Publications by authors named "Timothy T Houle"

155 Publications

Development and external validation of a prognostic model for ischaemic stroke after surgery.

Br J Anaesth 2021 Jul 21. Epub 2021 Jul 21.

Department of Anesthesia, Critical Care and Pain Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA, USA; Department of Anesthesiology, Montefiore Medical Center and Albert Einstein College of Medicine, Bronx, NY, USA; Klinik für Anästhesiologie, Universitätsklinikum Essen, Essen, Germany. Electronic address:

Background: There is an under-recognised patient cohort at elevated risk of postoperative ischaemic stroke. We aimed to develop and validate a prognostic model for the identification of such patients at high risk of ischaemic stroke within 1 yr after noncardiac surgery.

Methods: This was a hospital registry study of adult patients undergoing noncardiac surgery between 2005 and 2017 at two independent healthcare networks in Massachusetts, USA without a preoperative indication for therapeutic anticoagulation. Logistic regression was used to fit a model from a priori defined candidate predictors for the outcome 1 yr postoperative ischaemic stroke. To enhance clinical applicability, the model was simplified to a scoring system and externally validated.

Results: In the development (n=107 756) and validation (n=141 724) cohorts, 1.4% and 0.5% of patients had an ischaemic stroke up to 1 yr postoperatively. The final model included 13 variables (patient characteristics, comorbidities, procedural factors), considering sub-models conditional on a previous history of ischaemic stroke. Areas under the curve were 0.89 (95% confidence interval 0.89-0.90) and 0.88 (95% confidence interval 0.86-0.89) in the development and validation cohorts. Decision curve analysis indicated positive net benefits superior to other prediction instruments.

Conclusions: Stroke after surgery (STRAS) screening can reliably identify patients with a high risk for ischaemic stroke during the first year after surgery. A STRAS-guided risk stratification may inform the recruitment to future randomised trials testing the efficacy of treatments for the prevention of postoperative ischaemic stroke.
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http://dx.doi.org/10.1016/j.bja.2021.05.035DOI Listing
July 2021

Effect of Intraoperative Arterial Hypotension on the Risk of Perioperative Stroke After Noncardiac Surgery: A Retrospective Multicenter Cohort Study.

Anesth Analg 2021 Jul 12. Epub 2021 Jul 12.

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

Background: Intraoperative cerebral blood flow is mainly determined by cerebral perfusion pressure and cerebral autoregulation of vasomotor tone. About 1% of patients undergoing noncardiac surgery develop ischemic stroke. We hypothesized that intraoperative hypotension within a range frequently observed in clinical practice is associated with an increased risk of perioperative ischemic stroke within 7 days after surgery.

Methods: Adult noncardiac surgical patients undergoing general anesthesia at Beth Israel Deaconess Medical Center and Massachusetts General Hospital between 2005 and 2017 were included in this retrospective cohort study. The primary exposure was intraoperative hypotension, defined as a decrease in mean arterial pressure (MAP) below 55 mm Hg, categorized into no intraoperative hypotension, short (<15 minutes, median [interquartile range {IQR}], 2 minutes [1-5 minutes]) and prolonged (≥15 minutes, median [IQR], 21 minutes [17-31 minutes]) durations. The primary outcome was a new diagnosis of early perioperative ischemic stroke within 7 days after surgery. In secondary analyses, we assessed the effect of a MAP decrease by >30% from baseline on perioperative stroke. Analyses were adjusted for the preoperative STRoke After Surgery (STRAS) prediction score, work relative value units, and duration of surgery.

Results: Among 358,391 included patients, a total of 1553 (0.4%) experienced an early perioperative ischemic stroke. About 42% and 3% of patients had a MAP of below 55 mm Hg for a short and a prolonged duration, and 49% and 29% had a MAP decrease by >30% from baseline for a short and a prolonged duration, respectively. In an adjusted analysis, neither a MAP <55 mm Hg (short duration: adjusted odds ratio [ORadj], 0.95; 95% confidence interval [CI], 0.85-1.07; P = .417 and prolonged duration: ORadj, 1.18; 95% CI, 0.91-1.55; P = .220) nor a MAP decrease >30% (short duration: ORadj, 0.97; 95% CI, 0.67-1.42; P = .883 and prolonged duration: ORadj, 1.30; 95% CI, 0.89-1.90; P = .176) was associated with early perioperative stroke. A high a priori stroke risk quantified based on preoperatively available risk factors (STRAS prediction score) was associated with longer intraoperative hypotension (adjusted incidence rate ratio, 1.04; 95% CI, 1.04-1.05; P < .001 per 5 points of the STRAS prediction score).

Conclusions: This study found no evidence to conclude that intraoperative hypotension within the range studied was associated with early perioperative stroke within 7 days after surgery. These findings emphasize the importance of perioperative cerebral blood flow autoregulation to prevent ischemic stroke.
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http://dx.doi.org/10.1213/ANE.0000000000005604DOI Listing
July 2021

Labor prior to cesarean delivery associated with higher post-discharge opioid consumption.

