Systematic Reviews and Meta-analyses in Regional Anesthesia and Pain Medicine (Part I): Guidelines for Preparing the Review Protocol.

Comprehensive resources exist on how to plan a systematic review and meta-analysis. The objective of this article is to provide guidance to authors preparing their systematic review protocol in the fields of regional anesthesia and pain medicine. The focus is on systematic reviews of health care interventions, with or without an aggregate data meta-analysis. We describe and discuss elements of the systematic review methodology that review authors should prespecify, plan, and document in their protocol before commencing the review. Importantly, authors should explain their rationale for planning their systematic review and describe the PICO framework-participants (P), interventions (I), comparators (C), outcomes (O)-and related elements central to constructing their clinical question, framing an informative review title, determining the scope of the review, designing the search strategy, specifying the eligibility criteria, and identifying potential sources of heterogeneity. We highlight the importance of authors defining and prioritizing the primary outcome, defining eligibility criteria for selecting studies, and documenting sources of information and search strategies. The review protocol should also document methods used to evaluate risk of bias, quality (certainty) of the evidence, and heterogeneity of results. Furthermore, the authors should describe their plans for managing key data elements, the statistical construct used to estimate the intervention effect, methods of evidence synthesis and meta-analysis, and conditions when meta-analysis may not be possible, including the provision of practical solutions. Authors should provide enough detail in their protocol so that the readers could conduct the study themselves.

Systematic Reviews and Meta-analyses in Regional Anesthesia and Pain Medicine (Part II): Guidelines for Performing the Systematic Review.

In Part I of this series, we provide guidance for preparing a systematic review protocol. In this article, we highlight important steps and supplement with exemplars on conducting and reporting the results of a systematic review. We suggest how authors can manage protocol violations, multiplicity of outcomes and analyses, and heterogeneity. The quality (certainty) of the evidence and strength of recommendations should follow the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. It is our goal that Part II of this series provides valid guidance to authors and peer reviewers who conduct systematic reviews to adhere to important constructs of transparency, structure, reproducibility, and accountability. This will likely result in more rigorous systematic reviews being submitted for publication to the journals like Regional Anesthesia & Pain Medicine and Anesthesia & Analgesia .

Association Between Age- and Sex-Specific Body Mass Index Percentile and Multiple Intubation Attempts: A Retrospective Cohort Analysis.

BACKGROUND: Obesity distorts airways and slightly complicates intubations in adults, but whether obesity complicates pediatric intubations remains unclear. We, therefore, tested the primary hypothesis that increasing age- and sex-specific body mass index (BMI) percentile is associated with difficult intubation, defined as >1 intubation attempt. METHODS: We conducted a retrospective analysis of pediatric patients between 2 and 18 years of age who had noncardiac surgery with oral endotracheal intubation. We assessed the association between BMI percentile and difficult intubation, defined as >1 intubation attempt, using a confounder-adjusted multivariable logistic regression model. Secondarily, we assessed whether the main association depended on preoperative substantial airway abnormality status or age group. RESULTS: A total of 9339 patients were included in the analysis. Median [quartiles] age- and sex-specific BMI percentile was 70 [33, 93], and 492 (5.3%) patients had difficult intubation. There was no apparent association between age- and sex-specific BMI percentile and difficult intubation. The estimated odds ratio (OR) for having difficult intubation for a 10-unit increase in BMI percentile was 0.98 (95% confidence interval [CI], 0.95-1.005) and was consistent across the 3 age groups of early childhood, middle childhood, and early adolescence (interaction P = .53). Patients with preoperative substantial airway abnormalities had lower odds of difficult intubation per 10-unit increase in BMI percentile, with OR (95% CI) of 0.83 (0.70-0.98), P = .01. CONCLUSIONS: Age- and sex-specific BMI percentile was not associated with difficult intubation in children between 2 and 18 years of age. As in adults, obesity in children does not much complicate intubation.

Association Between Cannabis Use and Opioid Consumption, Pain, and Respiratory Complications After Surgery: A Retrospective Cohort Analysis.

BACKGROUND: Cannabis is a widely used illicit drug with effects on different pain pathways. However, interactions between cannabis and postoperative pain are unclear. Cannabis smoking also affects the lungs, but the impact of cannabis use on postoperative pulmonary complications is unknown. We hypothesized that preoperative cannabis use in adults having elective surgery is associated with higher postoperative opioid consumption. Secondarily, we tested the hypothesis that cannabis use is associated with higher pain scores, hypoxemia (oxygen saturation [Spo2]/fraction of inspired oxygen [Fio2] ratio), and higher postoperative pulmonary complications compared to nonuse of cannabis. METHODS: In this retrospective study, we included adult patients who had elective surgeries at Cleveland Clinic Main Campus between January 2010 and December 2020. The exposure was use of cannabis within 30 days before surgery, and the control group never used cannabis. Patients who had regional anesthesia or chronic pain diagnosis were excluded. The primary outcome was postoperative opioid consumption; 3 secondary outcomes were time-weighted average (TWA) postoperative pain score, TWA Spo2/Fio2 ratio, and composite of pulmonary complications after surgery. We assessed the association between cannabis use and opioid consumption during the first 24 postoperative hours using linear regression on log-transformed opioid consumption with a propensity score-based method (inverse probability of treatment weighting [IPTW]) adjusting for confounders. We further adjusted for imbalanced confounding variables after IPTW was applied. RESULTS: In total, 1683 of 34,521 patients were identified as cannabis users. Cannabis use was associated with increased opioid consumption, with an adjusted ratio of geometric means (95% confidence interval [CI]) of 1.30 (1.22-1.38; P < .0001) for cannabis users versus nonusers. Secondarily, (1) cannabis use was associated with increased TWA pain score, with a difference in means of 0.57 (95% CI, 0.46-0.67; P < .0001); (2) cannabis use was not associated with TWA Spo2/Fio2, with an adjusted difference in means of 0.5 (95% CI, -3.1 to 4.2; P = .76); and (3) cannabis use was not associated with a collapsed composite of pulmonary complications, with estimated odds ratio of 0.90 (95% CI, 0.71-1.13; P = .34). CONCLUSIONS: Adult cannabis users undergoing surgeries were found to have significantly higher postoperative opioid consumption and pain scores than nonusers. Cannabis use did not have a clinically meaningful association with hypoxia or composite pulmonary complications.

