Tranexamic Acid in Patients Undergoing Noncardiac Surgery.

BACKGROUND: Perioperative bleeding is common in patients undergoing noncardiac surgery. Tranexamic acid is an antifibrinolytic drug that may safely decrease such bleeding. METHODS: We conducted a trial involving patients undergoing noncardiac surgery. Patients were randomly assigned to receive tranexamic acid (1-g intravenous bolus) or placebo at the start and end of surgery (reported here) and, with the use of a partial factorial design, a hypotension-avoidance or hypertension-avoidance strategy (not reported here). The primary efficacy outcome was life-threatening bleeding, major bleeding, or bleeding into a critical organ (composite bleeding outcome) at 30 days. The primary safety outcome was myocardial injury after noncardiac surgery, nonhemorrhagic stroke, peripheral arterial thrombosis, or symptomatic proximal venous thromboembolism (composite cardiovascular outcome) at 30 days. To establish the noninferiority of tranexamic acid to placebo for the composite cardiovascular outcome, the upper boundary of the one-sided 97.5% confidence interval for the hazard ratio had to be below 1.125, and the one-sided P value had to be less than 0.025. RESULTS: A total of 9535 patients underwent randomization. A composite bleeding outcome event occurred in 433 of 4757 patients (9.1%) in the tranexamic acid group and in 561 of 4778 patients (11.7%) in the placebo group (hazard ratio, 0.76; 95% confidence interval [CI], 0.67 to 0.87; absolute difference, -2.6 percentage points; 95% CI, -3.8 to -1.4; two-sided P<0.001 for superiority). A composite cardiovascular outcome event occurred in 649 of 4581 patients (14.2%) in the tranexamic acid group and in 639 of 4601 patients (13.9%) in the placebo group (hazard ratio, 1.02; 95% CI, 0.92 to 1.14; upper boundary of the one-sided 97.5% CI, 1.14; absolute difference, 0.3 percentage points; 95% CI, -1.1 to 1.7; one-sided P = 0.04 for noninferiority). CONCLUSIONS: Among patients undergoing noncardiac surgery, the incidence of the composite bleeding outcome was significantly lower with tranexamic acid than with placebo. Although the between-group difference in the composite cardiovascular outcome was small, the noninferiority of tranexamic acid was not established. (Funded by the Canadian Institutes of Health Research and others; POISE-3 ClinicalTrials.gov number, NCT03505723.).

Evaluation and Management of Pulmonary Hypertension in Noncardiac Surgery: A Scientific Statement From the American Heart Association.

Pulmonary hypertension, defined as an elevation in blood pressure in the pulmonary arteries, is associated with an increased risk of death. The prevalence of pulmonary hypertension is increasing, with an aging population, a rising prevalence of heart and lung disease, and improved pulmonary hypertension survival with targeted therapies. Patients with pulmonary hypertension frequently require noncardiac surgery, although pulmonary hypertension is associated with excess perioperative morbidity and death. This scientific statement provides guidance on the evaluation and management of pulmonary hypertension in patients undergoing noncardiac surgery. We advocate for a multistep process focused on (1) classification of pulmonary hypertension group to define the underlying pathology; (2) preoperative risk assessment that will guide surgical decision-making; (3) pulmonary hypertension optimization before surgery to reduce perioperative risk; (4) intraoperative management of pulmonary hypertension to avoid right ventricular dysfunction and to maintain cardiac output; and (5) postoperative management of pulmonary hypertension to ensure recovery from surgery. Last, this scientific statement highlights the paucity of evidence to support perioperative pulmonary hypertension management and identifies areas of uncertainty and opportunities for future investigation.

Metformin Use in Type 2 Diabetics and Delirium After Noncardiac Surgery: A Retrospective Cohort Analysis.

INTRODUCTION: The cause of postoperative delirium is unknown, but it is thought to result at least in part from inflammation. Metformin, besides its hypoglycemic properties, demonstrates anti-inflammatory effects systemically and in the brain. We tested the primary hypothesis that chronic metformin use in adults with type 2 diabetes is associated with less delirium during the first 5 days after major noncardiac surgery. Secondary outcomes were a composite of serious complications (myocardial infarction, cardiac arrest, stage 2-3 acute kidney injury [AKI], and mortality) and time to discharge alive. METHODS: We considered adults with type 2 diabetes who did or did not routinely use metformin daily and had noncardiac surgery. Delirium was assessed by Confusion Assessment Method for Intensive Care Unit (CAM-ICU) or brief Confusion Assessment Method (bCAM) for 5 postoperative days. Postoperative AKI was defined by Kidney Disease Improving Global Guidelines. Logistic regression and generalized estimating equation models accounted for within-patient correlation across multiple surgeries and explored the association between metformin use and postoperative delirium and complications. Inverse propensity score weighting and propensity score calibration (PSC) adjusted for confounding variables. RESULTS: No significant difference was observed in the incidence of postoperative delirium between the 2 groups, with 260 of 4744 cases (5.5%) among metformin users and 502 of 5918 cases (8.5%) cases in nonmetformin users, for an odds ratio of 0.88 (95% confidence interval [CI], 0.73-1.05; P = .155), number-needed-to-expose = 118 patients. Similarly, there were fewer composite complications in metformin users (3.3%) than in nonusers (11.7%); However, the common-effect odds ratio of 0.67 was not statistically significant (97.5% CI, 0.39-1.17; P = .106). Discharge from the hospital was significantly faster in patients who took metformin (3 [interquartile range, IQR, 1-5] days for metformin users and 3 [IQR, 2-6] days for nonmetformin users), with a hazard ratio of 1.07 for early discharge, and tight CIs (1.01-1.13). CONCLUSIONS: Chronic metformin use was associated with slightly and nonsignificantly less delirium. However, patients who used metformin had clinically meaningfully fewer major complications, mostly stage 2 to 3 kidney injury. While not statistically significant, the reduction was substantial and warrants further investigation because there is currently no effective preventive measure for perioperative renal injury. Benefit would be especially meaningful if it could be produced by acute perioperative treatment. Finally, metformin was associated with faster hospital discharge, although not by a clinically meaningful amount.