PLoS One 2021 9;16(7):e0253990. Epub 2021 Jul 9.

Department of Anesthesiology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, United States of America.

Background: Severe acute post-cesarean delivery (CD) pain has been associated with an increased risk for persistent pain and postpartum depression. Identification of women at increased risk for pain can be used to optimize post-cesarean analgesia. The impact of labor prior to CD (intrapartum CD) on acute post-operative pain and opioid use is unclear. We hypothesized that intrapartum CD, which has been associated with both increased inflammation and affective distress related to an unexpected surgical procedure, would result in higher postoperative pain scores and increased opioid intake.

Methods: This is a secondary analysis of a prospective cohort study examining opioid use up to 2 weeks following CD. Women undergoing CD at six academic medical centers in the United States 9/2014-3/2016 were contacted by phone two weeks following discharge. Participants completed a structured interview that included questions about postoperative pain scores and opioid utilization. They were asked to retrospectively estimate their maximal pain score on an 11-point numeric rating scale at multiple time points, including day of surgery, during hospitalization, immediately after discharge, 1st week, and 2nd week following discharge. Pain scores over time were assessed utilizing a generalized linear mixed-effects model with the patient identifier being a random effect, adjusting for an a priori defined set of confounders. A multivariate negative binomial model was utilized to assess the association between intrapartum CD and opioid utilization after discharge, also adjusting for the same confounders. In the context of non-random prescription distribution, this model was constructed with an offset for the number of tablets dispensed.

Results: A total of 720 women were enrolled, 392 with and 328 without labor prior to CD. Patients with intrapartum CD were younger, less likely to undergo repeat CD or additional surgical procedures, and more likely to experience a complication of CD. Women with intrapartum CD consumed more opioid tablets following discharge than women without labor (median 20, IQR 10-30 versus 17, IQR 6-30; p = 0.005). This association persisted after adjustment for confounders (incidence rate ratio 1.16, 95% CI 1.05-1.29; p = 0.004). Pain scores on the day of surgery were higher in women with intrapartum CD (difference 0.91, 95% CI 0.52-1.30; adj. p = <0.001) even after adjustment for confounders. Pain scores at other time points were not meaningfully different between the two groups.

Conclusion: Intrapartum CD is associated with worse pain on the day of surgery but not other time points. Opioid requirements following discharge were modestly increased following intrapartum CD.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0253990PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8270408PMC
July 2021

Stay in treatment: Predicting dropout from pediatric weight management study protocol.

Contemp Clin Trials Commun 2021 Jun 9;22:100799. Epub 2021 Jun 9.

Department of Epidemiology and Prevention, Division of Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, NC, USA.

Introduction: Childhood obesity is a serious public health concern. Multidisciplinary pediatric weight management programs have been deemed effective. However, effectiveness of these programs is impacted by attrition, limiting health benefits to children, and inefficiently utilizing scarce resources.

Methods: We have developed a model (the Outcomes Forecasting System, OFS) that isolates variables associated with attrition from pediatric weight management, with the potential to forecast participant dropout. In Aim 1, we will increase the power and precision of the OFS and then validate the model through the consistent acquisition of key patient, family, and treatment data, from three different weight management sites. In Aim 2, external validity will be established through the application of the OFS at a fourth pediatric weight management program. Aim 3 will be a pilot clinical trial, incorporating an intervention built on the results of Aims 1 and 2 and utilizing the OFS to reduce attrition.

Discussion: A greater understanding of the patient, family, and disease-specific factors that predict dropout from pediatric weight management can be utilized to prevent attrition. The goal of the current study is to refine the OFS to a level of precision and efficiency to be a valuable tool to any weight management program. By identifying the most pertinent factors driving attrition across weight management sites, new avenues for treatment will be identified. This study will result in a valuable forecasting tool that will be applicable for diverse programs and populations, decrease program costs, and improve patient retention, adherence, and outcomes.

Clinicaltrialsgov Identifier: NCT04364282.
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http://dx.doi.org/10.1016/j.conctc.2021.100799DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8209185PMC
June 2021

D-Amphetamine Rapidly Reverses Dexmedetomidine-Induced Unconsciousness in Rats.

Front Pharmacol 2021 18;12:668285. Epub 2021 May 18.

Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, MA, United States.

