Effectiveness of Fludrocortisone Plus Hydrocortisone versus Hydrocortisone Alone in Septic Shock: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials.

Rationale: The use of hydrocortisone in adult patients with septic shock is controversial, and the effectiveness of adding fludrocortisone to hydrocortisone remains uncertain. Objectives: To assess the comparative effectiveness and safety of fludrocortisone plus hydrocortisone, hydrocortisone alone, and placebo or usual care in adults with septic shock. Methods: A systematic review and a Bayesian network meta-analysis of peer-reviewed randomized trials were conducted. The primary outcome was all-cause mortality at last follow-up. Treatment effects are presented as relative risks (RRs) with 95% credible intervals (CrIs). Placebo or usual care was the reference treatment. Measurements and Main Results: Among 7,553 references, we included 17 trials (7,688 patients). All-cause mortality at last follow-up was lowest with fludrocortisone plus hydrocortisone (RR, 0.85; 95% CrI, 0.72-0.99; 98.3% probability of superiority, moderate-certainty evidence), followed by hydrocortisone alone (RR, 0.97; 95% CrI, 0.87-1.07; 73.1% probability of superiority, low-certainty evidence). The comparison of fludrocortisone plus hydrocortisone versus hydrocortisone alone was based primarily on indirect evidence (only two trials with direct evidence). Fludrocortisone plus hydrocortisone was associated with a 12% lower risk of all-cause mortality compared with hydrocortisone alone (RR, 0.88; 95% CrI, 0.74-1.03; 94.2% probability of superiority, moderate-certainty evidence). Conclusions: In adult patients with septic shock, fludrocortisone plus hydrocortisone was associated with lower risk of all-cause mortality at last follow-up than placebo and hydrocortisone alone. The scarcity of head-to-head trials comparing fludrocortisone plus hydrocortisone versus hydrocortisone alone led our network meta-analysis to rely primarily on indirect evidence for this comparison. Although we undertook several sensitivity analyses and assessments, these findings should be considered while also acknowledging the heterogeneity of included trials.

Intraoperative Use of Phenylephrine versus Ephedrine and Postoperative Delirium: A Multicenter Retrospective Cohort Study.

BACKGROUND: The treatment of intraoperative hypotension with phenylephrine may impair cerebral perfusion through vasoconstriction, which has been linked to postoperative delirium. The hypothesis was that intraoperative administration of phenylephrine, compared to ephedrine, is associated with higher odds of postoperative delirium. METHODS: A total of 103,094 hospitalized adults undergoing general anesthesia for noncardiac, non-neurosurgical procedures between 2008 and 2020 at two tertiary academic healthcare networks in Massachusetts were included in this multicenter hospital registry study. The primary exposure was the administration of phenylephrine versus ephedrine during surgery, and the primary outcome was postoperative delirium within 7 days. Multivariable logistic regression analyses adjusted for a priori defined confounding variables including patient demographics, comorbidities, and procedural factors including magnitude of intraoperative hypotension were applied. RESULTS: Between the two healthcare networks, 78,982 (76.6%) patients received phenylephrine, and 24,112 (23.4%) patients received ephedrine during surgery; 770 patients (0.8%) developed delirium within 7 days. The median (interquartile range) total intraoperative dose of phenylephrine was 1.0 (0.2 to 3.3) mg and 10.0 (10.0 to 20.0) mg for ephedrine. In adjusted analyses, the administration of phenylephrine, compared to ephedrine, was associated with higher odds of developing postoperative delirium within 7 days (adjusted odds ratio, 1.35; 95% CI, 1.06 to 1.71; and adjusted absolute risk difference, 0.2%; 95% CI, 0.1 to 0.3%; P = 0.015). A keyword and manual chart review-based approach in a subset of 45,465 patients further validated these findings (delirium incidence, 3.2%; adjusted odds ratio, 1.88; 95% CI, 1.49 to 2.37; P < 0.001). Fractional polynomial regression analysis further indicated a dose-dependent effect of phenylephrine (adjusted coefficient, 0.08; 95% CI, 0.02 to 0.14; P = 0.013, per each µg/kg increase in the cumulative phenylephrine dose). CONCLUSIONS: The administration of phenylephrine compared to ephedrine during general anesthesia was associated with higher odds of developing postoperative delirium. Based on these data, clinical trials are warranted to determine whether favoring ephedrine over phenylephrine for treatment of intraoperative hypotension can reduce delirium after surgery.

