Daily Anesthesiology Research Analysis
Three impactful studies refine pediatric and neonatal anesthetic practice. A multicenter cohort in JAMA Pediatrics identifies expiratory tidal volume targets linked to successful lung aeration during preterm resuscitation. Two pediatric anesthesia trials advance safety: remimazolam markedly reduces emergence delirium after brief surgery, and multicohort pharmacodynamic data quantify propofol dose margins to apnea by age and sex.
Summary
Three impactful studies refine pediatric and neonatal anesthetic practice. A multicenter cohort in JAMA Pediatrics identifies expiratory tidal volume targets linked to successful lung aeration during preterm resuscitation. Two pediatric anesthesia trials advance safety: remimazolam markedly reduces emergence delirium after brief surgery, and multicohort pharmacodynamic data quantify propofol dose margins to apnea by age and sex.
Research Themes
- Neonatal resuscitation targets and lung aeration
- Pediatric emergence delirium prevention with remimazolam
- Age- and sex-specific propofol safety margins in children
Selected Articles
1. Respiratory Targets Associated With Lung Aeration During Delivery Room Resuscitation of Preterm Neonates.
In a multicenter prospective cohort with a confirmatory dataset, expiratory tidal volume (VTE) was the only respiratory parameter associated with achieving heart rate ≥100 bpm during preterm resuscitation. The association was strongest up to 4 mL/kg VTE and attenuated above that threshold, consistent across datasets. Birth weight favored success, while frequent mask removals impeded it.
Impact: Defines a data-driven VTE target for effective lung aeration during preterm resuscitation, addressing a key evidence gap. Findings are replicated in an independent dataset, strengthening external validity.
Clinical Implications: Use of respiratory function monitoring to target VTE up to 4 mL/kg may improve the efficiency of positive pressure ventilation and timely heart rate response in preterm neonates. Minimizing unnecessary mask removals and considering birth weight in titration may further enhance outcomes.
Key Findings
- VTE was the only respiratory parameter associated with HR ≥100 bpm during resuscitation (AHR 1.10; 95% CI 1.01–1.20).
- Strongest association observed for VTE increases up to 4 mL/kg (AHR 1.55; 95% CI 1.20–2.00), with attenuation above 4 mL/kg.
- Findings replicated in a confirmatory dataset; birth weight improved and mask removal frequency reduced the likelihood of success.
Methodological Strengths
- Multicenter prospective cohort with an independent confirmatory dataset
- Objective respiratory function monitoring and cause-specific Cox modeling
Limitations
- Observational design; heart rate used as a surrogate for lung aeration
- Generalizability limited to centers with respiratory function monitoring and specific gestational age ranges
Future Directions: Randomized trials testing VTE-targeted ventilation strategies and implementation studies integrating RFM-guided protocols in delivery rooms.
IMPORTANCE: Effective lung aeration is crucial for successful postnatal transition. Goal targets to achieve lung aeration during positive pressure ventilation have not been established for preterm neonates. OBJECTIVE: To identify respiratory parameters associated with successful lung aeration during delivery room resuscitation. DESIGN, SETTING, AND PARTICIPANTS: This multicenter prospective cohort study was conducted from March 2016 to April 2021. The primary population included preterm neonates from 3 centers of 22 weeks to 31 weeks 6 days' gestation with bradycardia who received positive pressure ventilation during resuscitation after birth. An independent population of preterm neonates (24 weeks to 27 weeks 6 days' gestation) in the multicenter Monitoring Neonatal Resuscitation randomized clinical trial served as a confirmatory dataset. Data were analyzed January 2022 to May 2025. EXPOSURES: Rolling means of pressure, inspiratory and expiratory tidal volumes (VTE), and mask leak, as measured with a respiratory function monitor (RFM). Counts of spontaneous breaths between inflations and mask removal instances. MAIN OUTCOMES AND MEASURES: The primary outcome was a sustained increase in heart rate to at least 100 beats per minute, indicating effective lung aeration, within the first 10 minutes of resuscitation. Associations between clinical covariates, respiratory parameters, and heart rate increase were examined using cause-specific Cox proportional hazards regression models. RESULTS: There were 132 neonates in the primary dataset (median [IQR] gestation, 26.6 [25.1-29.2] weeks; 67 [50.8%] male) and 115 in the confirmatory dataset (median [IQR] gestation, 26.7 [25.6-27.4] weeks; 65 [56.5%] male). Of 132 primary dataset participants, 125 (94.7%) achieved the primary outcome. Among the measured respiratory parameters, only VTE was associated with an increase in heart rate (adjusted hazard ratio [AHR], 1.10 [95% CI, 1.01-1.20]). The AHR was higher for increases in VTE up to 4 mL/kg (AHR, 1.55 [95% CI, 1.20-2.00]) than for VTEs higher than 4 mL/kg (AHR, 1.04 [95% CI, 0.98-1.10]). These results were consistent with those in the confirmatory dataset: an association for an increase in heart rate with VTE values up to 4 mL/kg (AHR, 1.31 [95% CI, 1.01-1.70]) but not higher than 4 mL/kg (AHR, 1.02 [95% CI, 0.96-1.08]). Other covariates associated with an increase in heart rate included birth weight (per 100 g) (AHR, 1.12 [95% CI, 1.05-1.20]) and mask removal count (AHR, 0.83 [95% CI, 0.70-0.98]). CONCLUSIONS AND RELEVANCE: This cohort study observed in one neonatal population and confirmed in another that a minimum VTE of 4 mL/kg was associated with successful lung aeration as assessed by an increase in heart rate to at least 100 beats per minute during preterm neonate resuscitation. These results may inform future studies to determine the clinical impact of incorporating data-based targets for delivery room resuscitation of preterm neonates.