Timing of Intraoperative Transitions of Care Among Anesthesiologists Is Not Associated With Postoperative Adverse Outcomes: Retrospective Cohort Study.

BACKGROUND: The majority of published research suggests that anesthesia handovers during major surgical procedures are associated with unintended harmful consequences. It is still unclear if the number or quality of the transition of care is the main driver of the adverse outcomes. There is even less data if the timing of the anesthesiologist handovers during the critical portion of the anesthetic continuum (induction or emergence versus surgical period) plays a role in patient outcomes. Therefore, we investigated if the anesthesiologist handovers during induction and emergence are associated with adverse patient outcomes. METHODS: This retrospective investigation included noncardiac surgical procedures occurring between January 1, 2012 and December 31, 2019 that had exactly 1 attending anesthesiologist handover. We categorized transitions of care between attending anesthesiologists as being before incision, between incision and closing, and after closing. Our primary outcome was a composite of 6 categories of surgical complications and in-hospital mortality. We created logistic generalized estimating equation models to estimate the average relative effect odds ratio between each pair of the 3 transition timing groups across the components of the composite outcome. Inverse probability of treatment weights were used to mitigate confounding on a host of baseline variables. We used Bonferroni correction to adjust for multiple comparisons between the transition groups. RESULTS: In total, we studied 36,937 procedures with exactly 1 attending anesthesiologist handover. Of these records, 4370 had the transition during induction, 24,999 between incision and closure, and 7568 during emergence. No differences were found between the transition periods and the composite outcome. The estimated average relative effect odds ratio (98.3% confidence interval [CI]) across the components of the composite outcome was as follows: (1.0002 [0.81-1.24], P = .99) between the induction and surgical period; (1.10 [0.87-1.40], P = .32) between the induction and emergence periods; and (0.91 [0.79-1.04], P = .08) between the emergence and surgical periods. CONCLUSIONS: Timing of intraoperative handover among attending anesthesiologists during noncardiac surgery is not associated with adverse patient outcomes.

Smallest Clinically Meaningful Improvement in Amputation-Related Pain and Brief Pain Inventory Scores as Defined by Patient Reports of Global Improvement After Cryoneurolysis: a Retrospective Analysis of a Randomized, Controlled Clinical Trial.

BACKGROUND: The smallest meaningful improvement in pain scores (minimal clinically important difference [MCID]) after an analgesic intervention is essential information when both interpreting published data and designing a clinical trial. However, limited information is available for patients with chronic pain conditions, and what is published is derived from studies involving pharmacologic and psychological interventions. We here calculate these values based on data collected from 144 participants of a previously published multicenter clinical trial investigating the effects of a single treatment with percutaneous cryoneurolysis. METHODS: In the original trial, we enrolled patients with a lower-limb amputation and established phantom pain. Each received a single-injection femoral and sciatic nerve block with lidocaine and was subsequently randomized to receive either ultrasound-guided percutaneous cryoneurolysis or sham treatment at these same locations. Investigators, participants, and clinical staff were masked to treatment group assignment with the exception of the treating physician performing the cryoneurolysis, who had no subsequent participant interaction. At both baseline and 4 months (primary end point), participants rated their phantom limb pain based on a numeric rating scale (NRS) and their interference of pain on physical and emotional functioning as measured with the Brief Pain Inventory's interference subscale. They subsequently qualitatively defined the change using the 7-point ordinal Patient Global Impression of Change (PGIC). The smallest clinically meaningful improvements in phantom limb pain and Brief Pain Inventory scores were calculated using an anchor-based method based on the PGIC. RESULTS: The median (interquartile range [IQR]) phantom pain NRS (0-10) improvements at 4 months considered small, medium, and large were 1 [1-1], 3 [3-4], and 4 [3-6], respectively. The median improvements in the Brief Pain Inventory interference subscale (0-70) associated with a small, medium, and large analgesic changes were 16 [6-18], 24 [22-31], and 34 [22-46]. The proportions of patients that experienced PGIC ≥5 were 33% and 36% in the active and placebo groups, respectively. The relative risk of a patient experiencing PGIC ≥5 in the active group compared to the sham group with 95% confidence interval was 0.9 (0.6-1.4), P = .667. CONCLUSIONS: Amputees with phantom limb pain treated with percutaneous cryoneurolysis rate analgesic improvements as clinically meaningful similar to pharmacologic treatments, although their MCID for the Brief Pain Inventory was somewhat larger than previously published values. This information on patient-defined clinically meaningful improvements will facilitate interpretation of available studies and guide future trial design.

Perioperative Supplemental Oxygen and Postoperative Nausea and Vomiting: Subanalysis of a Trial, Systematic Review, and Meta-analysis.