Association of Intravenous Neostigmine and Anticholinergics or Sugammadex with Postoperative Delirium: A Retrospective Cohort Study.

BACKGROUND: Administration of cholinesterase inhibitors in combination with anticholinergic drugs for reversal of neuromuscular blocks may precipitate delirium through impairment of central cholinergic transmission, which could be avoided by using sugammadex. Therefore, we tested the primary hypothesis that postoperative delirium is less common when neuromuscular block is reversed with sugammadex than with neostigmine combined with glycopyrrolate or atropine. METHODS: We conducted a single-center retrospective cohort study, analyzing all adult patients having general anesthesia for noncardiac surgery who received neostigmine or sugammadex from January 2016 to March 2022. Inverse propensity score weighting and propensity score calibration were used to adjust for appropriate confounders. Our primary outcome was presence of delirium within the first 4 days after surgery, defined as at least 1 positive brief Confusion Assessment Method (bCAM) screening. The secondary outcome was the presence of early delirium within 24 hours of surgery. RESULTS: Among 49,468 cases in our analysis, 6881 received sugammadex and 42,587 received neostigmine. After propensity weighting, the incidence of delirium was 1.09% in the sugammadex group and 0.82% in the neostigmine group. The odds of postoperative delirium did not differ between the sugammadex and neostigmine groups, with an estimated odds ratio (95% confidence interval) of 1.33 (0.91-1.95), P = .147. A sensitivity analysis restricted to only include cases with at least 6 bCAM measurements over postoperative day (POD) 1 to 4 had consistent results, as sugammadex compared with neostigmine was associated with an estimated odds ratio for postoperative delirium of 1.20 (0.82-1.77), P = .346. Sugammadex was significantly associated with an increased incidence of early postoperative delirium, with an estimated odds ratio of 1.71 (1.07-2.72), P = .025. Further analysis showed no treatment-by-age interaction for either postoperative delirium (P = .637) or postoperative early delirium (P = .904). CONCLUSIONS: Compared to neostigmine, use of sugammadex for reversal of neuromuscular block was not associated with an increased risk of postoperative delirium in this retrospective single-center study. Though sugammadex was associated with a statistically significant increased risk of postoperative early delirium, the difference was small and not clinically relevant, and may reflect the presence of unknown confounders.

Association Between Age- and Sex-Specific Body Mass Index Percentile and Multiple Intubation Attempts: A Retrospective Cohort Analysis.

BACKGROUND: Obesity distorts airways and slightly complicates intubations in adults, but whether obesity complicates pediatric intubations remains unclear. We, therefore, tested the primary hypothesis that increasing age- and sex-specific body mass index (BMI) percentile is associated with difficult intubation, defined as >1 intubation attempt. METHODS: We conducted a retrospective analysis of pediatric patients between 2 and 18 years of age who had noncardiac surgery with oral endotracheal intubation. We assessed the association between BMI percentile and difficult intubation, defined as >1 intubation attempt, using a confounder-adjusted multivariable logistic regression model. Secondarily, we assessed whether the main association depended on preoperative substantial airway abnormality status or age group. RESULTS: A total of 9339 patients were included in the analysis. Median [quartiles] age- and sex-specific BMI percentile was 70 [33, 93], and 492 (5.3%) patients had difficult intubation. There was no apparent association between age- and sex-specific BMI percentile and difficult intubation. The estimated odds ratio (OR) for having difficult intubation for a 10-unit increase in BMI percentile was 0.98 (95% confidence interval [CI], 0.95-1.005) and was consistent across the 3 age groups of early childhood, middle childhood, and early adolescence (interaction P = .53). Patients with preoperative substantial airway abnormalities had lower odds of difficult intubation per 10-unit increase in BMI percentile, with OR (95% CI) of 0.83 (0.70-0.98), P = .01. CONCLUSIONS: Age- and sex-specific BMI percentile was not associated with difficult intubation in children between 2 and 18 years of age. As in adults, obesity in children does not much complicate intubation.