Subjective Assessment of Motor Function by the Bedside Nurses in Mechanically Ventilated Surgical Intensive Care Unit Patients Predicts Tracheostomy.

OBJECTIVE: In many institutions, intensive care unit (ICU) nurses assess their patients' muscle function as part of their routine bedside examination. We tested the research hypothesis that this subjective examination of muscle function prior to extubation predicts tracheostomy requirement. METHODS: Adult, mechanically ventilated patients admitted to 7 ICUs at Beth Israel Deaconess Medical Center (BIDMC) between 2008 and 2019 were included in this observational study. Assessment of motor function was performed every four hours by ICU nurses. Multivariable logistic regression analysis controlled for acute disease severity, delirium risk assessment through the confusion assessment method for the ICU (CAM-ICU), and pre-defined predictors of extubation failure was applied to examine the association of motor function and tracheostomy within 30 days after extubation. RESULTS: Within 30 days after extubation, 891 of 9609 (9.3%) included patients required a tracheostomy. The inability to spontaneously move and hold extremities against gravity within 24 h prior to extubation was associated with significantly higher odds of 30-day tracheostomy (adjusted OR 1.56, 95% CI 1.27-1.91, p < 0.001, adjusted absolute risk difference (aARD) 2.8% (p < 0.001)). The effect was magnified among patients who were mechanically ventilated for >7 days (aARD 21.8%, 95% CI 12.4-31.2%, p-for-interaction = 0.015). CONCLUSIONS: ICU nurses' subjective assessment of motor function is associated with 30-day tracheostomy risk, independent of known risk factors. Muscle function measurements by nursing staff in the ICU should be discussed during interprofessional rounds.

Differential Effects of Gamma-Aminobutyric Acidergic Sedatives on Risk of Post-Extubation Delirium in the ICU: A Retrospective Cohort Study From a New England Health Care Network.

OBJECTIVES: To evaluate whether different gamma-aminobutyric acidergic (GABAergic) sedatives such as propofol and benzodiazepines carry differential risks of post-extubation delirium in the ICU. DESIGN: Retrospective cohort study. SETTING: Seven ICUs in an academic hospital network, Beth Israel Deaconess Medical Center (Boston, MA). PATIENTS: Ten thousand five hundred and one adult patients mechanically ventilated for over 24 hours. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We tested the hypothesis that benzodiazepine versus propofol-based sedation is associated with fewer delirium-free days within 14 days after extubation. Further, we hypothesized that the measured sedation level evoked by GABAergic drugs is a better predictor of delirium than the drug dose administered. The proportion of GABAergic drug-induced deep sedation was defined as the ratio of days with a mean Richmond Agitation-Sedation Scale of less than or equal to -3 during mechanical ventilation. Multivariable regression and effect modification analyses were used. Delirium-free days were lower in patients who received a high proportion of deep sedation using benzodiazepine compared with propofol-based sedation (adjusted absolute difference, -1.17 d; 95% CI, -0.64 to -1.69; p < 0.001). This differential effect was magnified in elderly patients (age > 65) and in patients with liver or kidney failure (p-for-interaction < 0.001) but not observed in patients who received a low proportion of deep sedation (p = 0.95). GABAergic-induced deep sedation days during mechanical ventilation was a better predictor of post-extubation delirium than the GABAergic daily average effective dose (area under the curve 0.76 vs 0.69; p < 0.001). CONCLUSIONS: Deep sedation during mechanical ventilation with benzodiazepines compared with propofol is associated with increased risk of post-extubation delirium. Our data do not support the view that benzodiazepine-based compared with propofol-based sedation in the ICU is an independent risk factor of delirium, as long as deep sedation can be avoided in these patients.

Association between intraoperative tidal volume and postoperative respiratory complications is dependent on respiratory elastance: a retrospective, multicentre cohort study.

