Publications by authors named "Xinling Xu"

52 Publications

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

BMJ Open 2021 Apr 14;11(4):e048509. Epub 2021 Apr 14.

Department of Anesthesia, Critical Care and Pain Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA.

Objective: To assess variability in the intraoperative use of non-depolarising neuromuscular blocking agents (NMBAs) across individual anaesthesia providers, surgeons and hospitals.

Design: Retrospective observational cohort study.

Setting: Two major tertiary referral centres, Boston, Massachusetts, USA.

Participants: 265 537 adult participants undergoing non-cardiac surgery between October 2005 and September 2017.

Main Outcome Measures: We analysed the variances in NMBA use across 958 anaesthesia and 623 surgical providers, across anaesthesia provider types (anaesthesia residents, certified registered nurse anaesthetists, attendings) and across hospitals using multivariable-adjusted mixed effects logistic regression. Intraclass correlations (ICC) were calculated to further quantify the variability in NMBA use that was unexplained by other covariates. Procedure-specific subgroup analyses were performed.

Results: NMBAs were used in 183 242 (69%) surgical cases. Variances in NMBA use were significantly higher among individual surgeons than among anaesthesia providers (variance 1.32 (95% CI 1.06 to 1.60) vs 0.24 (95% CI 0.19 to 0.28), p<0.001). Procedure-specific subgroup analysis of hernia repairs, spine surgeries and mastectomies confirmed our findings: the total variance in NMBA use that was unexplained by the covariate model was higher for surgeons versus anaesthesia providers (ICC 37.0% vs 13.0%, 69.7% vs 25.5%, 69.8% vs 19.5%, respectively; p<0.001). Variances in NMBA use were also partially explained by the anaesthesia provider's hospital network (Massachusetts General Hospital: variance 0.35 (95% CI 0.27 to 0.43) vs Beth Israel Deaconess Medical Center: 0.15 (95% CI 0.12 to 0.19); p<0.001). Across provider types, surgeons showed the highest variance, and anaesthesia residents showed the lowest variance in NMBA use.

Conclusions: There is wide variability across individual surgeons and anaesthesia providers and institutions in the use of NMBAs, which could not sufficiently be explained by a large number of patient-related and procedure-related characteristics, but may instead be driven by preference. Surgeons may have a stronger influence on a key aspect of anaesthesia management than anticipated.
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http://dx.doi.org/10.1136/bmjopen-2020-048509DOI Listing
April 2021

Optimal Sedation in Patients Who Receive Neuromuscular Blocking Agent Infusions for Treatment of Acute Respiratory Distress Syndrome-A Retrospective Cohort Study From a New England Health Care Network.

Crit Care Med 2021 03 12. Epub 2021 Mar 12.

Department of Anesthesia, Critical Care and Pain Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA. Department of Anesthesiology, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand. Klinik für Anästhesiologie, operative Intensivmedizin, Schmerz- und Palliativmedizin, Marien Hospital Herne, Universitätsklinikum der Ruhr-Universität Bochum, Herne, Germany. Department of Medicine, Division of Pulmonary and Critical Care, Beth Israel Deaconess Medical Center, Boston, MA.

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.
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http://dx.doi.org/10.1097/CCM.0000000000004951DOI Listing
March 2021

Effects of Volatile Anesthetics on Postoperative Ischemic Stroke Incidence.

J Am Heart Assoc 2021 Feb 26;10(5):e018952. Epub 2021 Feb 26.

Department of Anesthesia, Critical Care and Pain Medicine Beth Israel Deaconess Medical CenterHarvard Medical School Boston MA.

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 <18 years, cardiac surgery, and missing covariate data. The exposure was defined as median age-adjusted minimum alveolar concentration of all intraoperative measurements of desflurane, sevoflurane, and isoflurane. The primary outcome was postoperative ischemic stroke within 30 days. Among 314 932 patients, 1957 (0.6%) experienced the primary outcome. Higher doses of volatile anesthetics had a protective effect on postoperative ischemic stroke incidence (adjusted odds ratio per 1 minimum alveolar concentration increase 0.49, 95% CI, 0.40-0.59, <0.001). In Cox proportional hazards regression, the effect was observed for 17 postoperative days (postoperative day 1: hazard ratio (HR), 0.56; 95% CI, 0.48-0.65; versus day 17: HR, 0.85; 95% CI, 0.74-0.99). Volatile anesthetics were also associated with lower stroke severity: Every 1-unit increase in minimum alveolar concentration was associated with a 0.006-unit decrease in the National Institutes of Health Stroke Scale (95% CI, -0.01 to -0.002, =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.
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http://dx.doi.org/10.1161/JAHA.120.018952DOI Listing
February 2021

Preoperative Heart Failure Treatment Prevents Postoperative Cardiac Complications in Patients With Lower Risk: A Retrospective Cohort Study.

Ann Surg 2021 Feb 1. Epub 2021 Feb 1.

Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA Department of Anesthesia, Critical Care and Pain Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA Division of Respiratory and Critical Care Medicine, Department of Medicine, The University of Hong Kong, Hong Kong Cardiology Division, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA Brigham and Women's Hospital Heart & Vascular Center, Harvard Medical School, Boston, MA, USA Klinik für Anästhesiologie und Intensivmedizin, Universitätsklinikum Essen, Essen, Germany.

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.
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http://dx.doi.org/10.1097/SLA.0000000000004779DOI Listing
February 2021

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

Anesth Analg 2021 Jan 22. Epub 2021 Jan 22.

From the Department of Anesthesia, Critical Care and Pain Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts.