D-amphetamine induces emergence from sevoflurane and propofol anesthesia in rats. Dexmedetomidine is an α-adrenoreceptor agonist that is commonly used for procedural sedation, whereas ketamine is an anesthetic that acts primarily by inhibiting NMDA-type glutamate receptors. These drugs have different molecular mechanisms of action from propofol and volatile anesthetics that enhance inhibitory neurotransmission mediated by GABA receptors. In this study, we tested the hypothesis that d-amphetamine accelerates recovery of consciousness after dexmedetomidine and ketamine. Sixteen rats (Eight males, eight females) were used in a randomized, blinded, crossover experimental design and all drugs were administered intravenously. Six additional rats with pre-implanted electrodes in the prefrontal cortex (PFC) were used to analyze changes in neurophysiology. After dexmedetomidine, d-amphetamine dramatically decreased mean time to emergence compared to saline (saline:112.8 ± 37.2 min; d-amphetamine:1.8 ± 0.6 min, < 0.0001). This arousal effect was abolished by pre-administration of the D/D dopamine receptor antagonist, SCH-23390. After ketamine, d-amphetamine did not significantly accelerate time to emergence compared to saline (saline:19.7 ± 18.0 min; d-amphetamine:20.3 ± 16.5 min, = 1.00). Prefrontal cortex local field potential recordings revealed that d-amphetamine broadly decreased spectral power at frequencies <25 Hz and restored an awake-like pattern after dexmedetomidine. However, d-amphetamine did not produce significant spectral changes after ketamine. The duration of unconsciousness was significantly longer in females for both dexmedetomidine and ketamine. In conclusion, d-amphetamine rapidly restores consciousness following dexmedetomidine, but not ketamine. Dexmedetomidine reversal by d-amphetamine is inhibited by SCH-23390, suggesting that the arousal effect is mediated by D and/or D receptors. These findings suggest that d-amphetamine may be clinically useful as a reversal agent for dexmedetomidine.
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http://dx.doi.org/10.3389/fphar.2021.668285DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8167047PMC
May 2021

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

BMJ Open 2021 04 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
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8054197PMC
April 2021

The Society for Obstetric Anesthesia and Perinatology Coronavirus Disease 2019 Registry: An Analysis of Outcomes Among Pregnant Women Delivering During the Initial Severe Acute Respiratory Syndrome Coronavirus-2 Outbreak in the United States.

Anesth Analg 2021 08;133(2):462-473

Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Boston, Massachusetts.

Background: Early reports associating severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection with adverse pregnancy outcomes were biased by including only women with severe disease without controls. The Society for Obstetric Anesthesia and Perinatology (SOAP) coronavirus disease 2019 (COVID-19) registry was created to compare peripartum outcomes and anesthetic utilization in women with and without SARS-CoV-2 infection delivering at institutions with widespread testing.

Methods: Deliveries from 14 US medical centers, from March 19 to May 31, 2020, were included. Peripartum infection was defined as a positive SARS-CoV-2 polymerase chain reaction test within 14 days of delivery. Consecutive SARS-CoV-2-infected patients with randomly selected control patients were sampled (1:2 ratio) with controls delivering during the same day without a positive test. Outcomes were obstetric (eg, delivery mode, hypertensive disorders of pregnancy, and delivery <37 weeks), an adverse neonatal outcome composite measure (primary), and anesthetic utilization (eg, neuraxial labor analgesia and anesthesia). Outcomes were analyzed using generalized estimating equations to account for clustering within centers. Sensitivity analyses compared symptomatic and asymptomatic patients to controls.

Results: One thousand four hundred fifty four peripartum women were included: 490 with SARS-CoV-2 infection (176 [35.9%] symptomatic) and 964 were controls. SARS-CoV-2 patients were slightly younger, more likely nonnulliparous, nonwhite, and Hispanic than controls. They were more likely to have diabetes, obesity, or cardiac disease and less likely to have autoimmune disease. After adjustment for confounders, individuals experiencing SARS-CoV-2 infection exhibited an increased risk for delivery <37 weeks of gestation compared to controls, 73 (14.8%) vs 98 (10.2%) (adjusted odds ratio [aOR], 1.47; 95% confidence interval [CI], 1.03-2.09). Effect estimates for other obstetric outcomes and the neonatal composite outcome measure were not meaningfully different between SARS-CoV-2 patients versus controls. In sensitivity analyses, compared to controls, symptomatic SARS-CoV-2 patients exhibited increases in cesarean delivery (aOR, 1.57; 95% CI, 1.09-2.27), postpartum length of stay (aOR, 1.89; 95% CI, 1.18-2.60), and delivery <37 weeks of gestation (aOR, 2.08; 95% CI, 1.29-3.36). These adverse outcomes were not found in asymptomatic women versus controls. SARS-CoV-2 patients (asymptomatic and symptomatic) were less likely to receive neuraxial labor analgesia (aOR, 0.52; 95% CI, 0.35-0.75) and more likely to receive general anesthesia for cesarean delivery (aOR, 3.69; 95% CI, 1.40-9.74) due to maternal respiratory failure.

Conclusions: In this large, multicenter US cohort study of women with and without peripartum SARS-CoV-2 infection, differences in obstetric and neonatal outcomes seem to be mostly driven by symptomatic patients. Lower utilization of neuraxial analgesia in laboring patients with asymptomatic or symptomatic infection compared to patients without infection requires further investigation.
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http://dx.doi.org/10.1213/ANE.0000000000005592DOI Listing
August 2021

Reporting heterogeneity of treatment effects.

