Reitze N. Rodseth

Relationship between intraoperative mean arterial pressure and clinical outcomes after noncardiac surgery: toward an empirical definition of hypotension.

Background:Intraoperative hypotension may contribute to postoperative acute kidney injury (AKI) and myocardial injury, but what blood pressures are unsafe is unclear. The authors evaluated the association between the intraoperative mean arterial pressure (MAP) and the risk of AKI and myocardial injury. Methods:The authors obtained perioperative data for 33,330 noncardiac surgeries at the Cleveland Clinic, Ohio. The authors evaluated the association between intraoperative MAP from less than 55 to 75 mmHg and postoperative AKI and myocardial injury to determine the threshold of MAP where risk is increased. The authors then evaluated the association between the duration below this threshold and their outcomes adjusting for potential confounding variables. Results:AKI and myocardial injury developed in 2,478 (7.4%) and 770 (2.3%) surgeries, respectively. The MAP threshold where the risk for both outcomes increased was less than 55 mmHg. Compared with never developing a MAP less than 55 mmHg, those with a MAP less than 55 mmHg for 1–5, 6–10, 11–20, and more than 20 min had graded increases in their risk of the two outcomes (AKI: 1.18 [95% CI, 1.06–1.31], 1.19 [1.03–1.39], 1.32 [1.11–1.56], and 1.51 [1.24–1.84], respectively; myocardial injury 1.30 [1.06–1.5], 1.47 [1.13–1.93], 1.79 [1.33–2.39], and 1.82 [1.31–2.55], respectively]. Conclusions:Even short durations of an intraoperative MAP less than 55 mmHg are associated with AKI and myocardial injury. Randomized trials are required to determine whether outcomes improve with interventions that maintain an intraoperative MAP of at least 55 mmHg.

Myocardial injury after noncardiac surgery: a large, international, prospective cohort study establishing diagnostic criteria, characteristics, predictors, and 30-day outcomes.

Background:Myocardial injury after noncardiac surgery (MINS) was defined as prognostically relevant myocardial injury due to ischemia that occurs during or within 30 days after noncardiac surgery. The study’s four objectives were to determine the diagnostic criteria, characteristics, predictors, and 30-day outcomes of MINS. Methods:In this international, prospective cohort study of 15,065 patients aged 45 yr or older who underwent in-patient noncardiac surgery, troponin T was measured during the first 3 postoperative days. Patients with a troponin T level of 0.04 ng/ml or greater (elevated “abnormal” laboratory threshold) were assessed for ischemic features (i.e., ischemic symptoms and electrocardiography findings). Patients adjudicated as having a nonischemic troponin elevation (e.g., sepsis) were excluded. To establish diagnostic criteria for MINS, the authors used Cox regression analyses in which the dependent variable was 30-day mortality (260 deaths) and independent variables included preoperative variables, perioperative complications, and potential MINS diagnostic criteria. Results:An elevated troponin after noncardiac surgery, irrespective of the presence of an ischemic feature, independently predicted 30-day mortality. Therefore, the authors’ diagnostic criterion for MINS was a peak troponin T level of 0.03 ng/ml or greater judged due to myocardial ischemia. MINS was an independent predictor of 30-day mortality (adjusted hazard ratio, 3.87; 95% CI, 2.96–5.08) and had the highest population-attributable risk (34.0%, 95% CI, 26.6–41.5) of the perioperative complications. Twelve hundred patients (8.0%) suffered MINS, and 58.2% of these patients would not have fulfilled the universal definition of myocardial infarction. Only 15.8% of patients with MINS experienced an ischemic symptom. Conclusion:Among adults undergoing noncardiac surgery, MINS is common and associated with substantial mortality.