BACKGROUND: The impact of high vs low intraoperative tidal volumes on postoperative respiratory complications remains unclear. We hypothesised that the effect of intraoperative tidal volume on postoperative respiratory complications is dependent on respiratory system elastance. METHODS: We retrospectively recorded tidal volume (Vt; ml kg-1 ideal body weight [IBW]) in patients undergoing elective, non-cardiothoracic surgery from hospital registry data. The primary outcome was respiratory failure (requiring reintubation within 7 days of surgery, desaturation after extubation, or both). The primary exposure was defined as the interaction between Vt and standardised respiratory system elastance (driving pressure divided by Vt; cm H2O/[ml kg-1]). Multivariable logistic regression models, with and without interaction terms (which categorised Vt as low [Vt ≤8 ml kg-1] or high [Vt >8 ml kg-1]), were adjusted for potential confounders. Additional analyses included path mediation analysis and fractional polynomial modelling. RESULTS: Overall, 10 821/197 474 (5.5%) patients sustained postoperative respiratory complications. Higher Vt was associated with greater risk of postoperative respiratory complications (adjusted odds ratio=1.42 per ml kg-1; 95% confidence interval [CI], 1.35-1.50]; P<0.001). This association was modified by respiratory system elastance (P<0.001); in patients with low compliance (<42.4 ml cm H2O-1), higher Vt was associated with greater risk of postoperative respiratory complications (adjusted risk difference=0.3% [95% CI, 0.0-0.5] at 41.2 ml cm H2O-1 compliance, compared with 5.8% [95% CI, 3.8-7.8] at 14 ml cm H2O-1 compliance). This association was absent when compliance exceeded 41.2 ml cm H2O-1. Adverse effects associated with high Vt were entirely mediated by driving pressures (P<0.001). CONCLUSIONS: The association of harm with higher tidal volumes during intraoperative mechanical ventilation is modified by respiratory system elastance. These data suggest that respiratory elastance should inform the design of perioperative trials testing intraoperative ventilatory strategies.

Association Between Intraoperative Arterial Hypotension and Postoperative Delirium After Noncardiac Surgery: A Retrospective Multicenter Cohort Study.

BACKGROUND: It is unclear whether intraoperative arterial hypotension is associated with postoperative delirium. We hypothesized that intraoperative hypotension within a range frequently observed in clinical practice is associated with increased odds of delirium after surgery. METHODS: Adult noncardiac surgical patients undergoing general anesthesia at 2 academic medical centers between 2005 and 2017 were included in this retrospective cohort study. The primary exposure was intraoperative hypotension, defined as the cumulative duration of an intraoperative mean arterial pressure (MAP) <55 mm Hg, categorized into and short (<15 minutes; median [interquartile range {IQR}], 2 [1-4] minutes) and prolonged (≥15 minutes; median [IQR], 21 [17-31] minutes) durations of intraoperative hypotension. The primary outcome was a new diagnosis of delirium within 30 days after surgery. In secondary analyses, we assessed the association between a MAP decrease of >30% from baseline and postoperative delirium. Multivariable logistic regression adjusted for patient- and procedure-related factors, including demographics, comorbidities, and markers of procedural severity, was used. RESULTS: Among 316,717 included surgical patients, 2183 (0.7%) were diagnosed with delirium within 30 days after surgery; 41.7% and 2.6% of patients had a MAP <55 mm Hg for a short and a prolonged duration, respectively. A MAP <55 mm Hg was associated with postoperative delirium compared to no hypotension (short duration of MAP <55 mm Hg: adjusted odds ratio [ORadj], 1.22; 95% confidence interval [CI], 1.11-1.33; P < .001 and prolonged duration of MAP <55 mm Hg: ORadj, 1.57; 95% CI, 1.27-1.94; P < .001). Compared to a short duration of a MAP <55 mm Hg, a prolonged duration of a MAP <55 mm Hg was associated with greater odds of postoperative delirium (ORadj, 1.29; 95% CI, 1.05-1.58; P = .016). The association between intraoperative hypotension and postoperative delirium was duration-dependent (ORadj for every 10 cumulative minutes of MAP <55 mm Hg: 1.06; 95% CI, 1.02-1.09; P =.001) and magnified in patients who underwent surgeries of longer duration (P for interaction = .046; MAP <55 mm Hg versus no MAP <55 mm Hg in patients undergoing surgery of >3 hours: ORadj, 1.40; 95% CI, 1.23-1.61; P < .001). A MAP decrease of >30% from baseline was not associated with postoperative delirium compared to no hypotension, also when additionally adjusted for the cumulative duration of a MAP <55 mm Hg (short duration of MAP decrease >30%: ORadj, 1.13; 95% CI, 0.91-1.40; P = .262 and prolonged duration of MAP decrease >30%: ORadj, 1.19; 95% CI, 0.95-1.49; P = .141). CONCLUSIONS: In patients undergoing noncardiac surgery, a MAP <55 mm Hg was associated with a duration-dependent increase in odds of postoperative delirium. This association was magnified in patients who underwent surgery of long duration.

