inversely related to their baseline Hb concentration. Current transfusion guidelines do not account for this relationship.

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.

Background: In cardiac surgery, excessive blood loss requiring large-volume red blood cell (RBC) transfusion is a common occurrence that is associated with significant morbidity and mortality. The objectives of this study were to measure the interinstitution variation and predictability of large-volume RBC transfusion., Study Design and Methods: Data were retrospectively collected on 3500 consecutive cardiac surgical patients at seven Canadian hospitals during 2004. The crude and risk-adjusted institutional odds ratios (ORs) for large-volume (>or=5 U) RBC transfusion were calculated with logistic regression. The predictive accuracy of an existing prediction rule for large-volume RBC transfusion was calculated for each institution., Results: Large-volume RBC transfusion occurred in 538 (15%) patients. When compared to the reference hospital (median crude rate), the institutional unadjusted and adjusted ORs for large-volume RBC transfusion ranged from 0.29 to 1.26 and 0.14 to 1.15, respectively (p<0.0001 for interinstitution variation). The variation was lower, but still considerable, for excessive blood loss, defined as at least 5-U RBC transfusion or reexploration; the ORs ranged from 0.42 to 1.22 (p<0.0001). The prediction rule performed well at most sites; its pooled positive predictive value for excessive blood loss was 71 percent (range, 63%-89%), and its negative predictive value was 90 percent (range, 87%-93%)., Conclusions: There is marked interinstitution variation in large-volume RBC transfusion in cardiac surgery that is not explained by patient- or surgery-related factors. Despite this variation, patients at high or low risk for large-volume RBC transfusion can be accurately identified by a prediction rule composed of readily available clinical variables.

Purpose: N-acetylcysteine may prevent acute kidney injury after cardiac surgery. To determine if N-acetylcysteine warrants definitive evaluation in a large multicentre trial, we evaluated its effects on a surrogate outcome, estimated glomerular filtration rate (eGFR), in a randomized trial., Methods: One-hundred-seventy-seven cardiac surgery patients with moderate pre-existing renal insufficiency (eGFR

Objective: The added value of a preoperative electrocardiogram (ECG) in the prediction of postoperative myocardial infarction (POMI) and death was compared with clinical risk factors identified from the patient's history., Summary of Background Data: An ECG is frequently performed before surgery to screen for asymptomatic coronary artery disease. However, the value of ECG abnormalities to predict POMI has been questioned., Methods: The study included 2967 noncardiac surgery patients >50 years of age from 2 university hospitals, who were expected to stay in the hospital for >24 hours. All data were obtained from electronic record-keeping systems. Patient history and ECG abnormalities were considered as potential predictors. Multivariate logistic regression analysis was used to obtain the independent predictors of POMI and all-cause in-hospital mortality. The area under the receiver operating characteristic curve (ROC area) was estimated to evaluate the ability of different models to discriminate between patients with and without the outcome., Results: A preoperative ECG was available in 2422 patients (80%) and 1087 (45%) of the ECGs showed at least one abnormality. The ROC area of the model that included the independent predictors of POMI obtained from patient history, ie, ischemic heart disease and high-risk surgery, was 0.80. ECG abnormalities that were associated with POMI were a right and a left bundle branch block. After adding these abnormalities in the regression model, the ROC area remained 0.80. Similar results were found for all-cause mortality., Conclusions: Bundle branch blocks identified on the preoperative ECG were related to POMI and death but did not improve prediction beyond risk factors identified on patient history.

Purpose: Recombinant activated factor VII (rFVIIa) is currently not approved by Health Canada or the Food and Drug Administration for treating excessive blood loss in nonhemophiliac patients undergoing on-pump cardiac surgery, but is increasingly being used "off-label" for this indication. A Canadian Consensus Conference was convened to generate recommendations for rFVIIa use in on-pump cardiac surgery., Methods: The panel undertook a literature review of the use of rFVIIa in both cardiac and non-cardiac surgery. Appropriateness, timing, and dosage considerations were addressed for three cardiac surgery indications: prophylactic, routine, and rescue uses. Recommendations were based on evidence from the literature and derived by consensus following recognized grading procedures., Results: The panel recommended against prophylactic or routine use of rFVIIa, as there is no evidence at this time that the benefits of rFVIIa outweigh its potential risks compared with standard hemostatic therapies. On the other hand, the panel made a weak recommendation (grade 2C) for the use of rFVIIa (one to two doses of 35-70 microg.kg(-1)) as rescue therapy for blood loss that is refractory to standard hemostatic therapies, despite the lack of randomized controlled trial data for this indication., Conclusions: In cardiac surgery, the risks and benefits of rFVIIa are unclear, but current evidence suggests that its benefits may outweigh its risks for rescue therapy in selected patients. Methodologically rigorous studies are needed to clarify its riskbenefit profile in cardiac surgery patients.

Context: A predictive index for renal replacement therapy (RRT; hemodialysis or continuous venovenous hemodiafiltration) after cardiac surgery may improve clinical decision making and research design., Objectives: To develop a predictive index for RRT using preoperative information., Design, Setting, and Participants: Retrospective cohort of 20 131 cardiac surgery patients at 2 hospitals in Ontario, Canada. The derivation cohort consisted of 10,751 patients at Toronto General Hospital (1999-2004). The validation cohorts consisted of 2566 patients at Toronto General Hospital (2004-2005) and 6814 patients at Ottawa Heart Institute (1999-2003)., Main Outcome Measure: Postoperative RRT., Results: RRT rates in the derivation, Toronto validation, and Ottawa validation cohorts were 1.3%, 1.8%, and 2.2%, respectively. Multivariable predictors of RRT were preoperative estimated glomerular filtration rate, diabetes mellitus requiring medication, left ventricular ejection fraction, previous cardiac surgery, procedure, urgency of surgery, and preoperative intra-aortic balloon pump. The predictive index was scored from 0 to 8 points. An estimated glomerular filtration rate less than or equal to 30 mL/min was assigned 2 points; other components were assigned 1 point each: estimated glomerular filtration rate 31 to 60 mL/min, diabetes mellitus, ejection fraction less than or equal to 40%, previous cardiac surgery, procedure other than coronary artery bypass grafting, intra-aortic balloon pump, and nonelective case. Among the 53% of patients with low risk scores (< or =1), the risk of RRT was 0.4%; by comparison, this risk was 10% among the 6% of patients with high-risk scores (> or =4). The predictive index had areas under the receiver operating characteristic curve in the derivation, Toronto validation, and Ottawa validation cohorts of 0.81, 0.78, and 0.78, respectively. When these cohorts were stratified based on index scores, likelihood ratios for RRT were more concordant than observed RRT rates., Conclusions: RRT after cardiac surgery is predicted by readily available preoperative information. A simple predictive index based on this information discriminated well between low- and high-risk patients in derivation and validation cohorts. The index had improved generalizability when used to predict likelihood ratios for RRT.