The 50 most-cited articles in Anesthesiology, 2024

The imbalance in anesthesia workforce supply and demand has been exacerbated post-COVID due to a surge in demand for anesthesia care, especially in non-operating room anesthetizing sites, at a faster rate than the increase in anesthesia clinicians. The consequences of this imbalance or labor shortage compromise healthcare facilities, adversely affect the cost of care, worsen anesthesia workforce burnout, disrupt procedural and surgical schedules, and threaten academic missions and the ability to educate future anesthesiologists. In developing possible solutions, one must examine emerging trends that are affecting the anesthesia workforce, new technologies that will transform anesthesia care and the workforce, and financial considerations, including governmental payment policies. Possible practice solutions to this imbalance will require both short- and long-term multifactorial approaches that include increasing training positions and retention policies, improving capacity through innovations, leveraging technology, and addressing financial constraints.

BACKGROUND: The Hypotension Prediction Index is designed to predict intraoperative hypotension in a timely manner and is based on arterial waveform analysis using machine learning. It has recently been suggested that this algorithm is highly correlated with the mean arterial pressure itself. Therefore, the aim of this study was to compare the index with mean arterial pressure-based prediction methods, and it is hypothesized that their ability to predict hypotension is comparable. METHODS: In this observational study, the Hypotension Prediction Index was used in addition to routine intraoperative monitoring during moderate- to high-risk elective noncardiac surgery. The agreement in time between the default Hypotension Prediction Index alarm (greater than 85) and different concurrent mean arterial pressure thresholds was evaluated. Additionally, the predictive performance of the index and different mean arterial pressure-based methods were assessed within 5, 10, and 15 min before hypotension occurred. RESULTS: A total of 100 patients were included. A mean arterial pressure threshold…

BACKGROUND: Liposomal bupivacaine is reported to prolong the duration of analgesia when used for abdominal fascial plane blocks compared to plain local anesthetics; however, evidence from randomized trials is mixed. This meta-analysis aims to compare the analgesic effectiveness of liposomal bupivacaine to plain local anesthetics in adults receiving abdominal fascial plane blocks. METHODS: Randomized trials comparing liposomal bupivacaine and plain (nonliposomal) local anesthetics in abdominal fascial plane blocks were sought. The primary outcome was area under the curve rest pain between 24 to 72 h postoperatively. Secondary outcomes included rest pain at individual timepoints (1, 6, 12, 24, 48, and 72 h); analgesic consumption at 0 to 24, 25 to 48, and 49 to 72 h; time to analgesic request; hospital stay duration; and opioid-related side effects. Data were pooled using the Hartung-Knapp-Sidik-Jonkman random effects method. RESULTS: Sixteen trials encompassing 1,287 patients (liposomal bupivacaine, 667; plain local anesthetics, 620) were included. The liposomal bupivacaine group…

BACKGROUND: Intraoperative hypotension might contribute to the development of postoperative delirium through inadequate cerebral perfusion. However, evidence regarding the association between intraoperative hypotension and postoperative delirium is equivocal. Therefore, the hypothesis that intraoperative hypotension is associated with postoperative delirium in patients older than 70 yr having elective noncardiac surgery was tested . METHODS: This was a retrospective cohort analysis of patients older than 70 yr who underwent elective noncardiac surgery in a single tertiary academic center between 2020 and 2021. Intraoperative hypotension was quantified as the area under a mean arterial pressure (MAP) threshold of 65 mmHg. Postoperative delirium was defined as a collapsed composite outcome including a positive 4 A's test during the initial 2 postoperative days, and/or delirium identification using the Chart-based Delirium Identification Instrument. The association between hypotension and postoperative delirium was assessed using multivariable logistic regression, adjusting for…

BACKGROUND: Preventing emergence delirium is a clinical goal for pediatric anesthesia, yet there is no consensus on its prevention. This study investigated the hypothesis that a continuous infusion or a single bolus of remimazolam can reduce the incidence of emergence delirium in children. METHODS: A total of 120 children aged 1 to 6 yr were randomly and equally allocated into three groups: group RC, which received a continuous infusion of remimazolam at 1 mg · kg-1 · h-1; group RB, which received a single bolus of remimazolam at 0.2 mg · kg-1 at the beginning of wound closure; and group C, which received a continuous infusion of saline at 1 ml · kg-1 · h-1 and a single bolus of saline at 0.2 ml · kg-1 at the beginning of sutures. The primary outcome was the incidence of emergence delirium assessed by the Pediatric Anesthesia Emergence Delirium scale. Secondary outcomes included the number of rescue propofol administrations in the postanesthesia care unit, recovery time, and adverse events. RESULTS: Emergence delirium was observed in 14 of 40 (35%) patients in group C, 2 of 40 (5%)…