Background: Residual neuromuscular blockade is associated with an increased incidence of postoperative respiratory complications. The REsidual neuromuscular block Prediction Score (REPS) identifies patients at high risk for residual neuromuscular blockade after surgery.

Methods: A total of 101,510 adults undergoing noncardiac surgery under general anesthesia from October 2005 to December 2018 at a tertiary care center in Massachusetts were analyzed for the primary outcome of postoperative respiratory complications (invasive mechanical ventilation requirement within 7 postoperative days or immediate postextubation desaturation [oxygen saturation {Spo2} <90%] within 10 minutes). The primary objective was to assess the association between the REPS and respiratory complications. The secondary objective was to compare REPS and train-of-four (TOF) ratio <0.90 on the strength of their association with respiratory complications.

Results: A high REPS (≥4) was associated with an increase in odds of respiratory complications (adjusted odds ratio [OR], 1.13 [95% confidence interval {CI}, 1.06-1.21]; P < .001). In 6224 cases with available TOF ratio measurements, a low TOF ratio (<0.9) was associated with respiratory complications (adjusted OR, 1.43 [95% CI, 1.11-1.85]; P = .006), whereas a high REPS was not (adjusted OR, 0.96 [95% CI, 0.74-1.23]; P = .73) (P = .018 for comparison between ORs).

Conclusions: The REPS may be implemented as a screening tool to encourage clinicians to use quantitative neuromuscular monitoring in patients at risk of residual neuromuscular blockade. A positive REPS should be followed by a quantitative assessment of the TOF ratio.
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http://dx.doi.org/10.1213/ANE.0000000000005363DOI Listing
January 2021

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.

Crit Care Med 2021 03;49(3):e247-e257

Department of Anesthesia, Critical Care and Pain Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA.

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.
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http://dx.doi.org/10.1097/CCM.0000000000004808DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7902391PMC
March 2021

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

Acta Anaesthesiol Scand 2021 May 19;65(5):607-617. Epub 2021 Jan 19.

Department of Anesthesia, Critical Care and Pain Medicine, Beth Israel Deaconess Medical Center (BIDMC), Harvard Medical School, Boston, MA, USA.

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.
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http://dx.doi.org/10.1111/aas.13778DOI Listing
May 2021

Supraglottic airway device versus tracheal intubation and the risk of emergent postoperative intubation after general anaesthesia in adults: a retrospective cohort study.

Br J Anaesth 2021 Mar 17;126(3):738-745. Epub 2020 Dec 17.

Department of Anaesthesia, Critical Care and Pain Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA; Klinik für Anästhesiologie, Operative Intensivmedizin, Schmerz- und Palliativmedizin, Marien Hospital Herne, Universitätsklinikum der Ruhr-Universität Bochum, Bochum, Germany.

Background: We examined the association between emergent postoperative tracheal intubation and the use of supraglottic airway devices (SGAs) vs tracheal tubes.

Methods: We included data from adult noncardiac surgical cases under general anaesthesia between 2008 and 2018. We only included cases (n=59 991) in which both airways were deemed to be feasible options. Multivariable logistic regression, instrumental variable analysis, propensity matching, and mediation analysis were used.

Results: Use of a tracheal tube was associated with a higher risk of emergent postoperative intubation (adjusted absolute risk difference [ARD]=0.80%; 95% confidence interval (CI), 0.64-0.97; P<0.001), and a higher risk of post-extubation hypoxaemia (ARD=3.9%; 95% CI, 3.4-4.4; P<0.001). The effect was modified by the use of non-depolarising neuromuscular blocking agents (NMBAs); mediation analyses revealed that 28.9% (95% CI, 14.4-43.4%; P<0.001) of the main effect was attributable to NMBA. Airway management modified the association of NMBA and risk of emergent postoperative intubation (P=0.02). Patients managed with an SGA had higher odds of NMBA-associated reintubation compared to patients managed with a tracheal tube (adjusted odds ratio [aOR]=3.65, 95% CI, 1.99-6.67 vs aOR=1.68, 95% CI, 1.29-2.18 [P<0.001], respectively).

Conclusions: In patients undergoing procedures under general anaesthesia that could be managed with either SGA or tracheal tube, use of an SGA was associated with lower risk of emergent postoperative intubation. The effect can partly be explained by use of NMBAs. Use of NMBAs in patients with an SGA appears to increase the risk of emergent postoperative intubation.
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http://dx.doi.org/10.1016/j.bja.2020.10.040DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8014944PMC
March 2021

Joint preoperative transthoracic and intraoperative transoesophageal echocardiographic assessment of functional mitral regurgitation severity provides better association with long-term mortality.

Interact Cardiovasc Thorac Surg 2021 Jan;32(1):9-19

Department of Anesthesiology, Boston University School of Medicine, Boston, MA, USA.

Objectives: Functional mitral regurgitation (MR) is observed with ischaemic heart disease or aortic valve disease. Assessing the value of mitral valve repair or replacement (MVR/P) is complicated by frequent discordance between preoperative transthoracic echocardiographic (pTTE) and intraoperative transoesophageal echocardiographic (iTOE) assessment of MR severity. We examined the association of pTTE and iTOE with postoperative mortality in patients with or without MR, at the time of coronary artery bypass grafting (CABG) and/or aortic valve replacement without MVR/P.

Methods: Medical records of 6629 patients undergoing CABG and/or aortic valve replacement surgery with or without functional MR and who did not undergo MVR/P were reviewed. MR severity assessed by pTTE and iTOE were examined for association with postoperative mortality using proportional hazards regression while accounting for patient and operative characteristics.