The prognostic value of pre-operative and post-operative B-type natriuretic peptides in patients undergoing noncardiac surgery: B-type natriuretic peptide and N-terminal fragment of pro-B-type natriuretic peptide: A systematic review and individual patient data meta-analysis

OBJECTIVES The objective of this study was to determine whether measuring post-operative B-type natriuretic peptides (NPs) (i.e., B-type natriuretic peptide [BNP] and N-terminal fragment of proBNP [NT-proBNP]) enhances risk stratification in adult patients undergoing noncardiac surgery, in whom a pre-operative NP has been measured. BACKGROUND Pre-operative NP concentrations are powerful independent predictors of perioperative cardiovascular complications, but recent studies have reported that elevated post-operative NP concentrations are independently associated with these complications. It is not clear whether there is value in measuring post-operative NP when a pre-operative measurement has been done. METHODS We conducted a systematic review and individual patient data meta-analysis to determine whether the addition of post-operative NP levels enhanced the prediction of the composite of death and nonfatal myocardial infarction at 30 and ≥180 days after surgery. RESULTS Eighteen eligible studies provided individual patient data (n = 2,179). Adding post-operative NP to a risk prediction model containing pre-operative NP improved model fit and risk classification at both 30 days (corrected quasi-likelihood under the independence model criterion: 1,280 to 1,204; net reclassification index: 20%; p < 0.001) and ≥180 days (corrected quasi-likelihood under the independence model criterion: 1,320 to 1,300; net reclassification index: 11%; p = 0.003). Elevated post-operative NP was the strongest independent predictor of the primary outcome at 30 days (odds ratio: 3.7; 95% confidence interval: 2.2 to 6.2; p < 0.001) and ≥180 days (odds ratio: 2.2; 95% confidence interval: 1.9 to 2.7; p < 0.001) after surgery. CONCLUSIONS Additional post-operative NP measurement enhanced risk stratification for the composite outcomes of death or nonfatal myocardial infarction at 30 days and ≥180 days after noncardiac surgery compared with a pre-operative NP measurement alone.

A meta-analysis of the utility of pre-operative brain natriuretic peptide in predicting early and intermediate-term mortality and major adverse cardiac events in vascular surgical patients

We conducted a meta‐analysis of the utility of pre‐operative B‐type natriuretic peptide (BNP) and N‐terminal‐pro B‐type natriuretic peptide in predicting early (< 30 days) and intermediate (< 180 days) term mortality and major adverse cardiac events (cardiac death and nonfatal myocardial infarction) in patients following vascular surgery. A Pubmed Central and EMBASE search was conducted up to January 2008. Of 81 studies identified, seven prospective observational studies were included in the meta‐analysis representing five patient cohorts: early outcomes (504 patients) and intermediate‐term outcomes (623 patients). A B‐type natriuretic peptide or N‐terminal‐pro B‐type natriuretic peptide above the optimal discriminatory threshold determined by receiver operating characteristic curve analysis was associated with 30‐day cardiac death (OR 7.6, 95% CI 1.33–43.4, p = 0.02), nonfatal myocardial infarction (OR 6.24, 95% CI 1.82–21.4, p = 0.004) and major adverse cardiac events (OR 17.37, 95% CI 3.31–91.15, p = 0.0007), and intermediate‐term, all‐cause mortality (OR 3.1, 95% CI 1.85–5.2, p < 0.0001), nonfatal myocardial infarction (OR 2.95, 95% CI 1.17–7.46, p = 0.02) and major adverse cardiac events (OR 3.31, 95% CI 2.1–5.24, p < 0.00001). B‐type natriuretic peptide and N‐terminal‐pro B‐type natriuretic peptide are potentially useful pre‐operative prognostic tests in vascular surgical patients.

Effects of dexamethasone as a local anaesthetic adjuvant for brachial plexus block: a systematic review and meta-analysis of randomized trials