Association Between Cannabis Use and Opioid Consumption, Pain, and Respiratory Complications After Surgery: A Retrospective Cohort Analysis.

BACKGROUND: Cannabis is a widely used illicit drug with effects on different pain pathways. However, interactions between cannabis and postoperative pain are unclear. Cannabis smoking also affects the lungs, but the impact of cannabis use on postoperative pulmonary complications is unknown. We hypothesized that preoperative cannabis use in adults having elective surgery is associated with higher postoperative opioid consumption. Secondarily, we tested the hypothesis that cannabis use is associated with higher pain scores, hypoxemia (oxygen saturation [Spo2]/fraction of inspired oxygen [Fio2] ratio), and higher postoperative pulmonary complications compared to nonuse of cannabis. METHODS: In this retrospective study, we included adult patients who had elective surgeries at Cleveland Clinic Main Campus between January 2010 and December 2020. The exposure was use of cannabis within 30 days before surgery, and the control group never used cannabis. Patients who had regional anesthesia or chronic pain diagnosis were excluded. The primary outcome was postoperative opioid consumption; 3 secondary outcomes were time-weighted average (TWA) postoperative pain score, TWA Spo2/Fio2 ratio, and composite of pulmonary complications after surgery. We assessed the association between cannabis use and opioid consumption during the first 24 postoperative hours using linear regression on log-transformed opioid consumption with a propensity score-based method (inverse probability of treatment weighting [IPTW]) adjusting for confounders. We further adjusted for imbalanced confounding variables after IPTW was applied. RESULTS: In total, 1683 of 34,521 patients were identified as cannabis users. Cannabis use was associated with increased opioid consumption, with an adjusted ratio of geometric means (95% confidence interval [CI]) of 1.30 (1.22-1.38; P < .0001) for cannabis users versus nonusers. Secondarily, (1) cannabis use was associated with increased TWA pain score, with a difference in means of 0.57 (95% CI, 0.46-0.67; P < .0001); (2) cannabis use was not associated with TWA Spo2/Fio2, with an adjusted difference in means of 0.5 (95% CI, -3.1 to 4.2; P = .76); and (3) cannabis use was not associated with a collapsed composite of pulmonary complications, with estimated odds ratio of 0.90 (95% CI, 0.71-1.13; P = .34). CONCLUSIONS: Adult cannabis users undergoing surgeries were found to have significantly higher postoperative opioid consumption and pain scores than nonusers. Cannabis use did not have a clinically meaningful association with hypoxia or composite pulmonary complications.

Hypotension-Avoidance Versus Hypertension-Avoidance Strategies in Noncardiac Surgery : An International Randomized Controlled Trial.

BACKGROUND: Among patients having noncardiac surgery, perioperative hemodynamic abnormalities are associated with vascular complications. Uncertainty remains about what intraoperative blood pressure to target and how to manage long-term antihypertensive medications perioperatively. OBJECTIVE: To compare the effects of a hypotension-avoidance and a hypertension-avoidance strategy on major vascular complications after noncardiac surgery. DESIGN: Partial factorial randomized trial of 2 perioperative blood pressure management strategies (reported here) and tranexamic acid versus placebo. (ClinicalTrials.gov: NCT03505723). SETTING: 110 hospitals in 22 countries. PATIENTS: 7490 patients having noncardiac surgery who were at risk for vascular complications and were receiving 1 or more long-term antihypertensive medications. INTERVENTION: In the hypotension-avoidance strategy group, the intraoperative mean arterial pressure target was 80 mm Hg or greater; before and for 2 days after surgery, renin-angiotensin-aldosterone system inhibitors were withheld and the other long-term antihypertensive medications were administered only for systolic blood pressures 130 mm Hg or greater, following an algorithm. In the hypertension-avoidance strategy group, the intraoperative mean arterial pressure target was 60 mm Hg or greater; all antihypertensive medications were continued before and after surgery. MEASUREMENTS: The primary outcome was a composite of vascular death and nonfatal myocardial injury after noncardiac surgery, stroke, and cardiac arrest at 30 days. Outcome adjudicators were masked to treatment assignment. RESULTS: The primary outcome occurred in 520 of 3742 patients (13.9%) in the hypotension-avoidance group and in 524 of 3748 patients (14.0%) in the hypertension-avoidance group (hazard ratio, 0.99 [95% CI, 0.88 to 1.12]; P = 0.92). Results were consistent for patients who used 1 or more than 1 antihypertensive medication in the long term. LIMITATION: Adherence to the assigned strategies was suboptimal; however, results were consistent across different adherence levels. CONCLUSION: In patients having noncardiac surgery, our hypotension-avoidance and hypertension-avoidance strategies resulted in a similar incidence of major vascular complications. PRIMARY FUNDING SOURCE: Canadian Institutes of Health Research, National Health and Medical Research Council (Australia), and Research Grant Council of Hong Kong.

