Efficacy and safety of ketamine-assisted electroconvulsive therapy in major depressive episode: a systematic review and network meta-analysis.

OBJECTIVE: To meta-analyze clinical efficacy and safety of ketamine compared with other anesthetic agents in the course of electroconvulsive therapy (ECT) in major depressive episode (MDE). METHODS: PubMed/MEDLINE, Cochrane Library, Embase, GoogleScholar, and US and European trial registries were searched from inception through May 23, 2023, with no language limits. We included RCTs with (1) a diagnosis of MDE; (2) ECT intervention with ketamine and/or other anesthetic agents; and (3) measures included: depressive symptoms, cognitive performance, remission or response rates, and serious adverse events. Network meta-analysis (NMA) was performed to compare ketamine and 7 other anesthetic agents. Hedges' g standardized mean differences (SMDs) were used for continuous measures, and relative risks (RRs) were used for other binary outcomes using random-effects models. RESULTS: Twenty-two studies were included in the systematic review. A total of 2322 patients from 17 RCTs were included in the NMA. The overall pooled SMD of ketamine, as compared with propofol as a reference group, was -2.21 (95% confidence interval [CI], -3.79 to -0.64) in depressive symptoms, indicating that ketamine had better antidepressant efficacy than propofol. In a sensitivity analysis, however, ketamine-treated patients had a worse outcome in cognitive performance than propofol-treated patients (SMD, -0.18; 95% CI, -0.28 to -0.09). No other statistically significant differences were found. CONCLUSIONS: Ketamine-assisted ECT is tolerable and may be efficacious in improving depressive symptoms, but a relative adverse impact on cognition may be an important clinical consideration. Anesthetic agents should be considered based on patient profiles and/or preferences to improve effectiveness and safety of ECT use.

Anesthetics fragment hippocampal network activity, alter spine dynamics, and affect memory consolidation.

General anesthesia is characterized by reversible loss of consciousness accompanied by transient amnesia. Yet, long-term memory impairment is an undesirable side effect. How different types of general anesthetics (GAs) affect the hippocampus, a brain region central to memory formation and consolidation, is poorly understood. Using extracellular recordings, chronic 2-photon imaging, and behavioral analysis, we monitor the effects of isoflurane (Iso), medetomidine/midazolam/fentanyl (MMF), and ketamine/xylazine (Keta/Xyl) on network activity and structural spine dynamics in the hippocampal CA1 area of adult mice. GAs robustly reduced spiking activity, decorrelated cellular ensembles, albeit with distinct activity signatures, and altered spine dynamics. CA1 network activity under all 3 anesthetics was different to natural sleep. Iso anesthesia most closely resembled unperturbed activity during wakefulness and sleep, and network alterations recovered more readily than with Keta/Xyl and MMF. Correspondingly, memory consolidation was impaired after exposure to Keta/Xyl and MMF, but not Iso. Thus, different anesthetics distinctly alter hippocampal network dynamics, synaptic connectivity, and memory consolidation, with implications for GA strategy appraisal in animal research and clinical settings.

State-related Electroencephalography Microstate Complexity during Propofol- and Esketamine-induced Unconsciousness.

BACKGROUND: Identifying the state-related "neural correlates of consciousness" for anesthetics-induced unconsciousness is challenging. Spatiotemporal complexity is a promising tool for investigating consciousness. The authors hypothesized that spatiotemporal complexity may serve as a state-related but not drug-related electroencephalography (EEG) indicator during an unconscious state induced by different anesthetic drugs (e.g., propofol and esketamine). METHODS: The authors recorded EEG from patients with unconsciousness induced by propofol (n = 10) and esketamine (n = 10). Both conventional microstate parameters and microstate complexity were analyzed. Spatiotemporal complexity was constructed by microstate sequences and complexity measures. Two different EEG microstate complexities were proposed to quantify the randomness (type I) and complexity (type II) of the EEG microstate series during the time course of the general anesthesia. RESULTS: The coverage and occurrence of microstate E (prefrontal pattern) and the duration of microstate B (right frontal pattern) could distinguish the states of preinduction wakefulness, unconsciousness, and recovery under both anesthetics. Type I EEG microstate complexity based on mean information gain significantly increased from awake to unconsciousness state (propofol: from mean ± SD, 1.562 ± 0.059 to 1.672 ± 0.023, P < 0.001; esketamine: 1.599 ± 0.051 to 1.687 ± 0.013, P < 0.001), and significantly decreased from unconsciousness to recovery state (propofol: 1.672 ± 0.023 to 1.537 ± 0.058, P < 0.001; esketamine: 1.687 ± 0.013 to 1.608 ± 0.028, P < 0.001) under both anesthetics. In contrast, type II EEG microstate fluctuation complexity significantly decreased in the unconscious state under both drugs (propofol: from 2.291 ± 0.771 to 0.782 ± 0.163, P < 0.001; esketamine: from 1.645 ± 0.417 to 0.647 ± 0.252, P < 0.001), and then increased in the recovery state (propofol: 0.782 ± 0.163 to 2.446 ± 0.723, P < 0.001; esketamine: 0.647 ± 0.252 to 1.459 ± 0.264, P < 0.001). CONCLUSIONS: Both type I and type II EEG microstate complexities are drug independent. Thus, the EEG microstate complexity measures that the authors proposed are promising tools for building state-related neural correlates of consciousness to quantify anesthetic-induced unconsciousness.