Results: In 72% of 709 patients with clinically significant (moderate or greater) functional MR detected by pTTE, iTOE performed after induction of anaesthesia demonstrated a reduction in MR severity, while 2% of patients had increased severity of MR by iTOE. iTOE assessment of MR was better associated with long-term postoperative mortality than pTTE in patients with moderate MR [hazard ratio (HR) 1.31 (1.11-1.55) vs 1.02 (0.89-1.17), P-value for comparison of HR 0.025] but was not different for more than moderate MR [1.43 (0.96-2.14) vs 1.27 (0.80-2.02)].

Conclusions: In patients undergoing CABG and/or aortic valve replacement without MVR/P, these findings support intraoperative reassessment of MR severity by iTOE as an adjunct to pTTE in the prediction of mortality. Alone, these findings do not yet provide evidence for an operative strategy.
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http://dx.doi.org/10.1093/icvts/ivaa230DOI Listing
January 2021

Transcriptomic Analysis of circRNAs in the Peripheral Blood of Nonarteritic Anterior Ischemic Optic Neuropathy.

Biomed Res Int 2020 26;2020:5732124. Epub 2020 Nov 26.

Department of Ophthalmology, The Fourth Affiliated Hospital of China Medical University, Key Laboratory of Lens Research of Liaoning Province, Eye Hospital of China Medical University, Shenyang, 110005 Liaoning Province, China.

The aim of the study is to explore the expression profile variation of circular RNAs (circRNAs) in the peripheral blood of subjects with nonarteritic anterior ischemic optic neuropathy (NAION) and without NAION, to analyze the differential expression results, and to predict the role of circRNAs in disease development, providing novel ideas and methods for treatment and diagnosis. High-throughput sequencing to explore the expression profiles of RNAs in the peripheral blood of 6 NAION patients and 5 healthy controls was applied. Quality control obtained the advanced data from the original data by ticking out the unqualified data. Then, cluster analysis, volcano plot, coexpression network, and protein-protein interaction network (PPI) were performed. Gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway were used to analyze the whole expressed genes. Lastly, the quantitative real-time Polymerase Chain Reaction (qRT-PCR) was used to verify those significantly differentially expressed circRNAs and do some bioinformatics analysis and prediction in 12 NAION patients and 12 controls. There were significant differences in the expression of 49 circRNAs in the peripheral blood of NAION patients, in which there were 24 upregulations and 25 downregulations (variation folds > 2 and < 0.05), and it was confirmed that hsa_circ_0005583, hsa_circ_0003922, hsa_circ_0002021, and hsa_circ_0000462 were significantly downregulated (variation folds > 2 and < 0.05), especially hsa_circ_0005583 which was the most significantly changed one ( < 0.001), and are related to processes such as neurodegeneration, oxidative stress, immunity, and metabolism. The expression profile of circRNAs in the peripheral blood of NAION patients is significantly changed, enriching our understanding of the disease.
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http://dx.doi.org/10.1155/2020/5732124DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7718056PMC
November 2020

Association Between Intraoperative Hypotension and Postoperative Adverse Outcomes in Patients Undergoing Vascular Surgery - A Retrospective Observational Study.

J Cardiothorac Vasc Anesth 2021 May 5;35(5):1431-1438. Epub 2020 Nov 5.

Center for Anesthesia Research Excellence (CARE), Department of Anesthesia, Critical Care, and Pain Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA. Electronic address:

Objective: Intraoperative hypotension (IOH) is associated with adverse outcomes. It could be challenging to define IOH in vascular surgical patients with increased baseline blood pressure (BP). The authors studied the relationship between (1) absolute and relative BP thresholds of IOH, (2) preoperative pulse pressure (PP) and isolated systolic hypertension, and (3) endovascular versus open surgical approach with adverse outcomes in vascular surgical patients.

Design: Retrospective observational study.

Setting: Teaching hospital.

Patients: A total of 566 vascular surgical patients from 2011 to 2018.

Intervention: None.

Measurements And Main Results: BP thresholds were as follows: IOH - absolute mean arterial pressure (MAP) <65 mmHg, relative MAP >20% decrease from baseline, preoperative PP hypertension - PP >40 mmHg, isolated systolic hypertension - baseline systolic BP ≥140 mmHg with diastolic BP <90 mmHg. Thresholds were characterized by (1) total duration and (2) area under the curve. Primary outcome was a composite of postoperative in-hospital complications (acute kidney injury, stroke, myocardial infarction, congestive heart failure, and mortality). Forty-six (8.1%) patients had in-hospital complications. Only IOH duration-MAP <65 mmHg (odds ratio 1.01; 95% confidence interval 1.00-1.02; p = 0.004) was significantly associated with outcome. No associations were found with MAP >20% decrease from baseline and preoperative BP. Significant interaction was observed with the surgical approach and outcome (p = 0.031), which was stronger after 60 minutes of IOH in endovascular approach.

Conclusion: Longer periods of IOH (MAP <65 mmHg for >60 minutes) during endovascular surgery were associated with adverse outcomes. Relative fall in BP from baseline, preoperative isolated systolic, and PP hypertension were not associated with postoperative complications.
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http://dx.doi.org/10.1053/j.jvca.2020.11.005DOI Listing
May 2021

Outcomes after endoscopic retrograde cholangiopancreatography with general anaesthesia versus sedation.

Br J Anaesth 2021 01 10;126(1):191-200. Epub 2020 Oct 10.