BACKGROUND: Midazolam is a short-acting benzodiazepine frequently used in the perioperative setting. This study aimed to investigate the potential impact of intraoperative midazolam on postoperative delirium in older patients undergoing noncardiac surgery. METHODS: This study included patients aged 65 yr and older who received general anesthesia between April 2020 and April 2022 in multiple hospitals across China. Postoperative delirium occurring within 7 days was assessed using the 3-min Diagnostic Interview for Confusion Assessment Method. Univariable and multivariable logistic regression models based on the random effects were used to determine the association between midazolam administration and the occurrence of postoperative delirium, presented as the risk ratio and 95% CI. A Kaplan-Meier cumulative incidence curve was plotted to compare the distribution of time to postoperative delirium onset between patients who received midazolam and those who did not. Subgroup analyses based on specific populations were performed to explore the relationship between midazolam and…

BACKGROUND: The analgesic effect of adding liposomal bupivacaine to standard bupivacaine in supraclavicular brachial plexus block is not known. The authors hypothesized that addition of liposomal bupivacaine would reduce acute postoperative pain compared to standard bupivacaine alone. METHODS: A randomized controlled trial was conducted. Patients and outcome assessors were blinded. Eighty patients undergoing distal radial fracture fixation during regional anesthesia with supraclavicular brachial plexus block were randomized into two groups. The liposomal bupivacaine group received 10 ml 0.5% plain bupivacaine immediately followed by 10 ml 1.33% liposomal bupivacaine (n = 40). The standard bupivacaine group received 20 ml 0.5% plain bupivacaine (n = 40). The primary outcome was weighted area under curve (AUC) numerical rating scale pain score at rest during the first 48 h after surgery. Secondary outcomes included weighted AUC scores for pain with movement, overall benefit with analgesia score, and other functional scores. RESULTS: For the primary outcome, the liposomal bupivacaine…

BACKGROUND: Postoperative delirium is a common complication in elderly patients undergoing anesthesia. Even though it is increasingly recognized as an important health issue, the early detection of patients at risk for postoperative delirium remains a challenge. This study aims to identify predictors of postoperative delirium by analyzing frontal electroencephalogram at propofol-induced loss of consciousness. METHODS: This prospective, observational single-center study included patients older than 70 yr undergoing general anesthesia for a planned surgery. Frontal electroencephalogram was recorded on the day before surgery (baseline) and during anesthesia induction (1, 2, and 15 min after loss of consciousness). Postoperative patients were screened for postoperative delirium twice daily for 5 days. Spectral analysis was performed using the multitaper method. The electroencephalogram spectrum was decomposed in periodic and aperiodic (correlates to asynchronous spectrum wide activity) components. The aperiodic component is characterized by its offset (y intercept) and exponent (the…

BACKGROUND: The Hypotension Prediction Index (the index) software is a machine learning algorithm that detects physiologic changes that may lead to hypotension. The original validation used a case control (backward) analysis that has been suggested to be biased. This study therefore conducted a cohort (forward) analysis and compared this to the original validation technique. METHODS: A retrospective analysis of data from previously reported studies was conducted. All data were analyzed identically with two different methodologies, and receiver operating characteristic curves were constructed. Both backward and forward analyses were performed to examine differences in area under the receiver operating characteristic curves for the Hypotension Prediction Index and other hemodynamic variables to predict a mean arterial pressure (MAP) less than 65 mmHg for at least 1 min 5, 10, and 15 min in advance. RESULTS: The analysis included 2,022 patients, yielding 4,152,124 measurements taken at 20-s intervals. The area under the curve for the index predicting hypotension analyzed by backward…

BACKGROUND: Electroencephalogram burst suppression can be associated with postoperative delirium; however, the results of relevant studies are discrepant. This systematic review and meta-analysis aimed to assess the association between intraoperative burst suppression and postoperative delirium in adult surgical patients. METHODS: PubMed, MEDLINE, Embase, Google Scholar, and the Cochrane Central Register of Controlled Trials were systematically searched and updated in May 2023. The authors included cohort studies, case-control studies, and randomized controlled studies reporting on postoperative delirium incidence with documented intraoperative burst suppression in adults receiving general anesthesia for any surgery. The primary outcome was the pooled odds ratio for postoperative delirium in cases with intraoperative burst suppression compared to those without burst suppression, calculated using a random-effects model. Two independent investigators extracted the data. The protocol was prospectively registered in the International Prospective Register of Systematic Reviews…

BACKGROUND: The accuracy and precision of currently available, widely used acceleromyograph and electromyograph neuromuscular blockade monitors have not been well studied. In addition, the normalization of the train-of-four ratio from acceleromyography (train-of-four ratio [T4/T1] divided by the baseline train-of-four ratio) has not been validated in comparison to mechanomyography. METHODS: Enrolled patients had surgery under general anesthesia with a supraglottic airway and without any neuromuscular blocking drugs. Three acceleromyograph monitors, three electromyograph monitors, and a mechanomyograph built in the authors' laboratory were tested. Most patients had an electromyograph and the mechanomyograph on one arm and a third monitor on the contralateral arm. Train-of-four ratios were collected every 12 to 20 s for the duration of the anesthetic. At least 1,000 train-of-four ratios were recorded for each device. Gauge repeatability and reproducibility analysis was performed. RESULTS: Twenty-eight patients were enrolled. In total, 9,498 train-of-four ratio measurements were…