Headache 2021 03;61(3):407-408

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

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http://dx.doi.org/10.1111/head.14083DOI 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
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8174248PMC
February 2021

Activation of GABAergic Neurons in the Rostromedial Tegmental Nucleus and Other Brainstem Regions Promotes Sedation and Facilitates Sevoflurane Anesthesia in Mice.

Anesth Analg 2021 04;132(4):e50-e55

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

Many general anesthetics potentiate gamma-aminobutyric acid (GABA) A receptors but their neuroanatomic sites of action are less clear. GABAergic neurons in the rostromedial tegmental nucleus (RMTg) send inhibitory projections to multiple arousal-promoting nuclei, but the role of these neurons in modulating consciousness is unknown. In this study, designer receptors exclusively activated by designer drugs (DREADDs) were targeted to RMTg GABAergic neurons of Vgat-ires-Cre mice. DREADDs expression was found in the RMTg and other brainstem regions. Activation of these neurons decreased movement and exploratory behavior, impaired motor coordination, induced electroencephalogram (EEG) oscillations resembling nonrapid eye movement (NREM) sleep without loss of righting and reduced the dose requirement for sevoflurane-induced unconsciousness. These results suggest that GABAergic neurons in the RMTg and other brainstem regions promote sedation and facilitate sevoflurane-induced unconsciousness.
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http://dx.doi.org/10.1213/ANE.0000000000005387DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7969415PMC
April 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

Study design for a randomized clinical trial of cognitive-behavioral therapy for posttraumatic headache.

Contemp Clin Trials Commun 2021 Mar 6;21:100699. Epub 2021 Jan 6.

Department of Psychiatry and Behavioral Sciences, The University of Texas Health Science Center San Antonio, San Antonio, TX, USA.

Posttraumatic headache (PTH) is a common debilitating condition arising from head injury and is highly prevalent among military service members and veterans with traumatic brain injury (TBI). Diagnosis and treatment for PTH is still evolving, and surprisingly little is known about the putative mechanisms that drive these headaches. This manuscript describes the design of a randomized clinical trial of two nonpharmacological (i.e., behavioral) interventions for posttraumatic headache. Design of this trial required careful consideration of PTH diagnosis and inclusion criteria, which was challenging due to the lack of standard clinical characteristics in PTH unique from other types of headaches. The treatments under study differed in clinical focus and dose (i.e., number of treatment sessions), but the trial was designed to balance the treatments as well as possible. Finally, while the primary endpoints for pain research can vary from assessments of pain intensity to objective and subjective functional measures, this trial of PTH interventions chose carefully to establish clinically relevant endpoints and to maximize the opportunity to detect significant differences between groups with two primary outcomes. All these issues are discussed in this manuscript.
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http://dx.doi.org/10.1016/j.conctc.2021.100699DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7806520PMC
March 2021

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

Acta Anaesthesiol Scand 2021 05 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

Effectiveness of Mindfulness Meditation vs Headache Education for Adults With Migraine: A Randomized Clinical Trial.

JAMA Intern Med 2021 Mar;181(3):317-328

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

Importance: Migraine is the second leading cause of disability worldwide. Most patients with migraine discontinue medications due to inefficacy or adverse effects. Mindfulness-based stress reduction (MBSR) may provide benefit.

Objective: To determine if MBSR improves migraine outcomes and affective/cognitive processes compared with headache education.

Design, Setting, And Participants: This randomized clinical trial of MBSR vs headache education included 89 adults who experienced between 4 and 20 migraine days per month. There was blinding of participants (to active vs comparator group assignments) and principal investigators/data analysts (to group assignment).

Interventions: Participants underwent MBSR (standardized training in mindfulness/yoga) or headache education (migraine information) delivered in groups that met for 2 hours each week for 8 weeks.

Main Outcomes And Measures: The primary outcome was change in migraine day frequency (baseline to 12 weeks). Secondary outcomes were changes in disability, quality of life, self-efficacy, pain catastrophizing, depression scores, and experimentally induced pain intensity and unpleasantness (baseline to 12, 24, and 36 weeks).