Department of Anesthesia, Critical Care and Pain Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA; Essen-Duisburg University, Medical Faculty, Essen, Germany. Electronic address:

Background: 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).

Methods: 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.

Results: 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%; P<0.001) 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.

Conclusions: 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.
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http://dx.doi.org/10.1016/j.bja.2020.08.057DOI Listing
January 2021

Effects of night surgery on postoperative mortality and morbidity: a multicentre cohort study.

BMJ Qual Saf 2020 Oct 7. Epub 2020 Oct 7.

Anesthesia, Critical Care and Pain Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA

Background: Surgery at night (incision time 17:00 to 07:00 hours) may lead to increased postoperative mortality and morbidity. Mechanisms explaining this association remain unclear.

Methods: We 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.

Results: Among 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 (OR 1.26, 95% CI 1.15 to 1.38, p<0.001). In secondary analyses, night surgery was associated with increased morbidity (OR 1.41, 95% CI 1.33 to 1.48, p<0.001). The proportion of patients receiving intraoperative blood transfusion and anaesthesia handovers were higher during night-time, mediating 9.4% (95% CI 4.7% to 14.2%, p<0.001) of the effect of night surgery on 30-day mortality and 8.4% (95% CI 6.7% to 10.1%, p<0.001) of its effect on morbidity. The primary association was modified by the surgical setting (p-for-interaction<0.001), towards a greater effect in patients undergoing ambulatory/same-day surgery (OR 1.81, 95% CI 1.39 to 2.35) compared with inpatients (OR 1.17, 95% CI 1.02 to 1.34).

Conclusions: Night 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.
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http://dx.doi.org/10.1136/bmjqs-2020-011684DOI Listing
October 2020

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

J Intensive Care Med 2020 Aug 25:885066620949164. Epub 2020 Aug 25.

Department of Anesthesia, Critical Care and Pain Medicine, Beth Israel Deaconess Medical Center, 1811Harvard Medical School, Boston, MA, USA.

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.
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http://dx.doi.org/10.1177/0885066620949164DOI Listing
August 2020

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

BMJ Open 2020 07 19;10(7):e038474. Epub 2020 Jul 19.

Department of Anesthesia, Critical Care and Pain Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA

Introduction: Insomnia frequently occurs in patients admitted to an intensive care unit (ICU). Sleep-promoting agents may reduce rapid eye movement sleep and have deliriogenic effects. Suvorexant (Belsomra) is an orexin receptor antagonist with Food and Drug Administration (FDA) approval for the treatment of adult insomnia, which improves sleep onset and maintenance as well as subjective measures of quality of sleep. This trial will evaluate the efficacy of postoperative oral suvorexant treatment on night-time wakefulness after persistent sleep onset as well as the incidence and duration of delirium among adult cardiac surgical patients.

Methods And Analysis: In this single-centre, randomised, double-blind, placebo-controlled trial, we will enrol 120 patients, aged 60 years or older, undergoing elective cardiac surgery with planned postoperative admission to the ICU. Participants will be randomised to receive oral suvorexant (20 mg) or placebo one time a day starting the night after extubation. The primary outcome will be wakefulness after persistent sleep onset. The secondary outcome will be total sleep time. Exploratory outcomes will include time to sleep onset, incidence of postoperative in-hospital delirium, number of delirium-free days and subjective sleep quality.

Ethics And Dissemination: Ethics approval was obtained through the 'Committee on Clinical Investigations' at Beth Israel Deaconess Medical Center (protocol number 2019P000759). The findings will be published in peer-reviewed journals.

Trial Registration Number: This trial has been registered at clinicaltrials.gov on 17 September 2019 (NCT04092894).
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http://dx.doi.org/10.1136/bmjopen-2020-038474DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7371384PMC
July 2020

One-step controllable synthesis of amino-modification siloxene for enhanced solar water-splitting.

J Colloid Interface Sci 2020 Nov 16;579:205-211. Epub 2020 Jun 16.

School of Materials Science and Engineering, State Key Laboratory of Silicon Materials, Key Laboratory for Biomedical Engineering of Ministry of Education, Zhejiang University, Hangzhou 310027, China. Electronic address:

Novel two-dimensional silicon-based material siloxene has been synthesized handily by a one-step method, which utilizes the characteristics of the topological exfoliation to simplify the process of synthesis and modification. It is worth mentioning that for the first time amino-modified derivative has been investigated. Amino modification can promote the oxidation of siloxene, enlarge the bandgap and extend the carrier lifetime of siloxene. The application of siloxene before and after modification in water-splitting has been investigated. In addition, the superiority of the resultant two-dimensional materials was concisely elaborated, which revealed that owing to more effective photogenerated carriers' separation in amino modification siloxene, hydrogen production could be greatly promoted.
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http://dx.doi.org/10.1016/j.jcis.2020.06.066DOI Listing
November 2020

Does Sugammadex Reduce Postoperative Airway Failure?

Anesth Analg 2020 07;131(1):137-140

Department of Anesthesia, Critical Care and Pain Medicine, Beth Israel Deaconess Medical Center, Boston, Massachusetts.

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http://dx.doi.org/10.1213/ANE.0000000000004739DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7755126PMC
July 2020

Associations between Bottle-Feeding during Infancy and Obesity at Age 6 Years Are Mediated by Greater Infancy Weight Gain.

Child Obes 2020 07 4;16(5):316-326. Epub 2020 Jun 4.

Department of Anesthesia Critical Care and Pain Medicine, Beth Israel Deaconess Medical Center, Center for Anesthesia Research Excellence (CARE), Boston, MA, USA.