Video Laryngoscopy vs Direct Laryngoscopy for Endotracheal Intubation in the Operating Room: A Cluster Randomized Clinical Trial.

Importance: Endotracheal tubes are typically inserted in the operating room using direct laryngoscopy. Video laryngoscopy has been reported to improve airway visualization; however, whether improved visualization reduces intubation attempts in surgical patients is unclear. Objective: To determine whether the number of intubation attempts per surgical procedure is lower when initial laryngoscopy is performed using video laryngoscopy or direct laryngoscopy. Design, Setting, and Participants: Cluster randomized multiple crossover clinical trial conducted at a single US academic hospital. Patients were adults aged 18 years or older having elective or emergent cardiac, thoracic, or vascular surgical procedures who required single-lumen endotracheal intubation for general anesthesia. Patients were enrolled from March 30, 2021, to December 31, 2022. Data analysis was based on intention to treat. Interventions: Two sets of 11 operating rooms were randomized on a 1-week basis to perform hyperangulated video laryngoscopy or direct laryngoscopy for the initial intubation attempt. Main Outcomes and Measures: The primary outcome was the number of operating room intubation attempts per surgical procedure. Secondary outcomes were intubation failure, defined as the responsible clinician switching to an alternative laryngoscopy device for any reason at any time, or by more than 3 intubation attempts, and a composite of airway and dental injuries. Results: Among 8429 surgical procedures in 7736 patients, the median patient age was 66 (IQR, 56-73) years, 35% (2950) were women, and 85% (7135) had elective surgical procedures. More than 1 intubation attempt was required in 77 of 4413 surgical procedures (1.7%) randomized to receive video laryngoscopy vs 306 of 4016 surgical procedures (7.6%) randomized to receive direct laryngoscopy, with an estimated proportional odds ratio for the number of intubation attempts of 0.20 (95% CI, 0.14-0.28; P < .001). Intubation failure occurred in 12 of 4413 surgical procedures (0.27%) using video laryngoscopy vs 161 of 4016 surgical procedures (4.0%) using direct laryngoscopy (relative risk, 0.06; 95% CI, 0.03-0.14; P < .001) with an unadjusted absolute risk difference of -3.7% (95% CI, -4.4% to -3.2%). Airway and dental injuries did not differ significantly between video laryngoscopy (41 injuries [0.93%]) vs direct laryngoscopy (42 injuries [1.1%]). Conclusion and Relevance: In this study among adults having surgical procedures who required single-lumen endotracheal intubation for general anesthesia, hyperangulated video laryngoscopy decreased the number of attempts needed to achieve endotracheal intubation compared with direct laryngoscopy at a single academic medical center in the US. Results suggest that video laryngoscopy may be a preferable approach for intubating patients undergoing surgical procedures. Trial Registration: ClinicalTrials.gov Identifier: NCT04701762.

Perioperative bleeding and outcomes after noncardiac surgery.

BACKGROUND: Perioperative bleeding is a common and potentially life-threatening complication after surgery. We sought to identify the frequency, patient characteristics, causes, and outcomes of perioperative bleeding in patients undergoing noncardiac surgery. METHODS: In a retrospective cohort study of a large administrative database, adults aged ≥45 years hospitalized for noncardiac surgery in 2018 were identified. Perioperative bleeding was defined using ICD-10 diagnosis and procedure codes. Clinical characteristics, in-hospital outcomes, and first hospital readmission within 6 months were assessed by perioperative bleeding status. RESULTS: We identified 2,298,757 individuals undergoing noncardiac surgery, among which 35,429 (1.54%) had perioperative bleeding. Patients with bleeding were older, less likely to be female, and more likely to have renal and cardiovascular disease. All-cause, in-hospital mortality was higher in patients with vs without perioperative bleeding (6.0% vs 1.3%; adjusted OR [aOR] 2.38, 95% CI 2.26-2.50). Patients with vs without bleeding had a prolonged inpatient length of stay (6 [IQR 3-13] vs 3 [IQR 2-6] days, P < .001). Among those who were discharged alive, hospital readmission was more common within 6 months among patients with bleeding (36.0% vs 23.6%; adjusted HR 1.21, 95% CI 1.18-1.24). The risk of in-hospital death or readmission was greater in patients with vs without bleeding (39.8% vs 24.5%; aOR 1.33, 95% CI 1.29-1.38). When stratified by revised cardiac risk index , there was a stepwise increase in surgical bleeding risk with increasing perioperative cardiovascular risks. CONCLUSIONS: Perioperative bleeding is reported in 1 out of every 65 noncardiac surgeries, with a higher incidence in patients at elevated cardiovascular risk. Among postsurgical inpatients with perioperative bleeding, approximately 1 of every 3 patients died during hospitalization or were readmitted within 6-months. Strategies to reduce perioperative bleeding are warranted to improve outcomes following non-cardiac surgery.