BACKGROUND: Intraoperative supplemental oxygen may reduce postoperative nausea and vomiting by mitigating hypoxic stress on the gastrointestinal tract. The authors therefore tested the hypothesis that supplemental oxygen reduces nausea and vomiting in adults recovering from colorectal surgery at the Cleveland Clinic between January 28, 2013, and March 11, 2016. METHODS: Initially, the authors conducted an unplanned subanalysis of a previous trial that evaluated the effect of 80% versus 30% intraoperative inspired oxygen on surgical site infection. Specifically, they assessed the effect of 80% versus 30% oxygen concentration on the incidence of postoperative nausea and/or vomiting. Thereafter, the authors conducted a systematic review and meta-analysis of the effect of supplemental oxygen on postoperative nausea and vomiting. RESULTS: The authors' underlying analysis included 5,057 colorectal surgeries on 4,001 patients. For 2,554 surgeries, assignment was to 80% oxygen, and in 2,503 surgeries, to 30%. Postoperative nausea and vomiting was 852 of 2,554 (33%) in 80% oxygen and 814 of 2,503 (33%) in 30% oxygen. The estimated relative risk (95% CI) of 80% versus 30% oxygen on postoperative nausea and vomiting was 1.04 (0.96 to 1.12) in a generalized estimating equation model adjusting for within-patient correlation for patients with multiple surgeries, P = 0.355. Furthermore, supplemental oxygen did not reduce antiemetic use (P = 0.911) or the severity of nausea and vomiting (P = 0.924). The authors' meta-analysis included 10 qualifying trials (6,749 patients) and did not find a difference in postoperative nausea and vomiting: relative risk, 0.97 [95% CI, 0.86 to 1.08], P = 0.55, I2 = 52%. CONCLUSIONS: The incidence of postoperative nausea and vomiting did not differ in patients assigned to 80% or 30% inspired oxygen. A meta-analysis of available trials similarly indicated that supplemental intraoperative oxygen does not reduce postoperative nausea and vomiting. Therefore, supplemental oxygen should not be given in the expectation that it will reduce nausea and vomiting.

Best Practice Alerts Informed by Inpatient Opioid Intake to Reduce Opioid Prescribing after Surgery (PRIOR): A Cluster Randomized Multiple Crossover Trial.

BACKGROUND: Overprescription of opioids after surgery remains common. Residual and unnecessarily prescribed opioids can provide a reservoir for nonmedical use. This study therefore tested the hypothesis that a decision-support tool embedded in electronic health records guides clinicians to prescribe fewer opioids at discharge after inpatient surgery. METHODS: This study included 21,689 surgical inpatient discharges in a cluster randomized multiple crossover trial from July 2020 to June 2021 in four Colorado hospitals. Hospital-level clusters were randomized to alternating 8-week periods during which an electronic decision-support tool recommended tailored discharge opioid prescriptions based on previous inpatient opioid intake. During active alert periods, the alert was displayed to clinicians when the proposed opioid prescription exceeded recommended amounts. No alerts were displayed during inactive periods. Carryover effects were mitigated by including 4-week washout periods. The primary outcome was oral morphine milligram equivalents prescribed at discharge. Secondary outcomes included combination opioid and nonopioid prescriptions and additional opioid prescriptions until day 28 after discharge. A vigorous state-wide opioid education and awareness campaign was in place during the trial. RESULTS: The total postdischarge opioid prescription was a median [quartile 1, quartile 3] of 75 [0, 225] oral morphine milligram equivalents among 11,003 patients discharged when the alerts were active and 100 [0, 225] morphine milligram equivalents in 10,686 patients when the alerts were inactive, with an estimated ratio of geometric means of 0.95 (95% CI, 0.80 to 1.13; P = 0.586). The alert was displayed in 28% (3,074 of 11,003) of the discharges during the active alert period. There was no relationship between the alert and prescribed opioid and nonopioid combination medications or additional opioid prescriptions written after discharge. CONCLUSIONS: A decision-support tool incorporated into electronic medical records did not reduce discharge opioid prescribing for postoperative patients in the context of vigorous opioid education and awareness efforts. Opioid prescribing alerts might yet be valuable in other contexts.(Anesthesiology 2023; 139:186-96).

Ultrasound-guided Percutaneous Cryoneurolysis to Treat Chronic Postamputation Phantom Limb Pain: A Multicenter Randomized Controlled Trial.

BACKGROUND: Postamputation phantom pain is notoriously persistent with few validated treatments. Cryoneurolysis involves the application of low temperatures to reversibly ablate peripheral nerves. The authors tested the hypothesis that a single cryoneurolysis treatment would decrease phantom pain 4 months later. METHODS: The authors enrolled patients with a lower-limb amputation and established phantom pain. Each received a single-injection femoral and sciatic nerve block with lidocaine and was subsequently randomized to receive either ultrasound-guided percutaneous cryoneurolysis or sham treatment at these same locations. The primary outcome was the change in average phantom pain intensity between baseline and 4 months as measured with a numeric rating scale (0 to 10), after which an optional crossover treatment was offered. Investigators, participants, and clinical staff were masked to treatment group assignment with the exception of the treating physician performing the cryoneurolysis, who had no subsequent participant interaction. RESULTS: Pretreatment phantom pain scores were similar in both groups, with a median [quartiles] of 5.0 [4.0, 6.0] for active treatment and 5.0 [4.0, 7.0] for sham. After 4 months, pain intensity decreased by 0.5 [-0.5, 3.0] in patients given cryoneurolysis (n = 71) versus 0 [0, 3] in patients given sham (n = 73), with an estimated difference (95% CI) of -0.1 (-1.0 to 0.7), P = 0.759. Following their statistical gatekeeping protocol, the authors did not make inferences or draw conclusions on secondary endpoints. One serious adverse event occurred after a protocol deviation in which a femoral nerve cryolesion was induced just below the inguinal ligament-instead of the sensory-only saphenous nerve-which resulted in quadriceps weakness, and possibly a fall and clavicle fracture. CONCLUSIONS: Percutaneous cryoneurolysis did not decrease chronic lower extremity phantom limb pain 4 months after treatment. However, these results were based upon the authors' specific study protocol, and since the optimal cryoneurolysis treatment parameters such as freeze duration and anatomic treatment location remain unknown, further research is warranted.

