The 50 most-cited articles in Anesthesiology, 2022

These practice guidelines provide evidence-based recommendations on the management of neuromuscular monitoring and antagonism of neuromuscular blocking agents during and after general anesthesia. The guidance focuses primarily on the type and site of monitoring and the process of antagonizing neuromuscular blockade to reduce residual neuromuscular blockade.

BACKGROUND: It is speculated that the anesthetic strategy during endovascular therapy for stroke may have an impact on the outcome of the patients. The authors hypothesized that conscious sedation is associated with a better functional outcome 3 months after endovascular therapy for the treatment of stroke compared with general anesthesia. METHODS: In this single-blind, randomized trial, patients received either a standardized general anesthesia or a standardized conscious sedation. Blood pressure control was also standardized in both groups. The primary outcome measure was a modified Rankin score less than or equal to 2 (0 = no symptoms; 5 = severe disability) assessed 3 months after treatment. The main secondary outcomes were complications, mortality, reperfusion results, and National Institutes of Health Stroke Scores at days 1 and 7. RESULTS: Of 351 randomized patients, 345 were included in the analysis. The primary outcome occurred in 129 of 341 (38%) of the patients: 63 (36%) in the conscious sedation group and 66 (40%) in the general anesthesia group (relative risk, 0.91 [95%…

Anesthetic agents disrupt neurodevelopment in animal models, but evidence in humans is mixed. The morphologic and behavioral changes observed across many species predicted that deficits should be seen in humans, but identifying a phenotype of injury in children has been challenging. It is increasingly clear that in children, a brief or single early anesthetic exposure is not associated with deficits in a range of neurodevelopmental outcomes including broad measures of intelligence. Deficits in other domains including behavior, however, are more consistently reported in humans and also reflect findings from nonhuman primates. The possibility that behavioral deficits are a phenotype, as well as the entire concept of anesthetic neurotoxicity in children, remains a source of intense debate. The purpose of this report is to describe consensus and disagreement among experts, summarize preclinical and clinical evidence, suggest pathways for future clinical research, and compare studies of anesthetic agents to other suspected neurotoxins.

BACKGROUND: Mechanical power during ventilation estimates the energy delivered to the respiratory system through integrating inspiratory pressures, tidal volume, and respiratory rate into a single value. It has been linked to lung injury and mortality in the acute respiratory distress syndrome, but little evidence exists regarding whether the concept relates to lung injury in patients with healthy lungs. This study hypothesized that higher mechanical power is associated with greater postoperative respiratory failure requiring reintubation in patients undergoing general anesthesia. METHODS: In this multicenter, retrospective study, 230,767 elective, noncardiac adult surgical out- and inpatients undergoing general anesthesia between 2008 and 2018 at two academic hospital networks in Boston, Massachusetts, were included. The risk-adjusted association between the median intraoperative mechanical power, calculated from median values of tidal volume (Vt), respiratory rate (RR), positive end-expiratory pressure (PEEP), plateau pressure (Pplat), and peak inspiratory pressure (Ppeak), using…

BACKGROUND: Delirium is a critical postoperative complication in older patients. Based on the hypothesis that intraoperative dexmedetomidine sedation would lower postoperative delirium than propofol sedation would, the authors compared the incidence of postoperative delirium in older adults, using the mentioned sedatives. METHODS: This double-blinded, randomized controlled study included 748 patients, aged 65 yr or older, who were scheduled for elective lower extremity orthopedic surgery, between June 2017 and October 2021. Patients were randomized equally into two groups in a 1:1 ratio according to the intraoperative sedative used (dexmedetomidine vs. propofol). The postoperative delirium incidence was considered the primary outcome measure; it was determined using the confusion assessment method, on the first three postoperative days. The mean arterial pressure and heart rate were evaluated as secondary outcomes. RESULTS: The authors enrolled 732 patients in the intention-to-treat analyses. The delirium incidence was lower in the dexmedetomidine group than in the propofol group…

BACKGROUND: In cardiac surgery, the association between hypotension during specific intraoperative phases or vasopressor-inotropes with adverse outcomes remains unclear. This study's hypothesis was that intraoperative hypotension duration throughout the surgery or when separated into hypotension during and outside cardiopulmonary bypass may be associated with postoperative major adverse events. METHODS: This retrospective observational cohort study included data for adults who had cardiac surgery between 2008 and 2016 in a tertiary hospital. Intraoperative hypotension was defined as mean arterial pressure of less than 65 mmHg. The total duration of hypotension was divided into three categories based on the fraction of overall hypotension duration that occurred during cardiopulmonary bypass (more than 80%, 80 to 60%, and less than 60%). The primary outcome was a composite of stroke, acute kidney injury, or mortality during the index hospitalization. The association with the composite outcome was evaluated for duration of hypotension during the entire surgery, outside cardiopulmonary…