Prolonged mechanical ventilation after cardiac surgery: substudy of the Transfusion Requirements in Cardiac Surgery III trial.

PURPOSE: Prolonged mechanical ventilation (MV) is a major complication following cardiac surgery. We conducted a secondary analysis of the Transfusion Requirements in Cardiac Surgery (TRICTS) III trial to describe MV duration, identify factors associated with prolonged MV, and examine associations of prolonged MV with mortality and complications. METHODS: Four thousand, eight hundred and nine participants undergoing cardiac surgery at 71 hospitals worldwide were included. Prolonged MV was defined based on the Society of Thoracic Surgeons definition as MV lasting 24 hr or longer. Adjusted associations of patient and surgical factors with prolonged MV were examined using multivariable logistic regression. Associations of prolonged MV with complications were assessed using odds ratios, and adjusted associations between prolonged MV and mortality were evaluated using multinomial regression. Associations of shorter durations of MV with survival and complications were explored. RESULTS: Prolonged MV occurred in 15% (725/4,809) of participants. Prolonged MV was associated with surgical factors indicative of complexity, such as previous cardiac surgery, cardiopulmonary bypass duration, and separation attempts; and patient factors such as critical preoperative state, left ventricular impairment, renal failure, and pulmonary hypertension. Prolonged MV was associated with perioperative but not long-term complications. After risk adjustment, prolonged MV was associated with perioperative mortality; its association with long-term mortality among survivors was weaker. Shorter durations of MV were not associated with increased risk of mortality or complications. CONCLUSION: In this substudy of the TRICS III trial, prolonged MV was common after cardiac surgery and was associated with patient and surgical risk factors. Although prolonged MV showed strong associations with perioperative complications and mortality, it was not associated with long-term complications and had weaker association with long-term mortality among survivors. STUDY REGISTRATION: www. CLINICALTRIALS: gov (NCT02042898); registered 23 January 2014. This is a substudy of the Transfusion Requirements in Cardiac Surgery (TRICS) III trial.

RéSUMé: OBJET: La ventilation mécanique (VM) prolongée est une complication majeure après chirurgie cardiaque. Nous avons effectué une analyze secondaire de l'étude TRICS III sur les besoins de transfusion au cours de la chirurgie cardiaque pour décrire la durée de la VM, identifier les facteurs associés à une VM prolongée et examiner les associations de la VM prolongée avec la mortalité et les complications. MéTHODES: Quatre mille huit cent neuf participants subissant une chirurgie cardiaque dans 71 hôpitaux à travers le monde ont été inclus. La VM prolongée a été définie à partir de la définition de la Society of Thoracic Surgeons comme un événement durant 24 heures ou plus. Des associations ajustées de facteurs liés aux patients et à la chirurgie avec la VM prolongée ont été examinées en utilisant une régression logistique multifactorielle. Des associations de la VM prolongée avec des complications ont été évaluées en utilisant des rapports de cotes; les associations ajustées entre VM prolongée et mortalité ont été évaluées au moyen d'une régression multinominale. Les associations d'une VM de plus courte durée avec la survie et des complications ont été explorées. RéSULTATS: La VM prolongée est survenue chez 15 % (725/4 809) des participants. Une VM prolongée a été associée à des facteurs chirurgicaux indicateurs de complexité (comme une chirurgie cardiaque antérieure, la durée de la circulation extracorporelle et les tentatives de débranchement) et à des facteurs liés au patient (comme un état préopératoire critique, une défaillance ventriculaire gauche, une insuffisance rénale et une hypertension pulmonaire). La VM prolongée a été associée à des complications périopératoires, mais pas à des complications à long terme. Après ajustement pour le risque, la VM prolongée a été associée à la mortalité périopératoire; son association avec la mortalité à long terme des survivants a été plus faible. Les durées plus courtes de VM n'ont pas été associées à une augmentation du risque de mortalité ou à des complications. CONCLUSION: Dans cette étude auxiliaire de l'essai TRICS III, la VM prolongée a été fréquente après chirurgie cardiaque et a été associée à des facteurs de risque liés au patient et à la chirurgie. Bien que la VM prolongée ait présenté de fortes associations avec les complications périopératoires et la mortalité, elle n'a pas été associée avec des complications à long terme et était plus faiblement associée à la mortalité à long terme parmi les survivants. ENREGISTREMENT DE L'éTUDE: www.ClinicalTrials.gov (NCT02042898); enregistrée le 23 janvier 2014. Il s'agit d'une étude auxiliaire de l'étude TRICS III sur les besoins de transfusion en chirurgie cardiaque.

