The relative merits of using a high-sensitivity cardiac Troponin T assay compared to a nonhigh-sensitivity troponin T assay after noncardiac surgery.

INTRODUCTION: Troponin elevation after noncardiac surgery is associated with an elevated risk of 30-day mortality. Little is known about relative merit of using a high-sensitivity Troponin T (hsTnT), the fifth-generation assay, vs the nonhigh sensitivity Troponin T (non-hsTnT), the fourth-generation assay, in the noncardiac surgery setting. We aimed to identify whether hsTnT can identify additional patients at risk that would have gone undetected with non-hsTnT measurement. METHODS: The VISION Study included 40,004 noncardiac surgery patients with postoperative troponin measurements. Among them, 1,806 patients had both fourth-generation non-hsTnT and fifth-generation hsTnT concomitant measurements (4,451 paired results). We compared the absolute concentrations, the timing, and the impact of different thresholds on predicting 30-day major cardiovascular complications (composite of death, nonfatal cardiac arrest, coronary revascularization, and congestive heart failure). RESULTS: Based on the manufacturers' threshold of 14 ng/L, 580 (32.1%) patients had postoperative hsTnT concentrations greater than the threshold, while their non-hsTnT concentrations were below the manufacturer's threshold. These 580 patients had higher risk of major cardiovascular events (OR 2.33; CI 95% 1.04-5.23; P = .049) than patients with hsTnT concentrations below the manufacturer threshold. Among patients with myocardial injury after noncardiac surgery, only 50% would be detected by the fourth-generation non-hsTnT assay at 6 to 12 hours postoperative as compared to 85% with the fifth-generation hsTnT assay (P-value < .001). CONCLUSIONS: Within the first 3 postoperative days, fifth-generation hsTnT identified at least 1 in 3 patients with troponin elevation that would have gone undetected by fourth-generation non-hsTnT using published thresholds in this setting. Furthermore, fifth-generation hsTnT identified patients with an elevation earlier than fourth-generation non-hsTnT, indicating potential to improve postoperative risk stratification.

Timing of Intraoperative Transitions of Care Among Anesthesiologists Is Not Associated With Postoperative Adverse Outcomes: Retrospective Cohort Study.

BACKGROUND: The majority of published research suggests that anesthesia handovers during major surgical procedures are associated with unintended harmful consequences. It is still unclear if the number or quality of the transition of care is the main driver of the adverse outcomes. There is even less data if the timing of the anesthesiologist handovers during the critical portion of the anesthetic continuum (induction or emergence versus surgical period) plays a role in patient outcomes. Therefore, we investigated if the anesthesiologist handovers during induction and emergence are associated with adverse patient outcomes. METHODS: This retrospective investigation included noncardiac surgical procedures occurring between January 1, 2012 and December 31, 2019 that had exactly 1 attending anesthesiologist handover. We categorized transitions of care between attending anesthesiologists as being before incision, between incision and closing, and after closing. Our primary outcome was a composite of 6 categories of surgical complications and in-hospital mortality. We created logistic generalized estimating equation models to estimate the average relative effect odds ratio between each pair of the 3 transition timing groups across the components of the composite outcome. Inverse probability of treatment weights were used to mitigate confounding on a host of baseline variables. We used Bonferroni correction to adjust for multiple comparisons between the transition groups. RESULTS: In total, we studied 36,937 procedures with exactly 1 attending anesthesiologist handover. Of these records, 4370 had the transition during induction, 24,999 between incision and closure, and 7568 during emergence. No differences were found between the transition periods and the composite outcome. The estimated average relative effect odds ratio (98.3% confidence interval [CI]) across the components of the composite outcome was as follows: (1.0002 [0.81-1.24], P = .99) between the induction and surgical period; (1.10 [0.87-1.40], P = .32) between the induction and emergence periods; and (0.91 [0.79-1.04], P = .08) between the emergence and surgical periods. CONCLUSIONS: Timing of intraoperative handover among attending anesthesiologists during noncardiac surgery is not associated with adverse patient outcomes.

Perioperative Supplemental Oxygen and Postoperative Nausea and Vomiting: Subanalysis of a Trial, Systematic Review, and Meta-analysis.

