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PURPOSE: Prematurity, prenatal growth restriction, and retinopathy of prematurity (ROP) are associated with altered ocular geometry, such as a steeper corneal shape in childhood, but it is unclear whether perinatal history affects corneal thickness development, so this study investigated whether corneal thickness in adulthood is affected by perinatal history. MARTERIALS AND METHODS: The Gutenberg Prematurity Eye Study (GPES) is a retrospective cohort study with a prospective ophthalmologic examination in Germany. The corneal thickness was measured by Scheimpflug imaging (Pentacam HR, Oculus Optikgeräte GmbH, Wetzlar, Germany), and the relationship between perinatal parameters respective birth weight percentile and corneal thickness at different locations was assessed using uni- and multivariable linear regression models. Covariates included age, sex, mean corneal radius, white-to-white distance, gestational age, birth weight percentile, ROP occurrence, and treatment. The main outcome measures were corneal thickness at the apex, the pupil center, and the corneal periphery. RESULTS: The corneal thickness was measured in 390 participants (754 eyes, mean age 29.7+/-8.7 years, 224 females). In multivariable analyses, a lower birth weight percentile was associated with a lower corneal thickness at the apex (B = 0.20, p = 0.003) and the pupil (B = 0.19, p = 0.007). These effects diminished towards the corneal periphery and were not observed beyond the 4-mm diameter circle around the thinnest corneal position. Neither gestational age, ROP occurrence, or ROP treatment affected the corneal thickness. CONCLUSION: A lower birth weight percentile in subjects born preterm as a proxy for restricted fetal growth is associated with corneal thickness thinning in adults aged 18 to 52 years, indicating that corneal thickness development, particularly in the corneal center, may originate in the fetal stage.

Purpose: Graft failure after penetrating keratoplasty (PK) is a serious complication, especially in eyes with herpetic keratitis (HK). This study evaluated the prevalence and graft survival of herpes simplex virus type 1 (HSV-1) and varicella zoster virus (VZV) DNA in recipient corneas during PK. Methods: The retrospective study was performed at the Department of Ophthalmology at University Hospital in Mainz, Germany. We analyzed data from every patient who underwent PK between January 2020 and June 2021. According to our clinical routine, we performed HSV-1 and VZV polymerase chain reaction (PCR) on all excised corneal buttons regardless of the primary clinical diagnosis. Results: We included 112 eyes of 112 consecutive patients who underwent PK. At the time of PK, 91 (81.25%) patients had no history of HK and 21 (18.75%) patients did. The recipient corneas of 91 patients without a history of HK tested positive for HSV-1 DNA in 12 (13.2%) eyes, for VZV DNA in 3 (3.3%) eyes, and for HSV-1 and VZV DNA simultaneously in 2 (2.2%) eyes. The recipient corneas of 21 patients with a preoperative history of HK tested positive for HSV-1 DNA in 13 (61.9%) eyes and VZV DNA in 1 (4.8%) eye. All patients with positive herpes DNA and no history of HK prior to PK received antiherpetic treatment and had a 100% graft survival rate after 1 year. Conclusions: We found herpesvirus DNA in 18.7% of recipient corneas without clinical suspicion or history of herpes keratitis. This suggests the need of routine HSV-1 and VZV PCR testing in all explanted corneas regardless of clinical suspicion, to detect, treat and prevent possible recurrence of herpes infection in corneal grafts and support graft survival.

BACKGROUND Intraoperative cerebral blood flow is mainly determined by cerebral perfusion pressure and cerebral autoregulation of vasomotor tone. About 1% of patients undergoing noncardiac surgery develop ischemic stroke. We hypothesized that intraoperative hypotension within a range frequently observed in clinical practice is associated with an increased risk of perioperative ischemic stroke within 7 days after surgery. METHODS Adult noncardiac surgical patients undergoing general anesthesia at Beth Israel Deaconess Medical Center and Massachusetts General Hospital between 2005 and 2017 were included in this retrospective cohort study. The primary exposure was intraoperative hypotension, defined as a decrease in mean arterial pressure (MAP) below 55 mm Hg, categorized into no intraoperative hypotension, short ( 30% from baseline on perioperative stroke. Analyses were adjusted for the preoperative STRoke After Surgery (STRAS) prediction score, work relative value units, and duration of surgery. RESULTS Among 358,391 included patients, a total of 1553 (0.4%) experienced an early perioperative ischemic stroke. About 42% and 3% of patients had a MAP of below 55 mm Hg for a short and a prolonged duration, and 49% and 29% had a MAP decrease by >30% from baseline for a short and a prolonged duration, respectively. In an adjusted analysis, neither a MAP 30% (short duration: ORadj, 0.97; 95% CI, 0.67-1.42; P = .883 and prolonged duration: ORadj, 1.30; 95% CI, 0.89-1.90; P = .176) was associated with early perioperative stroke. A high a priori stroke risk quantified based on preoperatively available risk factors (STRAS prediction score) was associated with longer intraoperative hypotension (adjusted incidence rate ratio, 1.04; 95% CI, 1.04-1.05; P < .001 per 5 points of the STRAS prediction score). CONCLUSIONS This study found no evidence to conclude that intraoperative hypotension within the range studied was associated with early perioperative stroke within 7 days after surgery. These findings emphasize the importance of perioperative cerebral blood flow autoregulation to prevent ischemic stroke.

Objective Inability of home discharge occurs in nearly a third of patients undergoing cardiac surgery and is associated with increased mortality. The authors aimed to evaluate the incidence and risk factors for adverse discharge disposition (ADD) after cardiac surgery and develop a prediction tool for preoperative risk assessment. Design This retrospective cohort study included adult patients undergoing cardiac surgery between 2010 and 2018. The primary outcome was ADD, defined as in-hospital mortality, discharge to a skilled nursing facility, or transfer to a long-term care hospital. The authors created a prediction tool using stepwise backward logistic regression and used 5-fold and leave-one-out cross-validation. Setting University hospital network. Participants Adult patients living at home prior to surgery, who underwent coronary artery bypass grafting and/or valve procedures at the authors’ institution. Interventions None. Measurements and Main Results A total of 3,760 patients were included in the final study cohort. The observed rate of ADD was 33.3%. The prediction model showed good discrimination and accuracy, with C-statistic of 0.78 (95% confidence interval [CI] 0.76-0.79) and unmodified Brier score of 0.177 (reliability 0.001). The final model comprised 14 predictors. Patients who experienced ADD were more likely to be older, of female sex, to have had higher length of hospital stay prior to surgery, and to have undergone emergency surgery. Conclusions The authors present an instrument for prediction of loss of the ability to live independently in patients undergoing cardiac surgery. The authors’ score may be useful in identifying high-risk patients such that earlier coordination of care can be initiated in this vulnerable patient population.

