REsidual Neuromuscular Block Prediction Score Versus Train-of-Four Ratio and Respiratory Outcomes: A Retrospective Cohort Study.

BACKGROUND: Residual neuromuscular blockade is associated with an increased incidence of postoperative respiratory complications. The REsidual neuromuscular block Prediction Score (REPS) identifies patients at high risk for residual neuromuscular blockade after surgery. METHODS: A total of 101,510 adults undergoing noncardiac surgery under general anesthesia from October 2005 to December 2018 at a tertiary care center in Massachusetts were analyzed for the primary outcome of postoperative respiratory complications (invasive mechanical ventilation requirement within 7 postoperative days or immediate postextubation desaturation [oxygen saturation {Spo2} <90%] within 10 minutes). The primary objective was to assess the association between the REPS and respiratory complications. The secondary objective was to compare REPS and train-of-four (TOF) ratio <0.90 on the strength of their association with respiratory complications. RESULTS: A high REPS (≥4) was associated with an increase in odds of respiratory complications (adjusted odds ratio [OR], 1.13 [95% confidence interval {CI}, 1.06-1.21]; P < .001). In 6224 cases with available TOF ratio measurements, a low TOF ratio (<0.9) was associated with respiratory complications (adjusted OR, 1.43 [95% CI, 1.11-1.85]; P = .006), whereas a high REPS was not (adjusted OR, 0.96 [95% CI, 0.74-1.23]; P = .73) (P = .018 for comparison between ORs). CONCLUSIONS: The REPS may be implemented as a screening tool to encourage clinicians to use quantitative neuromuscular monitoring in patients at risk of residual neuromuscular blockade. A positive REPS should be followed by a quantitative assessment of the TOF ratio.

Succinylcholine and postoperative pulmonary complications: a retrospective cohort study using registry data from two hospital networks.

BACKGROUND: Neuromuscular blocking agents (NMBAs) with a non-depolarising mechanism of action carry the risk of postoperative residual paralysis and are associated with postoperative pulmonary complications (POPC). Owing to the shorter duration of action, the depolarising NMBA succinylcholine may be associated with less postoperative residual paralysis, and hence fewer POPC. We tested the association of succinylcholine administration during anaesthesia and POPC. METHODS: In a retrospective cohort study of registry data from two large US academic medical centres, 244 850 adult noncardiac surgical patients undergoing general anaesthesia were included. The primary outcome was POPC, defined as post-extubation haemoglobin oxygen de-saturation to <90%, or re-intubation requiring intensive care unit admission within 7 days after surgery. The association between succinylcholine and POPC and its dose-dependency were tested in a hierarchical fashion using a multivariable logistic regression model. RESULTS: A total of 13 206 patients (5.4%) experienced POPC. Use of succinylcholine was associated with increased risk of POPC (adjusted odds ratio [ORAdj]=1.11; 95% confidence interval [CI], 1.06-1.16; P<0.001; adjusted risk=5.18%; 95% CI, 5.06-5.30 without and 5.69%; 95% CI, 5.53-5.85 with succinylcholine), with a dose-dependent relationship (ORAdj=1.08; 95% CI, 1.05-1.11 per mg kg-1; P<0.001). In patients receiving non-depolarising NMBAs, succinylcholine further increased the risk of POPC (ORAdj=1.08; 95% CI, 1.03-1.14; P=0.001). The association between succinylcholine and POPC was modified (P=0.03 for interaction) by the duration of surgery with higher odds of POPC in patients undergoing surgeries of <2 vs ≥2 h (ORAdj=1.24; 95% CI, 1.15-1.33 and 1.05; 95% CI, 1.00-1.10, respectively). CONCLUSIONS: In contrast to our prediction, succinylcholine administration was associated with an increased risk of POPC. This association was dose-dependent and magnified in surgeries of shorter duration.

Incidence, Prediction, and Causes of Unplanned 30-Day Hospital Admission After Ambulatory Procedures.