Unveiling the hidden dangers: a review of non-apoptotic programmed cell death in anesthetic-induced developmental neurotoxicity.

Anesthetic-induced developmental neurotoxicity (AIDN) can arise due to various factors, among which aberrant nerve cell death is a prominent risk factor. Animal studies have reported that repeated or prolonged anesthetic exposure can cause significant neuroapoptosis in the developing brain. Lately, non-apoptotic programmed cell deaths (PCDs), characterized by inflammation and oxidative stress, have gained increasing attention. Substantial evidence suggests that non-apoptotic PCDs are essential for neuronal cell death in AIDN compared to apoptosis. This article examines relevant publications in the PubMed database until April 2024. Only original articles in English that investigated the potential manifestations of non-apoptotic PCD in AIDN were analysed. Specifically, it investigates necroptosis, pyroptosis, ferroptosis, and parthanatos, elucidating the signaling mechanisms associated with each form. Furthermore, this study explores the potential relevance of these non-apoptotic PCDs pathways to the pathological mechanisms underlying AIDN, drawing upon their distinctive characteristics. Despite the considerable challenges involved in translating fundamental scientific knowledge into clinical therapeutic interventions, this comprehensive review offers a theoretical foundation for developing innovative preventive and treatment strategies targeting non-apoptotic PCDs in the context of AIDN.

Correlation between anesthetic concentration and low Apgar scores in neonates born via Cesarean sections under general anesthesia.

OBJECTIVES: This study aimed to compare plasma concentrations of anesthetic drugs administered during Cesarean section with low Apgar score in neonates deliveried under general anesthesia and analyze associated risk factors. METHODS: Data from 76 neonates undergoing Cesarean section under general anesthesia with blood concentrations of anesthetic drugs were analyzed. A low Apgar score was defined as ≤ 7. Perioperative maternal and neonatal data were collected and analyzed. Neonates were divided into a control group (Group CON, n = 65) and a low Apgar score group (Group LAS, n = 11) based on Apgar score. RESULTS: There were no significant differences in the plasma concentrations of anesthetic drugs in maternal artery, umbilical vein or umbilical artery blood between the two groups. Risk factors for neonatal low Apgar scores during Cesarean section under general anesthesia were premature delivery (aOR 10.2, 95% CI = 1.8-56.9) and preoperative fetal distress (aOR 9.6, 95% CI = 1.3-69.0). The prediction model was: probability = 1/(e­Y), Y= -4.607 + 2.318× (premature delivery) + 2.261× (fetal distress) (yes = 1, no = 0). The Hosmer-Lemeshow test showed χ²= 9.587, P = 0.213, and the area under the curve (AUC) was 0.850 (0.670 ~ 1.000). With a cutoff value of 0.695, sensitivity and specificity were 81.8% and 87.7%, respectively. CONCLUSIONS: There was no correlation between blood concentration of general anesthetic drugs and Apgar score or occurrence of neonatal low Apgar scores. Premature delivery and preoperative fetal distress were identified as independent risk factors for neonatal low Apgar scores after Cesarean section under general anesthesia.

Neutrophils and Anesthetic Drugs: Implications in Onco-Anesthesia.

Apart from being a significant line of defense in the host defense system, neutrophils have many immunological functions. Although there are not many publications that accurately present the functions of neutrophils in relation to oncological pathology, their activity and implications have been studied a lot recently. This review aims to extensively describe neutrophils functions'; their clinical implications, especially in tumor pathology; the value of clinical markers related to neutrophils; and the implications of neutrophils in onco-anesthesia. This review also aims to describe current evidence on the influence of anesthetic drugs on neutrophils' functions and their potential influence on perioperative outcomes.