Cooling vest improves surgeons' thermal comfort without affecting cognitive performance: a randomised cross-over trial.

OBJECTIVES: Surgeons become uncomfortable while performing surgery because heat transfer and evaporative cooling are restricted by insulating surgical gowns. Consequently, perceptions of thermal discomfort during surgery may impair cognitive performance. We, therefore, aimed to evaluate surgeons' thermal comfort, cognitive performance, core and mean skin temperatures, perceptions of sweat-soaked clothing, fatigue and exertion with and without a CoolSource cooling vest (Cardinal Health, Dublin, Ohio, USA). METHODS: Thirty orthopaedic surgeons participated in a randomised cross-over trial, each performing four total-joint arthroplasties with randomisation to one of four treatment sequences. The effects of cooling versus no cooling were measured using a repeated-measures linear model accounting for within-subject correlations. RESULTS: The cooling vest improved thermal comfort by a mean (95% CI) of -2.1 (-2.7 to -1.6) points on a 0-10 scale, p<0.001, with no evidence of treatment-by-period interaction (p=0.94). In contrast, cooling had no perceptible effect on cognition, with an estimated mean difference (95% CI) in Cleveland Clinic Cognitive Battery (C3B) Processing Speed Test score of 0.03 (95% CI -2.44 to 2.51), p=0.98, or in C3B Visual Memory Test score with difference of 0.88 (95% CI -2.25 to 4.01), p=0.57. Core temperature was not lower with the cooling vest, with mean difference (95% CI) of -0.13 (-0.33°C to 0.07°C), p=0.19, while mean skin temperature was lower, with mean difference of -0.23 (95% CI -0.40°C to -0.06°C) lower, p=0.011. The cooling vest significantly reduced surgeons' perceptions of sweat-soaked clothing, fatigue and exertion. CONCLUSIONS: A cooling vest worn during surgery lowered core and skin temperatures, improved thermal comfort, and decreased perceptions of sweating and fatigue, but did not improve cognition. Thermal discomfort during major orthopaedic surgery is thus largely preventable, but cooling does not affect cognition. TRIAL REGISTRATION NUMBER: NCT04511208.

Using Preanesthesia Clinic Visits to Improve Advance Directives Completion: An Interrupted Time Series Analysis.

BACKGROUND: Advance directives documentation can increase the likelihood that patient's wishes are respected if they become incapacitated. Unfortunately, completion rates are suboptimal overall, and disparities may exist, especially for vulnerable groups. We assessed whether implementing an initiative to standardize advance directives discussions during preanesthesia visits was associated with changes in rates of advance directives completion over time, and whether the association depends on race, insurance type, or income. METHODS: We conducted a before-after interrupted time series evaluation between January 1, 2015 and June 30, 2019 in a single-center, outpatient preanesthesia clinic. Participants were adults who visited the preanesthesia clinic at Cleveland Clinic and had >1 comorbidity before a noncardiac surgery of either medium or high risk. The intervention in March of 2017 consisted of training staff to help patients complete and witness advance directives documents during visits. We measured advance directives completion, by race, payor, and income (using the 2019 Federal Poverty Line). We assessed the confounder-adjusted association between intervention (pre versus post) and proportion of patients completing advanced directives over time using segmented regression to compare slopes between periods and assess changes at start of the intervention. We used similar models to assess whether changes depended on race, insurance type, or income level. RESULTS: We included 26,368 visits from 22,430 patients. We analyzed financial status for 16,788 visits from 14,274 patients who had address data. There were 11,242 (43%) visits preintervention and 15,126 (57%) visits postintervention. Crude completion rates for advance directives increased from 29% to 78%, with odds of completion an estimated 18 times higher than preintervention (odds ratio [95% CI] of 18 [16-21]; P < 0.001). Regarding race, Black patients had lower completion rates preintervention than White patients, although the gap steadily closed after the intervention ( P = .001). Postintervention, both race groups immediately increased, with no difference in amount of increase ( P = .17) or postintervention change in slope difference ( P = .17). Regarding insurance, patients with Medicaid had lower preintervention completion rates than those with private. Intervention was associated with increases in both groups, but the difference in slopes ( P = .43) or proportions ( P = .23) between the groups did not change after intervention. Regarding the Federal Poverty Line, the completion rate gap between those below (<100%) and above (139%-400%) narrowed by approximately half (0.51: 95% CI, 0.27-0.98; P = .04). CONCLUSIONS: Standardizing advance directives discussions during preanesthesia visits was associated with more patients completing advance directives, particularly in vulnerable patient groups.

Derivation and Validation of Clinical Phenotypes of the Cardiopulmonary Bypass-Induced Inflammatory Response.