BACKGROUND: Intraoperative supplemental oxygen may reduce postoperative nausea and vomiting by mitigating hypoxic stress on the gastrointestinal tract. The authors therefore tested the hypothesis that supplemental oxygen reduces nausea and vomiting in adults recovering from colorectal surgery at the Cleveland Clinic between January 28, 2013, and March 11, 2016. METHODS: Initially, the authors conducted an unplanned subanalysis of a previous trial that evaluated the effect of 80% versus 30% intraoperative inspired oxygen on surgical site infection. Specifically, they assessed the effect of 80% versus 30% oxygen concentration on the incidence of postoperative nausea and/or vomiting. Thereafter, the authors conducted a systematic review and meta-analysis of the effect of supplemental oxygen on postoperative nausea and vomiting. RESULTS: The authors' underlying analysis included 5,057 colorectal surgeries on 4,001 patients. For 2,554 surgeries, assignment was to 80% oxygen, and in 2,503 surgeries, to 30%. Postoperative nausea and vomiting was 852 of 2,554 (33%) in 80% oxygen and 814 of 2,503 (33%) in 30% oxygen. The estimated relative risk (95% CI) of 80% versus 30% oxygen on postoperative nausea and vomiting was 1.04 (0.96 to 1.12) in a generalized estimating equation model adjusting for within-patient correlation for patients with multiple surgeries, P = 0.355. Furthermore, supplemental oxygen did not reduce antiemetic use (P = 0.911) or the severity of nausea and vomiting (P = 0.924). The authors' meta-analysis included 10 qualifying trials (6,749 patients) and did not find a difference in postoperative nausea and vomiting: relative risk, 0.97 [95% CI, 0.86 to 1.08], P = 0.55, I2 = 52%. CONCLUSIONS: The incidence of postoperative nausea and vomiting did not differ in patients assigned to 80% or 30% inspired oxygen. A meta-analysis of available trials similarly indicated that supplemental intraoperative oxygen does not reduce postoperative nausea and vomiting. Therefore, supplemental oxygen should not be given in the expectation that it will reduce nausea and vomiting.

Prolonged Opioid Use and Pain Outcome and Associated Factors after Surgery under General Anesthesia: A Prospective Cohort Association Multicenter Study.

BACKGROUND: There is insufficient prospective evidence regarding the relationship between surgical experience and prolonged opioid use and pain. The authors investigated the association of patient characteristics, surgical procedure, and perioperative anesthetic course with postoperative opioid consumption and pain 3 months postsurgery. The authors hypothesized that patient characteristics and intraoperative factors predict opioid consumption and pain 3 months postsurgery. METHODS: Eleven U.S. and one European institution enrolled patients scheduled for spine, open thoracic, knee, hip, or abdominal surgery, or mastectomy, in this multicenter, prospective observational study. Preoperative and postoperative data were collected using patient surveys and electronic medical records. Intraoperative data were collected from the Multicenter Perioperative Outcomes Group database. The association between postoperative opioid consumption and surgical site pain at 3 months, elicited from a telephone survey conducted at 3 months postoperatively, and demographics, psychosocial scores, pain scores, pain management, and case characteristics, was analyzed. RESULTS: Between September and October 2017, 3,505 surgical procedures met inclusion criteria. A total of 1,093 cases were included; 413 patients were lost to follow-up, leaving 680 (64%) for outcome analysis. Preoperatively, 135 (20%) patients were taking opioids. Three months postsurgery, 96 (14%) patients were taking opioids, including 23 patients (4%) who had not taken opioids preoperatively. A total of 177 patients (27%) reported surgical site pain, including 45 (13%) patients who had not reported pain preoperatively. The adjusted odds ratio for 3-month opioid use was 18.6 (credible interval, 10.3 to 34.5) for patients who had taken opioids preoperatively. The adjusted odds ratio for 3-month surgical site pain was 2.58 (1.45 to 4.4), 4.1 (1.73 to 8.9), and 2.75 (1.39 to 5.0) for patients who had site pain preoperatively, knee replacement, or spine surgery, respectively. CONCLUSIONS: Preoperative opioid use was the strongest predictor of opioid use 3 months postsurgery. None of the other variables showed clinically significant association with opioid use at 3 months after surgery.

Systematic reviews and consensus definitions for the Standardised Endpoints in Perioperative Medicine (StEP) initiative: mortality, morbidity, and organ failure.

BACKGROUND: Mortality, morbidity, and organ failure are important and common serious harms after surgery. However, there are many candidate measures to describe these outcome domains. Definitions of these measures are highly variable, and validity is often unclear. As part of the International Standardised Endpoints in Perioperative Medicine (StEP) initiative, this study aimed to derive a set of standardised and valid measures of mortality, morbidity, and organ failure for use in perioperative clinical trials. METHODS: Three domains of endpoints (mortality, morbidity, and organ failure) were explored through systematic literature review and a three-stage Delphi consensus process using methods consistently applied across the StEP initiative. Reliability, feasibility, and patient-centredness were assessed in round 3 of the consensus process. RESULTS: A high level of consensus was achieved for two mortality time points, 30-day and 1-yr mortality, and these two measures are recommended. No organ failure endpoints achieved threshold criteria for consensus recommendation. The Clavien-Dindo classification of complications achieved threshold criteria for consensus in round 2 of the Delphi process but did not achieve the threshold criteria in round 3 where it scored equivalently to the Post Operative Morbidity Survey. Clavien-Dindo therefore received conditional endorsement as the most widely used measure. No composite measures of organ failure achieved an acceptable level of consensus. CONCLUSIONS: Both 30-day and 1-yr mortality measures are recommended. No measure is recommended for organ failure. One measure (Clavien-Dindo) is conditionally endorsed for postoperative morbidity, but our findings suggest that no single endpoint offers a reliable and valid measure to describe perioperative morbidity that is not dependent on the quality of deli-vered care. Further refinement of current measures, or development of novel measures, of postoperative morbidity might improve consensus in this area.

Intra-abdominal hypertension in cardiac surgery patients: a multicenter observational sub-study of the Accuryn registry.