Medication errors in veterinary anesthesia: a literature review.

OBJECTIVE: To provide an overview of medication errors (MEs) in veterinary medicine, with a focus on the perianesthetic period; to compare MEs in veterinary medicine with human anesthesia practice, and to describe factors contributing to the risk of MEs and strategies for error reduction. DATABASES USED: PubMed and CAB abstracts; search terms: [("patient safety" or "medication error∗") AND veterin∗]. CONCLUSIONS: Human anesthesia is recognized as having a relatively high risk of MEs. In veterinary medicine, MEs were among the most commonly reported medical error. Predisposing factors for MEs in human and veterinary anesthesia include general (e.g. distraction, fatigue, workload, supervision) and specific factors (e.g. requirement for dose calculations when dosing for body mass, using several medications within a short time period and preparing syringes ahead of time). Data on MEs are most commonly collected in self-reporting systems, which very likely underestimate the true incidence, a problem acknowledged in human medicine. Case reports have described a variety of MEs in the perianesthetic period, including prescription, preparation and administration errors. Dogs and cats were the most frequently reported species, with MEs in cats more commonly associated with harmful outcomes compared with dogs. In addition to education and raising awareness, other strategies described for reducing the risk of MEs include behavioral, communication, identification, organizational, engineering and cognitive aids.

Neurosteroids and their potential as a safer class of general anesthetics.

Neurosteroids (NS) are a class of steroids that are synthesized within the central nervous system (CNS). Various NS can either enhance or inhibit CNS excitability and they play important biological roles in brain development, brain function and as mediators of mood. One class of NS, 3α-hydroxy-pregnane steroids such as allopregnanolone (AlloP) or pregnanolone (Preg), inhibits neuronal excitability; these endogenous NS and their analogues have been therapeutically applied as anti-depressants, anti-epileptics and general anesthetics. While NS have many favorable properties as anesthetics (e.g. rapid onset, rapid recovery, minimal cardiorespiratory depression, neuroprotection), they are not currently in clinical use, largely due to problems with formulation. Recent advances in understanding NS mechanisms of action and improved formulations have rekindled interest in development of NS as sedatives and anesthetics. In this review, the synthesis of NS, and their mechanism of action will be reviewed with specific emphasis on their binding sites and actions on γ-aminobutyric acid type A (GABAA) receptors. The potential advantages of NS analogues as sedative and anesthetic agents will be discussed.

Environmental impact of anesthetic drugs.

PURPOSE OF REVIEW: The environmental impact of anesthesia far exceeds that of other medical specialties due to our use of inhaled anesthetic agents (which are potent greenhouse gases) and many intravenous medications. RECENT FINDINGS: Calls for reducing the carbon footprint of anesthesia are ubiquitous in the anesthesia societies of developed nations and are appearing in proposed changes for hospital accreditation and funding in the United States. The body of research on atmospheric, land and water impacts of anesthetic pharmaceuticals is growing and generally reinforces existing recommendations to reduce the greenhouse gas emissions of anesthesia care. SUMMARY: The environmental impact of anesthesia care should factor into our clinical decisions. The onus is on clinicians to safely care for our patients in ways that contribute the least harm to the environment. Intravenous anesthesia and regional techniques have less environmental impact than the use of inhaled agents; efforts to reduce and properly dispose of pharmaceutical waste are central to reducing environmental burden; desflurane should not be used; nitrous oxide should be avoided except where clinically necessary; central nitrous pipelines should be abandoned; low fresh gas flows should be utilized whenever inhaled agents are used.

Anesthesia for traumatic brain injury.

PURPOSE OF REVIEW: Traumatic brain injury (TBI) presents complex clinical challenges, requiring a nuanced understanding of its pathophysiology and current management principles to improve patient outcomes. Anesthetists play a critical role in care and need to stay updated with recent evidence and trends to ensure high-quality treatment. The Brain Trauma Foundation Guidelines, last updated in 2016, have shown moderate adherence, and much of the current management relies on expert opinions. This literature review synthesizes the current evidence and provides insights into the role of anesthetists in TBI management. RECENT FINDINGS: Recent literature has emphasized the importance of tailored anesthetic management principles in treating TBI, focusing on minimizing secondary brain injury during neurosurgical interventions or extracranial surgery. Emerging trends include individualized intracranial pressure approaches and multimodal neuromonitoring for comprehensive assessment of cerebral physiology. SUMMARY: Anesthesia for TBI patients requires a comprehensive approach that balances anesthetic goals with the unique pathophysiological factors of brain injury. Despite recent research expanding our understanding, challenges remain in standardizing protocols and addressing individual patient response variability. Adherence to established management principles, personalized approaches, and ongoing research is crucial for improving the outcomes.