Results: Most participants were female (n = 82, 92%), with a mean (SD) age of 43.9 (13.0) years, and had a mean (SD) of 7.3 (2.7) migraine days per month and high disability (Headache Impact Test-6: 63.5 [5.7]), attended class (median attendance, 7 of 8 classes), and followed up through 36 weeks (33 of 45 [73%] of the MBSR group and 32 of 44 [73%] of the headache education group). Participants in both groups had fewer migraine days at 12 weeks (MBSR: -1.6 migraine days per month; 95% CI, -0.7 to -2.5; headache education: -2.0 migraine days per month; 95% CI, -1.1 to -2.9), without group differences (P = .50). Compared with those who participated in headache education, those who participated in MBSR had improvements from baseline at all follow-up time points (reported in terms of point estimates of effect differences between groups) on measures of disability (5.92; 95% CI, 2.8-9.0; P < .001), quality of life (5.1; 95% CI, 1.2-8.9; P = .01), self-efficacy (8.2; 95% CI, 0.3-16.1; P = .04), pain catastrophizing (5.8; 95% CI, 2.9-8.8; P < .001), depression scores (1.6; 95% CI, 0.4-2.7; P = .008), and decreased experimentally induced pain intensity and unpleasantness (MBSR group: 36.3% [95% CI, 12.3% to 60.3%] decrease in intensity and 30.4% [95% CI, 9.9% to 49.4%] decrease in unpleasantness; headache education group: 13.5% [95% CI, -9.9% to 36.8%] increase in intensity and an 11.2% [95% CI, -8.9% to 31.2%] increase in unpleasantness; P = .004 for intensity and .005 for unpleasantness, at 36 weeks). One reported adverse event was deemed unrelated to study protocol.

Conclusions And Relevance: Mindfulness-based stress reduction did not improve migraine frequency more than headache education, as both groups had similar decreases; however, MBSR improved disability, quality of life, self-efficacy, pain catastrophizing, and depression out to 36 weeks, with decreased experimentally induced pain suggesting a potential shift in pain appraisal. In conclusion, MBSR may help treat total migraine burden, but a larger, more definitive study is needed to further investigate these results.

Trial Registration: ClinicalTrials.gov Identifier: NCT02695498.
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http://dx.doi.org/10.1001/jamainternmed.2020.7090DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7737157PMC
March 2021

Understanding and Applying Confidence Intervals.

Headache 2020 11;60(10):2118-2124

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

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http://dx.doi.org/10.1111/head.13991DOI Listing
November 2020

Low Frontal Alpha Power Is Associated With the Propensity for Burst Suppression: An Electroencephalogram Phenotype for a "Vulnerable Brain".

Anesth Analg 2020 11;131(5):1529-1539

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

Background: A number of recent studies have reported an association between intraoperative burst suppression and postoperative delirium. These studies suggest that anesthesia-induced burst suppression may be an indicator of underlying brain vulnerability. A prominent feature of electroencephalogram (EEG) under propofol and sevoflurane anesthesia is the frontal alpha oscillation. This frontal alpha oscillation is known to decline significantly during aging and is generated by prefrontal brain regions that are particularly prone to age-related neurodegeneration. Given that burst suppression and frontal alpha oscillations are both associated with brain vulnerability, we hypothesized that anesthesia-induced frontal alpha power could also be associated with burst suppression.

Methods: We analyzed EEG data from a previously reported cohort in which 155 patients received propofol (n = 60) or sevoflurane (n = 95) as the primary anesthetic. We computed the EEG spectrum during stable anesthetic maintenance and identified whether or not burst suppression occurred during the anesthetic. We characterized the relationship between burst suppression and alpha power using logistic regression. We proposed 5 different models consisting of different combinations of potential contributing factors associated with burst suppression: (1) a Base Model consisting of alpha power; (2) an Extended Mechanistic Model consisting of alpha power, age, and drug dosing information; (3) a Clinical Confounding Factors Model consisting of alpha power, hypotension, and other confounds; (4) a Simplified Model consisting only of alpha power and propofol bolus administration; and (5) a Full Model consisting of all of these variables to control for as much confounding as possible.

Results: All models show a consistent significant association between alpha power and burst suppression while adjusting for different sets of covariates, all with consistent effect size estimates. Using the Simplified Model, we found that for each decibel decrease in alpha power, the odds of experiencing burst suppression increased by 1.33-fold.

Conclusions: In this study, we show how a decrease in anesthesia-induced frontal alpha power is associated with an increased propensity for burst suppression, in a manner that captures individualized information above and beyond a patient's chronological age. Lower frontal alpha band power is strongly associated with higher propensity for burst suppression and, therefore, potentially higher risk of postoperative neurocognitive disorders. We hypothesize that low frontal alpha power and increased propensity for burst suppression together characterize a "vulnerable brain" phenotype under anesthesia that could be mechanistically linked to brain metabolism, cognition, and brain aging.
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http://dx.doi.org/10.1213/ANE.0000000000004781DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7553194PMC
November 2020

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

BMJ Qual Saf 2021 Aug 7;30(8):678-688. 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
August 2021

Bayesian Approaches to Statistical Inferences.

Headache 2020 10;60(9):1879-1885

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

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http://dx.doi.org/10.1111/head.13952DOI Listing
October 2020

Patterns of Perceived Stress Throughout the Migraine Cycle: A Longitudinal Cohort Study Using Daily Prospective Diary Data.

Headache 2021 Jan 12;61(1):90-102. Epub 2020 Sep 12.

Department of Pediatrics, Alberta Children's Hospital, Calgary, Canada.