Sevoflurane and desflurane are the most commonly used volatile anaesthetics for maintenance of anaesthesia. In this study, we aimed to evaluate the relationship between choice of volatile anaesthetic and early postoperative respiratory complications, and to address a critical knowledge gap in safety outcomes between these two commonly used agents. We performed a retrospective analysis of adult (non-cardiac surgery) patients who received sevoflurane or desflurane for the maintenance of general anaesthesia at our institution between 2005 and 2018. We evaluated the association between desflurane exposure (when compared with sevoflurane) and the primary outcome of postoperative respiratory complications, defined by early post-extubation desaturation (Sp O2 35 kg.m-2 ); elderly (age > 65 years); and high risk of respiratory complications as well as the primary outcome at 24 h. Desflurane was used for 23,830 patients and sevoflurane for 84,608 patients. Patients exposed to desflurane did not demonstrate a reduced risk of postoperative respiratory complications when compared with sevoflurane (adjusted odds ratio 0.99, 95%CI 0.94-1.04, p = 0.598). These findings were consistent across all sub-groups of high-risk patients and in the propensity score matched cohort. In summary, desflurane use was not associated with reduced postoperative respiratory complications when compared with sevoflurane. In the context of environmental and cost concerns with volatile anaesthetic agents, our study provides important data to support organisational decisions regarding the use of desflurane.

Background Reexposure to methamphetamine with a single “priming dose” can trigger intense cravings and precipitate relapse in methamphetamine-dependent individuals. The acyclic cucurbit[n]uril “molecular container” calabadion-2 shows a high affinity to bind and sequester methamphetamine in vitro and attenuates its locomotor-stimulating effect in rats. The present study investigates whether pretreatment with calabadion-2 is sufficient to prevent the reinstatement of drug seeking by a priming dose of methamphetamine in rats. Methods Male Long-Evans rats were trained to self-administer i.v. methamphetamine (0.06 mg/kg/infusion). Following 10 days of stable self-administration, rats underwent extinction training and were subsequently tested on a multi-phase reinstatement procedure. Drug-primed reinstatement sessions (0.3 mg/kg methamphetamine, i.v.) were preceded by either saline or calabadion-2 (130 mg/kg). Additional reinstatement tests were conducted after administration of yohimbine (1.0 mg/kg, i.v.) to define the pharmacological specificity of calabadion-2. Results Pretreatment with calabadion-2 significantly attenuated methamphetamine-induced reinstatement of responding. Cal2 did not affect drug-seeking behavior stimulated by the pharmacological stressor yohimbine, indicating a mechanism of action specific to methamphetamine. Conclusions These results demonstrate the effectiveness of calabadion-2 in a preclinical model relapse-like behavior. With further structural optimization, molecular containers may provide a novel and efficacious pharmacokinetic approach to relapse prevention for methamphetamine-dependent individuals.

Background Preclinical data suggest suppression of cancer proliferation by propofol, and retrospective studies suggest improved survival after cancer surgery with propofol-based anaesthesia. Methods To determine whether propofol dose administered for anaesthesia is associated with 1-yr mortality in patients with and without a diagnosis of solid cancer, we analysed adult patients undergoing monitored anaesthesia care or general anaesthesia at two academic medical centres in Boston, MA, USA. Logistic regression with interaction term analysis was applied with propofol dose (mg kg−1) as primary and diagnosis of solid cancer as co-primary exposure, and 1-yr mortality as the primary outcome. Results Of 280 081 patient cases, 10 744 (3.8%) died within 1 yr. Increasing propofol dose was associated with reduced odds of 1-yr mortality (adjusted odds ratio [aOR] 0.93 per 10 mg kg−1; 95% confidence interval [CI]: 0.89–0.98; absolute risk reduction fifth vs first quintile 0.5%; 95% CI: 0.2–0.7). This association was modified by a diagnosis of solid cancer (P Conclusions Increasing propofol dose is associated with lower 1-yr mortality in patients without, but not in patients with, a diagnosis of solid cancer. We found evidence for competing effects, modifying the association between propofol dose and mortality.

Intraoperative cerebral blood flow is mainly determined by cerebral perfusion pressure and cerebral autoregulation of vasomotor tone. About 1% of patients undergoing noncardiac surgery develop ischemic stroke. We hypothesized that intraoperative hypotension within a range frequently observed in clinical practice is associated with an increased risk of perioperative ischemic stroke within 7 days after surgery.Adult noncardiac surgical patients undergoing general anesthesia at Beth Israel Deaconess Medical Center and Massachusetts General Hospital between 2005 and 2017 were included in this retrospective cohort study. The primary exposure was intraoperative hypotension, defined as a decrease in mean arterial pressure (MAP) below 55 mm Hg, categorized into no intraoperative hypotension, short (15 minutes, median [interquartile range {IQR}], 2 minutes [1-5 minutes]) and prolonged (≥15 minutes, median [IQR], 21 minutes [17-31 minutes]) durations. The primary outcome was a new diagnosis of early perioperative ischemic stroke within 7 days after surgery. In secondary analyses, we assessed the effect of a MAP decrease by30% from baseline on perioperative stroke. Analyses were adjusted for the preoperative STRoke After Surgery (STRAS) prediction score, work relative value units, and duration of surgery.Among 358,391 included patients, a total of 1553 (0.4%) experienced an early perioperative ischemic stroke. About 42% and 3% of patients had a MAP of below 55 mm Hg for a short and a prolonged duration, and 49% and 29% had a MAP decrease by30% from baseline for a short and a prolonged duration, respectively. In an adjusted analysis, neither a MAP55 mm Hg (short duration: adjusted odds ratio [ORadj], 0.95; 95% confidence interval [CI], 0.85-1.07; P = .417 and prolonged duration: ORadj, 1.18; 95% CI, 0.91-1.55; P = .220) nor a MAP decrease30% (short duration: ORadj, 0.97; 95% CI, 0.67-1.42; P = .883 and prolonged duration: ORadj, 1.30; 95% CI, 0.89-1.90; P = .176) was associated with early perioperative stroke. A high a priori stroke risk quantified based on preoperatively available risk factors (STRAS prediction score) was associated with longer intraoperative hypotension (adjusted incidence rate ratio, 1.04; 95% CI, 1.04-1.05; P.001 per 5 points of the STRAS prediction score).This study found no evidence to conclude that intraoperative hypotension within the range studied was associated with early perioperative stroke within 7 days after surgery. These findings emphasize the importance of perioperative cerebral blood flow autoregulation to prevent ischemic stroke.

The present study investigated the long-lasting effect of prematurity, prenatal growth restriction, and associated factors on foveal and peripapillary choroidal thickness in adulthood.The Gutenberg Prematurity Eye Study (GPES) is a retrospective cohort study with a prospective ophthalmologic examination in Germany. Foveal and peripapillary choroidal thicknesses were measured at different sectors using spectral-domain optical coherence tomography. Multivariable linear regression analyses were performed to determine associations among gestational age, birth weight percentile, retinopathy of prematurity (ROP) occurrence and treatment, and other perinatal factors, such as maternal smoking and others with foveal and global peripapillary choroidal thickness.A total of 735 eyes of 408 study participants were included (age = 28.4 ± 8.6 years, 229 women). Multivariable regression analyses revealed that foveal choroidal thinning was associated with maternal smoking during pregnancy (B = -38.1, 95% confidence interval [CI] = -65.5 to -10.7, P = 0.006), whereas other perinatal factors revealed no association. Global peripapillary choroidal thinning showed a trend to a lower birth weight percentile (B = 0.22, 95% CI = -0.01 to 0.45, P = 0.057). No correlation was observed between foveal and peripapillary choroidal thicknesses with visual acuity.This study indicates that maternal cigarette smoking during pregnancy has adverse long-lasting effects on choroidal development in the fovea and low birth weight percentile as a surrogate marker for adverse perinatal growth might be linked with peripapillary choroidal thinning whereas prematurity showed no long-term effects.Altered choroidal layer development caused by perinatal influence factors might be a risk factor for reduced visual function and predispose affected individuals to eye diseases in later life.