There is an exponential increase in the use of glucagon-like peptide-1 receptor agonists (GLP-1RAs) in recent years due to their numerous clinical benefits.1–3 However, GLP-1RAs delay gastric emptying with recent reports of aspiration of gastric contents during sedation and general anesthesia despite traditional, preoperative fasting requirements.4 The optimal approach to mitigation of aspiration risk remains controversial because of sparse and inconsistent evidence. In 2023, the American Society of Anesthesiologists (Schaumburg, Illinois) published guidance for management of patients on GLP-1RAs with the primary aim of informing clinicians and patients of the heightened risk of aspiration and emphasizing shared decision-making.5 Subsequently, other professional societies have also published recommendations for perioperative or periprocedure management of patients on GLP-1RAs.6,7A multisociety consensus for the management of patients on GLP-1RAs was developed by representatives from the American Society of Anesthesiologists, the American Gastroenterological Association (Bethesda,…

BACKGROUND: Aeration heterogeneity affects lung stress and influences outcomes in adults with acute respiratory distress syndrome (ARDS). The authors hypothesize that aeration heterogeneity may differ between neonatal respiratory disorders and is associated with oxygenation, so its evaluation may be relevant in managing respiratory support. METHODS: This was an observational prospective study. Neonates with respiratory distress syndrome, transient tachypnea of the neonate, evolving bronchopulmonary dysplasia, and neonatal ARDS were enrolled. Quantitative lung ultrasound and transcutaneous blood gas measurements were simultaneously performed. Global aeration heterogeneity (with its intra- and interpatient components) and regional aeration heterogeneity were primary outcomes; oxygenation metrics were the secondary outcomes. RESULTS: A total of 230 (50 respiratory distress syndrome, transient tachypnea of the neonate or evolving bronchopulmonary dysplasia, and 80 neonatal ARDS) patients were studied. Intrapatient aeration heterogeneity was higher in transient tachypnea of the neonate…

BACKGROUND: The GAS trial demonstrated evidence that most neurodevelopmental outcomes at 2 years and 5 years of age in infants who received a single general anaesthetic (GA) for elective inguinal herniorrhaphy were clinically equivalent when compared to infants who did not receive GA. More than 20% of the children in the trial had at least one subsequent anaesthetic exposure after their initial surgery. Using the GAS database, this study aimed to address whether multiple (2 or more) GA exposures compared to one or no GA exposure in early childhood were associated with worse neurodevelopmental outcomes at 5 years. METHODS: Children with multiple GA exposures and children with one or no GA exposure were identified from the GAS database. The primary outcome was the full-scale intelligence quotient (FSIQ) on the Wechsler Preschool and Primary Scale of Intelligence third edition (WPPSI-III) at 5 years of age. Secondary outcomes included neurocognitive tests addressing all major developmental domains and caregiver-reported questionnaires assessing emotional and behavioural problems.…

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) is associated with a high risk of bleeding complications. The specific impact of ECMO on fibrinolysis remains unexplored. The objective of the current pilot observational prospective study was to investigate the longitudinal dynamics of fibrinolytic markers-i.e., changes over time-in the context of bleeding events in patients on ECMO. METHODS: Longitudinal dynamics of contact phase components (kininogen and bradykinin) and fibrinolysis markers (tissue plasminogen activator [tPA], plasminogen activator inhibitor-1 [PAI-1], their complexes [tPA•PAI-1], plasmin-antiplasmin complexes, plasminogen, and D-dimer) were measured in patients undergoing venovenous and venoarterial ECMO, before implantation, at 0, 6, and 12 h after implantation, and daily thereafter. RESULTS: The cohort consisted of 30 patients (214 ECMO days). The concentrations of tPA, D-dimer, plasmin-antiplasmin complexes, PAI-1, and tPA•PAI-1 complexes were increased, whereas plasminogen decreased compared to normal values. A noteworthy divergence was observed between…

BACKGROUND: In the PROTECTION trial (Intravenous Amino Acid Therapy for Kidney Protection in Cardiac Surgery), intravenous amino acids decreased the occurrence of acute kidney injury in cardiac surgery patients with cardiopulmonary bypass. Recruitment of renal functional reserve may be responsible for such protection. However, patients with chronic kidney disease have diminished renal functional reserve, and amino acids may be less protective in such patients. Thus, a separate investigation of such patients is warranted. METHODS: For this study chronic kidney disease was defined as an estimated glomerular filtration rate of less than 60 ml · min -1 · 1.73 m -2 , and patients with estimated glomerular filtration rates greater than or equal to 60 ml · min -1 · 1.73 m -2 served as controls. The primary outcome was the occurrence of acute kidney injury. Secondary outcomes included severity of acute kidney injury, need for and duration of renal replacement therapy, and all-cause mortality. RESULTS: Among chronic kidney disease patients (n = 812), compared with placebo, amino acids…