BACKGROUND: Monitoring and controlling lung stress and diaphragm effort has been hypothesized to limit lung injury and diaphragm injury. The occluded inspiratory airway pressure (Pocc) and the airway occlusion pressure at 100 ms (P0.1) have been used as noninvasive methods to assess lung stress and respiratory muscle effort, but comparative performance of these measures and their correlation to diaphragm effort is unknown. The authors hypothesized that Pocc and P0.1 correlate with diaphragm effort and lung stress and would have strong discriminative performance in identifying extremes of lung stress and diaphragm effort. METHODS: Change in transdiaphragmatic pressure and transpulmonary pressure was obtained with double-balloon nasogastric catheters in critically ill patients (n = 38). Pocc and P0.1 were measured every 1 to 3 h. Correlations between Pocc and P0.1 with change in transdiaphragmatic pressure and transpulmonary pressure were computed from patients from the first cohort. Accuracy of Pocc and P0.1 to identify patients with extremes of lung stress (change in transpulmonary…

BACKGROUND: The interscalene nerve block provides analgesia for shoulder surgery. To extend block duration, provide adequate analgesia, and minimize opioid consumption, the use of adjuvants such as dexamethasone as well as the application of perineural liposomal bupivacaine have been proposed. This randomized, double-blinded, noninferiority trial hypothesized that perineural liposomal bupivacaine is noninferior to standard bupivacaine with perineural dexamethasone in respect to average pain scores in the first 72 h after surgery. METHODS: A total of 112 patients undergoing ambulatory shoulder surgery were randomized into two groups. The liposomal bupivacaine group received a 15-ml premixed admixture of 10 ml of 133 mg liposomal bupivacaine and 5 ml of 0.5% bupivacaine (n = 55), while the bupivacaine with dexamethasone group received an admixture of 15 ml of 0.5% standard bupivacaine with 4 mg dexamethasone (n = 56), respectively. The primary outcome was the average numerical rating scale pain scores at rest over 72 h. The mean difference between the two groups was compared against a…

SUMMARY: For the task of estimating a target benchmark dose such as the ED50 (the dose that would be effective for half the population), an adaptive dose-finding design is more effective than the standard approach of treating equal numbers of patients at a set of equally spaced doses. Up-and-down is the most popular family of dose-finding designs and is in common use in anesthesiology. Despite its widespread use, many aspects of up-and-down are not well known, implementation is often misguided, and standard, up-to-date reference material about the design is very limited. This article provides an overview of up-and-down properties, recent methodologic developments, and practical recommendations, illustrated with the help of simulated examples. Additional reference material is offered in the Supplemental Digital Content.

The Hypotension Prediction Index is a proprietary prediction model incorporated into a commercially available intraoperative hemodynamic monitoring system. The Hypotension Prediction Index uses multiple features of the arterial blood pressure waveform to predict hypotension. The index publication introducing the Hypotension Prediction Index describes the selection of training and validation data. Although precise details of the Hypotension Prediction Index algorithm are proprietary, the authors describe a selection process whereby a mean arterial pressure (MAP) less than 75 mmHg will always predict hypotension. We hypothesize that the data selection process introduced a systematic bias that resulted in an overestimation of the current MAP value's ability to predict future hypotension. Since current MAP is a predictive variable contributing to Hypotension Prediction Index, this exaggerated predictive performance likely also applies to the corresponding Hypotension Prediction Index value. Other existing validation studies appear similarly problematic, suggesting that additional…

BACKGROUND: The dural puncture epidural technique may improve analgesia quality by confirming midline placement and increasing intrathecal translocation of epidural medications. This would be advantageous in obese parturients with increased risk of block failure. This study hypothesizes that quality of labor analgesia will be improved with dural puncture epidural compared to standard epidural technique in obese parturients. METHODS: Term parturients with body mass index greater than or equal to 35 kg · m-2, cervical dilation of 2 to 7 cm, and pain score of greater than 4 (where 0 indicates no pain and 10 indicates the worst pain imaginable) were randomized to dural puncture epidural (using 25-gauge Whitacre needle) or standard epidural techniques. Analgesia was initiated with 15 ml of 0.1% ropivacaine with 2 µg · ml-1 fentanyl, followed by programed intermittent boluses (6 ml every 45 min), with patient-controlled epidural analgesia. Parturients were blinded to group allocation. The data were collected by blinded investigators every 3 min for 30 min and then every 2 h until…

BACKGROUND: Estimates for the incidence of difficult intubation in the obstetric population vary widely, although previous studies reporting rates of difficult intubation in obstetrics are older and limited by smaller samples. The goals of this study were to provide a contemporary estimate of the frequency of difficult and failed intubation in women undergoing general anesthesia for cesarean delivery and to elucidate risk factors for difficult intubation in women undergoing general anesthesia for cesarean delivery. METHODS: This is a multicenter, retrospective cohort study utilizing the Multicenter Perioperative Outcomes Group database. The study population included women aged 15 to 44 yr undergoing general anesthesia for cesarean delivery between 2004 and 2019 at 1 of 45 medical centers. Coprimary outcomes included the frequencies of difficult and failed intubation. Difficult intubation was defined as Cormack-Lehane view of 3 or greater, three or more intubation attempts, rescue fiberoptic intubation, rescue supraglottic airway, or surgical airway. Failed intubation was defined as…