Anesthetic recommendations for maternal and fetal safety in nonobstetric surgery: a balancing act.

PURPOSE OF REVIEW: Nonobstetric surgery during pregnancy is associated with maternal and fetal risks. Several physiologic changes create unique challenges for anesthesiologists. This review highlights physiologic changes of pregnancy and presents clinical recommendations based on recent literature to guide anesthetic management for the pregnant patient undergoing nonobstetric surgery. RECENT FINDINGS: Nearly every anesthetic technique has been safely used in pregnant patients. Although it is difficult to eliminate confounding factors, exposure to anesthetics could endanger fetal brain development. Perioperative fetal monitoring decisions require an obstetric consult based on anticipated maternal and fetal concerns. Given the limitations of fasting guidelines, bedside gastric ultrasound is useful in assessing aspiration risk in pregnant patients. Although there is concern about appropriateness of sugammadex for neuromuscular blockade reversal due its binding to progesterone, preliminary literature supports its safety. SUMMARY: These recommendations will equip anesthesiologists to provide safe care for the pregnant patient and fetus undergoing nonobstetric surgery.

Tumour excisional surgery, anaesthetic-analgesic techniques, and oncologic outcomes: a narrative review.

Cancer is a growing global burden; there were an estimated 18 million new cancer diagnoses worldwide in 2020. Excisional surgery remains one of the main treatments for solid organ tumours in cancer patients and is potentially curative. Cancer- and surgery-induced inflammatory processes can facilitate residual tumour cell survival, growth, and subsequent recurrence. However, it has been hypothesised that anaesthetic and analgesic techniques during surgery might influence the risk of cancer recurrence. This narrative review aims to provide an updated summary of recent observational studies and new randomised controlled clinical trials on whether certain specific anaesthetic and analgesic techniques or perioperative interventions during tumour resection surgery of curative intent materially affect long-term oncologic outcomes.

Anesthetic Considerations in the Electrophysiology Laboratory: A Comprehensive Review.

Catheter ablation procedures for arrhythmias or implantation and/or extraction of cardiac pacemakers can present many clinical challenges. It is imperative that there is clear communication and understanding between the anesthesiologist and electrophysiologist during the perioperative period regarding the mode of ventilation, hemodynamic considerations, and various procedural complications. This article provides a comprehensive narrative review of the anesthetic techniques and considerations for catheter ablation procedures, ventilatory modes using techniques such as high-frequency jet ventilation, and strategies such as esophageal deviation and luminal temperature monitoring to decrease the risk of esophageal injury during catheter ablation. Various hemodynamic considerations, such as the intraprocedural triaging of cardiac tamponade and fluid administration during catheter ablation, also are discussed. Finally, this review briefly highlights the early research findings on pulse-field ablation, a new and evolving ablation modality.

Unanswered questions of anesthesia neurotoxicity in the developing brain.

PURPOSE OF REVIEW: This article reviews recent advances and controversies of developmental anesthesia neurotoxicity research with a special focus on the unanswered questions in the field both from clinical and preclinical perspectives. RECENT FINDINGS: Observational cohort studies of prenatal and early childhood exposure to anesthesia have reported mixed evidence of an association with impaired neurodevelopment. Meta-analyses of currently available studies of early childhood exposure to anesthesia suggest that, while limited to no change in general intelligence can be detected, more subtle deficits in specific neurodevelopmental domains including behavior and executive function may be seen. Several studies have evaluated intraoperative blood pressure values and neurocognitive outcomes and have not found an association. Although many animal studies have been performed, taking into consideration other peri-operative exposures such as pain and inflammation may help with translation of results from animal models to humans. SUMMARY: Advances have been made in the field of developmental anesthetic neurotoxicity over the past few years, including the recognition that anesthetic exposure is associated with deficits in certain cognitive domains but not others. Although the most important question of whether anesthetic agents actually cause long-term neurodevelopmental effects in children has still not been answered, results from recent studies will guide further studies necessary to inform clinical decision-making in children.