To explore whether the association between bottle-feeding during the first year and childhood obesity at age 6 years is mediated by change in weight-for-age z-score (ΔWAZ) during infancy. Participants were 1062 mother-child pairs who participated in the Infant Feeding Practices Study II and Year 6 Follow-Up. Mothers completed 1 prenatal questionnaire, 10 postpartum questionnaires during the first year, and 1 follow-up questionnaire at 6 years. Child weights were reported by mothers and used to determine ΔWAZ from birth to later infancy. Causal mediation analysis was used to determine the average direct effect of bottle-feeding on obesity at age 6 years and the average causal mediation effect of bottle-feeding through ΔWAZ. Infants who experienced rapid increases in bottle-feeding frequency during the first 6 months had significantly greater ΔWAZ compared with infants who had consistently low bottle-feeding frequency until 12 months of age [ = 0.45, 95% confidence interval (CI) 0.11-0.80]. Significant predictors of obesity at age 6 years were larger birth weight [adjusted odds ratio (AOR) = 4.27, 95% CI 2.42-7.64] and larger ΔWAZ (AOR = 1.59, 95% CI 1.29-1.98). An indirect effect of bottle-feeding, mediated via ΔWAZ, accounted for 59% of the total effect of bottle-feeding on obesity at age 6 years. Rapid increases in bottle use during the first 6 months postpartum predicted greater risk for obesity at age 6 years via an indirect mediation effect of larger ΔWAZ from birth to later infancy.
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http://dx.doi.org/10.1089/chi.2019.0299DOI Listing
July 2020

Impact of Left Atrial Appendage Exclusion on Short-Term Outcomes in Isolated Coronary Artery Bypass Graft Surgery.

Circulation 2020 Jul 3;142(1):20-28. Epub 2020 Jun 3.

Departments of Cardiothoracic Surgery (E.M., K.K.), Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA.

Background: The objective of this study was to evaluate the impact of left atrial appendage (LAA) exclusion on short-term outcomes in patients with atrial fibrillation undergoing isolated coronary artery bypass graft surgery.

Methods: We queried the 2010 to 2014 National Readmissions Database for patients who underwent coronary artery bypass graft repair with and without LAA ligation by using procedure codes (: 36.1xx). Only patients with a history of atrial fibrillation were included in our analysis. The primary outcome of our study was 30-day readmissions following discharge. Secondary outcomes were in-hospital mortality and stroke. To assess the postoperative outcomes, we used multivariate logistic regression models to adjust for clinical and demographic covariates.

Results: In total, we analyzed 253 287 patients undergoing coronary artery bypass graft surgery, 7.0% of whom received LAA closure. LAA exclusion was associated with a greater risk of postoperative respiratory failure (8.2% versus 6.2%, <0.0001) and acute kidney injury (21.8% versus 18.5%, <0.0001), but it did not significantly change the rate of blood transfusions or occurrence of cardiac tamponade. LAA exclusion was associated with a nonsignificant reduction in stroke (7.9% versus 8.6%, =0.12), no difference in in-hospital mortality (2.2% versus 2.2% =0.99), and a greater risk of 30-day readmission (16.0% versus 9.6%, <0.0001). After covariate adjustment, LAA ligation remained a significant predictor of 30-day readmission (odds ratio, 1.640 [95% CI, 1.603-1.677], <0.0001).

Conclusions: LAA exclusion during isolated coronary artery bypass graft surgery in patients with atrial fibrillation is associated with a higher rate of 30-day readmission. Postoperative measures to mitigate the loss of the hormonal and hemodynamic effects of the LAA may increase the therapeutic benefit of this procedure.
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http://dx.doi.org/10.1161/CIRCULATIONAHA.119.044642DOI Listing
July 2020

Cardiac surgical outcome prediction by blood pressure variability indices Poincaré plot and coefficient of variation: a retrospective study.

BMC Anesthesiol 2020 03 3;20(1):56. Epub 2020 Mar 3.

Department of Anesthesia, Critical Care, and Pain Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.

Background: Recent literature suggests a significant association between blood pressure variability (BPV) and postoperative outcomes after cardiac surgery. However, its outcome prediction ability remains unclear. Current prediction models use static preoperative patient factors. We explored the ability of Poincaré plots and coefficient of variation (CV) by measuring intraoperative BPV in predicting adverse outcomes.

Methods: In this retrospective, observational, cohort study, 3687 adult patients (> 18 years) undergoing cardiac surgery requiring cardio-pulmonary bypass from 2008 to 2014 were included. Blood pressure variability was computed by Poincare plots and CV. Standard descriptors (SD) SD1, SD2 were measured with Poincare plots by ellipse fitting technique. The outcomes analyzed were the 30-day mortality and postoperative renal failure. Logistic regression models adjusted for preoperative and surgical factors were constructed to evaluate the association between BPV parameters and outcomes. C-statistics were used to analyse the predictive ability.

Results: Analysis found that, 99 (2.7%) patients died within 30 days and 105 (2.8%) patients suffered from in-hospital renal failure. Logistic regression models including BPV parameters (standard descriptors from Poincare plots and CV) performed poorly in predicting postoperative 30-day mortality and renal failure [Concordance(C)-Statistic around 0.5]. They did not add any significant value to the standard STS risk score [C-statistic: STS alone 0.7, STS + BPV parmeters 0.7].