Intra-abdominal hypertension (IAH) is frequently present in the critically ill and is associated with increased morbidity and mortality. Conventionally, intermittent 'spot-check' manual measurements of bladder pressure in those perceived as high risk are used as surrogates for intra-abdominal pressure (IAP). True patterns of IAH remain unknown. We explored the incidence of IAH in cardiac surgery patients and describe the intra-and postoperative course of IAP using a novel, high frequency, automated bladder pressure measurement system. Sub-analysis of a prospective, multicenter, observational study (NCT04669548) conducted in three large academic medical centers. Continuous urinary output (CUO) and IAP measurements were observed using the Accuryn Monitoring System (Potrero Medical, Hayward, CA). Data collected included demographics, hemodynamic support, and high-frequency IAP and CUO. One Hundred Thirty-Seven cardiac surgery patients were analyzed intraoperatively and followed 48 h postoperatively in the intensive care unit. Median age was 66.4 [58.3, 72.0] years, and 61% were men. Median Foley catheter dwell time was 56.0 [46.8, 77.5] hours, and median baseline IAP was 6.3 [4.0, 8.1] mmHg. 93% (128/137) of patients were in IAH grade I, 82% (113/137) in grade II, 39% (53/137) in grade III, and 5% (7/137) in grade IV for at least 12 cumulative hours. For maximum consecutive duration of IAH, 84% (115/137) of patients spent at least 12 h in grade I, 62% (85/137) in grade II, 18% (25/137) in grade III, and 2% (3/137) in grade IV IAH. During the first 48 h after cardiac surgery, IAH is common and persistent. Improved and automated monitoring of IAP will increase the detection of IAH-which normally would remain undetected using traditional intermittent monitoring methods.

Hemodynamic Responses to Crystalloid and Colloid Fluid Boluses during Noncardiac Surgery.

BACKGROUND: Colloids are thought to sustain blood pressure and cardiac index better than crystalloids. However, the relative effects of intraoperative hydroxyethyl starch and crystalloid administration on the cardiac index and blood pressure remain unclear. This study therefore tested in this subanalysis of a previously published large randomized trial the hypothesis that intraoperative goal-directed colloid administration increases the cardiac index more than goal-directed crystalloid administration. Further, the effects of crystalloid and colloid boluses on blood pressure were evaluated. METHODS: This planned subanalysis of a previous trial analyzed data from 973 patients, of whom 480 were randomized to colloids and 493 were randomized to crystalloids. Fluid administration was guided by esophageal Doppler. The primary outcome was the time-weighted average cardiac index during surgery between the colloid and crystalloid group. The secondary outcomes were the cardiac index just after bolus administration, time elapsed between boluses, and the average real variability during surgery. The study recorded cardiac index, corrected flow time, and blood pressure at 10-min intervals, as well as before and after each bolus. RESULTS: Time-weighted average of cardiac index over the duration of anesthesia was only slightly greater in patients given colloid than crystalloid, with the difference being just 0.20 l · min-1 · m-2 (95% CI, 0.11 to 0.29; P < 0.001). However, the hazard for needing additional boluses was lower after colloid administration (hazard ratio [95% CI], 0.60 [0.55 to 0.66]; P < 0.001) in a frailty time-to-event model accounting for within-subject correlation. The median [quartiles] number of boluses per patient was 4 [2, 6] for colloids and 6 [3, 8] for crystalloids, with a median difference (95% CI) of -1.5 (-2 to -1; P < 0.001). The average real mean arterial pressure variability did not differ significantly between the groups (difference in means [95% CI] of -0.03 (-0.07 to 0.02) mmHg, P = 0.229). CONCLUSIONS: There were not clinically meaningful differences in the cardiac index or mean pressure variability in patients given goal-directed colloid and crystalloids. As might be expected from longer intravascular dwell time, the interval between boluses was longer with colloids. However, on a case basis, the number of boluses differed only slightly. Colloids do not appear to provide substantial hemodynamic benefit.

Prolonged Blood Storage and Risk of Posttransfusion Acute Kidney Injury.

BACKGROUND: Erythrocyte transfusions are independently associated with acute kidney injury. Kidney injury may be consequent to the progressive hematologic changes that develop during storage. This study therefore tested the hypothesis that prolonged erythrocyte storage increases posttransfusion acute kidney injury. METHODS: The Informing Fresh versus Old Red Cell Management (INFORM) trial randomized 31,497 patients to receive either the freshest or oldest available matching erythrocyte units and showed comparable mortality with both. This a priori substudy compared the incidence of posttransfusion acute kidney injury in the randomized groups. Acute kidney injury was defined by the creatinine component of the Kidney Disease: Improving Global Outcomes criteria. RESULTS: The 14,461 patients included in this substudy received 40,077 erythrocyte units. For patients who received more than one unit, the mean age of the blood units was used as the exposure. The median of the mean age of blood units transfused per patient was 11 days [interquartile range, 8, 15] in the freshest available blood group and 23 days [interquartile range, 17, 30] in the oldest available blood group. In the primary analysis, posttransfusion acute kidney injury was observed in 688 of 4,777 (14.4%) patients given the freshest available blood and 1,487 of 9,684 (15.4%) patients given the oldest available blood, with an estimated relative risk (95% CI) of 0.94 (0.86 to 1.02; P = 0.132). The secondary analysis treated blood age as a continuous variable (defined as duration of storage in days), with an estimated relative risk (95% CI) of 1.00 (0.96 to 1.04; P = 0.978) for a 10-day increase in the mean age of erythrocyte units. CONCLUSIONS: In a population of patients without severely impaired baseline renal function receiving fewer than 10 erythrocyte units, duration of blood storage had no effect on the incidence of posttransfusion acute kidney injury.