Postoperative Risk of Transfusion After Reversal of Residual Neuromuscular Block With Sugammadex Versus Neostigmine: A Retrospective Cohort Study.

BACKGROUND: Sugammadex and neostigmine are routinely used to reverse residual neuromuscular blocks at the end of surgery. Sugammadex has been linked with prolongation of laboratory coagulation markers, but clinical relevance on postoperative blood loss and transfusions remains unclear. METHODS: In this retrospective, single-center, cohort study, we analyzed medical records of adult patients having noncardiac surgery who were given sugammadex or neostigmine from May 2016 to December 2020. Our primary outcome was the incidence of any postoperative transfusion of red blood cells, and/or fresh-frozen plasma, and/or platelets. Secondary outcomes were duration of hospitalization, need for resurgery, and postoperative intensive care unit (ICU) admission. After propensity score weighting, the odds ratio (OR) for postoperative transfusion was assessed in both groups (sugammadex versus neostigmine) using a generalized estimation equation to count within-subject correlation weighted by the inverse propensity score. RESULTS: Out of 39,325 eligible surgeries, 33,903 surgeries in 29,062 patients were included in the analysis; with 4581 patients receiving sugammadex and 29,322 patients receiving neostigmine. The raw incidence of postoperative transfusion was 7.40% in sugammadex and 7.45% in the neostigmine group. After weighting by propensity score, the incidence of postoperative transfusion was 8.01% in the sugammadex and 7.38% in the neostigmine group (OR, 1.11 [95% confidence interval [CI], 0.97-1.26; P = .118]). There was no difference in duration of hospitalization and need for resurgery, but odds of postoperative ICU admission were significantly higher for patients receiving sugammadex than those receiving neostigmine (OR, 1.33 [98.33% CI, 1.17-1.52; P < .0001]). Our a priori planned analysis of coagulation laboratory parameters could not be completed because of a high amount of missing laboratory data. CONCLUSIONS: There is no statistically significant nor clinically important difference in the risk of postoperative transfusion in patients receiving sugammadex or neostigmine.

Nociception Level Index-Guided Intraoperative Analgesia for Improved Postoperative Recovery: A Randomized Trial.

BACKGROUND: Nociception is the physiological response to nociceptive stimuli, normally experienced as pain. During general anesthesia, patients experience and respond to nociceptive stimuli by increasing blood pressure and heart rate if not controlled by preemptive analgesia. The PMD-200 system from Medasense (Ramat Gan, Israel) evaluates the balance between nociceptive stimuli and analgesia during general anesthesia and generates the nociception level (NOL) index from a single finger probe. NOL is a unitless index ranging from 0 to 100, with values exceeding 25 indicating that nociception exceeds analgesia. We aimed to demonstrate that titrating intraoperative opioid administration to keep NOL <25 optimizes intraoperative opioid dosing. Specifically, we tested the hypothesis that pain scores during the initial 60 minutes of recovery are lower in patients managed with NOL-guided fentanyl than in patients given fentanyl per clinical routine. METHODS: We conducted a randomized, single-center trial of patients having major abdominal open and laparoscopic surgeries. Patients were randomly assigned 1:1 to intraoperative NOL-guided fentanyl administration or fentanyl given per clinical routine. The primary outcome was pain score (0-10 verbal response scale) at 10-minute intervals during the initial 60 minutes of recovery. Our secondary outcome was a measure of adequate analgesia, defined as a pain score <5, assessed separately at each interval. RESULTS: With a planned maximum sample size of 144, the study was stopped for futility after enrolling 72 patients from November 2020 to October 2021. Thirty-five patients were assigned to NOL-guided analgesic dosing and 37 to routine care. Patients in the NOL group spent significantly less time with a NOL index >25 (median reduction [95% confidence interval {CI}] of 14 [4-25] minutes) were given nearly twice as much intraoperative fentanyl (median [quartiles] 500 [330, 780] vs 300 [200, 330] µg), and required about half as much morphine in the recovery period (3.3 [0, 8] vs 7.7 [0, 13] mg). However, in the primary outcome analysis, NOL did not reduce pain scores in the first 60 minutes after awakening, assessed in a linear mixed effects model with mean (standard error [SE]) of 4.12 (0.59) for NOL and 4.04 (0.58) for routine care, and estimated difference in means of 0.08 (-1.43, 1.58), P = .895. CONCLUSIONS: More intraoperative fentanyl was given in NOL-guided patients, but NOL guidance did not reduce initial postoperative pain scores.

The effect of intraoperative positive end expiratory pressure and tidal volume on postoperative acute kidney injury after orthopedic surgery.