The gut microbiome plays critical roles in human health and disease. Recent studies suggest it may also be associated with chronic pain and postoperative pain outcomes. In animal models, the composition of the gut microbiome changes after general anesthesia and affects the host response to medications, including anesthetics and opioids. In humans, the gut microbiome is associated with the development of postoperative pain and neurocognitive disorders. Additionally, the composition of the gut microbiome has been associated with pain conditions including visceral pain, nociplastic pain, complex regional pain syndrome, and headaches, partly through altered concentration of circulating bacterial-derived metabolites. Furthermore, animal studies demonstrate the critical role of the gut microbiome in neuropathic pain via immunomodulatory mechanisms. This article reviews basic concepts of the human gut microbiome and its interactions with the host and provide a comprehensive overview of the evidence linking the gut microbiome to anesthesiology, critical care, and pain medicine.

BACKGROUND: Pulse oximetry is ubiquitous in anesthesia and is generally a reliable noninvasive measure of arterial oxygen saturation. Concerns regarding the impact of skin pigmentation and race/ethnicity on the accuracy of pulse oximeter accuracy exist. The authors hypothesized a greater prevalence of occult hypoxemia (arterial oxygen saturation [Sao2] less than 88% despite oxygen saturation measured by pulse oximetry [Spo2] greater than 92%) in patients undergoing anesthesia who self-reported a race/ethnicity other than White. METHODS: Demographic and physiologic data, including self-reported race/ethnicity, were extracted from a departmental data warehouse for patients receiving an anesthetic that included at least one arterial blood gas between January 2008 and December 2019. Calculated Sao2 values were paired with concurrent Spo2 values for each patient. Analysis to determine whether Black, Hispanic, Asian, or Other race/ethnicities were associated with occult hypoxemia relative to White race/ethnicity within the Spo2 range of 92 to 100% was completed. RESULTS: In total, 151,070…

In Brief This review summarizes current evidence related to perioperative opioid prescription fulfillment and use and discusses the role of personalized anesthesia care in mitigating opioid-related harms without compromising analgesia.

Anesthesiologists routinely manage patients receiving drugs and agents, all of which have the potential for anaphylaxis, the life-threatening presentation of an allergic reaction. Clinicians must be ready to diagnose and manage the acute cardiopulmonary dysfunction that occurs.

BACKGROUND: Delirium poses significant risks to patients, but countermeasures can be taken to mitigate negative outcomes. Accurately forecasting delirium in intensive care unit (ICU) patients could guide proactive intervention. Our primary objective was to predict ICU delirium by applying machine learning to clinical and physiologic data routinely collected in electronic health records. METHODS: Two prediction models were trained and tested using a multicenter database (years of data collection 2014 to 2015), and externally validated on two single-center databases (2001 to 2012 and 2008 to 2019). The primary outcome variable was delirium defined as a positive Confusion Assessment Method for the ICU screen, or an Intensive Care Delirium Screening Checklist of 4 or greater. The first model, named "24-hour model," used data from the 24 h after ICU admission to predict delirium any time afterward. The second model designated "dynamic model," predicted the onset of delirium up to 12 h in advance. Model performance was compared with a widely cited reference model. RESULTS: For the 24-h…

BACKGROUND: Heterogeneity among reported outcomes from enhanced recovery after cesarean delivery impact studies is high. This study aimed to develop a standardized enhanced recovery core outcome set for use in future enhanced recovery after cesarean delivery studies. METHODS: An international consensus study involving physicians, patients, and a director of midwifery and nursing services was conducted using a three-round modified Delphi approach (two rounds of electronic questionnaires and a third-round e-discussion) to produce the core outcome set. An initial list of outcomes was based on a previously published systematic review. Consensus was obtained for the final core outcome set, including definitions for key terms and preferred units of measurement. Strong consensus was defined as 70% or greater agreement and weak consensus as 50 to 69% agreement. Of the 64 stakeholders who were approached, 32 agreed to participate. All 32, 31, and 26 stakeholders completed Rounds 1, 2 and 3, respectively. RESULTS: The number of outcomes in the final core outcome set was reduced from 98 to 15.…

BACKGROUND: The neural circuitry underlying sevoflurane-induced modulation of consciousness is poorly understood. This study hypothesized that the paraventricular thalamus bed nucleus of the stria terminalis pathway plays an important role in regulating states of consciousness during sevoflurane anesthesia. METHODS: Rabies virus-based transsynaptic tracing techniques were employed to reveal the neural pathway from the paraventricular thalamus to the bed nucleus of the stria terminalis. This study investigated the role of this pathway in sevoflurane anesthesia induction, maintenance, and emergence using chemogenetic and optogenetic methods combined with cortical electroencephalogram recordings. Both male and female mice were used in this study. RESULTS: Both γ-aminobutyric acid-mediated and glutamatergic neurons in the bed nucleus of the stria terminalis receive paraventricular thalamus glutamatergic projections. Chemogenetic inhibition of paraventricular thalamus glutamatergic neurons prolonged the sevoflurane anesthesia emergence time (mean ± SD, hM4D-clozapine N-oxide vs.…

Nonsteroidal anti-inflammatory drugs are among the most commonly administered drugs in the perioperative period due to their prominent role in pain management. However, they potentially have perioperative consequences due to immune-modulating effects through the inhibition of prostanoid synthesis, thereby affecting the levels of various cytokines. These effects may have a direct impact on the postoperative outcome of patients since the immune system aims to restore homeostasis and plays an indispensable role in regeneration and repair. By affecting the immune response, consequences can be expected on various organ systems. This narrative review aims to highlight these potential immune system-related consequences, which include systemic inflammatory response syndrome, acute respiratory distress syndrome, immediate and persistent postoperative pain, effects on oncological and neurologic outcome, and wound, anastomotic, and bone healing.