BACKGROUND: Unanticipated hospital admission is regarded as a measure of adverse perioperative patient care. However, previously published studies for risk prediction after ambulatory procedures are sparse compared to those examining readmission after inpatient surgery. We aimed to evaluate the incidence and reasons for unplanned admission after ambulatory surgery and develop a prediction tool for preoperative risk assessment. METHODS: This retrospective cohort study included adult patients undergoing ambulatory, noncardiac procedures under anesthesia care at 2 tertiary care centers in Massachusetts, United States, between 2007 and 2017 as well as all hospitals and ambulatory surgery centers in New York State, United States, in 2014. The primary outcome was unplanned hospital admission within 30 days after discharge. We created a prediction tool (the PREdicting admission after Outpatient Procedures [PREOP] score) using stepwise backward regression analysis to predict unplanned hospital admission, based on criteria used by the Centers for Medicare & Medicaid Services, within 30 days after surgery in the Massachusetts hospital network registry. Model predictors included patient demographics, comorbidities, and procedural factors. We validated the score externally in the New York state registry. Reasons for unplanned admission were assessed. RESULTS: A total of 170,983 patients were included in the Massachusetts hospital network registry and 1,232,788 in the New York state registry. Among those, the observed rate of unplanned admission was 2.0% (3504) and 1.7% (20,622), respectively. The prediction model showed good discrimination in the training set with C-statistic of 0.77 (95% confidence interval [CI], 0.77-0.78) and satisfactory discrimination in the validation set with C-statistic of 0.71 (95% CI, 0.70-0.71). The risk of unplanned admission varied widely from 0.4% (95% CI, 0.3-0.4) among patients whose calculated PREOP scores were in the first percentile to 21.3% (95% CI, 20.0-22.5) among patients whose scores were in the 99th percentile. Predictions were well calibrated with an overall ratio of observed-to-expected events of 99.97% (95% CI, 96.3-103.6) in the training and 92.6% (95% CI, 88.8-96.4) in the external validation set. Unplanned admissions were most often related to malignancy, nonsurgical site infections, and surgical complications. CONCLUSIONS: We present an instrument for prediction of unplanned 30-day admission after ambulatory procedures under anesthesia care validated in a statewide cohort comprising academic and nonacademic hospitals as well as ambulatory surgery centers. The instrument may be useful in identifying patients at high risk for 30-day unplanned hospital admission and may be used for benchmarking hospitals, ambulatory surgery centers, and practitioners.

Effects of high neuromuscular blocking agent dose on post-operative respiratory complications in infants and children.

BACKGROUND: This study evaluated the association between neuromuscular blocking agent dose and post-operative respiratory complications in infants and children. METHODS: Data from 6507 general anaesthetics provided to children aged 0-10 years undergoing surgery were analysed to examine the effects of neuromuscular blocking agent dose on post-operative respiratory complications (primary endpoint) and secondary endpoints. Confounder-adjusted analyses addressed age, surgical duration, and comorbidity burden. RESULTS: In confounder-adjusted analyses, high doses of neuromuscular blocking agents were associated with higher risk of post-operative respiratory complications (OR 2.27; 95% CI 1.12-4.59; P = .022). The effect was modified by age (P-for-interaction = .016) towards a more substantial risk in infants ≤1 year (OR 3.84; 95% CI 1.35-10.94; P = .012), by duration of surgery (P-for-interaction = .006) towards a higher difference in odds for surgeries <90 minutes (OR 4.25; 95% CI 1.19-15.18; P = .026), and by ASA physical status (P-for-interaction = .015) with a greater effect among patients with higher operative risk (ASA >1: OR 3.17; 95% CI 1.43-7.04; P = .005). Neostigmine reversal did not modify the association between neuromuscular blocking agents and post-operative respiratory complications (P-for-interaction = .38). Instrumental variable analysis confirmed that high doses of neuromuscular blocking agents were associated with post-operative respiratory complications (probit coefficient 0.25; 95% CI 0.04-0.46; P = .022), demonstrating robust results regarding concerns of unobserved confounding. CONCLUSIONS: High dose of neuromuscular blocking agents is associated with post-operative respiratory complications. We have identified subcohorts of paediatric patients who are particularly vulnerable to the respiratory side-effects of neuromuscular blocking agents: infants, paediatric patients undergoing surgeries of short duration, and those with a high ASA risk score.