BACKGROUND: To test whether higher intraoperative PEEP levels and/or higher TV levels are associated with higher incidence of postoperative AKI within the first postoperative week, in adult patients having orthopedic surgeries under general anesthesia. METHODS: We conducted a sub analysis of a non-randomized alternating intervention cross over study performed in patients undergoing orthopedic surgery under general anesthesia at Cleveland Clinic, Cleveland, OH. We included four different combinations of PEEP (5 or 8 cm H2 O) and TV (6 or 10 mL/kg of PBW) that alternated each week in the six orthopedic operating rooms. Our primary outcome was postoperative AKI defined by the KDIGO criteria with baseline creatinine as the closest preoperative value to the time of surgery obtained within 30 days and postoperative value as the highest creatinine value within 7 days after surgery. Secondary outcome was the maximum postoperative in-hospital creatinine level within seven postoperative days. MAIN RESULTS: A total of 1933 patients were included in the analysis. The incidence of AKI was 6.8% in the study population and similar in high TV versus low TV group and high PEEP versus low PEEP group. Neither TV nor PEEP significantly impacted AKI incidence. The estimated odds ratio of AKI comparing TV = 6 mL/kg to TV = 10 mL/kg was 0.96 (97.5% CI: 0.63, 1.46; p = .811); while the estimated odds ratio of AKI comparing PEEP = 5cm H2 O to PEEP = 8cm H2 O was 0.92 (97.5% CI: 0.60, 1.39; p = .623). No interaction was found between TV and PEEP on AKI. Additionally, neither TV nor PEEP had a significant effect on the seven postoperative day creatinine levels. CONCLUSION: Higher levels of PEEP or TV during mechanical ventilation in adult patients undergoing orthopedic surgeries under general anesthesia do not increase the odds of developing postoperative AKI within the narrow limits studied.

Generalizability of nociception level as a measure of intraoperative nociceptive stimulation: A retrospective analysis.

BACKGROUND: Nociception-guided intraoperative opioid administration might help reduce postoperative pain. A commonly used and validated nociception monitor system is nociception level (NOL), which provides the nociception index, ranging from 0 to 100, with 0 representing no nociception and 100 representing extreme nociception. We tested the hypothesis that NOL responses are similar in men and women given remifentanil and fentanyl, across various types of anesthesia, as a function of American Society of Anesthesiologists physical status designations, and over a range of ages and body morphologies. METHODS: We conducted a retrospective cohort analysis of trial data from eight prospective NOL validation studies. Among 522 noncardiac surgical patients enrolled in these studies, 447 were included in our analysis. We assessed NOL responses to various noxious and non-noxious stimuli. RESULTS: The average NOL in response to 315 noxious stimuli was 47 ± 15 (95% CI = 45-49). The average NOL in response to 361 non-noxious stimuli was 10 ± 12 (95% CI = 9-11). NOL responses were similar in men and women, in patients given remifentanil and fentanyl, across various types of anesthesia, as a function of American Society of Anesthesiologists physical status designations, and over a range of ages and body morphologies. CONCLUSION: Nociception level appears to provide accurate estimates of intraoperative nociception over a broad range of patients and anesthetic conditions.

Relative contributions of anaemia and hypotension to myocardial infarction and renal injury: Post hoc analysis of the POISE-2 trial.

BACKGROUND: Hypotension and postoperative anaemia are associated with myocardial and renal injury after noncardiac surgery, but the interaction between them remains unknown. OBJECTIVES: To test the hypothesis that a double-hit of postoperative anaemia and hypotension synergistically worsens a 30-day composite of myocardial infarction (MI) and mortality and acute kidney injury (AKI). Characterising the interaction when hypotension and anaemia occur at same time on myocardial infarction and acute kidney injury. DESIGN: Post hoc analysis of the POISE-2 trial. SETTING: Patients were enrolled between July 2010 and December 2013 at 135 hospitals in 23 countries. PATIENTS: Adults at least 45 years old with known or suspected cardiovascular disease. We excluded patients without available postoperative haemoglobin measurements or hypotension duration records. Exposures were the lowest haemoglobin concentration and the average daily duration of SBP less than 90 mmHg within the first four postoperative days. MAIN OUTCOME MEASURES: The primary outcome was a collapsed composite of nonfatal MI and all-cause mortality during the initial 30 postoperative days; our secondary outcome was AKI. RESULTS: We included 7940 patients. The mean ±â€ŠSD lowest postoperative haemoglobin was 10 ±â€Š2 g dl -1 , and 24% of the patients had SBP less than 90 mmHg with daily duration ranging from 0 to 15 h. Four hundred and nine (5.2%) patients had an infarction or died within 30 postoperative days, and 417 (6.4%) patients developed AKI. Lowest haemoglobin concentrations less than 11 g dl -1 , and duration of SBP less than 90 mmHg was associated with greater hazard of composite outcome of nonfatal MI and all-cause mortality, as well as with AKI. However, we did not find significant multiplicative interactions between haemoglobin splines and hypotension duration on the primary composite or on AKI. CONCLUSION: Postoperative anaemia and hypotension were meaningfully associated with both our primary composite and AKI. However, lack of significant interaction suggests that the effects of hypotension and anaemia are additive rather than multiplicative. TRIAL REGISTRATION: Clinicaltrials.gov: NCT01082874.