BACKGROUND: Precision medicine aims to change treatment from a "one-size-fits-all" approach to customized therapies based on the individual patient. Applying a precision medicine approach to a heterogeneous condition, such as the cardiopulmonary bypass (CPB)-induced inflammatory response, first requires identification of homogeneous subgroups that correlate with biological markers and postoperative outcomes. As a first step, we derived clinical phenotypes of the CPB-induced inflammatory response by identifying patterns in perioperative clinical variables using machine learning and simulation tools. We then evaluated whether these phenotypes were associated with biological response variables and clinical outcomes. METHODS: This single-center, retrospective cohort study used Cleveland Clinic registry data from patients undergoing cardiac surgery with CPB from January 2010 to March 2020. Biomarker data from a subgroup of patients enrolled in a clinical trial were also included. Patients undergoing emergent surgery, off-pump surgery, transplantation, descending thoracoabdominal aortic surgery, and planned ventricular assist device placement were excluded. Preoperative and intraoperative variables of patient baseline characteristics (demographics, comorbidities, and laboratory data) and perioperative data (procedural data, CPB duration, and hemodynamics) were analyzed to derive clinical phenotypes using K-means-based consensus clustering analysis. Proportion of ambiguously clustered was used to assess cluster size and optimal cluster numbers. After clusters were formed, we summarized perioperative profiles, inflammatory biomarkers (eg, interleukin [IL]-6 and IL-8), kidney biomarkers (eg, urine neutrophil gelatinase-associated lipocalin [NGAL] and IL-18), and clinical outcomes (eg, mortality and hospital length of stay). Pairwise standardized difference was reported for all summarized variables. RESULTS: Of 36,865 eligible cardiac surgery cases, 25,613 met inclusion criteria. Cluster analysis derived 3 clinical phenotypes: α, ß, and γ. Phenotype α (n = 6157 [24%]) included older patients with more comorbidities, including heart and kidney failure. Phenotype ß (n = 10,572 [41%]) patients were younger and mostly male. Phenotype γ (n = 8884 [35%]) patients were 58% female and had lower body mass index (BMI). Phenotype α patients had worse outcomes, including longer hospital length of stay (mean = 9 days for α versus 6 for both ß [absolute standardized difference {ASD} = 1.15] and γ [ASD = 1.08]), more kidney failure, and higher mortality. Inflammatory biomarkers (IL-6 and IL-8) and kidney injury biomarkers (urine NGAL and IL-18) were higher with the α phenotype compared to ß and γ immediately after surgery. CONCLUSIONS: Deriving clinical phenotypes that correlate with response biomarkers and outcomes represents an initial step toward a precision medicine approach for the management of CPB-induced inflammatory response and lays the groundwork for future investigation, including an evaluation of the heterogeneity of treatment effect.

Nociception Level Index-Guided Intraoperative Analgesia for Improved Postoperative Recovery: A Randomized Trial.

BACKGROUND: Nociception is the physiological response to nociceptive stimuli, normally experienced as pain. During general anesthesia, patients experience and respond to nociceptive stimuli by increasing blood pressure and heart rate if not controlled by preemptive analgesia. The PMD-200 system from Medasense (Ramat Gan, Israel) evaluates the balance between nociceptive stimuli and analgesia during general anesthesia and generates the nociception level (NOL) index from a single finger probe. NOL is a unitless index ranging from 0 to 100, with values exceeding 25 indicating that nociception exceeds analgesia. We aimed to demonstrate that titrating intraoperative opioid administration to keep NOL <25 optimizes intraoperative opioid dosing. Specifically, we tested the hypothesis that pain scores during the initial 60 minutes of recovery are lower in patients managed with NOL-guided fentanyl than in patients given fentanyl per clinical routine. METHODS: We conducted a randomized, single-center trial of patients having major abdominal open and laparoscopic surgeries. Patients were randomly assigned 1:1 to intraoperative NOL-guided fentanyl administration or fentanyl given per clinical routine. The primary outcome was pain score (0-10 verbal response scale) at 10-minute intervals during the initial 60 minutes of recovery. Our secondary outcome was a measure of adequate analgesia, defined as a pain score <5, assessed separately at each interval. RESULTS: With a planned maximum sample size of 144, the study was stopped for futility after enrolling 72 patients from November 2020 to October 2021. Thirty-five patients were assigned to NOL-guided analgesic dosing and 37 to routine care. Patients in the NOL group spent significantly less time with a NOL index >25 (median reduction [95% confidence interval {CI}] of 14 [4-25] minutes) were given nearly twice as much intraoperative fentanyl (median [quartiles] 500 [330, 780] vs 300 [200, 330] µg), and required about half as much morphine in the recovery period (3.3 [0, 8] vs 7.7 [0, 13] mg). However, in the primary outcome analysis, NOL did not reduce pain scores in the first 60 minutes after awakening, assessed in a linear mixed effects model with mean (standard error [SE]) of 4.12 (0.59) for NOL and 4.04 (0.58) for routine care, and estimated difference in means of 0.08 (-1.43, 1.58), P = .895. CONCLUSIONS: More intraoperative fentanyl was given in NOL-guided patients, but NOL guidance did not reduce initial postoperative pain scores.

Wearable device for prevention of postoperative and post-discharge hypoxemia: A randomized pilot trial.