BACKGROUND Brachial plexus nerve blocks (BPBs) have analgesic and opioid sparing benefits for upper extremity surgery. Single-injection techniques are limited by the pharmacological duration and therapeutic index of local anaesthetics (LAs). Continuous catheter techniques, while effective can present management challenges. Off-label use of perineural dexamethasone as an LA adjuvant has been utilized to prolong single-injection techniques. The objectives of this systematic review and meta-analysis are to assess the contemporary literature and quantify the effects of dexamethasone on BPB. METHODS The authors searched for randomized, placebo-controlled trials that compared BPB performed with LA alone with that performed with LA and perineural dexamethasone. Meta-analysis was performed using a random effects model with subgroup analysis stratified by LA (long vs intermediate). The primary outcome was duration of sensory block or analgesia; the secondary outcomes were motor block duration, opioid consumption, and BPB complications. RESULTS Nine trials (801 patients) were included with 393 patients receiving dexamethasone (4-10 mg). Dexamethasone prolonged the analgesic duration for long-acting LA from 730 to 1306 min [mean difference 576 min, 95% confidence interval (CI) 522-631] and for intermediate from 168 to 343 min (mean 175, 95% CI 73-277). Motor block was prolonged from 664 to 1102 min (mean 438, 95% CI 89-787). The most recent trial demonstrated equivalent prolongation with perineural or systemic administration of dexamethasone compared with placebo. CONCLUSIONS Perineural administration of dexamethasone with LA prolongs BPB effects with no observed adverse events. The effects of systemic administration of dexamethasone on BPB must be investigated.

The endothelial glycocalyx: a review of the vascular barrier

The endothelial glycocalyx is an important part of the vascular barrier. The glycocalyx is intimately linked to the homoeostatic functions of the endothelium. Damage to the glycocalyx precedes vascular pathology. In the first part of this paper, we have reviewed the structure, physiology and pathology of the endothelial glycocalyx, based on a literature search of the past five years. In the second part, we have systematically reviewed interventions to protect or repair the glycocalyx. Glycocalyx damage can be caused by hypervolaemia and hyperglycaemia and can be prevented by maintaining a physiological concentration of plasma protein, particularly albumin. Other interventions have been investigated in animal models: these require clinical research before their introduction into medical practice.

The Predictive Ability of Pre-Operative B-Type Natriuretic Peptide in Vascular Patients for Major Adverse Cardiac Events: An Individual Patient Data Meta-Analysis

OBJECTIVES The aims of this study were to perform an individual patient data meta-analysis of studies using B-type natriuretic peptides (BNPs) to predict the primary composite endpoint of cardiac death and nonfatal myocardial infarction (MI) within 30 days of vascular surgery and to determine: 1) the cut points for a natriuretic peptide (NP) diagnostic, optimal, and screening test; and 2) if pre-operative NPs improve the predictive accuracy of the revised cardiac risk index (RCRI). BACKGROUND NPs are independent predictors of cardiovascular events in noncardiac and vascular surgery. Their addition to clinical risk indexes may improve pre-operative risk stratification. METHODS Studies reporting the association of pre-operative NP concentrations and the primary study endpoint, post-operative major adverse cardiovascular events (defined as cardiovascular death and nonfatal MI) in vascular surgery, were identified by electronic database search. Secondary study endpoints included all-cause mortality, cardiac death, and nonfatal MI. RESULTS Six data sets were obtained, 5 for BNP (n = 632) and 1 for N-terminal pro-BNP (n = 218). An NP level higher than the optimal cut point was an independent predictor for the primary composite endpoint (odds ratio: 7.9; 95% confidence interval: 4.7 to 13.3). BNP cut points were 30 pg/ml for screening (95% sensitivity, 44% specificity), 116 pg/ml for optimal (highest accuracy point; 66% sensitivity, 82% specificity), and 372 pg/ml for diagnostic (32% sensitivity, 95% specificity). Subsequent to revised cardiac risk index stratification, reclassification using the optimal cut point significantly improved risk prediction in all groups (net reclassification improvement 58%, p < 0.000001), particularly in the intermediate-risk group (net reclassification improvement 84%, p < 0.001). CONCLUSIONS Pre-operative NP levels can be used to independently predict cardiovascular events in the first 30 days after vascular surgery and to significantly improve the predictive performance of the revised cardiac risk index.