BACKGROUND: Ultrasound-guided percutaneous cryoneurolysis is an analgesic technique in which a percutaneous probe is used to reversibly ablate a peripheral nerve(s) using exceptionally low temperature, and has yet to be evaluated with randomized, controlled trials. Pain after mastectomy can be difficult to treat, and the authors hypothesized that the severity of surgically related pain would be lower on postoperative day 2 with the addition of cryoanalgesia compared with patients receiving solely standard-of-care treatment. METHODS: Preoperatively, participants at one enrolling center received a single injection of ropivacaine, 0.5%, paravertebral nerve block at T3 or T4, and perineural catheter. Participants subsequently underwent an active or sham ultrasound-guided percutaneous cryoneurolysis procedure of the ipsilateral T2 to T5 intercostal nerves in a randomized, patient- and observer-masked fashion. Participants all received a continuous paravertebral block with ropivacaine, 0.2%, until the early morning of discharge (usually postoperative day 2). The primary endpoint was the…

BACKGROUND: Residual neuromuscular blockade can be avoided with quantitative neuromuscular monitoring. The authors embarked on a professional practice initiative to attain documented train-of-four ratios greater than or equal to 0.90 in all patients for improved patient outcomes through reducing residual paralysis. METHODS: The authors utilized equipment trials, educational videos, quantitative monitors in all anesthetizing locations, and electronic clinical decision support with real-time alerts, and initiated an ongoing professional practice metric. This was a retrospective assessment (2016 to 2020) of train-of-four ratios greater than or equal to 0.9 that were documented before extubation. Anesthesia records were manually reviewed for neuromuscular blockade management details. Medical charts of surgical patients who received a neuromuscular blocking drug were electronically searched for patient characteristics and outcomes. RESULTS: From pre- to postimplementation, more patients were assigned American Society of Anesthesiologists Physical Status III to V, fewer were inpatients,…

BACKGROUND: Accurate estimation of surgical transfusion risk is essential for efficient allocation of blood bank resources and for other aspects of anesthetic planning. This study hypothesized that a machine learning model incorporating both surgery- and patient-specific variables would outperform the traditional approach that uses only procedure-specific information, allowing for more efficient allocation of preoperative type and screen orders. METHODS: The American College of Surgeons National Surgical Quality Improvement Program Participant Use File was used to train four machine learning models to predict the likelihood of red cell transfusion using surgery-specific and patient-specific variables. A baseline model using only procedure-specific information was created for comparison. The models were trained on surgical encounters that occurred at 722 hospitals in 2016 through 2018. The models were internally validated on surgical cases that occurred at 719 hospitals in 2019. Generalizability of the best-performing model was assessed by external validation on surgical cases…

BACKGROUND: The lack of reliable data on gastric emptying of solid food during labor has led to some discrepancies between current guidelines regarding fasting for solid food in the parturient. This prospective comparative study aimed to test the hypothesis that the gastric emptying fraction of a light meal would be reduced in parturients receiving epidural analgesia and with no labor analgesia compared with nonpregnant and pregnant women. METHODS: Ten subjects were enrolled and tested in each group: nonpregnant women, term pregnant women, parturients with no labor analgesia, and parturients with epidural labor analgesia. After a first ultrasound examination was performed to ensure an empty stomach, each subject ingested a light meal (125 g yogurt; 120 kcal) within 5 min. Then ultrasound measurements of the antral area were performed at 15, 60, 90, and 120 min. The fraction of gastric emptying at 90 min was calculated as [(antral area90 min / antral area15 min) - 1] × 100, and half-time to gastric emptying was also determined. For the Parturient-Epidural group, the test meal was…

BACKGROUND: Hyperoxia and oxidative stress may be associated with increased risk of myocardial injury. The authors hypothesized that a perioperative inspiratory oxygen fraction of 0.80 versus 0.30 would increase the degree of myocardial injury within the first 3 days of surgery, and that an antioxidant intervention would reduce degree of myocardial injury versus placebo. METHODS: A 2 × 2 factorial, randomized, blinded, multicenter trial enrolled patients older than 45 yr who had cardiovascular risk factors undergoing major noncardiac surgery. Factorial randomization allocated patients to one of two oxygen interventions from intubation and at 2 h after surgery, as well as antioxidant intervention or matching placebo. Antioxidants were 3 g IV vitamin C and 100 mg/kg N-acetylcysteine. The primary outcome was the degree of myocardial injury assessed by the area under the curve for high-sensitive troponin within the first 3 postoperative days. RESULTS: The authors randomized 600 participants from April 2018 to January 2020 and analyzed 576 patients for the primary outcome. Baseline and…