BACKGROUND: Impaired cognition is a major predisposing factor for postoperative delirium, but it is not systematically assessed. Anesthesia and surgery may cause postoperative delirium by affecting brain integrity. Neurofilament light in serum reflects axonal injury. Studies evaluating the perioperative course of neurofilament light in cardiac surgery have shown conflicting results. The authors hypothesized that postoperative serum neurofilament light values would be higher in delirious patients, and that baseline concentrations would be correlated with patients' cognitive status and would identify patients at risk of postoperative delirium. METHODS: This preplanned secondary analysis included 220 patients undergoing elective cardiac surgery with cardiopulmonary bypass. A preoperative cognitive z score was calculated after a neuropsychological evaluation. Quantification of serum neurofilament light was performed by the Simoa (Quanterix, USA) technique before anesthesia, 2 h after surgery, on postoperative days 1, 2, and 5. Postoperative delirium was assessed using the Confusion…

BACKGROUND: The influence of high positive end-expiratory pressure (PEEP) with recruitment maneuvers on the occurrence of postoperative pulmonary complications after surgery is still not definitively established. Bayesian analysis can help to gain further insights from the available data and provide a probabilistic framework that is easier to interpret. The objective was to estimate the posterior probability that the use of high PEEP with recruitment maneuvers is associated with reduced postoperative pulmonary complications in patients with intermediate-to-high risk under neutral, pessimistic, and optimistic expectations regarding the treatment effect. METHODS: Multilevel Bayesian logistic regression analysis was performed on individual patient data from three randomized clinical trials carried out on surgical patients at intermediate to high risk for postoperative pulmonary complications. The main outcome was the occurrence of postoperative pulmonary complications in the early postoperative period. This study examined the effect of high PEEP with recruitment maneuvers versus low…

In Brief Artificial intelligence applications have great potential to enhance perioperative care. This article explores promising areas for artificial intelligence in anesthesiology; expertise, stakeholders, and infrastructure for development; and barriers and challenges to implementation.

Anesthesiologists are currently in demand and highly compensated. What appears to be a great success from our perspective is considered problematic from every other healthcare perspective. Consequently, there are powerful healthcare forces seeking to improve anesthesia access and reduce service cost. They will try to impose solutions that may radically change operative anesthesia. The Rovenstine lecture, delivered on World Anesthesia Day 2023, identified substantial challenges our specialty faces and discusses solutions that might be forced on us. It also presented opportunities in perioperative care.

BACKGROUND: Little is known about the pharmacodynamic characteristics of liposomal bupivacaine. Hypothesizing that they would not identify pharmacodynamic differences from plain bupivacaine during the initial period after administration, but would find better long-term pharmacodynamic characteristics, the authors designed a randomized, controlled, triple-blinded, single-center study in volunteers. METHODS: Volunteers aged 18 to 55 yr (body mass index, 18 to 35 kg/m2) received two ulnar nerve blocks under ultrasound guidance. Using a crossover design with a washout phase of 36 days or more, one block was performed with liposomal and one with plain bupivacaine. Which came first was determined by randomization. Sensory data were collected by pinprick testing and motor data by thumb adduction, either way in comparison with the contralateral arm. Endpoints included success, time to onset, and duration of blockade. Residual efficacy was assessed by the volunteers keeping a diary. Statistical analysis included Wilcoxon signed-rank and exact McNemar's tests, as well as a generalized…

BACKGROUND: Fluid therapy during major hepatic resection aims at minimizing fluids during the dissection phase to reduce central venous pressure, retrograde liver blood flow, and venous bleeding. This strategy, however, may lead to hyperlactatemia. The Acumen assisted fluid management system uses novel decision support software, the algorithm of which helps clinicians optimize fluid therapy. The study tested the hypothesis that using this decision support system could decrease arterial lactate at the end of major hepatic resection when compared to a more restrictive fluid strategy. METHODS: This two-arm, prospective, randomized controlled, assessor- and patient-blinded superiority study included consecutive patients undergoing major liver surgery equipped with an arterial catheter linked to an uncalibrated stroke volume monitor. In the decision support group, fluid therapy was guided throughout the entire procedure using the assisted fluid management software. In the restrictive fluid group, clinicians were recommended to restrict fluid infusion to 1 to 2 ml · kg-1 · h-1 until the…

“[T]he clinical meaningfulness of group differences in pain scores cannot alone determine the overall clinical importance of that difference: tolerability, safety, convenience, durability of benefits, and cost along with a host of additional factors must be considered including comparisons with alternatives.”Image: J. P. Rathmell.Postoperative pain usually lasts considerably longer than the duration of plain bupivacaine HCl when used for single-injection peripheral nerve blocks, even with unapproved additives such as epinephrine, clonidine, and steroids. A formulation of bupivacaine HCl within liposomes (Exparel, Pacira BioSciences, USA) is approved by the U.S. Food and Drug Administration (Silver Spring, Maryland) for use in interscalene, adductor canal, transversus abdominis plane, and popliteal–sciatic nerve blocks. Pacira proposes that liposomal bupivacaine lasts 48 to 72 h, which far exceeds the duration of plain bupivacaine (usually less than 24 h). However, the extent to which liposomal bupivacaine prolongs analgesia remains controversial.1–5 A trial by Chan et al. in this…