Association of Sedation, Coma, and In-Hospital Mortality in Mechanically Ventilated Patients With Coronavirus Disease 2019-Related Acute Respiratory Distress Syndrome: A Retrospective Cohort Study.

OBJECTIVES: In patients with coronavirus disease 2019-associated acute respiratory distress syndrome, sedatives and opioids are commonly administered which may lead to increased vulnerability to neurologic dysfunction. We tested the hypothesis that patients with coronavirus disease 2019-associated acute respiratory distress syndrome are at higher risk of in-hospital mortality due to prolonged coma compared with other patients with acute respiratory distress syndrome matched for disease severity. DESIGN: Propensity-matched cohort study. SETTING: Seven ICUs in an academic hospital network, Beth Israel Deaconess Medical Center (Boston, MA). PATIENTS: All mechanically ventilated coronavirus disease 2019 patients between March and May 2020 were identified and matched with patients with acute respiratory distress syndrome of other etiology. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Using clinical data obtained from a hospital registry, we matched 114 coronavirus disease 2019 patients to 228 noncoronavirus disease 2019-related acute respiratory distress syndrome patients based on baseline disease severity. Coma was identified using the Richmond Agitation Sedation Scale less than or equal to -3. Multivariable logistic regression and mediation analyses were used to assess the percentage of comatose days, sedative medications used, and the association between coronavirus disease 2019 and in-hospital mortality. In-hospital mortality (48.3% vs 31.6%, adjusted odds ratio, 2.15; 95% CI, 1.34-3.44; p = 0.002), the percentage of comatose days (66.0% ± 31.3% vs 36.0% ± 36.9%, adjusted difference, 29.35; 95% CI, 21.45-37.24; p < 0.001), and the hypnotic agent dose (51.3% vs 17.1% of maximum hypnotic agent dose given in the cohort; p < 0.001) were higher among patients with coronavirus disease 2019. Brain imaging did not show a higher frequency of structural brain lesions in patients with coronavirus disease 2019 (6.1% vs 7.0%; p = 0.76). Hypnotic agent dose was associated with coma (adjusted coefficient, 0.61; 95% CI, 0.45-0.78; p < 0.001) and mediated (p = 0.001) coma. Coma was associated with in-hospital mortality (adjusted odds ratio, 5.84; 95% CI, 3.58-9.58; p < 0.001) and mediated 59% of in-hospital mortality (p < 0.001). CONCLUSIONS: Compared with matched patients with acute respiratory distress syndrome of other etiology, patients with coronavirus disease 2019 received higher doses of hypnotics, which was associated with prolonged coma and higher mortality.

Effects of the Level and Duration of Mobilization Therapy in the Surgical ICU on the Loss of the Ability to Live Independently: An International Prospective Cohort Study.

OBJECTIVES: It is unclear whether early mobilization in the surgical ICU helps improve patients' functional recovery to a level that enables independent living. We assessed dose of mobilization (level + duration). We tested the research hypotheses that dose of mobilization predicts adverse discharge and that both duration of mobilization and maximum mobilization level predict adverse discharge. DESIGN: International, prospective cohort study. SETTING: Study conducted in five surgical ICUs at four different institutions. PATIENTS: One hundred fifty patients who were functionally independent before admission (Barthel Index ≥ 70) and who were expected to stay in the ICU for greater than or equal to 72 hours. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Mobilization was quantified daily, and treatments from all healthcare providers were included. We developed and used the Mobilization Quantification Score that quantifies both level and duration of mobilization. We assessed the association between the dose of mobilization (level + duration; exposure) and adverse discharge disposition (loss of the ability to live independently; primary outcome). There was wide variability in the dose of mobilization across centers and patients, which could not be explained by patients' comorbidity or disease severity. Dose of mobilization was associated with reduced risk of adverse discharge (adjusted odds ratio, 0.21; 95%CI, 0.09-0.50; p < 0.001). Both level and duration explained variance of adverse discharge (adjusted odds ratio, 0.28; 95% CI, 0.12-0.65; p = 0.003; adjusted odds ratio, 0.14; 95% CI, 0.06-0.36; p < 0.001, respectively). Duration compared with the level of mobilization tended to explain more variance in adverse discharge (area under the curve duration 0.73; 95% CI, 0.64-0.82; area under the curve mobilization level 0.68; 95% CI, 0.58-0.77; p = 0.10). CONCLUSIONS: We observed wide variability in dose of mobilization treatment applied, which could not be explained by patients' comorbidity or disease severity. High dose of mobilization is an independent predictor of patients' ability to live independently after discharge. Duration of mobilization sessions should be taken into account in future quality improvement and research projects.