Cardiac arrest in the perioperative period: a consensus guideline for identification, treatment, and prevention from the European Society of Anaesthesiology and Intensive Care and the European Society for Trauma and Emergency Surgery.

INTRODUCTION: Cardiac arrest in the operating room is a rare but potentially life-threatening event with mortality rates of more than 50%. Contributing factors are often known, and the event is recognised rapidly as patients are usually under full monitoring. This guideline covers the perioperative period and is complementary to the European Resuscitation Council (ERC) guidelines. MATERIAL AND METHODS: The European Society of Anaesthesiology and Intensive Care and the European Society for Trauma and Emergency Surgery jointly nominated a panel of experts to develop guidelines for the recognition, treatment and prevention of cardiac arrest in the perioperative period. A literature search was conducted in MEDLINE, EMBASE, CINAHL and the Cochrane Central Register of Controlled Trials. All searches were restricted to publications from 1980 to 2019 inclusive and to the English, French, Italian and Spanish languages. The authors also contributed individual, independent literature searches. RESULTS: This guideline contains background information and recommendation for the treatment of cardiac arrest in the operating room environment, and addresses controversial topics such as open chest cardiac massage (OCCM), resuscitative endovascular balloon occlusion (REBOA) and resuscitative thoracotomy, pericardiocentesis, needle decompression and thoracostomy. CONCLUSION: Successful prevention and management of cardiac arrest during anaesthesia and surgery requires anticipation, early recognition and a clear treatment plan. The ready availability of expert staff and equipment must also be taken into consideration. Success not only depends on medical knowledge, technical skills and a well organised team using crew resource management but also on an institutional safety culture embedded in everyday practice through continuous education, training and multidisciplinary co-operation.

Diagnosis and Management of Patients With Myocardial Injury After Noncardiac Surgery: A Scientific Statement From the American Heart Association.

Myocardial injury after noncardiac surgery is defined by elevated postoperative cardiac troponin concentrations that exceed the 99th percentile of the upper reference limit of the assay and are attributable to a presumed ischemic mechanism, with or without concomitant symptoms or signs. Myocardial injury after noncardiac surgery occurs in ≈20% of patients who have major inpatient surgery, and most are asymptomatic. Myocardial injury after noncardiac surgery is independently and strongly associated with both short-term and long-term mortality, even in the absence of clinical symptoms, electrocardiographic changes, or imaging evidence of myocardial ischemia consistent with myocardial infarction. Consequently, surveillance of myocardial injury after noncardiac surgery is warranted in patients at high risk for perioperative cardiovascular complications. This scientific statement provides diagnostic criteria and reviews the epidemiology, pathophysiology, and prognosis of myocardial injury after noncardiac surgery. This scientific statement also presents surveillance strategies and treatment approaches.

Tidal Volume and Positive End-expiratory Pressure and Postoperative Hypoxemia during General Anesthesia: A Single-center Multiple Crossover Factorial Cluster Trial.

BACKGROUND: Intraoperative mechanical ventilation is a major component of general anesthesia. The extent to which various intraoperative tidal volumes and positive end-expiratory pressures (PEEP) effect on postoperative hypoxia and lung injury remains unclear. We hypothesized that adults having orthopedic surgery, ventilation using different tidal volumes and PEEP levels affect the oxygenation within first hour in the postoperative care unit. METHODS: We conducted a two-by-two factorial crossover cluster trial at the Cleveland Clinic Main Campus. We enrolled patients having orthopedic surgery with general anesthesia who were assigned to factorial clusters with tidal volumes of 6 or 10 ml/kg of predicted body weight and to PEEP of 5 or 8 cm H2O in 1-week clusters. The primary outcome was the effect of tidal volume or PEEP on time-weighted average peripheral oxygen saturation measured by pulse oximetry divided by the fraction of inspired oxygen (Spo2/Fio2 ratio) during the initial postoperative hour. RESULTS: We enrolled 2,860 patients who had general anesthesia for orthopedic surgery from September 2018 through October 2020. The interaction between tidal volume and PEEP was not significant (P = 0.565). The mean ± SD time-weighted average of Spo2/Fio2 ratio was 353 ± 47 and not different in patients assigned to high and low tidal volume (estimated effect, 3.5%; 97.5% CI, -0.4% to 7.3%; P = 0.042), for those assigned to high and low PEEP (estimated effect, -0.2%; 97.5% CI, -4.0% to 3.6%; P = 0.906). We did not find significant difference in ward Spo2/Fio2 ratio, pulmonary complications, and duration of hospitalization among patients assigned to various tidal volumes and PEEP levels. CONCLUSIONS: Among adults having major orthopedic surgery, postoperative oxygenation is similar, with tidal volumes between 6 and 10 ml/kg and PEEP between 5 and 8 cm H2O. Our results suggest that any combination of tidal volumes between 6 and 10 ml/kg and PEEP between 5 versus 8 ml cm H2O can be used safely for orthopedic surgery.