BACKGROUND: Pulmonary aspiration of gastric content is a serious anesthetic complication. Gastric point-of-care ultrasound can determine the type and volume of gastric content when clinical information is equivocal. However, a cutoff value of either antral cross-sectional area or volume that may be considered as the upper limit of normal in fasting subjects is still controversial. The aim of this study is to characterize the distribution of baseline antral area and volume in fasting adult subjects and to identify an upper limit (95th percentile) of these distributions. METHODS: The authors conducted a meta-analysis of individual participant data of primary studies from an academic research network of investigators collaborating in gastric ultrasound. Studies between January 2009 and December 2020 were included. RESULTS: Twelve primary studies met inclusion criteria and were included in the analysis with a sample size of 1,203 subjects. The 95th percentile of area values (measured in the right lateral decubitus) was 9.9 cm2 (95% CI, 9.4 to 10.4), and of volume, 2.3 ml/kg (95% CI, 2.3…

In this review, the authors define acute kidney injury in the perioperative setting, describe the epidemiologic burden, discuss procedure-specific risk factors, detail principles of management, and highlight areas of ongoing controversy and research.

BACKGROUND: Dexmedetomidine has repeatedly shown to improve anxiety, but the precise neural mechanisms underlying this effect remain incompletely understood. This study aims to explore the role of corticotropin-releasing hormone-producing hypothalamic paraventricular nucleus (CRHPVN) neurons in mediating the anxiolytic effects of dexmedetomidine. METHODS: A social defeat stress mouse model was used to evaluate the anxiolytic effects induced by dexmedetomidine through the elevated plus maze, open-field test, and measurement of serum stress hormone levels. In vivo Ca2+ signal fiber photometry and ex vivo patch-clamp recordings were used to determine the excitability of CRHPVN neurons and investigate the specific mechanism involved. CRHPVN neuron modulation was achieved through chemogenetic activation or inhibition. RESULTS: Compared with saline, dexmedetomidine (40 µg/kg) alleviated anxiety-like behaviors. Additionally, dexmedetomidine reduced CRHPVN neuronal excitability. Chemogenetic activation of CRHPVN neurons decreased the time spent in the open arms of the elevated plus maze and…

BACKGROUND: Perioperative strokes may promote postoperative neurocognitive dysfunction. This study thus evaluated the incidence of postoperative strokes and the association between strokes and postoperative neurocognitive outcomes in older patients recovering from noncardiac surgery. METHODS: The Postoperative Covert Stroke and Cognitive Dysfunction among Elderly Patients Undergoing Noncardiac Surgery study (PRECISION) was a two-center prospective cohort study evaluating patients aged 60 yr or older who had elective, noncardiac inpatient surgery at two Chinese academic centers. Postoperative strokes were evaluated by scheduled magnetic resonance brain imaging within 7 days. The primary outcome was the cumulative incidence of postoperative stroke. Secondary outcomes included postoperative delirium within the first 5 days after surgery, neurocognitive decline at 12 months, and the association between stroke and neurocognitive dysfunction. RESULTS: Among 934 patients (mean age, 67 yr; 45% male) included in the analyses, two thirds had neurosurgical craniotomies. There were 111 (11.9%;…

How general anesthetics work remains a topic of ongoing study. A parallel field of research has sought to identify methods to reverse general anesthesia. Reversal agents could shorten patients' recovery time and potentially reduce the risk of postoperative complications. An incomplete understanding of the mechanisms of general anesthesia has hampered the pursuit for reversal agents. Nevertheless, the search for reversal agents has furthered understanding of the mechanisms underlying general anesthesia. The study of potential reversal agents has highlighted the importance of rigorous criteria to assess recovery from general anesthesia in animal models, and has helped identify key arousal systems (e.g., cholinergic, dopaminergic, and orexinergic systems) relevant to emergence from general anesthesia. Furthermore, the effects of reversal agents have been found to be inconsistent across different general anesthetics, revealing differences in mechanisms among these drugs. The presynapse and glia probably also contribute to general anesthesia recovery alongside postsynaptic receptors. The…

Extracorporeal Circulation in Neonatal Respiratory Failure: A Prospective Randomized Study. By RH Bartlett, DW Roloff, RG Cornell, AF Andrews, PW Dillon, JB Zwischenberger. Pediatrics 1985; 76:479-87. Extracorporeal membrane oxygenation (ECMO) is the use of mechanical devices to replace cardiac and pulmonary function in critical care. In the 1960s, laboratory research showed that extracorporeal circulation could be maintained for days using a membrane oxygenator. In the 1970s, the first clinical trials showed that ECMO could sustain life in severe cardiac and pulmonary failure for days or weeks, leading to organ recovery. From 1980 to 2000, ECMO became standard practice for neonatal and pediatric respiratory and cardiac failure. The critical clinical trial was a prospective randomized trial of ECMO in newborn respiratory failure, published in 1985. This is the classic article reviewed in this publication. This was the first use of a randomized, adaptive design trial to minimize the potential ethical dilemma inherent to clinical trials in which the endpoint is death. Other randomized…