Preoperative Vitamin D Deficiency Is Associated With Postoperative Delirium in Critically Ill Patients.

INTRODUCTION: Postoperative delirium is common, with a reported incidence of 11% to 80% in critically ill patients. Delirium is an independent prognostic factor for poor hospital outcomes. Low vitamin D concentrations are associated with a decline in cognitive function. We therefore tested the hypothesis that low preoperative serum 25-hydroxyvitamin D [25(OH)D] concentrations are associated with postoperative delirium in critically ill patients. METHOD: We conducted a retrospective analysis of adults in a surgical intensive care unit for at least 48 hours immediately after non-cardiac and non-neurosurgical operations at Cleveland Clinic between 2013 and 2018. Delirium was assessed by trained nurses using CAM-ICU twice daily for the initial 5 postoperative days. Any positive value was considered evidence of delirium. We assessed the association between 25(OH)D concentrations within a year before surgery and the incidence of postoperative delirium using logistic regression, adjusted for potential confounders. A linear spline term with a knot at 30 ng/ml, the threshold for normal 25(OH)D concentration, was added to accommodate a nonlinear relationship between 25(OH)D concentrations and delirium. RESULTS: We included 632 patients, who had a mean (SD) 25(OH)D concentration of 25 (15) ng/ml; 55% (346/632) experienced delirium. We observed an adjusted odds ratio of 1.4 (95% CI: [1.1, 1.8], P = 0.01) for delirium per 10 ng/ml decrease in 25(OH)D concentrations when patients' 25(OH)D concentrations were less than 30 ng/ml. In patients whose 25(OH)D concentrations were at least 30 ng/ml, the adjusted odds ratio was 0.9 (95% CI: [0.7, 1.1], P = 0.36). CONCLUSION: Preoperative 25(OH)D concentrations are associated with postoperative delirium in patients whose concentrations are below the normal threshold, but not at concentrations ≥30 ng/ml. A trial will be needed to determine whether the relationship is causal, and whether vitamin D supplementation before surgery might reduce the incidence of delirium.

Intraoperative Inspiratory Oxygen Fraction and Myocardial Injury After Noncardiac Surgery: Results From an International Observational Study in Relation to Recent Controlled Trials.

BACKGROUND: Two trials reported that a high inspiratory oxygen fraction (F io2 ) does not promote myocardial infarction or death. Observational studies can provide larger statistical strength, but associations can be due to unobserved confounding. Therefore, we evaluated the association between intraoperative F io2 and cardiovascular complications in a large international cohort study to see if spurious associations were observed. METHODS: We included patients from the Vascular events In noncardiac Surgery patIents cOhort evaluatioN (VISION) study, who were ≥45 years of age, scheduled for overnight hospital admission, and had intraoperative F io2 recorded. The primary outcome was myocardial injury after noncardiac surgery (MINS), and secondary outcomes included mortality and pneumonia, all within 30 postoperative days. Data were analyzed with logistic regression, adjusted for many baseline cardiovascular risk factors, and illustrated in relation to findings from 2 recent controlled trials. RESULTS: We included 6588 patients with mean age of 62 years of whom 49% had hypertension. The median intraoperative F io2 was 0.46 (5%-95% range, 0.32-0.94). There were 808 patients (12%) with MINS. Each 0.10 increase in median F io2 was associated with a confounder-adjusted increase in odds for MINS: odds ratio (OR), 1.17 (95% confidence interval [CI], 1.12-1.23; P < .0001). MINS occurred in contrast with similar frequencies and no significant difference in controlled trials (2240 patients, 194 events), in which patients were given 80% vs 30% oxygen. Mortality was 2.4% and was not significantly associated with a median F io2 (OR, 1.07; 95% CI, 0.97-1.19 per 0.10 increase; P = .18), and 2.9% of patients had pneumonia (OR, 1.05; 95% CI, 0.95-1.15 per 0.10 increase; P = .34). CONCLUSIONS: We observed an association between intraoperative F io2 and risk of myocardial injury within 30 days after noncardiac surgery, which contrasts with recent controlled clinical trials. F io2 was not significantly associated with mortality or pneumonia. Unobserved confounding presumably contributed to the observed association between F io2 and myocardial injury that is not supported by trials.

Supplemental Intraoperative Oxygen and Long-term Mortality: Subanalysis of a Multiple Crossover Cluster Trial.