OBJECTIVES Two previously published trials (ARDS et Curarisation Systematique [ACURASYS] and Reevaluation of Systemic Early Neuromuscular Blockade [ROSE]) presented equivocal evidence on the effect of neuromuscular blocking agent infusions in patients with acute respiratory distress syndrome (acute respiratory distress syndrome). The sedation regimen differed between these trials and also within the ROSE trial between treatment and control groups. We hypothesized that the proportion of deeper sedation is a mediator of the effect of neuromuscular blocking agent infusions on mortality. DESIGN Retrospective cohort study. SETTING Seven ICUs in an academic hospital network, Beth Israel Deaconess Medical Center (Boston, MA). PATIENTS Intubated and mechanically ventilated ICU patients with acute respiratory distress syndrome (Berlin definition) admitted between January 2008 until June 2019. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS The proportion of deeper sedation was defined as days with nonlight sedation as a fraction of mechanical ventilation days in the ICU after acute respiratory distress syndrome diagnosis. Using clinical data obtained from a hospital network registry, 3,419 patients with acute respiratory distress syndrome were included, of whom 577 (16.9%) were treated with neuromuscular blocking agent infusions, for a mean (sd) duration of 1.8 (±1.9) days. The duration of deeper sedation was prolonged in patients receiving neuromuscular blocking agent infusions (4.6 ± 2.2 d) compared with patients without neuromuscular blocking agent infusions (2.4 ± 2.2 d; p < 0.001). The proportion of deeper sedation completely mediated the negative effect of neuromuscular blocking agent infusions on in-hospital mortality (p < 0.001). Exploratory analysis in patients who received deeper sedation revealed a beneficial effect of neuromuscular blocking agent infusions on mortality (49% vs 51%; adjusted odds ratio, 0.80; 95% CI, 0.63-0.99, adjusted absolute risk difference, -0.05; p = 0.048). CONCLUSIONS In acute respiratory distress syndrome patients who receive neuromuscular blocking agent infusions, a prolonged, high proportion of deeper sedation is associated with increased mortality. Our data support the view that clinicians should minimize the duration of deeper sedation after recovery from neuromuscular blocking agent infusion.

OBJECTIVE The objective of this study was to identify undertreated subgroups of patients with heart failure who would benefit from better perioperative optimization. SUMMARY BACKGROUND DATA Patients with heart failure have increased risks of postoperative cardiac complications after noncardiac surgery. METHODS In this analysis of hospital registry data of 130,677 patients undergoing noncardiac surgery, the exposure was preoperative history of heart failure. The outcome, cardiac complications, was defined as a composite of myocardial infarction, cardiac arrest, acute heart failure, and mortality within 30 postoperative days. RESULTS History of heart failure (n = 10,256; 7.9%) was associated with increased risk of cardiac complications (8.1% vs. 1.1%; adjusted odds ratio, 2.28 [95% CI, 2.02-2.56]; P < 0.001). Patients with heart failure and who carried a lower risk profile had increased risks of postoperative cardiac complications secondary to heart failure (adjusted absolute risk difference [aARD], 1.7% [95% CI, 1.4%-2.0%, lower risk]; P < 0.001 vs. 0.5% [95% CI, -0.6% to 1.6%, higher risk]; P = 0.38). Patients with heart failure and lower risk received a lower level of health care utilization preoperatively, and less frequently received anti-heart failure medications (59% vs. 72% and 61% vs. 82%; both P < 0.001). These preventive therapies significantly decreased the risk of cardiac complications in patients with heart failure. CONCLUSIONS In patients with heart failure who have a lower preoperative risk profile, clinicians often make insufficient attempts to optimize their clinical condition preoperatively. Preoperative preventive treatment reduces the risk of postoperative cardiac complications in these lower-risk patients with heart failure.

Background Preclinical studies suggest that volatile anesthetics decrease infarct volume and improve the outcome of ischemic stroke. This study aims to determine their effect during noncardiac surgery on postoperative ischemic stroke incidence. Methods and Results This was a retrospective cohort study of surgical patients undergoing general anesthesia at 2 tertiary care centers in Boston, MA, between October 2005 and September 2017. Exclusion criteria comprised brain death, age P P =0.002). The effects were robust throughout various sensitivity analyses including adjustment for anesthesia providers as random effect. Conclusions Among patients undergoing noncardiac surgery, volatile anesthetics showed a dose‐dependent protective effect on the incidence and severity of early postoperative ischemic stroke.

Background There is an under-recognised patient cohort at elevated risk of postoperative ischaemic stroke. We aimed to develop and validate a prognostic model for the identification of such patients at high risk of ischaemic stroke within 1 yr after noncardiac surgery. Methods This was a hospital registry study of adult patients undergoing noncardiac surgery between 2005 and 2017 at two independent healthcare networks in Massachusetts, USA without a preoperative indication for therapeutic anticoagulation. Logistic regression was used to fit a model from a priori defined candidate predictors for the outcome 1 yr postoperative ischaemic stroke. To enhance clinical applicability, the model was simplified to a scoring system and externally validated. Results In the development (n=107 756) and validation (n=141 724) cohorts, 1.4% and 0.5% of patients had an ischaemic stroke up to 1 yr postoperatively. The final model included 13 variables (patient characteristics, comorbidities, procedural factors), considering sub-models conditional on a previous history of ischaemic stroke. Areas under the curve were 0.89 (95% confidence interval 0.89–0.90) and 0.88 (95% confidence interval 0.86–0.89) in the development and validation cohorts. Decision curve analysis indicated positive net benefits superior to other prediction instruments. Conclusions Stroke after surgery (STRAS) screening can reliably identify patients with a high risk for ischaemic stroke during the first year after surgery. A STRAS-guided risk stratification may inform the recruitment to future randomised trials testing the efficacy of treatments for the prevention of postoperative ischaemic stroke.

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}

We tested the primary hypothesis that use of general anaesthesia vs sedation increases vulnerability to adverse discharge (in-hospital mortality or new discharge to a nursing facility) after endoscopic retrograde cholangiopancreatography (ERCP).In this retrospective cohort study, adult patients undergoing ERCP with general anaesthesia or sedation at a tertiary care hospital were included. We calculated adjusted absolute risk differences between patients receiving general anaesthesia vs sedation using provider preference-based instrumental variable analysis. We also used mediation analysis to determine whether intraoperative hypotension during general anaesthesia mediated its effect on adverse discharge.Among 17 538 patients undergoing ERCP from 2007 through 2018, 16 238 received sedation and 1300 received GA. Rates of adverse discharge were 5.8% (n=938) after sedation and 16.2% (n=210) after general anaesthesia. Providers' adjusted mean predicted probabilities of using general anaesthesia for ERCP ranged from 0.2% to 63.2% of individual caseloads. Utilising provider-related variability in the use of general anaesthesia for instrumental variable analysis resulted in an 8.6% risk increase (95% confidence interval, 4.5-12.6%; P0.001) in adverse discharge among patients receiving general anaesthesia vs sedation. Intraoperative hypotensive events occurred more often during general anaesthesia and mediated 23.8% (95% confidence interval, 3.9-43.7%: P=0.019) of the primary association.These results suggest that use of sedation during ERCP facilitates reduced adverse discharge for patients for whom general anaesthesia is not clearly indicated. Intraoperative hypotension during general anaesthesia for ERCP partly mediates the increased vulnerability to adverse discharge.