During the last 100 years, the role of anesthesiologists in psychiatry has focused primarily on facilitating electroconvulsive therapy and mitigating postoperative delirium and other perioperative neurocognitive disorders. The discovery of the rapid and sustained antidepressant properties of ketamine, and early results suggesting that other general anesthetic drugs (including nitrous oxide, propofol, and isoflurane) have antidepressant properties, has positioned anesthesiologists at a new frontier in the treatment of neuropsychiatric disorders. Moreover, shared interest in understanding the biologic underpinnings of anesthetic drugs as psychotropic agents is eroding traditional academic boundaries between anesthesiology and psychiatry. This article presents a brief overview of anesthetic drugs as novel antidepressants and identifies promising future candidates for the treatment of depression. The authors issue a call to action and outline strategies to foster collaborations between anesthesiologists and psychiatrists as they work toward the common goals of repurposing anesthetic…

BACKGROUND: Postoperative nausea and vomiting (PONV) is a key driver of unplanned admission and patient satisfaction after surgery. Because traditional risk factors do not completely explain variability in risk, this study hypothesized that genetics may contribute to the overall risk for this complication. The objective of this research is to perform a genome-wide association study of PONV, derive a polygenic risk score for PONV, assess associations between the risk score and PONV in a validation cohort, and compare any genetic contributions to known clinical risks for PONV. METHODS: Surgeries with integrated genetic and perioperative data performed under general anesthesia at Michigan Medicine (Ann Arbor, Michigan) and Vanderbilt University Medical Center (Nashville, Tennessee) were studied. PONV was defined as nausea or emesis occurring and documented in the postanesthesia care unit. In the discovery phase, genome-wide association studies were performed on each genetic cohort, and the results were meta-analyzed. Next, the polygenic phase assessed whether a polygenic score, derived…

Volatile anesthetics have multiple properties that make them useful for sedation in the intensive care unit. The team-based approach to volatile anesthetic sedation leverages these properties to provide a safe and effective alternative to intravenous sedatives.

BACKGROUND: The use of anesthetics may result in depression of the hypoxic ventilatory response. Since there are no receptor-specific antagonists for most anesthetics, there is the need for agnostic respiratory stimulants that increase respiratory drive irrespective of its cause. The authors tested whether ENA-001, an agnostic respiratory stimulant that blocks carotid body BK-channels, could restore the hypoxic ventilatory response during propofol infusion. They hypothesize that ENA-001 is able to fully restore the hypoxic ventilatory response. METHODS: In this randomized, double-blind crossover trial, 14 male and female healthy volunteers were randomized to receive placebo and low- and high-dose ENA-001 on three separate occasions. On each occasion, isohypercapnic hypoxic ventilatory responses were measured during a fixed sequence of placebo, followed by low- and high-dose propofol infusion. The authors conducted a population pharmacokinetic/pharmacodynamic analysis that included oxygen and carbon dioxide kinetics. RESULTS: Twelve subjects completed the three sessions; no serious…

BACKGROUND: Impaired glymphatic clearance of cerebral metabolic products and fluids contribute to traumatic and ischemic brain edema and neurodegeneration in preclinical models. Glymphatic perivascular cerebrospinal fluid flow varies between anesthetics possibly due to changes in vasomotor tone and thereby in the dynamics of the periarterial cerebrospinal fluid (CSF)-containing space. To better understand the influence of anesthetics and carbon dioxide levels on CSF dynamics, this study examined the effect of periarterial size modulation on CSF distribution by changing blood carbon dioxide levels and anesthetic regimens with opposing vasomotor influences: vasoconstrictive ketamine-dexmedetomidine (K/DEX) and vasodilatory isoflurane. METHODS: End-tidal carbon dioxide (ETco2) was modulated with either supplemental inhaled carbon dioxide to reach hypercapnia (Etco2, 80 mmHg) or hyperventilation (Etco2, 20 mmHg) in tracheostomized and anesthetized female rats. Distribution of intracisternally infused radiolabeled CSF tracer 111In-diethylamine pentaacetate was assessed for 86 min in (1)…

BACKGROUND: Observational studies of anesthetic neurotoxicity may be biased because children requiring anesthesia commonly have medical conditions associated with neurobehavioral problems. This study takes advantage of a natural experiment associated with appendicitis to determine whether anesthesia and surgery in childhood were specifically associated with subsequent neurobehavioral outcomes. METHODS: This study identified 134,388 healthy children with appendectomy and examined the incidence of subsequent externalizing or behavioral disorders (conduct, impulse control, oppositional defiant, attention-deficit hyperactivity disorder) or internalizing or mood or anxiety disorders (depression, anxiety, or bipolar disorder) when compared to 671,940 matched healthy controls as identified in Medicaid data between 2001 and 2018. For comparison, this study also examined 154,887 otherwise healthy children admitted to the hospital for pneumonia, cellulitis, and gastroenteritis, of which only 8% received anesthesia, and compared them to 774,435 matched healthy controls. In addition, this study…