Intravenous and Intramuscular Allopregnanolone for Early Treatment of Status Epilepticus: Pharmacokinetics, Pharmacodynamics, and Safety in Dogs.

Allopregnanolone (ALLO) is a neurosteroid that modulates synaptic and extrasynaptic GABAA receptors. We hypothesize that ALLO may be useful as first-line treatment of status epilepticus (SE). Our objectives were to (1) characterize ALLO pharmacokinetics-pharmacodynamics PK-PD after intravenous (IV) and intramuscular (IM) administration and (2) compare IV and IM ALLO safety and tolerability. Three healthy dogs and two with a history of epilepsy were used. Single ALLO IV doses ranging from 1-6 mg/kg were infused over 5 minutes or injected IM. Blood samples, vital signs, and sedation assessment were collected up to 8 hours postdose. Intracranial EEG (iEEG) was continuously recorded in one dog. IV ALLO exhibited dose-proportional increases in exposure, which were associated with an increase in absolute power spectral density in all iEEG frequency bands. This relationship was best described by an indirect link PK-PD model where concentration-response was described by a sigmoidal maximum response (Emax) equation. Adverse events included site injection pain with higher IM volumes and ataxia and sedation associated with higher doses. IM administration exhibited incomplete absorption and volume-dependent bioavailability. Robust iEEG changes after IM administration were not observed. Based on PK-PD simulations, a 2 mg/kg dose infused over 5 minutes is predicted to achieve plasma concentrations above the EC50, but below those associated with heavy sedation. This study demonstrates that ALLO is safe and well tolerated when administered at 1-4 mg/kg IV and up to 2 mg/kg IM. The rapid onset of effect after IV infusion suggests that ALLO may be useful in the early treatment of SE. SIGNIFICANCE STATEMENT: The characterization of the pharmacokinetics and pharmacodynamics of allopregnanolone is essential in order to design clinical studies evaluating its effectiveness as an early treatment for status epilepticus in dogs and people. This study has proposed a target dose/therapeutic range for a clinical trial in canine status epilepticus.

Ketamine and the At-Risk Brain.

Postoperative cognitive dysfunction and delirium are undesirable consequences of surgery and anesthesia that regrettably do not have consistent predictive markers. Nor do they have reliable prophylactic or treatment methodologies. In an effort to better understand how anesthetic drugs alter the rate of postoperative delirium, Chang et al explore how patients with preoperative cognitive impairment respond to the influence of intraoperative ketamine. Patients aged 65 or older presenting for spine surgery lasting over three hours were assessed and divided into those with and without baseline cognitive impairment. Both groups either received intraoperative ketamine or did not. All patients who received intraoperative ketamine demonstrated an increase in power spectral density via electroencephalographic assessment. However, patients with preoperatively established cognitive impairment displayed a significantly diminished electroencephalographic response to ketamine. Furthermore, this subgroup also suffered an increased incidence of postoperative delirium. What is the interpretation of this finding? An accompanying editorial elegantly describes how disorders of cognition result from both predisposing and precipitating factors. In this case, patients with known cognitive impairment were more likely to endure delirium when exposed to ketamine. Is it possible that ketamine and other drugs could be used as agents to stratify cognitive risk? Should we definitively avoid such drugs as potentiators of cognitive dysfunction? A variety of contextual limitations must be entertained when interpreting the results of this study as summarized in this infographic. These are also elaborated in greater detail in both the primary article as well as its attendant editorial. The reader is encouraged to review both in their entirety for an in-depth scope of understanding.

Perioperative Diabetes Insipidus Caused by Anesthetic Medications: A Review of the Literature.

Diabetes insipidus (DI) is an uncommon perioperative complication that can occur secondary to medications or surgical manipulation and can cause significant hypovolemia and electrolyte abnormalities. We reviewed and evaluated the current literature and identified 29 cases of DI related to medications commonly used in anesthesia such as propofol, dexmedetomidine, sevoflurane, ketamine, and opioids. This review summarizes the case reports and frequency of DI with each medication and presents possible pathophysiology. Medication-induced DI should be included in the differential diagnosis when intraoperative polyuria is identified. Early identification, removal of the agent, and treatment of intraoperative DI are critical to minimize complications.

Impact of surgery and anesthesia during early brain development: A perfect storm.