BACKGROUND: The antitumor effects of natural killer cells, helper T cells, and cytotoxic T cells after cancer surgery were reported previously. This study hypothesized that propofol-based anesthesia would have fewer harmful effects on immune cells than volatile anesthetics-based anesthesia during colorectal cancer surgery. METHODS: In total, 153 patients undergoing colorectal cancer surgery were randomized and included in the analysis. The primary outcome was the fraction of circulating natural killer cells over time in the propofol and sevoflurane groups. The fractions of circulating natural killer, type 1, type 17 helper T cells, and cytotoxic T cells were investigated. The fractions of CD39 and CD73 expressions on circulating regulatory T cells were investigated, along with the proportions of circulating neutrophils, lymphocytes, and monocytes. RESULTS: The fraction of circulating natural killer cells was not significantly different between the propofol and sevoflurane groups until 24 h postoperatively (20.4 ± 13.4% vs. 20.8 ± 11.3%, 17.9 ± 12.7% vs. 20.7 ± 11.9%, and 18.6 ±…

BACKGROUND: Oliceridine is a G protein-biased µ-opioid, a drug class that is associated with less respiratory depression than nonbiased opioids, such as morphine. The authors quantified the respiratory effects of oliceridine and morphine in elderly volunteers. The authors hypothesized that these opioids differ in their pharmacodynamic behavior, measured as effect on ventilation at an extrapolated end-tidal Pco2 at 55 mmHg, V̇E55. METHODS: This four-arm double-blind, randomized, crossover study examined the respiratory effects of intravenous 0.5 or 2 mg oliceridine and 2 or 8 mg morphine in 18 healthy male and female volunteers, aged 55 to 89 yr, on four separate occasions. Participants' CYP2D6 genotypes were determined, hypercapnic ventilatory responses were obtained, and arterial blood samples were collected before and for 6 h after treatment. A population pharmacokinetic-pharmacodynamic analysis was performed on V̇E55, the primary endpoint; values reported are median ± standard error of the estimate. RESULTS: Oliceridine at low dose was devoid of significant respiratory effects.…

BACKGROUND: Acute kidney injury (AKI) after noncardiac surgery is common and has substantial health impact. Preclinical and clinical studies examining the influence of sex on AKI have yielded conflicting results, although they typically do not account for age-related changes. The objective of the study was to determine the association of age and sex groups on postoperative AKI. The authors hypothesized that younger females would display lower risk of postoperative AKI than males of similar age, and the protection would be lost in older females. METHODS: This was a multicenter retrospective cohort study across 46 institutions between 2013 and 2019. Participants included adult inpatients without pre-existing end-stage kidney disease undergoing index major noncardiac, nonkidney/urologic surgeries. The authors' primary exposure was age and sex groups defined as females 50 yr or younger, females older than 50 yr, males 50 yr or younger, and males older than 50 yr. The authors' primary outcome was development of AKI by Kidney Disease-Improving Global Outcomes serum creatinine criteria.…

BACKGROUND: There are no effective pharmacologic interventions for preventing postoperative cognitive dysfunction in daily practice. Since the antibiotic minocycline is known to suppress postoperative neuroinflammation, this study hypothesized and investigated whether minocycline might have a preventive effect on postoperative cognitive dysfunction after noncardiac surgery. METHODS: This study included patients aged more than 60 yr undergoing total knee arthroplasty under general anesthesia. They were randomly assigned to minocycline and placebo groups, to orally receive 100 mg of minocycline or placebo twice daily from the day before surgery until the seventh day after surgery. Cognitive function was evaluated before surgery, and 1 week and 3 months after surgery, using a battery of four cognitive function tests, including Visual Verbal Learning Test, Trail Making Test, Stroop Color and Word Test, and Letter-Digit Coding Task. Additionally, 30 healthy volunteers were subjected to the same tests as the patients to examine the learning effect of repeated tests. The occurrence of…

This article summarizes new scientific evidence on the pathogenesis of surgical site infection, including the roles of the patient microbiome and antimicrobial resistance, and reviews changes in guidelines and clinical practices for prevention.

BACKGROUND: Ketamine produces potent analgesia combined with psychedelic effects. It has been suggested that these two effects are associated and possibly that analgesia is generated by ketamine-induced dissociation. The authors performed a post hoc analysis of previously published data to quantify the pharmacodynamic properties of ketamine-induced antinociception and psychedelic symptoms. The hypothesis was that ketamine pharmacodynamics (i.e., concentration-effect relationship as well as effect onset and offset times) are not different for these two endpoints. METHODS: Seventeen healthy male volunteers received escalating doses of S- and racemic ketamine on separate occasions. Before, during, and after ketamine infusion, changes in external perception were measured together with pain pressure threshold. A population pharmacokinetic-pharmacodynamic analysis was performed that took S- and R-ketamine and S- and R-norketamine plasma concentrations into account. RESULTS: The pharmacodynamics of S-ketamine did not differ for antinociception and external perception with potency parameter…