During the past 70 years, patient safety science has evolved through four organizational frameworks known as Safety-0, Safety -1, Safety-2, and Safety-3. Their evolution reflects the realization over time that blaming people, chasing errors, fixing one-offs, and regulation would not create the desired patient safety. In Safety-0, the oldest framework, harm events arise from clinician failure; event prevention relies on better staffing, education, and basic standards. In Safety-1, used by hospitals, harm events arise from individual and/or system failures. Safety is improved through analytics, workplace culture, high reliability principles, technology, and quality improvement. Safety-2 emphasizes clinicians' adaptability to prevent harm events in an everchanging environment, using resilience engineering principles. Safety-3, used by aviation, adds system design and control elements to Safety-1 and Safety-2, deploying human factors, design-thinking, and operational control or feedback to prevent and respond to harm events. Safety-3 represents a potential way for anesthesia and…

BACKGROUND: The efficacy of serratus anterior plane block for treatment of pain after minimally invasive thoracic surgery remains unclear. This trial assesses the impact of serratus anterior plane block on postoperative opioid consumption and on measures of early recovery after thoracoscopic lung resection. METHODS: Patients undergoing minimally invasive anatomic lung resection at a single center were randomized to undergo serratus anterior plane block with 40 ml injectate containing bupivacaine 0.25%, clonidine 100 μg, and dexamethasone 4 mg (serratus anterior plane block group) or sham block with 40 ml normal saline (placebo group) at the conclusion of surgery. The primary outcome was cumulative intravenous morphine equivalents during the first 24 h postoperatively. Secondary outcomes were intravenous morphine equivalents, pain scores at rest and with cough, inspiratory volume on incentive spirometry, incidence of nausea or vomiting during the first 48 h postoperatively, Quality of Recovery-15 score on postoperative day 7, and length of stay. RESULTS: Using the protocol-specified…

BACKGROUND: Unfractionated heparin, administered during venoarterial extracorporeal membrane oxygenation to prevent thromboembolic events, largely depends on plasma antithrombin for its antithrombotic effects. Decreased heparin responsiveness seems frequent on extracorporeal membrane oxygenation; however, its association with acquired antithrombin deficiency is poorly understood. The objective of this study was to describe longitudinal changes in plasma antithrombin levels during extracorporeal membrane oxygenation support and evaluate the association between antithrombin levels and heparin responsiveness. The hypothesis was that extracorporeal membrane oxygenation support would be associated with acquired antithrombin deficiency and related decreased heparin responsiveness. METHODS: Adults receiving venoarterial extracorporeal membrane oxygenation were prospectively included. All patients received continuous intravenous unfractionated heparin using a standardized protocol (target anti-Xa 0.3 to 0.5 IU/ml). For each patient, arterial blood was withdrawn into citrate-containing tubes…

BACKGROUND: The Trial Remifentanil DEXmedetomidine (TREX) trial aimed to determine whether, in children less than 2 yr old, low-dose sevoflurane/dexmedetomidine/remifentanil anesthesia is superior to standard-dose sevoflurane anesthesia in terms of global cognitive function at 3 yr of age. The aim of the current secondary analyses was to compare incidence of intraoperative hypotension and bradycardia, postoperative pain, time to recovery, need for treatment of intraoperative hypotension and bradycardia, incidence of light anesthesia and need for treatment, need for postoperative pain medications, and morbidity and mortality outcomes at 5 days between the two arms. METHODS: This phase III randomized active controlled, parallel group, assessor blinded, multicenter, superiority trial was performed in 20 centers in Australia, Italy, and the United States. A total of 455 infants less than 2 yr of age expected to undergo general anesthesia for at least 2 h were enrolled. They were randomized between low-dose sevoflurane/dexmedetomidine/remifentanil anesthesia and standard-dose…

Cardiopulmonary bypass–induced hemolysis is linked to acute kidney injury in cardiac surgery. Emerging therapies targeting cell-free hemoglobin (CFHb), like haptoglobin, nitric oxide (NO), and antioxidants, show promise in reducing kidney injury, highlighting the need for further research.

BACKGROUND: High-dose corticosteroids have been used to attenuate the inflammatory response to cardiac surgery and cardiopulmonary bypass, but patient outcome benefits remain unclear. The primary aim was to determine whether using dexamethasone was superior to not using dexamethasone to increase the number of home days in the first 30 days after cardiac surgery. The secondary aim was to evaluate efficiency, value, and impact of the novel trial design. METHODS: This pragmatic, international trial incorporating a prerandomized consent design favoring local practice enrolled patients undergoing cardiac surgery across seven hospitals in Australia and The Netherlands. Patients were randomly assigned to dexamethasone 1 mg/kg or not (control). The primary outcome was the number of days alive and at home up to 30 days after surgery ("home days"). Secondary outcomes included prolonged mechanical ventilation (more than 48 h), sepsis, renal failure, myocardial infarction, stroke, and death. RESULTS: Of 2,562 patients assessed for eligibility, 1,951 were randomized (median age, 63 yr; 80%…

BACKGROUND: The amount of same-day surgery has increased markedly worldwide in recent decades, but there remains limited evidence on chronic postsurgical pain in this setting. METHODS: This study assessed pain 90 days after ambulatory surgery in an international, multicenter prospective cohort study of patients at least 45 yr old with comorbidities or at least 65 yr old. Pain was assessed using the Brief Pain Inventory. Chronic postsurgical pain was defined as a change of more than 1 point in self-rated average pain at the surgical site between baseline and 90 days, and moderate to severe chronic postsurgical pain was defined as a score greater than 4 in self-rated average pain at the surgical site at 90 days. Risk factors for chronic postsurgical pain were identified using multivariable logistic regression. RESULTS: Between November 2021 and January 2023, a total of 2,054 participants were included, and chronic postsurgical pain occurred in 12% of participants, of whom 93.1% had new chronic pain at the surgical site (i.e., participants without pain before surgery). Moderate to…