Background: Readmission to the Intensive Care Unit (ICU) is associated with a high risk of in-hospital mortality and higher health care costs. Previously published tools to predict ICU readmission in surgical ICU patients have important limitations that restrict their clinical implementation. We sought to develop a clinically intuitive score that can be implemented to predict readmission to the ICU after surgery or trauma. We designed the score to emphasize modifiable predictors. Methods: In this retrospective cohort study, we included surgical patients requiring critical care between June 2015 and January 2019 at Beth Israel Deaconess Medical Center, Harvard Medical School, MA, USA. We used logistic regression to fit a prognostic model for ICU readmission from a priori defined, widely available candidate predictors. The score performance was compared with existing prediction instruments. Results: Of 7,126 patients, 168 (2.4%) were readmitted to the ICU during the same hospitalization. The final score included 8 variables addressing demographical factors, surgical factors, physiological parameters, ICU treatment and the acuity of illness. The maximum score achievable was 13 points. Potentially modifiable predictors included the inability to ambulate at ICU discharge, substantial positive fluid balance (>5 liters), severe anemia (hemoglobin 180 mg/dl), and long ICU length of stay (>5 days). The score yielded an area under the receiver operating characteristic curve of 0.78 (95% CI 0.74-0.82) and significantly outperformed previously published scores. The performance of the underlying model was confirmed by leave-one-out cross-validation. Conclusion: The RISC-score is a clinically intuitive prediction instrument that helps identify surgical ICU patients at high risk for ICU readmission. The simplicity of the score facilitates its clinical implementation across surgical divisions.

IntroductionInsomnia 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 analysisIn 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 disseminationEthics 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 numberThis trial has been registered at clinicaltrials.gov on 17 September 2019 (NCT04092894).

BackgroundSurgery at night (incision time 17:00 to 07:00 hours) may lead to increased postoperative mortality and morbidity. Mechanisms explaining this association remain unclear.MethodsWe conducted a multicentre retrospective cohort study of adult patients undergoing non-cardiac surgery with general anaesthesia at two major, competing tertiary care hospital networks. In primary analysis, we imputed missing data and determined whether exposure to night surgery affects 30-day mortality using a mixed-effects model with individual anaesthesia and surgical providers as random effects. Secondary outcomes were 30-day morbidity and the mediating effect of blood transfusion rates and provider handovers on the effect of night surgery on outcomes. We further tested for effect modification by surgical setting.ResultsAmong 350 235 participants in the primary imputed cohort, the mortality rate was 0.9% (n=2804/322 327) after day and 3.4% (n=940/27 908) after night surgery. Night surgery was associated with an increased risk of mortality (ORadj1.26, 95% CI 1.15 to 1.38, padj1.41, 95% CI 1.33 to 1.48, padj1.81, 95% CI 1.39 to 2.35) compared with inpatients (ORadj1.17, 95% CI 1.02 to 1.34).ConclusionsNight surgery was associated with an increased risk of postoperative mortality and morbidity. The effect was independent of case acuity and was mediated by potentially preventable factors: higher blood transfusion rates and more frequent provider handovers.

OBJECTIVE: Evaluate the dose-response relationship between intraoperative fluid administration and postoperative outcomes in a large cohort of surgical patients.BACKGROUND: Healthy humans may live in a state of fluid responsiveness without the need for fluid supplementation. Goal-directed protocols driven by such measures are limited in their ability to define the optimal fluid state during surgery.METHODS: This analysis of data on file included 92,094 adult patients undergoing noncardiac surgery with endotracheal intubation between 2007 and 2014 at an academic tertiary care hospital and two affiliated community hospitals. The primary exposure variable was total intraoperative volume of crystalloid and colloid administered. The primary outcome was 30-day survival. Secondary outcomes were respiratory complications within three postoperative days (pulmonary edema, reintubation, pneumonia, or respiratory failure) and acute kidney injury. Exploratory outcomes were postoperative length of stay and total cost of care. Our models were adjusted for patient-, procedure-, and anesthesia-related factors.RESULTS: A U-shaped association was observed between the volume of fluid administered intraoperatively and 30-day mortality, costs, and postoperative length of stay. Liberal fluid volumes (highest quintile of fluid administration practice) were significantly associated with respiratory complications whereas both liberal and restrictive (lowest quintile) volumes were significantly associated with acute kidney injury. Moderately restrictive volumes (second quintile) were consistently associated with optimal postoperative outcomes and were characterized by volumes approximately 40% less than traditional textbook estimates: infusion rates of approximately 6-7 mL/kg/hr or 1 L of fluid for a 3-hour case.CONCLUSIONS: Intraoperative fluid dosing at the liberal and restrictive margins of observed practice is associated with increased morbidity, mortality, cost, and length of stay.

Background The use of intraoperative opioids may influence the rate of postoperative complications. This study evaluated the association between intraoperative opioid dose and the risk of 30-day hospital readmission. Methods We conducted a pre-specified analysis of existing registry data for 153 902 surgical cases performed under general anaesthesia at Massachusetts General Hospital and two affiliated medical centres. We examined the association between total intraoperative opioid dose (categorised in quintiles) and 30-day hospital readmission, controlling for several patient-, anaesthetist-, and case-specific factors. Results Compared with low intraoperative opioid dosing [quintile 1, median (inter-quartile range): 8 (4–9) mg morphine equivalents], exposure to high-dose opioids during surgery [quintile 5: 32 (27–41) equivalents] is an independent predictor of 30-day readmission [odds ratio (OR) 1.15 (95% confidence interval 1.07–1.24); P Conclusions High intraoperative opioid dose is a modifiable anaesthetic factor that varies in the practice of individual anaesthetists and affects postoperative outcomes. Conservative standards for intraoperative opioid dosing may reduce the risk of postoperative readmission, particularly in ambulatory surgery.

We measured the affinity of five molecular container compounds (calabadions 1 and 2, CB[7], sulfocalix[4]arene, and HP-β-CD) toward seven drugs of abuse in homogenous aqueous solution at physiological pH by various methods (1 H NMR, UV/Vis, isothermal titration calorimetry [ITC]) and found binding constants (Ka values) spanning from 108 m-1 . We also report X-ray crystal structures of CB[7]⋅methamphetamine and 1⋅methamphetamine. We found that 2, but not CB[7], was able to ameliorate the hyperlocomotive activity of rats treated with methamphetamine. The bioavailability of the calabadions and their convergent building block synthesis suggest potential for further structural optimization as reversal agents for intoxication with nonopioid drugs of abuse for which no treatments are currently available.