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…

BACKGROUND: Neurofilament light is a marker of neuronal injury and can be measured in blood. Postoperative increases in neurofilament light have been associated with delirium after noncardiac surgery. However, few studies have examined the association of neurofilament light changes with postdischarge cognition in cardiac surgery patients, who are at highest risk for neuronal injury and cognitive decline. The authors hypothesized that increased neurofilament light (both baseline and change) would be associated with worse neuropsychological status up to 1 yr after cardiac surgery. METHODS: This observational study was nested in a trial of cardiac surgery patients, in which blood pressure during bypass was targeted using cerebral autoregulation monitoring. Plasma concentrations of neurofilament light were measured at baseline and postoperative day 1. Neuropsychological testing was performed at baseline, 1 month after surgery, and 1 yr after surgery. Primary outcomes were baseline and change from baseline in a composite z-score of all cognitive tests. RESULTS: Among 167 patients,…

BACKGROUND: The mechanisms underlying oxygenation improvement after prone positioning in COVID-19 acute respiratory distress syndrome have not been fully elucidated yet. The authors hypothesized that the oxygenation increase with prone positioning is secondary to the improvement of ventilation-perfusion matching. METHODS: In a series of consecutive intubated COVID-19 acute respiratory distress syndrome patients receiving volume-controlled ventilation, the authors prospectively assessed the percent variation of ventilation-perfusion matching by electrical impedance tomography before and 90 min after the first cycle of prone positioning (primary endpoint). The authors also assessed changes in the distribution and homogeneity of lung ventilation and perfusion, lung overdistention and collapse, respiratory system compliance, driving pressure, optimal positive end-expiratory pressure, as assessed by electrical impedance tomography, and the ratio of partial pressure to fraction of inspired oxygen (Pao2/Fio2; secondary endpoints). Data are reported as medians [25th to 75th] or percentages.…

BACKGROUND: Intraoperative isoelectric electroencephalography (EEG) has been associated with hypotension and postoperative delirium in adults. This international prospective observational study sought to determine the prevalence of isoelectric EEG in young children during anesthesia. The authors hypothesized that the prevalence of isoelectric events would be common worldwide and associated with certain anesthetic practices and intraoperative hypotension. METHODS: Fifteen hospitals enrolled patients age 36 months or younger for surgery using sevoflurane or propofol anesthetic. Frontal four-channel EEG was recorded for isoelectric events. Demographics, anesthetic, emergence behavior, and Pediatric Quality of Life variables were analyzed for association with isoelectric events. RESULTS: Isoelectric events occurred in 32% (206 of 648) of patients, varied significantly among sites (9 to 88%), and were most prevalent during pre-incision (117 of 628; 19%) and surgical maintenance (117 of 643; 18%). Isoelectric events were more likely with infants younger than 3 months (odds ratio, 4.4; 95%…

BACKGROUND: Despite expanding use, knowledge on extracorporeal membrane oxygenation support during the COVID-19 pandemic remains limited. The objective was to report characteristics, management, and outcomes of patients receiving extracorporeal membrane oxygenation with a diagnosis of COVID-19 in France and to identify pre-extracorporeal membrane oxygenation factors associated with in-hospital mortality. A hypothesis of similar mortality rates and risk factors for COVID-19 and non-COVID-19 patients on venovenous extracorporeal membrane oxygenation was made. METHODS: The Extracorporeal Membrane Oxygenation for Respiratory Failure and/or Heart failure related to Severe Acute Respiratory Syndrome-Coronavirus 2 (ECMOSARS) registry included COVID-19 patients supported by extracorporeal membrane oxygenation in France. This study analyzed patients included in this registry up to October 25, 2020, and supported by venovenous extracorporeal membrane oxygenation for respiratory failure with a minimum follow-up of 28 days after cannulation. The primary outcome was in-hospital mortality. Risk…

BACKGROUND: Intraoperative mechanical ventilation is a major component of general anesthesia. The extent to which various intraoperative tidal volumes and positive end-expiratory pressures (PEEP) effect on postoperative hypoxia and lung injury remains unclear. We hypothesized that adults having orthopedic surgery, ventilation using different tidal volumes and PEEP levels affect the oxygenation within first hour in the postoperative care unit. METHODS: We conducted a two-by-two factorial crossover cluster trial at the Cleveland Clinic Main Campus. We enrolled patients having orthopedic surgery with general anesthesia who were assigned to factorial clusters with tidal volumes of 6 or 10 ml/kg of predicted body weight and to PEEP of 5 or 8 cm H2O in 1-week clusters. The primary outcome was the effect of tidal volume or PEEP on time-weighted average peripheral oxygen saturation measured by pulse oximetry divided by the fraction of inspired oxygen (Spo2/Fio2 ratio) during the initial postoperative hour. RESULTS: We enrolled 2,860 patients who had general anesthesia for orthopedic surgery…