Objectives: To describe patterns of perceived stress across stages of the migraine cycle, within and between individuals and migraine episodes as defined for this study.

Methods: Individuals with migraine aged ≥18 years, who were registered to use the digital health platform N1-Headache , and completed 90 days of daily data entry regarding migraine, headache symptoms, and lifestyle factors were eligible for inclusion. Perceived stress was rated once a day at the participant's chosen time with a single question, "How stressed have you felt today?" with response options graded on a 0-10 scale. Days were categorized into phases of the migraine cycle: P  = pre-migraine headache (the 2 days prior to the first day with migraine headache), P  = migraine headache days, P  = post-migraine headache (the 2 days following the last migraine day with migraine headache), and P  = interictal days (all other days). Episodes, defined as discrete occurrences of migraine with days in all 4 phases, were eligible if there was at least 1 reported daily perceived stress value in each phase. Individuals with ≥5 valid episodes, and ≥75% compliance (tracking 90 days in 120 calendar days or less) were eligible for inclusion in the analysis.

Results: Data from 351 participants and 2115 episodes were included in this analysis. Eighty-six percent of the sample (302/351) were female. The mean number of migraine days per month was 6.1 (range 2-13, standard deviation = 2.3) and the mean number of episodes was 6.0 (range 5-10, standard deviation = 1.0) over the 90-day period. Only 8 (8/351, 2.3%) participants had chronic migraine (defined as 15 or more headache days per month with at least 8 days meeting criteria for migraine). Cluster analysis revealed 3 common patterns of perceived stress variation across the migraine cycle. For cluster 1, the "let down" pattern, perceived stress in the interictal phase (P ) falls in the pre-headache phase (P ) and then decreases more in the migraine phase (P ) relative to P . For cluster 2, the "flat" pattern, perceived stress is relatively unchanging throughout the migraine cycle. For cluster 3, the "stress as a trigger/symptom" pattern, perceived stress in P increases relative to P , and increases further in P relative to P . Episodes were distributed across clusters as follows: cluster 1: 354/2115, 16.7%; cluster 2: 1253/2115, 59.2%, and cluster 3: 508/2115, 24.0%. Twelve participants (12/351, 3.4%) had more than 50% of their episodes fall into cluster 1, 216 participants (216/351, 61.5%) had more than 50% of their episodes fall into cluster 2, and 25 participants (25/351, 7.1%) had more than 50% of their episodes fall into cluster 3. There were 40 participants with ≥90% of their episodes in cluster 2, with no participants having ≥90% of their episodes in cluster 1 or 3.

Conclusions: On an aggregate level, perceived stress peaks during the pain phase of the migraine cycle. However, on an individual and episode basis, there are 3 dominant patterns of perceived stress variation across the migraine cycle. Elucidating how patterns of perceived stress vary across the migraine cycle may contribute insights into disease biology, triggers and protective factors, and provide a framework for targeting individualized treatment plans.
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http://dx.doi.org/10.1111/head.13943DOI Listing
January 2021

The treatment implications of forecasting headache.

Pain Manag 2020 Nov 4;10(6):349-352. Epub 2020 Sep 4.

Department of Anesthesia, Critical Care & Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.

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http://dx.doi.org/10.2217/pmt-2020-0027DOI Listing
November 2020

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

Intensive Care Med 2020 10 3;46(10):1884-1893. Epub 2020 Sep 3.

Department of Anesthesia, Critical Care and Pain Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, Boston, MA, 02215, USA.

Purpose: ICU discharge is often delayed by a requirement for intravenous vasopressor medications to maintain normotension. We hypothesised that the administration of midodrine, an oral α-adrenergic agonist, as adjunct to standard treatment shortens the duration of intravenous vasopressor requirement.

Methods: In this multicentre, randomised, controlled trial including three tertiary referral hospitals in the US and Australia, we enrolled adult patients with hypotension requiring a single-agent intravenous vasopressor for ≥ 24 h. Subjects received oral midodrine (20 mg) or placebo every 8 h in addition to standard care until cessation of intravenous vasopressors, ICU discharge, or occurrence of adverse events. The primary outcome was time to vasopressor discontinuation. Secondary outcomes included time to ICU discharge readiness, ICU and hospital lengths of stay, and ICU readmission rates.

Results: Between October 2012 and June 2019, 136 participants were randomised, of whom 132 received the allocated intervention and were included in the analysis (modified intention-to-treat approach). Time to vasopressor discontinuation was not different between midodrine and placebo groups (median [IQR], 23.5 [10-54] vs 22.5 [10.4-40] h; difference, 1 h; 95% CI - 10.4 to 12.3 h; p = 0.62). No differences in secondary endpoints were observed. Bradycardia occurred more often after midodrine administration (5 [7.6%] vs 0 [0%], p = 0.02).