BACKGROUND: The Oxalert Enhanced Pulse Oximeter (EPO) is a wearable device that detects and alerts patients to hypoxemia. In a preplanned pilot trial, we estimated the effect of continuous saturation monitoring with patient alerts on in-hospital and post-discharge saturation; we further assessed the feasibility of the intervention. METHODS: Noncardiac surgical patients were randomized to either the Oxalert with patient alerts (Monitor + Alert, N = 25) or the Oxalert without patient alerts (Monitor Only, N = 24). Monitoring continued during hospitalization for up to 6 days and for 24 h after hospital discharge. Patients in each group were compared on time-weighted average (TWA) SpO2 <90% (%) and area under SpO2 <90% (% * min) in-hospital and after discharge using the Wilcoxon rank sum test, with the treatment effect median difference and 95% confidence interval (CI) estimated using the Hodges-Lehmann estimator of location shift. RESULTS: We enrolled ≥2 patients per week, for a total of 49 patients in whom recording were obtained for a median [quartiles] of 91 [85, 95]% of the time in hospital. In-hospital, TWA SpO2 <90% was a median [quartiles] of 0.11 [0.03, 0.25]% for Monitor + Alert and 0.29 [0.04, 0.71]% for Monitor-Only patients, with estimated median difference (95% CI) of -0.1 (-0.4, 0)%, p = .120. In hospital, the area under the curve (AUC) SpO2 <90% was a median [quartiles] of 635 [204, 1513] % * min for Monitor + Alert and 1260 [117, 5278] % * min for Monitor-Only patients, with estimated median difference (95% CI) of -407 (-1816, 208) % * min, p = .349. Post-discharge, the estimated median difference (95% CI) was only -0.1 (-0.2, 0) %, p = .307. CONCLUSIONS: The Oxalert system was well tolerated in both groups and enrollment was strong. Patients randomized to active Oxalert systems experienced half as many postoperative desaturation events while hospitalized, although the difference was not statistically significant in this small pilot trial. In contrast, the Oxalert system did not reduce post-discharge desaturation. Detecting postoperative deterioation in surgical patients after they arrive on regular hospital wards, and even after they have been discharged home, can potentially facilitate necessary "rescue" interventions. Wearable devices assessing vital signs, including oxygenation, are a practical requirement. In this pilot study, a wearable pulse oximeter, with and without hypoxemia alarms, was tested for feasibility and acceptability for signal collection in postoperative cases, including at home. Results indicate that a full-scale trial is warranted to test for possible clinical benefit with this type of "wearable" where late postoperative hypoxia could be a concern. The trial was registered at ClincialTrial.gov (NCT04453722).

Association between postoperative hypotension and acute kidney injury after noncardiac surgery: a historical cohort analysis.

PURPOSE: The extent to which postoperative hypotension contributes to renal injury remains unclear, much less what the harm thresholds might be. We therefore tested the primary hypothesis that there is an absolute hypotensive arterial pressure threshold for acute kidney injury during the initial seven days after noncardiac surgery. METHODS: We conducted a single-centre historical cohort analysis of adults who had noncardiac surgery and had creatinine recorded preoperatively and postoperatively. Our exposure was the lowest postoperative mean arterial pressure, defined as the average of the three lowest postoperative pressure measurements. Our primary analysis was the association between the lowest mean arterial pressure and acute kidney injury, defined according to Kidney Disease: Improving Global Outcomes initiative criteria. Our analysis was adjusted for potentially relevant confounding factors including intraoperative hypotension. RESULTS: Among 64,349 patients analyzed, 2,812 (4.4%) patients had postoperative acute kidney injury. Each 5-mm Hg decrease in the lowest mean arterial pressure was associated with a 28% (97.5% confidence interval [CI], 23 to 32; P < 0.001) increase in the odds of acute kidney injury for lowest mean arterial pressures < 80 mm Hg. Higher lowest pressures were not associated with acute kidney injury (odds ratio, 1.08; 97.5% CI, 0.99 to 1.17; P = 0.04) for each 5-mm Hg decrease in the lowest mean arterial pressure. CONCLUSION: Postoperative hypotension, defined as the lowest postoperative mean arterial pressure < 80 mm Hg, was associated with acute kidney injury after noncardiac surgery. A prospective trial will be required to determine whether the observed association is causal and thus amenable to modification.

RéSUMé: OBJECTIF: Nous ne savons pas dans quelle mesure l'hypotension postopératoire contribue aux lésions rénales, et nous connaissons encore moins les seuils de lésion. Nous avons donc testé l'hypothèse primaire selon laquelle il existerait un seuil absolu de tension artérielle hypotensive pour l'insuffisance rénale aiguë au cours des sept premiers jours suivant une chirurgie non cardiaque. MéTHODE: Nous avons mené une analyse de cohorte historique monocentrique auprès d'adultes ayant bénéficié d'une chirurgie non cardiaque et pour lesquel·les les taux de créatinine avant et après l'opération avaient été enregistrés. Notre exposition était la tension artérielle moyenne postopératoire la plus basse, définie comme la moyenne des trois mesures de tension postopératoire les plus basses. Notre analyse principale a porté sur l'association entre la tension artérielle moyenne la plus basse et l'insuffisance rénale aiguë, définies selon les critères de l'initiative KDIGO (Kidney Disease: Improving Global Outcomes). Notre analyse a été ajustée pour tenir compte des facteurs de confusion potentiellement pertinents, notamment de l'hypotension peropératoire. RéSULTATS: Parmi les 64 349 patient·es analysé·es, 2812 (4,4 %) ont présenté une insuffisance rénale aiguë postopératoire. Chaque diminution de 5 mm Hg de la tension artérielle moyenne la plus faible était associée à une augmentation de 28 % (intervalle de confiance [IC] de 97,5 %, 23 à 32; P < 0,001) des risques d'insuffisance rénale aiguë pour les tensions artérielles moyennes les plus faibles < 80 mm Hg. Des tensions les plus faibles plus hautes n'ont pas été associées à une insuffisance rénale aiguë (rapport de cotes, 1,08; IC 97,5 %, 0,99 à 1,17; P = 0,04) pour chaque diminution de 5 mm Hg de la tension artérielle moyenne la plus faible. CONCLUSION: L'hypotension postopératoire, définie comme la tension artérielle moyenne postopératoire < 80 mm Hg la plus basse, a été associée à une insuffisance rénale aiguë après une chirurgie non cardiaque. Une étude prospective sera nécessaire pour déterminer si l'association observée est causale et donc susceptible d'être modifiée.