Background Adverse discharge disposition, which is discharge to a long-term nursing home or skilled nursing facility is frequent and devastating in older patients after lower-extremity orthopaedic surgery. Predicting individual patient risk allows for preventive interventions to address modifiable risk factors and helps managing expectations. Despite a variety of risk prediction tools for perioperative morbidity in older patients, there is no tool available to predict successful recovery of a patient's ability to live independently in this highly vulnerable population. Questions/purposes In this study, we asked: (1) What factors predict adverse discharge disposition in patients older than 60 years after lower-extremity surgery? (2) Can a prediction instrument incorporating these factors be applied to another patient population with reasonable accuracy? (3) How does the instrument compare with other predictions scores that account for frailty, comorbidities, or procedural risk alone? Methods In this retrospective study at two competing New England university hospitals and Level 1 trauma centers with 673 and 1017 beds, respectively; 83% (19,961 of 24,095) of patients 60 years or older undergoing lower-extremity orthopaedic surgery were included. In all, 5% (1316 of 24,095) patients not living at home and 12% (2797 of 24,095) patients with missing data were excluded. All patients were living at home before surgery. The mean age was 72 ± 9 years, 60% (11,981 of 19,961) patients were female, 21% (4155 of 19,961) underwent fracture care, and 34% (6882 of 19,961) underwent elective joint replacements. Candidate predictors were tested in a multivariable logistic regression model for adverse discharge disposition in a development cohort of all 14,123 patients from the first hospital, and then included in a prediction instrument that was validated in all 5838 patients from the second hospital by calculating the area under the receiver operating characteristics curve (ROC-AUC).Thirty-eight percent (5360 of 14,262) of patients in the development cohort and 37% (2184 of 5910) of patients in the validation cohort had adverse discharge disposition. Score performance in predicting adverse discharge disposition was then compared with prediction scores considering frailty (modified Frailty Index-5 or mFI-5), comorbidities (Charlson Comorbidity Index or CCI), and procedural risks (Procedural Severity Scores for Morbidity and Mortality or PSS). Results After controlling for potential confounders like BMI, cardiac, renal and pulmonary disease, we found that the most prominent factors were age older than 90 years (10 points), hip or knee surgery (7 or 8 points), fracture management (6 points), dementia (5 points), unmarried status (3 points), federally provided insurance (2 points), and low estimated household income based on ZIP code (1 point). Higher score values indicate a higher risk of adverse discharge disposition. The score comprised 19 variables, including socioeconomic characteristics, surgical management, and comorbidities with a cutoff value of ≥ 23 points. Score performance yielded an ROC-AUC of 0.85 (95% confidence interval 0.84 to 0.85) in the development and 0.72 (95% CI 0.71 to 0.73) in the independent validation cohort, indicating excellent and good discriminative ability. Performance of the instrument in predicting adverse discharge in the validation cohort was superior to the mFI-5, CCI, and PSS (ROC-AUC 0.72 versus 0.58, 0.57, and 0.57, respectively). Conclusion The Adverse Discharge in Older Patients after Lower Extremity Surgery (ADELES) score predicts adverse discharge disposition after lower-extremity surgery, reflecting loss of the ability to live independently. Its discriminative ability is better than instruments that consider frailty, comorbidities, or procedural risk alone. The ADELES score identifies modifiable risk factors, including general anesthesia and prolonged preoperative hospitalization, and should be used to streamline patient and family expectation management and improve shared decision making. Future studies need to evaluate the score in community hospitals and in institutions with different rates of adverse discharge disposition and lower income. A non-commercial calculator can be accessed at www.adeles-score.org. Level of evidence Level III, diagnostic study.

BACKGROUND: We hypothesised that Calabadion 1, an acyclic cucurbit[n]uril molecular container, reverses fentanyl-induced respiratory depression and dysfunction of the CNS. METHODS: Experiments were conducted in male Sprague-Dawley rats. A constant-rate i.v. infusion of fentanyl (12.5 or 25 μg kg(−1) over 15 min) was administered followed by an i.v. bolus of Calabadion 1 (0.5–200 mg kg(−1)) or placebo. The primary outcome was reversal of ventilatory and respiratory depression, assessed by pneumotachography and arterial blood gas analysis, respectively. Key secondary outcomes were effects on fentanyl-induced central nervous dysfunction quantified by righting reflex, balance beam test, and electromyography (EMG). RESULTS: Calabadion 1 reversed fentanyl-induced respiratory depression across the endpoints minute ventilation, pH, and Paco(2) (P=0.001). Compared with placebo, Calabadion 1 dose dependently (P for trend

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.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 to90%, 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.A total of 13 206 patients (5.4%) experienced POPC. Use of succinylcholine was associated with increased risk of POPC (adjusted odds ratio [ORIn 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.

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.

Postoperative residual neuromuscular blockade continues to be a frequent occurrence with a reported incidence rate of up to 64%. However, the effect of postoperative residual neuromuscular blockade on health care utilization remains unclear. We conducted a retrospective cohort study to investigate the effects of postoperative residual neuromuscular blockade on hospital costs (primary outcome), intensive care unit admission rate, and hospital length of stay (secondary outcomes).We performed a prespecified secondary analysis of data obtained in 2233 adult patients undergoing surgery under general anesthesia. Postoperative residual neuromuscular blockade was defined as a train-of-four ratio0.9 in the postanesthesia care unit (PACU). Our confounder model adjusted for a variety of patient, surgical, and anesthesia-related factors. We fitted truncated negative binomial regression models for hospital cost and hospital length of stay analyses and a logistic regression model for our intensive care unit admission analysis.Overall, 457 (20.5%) patients in our cohort had residual neuromuscular blockade on admission to the PACU. Postoperative residual neuromuscular blockade was not independently associated with increased hospital costs (adjusted incidence rate ratio, 1.04, CI, 0.98-1.11; P = .22). There were significantly higher odds of intensive care unit admission in those with postoperative residual neuromuscular blockade compared to those without (adjusted odds ratio, 3.03, CI, 1.33-6.87; P.01). Further, we found a trend toward increased hospital length of stay in patients with postoperative residual neuromuscular blockade (adjusted incidence rate ratio, 1.09; P = .06). Sensitivity analysis using the same model in the day of surgery admissions and ambulatory surgery confirmed our findings.Postoperative residual neuromuscular blockade at PACU admission was not significantly associated with increased hospital costs, but was associated with higher rates of intensive care unit admission. These findings support the view that clinicians should continue to work to reduce the rate of postoperative residual neuromuscular blockade.