Conclusion: Midodrine did not accelerate liberation from intravenous vasopressors and was not effective for the treatment of hypotension in critically ill patients.
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http://dx.doi.org/10.1007/s00134-020-06216-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8273663PMC
October 2020

Reason to doubt the ICHD-3 7-day inclusion criterion for mild TBI-related posttraumatic headache: A nested cohort study.

Cephalalgia 2020 10 31;40(11):1155-1167. Epub 2020 Aug 31.

Department of Anaesthesia, Massachusetts General Hospital, Boston, MA, USA.

Background: Posttraumatic headache is difficult to define and there is debate about the specificity of the 7-day headache onset criterion in the current definition. There is limited evidence available to guide decision making about this criterion.

Method: A nested cohort study of 193 treatment-seeking veterans who met criteria for persistent headache attributed to mild traumatic injury to the head, including some veterans with delayed headache onset up to 90 days post-injury, was undertaken. Survival analysis examined the proportion of participants reporting headache over time and differences in these proportions based on sex, headache phenotype, and mechanism of injury.

Result: 127 participants (66%; 95% CI: 59-72%) reported headache onset within 7 days of head injury and 65 (34%) reported headache onset between 8 days and 3 months after head injury. Fourteen percent of participants reported pre-existing migraine before head injury, and there was no difference in the proportion of veterans with pre-existing migraine based on headache onset. Headache onset times were not associated with sex, headache phenotype, or mechanism of injury. There were no significant differences in proportion of veterans with headache onset within 7 days of head injury based on headache phenotype (70% migraine onset within 7 days, 70% tension-type headache within 7 days, 56% cluster headache within 7 days; ≥ .364). Similar findings were observed for head injury (64% blast, 60% blunt;  = .973). There were no significant differences observed between headache onset groups for psychiatric symptoms (Posttraumatic Stress Disorder Checklist for  = 1.3, 95% CI = -27.5, 30.1; Patient Health Questionnaire-9 Item = 3.5, 95% CI = -6.3, 3.7; Generalized Anxiety Disorder Screener = 6.5, 95% CI = -2.7, 15.6).

Conclusions: Although most of the sample reported headache onset within 7 days of head injury, one-third experienced an onset outside of the diagnostic range. Additionally, veterans with headache onset within 7 days of head injury were not meaningfully different from those with later onset based on sex, headache phenotype, or mechanism of head injury. The ICHD-3 diagnostic criteria for 7-day headache onset should be expanded to 3 months.

Clinicaltrials.gov Identifier: NCT02419131.
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http://dx.doi.org/10.1177/0333102420953109DOI Listing
October 2020

Migraine treatment and the risk of postoperative, pain-related hospital readmissions in migraine patients.

Cephalalgia 2020 12 24;40(14):1622-1632. Epub 2020 Aug 24.

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

Background: Migraine treatment may mitigate migraine and associated pain in the perioperative period.

Objective: The aim of the study was to estimate the effect of perioperative acute and prophylactic migraine treatment on the risk of postoperative 30-day hospital readmission with an admitting diagnosis specifying any pain complaints among migraine patients.

Design: Electronic health records were analysed for 21,932 adult migraine patients undergoing surgery between 2005 and 2017 at Beth Israel Deaconess Medical Center and Massachusetts General Hospital in Boston, Massachusetts, USA.

Methods: Perioperative abortive migraine treatment was defined as guideline-recommended medication (triptan, ergotamine, acetaminophen, nonsteroidal anti-inflammatory drug) prescription after surgery, within 30 days after discharge and prior readmission. Perioperatively continued prophylactic migraine treatment was defined as prescription both prior to surgery and perioperatively for recommended medications (beta-blockers, antidepressants, antiepileptics, onabotulinumtoxin A).

Results: Overall, 10,921 (49.8%) patients received a prescription for abortive migraine drugs. Of these, 1.2% and 1.5% of patients with and without such prescription were readmitted for pain, respectively. Patients with abortive treatment had lower odds of pain-related readmission (adjusted odds ratio 0.63 [95% confidence interval 0.49-0.81]). Prophylactic migraine treatment showed no effect on pain-related readmission independently of acute treatment (adjusted odds ratio 0.97 [95% confidence interval 0.72-1.32]).

Conclusions: Migraine patients undergoing surgery with a perioperative prescription for abortive migraine drugs were at decreased risk of pain-related hospital readmission.
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http://dx.doi.org/10.1177/0333102420949857DOI Listing
December 2020

Guidelines of the International Headache Society for controlled trials of preventive treatment of migraine attacks in episodic migraine in adults.

Cephalalgia 2020 09 28;40(10):1026-1044. Epub 2020 Jul 28.

Department of Neurology, Leiden University Medical Center, Leiden, the Netherlands.