Percutaneous Neuromodulation of the Brachial Plexus and Sciatic Nerve for the Treatment of Acute Pain Following Surgery: Secondary Outcomes From a Multicenter, Randomized, Controlled Pilot Study.

OBJECTIVES: We recently reported that percutaneous peripheral nerve stimulation (PNS or "neuromodulation") decreased pain and opioid consumption within the first two weeks following ambulatory surgery. However, the anatomic lead locations were combined for the analysis, and benefits for each location remain unknown. We therefore now report the effects of percutaneous PNS for brachial plexus and sciatic nerve leads separately. MATERIALS AND METHODS: Before surgery, leads were implanted percutaneously to target the brachial plexus (N = 21) for rotator cuff repair or sciatic nerve (N = 40) for foot/ankle surgery, followed by a single injection of local anesthetic. Postoperatively, subjects were randomized in a double masked fashion to 14 days of electrical stimulation (N = 30) or sham/placebo (N = 31) using an external pulse generator. The primary outcome of interest was opioid consumption and pain scores evaluated jointly. Thus, stimulation was deemed effective if superior on either outcome and at least noninferior on the other. RESULTS: For brachial plexus leads, during the first seven postoperative days pain measured with the numeric rating scale in participants given active stimulation was a median [interquartile range] of 0.8 [0.5, 1.6] versus 3.2 [2.7, 3.5] in patients given sham (p < 0.001). For this same group, opioid consumption in participants given active stimulation was 10 mg [5, 20] versus 71 mg [35, 125] in patients given sham (p = 0.043). For sciatic nerve leads, pain scores for the active treatment group were 0.7 [0, 1.4] versus 2.8 [1.6, 4.6] in patients given sham (p < 0.001). During this same period, participants given active stimulation consumed 5 mg [0, 30] of opioids versus 40 mg [20, 105] in patients given sham (p = 0.004). Treatment effects did not differ statistically between the two locations. CONCLUSIONS: Ambulatory percutaneous PNS of both the brachial plexus and sciatic nerve is an effective treatment for acute pain free of systemic side effects following painful orthopedic surgery.

Incidence of sedation-related adverse events during ERCP with anesthesia assistance: a multicenter observational study.

BACKGROUND AND AIMS: Anesthesia assistance is commonly used for ERCP. General anesthesia (GA) may provide greater airway protection but may lead to hypotension. We aimed to compare GA versus sedation without planned intubation (SWPI) on the incidence of hypoxemia and hypotension. We also explored risk factors for conversion from SWPI to GA. METHODS: This observational study used data from the Multicenter Perioperative Outcomes Group. Adults with American Society of Anesthesiologists physical status class I to IV undergoing ERCP between 2006 and 2019 were included. We compared GA and SWPI on incidence of hypoxemia (oxygen saturation <90% for ≥3 minutes) and hypotension (mean arterial pressure <65 mm Hg for ≥5 minutes) using joint hypothesis testing. The association between anesthetic approach and outcomes was assessed using logistic regression. The noninferiority delta for hypoxemia and hypotension was an odds ratio of 1.20. One approach was deemed better if it was noninferior on both outcomes and superior on at least 1 outcome. To explore risk factors associated with conversion from SWPI to GA, we constructed a logistic regression model. RESULTS: Among 61,735 cases from 42 institutions, 38,830 (63%) received GA and 22,905 (37%) received SWPI. The GA group had 1.27 times (97.5% confidence interval, 1.19-1.35) higher odds of hypotension but .71 times (97.5% confidence interval, .63-.80) lower odds of hypoxemia. Neither group was noninferior to the other on both outcomes. Conversion from SWPI to GA occurred in 6.5% of cases and was associated with baseline comorbidities and higher institutional procedure volume. CONCLUSIONS: GA for ERCP was associated with less hypoxemia, whereas SWPI was associated with less hypotension. Neither approach was better on the combined incidence of hypotension and hypoxemia.

Hemodynamic Responses to Crystalloid and Colloid Fluid Boluses during Noncardiac Surgery.