The Impact of Postoperative Intensive Care Unit Admission on Postoperative Hospital Length of Stay and Costs: A Prespecified Propensity-Matched Cohort Study.

BACKGROUND: In this prespecified cohort study, we investigated the influence of postoperative admission to the intensive care unit versus surgical ward on health care utilization among patients undergoing intermediate-risk surgery. METHODS: Of adult surgical patients who underwent general anesthesia without an absolute indication for postoperative intensive care unit admission, 3530 patients admitted postoperatively to an intensive care unit were matched to 3530 patients admitted postoperatively to a surgical ward using a propensity score based on 23 important preoperative and intraoperative predictor variables. Postoperative hospital length of stay and hospital costs were defined as primary and secondary end points, respectively. RESULTS: Among patients with low propensity for postoperative intensive care unit admission, initial triage to an intensive care unit was associated with increased postoperative length of stay (incidence rate ratio, 1.69 [95% CI, 1.59-1.79]; P < .001) and hospital costs (incidence rate ratio, 1.92 [95% CI, 1.81-2.03]; P < .001). By contrast, postoperative intensive care unit admission of patients with high propensity was associated with decreased postoperative length of stay (incidence rate ratio, 0.90 [95% CI, 0.85-0.95]; P < .001) and costs (incidence rate ratio, 0.92 [95% CI, 0.88-0.97]; P = .001). Decisions regarding postoperative intensive care unit resource utilization were influenced by individual preferences of anesthesiologists and surgeons. CONCLUSIONS: In patients with an unclear indication for postoperative critical care, intensive care unit admission may negatively impact postoperative hospital length of stay and costs. Postoperative discharge disposition varies substantially based on anesthesia and surgical provider preferences but should optimally be driven by an objective assessment of a patient's status at the end of surgery.

Provider variability in the intraoperative use of neuromuscular blocking agents: a retrospective multicentre cohort study.

OBJECTIVE: To assess variability in the intraoperative use of non-depolarising neuromuscular blocking agents (NMBAs) across individual anaesthesia providers, surgeons and hospitals. DESIGN: Retrospective observational cohort study. SETTING: Two major tertiary referral centres, Boston, Massachusetts, USA. PARTICIPANTS: 265 537 adult participants undergoing non-cardiac surgery between October 2005 and September 2017. MAIN OUTCOME MEASURES: We analysed the variances in NMBA use across 958 anaesthesia and 623 surgical providers, across anaesthesia provider types (anaesthesia residents, certified registered nurse anaesthetists, attendings) and across hospitals using multivariable-adjusted mixed effects logistic regression. Intraclass correlations (ICC) were calculated to further quantify the variability in NMBA use that was unexplained by other covariates. Procedure-specific subgroup analyses were performed. RESULTS: NMBAs were used in 183 242 (69%) surgical cases. Variances in NMBA use were significantly higher among individual surgeons than among anaesthesia providers (variance 1.32 (95% CI 1.06 to 1.60) vs 0.24 (95% CI 0.19 to 0.28), p<0.001). Procedure-specific subgroup analysis of hernia repairs, spine surgeries and mastectomies confirmed our findings: the total variance in NMBA use that was unexplained by the covariate model was higher for surgeons versus anaesthesia providers (ICC 37.0% vs 13.0%, 69.7% vs 25.5%, 69.8% vs 19.5%, respectively; p<0.001). Variances in NMBA use were also partially explained by the anaesthesia provider's hospital network (Massachusetts General Hospital: variance 0.35 (95% CI 0.27 to 0.43) vs Beth Israel Deaconess Medical Center: 0.15 (95% CI 0.12 to 0.19); p<0.001). Across provider types, surgeons showed the highest variance, and anaesthesia residents showed the lowest variance in NMBA use. CONCLUSIONS: There is wide variability across individual surgeons and anaesthesia providers and institutions in the use of NMBAs, which could not sufficiently be explained by a large number of patient-related and procedure-related characteristics, but may instead be driven by preference. Surgeons may have a stronger influence on a key aspect of anaesthesia management than anticipated.