BACKGROUND: Retracted articles represent research withdrawn from the existing body of literature after publication. Research articles may be retracted for several reasons ranging from honest errors to intentional misconduct. They should not be used as reliable sources, and it is unclear why they are cited occasionally by other articles. This study hypothesized that several mechanisms may contribute to citing retracted literature and aimed to analyze the characteristics of articles citing retracted literature in anesthesiology and critical care. METHODS: Using the Retraction Watch database, we retrieved retracted articles on anesthesiology and intensive care medicine up to August 16, 2021, and identified the papers citing these retracted articles. A survey designed to investigate the reasons for citing these articles was sent to the corresponding authors of the citing papers. RESULTS: We identified 478 retracted articles, 220 (46%) of which were cited at least once. We contacted 1297 corresponding authors of the papers that cited these articles, 417 (30%) of whom responded to our…

BACKGROUND: Long-lasting local anesthetic use for perioperative pain control is limited by possible cardiotoxicity (e.g., arrhythmias and contractile depression), potentially leading to cardiac arrest. Off-target cardiac sodium channel blockade is considered the canonical mechanism behind cardiotoxicity; however, it does not fully explain the observed toxicity variability between anesthetics. The authors hypothesize that more cardiotoxic anesthetics (e.g., bupivacaine) differentially perturb other important cardiomyocyte functions (e.g., calcium dynamics), which may be exploited to mitigate drug toxicity. METHODS: The authors investigated the effects of clinically relevant concentrations of racemic bupivacaine, levobupivacaine, or ropivacaine on human stem cell-derived cardiomyocyte tissue function. Contractility, rhythm, electromechanical coupling, field potential profile, and intracellular calcium dynamics were quantified using multielectrode arrays and optical imaging. Calcium flux differences between bupivacaine and ropivacaine were probed with pharmacologic calcium…

BACKGROUND: Interscalene blocks provide analgesia for shoulder surgery but also cause phrenic nerve paralysis. Liposomal bupivacaine is approved for use in interscalene blocks with the potential to provide longer pain control. However, the impact of liposomal bupivacaine on the phrenic nerve has not been evaluated. It was hypothesized that patients who received an interscalene block with both bupivacaine and liposomal bupivacaine would have a decreased diaphragmatic excursion when compared to bupivacaine alone at 24 h. METHODS: This was a double-blinded study of adult patients who were randomized to receive an interscalene block with either 20 ml 0.5% bupivacaine (bupivacaine group) or 10 ml 0.5% bupivacaine plus 10 ml liposomal bupivacaine (liposomal bupivacaine group). Twenty-six patients were randomized with 22 included in the analysis. Diaphragmatic excursion (via ultrasound) and spirometry were assessed before the block, in the postanesthesia care unit, and at 24 h postblock. The primary outcome was diaphragm excursion with sigh. No adverse events were observed. RESULTS: At 24…

BACKGROUND: An optimal opioid-sparing multimodal analgesic regimen to treat severe pain can enhance recovery after total knee arthroplasty. The hypothesis was that adding five recently described intravenous and regional interventions to multimodal analgesic regimen can further reduce opioid consumption. METHODS: In a double-blinded fashion, 78 patients undergoing elective total knee arthroplasty were randomized to either (1) a control group (n = 39) that received spinal anesthesia with intrathecal morphine, periarticular local anesthesia infiltration, intravenous dexamethasone, and a single injection adductor canal block or (2) a study group (n = 39) that received the same set of analgesic treatments plus five additional interventions: local anesthetic infiltration between the popliteal artery and capsule of the posterior knee, intraoperative intravenous dexmedetomidine and ketamine, and postoperatively, one additional intravenous dexamethasone bolus and two additional adductor canal block injections. The primary outcome measure was 24-h cumulative opioid consumption after surgery…

In Brief This article presents current literature and scientific evidence on hemoglobin thresholds and physiologic parameters to guide decisions regarding perioperative erythrocyte transfusions in pediatric patients based on the most up-to-date studies and expert consensus recommendations.

BACKGROUND: There are multiple preoperative risk scores for pediatric mortality. The aim of this study was to systematically describe and compare the existing studies of patient-specific multispecialty risk prediction scores for perioperative mortality in pediatric populations, with the goal of guiding clinicians on which may be most appropriate for use in the preoperative setting. METHODS: This study is a systematic literature review of published journal articles that presented the development, extension/updating, and/or validation of a risk core that predicted all-cause mortality (up to 30 days postoperatively) in pediatric patients undergoing a procedure in which anesthesia was used. Scores needed to be applicable to surgeries in more than one noncardiac surgical specialty and had to be able to be calculated by the anesthesiologist at the time of the preanesthetic assessment. Two investigators independently screened studies for inclusion and assessed study quality in the domains of clinical applicability, feasibility/ease of use in the clinical setting, and risk of bias. RESULTS:…

BACKGROUND: Risk stratification helps guide appropriate clinical care. Our goal was to develop and validate a broad suite of predictive tools based on International Classification of Diseases, Tenth Revision, diagnostic and procedural codes for predicting adverse events and care utilization outcomes for hospitalized patients. METHODS: Endpoints included unplanned hospital admissions, discharge status, excess length of stay, in-hospital and 90-day mortality, acute kidney injury, sepsis, pneumonia, respiratory failure, and a composite of major cardiac complications. Patient demographic and coding history in the year before admission provided features used to predict utilization and adverse events through 90 days after admission. Models were trained and refined on 2017 to 2018 Medicare admissions data using an 80 to 20 learn to test split sample. Models were then prospectively tested on 2019 out-of-sample Medicare admissions. Predictions based on logistic regression were compared with those from five commonly used machine learning methods using a limited dataset. RESULTS: The 2017 to…