Conclusions: In conclusion, BP variability computed from Poincare plots and CV were not predictive of mortality and renal failure in cardiac surgical patients. Patient comorbid conditions and other preoperative factors are still the gold standard for outcome prediction. Future directions include analysis of dynamic parameters such as complexity of physiological signals in identifying high risk patients and tailoring management accordingly.
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http://dx.doi.org/10.1186/s12871-020-00972-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7055104PMC
March 2020

Comparison of Glycemic Variability Indices: Blood Glucose, Risk Index, and Coefficient of Variation in Predicting Adverse Outcomes for Patients Undergoing Cardiac Surgery.

J Cardiothorac Vasc Anesth 2020 Jul 8;34(7):1794-1802. Epub 2020 Jan 8.

Center for Anesthesia Research Excellence, Department of Anesthesia, Critical Care, and Pain Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA. Electronic address:

Objectives: Fluctuations in blood glucose (glycemic variability) increase the risk of adverse outcomes. No universally accepted tool for glycemic variability exists during the perioperative period. The authors compared 2 measures of glycemic variability-(1) coefficient of variation (CV) and (2) the Blood Glucose Risk Index (BGRI)-in predicting adverse outcomes after cardiac surgery.

Design: Prospective, observational study.

Setting: Single-center, teaching hospital.

Participants: A total of 1,963 adult patients undergoing cardiac surgery.

Interventions: None.

Measurements And Main Results: Postoperative blood glucose levels were measured hourly for the first 24 hours and averaged every 4 hours (4, 8, 12, 16, 20, and 24 hours). Glycemic variability was measured by CV and the BGRI. The primary outcome, major adverse events (MAEs), was a predefined composite of postoperative complications (death, reoperation, deep sternal infection, stroke, pneumonia, renal failure, tamponade, and myocardial infarction). Logistic regression models were constructed to evaluate the association. Predictive ability was measured using C-statistics. Major adverse events were seen in 170 (8.7%) patients. Only the fourth quartile of CV showed association (odds ratio [OR] 1.91; 95% confidence interval [CI] [1.19-3.14]; p = 0.01), whereas BGRI was related significantly to MAE (OR 1.20; 95% CI [1.10-1.32]; p < 0.0001). The predictive ability of CV and BGRI increased on adding the standard Society of Thoracic Surgeons (STS) risk index. The C-statistic for STS was 0.68, whereas STS + CV was 0.70 (p = 0.012) and STS + BGRI was 0.70 (p = 0.012).

Conclusion: Both CV and the BGRI had good predictive ability. The BGRI being a continuous variable could be a preferred measure of glycemic variability in predicting adverse outcomes (cutoff value 2.24) after cardiac surgery.
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http://dx.doi.org/10.1053/j.jvca.2019.12.032DOI Listing
July 2020

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

Br J Anaesth 2020 03 3;124(3):271-280. Epub 2020 Jan 3.

Department of Anesthesia, Critical Care and Pain Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA; Department of Anaesthesiology and Intensive Care Medicine, University of Duisburg-Essen, Essen, Germany. Electronic address:

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) 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; 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.
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http://dx.doi.org/10.1016/j.bja.2019.11.028DOI Listing
March 2020

Response to Letter.

Obstet Gynecol 2020 01;135(1):220-221

Department of Anesthesia, Perioperative, and Pain Medicine and the Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.

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http://dx.doi.org/10.1097/AOG.0000000000003641DOI Listing
January 2020

Preoperative Blood Pressure Complexity Indices as a Marker for Frailty in Patients Undergoing Cardiac Surgery.

J Cardiothorac Vasc Anesth 2020 Mar 30;34(3):616-621. Epub 2019 Sep 30.

Center for Anesthesia Research and Excellence (CARE), Department of Anesthesia, Critical Care, and Pain Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA. Electronic address:

Objective: Frailty, a state of decreased physiological reserve, increases the risk of adverse outcomes. There is no standard tool for frailty during perioperative period. Autonomic dysfunction, an underlying process in frailty, could result in hemodynamic fluctuations. Complexity, the physiological adaptability of a system can quantify these fluctuations. The authors hypothesized that complexity could be a marker for frailty and explored their relationship in cardiac surgical patients.

Design: Prospective, observational study.

Setting: Single-center teaching hospital.

Participants: Three hundred and sixty-four adult patients undergoing cardiac surgery.

Intervention: None.

Measurements And Main Results: Preoperative beat-to-beat systolic arterial pressure (SAP) and mean arterial pressure (MAP) time series were obtained. Complexity indices were calculated using multiscale entropy (MSE) analysis. Frailty was assessed from: age >70 years, body mass index <18.5, hematocrit <35%, albumin <3.4 g/dL, and creatinine >2.0 mg/dL. The association between complexity indices and frailty was explored by logistic regression and predictive ability by C-statistics. In total, 190 (52%) patients had frailty. The complexity index (MSE) median (quartile 1, quartile 3) of SAP and MAP time series decreased significantly in frail patients (SAP: 8.32 [7.27, 9.24] v 9.13 [8.00, 9.72], p < 0.001 and MAP: 8.56 [7.56; 9.27] v 9.18 [8.26; 9.83], p < 0.001). MSE demonstrated a fair predictive ability of frailty (C-statistic: SAP 0.62 and MAP 0.64).

Conclusion: Preoperative BP complexity indices correlate and predict frailty. Impaired autonomic control is the underlying mechanism to explain this finding. A simple automated measure of preoperative BP complexity in the surgeon's office has the potential to reliably assess frailty.
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http://dx.doi.org/10.1053/j.jvca.2019.09.035DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6986993PMC
March 2020

Trends in Postpartum Hemorrhage in the United States From 2010 to 2014.