BACKGROUND: Whether supplemental oxygen worsens long-term mortality remains unclear, with contradictory trial results. The authors therefore tested the hypothesis that supplemental oxygen (80% vs. 30%) increases the hazard for long-term mortality. METHODS: The authors conducted a post hoc analysis of a large multiple crossover cluster trial in which more than 5,000 colorectal surgeries on 4,088 adults were allocated to receive either 30% or 80% inspired oxygen during general anesthesia. The authors assessed the effect of 80% versus 30% target-inspired oxygen on long-term mortality and calculated Kaplan-Meier survival estimates. Analysis was restricted to patients with a home address in Ohio because the authors could obtain reliable vital status information from the Ohio Department of Health (Columbus, Ohio) for them. RESULTS: A total of 3,471 qualifying colorectal surgeries performed in 2,801 patients were analyzed, including 1,753 (51%) surgeries in 1,577 patients given 80% oxygen and 1,718 surgeries in 1,551 patients given 30% oxygen. The observed incidence of death after a median of 3 yr was 13% (234 of 1,753) in the 80% oxygen group and 14% (245 of 1,718) in the 30% oxygen group. The estimated hazard ratio for mortality was 0.94 (95% CI, 0.78 to 1.13; P = 0.493). CONCLUSIONS: In this post hoc analysis of a large, controlled trial, supplemental oxygen did not increase postoperative mortality.

Systematic review and consensus definitions for the Standardized Endpoints in Perioperative Medicine (StEP) initiative: cardiovascular outcomes.

BACKGROUND: Adverse cardiovascular events are a leading cause of perioperative morbidity and mortality. The definitions of perioperative cardiovascular adverse events are heterogeneous. As part of the international Standardized Endpoints in Perioperative Medicine initiative, this study aimed to find consensus amongst clinical trialists on a set of standardised and valid cardiovascular outcomes for use in future perioperative clinical trials. METHODS: We identified currently used perioperative cardiovascular outcomes by a systematic review of the anaesthesia and perioperative medicine literature (PubMed/Ovid, Embase, and Cochrane Library). We performed a three-stage Delphi consensus-gaining process that involved 55 clinician researchers worldwide. Cardiovascular outcomes were first shortlisted and the most suitable definitions determined. These cardiovascular outcomes were then assessed for validity, reliability, feasibility, and clarity. RESULTS: We identified 18 cardiovascular outcomes. Participation in the three Delphi rounds was 100% (n=19), 71% (n=55), and 89% (n=17), respectively. A final list of nine cardiovascular outcomes was elicited from the consensus: myocardial infarction, myocardial injury, cardiovascular death, non-fatal cardiac arrest, coronary revascularisation, major adverse cardiac events, pulmonary embolism, deep vein thrombosis, and atrial fibrillation. These nine cardiovascular outcomes were rated by the majority of experts as valid, reliable, feasible, and clearly defined. CONCLUSIONS: These nine consensus cardiovascular outcomes can be confidently used as endpoints in clinical trials designed to evaluate perioperative interventions with the goal of improving perioperative outcomes.

Preoperative N-Terminal Pro-B-Type Natriuretic Peptide and Cardiovascular Events After Noncardiac Surgery: A Cohort Study.

Background: Preliminary data suggest that preoperative N-terminal pro-B-type natriuretic peptide (NT-proBNP) may improve risk prediction in patients undergoing noncardiac surgery. Objective: To determine whether preoperative NT-proBNP has additional predictive value beyond a clinical risk score for the composite of vascular death and myocardial injury after noncardiac surgery (MINS) within 30 days after surgery. Design: Prospective cohort study. Setting: 16 hospitals in 9 countries. Patients: 10 402 patients aged 45 years or older having inpatient noncardiac surgery. Measurements: All patients had NT-proBNP levels measured before surgery and troponin T levels measured daily for up to 3 days after surgery. Results: In multivariable analyses, compared with preoperative NT-proBNP values less than 100 pg/mL (the reference group), those of 100 to less than 200 pg/mL, 200 to less than 1500 pg/mL, and 1500 pg/mL or greater were associated with adjusted hazard ratios of 2.27 (95% CI, 1.90 to 2.70), 3.63 (CI, 3.13 to 4.21), and 5.82 (CI, 4.81 to 7.05) and corresponding incidences of the primary outcome of 12.3% (226 of 1843), 20.8% (542 of 2608), and 37.5% (223 of 595), respectively. Adding NT-proBNP thresholds to clinical stratification (that is, the Revised Cardiac Risk Index [RCRI]) resulted in a net absolute reclassification improvement of 258 per 1000 patients. Preoperative NT-proBNP values were also statistically significantly associated with 30-day all-cause mortality (less than 100 pg/mL [incidence, 0.3%], 100 to less than 200 pg/mL [incidence, 0.7%], 200 to less than 1500 pg/mL [incidence, 1.4%], and 1500 pg/mL or greater [incidence, 4.0%]). Limitation: External validation of the identified NT-proBNP thresholds in other cohorts would reinforce our findings. Conclusion: Preoperative NT-proBNP is strongly associated with vascular death and MINS within 30 days after noncardiac surgery and improves cardiac risk prediction in addition to the RCRI. Primary Funding Source: Canadian Institutes of Health Research.

Risk of stroke and other adverse outcomes in patients with perioperative atrial fibrillation 1 year after non-cardiac surgery.