Immobilisation predicts adverse outcomes in patients in the surgical intensive care unit (SICU). Attempts to mobilise critically ill patients early after surgery are frequently restricted, but we tested whether early mobilisation leads to improved mobility, decreased SICU length of stay, and increased functional independence of patients at hospital discharge.We did a multicentre, international, parallel-group, assessor-blinded, randomised controlled trial in SICUs of five university hospitals in Austria (n=1), Germany (n=1), and the USA (n=3). Eligible patients (aged 18 years or older, who had been mechanically ventilated for48 h, and were expected to require mechanical ventilation for ≥24 h) were randomly assigned (1:1) by use of a stratified block randomisation via restricted web platform to standard of care (control) or early, goal-directed mobilisation using an inter-professional approach of closed-loop communication and the SICU optimal mobilisation score (SOMS) algorithm (intervention), which describes patients' mobilisation capacity on a numerical rating scale ranging from 0 (no mobilisation) to 4 (ambulation). We had three main outcomes hierarchically tested in a prespecified order: the mean SOMS level patients achieved during their SICU stay (primary outcome), and patient's length of stay on SICU and the mini-modified functional independence measure score (mmFIM) at hospital discharge (both secondary outcomes). This trial is registered with ClinicalTrials.gov (NCT01363102).Between July 1, 2011, and Nov 4, 2015, we randomly assigned 200 patients to receive standard treatment (control; n=96) or intervention (n=104). Intention-to-treat analysis showed that the intervention improved the mobilisation level (mean achieved SOMS 2·2 [SD 1·0] in intervention group vs 1·5 [0·8] in control group, p0·0001), decreased SICU length of stay (mean 7 days [SD 5-12] in intervention group vs 10 days [6-15] in control group, p=0·0054), and improved functional mobility at hospital discharge (mmFIM score 8 [4-8] in intervention group vs 5 [2-8] in control group, p=0·0002). More adverse events were reported in the intervention group (25 cases [2·8%]) than in the control group (ten cases [0·8%]); no serious adverse events were observed. Before hospital discharge 25 patients died (17 [16%] in the intervention group, eight [8%] in the control group). 3 months after hospital discharge 36 patients died (21 [22%] in the intervention group, 15 [17%] in the control group).Early, goal-directed mobilisation improved patient mobilisation throughout SICU admission, shortened patient length of stay in the SICU, and improved patients' functional mobility at hospital discharge.Jeffrey and Judy Buzen.

Early mobilization within 72 h of intensive care unit (ICU) admission improves functional status at hospital discharge. We aimed to assess the effectiveness of early, goal-directed mobilization in critically ill patients across a broad spectrum of initial consciousness levels. Post hoc analysis of the international, randomized, controlled, outcome-assessor blinded SOMS trial conducted 2011–2015. Randomization was stratified according to the immediate post-injury Glasgow Coma Scale (GCS) (≤ 8 or > 8). Patients received either SOMS-guided mobility treatment with a facilitator or standard care. We used general linear models to test the hypothesis that immediate post-randomization GCS modulates the intervention effects on functional independence at hospital discharge. Two hundred patients were included in the intention-to-treat analysis. The significant effect of early, goal-directed mobilization was consistent across levels of GCS without evidence of effect modification, for the primary outcome functional independence at hospital discharge (p = 0.53 for interaction), as well as average achieved mobility level during ICU stay (mean achieved SOMS level) and functional status at hospital discharge measured with the functional independence measure. In patients with low GCS, delay to first mobilization therapy was longer (0.7 ± 0.2 days vs. 0.2 ± 0.1 days, p = 0.008), but early, goal-directed mobilization compared with standard care significantly increased functional independence at hospital discharge in this subgroup of patients with immediate post-randomization GCS ≤ 8 (OR 3.67; 95% CI 1.02–13.14; p = 0.046). This post hoc analysis of a randomized controlled trial suggests that early, goal-directed mobilization in patients with an impaired initial conscious state (GCS ≤ 8) is not harmful but effective.

Residual neuromuscular block (rNMB) after surgery is not difficult to identify if proper neuromuscular monitoring is used, but many clinicians do not use quantitative neuromuscular monitoring.The aim of this study was to develop a REsidual neuromuscular block Prediction Score (REPS) to predict postoperative rNMB and compare the predictive accuracy of the prediction score with train-of-four count (TOFC) measurement at the end of a surgical case.Retrospective cohort study of data on file.Electronic patient data and peri-operative data on vital signs, administered medications, and train-of-four ratio (TOFR) obtained in the postoperative recovery rooms [postanaesthesia care unit (PACU)] at Massachusetts General Hospital in Boston, Massachusetts, USA.Quantitative TOFR measurements obtained on admission to the PACU were available from 2144 adult noncardiac surgical patients.Presence of rNMB at PACU admission, defined as a TOFR of less than 0.9.In the score development cohort (n=2144), rNMB occurred in 432 cases (20.2%). Ten independent predictors for residual paralysis were identified and used for the score development. The final model included: hepatic failure, neurological disease, high-neostigmine dose, metastatic tumour, female sex, short time between neuromuscular blocking agent administration and extubation, aminosteroidal neuromuscular blocking agent, BMI more than 35, absence of nurse anaesthetist and having an experienced surgeon. The model discrimination by C statistics was 0.63, 95% confidence interval (0.60 to 0.66), and risk categories derived from the REPS had a higher accuracy than the last documented intra-operative TOFC for predicting rNMB (net reclassification improvement score 0.26, standard error 0.03, P 0.001).The REPS can be used to identify patients at greater risk of rNMB. This tool may inform anaesthetists better than an intra-operative TOFC and thus enable peri-operative anaesthetic practices to be tailored to the patient and minimise the undesirable effects of rNMB.Approved by Partners Human Research Committee (protocol number 2016P000940) at MGH in Boston, Massachusetts, USA on 25 April 2016.

Study Objectives Following extubation in the intensive care unit (ICU), upper airway (UA) edema and respiratory depressants may promote UA dysfunction. We tested the hypothesis that opioids increase the risk of sleep apnea early after extubation. Methods Fifty-six ICU patients underwent polysomnography the night after extubation. Airflow limitation during wakefulness was identified using bedside spirometry. Correlation and ordinal regression analyses were used to quantify the effects of preextubation opioid dose on postextubation apnea-hypopnea index (AHI) and severity of sleep apnea and whether or not inspiratory airway obstruction (ratio of maximum expiratory and inspiratory airflows at 50% of vital capacity [MEF50/MIF50] ≥ 1) during wakefulness predicts airway obstruction during sleep. Data were adjusted for age, gender, body mass index, as well as a generalized propensity score balanced for APACHE II, score for preoperative prediction of obstructive sleep apnea, duration of mechanical ventilation, chronic obstructive pulmonary disease, and a procedural severity score for morbidity. Results Sleep apnea (AHI ≥ 5) was present in 40 (71%) of the 56 patients. Morphine equivalent dose given 24 hours prior extubation predicted obstructive respiratory events during sleep (r = 0.35, p = .01) and sleep apnea (odds ratio [OR] 1.17; 95% confidence interval [CI] 1.02-1.34). Signs of inspiratory UA obstruction (MEF50/MIF50 ≥ 1) assessed by bedside spirometry were strongly associated with sleep apnea (OR 5.93; 95% CI 1.16-30.33). Conclusions High opioid dose given 24 hours prior to extubation increases the likelihood of postextubation sleep apnea in the ICU, particularly in patients with anatomical vulnerability following extubation.