Study protocol for a randomised controlled trial evaluating the effects of the orexin receptor antagonist suvorexant on sleep architecture and delirium in the intensive care unit.

INTRODUCTION: Insomnia frequently occurs in patients admitted to an intensive care unit (ICU). Sleep-promoting agents may reduce rapid eye movement sleep and have deliriogenic effects. Suvorexant (Belsomra) is an orexin receptor antagonist with Food and Drug Administration (FDA) approval for the treatment of adult insomnia, which improves sleep onset and maintenance as well as subjective measures of quality of sleep. This trial will evaluate the efficacy of postoperative oral suvorexant treatment on night-time wakefulness after persistent sleep onset as well as the incidence and duration of delirium among adult cardiac surgical patients. METHODS AND ANALYSIS: In this single-centre, randomised, double-blind, placebo-controlled trial, we will enrol 120 patients, aged 60 years or older, undergoing elective cardiac surgery with planned postoperative admission to the ICU. Participants will be randomised to receive oral suvorexant (20 mg) or placebo one time a day starting the night after extubation. The primary outcome will be wakefulness after persistent sleep onset. The secondary outcome will be total sleep time. Exploratory outcomes will include time to sleep onset, incidence of postoperative in-hospital delirium, number of delirium-free days and subjective sleep quality. ETHICS AND DISSEMINATION: Ethics approval was obtained through the 'Committee on Clinical Investigations' at Beth Israel Deaconess Medical Center (protocol number 2019P000759). The findings will be published in peer-reviewed journals. TRIAL REGISTRATION NUMBER: This trial has been registered at clinicaltrials.gov on 17 September 2019 (NCT04092894).

Effect of midodrine versus placebo on time to vasopressor discontinuation in patients with persistent hypotension in the intensive care unit (MIDAS): an international randomised clinical trial.

PURPOSE: ICU discharge is often delayed by a requirement for intravenous vasopressor medications to maintain normotension. We hypothesised that the administration of midodrine, an oral α1-adrenergic agonist, as adjunct to standard treatment shortens the duration of intravenous vasopressor requirement. METHODS: In this multicentre, randomised, controlled trial including three tertiary referral hospitals in the US and Australia, we enrolled adult patients with hypotension requiring a single-agent intravenous vasopressor for ≥ 24 h. Subjects received oral midodrine (20 mg) or placebo every 8 h in addition to standard care until cessation of intravenous vasopressors, ICU discharge, or occurrence of adverse events. The primary outcome was time to vasopressor discontinuation. Secondary outcomes included time to ICU discharge readiness, ICU and hospital lengths of stay, and ICU readmission rates. RESULTS: Between October 2012 and June 2019, 136 participants were randomised, of whom 132 received the allocated intervention and were included in the analysis (modified intention-to-treat approach). Time to vasopressor discontinuation was not different between midodrine and placebo groups (median [IQR], 23.5 [10-54] vs 22.5 [10.4-40] h; difference, 1 h; 95% CI - 10.4 to 12.3 h; p = 0.62). No differences in secondary endpoints were observed. Bradycardia occurred more often after midodrine administration (5 [7.6%] vs 0 [0%], p = 0.02). CONCLUSION: Midodrine did not accelerate liberation from intravenous vasopressors and was not effective for the treatment of hypotension in critically ill patients.