Clinical trials are a key component of the evidence base for the treatment of headache disorders. In 1991, the International Headache Society Clinical Trials Standing Committee developed and published the first edition of the . Advances in drugs, devices, and biologicals, as well as novel trial designs, have prompted several updates over the nearly 30 years since, including most recently the (2018), the (2019), and (2019). The present update incorporates findings from new research and is intended to optimize the design of controlled trials of preventive pharmacological treatment of episodic migraine in adults. A guideline for clinical trials with devices will be published separately.
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http://dx.doi.org/10.1177/0333102420941839DOI Listing
September 2020

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

Br J Anaesth 2020 10 10;125(4):629-636. Epub 2020 Jul 10.

Department of Anaesthesiology, Duesseldorf University Hospital, Duesseldorf, Germany.

Background: Neuromuscular blocking agents (NMBAs) with a non-depolarising mechanism of action carry the risk of postoperative residual paralysis and are associated with postoperative pulmonary complications (POPC). Owing to the shorter duration of action, the depolarising NMBA succinylcholine may be associated with less postoperative residual paralysis, and hence fewer POPC. We tested the association of succinylcholine administration during anaesthesia and POPC.

Methods: In a retrospective cohort study of registry data from two large US academic medical centres, 244 850 adult noncardiac surgical patients undergoing general anaesthesia were included. The primary outcome was POPC, defined as post-extubation haemoglobin oxygen de-saturation to <90%, or re-intubation requiring intensive care unit admission within 7 days after surgery. The association between succinylcholine and POPC and its dose-dependency were tested in a hierarchical fashion using a multivariable logistic regression model.

Results: A total of 13 206 patients (5.4%) experienced POPC. Use of succinylcholine was associated with increased risk of POPC (adjusted odds ratio [OR]=1.11; 95% confidence interval [CI], 1.06-1.16; P<0.001; adjusted risk=5.18%; 95% CI, 5.06-5.30 without and 5.69%; 95% CI, 5.53-5.85 with succinylcholine), with a dose-dependent relationship (OR=1.08; 95% CI, 1.05-1.11 per mg kg; P<0.001). In patients receiving non-depolarising NMBAs, succinylcholine further increased the risk of POPC (ORAdj=1.08; 95% CI, 1.03-1.14; P=0.001). The association between succinylcholine and POPC was modified (P=0.03 for interaction) by the duration of surgery with higher odds of POPC in patients undergoing surgeries of <2 vs ≥2 h (OR=1.24; 95% CI, 1.15-1.33 and 1.05; 95% CI, 1.00-1.10, respectively).

Conclusions: In contrast to our prediction, succinylcholine administration was associated with an increased risk of POPC. This association was dose-dependent and magnified in surgeries of shorter duration.
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http://dx.doi.org/10.1016/j.bja.2020.05.059DOI Listing
October 2020

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

Anesth Analg 2020 08;131(2):497-507

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

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.
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http://dx.doi.org/10.1213/ANE.0000000000004852DOI Listing
August 2020

Recovery from nerve injury induced behavioral hypersensitivity in rats parallels resolution of abnormal primary sensory afferent signaling.

Pain 2020 05;161(5):949-959

Pain Mechanisms Lab, Department of Anesthesiology, Wake Forest School of Medicine, Winston-Salem, NC, United States.

Pain and hypersensitivity months after peripheral injury reflect abnormal input from peripheral afferents likely in conjunction with central sensitization. We hypothesize that peripheral changes occur in defined sensory afferents and resolve as behavioral response to injury resolves. Male Sprague-Dawley rats underwent sham or partial L5 spinal nerve ligation, and paw withdrawal threshold (PWT) was sequentially measured during recovery. At 2, 4, 8, and 12 weeks after injury, randomized animals underwent electrophysiologic assessment of L4 fast-conducting high- and low-threshold mechanoreceptors, and individual neuronal mechanical thresholds (MTs) were contrasted with PWTs in the same animals. Paw withdrawal thresholds decreased after injury and resolved over time (P < 0.001). Similarly, MTs of fast-conducting high-threshold mechanoreceptors decreased after injury and resolved over time (P < 0.001). By contrast, MTs of low-threshold mechanoreceptors increased after injury and resolved over time (P < 0.001). Distributions of recordings from each afferent subtype were perturbed after injury, and this too resolved over time. After resolution of behavioral changes, several electrical abnormalities persisted in both neuronal subtypes. These data extend previous findings that mechanically sensitive nociceptors are sensitized, whereas tactile, largely Aβ afferents are desensitized after nerve injury by showing that the time course of resolution of these changes mirrors that of behavioral hypersensitivity in a surgical injury including neural damage. These data support a role of abnormal peripheral input, from both nociceptor and tactile afferents, during recovery from peripheral injury and underscore the potential importance of both classes of afferents as potential targets for pain treatment.
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http://dx.doi.org/10.1097/j.pain.0000000000001781DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7166146PMC
May 2020

Statistical Hypothesis Testing: Overview and Application.

Headache 2020 02;60(2):302-308

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

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http://dx.doi.org/10.1111/head.13706DOI Listing
February 2020
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