BACKGROUND: Colloids are thought to sustain blood pressure and cardiac index better than crystalloids. However, the relative effects of intraoperative hydroxyethyl starch and crystalloid administration on the cardiac index and blood pressure remain unclear. This study therefore tested in this subanalysis of a previously published large randomized trial the hypothesis that intraoperative goal-directed colloid administration increases the cardiac index more than goal-directed crystalloid administration. Further, the effects of crystalloid and colloid boluses on blood pressure were evaluated. METHODS: This planned subanalysis of a previous trial analyzed data from 973 patients, of whom 480 were randomized to colloids and 493 were randomized to crystalloids. Fluid administration was guided by esophageal Doppler. The primary outcome was the time-weighted average cardiac index during surgery between the colloid and crystalloid group. The secondary outcomes were the cardiac index just after bolus administration, time elapsed between boluses, and the average real variability during surgery. The study recorded cardiac index, corrected flow time, and blood pressure at 10-min intervals, as well as before and after each bolus. RESULTS: Time-weighted average of cardiac index over the duration of anesthesia was only slightly greater in patients given colloid than crystalloid, with the difference being just 0.20 l · min-1 · m-2 (95% CI, 0.11 to 0.29; P < 0.001). However, the hazard for needing additional boluses was lower after colloid administration (hazard ratio [95% CI], 0.60 [0.55 to 0.66]; P < 0.001) in a frailty time-to-event model accounting for within-subject correlation. The median [quartiles] number of boluses per patient was 4 [2, 6] for colloids and 6 [3, 8] for crystalloids, with a median difference (95% CI) of -1.5 (-2 to -1; P < 0.001). The average real mean arterial pressure variability did not differ significantly between the groups (difference in means [95% CI] of -0.03 (-0.07 to 0.02) mmHg, P = 0.229). CONCLUSIONS: There were not clinically meaningful differences in the cardiac index or mean pressure variability in patients given goal-directed colloid and crystalloids. As might be expected from longer intravascular dwell time, the interval between boluses was longer with colloids. However, on a case basis, the number of boluses differed only slightly. Colloids do not appear to provide substantial hemodynamic benefit.

Prolonged Blood Storage and Risk of Posttransfusion Acute Kidney Injury.

BACKGROUND: Erythrocyte transfusions are independently associated with acute kidney injury. Kidney injury may be consequent to the progressive hematologic changes that develop during storage. This study therefore tested the hypothesis that prolonged erythrocyte storage increases posttransfusion acute kidney injury. METHODS: The Informing Fresh versus Old Red Cell Management (INFORM) trial randomized 31,497 patients to receive either the freshest or oldest available matching erythrocyte units and showed comparable mortality with both. This a priori substudy compared the incidence of posttransfusion acute kidney injury in the randomized groups. Acute kidney injury was defined by the creatinine component of the Kidney Disease: Improving Global Outcomes criteria. RESULTS: The 14,461 patients included in this substudy received 40,077 erythrocyte units. For patients who received more than one unit, the mean age of the blood units was used as the exposure. The median of the mean age of blood units transfused per patient was 11 days [interquartile range, 8, 15] in the freshest available blood group and 23 days [interquartile range, 17, 30] in the oldest available blood group. In the primary analysis, posttransfusion acute kidney injury was observed in 688 of 4,777 (14.4%) patients given the freshest available blood and 1,487 of 9,684 (15.4%) patients given the oldest available blood, with an estimated relative risk (95% CI) of 0.94 (0.86 to 1.02; P = 0.132). The secondary analysis treated blood age as a continuous variable (defined as duration of storage in days), with an estimated relative risk (95% CI) of 1.00 (0.96 to 1.04; P = 0.978) for a 10-day increase in the mean age of erythrocyte units. CONCLUSIONS: In a population of patients without severely impaired baseline renal function receiving fewer than 10 erythrocyte units, duration of blood storage had no effect on the incidence of posttransfusion acute kidney injury.

Intraoperative Hypotension and Myocardial Injury After Noncardiac Surgery in Adults With or Without Chronic Hypertension: A Retrospective Cohort Analysis.

BACKGROUND: The risk of myocardial injury progressively increases at intraoperative mean arterial pressures (MAPs) ≤65 mm Hg. Higher pressures might be required in chronically hypertensive patients. We aimed to test the hypothesis that the harm threshold is higher in patients with chronic hypertension than in normotensive patients. METHODS: We conducted a single-center retrospective cohort analysis of adults >45 years old who had noncardiac surgery between 2010 and 2018 and scheduled, rather than symptom-driven, postoperative troponin measurements. The MAP thresholds under which risk started to increase were compared between patients with chronic hypertension (baseline MAP ≥110 mm Hg) and normotensive patients (baseline MAP <110 mm Hg). The primary outcome was a composite of in-hospital mortality and myocardial injury within 30 days, defined by any postoperative 4th-generation troponin T measurement ≥0.03 ng/mL apparently due to cardiac ischemia. Multivariable logistic regression and moving average smoothing methods were used to evaluate confounder-adjusted associations between the composite outcome and the lowest intraoperative MAP sustained for either 5 or 10 cumulative minutes, and whether the relationship depended on baseline pressure (normotensive versus hypertensive). RESULTS: Among 4576 eligible surgeries, 2066 were assigned to the normotensive group with mean (standard deviation [SD]) baseline MAP of 100 (7) mm Hg, and 2510 were assigned to the hypertensive group with mean baseline MAP of 122 (10) mm Hg. The overall incidence of the composite outcome was 5.6% in normotensive and 6.0% in hypertensive patients ( P = .55). The relationship between intraoperative hypotension and the composite outcome was not found to depend on baseline MAP in a multivariable mixed effects logistic regression model. Furthermore, no statistical change points were found for either baseline MAP group. CONCLUSIONS: Baseline blood pressure of the hypertensive patients was only moderately increased on average, and the event rate was low. Nonetheless, we were not able to demonstrate a difference in the harm threshold between normotensive and chronically hypertensive patients. Our results do not support the theory that hypertensive patients should be kept at higher intraoperative pressures than normotensive patients.