Background High inspiratory oxygen fraction ( F I O 2 ) may improve tissue oxygenation but also impair pulmonary function. We aimed to assess whether the use of high intraoperative F I O 2 increases the risk of major respiratory complications. Methods We studied patients undergoing non-cardiothoracic surgery involving mechanical ventilation in this hospital-based registry study. The cases were divided into five groups based on the median F I O 2 between intubation and extubation. The primary outcome was a composite of major respiratory complications (re-intubation, respiratory failure, pulmonary oedema, and pneumonia) developed within 7 days after surgery. Secondary outcomes included 30-day mortality. Several predefined covariates were included in a multivariate logistic regression model. Results The primary analysis included 73 922 cases, of whom 3035 (4.1%) developed a major respiratory complication within 7 days of surgery. For patients in the high- and low-oxygen groups, the median F I O 2 was 0.79 [range 0.64–1.00] and 0.31 [0.16–0.34], respectively. Multivariate logistic regression analysis revealed that the median F I O 2 was associated in a dose-dependent manner with increased risk of respiratory complications (adjusted odds ratio for high vs low F I O 2 1.99, 95% confidence interval [1.72–2.31], P -value for trend

Inhalational anesthetic agents (IAs) have been used for general anesthesia for more than 150 years. Since then, the safety profile of this class of anesthetics has improved markedly as drugs to control hypotension and techniques to secure the airway have been refined. However, it is only over the past few decades that we have begun to appreciate the versatility and benefits of using these agents for more than just anesthesia. We recently published a study reporting a dose-dependent protective effect of inhalational anesthetics against postoperative respiratory complications. These findings have generated great interest and discussion, and we thank Landoni et al . for their acknowledgement of and insight into the implications these findings may have for inhalational anesthetic use both within and outside of the operating room setting.

Purpose of review Postoperative respiratory complications (PRCs) increase hospitalization time, 30-day mortality and costs by up to $35 000. These outcomes measures have gained prominence as bundled payments have become more common. Recent findings Results of recent quantitative effectiveness studies and clinical trials provide a framework that helps develop center-specific treatment guidelines, tailored to minimize the risk of PRCs. The implementation of those protocols should be guided by a local, respected, and visible facilitator who leads proper implementation while inviting center-specific input from surgeons, anesthesiologists, and other perioperative stakeholders. Summary Preoperatively, patients should be risk-stratified for PRCs to individualize intraoperative choices and postoperative pathways. Laparoscopic compared with open surgery improves respiratory outcomes. High-risk patients should be treated by experienced providers based on locally developed bundle-interventions to optimize intraoperative treatment and ICU bed utilization. Intraoperatively, lung-protective ventilation (procedure-specific positive end-expiratory pressure utilization, and low driving pressure) and moderately restrictive fluid therapy should be used. To achieve surgical relaxation, high-dose neuromuscular blocking agents (and reversal agents) as well as high-dose opioids should be avoided; inhaled anesthetics improve surgical conditions while protecting the lungs. Patients should be extubated in reverse Trendelenburg position. Postoperatively, continuous positive airway pressure helps prevent airway collapse and protocolized, early mobilization improves cognitive and respiratory function.

Background Postoperative respiratory complications (PRCs) are associated with significant morbidity, mortality, and hospital costs. Obstructive sleep apnea (OSA), often undiagnosed in the surgical population, may be a contributing factor. Thus, we aimed to develop and validate a score for preoperative prediction of OSA (SPOSA) based on data available in electronic medical records preoperatively. Methods OSA was defined as the occurrence of an OSA diagnostic code preceded by a polysomnography procedure. A priori defined variables were analyzed by multivariable logistic regression analysis to develop our score. Score validity was assessed by investigating the score’s ability to predict non-invasive ventilation. We then assessed the effect of high OSA risk, as defined by SPOSA, on PRCs within seven postoperative days and in-hospital mortality. Results A total of 108,781 surgical patients at Partners HealthCare hospitals (2007–2014) were studied. Predictors of OSA included BMI >25 kg*m−2 and comorbidities, including pulmonary hypertension, hypertension, and diabetes. The score yielded an area under the curve of 0.82. Non-invasive ventilation was significantly associated with high OSA risk (OR 1.44, 95% CI 1.22–1.69). Using a dichotomized endpoint, 26,968 (24.8%) patients were identified as high risk for OSA and 7.9% of these patients experienced PRCs. OSA risk was significantly associated with PRCs (OR 1.30, 95% CI 1.19–1.43). Conclusion SPOSA identifies patients at high risk for OSA using electronic medical record-derived data. High risk of OSA is associated with the occurrence of PRCs. Electronic supplementary material The online version of this article (doi:10.1186/s12871-017-0361-z) contains supplementary material, which is available to authorized users.

We hypothesised that intraoperative non-depolarising neuromuscular blocking agent (NMBA) dose is associated with 30-day hospital readmission.Data from 13,122 adult patients who underwent abdominal surgery under general anaesthesia at a tertiary care hospital were analysed by multivariable regression, to examine the effects of intraoperatively administered NMBA dose on 30-day readmission (primary endpoint), hospital length of stay, and hospital costs.Clinicians used cisatracurium (mean dose [SD] 0.19 mg kg-1 [0.12]), rocuronium (0.83 mg kg-1 [0.53]) and vecuronium (0.14 mg kg-1 [0.07]). Intraoperative administration of NMBAs was dose-dependently associated with higher risk of 30-day hospital readmission (adjusted odds ratio 1.89 [95% Confidence Interval (CI) 1.26-2.84] for 5th quintile vs 1st quintile; P for trend: P0.001), prolonged hospital length of stay (adjusted incidence rate ratio [aIRR] 1.20 [95% CI 1.11-1.29]; P for trend: P0.001) and increased hospital costs (aIRR 1.18 [95% CI 1.13-1.24]; P for trend: P0.001). Admission type (same-day vs inpatient surgery) significantly modified the risk (interaction term: aOR 1.31 [95% CI 1.05-1.63], P=0.02), and the adjusted odds of readmission in patients undergoing ambulatory surgical procedures who received high-dose NMBAs vs low-dose NMBAs amounted to 2.61 [95% CI 1.11-6.17], P for trend: P0.001. Total intraoperative neostigmine dose increased the risk of 30-day readmission (aOR 1.04 [1.0-1.08], P=0.048).In a retrospective analysis, high doses of NMBAs given during abdominal surgery was associated with an increased risk of 30-day readmission, particularly in patients undergoing ambulatory surgery.

Background Bariatric surgery patients are vulnerable to sleep-disordered breathing (SDB) early after recovery from surgery and anesthesia. The authors hypothesized that continuous positive airway pressure (CPAP) improves postoperative oxygenation and SDB and mitigates opioid-induced respiratory depression. Methods In a randomized crossover trial, patients after bariatric surgery received 30% oxygen in the postanesthesia care unit (PACU) under two conditions: atmospheric pressure and CPAP (8 to 10 cm H2O). During 1 h of each treatment, breathing across cortical arousal states was analyzed using polysomnography and spirometry. Arousal state and respiratory events were scored in accordance with American Academy of Sleep Medicine guidelines. Data on opioid boluses in the PACU were collected. The primary and secondary outcomes were the apnea hypopnea index (AHI) and apnea after self-administration of opioids in the PACU. Linear mixed model analysis was used to compare physiologic measures of breathing. Results Sixty-four percent of the 33 patients with complete postoperative polysomnography data demonstrated SDB (AHI greater than 5/h) early after recovery from anesthesia. CPAP treatment decreased AHI (8 ± 2/h vs. 25 ± 5/h, P < 0.001), decreased oxygen desaturations (5 ± 10/h vs. 16 ± 20/h, P < 0.001), and increased the mean oxygen saturation by 3% (P = 0.003). CPAP significantly decreased the respiratory-depressant effects observed during wakefulness–sleep transitions without affecting hemodynamics. The interaction effects between CPAP treatment and opioid dose for the dependent variables AHI (P < 0.001), inspiratory flow (P = 0.002), and minute ventilation (P = 0.015) were significant. Conclusions This pharmacophysiologic interaction trial shows that supervised CPAP treatment early after surgery improves SDB and ameliorates the respiratory-depressant effects of opioids without undue hemodynamic effects.