Pain that accompanies deafferentation is one of the most mysterious and misunderstood medical conditions. Prevalence rates for the assorted conditions vary considerably but the most reliable estimates are greater than 50% for strokes involving the somatosensory system, brachial plexus avulsions, spinal cord injury, and limb amputation, with controversy surrounding the mechanistic contributions of deafferentation to ensuing neuropathic pain syndromes. Deafferentation pain has also been described for loss of other body parts (e.g., eyes and breasts) and may contribute to between 10% and upwards of 30% of neuropathic symptoms in peripheral neuropathies. There is no pathognomonic test or sign to identify deafferentation pain, and part of the controversy surrounding it stems from the prodigious challenges in differentiating cause and effect. For example, it is unknown whether cortical reorganization causes pain or is a byproduct of pathoanatomical changes accompanying injury, including pain. Similarly, ascertaining whether deafferentation contributes to neuropathic pain, or whether…

BACKGROUND: Drug shortages are a frequent challenge in current clinical practice. Certain drugs (e.g., protamine) lack alternatives, and inadequate supplies can limit access to services. Conventional protamine dosing uses heparin ratio-based calculations for heparin reversal after cardiopulmonary bypass and may result in excess protamine utilization and potential harm due to its intrinsic anticoagulation. This study hypothesized that a fixed 250-mg protamine dose would be comparable, as measured by the activated clotting time, to a 1:1 (1 mg for every 100 U) protamine-to-heparin ratio-based strategy for heparin reversal and that protamine would be conserved. METHODS: In a single-center, double-blinded trial, consenting elective adult cardiac surgical patients without preexisting coagulopathy or ongoing anticoagulation and a calculated initial heparin dose greater than or equal to 27,500 U were randomized to receive, after cardiopulmonary bypass, protamine as a fixed dose (250 mg) or a ratio-based dose (1 mg:100 U heparin). The primary outcome was the activated clotting time after…

To the Editor: Glucagon-like peptide-1 (GLP-1) receptor agonists are approved for type 2 diabetes mellitus and weight loss. However, concerns have emerged regarding their potential to increase the risk of perioperative regurgitation and aspiration pneumonitis, despite standard fasting protocols.1 The American Society of Anesthesiologists (ASA; Schaumburg, Illinois) published a consensus-based guideline in 2023 recommending holding GLP-1 agonists before procedures.2 In contrast, the American Gastroenterology Association (AGA; Bethesda, Maryland) recommended an individualized approach regarding the use of GLP-1 agonists during the pre-endoscopic period.3 These recommendations were based on observations of increased gastric content in fasting patients treated with semaglutide.1,3 A recent cohort study reported an increased risk of aspiration pneumonia among GLP-1 agonist users undergoing endoscopic procedures.4 However, in this study, there appeared to be differences in the baseline characteristics between patients who received GLP-1 agonists and those who did not, raising concerns…

BACKGROUND: Day-of-surgery cancellations impede healthcare access and contribute to inequities in pediatric healthcare. Socially disadvantaged families have many risk factors for surgical cancellation, including low health literacy, transportation barriers, and childcare constraints. These social determinants of health are captured by the Child Opportunity Index 2.0, a national quantification of neighborhood-level characteristics that contribute to a child's vulnerability to adversity. This study examined the association of neighborhood opportunity with pediatric day-of-surgery cancellations. METHODS: A retrospective cohort study of children younger than 18 yr of age scheduled for ambulatory surgery at a tertiary pediatric hospital between 2017 and 2022 was conducted. Primary addresses were geocoded to determine Child Opportunity Index 2.0 neighborhood opportunity. Log-binomial regression was used to estimate the relative risk of day-of-surgery cancellation comparing different levels of neighborhood opportunity. This study also estimated the relative risk of cancellations associated…

BACKGROUND: Although remimazolam is used as a general anesthetic in elderly patients due to its hemodynamic stability, the electroencephalogram characteristics of remimazolam are not well known. The purpose of this study was to identify the electroencephalographic features of remimazolam-induced unconsciousness in elderly patients and compare them with propofol. METHODS: Remimazolam (n = 26) or propofol (n = 26) were randomly administered for anesthesia induction in surgical patients. The hypnotic agent was blinded only to the patients. During the induction of anesthesia, remimazolam was administered at a rate of 6 mg · kg-1 · h-1, and propofol was administered at a target effect-site concentration of 3.5 μg/ml. The electroencephalogram signals from eight channels (Fp1, Fp2, Fz, F3, F4, Pz, P3, and P4, referenced to A2, using the 10 to 20 system) were acquired during the induction of anesthesia and in the postoperative care unit. Power spectrum analysis was performed, and directed functional connectivity between frontal and parietal regions was evaluated using normalized symbolic…