Anesth Analg 2020 05;130(5):e119-e122

From the Departments of Anesthesiology, Perioperative and Pain Medicine.

Postpartum hemorrhage (PPH) is a leading cause of morbidity and mortality in the United States; its prevalence increased during the 1990s-2000s. The purpose of this study was to reevaluate trends in PPH using the National Inpatient Sample. From 2010 to 2014, the prevalence of PPH increased from 2.9% (95% confidence interval [CI], 2.7%-3.1%) to 3.2% (95% CI, 3.1%-3.3%) of deliveries. Adjusting for PPH risk factors did not substantially attenuate this trend. Among patients with PPH, there was a decline in associated coagulopathy, acute respiratory failure, and maternal death, but an increase in sepsis and acute renal failure. Continued focus on PPH management is warranted.
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http://dx.doi.org/10.1213/ANE.0000000000004424DOI Listing
May 2020

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

Acta Anaesthesiol Scand 2020 02 14;64(2):156-167. Epub 2019 Oct 14.

Department of Anesthesia, Critical Care and Pain Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA.

Background: This study evaluated the association between neuromuscular blocking agent dose and post-operative respiratory complications in infants and children.

Methods: Data from 6507 general anaesthetics provided to children aged 0-10 years undergoing surgery were analysed to examine the effects of neuromuscular blocking agent dose on post-operative respiratory complications (primary endpoint) and secondary endpoints. Confounder-adjusted analyses addressed age, surgical duration, and comorbidity burden.

Results: In confounder-adjusted analyses, high doses of neuromuscular blocking agents were associated with higher risk of post-operative respiratory complications (OR 2.27; 95% CI 1.12-4.59; P = .022). The effect was modified by age (P-for-interaction = .016) towards a more substantial risk in infants ≤1 year (OR 3.84; 95% CI 1.35-10.94; P = .012), by duration of surgery (P-for-interaction = .006) towards a higher difference in odds for surgeries <90 minutes (OR 4.25; 95% CI 1.19-15.18; P = .026), and by ASA physical status (P-for-interaction = .015) with a greater effect among patients with higher operative risk (ASA >1: OR 3.17; 95% CI 1.43-7.04; P = .005). Neostigmine reversal did not modify the association between neuromuscular blocking agents and post-operative respiratory complications (P-for-interaction = .38). Instrumental variable analysis confirmed that high doses of neuromuscular blocking agents were associated with post-operative respiratory complications (probit coefficient 0.25; 95% CI 0.04-0.46; P = .022), demonstrating robust results regarding concerns of unobserved confounding.

Conclusions: High dose of neuromuscular blocking agents is associated with post-operative respiratory complications. We have identified subcohorts of paediatric patients who are particularly vulnerable to the respiratory side-effects of neuromuscular blocking agents: infants, paediatric patients undergoing surgeries of short duration, and those with a high ASA risk score.
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http://dx.doi.org/10.1111/aas.13478DOI Listing
February 2020

Potential Effects of Regionalized Maternity Care on U.S. Hospitals.

Obstet Gynecol 2019 09;134(3):545-552

Division of Maternal-Fetal Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts; the Division of Maternal-Fetal Medicine, University of North Carolina, Chapel Hill, North Carolina; the Department of International Health, Johns Hopkins Bloomberg School of Public Health, Department of Gynecology and Obstetrics, Johns Hopkins School of Medicine, Baltimore, Maryland; and the Department of Anesthesia, Perioperative, and Pain Medicine and the Division of Pharmacoepidemiology and Pharmacoeconomics, Department of Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.

Objective: To examine the current patterns of care for women at high risk for delivery-related morbidity to inform discussions about the feasibility of this regionalized approach.

Methods: We performed a cross-sectional study and linked 2014 American Hospital Association survey and State Inpatient Database data from seven representative states. We used American Hospital Association-reported hospital characteristics and State Inpatient Database procedure codes to assign a level of maternal care to each hospital. We then assigned each patient to a minimum required level of maternal care (I-IV) based on maternal comorbidities captured in the State Inpatient Database. Our outcome was delivery at a hospital with an inappropriately low level of maternal care. Comorbidities associated with delivery at an inappropriate hospital were assessed using descriptive statistics.

Results: The analysis included 845,545 deliveries occurring at 556 hospitals. The majority of women had risk factors appropriate for delivery at level I or II hospitals (85.1% and 12.6%, respectively). A small fraction (2.4%) of women at high risk for maternal morbidity warranted delivery in level III or IV hospitals. The majority (97.6%) of women delivered at a hospital with an appropriate level of maternal care, with only 2.4% of women delivering at a hospital with an inappropriate level of maternal care. However, 43.4% of the 19,988 high-risk patients warranting delivery at level III or IV hospitals delivered at level I or II hospitals. Women with comorbidities likely to benefit from specialized care (eg, maternal cardiac disease, placenta previa with prior uterine surgery) had high rates of delivery at hospitals with an inappropriate level of maternal care (68.2% and 37.7%, respectively).

Conclusion: Though only 2.41% of deliveries occurred at hospitals with an inappropriate level of maternal care, a substantial fraction of women at risk for maternal morbidity delivered at hospitals potentially unequipped with resources to manage their needs. Promoting triage of high-risk patients to hospitals optimized to provide risk-appropriate care may improve maternal outcomes with minimal effect on most deliveries.
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http://dx.doi.org/10.1097/AOG.0000000000003397DOI Listing
September 2019

BOSTN Bundle Intervention for Perioperative Screening and Management of Patients With Suspected Obstructive Sleep Apnea: A Hospital Registry Study.