A Tool to Predict Readmission to the Intensive Care Unit in Surgical Critical Care Patients-The RISC Score.

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 <7 mg/dl), hyperglycemia (>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.

Discharge Prediction for Patients Undergoing Inpatient Surgery: Development and validation of the DEPENDENSE score.

BACKGROUND: A substantial proportion of patients undergoing inpatient surgery each year is at risk for postoperative institutionalization and loss of independence. Reliable individualized preoperative prediction of adverse discharge can facilitate advanced care planning and shared decision making. METHODS: Using hospital registry data from previously home-dwelling adults undergoing inpatient surgery, we retrospectively developed and externally validated a score predicting adverse discharge. Multivariable logistic regression analysis and bootstrapping were used to develop the score. Adverse discharge was defined as in-hospital mortality or discharge to a skilled nursing facility. The model was subsequently externally validated in a cohort of patients from an independent hospital. RESULTS: In total, 106 164 patients in the development cohort and 92 962 patients in the validation cohort were included, of which 16 624 (15.7%) and 7717 (8.3%) patients experienced adverse discharge, respectively. The model was predictive of adverse discharge with an area under the receiver operating characteristic curve (AUC) of 0.87 (95% CI 0.87-0.88) in the development cohort and an AUC of 0.86 (95% CI 0.86-0.87) in the validation cohort. CONCLUSION: Using preoperatively available data, we developed and validated a prediction instrument for adverse discharge following inpatient surgery. Reliable prediction of this patient centered outcome can facilitate individualized operative planning to maximize value of care.

Association between propofol dose and 1-year mortality in patients with or without a diagnosis of solid cancer.

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<0.001 for interaction). Increasing propofol dose was associated with reduced odds of 1-yr mortality in patients without solid cancer (aOR: 0.78; 95% CI: 0.71-0.85), but not in patients with solid cancer (0.99; 0.94-1.04), a finding that was replicated when examining 5-yr mortality. 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.

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.

The Effects of Postoperative Residual Neuromuscular Blockade on Hospital Costs and Intensive Care Unit Admission: A Population-Based Cohort Study.

BACKGROUND: 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). METHODS: 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 ratio <0.9 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. RESULTS: 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. CONCLUSIONS: 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.

Cost-Effectiveness Research in Anesthesiology.

Perioperative interventions aimed at decreasing costs and improving outcomes have become increasingly popular in recent years. Anesthesiologists are often faced with a choice among different treatment strategies with little data available on the comparative cost-effectiveness. We performed a systematic review of the English language literature between 1980 and 2014 to identify cost-effectiveness analyses of anesthesiology and perioperative medicine interventions. We excluded interventions related to critical care or pediatric anesthesiology, and articles on interventions not normally ordered or performed by anesthesiologists. Of the >5000 cost-effectiveness analyses published to date, only 28 were applicable to anesthesiology and perioperative medicine and met inclusion criteria. Multidisciplinary interventions were the most cost-effective overall; 8 of 8 interventions were "dominant" (improved outcomes, reduced cost) or cost-effective, including accelerated, standardized perioperative recovery pathways, and perioperative delirium prevention bundles. Intraoperative measures were dominant in 3 of 5 cases, including spinal anesthesia for benign abdominal hysterectomy. With regard to prevention of perioperative infection, methicillin-resistant Staphylococcus aureus (MRSA) decolonization was dominant or cost-effective in 2 of 2 studies. Three studies assessing various antibiotic prophylaxis regimens had mixed results. Autologous blood donation was not found to be cost-effective in 5 of 7 studies, and intraoperative cell salvage therapy was also not cost-effective in 2 of 2 reports. Overall, there remains a paucity of cost-effectiveness literature in anesthesiology, particularly relating to intraoperative interventions and multidisciplinary perioperative interventions. Based on the available studies, multidisciplinary perioperative optimization interventions such as accelerated, standardized perioperative recovery pathways, and perioperative delirium prevention bundles tended to be most cost-effective. Our review demonstrates that there is a need for more rigorous cost-effective analyses in many areas of anesthesiology and that anesthesiologists should continue to lead collaborative, multidisciplinary efforts in perioperative medicine.