BACKGROUND: Intranasal dexmedetomidine provides noninvasive, effective procedural sedation for pediatric patients, and has been widely used in clinical practice. However, the dosage applied has varied fourfold in pediatric clinical studies. To validate an appropriate dosing regimen, this study investigated the pharmacokinetics of intranasal dexmedetomidine in Chinese children under 3 yr old. METHODS: Intranasal dexmedetomidine 2 µg · kg-1 was administered to children with simple vascular malformations undergoing interventional radiological procedures. A population pharmacokinetic analysis with data from an optimized sparse-sampling design was performed using nonlinear mixed-effects modeling. Clearance was modeled using allometric scaling and a sigmoid postmenstrual age maturation model. Monte Carlo simulations were performed to assess the different dosing regimens. RESULTS: A total of 586 samples from 137 children aged 3 to 36 months were included in the trial. The data were adequately described by a two-compartment model with first-order elimination. Body weight with allometric…

BACKGROUND: Postoperative pulmonary complications are common. Aging and respiratory disease provoke airway hyperresponsiveness, high-risk surgery induces diaphragmatic dysfunction, and general anesthesia contributes to atelectasis and peripheral airway injury. This study therefore tested the hypothesis that inhalation of penehyclidine, a long-acting muscarinic antagonist, reduces the incidence of pulmonary complications in high-risk patients over the initial 30 postoperative days. METHODS: This single-center double-blind trial enrolled 864 patients age over 50 yr who were scheduled for major upper-abdominal or noncardiac thoracic surgery lasting 2 h or more and who had an Assess Respiratory Risk in Surgical Patients in Catalonia score of 45 or higher. The patients were randomly assigned to placebo or prophylactic penehyclidine inhalation from the night before surgery through postoperative day 2 at 12-h intervals. The primary outcome was the incidence of a composite of pulmonary complications within 30 postoperative days, including respiratory infection, respiratory failure, pleural…

BACKGROUND: The relationship between intraoperative physiology and postoperative stroke is incompletely understood. Preliminary data suggest that either hypo- or hypercapnia coupled with reduced cerebrovascular inflow (e.g., due to hypotension) can lead to ischemia. This study tested the hypothesis that the combination of intraoperative hypotension and either hypo- or hypercarbia is associated with postoperative ischemic stroke. METHODS: We conducted a retrospective, case-control study via the Multicenter Perioperative Outcomes Group. Noncardiac, nonintracranial, and nonmajor vascular surgical cases (18 yr or older) were extracted from five major academic centers between January 2004 and December 2015. Ischemic stroke cases were identified via manual chart review and matched to controls (1:4). Time and reduction below key mean arterial blood pressure thresholds (less than 55 mmHg, less than 60 mmHg, less than 65 mmHg) and outside of specific end-tidal carbon dioxide thresholds (30 mmHg or less, 35 mmHg or less, 45 mmHg or greater) were calculated based on total area under the curve.…

BACKGROUND: Several retrospective studies using administrative or single-center data have failed to show any difference between general anesthesia using propofol versus inhaled volatiles on long-term survival after breast cancer surgery. Although randomized controlled trials are ongoing, validated data from national clinical registries may advance the reliability of existing knowledge. METHODS: Data on breast cancer surgery performed under general anesthesia between 2013 and 2019 from the Swedish PeriOperative Registry and the National Quality Registry for Breast Cancer were record-linked. Overall survival was compared between patients receiving propofol and patients receiving inhaled volatile for anesthesia maintenance. RESULTS: Of 18,674 subjects, 13,873 patients (74.3%) received propofol and 4,801 (25.7%) received an inhaled volatile for general anesthesia maintenance. The two cohorts differed in most respects. Patients receiving inhaled volatile were older (67 yr vs. 65 yr), sicker (888 [19.0%] American Society of Anesthesiologists status 3 to 5 vs. 1,742 [12.8%]), and the…

BACKGROUND: Sedated and awake tracheal intubation approaches are considered safest in adults with difficult airways, but little is known about the outcomes of sedated intubations in children. The primary aim of this study was to compare the first-attempt success rate of tracheal intubation during sedated tracheal intubation versus tracheal intubation under general anesthesia. The hypothesis was that sedated intubation would be associated with a lower first-attempt success rate and more complications than general anesthesia. METHODS: This study used data from an international observational registry, the Pediatric Difficult Intubation Registry, which prospectively collects data about tracheal intubation in children with difficult airways. The use of sedation versus general anesthesia for tracheal intubation were compared. The primary outcome was the first-attempt success of tracheal intubation. Secondary outcomes included the number of intubation attempts and nonsevere and severe complications. Propensity score matching was used with a matching ratio up to 1:15 to reduce bias due to…