Randomized Evidence for Reduction of Perioperative Mortality

OBJECTIVE With more than 220 million major surgical procedures performed annually, perioperative interventions leading to even minor mortality reductions would save thousands of lives per year. This international consensus conference aimed to identify all nonsurgical interventions that increase or reduce perioperative mortality as suggested by randomized evidence. DESIGN AND SETTING A web-based international consensus conference. PARTICIPANTS More than 1,000 physicians from 77 countries participated in this web-based consensus conference. INTERVENTIONS Systematic literature searches (MEDLINE/PubMed, June 8, 2011) were used to identify the papers with a statistically significant effect on mortality together with contacts with experts. Interventions were considered eligible for evaluation if they (1) were published in peer-reviewed journals, (2) dealt with a nonsurgical intervention (drug/technique/strategy) in adult patients undergoing surgery, and (3) provided a statistically significant mortality increase or reduction as suggested by a randomized trial or meta-analysis of randomized trials. MEASUREMENTS AND MAIN RESULTS Fourteen interventions that might change perioperative mortality in adult surgery were identified. Interventions that might reduce mortality include chlorhexidine oral rinse, clonidine, insulin, intra-aortic balloon pump, leukodepletion, levosimendan, neuraxial anesthesia, noninvasive respiratory support, hemodynamic optimization, oxygen, selective decontamination of the digestive tract, and volatile anesthetics. In contrast, aprotinin and extended-release metoprolol might increase mortality. CONCLUSIONS Future research and health care funding should be directed toward studying and evaluating these interventions.

Mortality reduction in cardiac anesthesia and intensive care: results of the first International Consensus Conference

There is no consensus on which drugs/techniques/strategies can affect mortality in the perioperative period of cardiac surgery. With the aim of identifying these measures, and suggesting measures for prioritized future investigation we performed the first International Consensus Conference on this topic. The consensus was a continuous international internet‐based process with a final meeting on 28 June 2010 in Milan at the Vita‐Salute University. Participants included 340 cardiac anesthesiologists, cardiac surgeons, and cardiologists from 65 countries all over the world. A comprehensive literature review was performed to identify topics that subsequently generated position statements for discussion, voting, and ranking. Of the 17 major topics with a documented mortality effect, seven were subsequently excluded after further evaluation due to concerns about clinical applicability and/or study methodology. The following topics are documented as reducing mortality: administration of insulin, levosimendan, volatile anesthetics, statins, chronic β‐blockade, early aspirin therapy, the use of pre‐operative intra‐aortic balloon counterpulsation, and referral to high‐volume centers. The following are documented as increasing mortality: administration of aprotinin and aged red blood cell transfusion. These interventions were classified according to the level of evidence and effect on mortality and a position statement was generated. This International Consensus Conference has identified the non‐surgical interventions that merit urgent study to achieve further reductions in mortality after cardiac surgery: insulin, intra‐aortic balloon counterpulsation, levosimendan, volatile anesthetics, statins, chronic β‐blockade, early aspirin therapy, and referral to high‐volume centers. The use of aprotinin and aged red blood cells may result in increased mortality.

Outcomes in vascular surgical patients with isolated postoperative troponin leak: a meta‐analysis

Although peri‐operative myocardial infarction remains a significant cause of morbidity and mortality following vascular surgery, the significance of an isolated troponin leak is uncertain. This is an elevation of troponin below the diagnostic threshold for a peri‐operative myocardial infarction, without symptoms or ischaemic electrocardiography changes or echocardiography signs such as new regional wall motion abnormalities. This meta‐analysis aimed to determine the early (< 30 days) and intermediate (< 180 days) outcomes of vascular surgical patients with an isolated troponin leak. A full literature search up to December 2010 identified 593 studies, of which nine (consisting of eight distinct patient cohorts) underwent analysis. An isolated troponin leak was strongly predictive of all‐cause mortality at 30 days (OR 5.03, 95% CI 2.88–8.79, p < 0.00001). The associated 30‐day mortality in patients with no troponin elevation, an isolated troponin leak or peri‐operative myocardial infarction was 2.3%, 11.6% and 21.6%, respectively (p = 0.000001). Insufficient data were available to analyse intermediate‐term outcomes. An isolated troponin leak following vascular surgery is strongly associated with short‐term mortality.