Background Calabadion 2 is a new drug-encapsulating agent. In this study, the authors aim to assess its utility as an agent to reverse general anesthesia with etomidate and ketamine and facilitate recovery. Methods To evaluate the effect of calabadion 2 on anesthesia recovery, the authors studied the response of rats to calabadion 2 after continuous and bolus intravenous etomidate or ketamine and bolus intramuscular ketamine administration. The authors measured electroencephalographic predictors of depth of anesthesia (burst suppression ratio and total electroencephalographic power), functional mobility impairment, blood pressure, and toxicity. Results Calabadion 2 dose-dependently reverses the effects of ketamine and etomidate on electroencephalographic predictors of depth of anesthesia, as well as drug-induced hypotension, and shortens the time to recovery of righting reflex and functional mobility. Calabadion 2 displayed low cytotoxicity in MTS-3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium–based cell viability and adenylate kinase release cell necrosis assays, did not inhibit the human ether-à-go-go-related channel, and was not mutagenic (Ames test). On the basis of maximum tolerable dose and acceleration of righting reflex recovery, the authors calculated the therapeutic index of calabadion 2 in recovery as 16:1 (95% CI, 10 to 26:1) for the reversal of ketamine and 3:1 (95% CI, 2 to 5:1) for the reversal of etomidate. Conclusions Calabadion 2 reverses etomidate and ketamine anesthesia in rats by chemical encapsulation at nontoxic concentrations.

To compare sarcopenia and frailty for outcome prediction in surgical intensive care unit (SICU) patients.Frailty has been associated with adverse outcomes and describes a status of muscle weakness and decreased physiological reserve leading to increased vulnerability to stressors. However, frailty assessment depends on patient cooperation. Sarcopenia can be quantified by ultrasound and the predictive value of sarcopenia at SICU admission for adverse outcome has not been defined.We conducted a prospective, observational study of SICU patients. Sarcopenia was diagnosed by ultrasound measurement of rectus femoris cross-sectional area. Frailty was diagnosed by the Frailty Index Questionnaire based on 50 variables. Relationship between variables and outcomes was assessed by multivariable regression analysis NCT02270502.Sarcopenia and frailty were quantified in 102 patients and observed in 43.1% and 38.2%, respectively. Sarcopenia predicted adverse discharge disposition (discharge to nursing facility or in-hospital mortality, odds ratio 7.49; 95% confidence interval 1.47-38.24; P = 0.015) independent of important clinical covariates, as did frailty (odds ratio 8.01; 95% confidence interval 1.82-35.27; P = 0.006); predictive ability did not differ between sarcopenia and frailty prediction model, reflected by χ values of 21.74 versus 23.44, respectively, and a net reclassification improvement (NRI) of -0.02 (P = 0.87). Sarcopenia and frailty predicted hospital length of stay and the frailty model had a moderately better predictive accuracy for this outcome.Bedside diagnosis of sarcopenia by ultrasound predicts adverse discharge disposition in SICU patients equally well as frailty. Sarcopenia assessed by ultrasound may be utilized as rapid beside modality for risk stratification of critically ill patients.

Objective To evaluate the effects of intraoperative protective ventilation on major postoperative respiratory complications and to define safe intraoperative mechanical ventilator settings that do not translate into an increased risk of postoperative respiratory complications. Design Hospital based registry study. Setting Academic tertiary care hospital and two affiliated community hospitals in Massachusetts, United States. Participants 69 265 consecutively enrolled patients over the age of 18 who underwent a non-cardiac surgical procedure between January 2007 and August 2014 and required general anesthesia with endotracheal intubation. Interventions Protective ventilation, defined as a median positive end expiratory pressure (PEEP) of 5 cmH 2 O or more, a median tidal volume of less than 10 mL/kg of predicted body weight, and a median plateau pressure of less than 30 cmH 2 O. Main outcome measure Composite outcome of major respiratory complications, including pulmonary edema, respiratory failure, pneumonia, and re-intubation. Results Of the 69 265 enrolled patients 34 800 (50.2%) received protective ventilation and 34 465 (49.8%) received non-protective ventilation intraoperatively. Protective ventilation was associated with a decreased risk of postoperative respiratory complications in multivariable regression (adjusted odds ratio 0.90, 95% confidence interval 0.82 to 0.98, P=0.013). The results were similar in the propensity score matched cohort (odds ratio 0.89, 95% confidence interval 0.83 to 0.97, P=0.004). A PEEP of 5 cmH 2 O and median plateau pressures of 16 cmH 2 O or less were associated with the lowest risk of postoperative respiratory complications. Conclusions Intraoperative protective ventilation was associated with a decreased risk of postoperative respiratory complications. A PEEP of 5 cmH 2 O and a plateau pressure of 16 cmH 2 O or less were identified as protective mechanical ventilator settings. These findings suggest that protective thresholds differ for intraoperative ventilation in patients with normal lungs compared with those used for patients with acute lung injury.

Objective To evaluate whether patients with migraine are at increased risk of perioperative ischemic stroke and whether this may lead to an increased hospital readmission rate. Design Prospective hospital registry study. Setting Massachusetts General Hospital and two satellite campuses between January 2007 and August 2014. Participants 124 558 surgical patients (mean age 52.6 years; 54.5% women). Main outcome measures The primary outcome was perioperative ischemic stroke occurring within 30 days after surgery in patients with and without migraine and migraine aura. The secondary outcome was hospital readmission within 30 days of surgery. Exploratory outcomes included post-discharge stroke and strata of neuroanatomical stroke location. Results 10 179 (8.2%) patients had any migraine diagnosis, of whom 1278 (12.6%) had migraine with aura and 8901 (87.4%) had migraine without aura. 771 (0.6%) perioperative ischemic strokes occurred within 30 days of surgery. Patients with migraine were at increased risk of perioperative ischemic stroke (adjusted odds ratio 1.75, 95% confidence interval 1.39 to 2.21) compared with patients without migraine. The risk was higher in patients with migraine with aura (adjusted odds ratio 2.61, 1.59 to 4.29) than in those with migraine without aura (1.62, 1.26 to 2.09). The predicted absolute risk is 2.4 (2.1 to 2.8) perioperative ischemic strokes for every 1000 surgical patients. This increases to 4.3 (3.2 to 5.3) for every 1000 patients with any migraine diagnosis, 3.9 (2.9 to 5.0) for migraine without aura, and 6.3 (3.2 to 9.5) for migraine with aura. Patients with migraine had a higher rate of readmission to hospital within 30 days of discharge (adjusted odds ratio 1.31, 1.22 to 1.41). Conclusions Surgical patients with a history of migraine are at increased risk of perioperative ischemic stroke and have an increased 30 day hospital readmission rate. Migraine should be considered in the risk assessment for perioperative ischemic stroke.