AIMS: To determine the 1-year risk of stroke and other adverse outcomes in patients with a new diagnosis of perioperative atrial fibrillation (POAF) after non-cardiac surgery. METHODS AND RESULTS: The PeriOperative ISchemic Evaluation (POISE)-1 trial evaluated the effects of metoprolol vs. placebo in 8351 patients, and POISE-2 compared the effect of aspirin vs. placebo, and clonidine vs. placebo in 10 010 patients. These trials included patients with, or at risk of, cardiovascular disease who were undergoing non-cardiac surgery. For the purpose of this study, we combined the POISE datasets, excluding 244 patients who were in atrial fibrillation (AF) at the time of randomization. Perioperative atrial fibrillation was defined as new AF that occurred within 30 days after surgery. Our primary outcome was the incidence of stroke at 1 year of follow-up; secondary outcomes were mortality and myocardial infarction (MI). We compared outcomes among patients with and without POAF using multivariable adjusted Cox proportional hazards models. Among 18 117 patients (mean age 69 years, 57.4% male), 404 had POAF (2.2%). The stroke incidence 1 year after surgery was 5.58 vs. 1.54 per 100 patient-years in patients with and without POAF, adjusted hazard ratio (aHR) 3.43, 95% confidence interval (CI) 2.00-5.90; P < 0.001. Patients with POAF also had an increased risk of death (incidence 31.37 vs. 9.34; aHR 2.51, 95% CI 2.01-3.14; P < 0.001) and MI (incidence 26.20 vs. 8.23; aHR 5.10, 95% CI 3.91-6.64; P < 0.001). CONCLUSION: Patients with POAF have a significantly increased risk of stroke, MI, and death at 1 year. Intervention studies are needed to evaluate risk reduction strategies in this high-risk population.

Recurrence of breast cancer after regional or general anaesthesia: a randomised controlled trial.

BACKGROUND: Three perioperative factors impair host defence against recurrence during cancer surgery: the surgical stress response, use of volatile anaesthetic, and opioids for analgesia. All factors are ameliorated by regional anaesthesia-analgesia. We tested the primary hypothesis that breast cancer recurrence after potentially curative surgery is lower with regional anaesthesia-analgesia using paravertebral blocks and the anaesthetic propofol than with general anaesthesia with the volatile anaesthetic sevoflurane and opioid analgesia. A second hypothesis was that regional anaesthesia-analgesia reduces persistent incisional pain. METHODS: We did a randomised controlled trial at 13 hospitals in Argentina, Austria, China, Germany, Ireland, New Zealand, Singapore, and the USA. Women (age <85 years) having potentially curative primary breast cancer resections were randomised by computer to either regional anaesthesia-analgesia (paravertebral blocks and propofol) or general anaesthesia (sevoflurane) and opioid analgesia. The primary outcome was local or metastatic breast cancer recurrence. The secondary outcome was incisional pain at 6 months and 12 months. Primary analyses were done under intention-to-treat principles. This trial is registered with ClinicalTrials.gov, NCT00418457. The study was stopped after a preplanned futility boundary was crossed. FINDINGS: Between Jan 30, 2007, and Jan 18, 2018, 2132 women were enrolled to the study, of whom 24 were excluded before surgery. 1043 were assigned to regional anaesthesia-analgesia and 1065 were allocated to general anaesthesia. Baseline characteristics were well balanced between study groups. Median follow-up was 36 (IQR 24-49) months. Among women assigned regional anaesthesia-analgesia, 102 (10%) recurrences were reported, compared with 111 (10%) recurrences among those allocated general anaesthesia (hazard ratio 0·97, 95% CI 0·74-1·28; p=0·84). Incisional pain was reported by 442 (52%) of 856 patients assigned to regional anaesthesia-analgesia and 456 (52%) of 872 patients allocated to general anaesthesia at 6 months, and by 239 (28%) of 854 patients and 232 (27%) of 852 patients, respectively, at 12 months (overall interim-adjusted odds ratio 1·00, 95% CI 0·85-1·17; p=0·99). Neuropathic breast pain did not differ by anaesthetic technique and was reported by 87 (10%) of 859 patients assigned to regional anaesthesia-analgesia and 89 (10%) of 870 patients allocated to general anaesthesia at 6 months, and by 57 (7%) of 857 patients and 57 (7%) of 854 patients, respectively, at 12 months. INTERPRETATION: In our study population, regional anaesthesia-analgesia (paravertebral block and propofol) did not reduce breast cancer recurrence after potentially curative surgery compared with volatile anaesthesia (sevoflurane) and opioids. The frequency and severity of persistent incisional breast pain was unaffected by anaesthetic technique. Clinicians can use regional or general anaesthesia with respect to breast cancer recurrence and persistent incisional pain. FUNDING: Sisk Healthcare Foundation (Ireland), Eccles Breast Cancer Research Fund, British Journal of Anaesthesia International, College of Anaesthetists of Ireland, Peking Union Medical College Hospital, Science Fund for Junior Faculty 2016, Central Bank of Austria, and National Healthcare Group.

Deficit Accumulation and Phenotype Assessments of Frailty Both Poorly Predict Duration of Hospitalization and Serious Complications after Noncardiac Surgery.