Neonatal surgery and concomitant anesthesia coincide with a timeframe of rapid brain development. The speed and complexity of early brain development superimposed on immature regulatory mechanisms that include incomplete cerebral autoregulation, insufficient free radical scavenging and an immature immune response puts the brain at risk. Brain injury may have long-term consequences for multiple functional domains including cognition, learning skills, and behavior. Neurodevelopmental follow-up studies have noted mild-to-moderate deficits in children who underwent major neonatal surgery and related anesthesia. The present review evaluates neonatal surgery against the background of neurobiological processes that unfold at a pace unparalleled by any other period of human brain development. First, a structured summary of early brain development is provided in order to establish theoretical groundwork. Next, literature on brain injury and neurodevelopmental outcome after neonatal surgery is discussed. Special attention is given to recent findings of structural brain damage reported after neonatal surgery. Notably, high-quality imaging data acquired before surgery are currently lacking. Third, mechanisms of injury are interrogated taking the perspective of early brain development into account. We propose a novel disease model that constitutes a triad of inflammation, vascular immaturity, and neurotoxicity of prolonged exposure to anesthetic drugs. With each of these components exacerbating the other, this amalgam incites the perfect storm, resulting in brain injury. When examining the brain, it seems intuitive to distinguish between neonates (i.e., <60 postconceptional weeks) and more mature infants, multiple and/or prolonged anesthesia exposure and single, short surgery. This review culminates in an outline of anesthetic considerations and future directions that we believe will help move the field forward.

Risk assessment and optimization strategies to reduce perioperative respiratory adverse events in Pediatric Anesthesia-Part 2: Anesthesia-related risk and treatment options.

Perioperative respiratory adverse events are the most common cause of critical events in children undergoing anesthesia and surgery. While many risk factors remain unmodifiable, there are numerous anesthetic management decisions which can impact the incidence and impact of these events, especially in at-risk children. Ongoing research continues to improve our understanding of both the influence of risk factors and the effect of specific interventions. This review discusses anesthesia risk factors and outlines strategies to reduce the rate and impact of perioperative respiratory adverse events with a chronologic based inquiry into anesthetic management decisions through the perioperative period from premedication to postoperative disposition.

Sugammadex for reversal of neuromuscular blockade in pediatric patients: Results from a phase IV randomized study.

BACKGROUND: Few randomized studies have assessed recovery from rocuronium- or vecuronium-induced moderate or deep neuromuscular blockade with sugammadex in pediatric participants. AIM: To assess sugammadex for reversal of neuromuscular blockade in pediatric participants. METHODS: This was a randomized, phase IV, active comparator-controlled, double-blind study. Participants aged 2 to <17 years, under moderate or deep neuromuscular blockade, were administered sugammadex (2 or 4 mg/kg) or neostigmine (50 µg/kg; for moderate neuromuscular blockade only). Predefined adverse events of clinical interest, including clinically relevant bradycardia, hypersensitivity, and anaphylaxis, were monitored. The primary efficacy endpoint was time to recovery to a train-of-four ratio of ≥0.9 in participants receiving sugammadex 2 mg/kg versus neostigmine for reversal of moderate neuromuscular blockade, analyzed by analysis of variance adjusted for neuromuscular blocking agent and age. RESULTS: Of 288 randomized participants, 272 completed the study and 276 were included in the analyses. Clinically relevant bradycardia was experienced by 2.0%, 1.6%, and 5.9% of participants in the sugammadex 2 mg/kg, sugammadex 4 mg/kg, and neostigmine groups, respectively. No hypersensitivity or anaphylaxis events were observed. Recovery to a train-of-four ratio of ≥0.9 with sugammadex 2 mg/kg was faster than neostigmine (1.6 min, 95% CI 1.3 to 2.0 vs. 7.5 min, 95% CI 5.6 to 10.0; p < .0001) and was comparable to sugammadex 4 mg/kg (2.0 min, 95% CI 1.8 to 2.3). CONCLUSIONS: Pediatric participants recovered from rocuronium- or vecuronium-induced moderate neuromuscular blockade significantly faster with sugammadex 2 mg/kg than with neostigmine. Time to reversal of deep neuromuscular blockade with sugammadex 4 mg/kg was consistent with that of moderate neuromuscular blockade reversal. No meaningful differences in clinically relevant bradycardia, hypersensitivity, or anaphylaxis were seen with sugammadex vs neostigmine. These results support the use of sugammadex for reversal of moderate and deep rocuronium- and vecuronium-induced neuromuscular blockade in patients aged 2 to <17 years. CLINICAL TRIAL REGISTRATION: NCT03351608/EudraCT 2017-000692-92.