Anesth Analg 2020 05;130(5):1415-1424

From the Department of Anesthesia, Critical Care and Pain Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts.

Background: We developed and implemented a perioperative guideline for obstructive sleep apnea (OSA), comprising a preoperative screening tool (BOSTN) and clinical management pathways. OSA was suspected with 2 or more of the following: body mass index ≥30 kg/m, observed apnea, loud snoring, daytime tiredness, and neck circumference ≥16.5 inches in women or ≥ 17.5 inches in men. The primary objective of this study was to assess the association between high BOSTN scores and the requirement of invasive mechanical ventilation after surgery.

Methods: In this hospital registry study, 169,662 noncardiac surgical cases performed at Beth Israel Deaconess Medical Center (BIDMC), Boston, MA, between May 2008 and September 2017 were analyzed. We assessed the association between a high BOSTN Score (score ≥2) and the primary outcome of requirement of invasive mechanical ventilation within 7 days after surgery using multivariable logistic regression adjusted for patient-specific factors and case-specific surgical and anesthesiological confounders. Patients with a BOSTN Score ≥2 were assumed to have a high likelihood of suffering from OSA. Key secondary outcome was postoperative desaturation, defined as a peripheral oxygen saturation measurement <90% within 10 minutes of extubation.

Results: Invasive mechanical ventilation within 7 days of surgery was necessary in 3170 (2.3%) low-risk cases (BOSTN Score <2) and 664 (2.1%) high-risk cases (BOSTN Score ≥2). A score ≥2 was associated with significantly lower odds of requiring postoperative invasive ventilation (adjusted odds ratio [aOR], 0.89; 95% confidence interval [CI], 0.80-0.98; P = .017), but with an increased risk of postextubation desaturation (aOR, 1.34; 99.3% CI, 1.21-1.48; P < .001). Patients with a score ≥2 were hospitalized for an average of 3.71 days after surgery, compared to 4.27 days with a score <2 (adjusted incidence rate ratio [aIRR], 0.87; 99.3% CI, 0.84-0.91; P < .001).

Conclusions: Patients at high risk of OSA required postoperative mechanical ventilation less frequently, had higher odds of postoperative desaturation, and were hospitalized for shorter periods of time.
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http://dx.doi.org/10.1213/ANE.0000000000004294DOI Listing
May 2020

Effects of Anticholinesterase Reversal Under General Anesthesia on Postoperative Cardiovascular Complications: A Retrospective Cohort Study.

Anesth Analg 2020 03;130(3):685-695

From the Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.

Background: The anticholinesterase neostigmine and the muscarinic inhibitor glycopyrrolate are frequently coadministered for the reversal of neuromuscular blockade. This practice can precipitate severe bradycardia or tachycardia, but whether it affects the incidence of cardiovascular complications remains unclear. We hypothesized that anticholinesterase reversal with neostigmine and glycopyrrolate versus no anticholinesterase reversal increases the risk of postoperative cardiovascular complications among adult patients undergoing noncardiac surgery with general anesthesia.

Methods: We conducted a prespecified retrospective analysis of hospital registry data from a major health care network for patients undergoing surgery with general anesthesia from January 2007 to December 2015. The primary outcome was a composite of cardiac dysrhythmia, acute heart failure, transient ischemic attack, ischemic stroke, and acute myocardial infarction within 30 days after surgery. We performed sensitivity analyses in subgroups and propensity score adjustment and explored the association between exposure and outcome in subgroups of patients with high risk of cardiovascular complications.

Results: Of the 98,147 cases receiving neuromuscular blockade, 73,181 (74.6%) received neostigmine and glycopyrrolate, while 24,966 (25.4%) did not. A total of 5612 patients (7.7%) in the anticholinesterase reversal group and 1651 (6.6%) in the control group (P < .001) experienced the primary outcome. After adjustment for clinical covariates, neostigmine and glycopyrrolate exposure was significantly associated in a dose-dependent fashion (P for trend <.001, respectively) with tachycardia (adjusted odds ratio = 2.1 [95% CI, 1.97-2.23]; P < .001) and bradycardia (adjusted odds ratio = 2.84 [95% CI, 2.49-3.24]; P < .001) but not with postoperative cardiovascular complications (adjusted odds ratio = 1.03 [95% CI, 0.97-1.1]; P = .33). We identified a significant effect modification of anticholinesterase reversal by high age, high-risk surgery, and history of atrial fibrillation (P for interaction = .002, .001, and .02, respectively). By using linear combinations of main effect and exposure-risk interaction terms, we detected significant associations between anticholinesterase reversal and cardiovascular complications toward a higher vulnerability in these patient subgroups.

Conclusions: Neuromuscular blockade reversal with neostigmine and glycopyrrolate was associated with an increased incidence of intraoperative tachycardia and bradycardia but not with 30-day postoperative cardiovascular complications. Exploratory analyses suggest that a high postoperative cardiovascular complication risk profile may modify the effects of anticholinesterase reversal toward clinical relevance.
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http://dx.doi.org/10.1213/ANE.0000000000004099DOI Listing
March 2020

Does reversal of neuromuscular block with sugammadex reduce readmission rate after surgery?

Br J Anaesth 2019 03 23;122(3):294-298. Epub 2019 Jan 23.

Department of Anesthesia, Critical Care and Pain Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA. Electronic address:

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http://dx.doi.org/10.1016/j.bja.2018.12.015DOI Listing
March 2019