BACKGROUND: Frailty is associated with adverse postoperative outcomes, but it remains unclear which measure of frailty is best. This study compared two approaches: the Modified Frailty Index, which is a deficit accumulation model (number of accumulated deficits), and the Hopkins Frailty Score, which is a phenotype model (consisting of shrinking, weakness, exhaustion, slowness, and low physical activity). The primary aim was to compare the ability of each frailty score to predict prolonged hospitalization. Secondarily, the ability of each score to predict 30-day readmission and/or postoperative complications was compared. METHODS: This study prospectively enrolled adults presenting for preanesthesia evaluation before elective noncardiac surgery. The Hopkins Frailty Score and Modified Frailty Index were both determined. The ability of each frailty score to predict the primary outcome (prolonged hospitalization) was compared using a ratio of root-mean-square prediction errors from linear regression models. The ability of each score to predict the secondary outcome (readmission and complications) was compared using ratio of root-mean-square prediction errors from logistic regression models. RESULTS: The study included 1,042 patients. The frailty rates were 23% (Modified Frailty Index of 4 or higher) and 18% (Hopkins Frailty Score of 3 or higher). In total, 12.9% patients were readmitted or had postoperative complications. The error of the Modified Frailty Index and Hopkins Frailty Score in predicting the primary outcome was 2.5 (95% CI, 2.2, 2.9) and 2.6 (95% CI, 2.2, 3.0) days, respectively, and their ratio was 1.0 (95% CI, 1.0, 1.0), indicating similarly poor prediction. Similarly, the error of respective frailty scores in predicting the probability of secondary outcome was high, specifically 0.3 (95% CI, 0.3, 0.4) and 0.3 (95% CI, 0.3, 0.4), and their ratio was 1.00 (95% CI, 1.0, 1.0). CONCLUSIONS: The Modified Frailty Index and Hopkins Frailty Score were similarly poor predictors of perioperative risk. Further studies, with different frailty screening tools, are needed to identify the best method to measure perioperative frailty.

Multimodal Analgesic Regimen for Spine Surgery: A Randomized Placebo-controlled Trial.

BACKGROUND: Various multimodal analgesic approaches have been proposed for spine surgery. The authors evaluated the effect of using a combination of four nonopioid analgesics versus placebo on Quality of Recovery, postoperative opioid consumption, and pain scores. METHODS: Adults having multilevel spine surgery who were at high risk for postoperative pain were double-blind randomized to placebos or the combination of single preoperative oral doses of acetaminophen 1,000 mg and gabapentin 600 mg, an infusion of ketamine 5 µg/kg/min throughout surgery, and an infusion of lidocaine 1.5 mg/kg/h intraoperatively and during the initial hour of recovery. Postoperative analgesia included acetaminophen, gabapentin, and opioids. The primary outcome was the Quality of Recovery 15-questionnaire (0 to 150 points, with 15% considered to be a clinically important difference) assessed on the third postoperative day. Secondary outcomes were opioid use in morphine equivalents (with 20% considered to be a clinically important change) and verbal-response pain scores (0 to 10, with a 1-point change considered important) over the initial postoperative 48 h. RESULTS: The trial was stopped early for futility per a priori guidelines. The average duration ± SD of surgery was 5.4 ± 2.1 h. The mean ± SD Quality of Recovery score was 109 ± 25 in the pathway patients (n = 150) versus 109 ± 23 in the placebo group (n = 149); estimated difference in means was 0 (95% CI, -6 to 6, P = 0.920). Pain management within the initial 48 postoperative hours was not superior in analgesic pathway group: 48-h opioid consumption median (Q1, Q3) was 72 (48, 113) mg in the analgesic pathway group and 75 (50, 152) mg in the placebo group, with the difference in medians being -9 (97.5% CI, -23 to 5, P = 0.175) mg. Mean 48-h pain scores were 4.8 ± 1.8 in the analgesic pathway group versus 5.2 ± 1.9 in the placebo group, with the difference in means being -0.4 (97.5% CI; -0.8, 0.1, P = 0.094). CONCLUSIONS: An analgesic pathway based on preoperative acetaminophen and gabapentin, combined with intraoperative infusions of lidocaine and ketamine, did not improve recovery in patients who had multilevel spine surgery.

Saline versus Lactated Ringer's Solution: The Saline or Lactated Ringer's (SOLAR) Trial.

BACKGROUND: Both saline and lactated Ringer's solutions are commonly given to surgical patients. However, hyperchloremic acidosis consequent to saline administration may provoke complications. The authors therefore tested the primary hypothesis that a composite of in-hospital mortality and major postoperative complications is less common in patients given lactated Ringer's solution than normal saline. METHODS: The authors conducted an alternating cohort controlled trial in which adults having colorectal and orthopedic surgery were given either lactated Ringer's solution or normal saline in 2-week blocks between September 2015 and August 2018. The primary outcome was a composite of in-hospital mortality and major postoperative renal, respiratory, infectious, and hemorrhagic complications. The secondary outcome was postoperative acute kidney injury. RESULTS: Among 8,616 qualifying patients, 4,187 (49%) were assigned to lactated Ringer's solution, and 4,429 (51%) were assigned to saline. Each group received a median 1.9 l of fluid. The primary composite of major complications was observed in 5.8% of lactated Ringer's versus 6.1% of normal saline patients, with estimated average relative risk across the components of the composite of 1.16 (95% CI, 0.89 to 1.52; P = 0.261). The secondary outcome, postoperative acute kidney injury, Acute Kidney Injury Network stage I-III versus 0, occurred in 6.6% of lactated Ringer's patients versus 6.2% of normal saline patients, with an estimated relative risk of 1.18 (99.3% CI, 0.99 to 1.41; P = 0.009, significance criterion of 0.007). Absolute differences between the treatment groups for each outcome were less than 0.5%, an amount that is not clinically meaningful. CONCLUSIONS: In elective orthopedic and colorectal surgery patients, there was no clinically meaningful difference in postoperative complications with lactated Ringer's or saline volume replacement. Clinicians can reasonably use either solution intraoperatively.