Pro-Con Debate: Prehospital Blood Transfusion-Should It Be Adopted for Civilian Trauma?

Exsanguination is the leading cause of death in severely injured patients; nevertheless, prehospital blood transfusion (PHT) remains a controversial topic. Here, we review the pros and cons of PHT, which is now routine in treatment of military trauma patients in the civilian setting. While PHT may improve survival in those who suffer blunt injury or require prolonged transport from the site of injury, PHT for civilian trauma generally is not supported by high-quality evidence. This article was originally presented as a pro-con debate at the 2020 meeting of the European Society of Anesthesiology and Intensive Care.

Sugammadex Versus Neostigmine for Reversal of Residual Neuromuscular Blocks After Surgery: A Retrospective Cohort Analysis of Postoperative Side Effects.

BACKGROUND: Sugammadex and neostigmine given to reverse residual neuromuscular blockade can cause side effects including bradycardia, anaphylaxis, bronchospasm, and even cardiac arrest. We tested the hypothesis that sugammadex is noninferior to neostigmine on a composite of clinically meaningful side effects, or vice versa. METHODS: We analyzed medical records of patients who had general, cardiothoracic, or pediatric surgery and were given neostigmine or sugammadex from June 2016 to December 2019. Our primary outcome was a collapsed composite of bradycardia, anaphylaxis, bronchospasm, and cardiac arrest occurring between administration of the reversal agent and departure from the operation room. We a priori restricted our analysis to side effects requiring pharmacologic treatment that were therefore presumably clinically meaningful. Sugammadex would be considered noninferior to neostigmine (or vice versa) if the odds ratio for composite of side effects did not exceed 1.2. RESULTS: Among 89,753 surgeries in 70,690 patients, 16,480 (18%) were given sugammadex and 73,273 (82%) were given neostigmine. The incidence of composite outcome was 3.4% in patients given sugammadex and 3.0% in patients given neostigmine. The most common individual side effect was bradycardia (2.4% in the sugammadex group versus 2.2% neostigmine). Noninferiority was not found, with an estimated odds ratio of 1.21 (sugammadex versus neostigmine; 95% confidence interval [CI], 1.09-1.34; noninferiority P = .57), and neostigmine was superior to sugammadex with an estimated odds ratio of 0.83 (0.74-0.92), 1-side superiority P < .001. CONCLUSIONS: The composite incidence was less with neostigmine than with sugammadex, but only by 0.4% (a negligible clinical effect). Since 250 patients would need to be given neostigmine rather than sugammadex to avoid 1 episode of a minor complication such as bradycardia or bronchospasm, we conclude that sugammadex and neostigmine are comparably safe.

Effect of a Rapid Response Team on the Incidence of In-Hospital Mortality.

BACKGROUND: Approximately half of the life-limiting events, such as cardiopulmonary arrests or cardiac arrhythmias occurring in hospitals, are considered preventable. These critical events are usually preceded by clinical deterioration. Rapid response teams (RRTs) were introduced to intervene early in the course of clinical deterioration and possibly prevent progression to an event. An RRT was introduced at the Cleveland Clinic in 2009 and transitioned to an anesthesiologist-led system in 2012. We evaluated the association between in-hospital mortality and: (1) the introduction of the RRT in 2009 (primary analysis), and (2) introduction of the anesthesiologist-led system in 2012 and other policy changes in 2014 (secondary analyses). METHODS: We conducted a single-center, retrospective analysis using the medical records of overnight hospitalizations from March 1, 2005, to December 31, 2018, at the Cleveland Clinic. We assessed the association between the introduction of the RRT in 2009 and in-hospital mortality using segmented regression in a generalized estimating equation model to account for within-subject correlation across repeated visits. Baseline potential confounders (demographic factors and surgery type) were controlled for using inverse probability of treatment weighting on the propensity score. We assessed whether in-hospital mortality changed at the start of the intervention and whether the temporal trend (slope) differed from before to after initiation. Analogous models were used for the secondary outcomes. RESULTS: Of 628,533 hospitalizations in our data set, 177,755 occurred before and 450,778 after introduction of our RRT program. Introduction of the RRT was associated with a slight initial increase in in-hospital mortality (odds ratio [95% confidence interval {CI}], 1.17 [1.09-1.25]; P < .001). However, while the pre-RRT slope in in-hospital mortality over time was flat (odds ratio [95% CI] per year, 1.01 [0.98-1.04]; P = .60), the post-RRT slope decreased over time, with an odds ratio per additional year of 0.961 (0.955-0.968). This represented a significant improvement (P < .001) from the pre-RRT slope. CONCLUSIONS: We found a gradual decrease in mortality over a 9-year period after introduction of an RRT program. Although mechanisms underlying this decrease are unclear, possibilities include optimization of RRT implementation, anesthesiology department leadership of the RRT program, and overall improvements in health care delivery over the study period. Our findings suggest that improvements in outcome after RRT introduction may take years to manifest. Further work is needed to better understand the effects of RRT implementation on in-hospital mortality.