Preoperative Vitamin D Concentration and Cardiac, Renal, and Infectious Morbidity after Noncardiac Surgery.

BACKGROUND: Low 25-hydroxyvitamin D is associated with cardiovascular, renal, and infectious risks. Postsurgical patients are susceptible to similar complications, but whether vitamin D deficiency contributes to postoperative complications remains unclear. We tested whether low preoperative vitamin D is associated with cardiovascular events within 30 days after noncardiac surgery. METHODS: We evaluated a subset of patients enrolled in the biobank substudy of the Vascular events In noncardiac Surgery patIents cOhort evaluatioN (VISION) study, who were at least 45 yr with at least an overnight hospitalization. Blood was collected preoperatively, and 25-hydroxyvitamin D was measured in stored samples. The primary outcome was the composite of cardiovascular events (death, myocardial injury, nonfatal cardiac arrest, stroke, congestive heart failure) within 30 postoperative days. Secondary outcomes were kidney injury and infectious complications. RESULTS: A total of 3,851 participants were eligible for analysis. Preoperative 25-hydroxyvitamin D concentration was 70 ± 30 nmol/l, and 62% of patients were vitamin D deficient. Overall, 26 (0.7%) patients died, 41 (1.1%) had congestive heart failure or nonfatal cardiac arrest, 540 (14%) had myocardial injury, and 15 (0.4%) had strokes. Preoperative vitamin D concentration was not associated with the primary outcome (average relative effect odds ratio [95% CI]: 0.93 [0.85, 1.01] per 10 nmol/l increase in preoperative vitamin D, P = 0.095). However, it was associated with postoperative infection (average relative effect odds ratio [95% CI]: 0.94 [0.90, 0.98] per 10 nmol/l increase in preoperative vitamin D, P adjusted value = 0.005) and kidney function (estimated mean change in postoperative estimated glomerular filtration rate [95% CI]: 0.29 [0.11, 0.48] ml min 1.73 m per 10 nmol/l increase in preoperative vitamin D, P adjusted value = 0.004). CONCLUSIONS: Preoperative vitamin D was not associated with a composite of postoperative 30-day cardiac outcomes. However, there was a significant association between vitamin D deficiency and a composite of infectious complications and decreased kidney function. While renal effects were not clinically meaningful, the effect of vitamin D supplementation on infectious complications requires further study.

One-year Results of a Factorial Randomized Trial of Aspirin versus Placebo and Clonidine versus Placebo in Patients Having Noncardiac Surgery.

BACKGROUND: The authors previously reported that perioperative aspirin and/or clonidine does not prevent a composite of death or myocardial infarction 30 days after noncardiac surgery. Moreover, aspirin increased the risk of major bleeding and clonidine caused hypotension and bradycardia. Whether these complications produce harm at 1 yr remains unknown. METHODS: The authors randomized 10,010 patients with or at risk of atherosclerosis and scheduled for noncardiac surgery in a 1:1:1:1 ratio to clonidine/aspirin, clonidine/aspirin placebo, clonidine placebo/aspirin, or clonidine placebo/aspirin placebo. Patients started taking aspirin or placebo just before surgery; those not previously taking aspirin continued daily for 30 days, and those taking aspirin previously continued for 7 days. Patients were also randomly assigned to receive clonidine or placebo just before surgery, with the study drug continued for 72 h. RESULTS: Neither aspirin nor clonidine had a significant effect on the primary 1-yr outcome, a composite of death or nonfatal myocardial infarction, with a 1-yr hazard ratio for aspirin of 1.00 (95% CI, 0.89 to 1.12; P = 0.948; 586 patients [11.8%] vs. 589 patients [11.8%]) and a hazard ratio for clonidine of 1.07 (95% CI, 0.96 to 1.20; P = 0.218; 608 patients [12.1%] vs. 567 patients [11.3%]), with effect on death or nonfatal infarction. Reduction in death and nonfatal myocardial infarction from aspirin in patients who previously had percutaneous coronary intervention at 30 days persisted at 1 yr. Specifically, the hazard ratio was 0.58 (95% CI, 0.35 to 0.95) in those with previous percutaneous coronary intervention and 1.03 (95% CI, 0.91to 1.16) in those without (interaction P = 0.033). There was no significant effect of either drug on death, cardiovascular complications, cancer, or chronic incisional pain at 1 yr (all P > 0.1). CONCLUSIONS: Neither perioperative aspirin nor clonidine have significant long-term effects after noncardiac surgery. Perioperative aspirin in patients with previous percutaneous coronary intervention showed persistent benefit at 1 yr, a plausible sub-group effect.