2. Remimazolam for preventing sevoflurane-induced emergence delirium after pediatric laparoscopic inguinal hernia repair: a placebo-controlled randomized clinical trial.
In a randomized, placebo-controlled trial of 184 children, a single 0.1 mg/kg dose of remimazolam at procedure end markedly reduced emergence delirium (7.6% vs 41.3%), improved hemodynamic stability, reduced pain and sufentanil requirements, and shortened PACU stays. Benefit likely stems from smoother emergence and anxiolysis.
Impact: Provides high-quality prospective evidence for a simple, low-dose intervention that substantially reduces emergence delirium in common pediatric day surgery.
Clinical Implications: Consider 0.1 mg/kg remimazolam at the end of sevoflurane-based pediatric procedures to lower emergence delirium risk, stabilize hemodynamics, and enhance recovery metrics and family satisfaction.
Key Findings
- Emergence delirium incidence reduced from 41.3% to 7.6% (RR 0.18; 95% CI 0.09–0.37).
- Lower PAED scores with large effect size (mean difference −2.28; Cohen’s d 1.12).
- Improved hemodynamic stability, lower pain, less sufentanil, shorter PACU stays, and higher parental satisfaction.
Methodological Strengths
- Randomized, placebo-controlled design with adequate sample size
- Clinically relevant, multisystem outcomes including hemodynamics and recovery
Limitations
- Single procedure type and age range; generalizability to other surgeries and settings uncertain
- Short-term outcomes without long-term neurobehavioral follow-up
Future Directions: Dose-response studies across procedures, comparison with other ED prevention strategies, and assessment of longer-term behavioral outcomes.
OBJECTIVE: To investigate the effectiveness and safety of remimazolam in preventing the emergence of delirium in children undergoing pediatric laparoscopic inguinal hernia surgery under combined intravenous and inhalation anesthesia. METHODS: A total of 184 pediatric patients aged 3-14 years who were undergoing laparoscopic inguinal hernia surgery were included. Patients were randomly assigned to receive either 0.1 mg/kg remimazolam (experimental group, n = 92) or 0.9 % normal saline (control group, n = 92) after the procedure. The primary outcome was the incidence of emergence delirium, which would manifest as a difference in the pediatric anesthesia emergence delirium (PAED) score between the two groups. The secondary outcomes included postoperative pain severity, duration of postanesthesia care unit (PACU) stay, sufentanil usage, parental satisfaction, mean arterial pressure (MAP), blood oxygen saturation (SpO₂), and heart rate (HR). RESULTS: The experimental group showed significantly lower overall PAED scores (mean difference = -2.28, 95 % CI:2.73 to -1.82; Cohen's d = 1.12, p < 0.001) and emergence delirium incidence (7.61 % vs 41.30 %; risk difference = 33.69 %, 95 % CI 21.60 % to 45.10 %; relative risk = 0.18, 95 % CI 0.09-0.37; p < 0.001). They also showed better hemodynamic stability (lower MAP/HR, higher SpO₂), reduced pain, shorter PACU stay, less sufentanil use, and higher parental satisfaction (all p < 0.05). CONCLUSION: Administration of 0.1 mg/kg remimazolam after pediatric laparoscopic inguinal hernia surgery could contribute to preventing the development of emergence delirium by smoothing hemodynamic changes and alleviating postoperative pain.
3. Pharmacodynamic Safety Endpoints for Propofol Anesthesia in Children by Age and Sex: A Multicohort Observational Study.
Across 318 children, the mean propofol dose to loss of eyelash reflex (LOER) was 2.65 mg/kg and was unaffected by age or sex, whereas the mean dose to apnea was 6.82 mg/kg, higher in boys and decreasing with age. Consequently, the therapeutic margin between LOER and apnea narrows in older and female children, warranting heightened vigilance when preserving spontaneous ventilation.
Impact: Provides actionable, quantitative safety thresholds for propofol induction across pediatric ages and sexes, enhancing individualized dosing and monitoring strategies.
Clinical Implications: When inducing anesthesia with propofol while maintaining spontaneous respiration, anticipate a narrower safety margin in older and female children. Titrate cautiously, consider adjunct monitoring (e.g., capnography, airway support readiness), and avoid rapid boluses near apnea thresholds.
Key Findings
- Mean dose to LOER was 2.65 mg/kg with no age or sex effect.
- Mean dose to apnea was 6.82 mg/kg; higher in males (+0.67 mg/kg) and decreased with age (−0.14 mg/kg per year).
- Older and female children have a narrower margin between LOER and apnea; 62 participants did not reach apnea under protocol.
Methodological Strengths
- Prospective, registered, stratified multicohort design across age and sex groups
- Standardized constant-rate propofol administration with objective endpoints
Limitations
- Observational design without randomization; potential confounding by concomitant medications or clinical context
- Truncated reporting of apneic endpoint protocol details; no EEG-based depth monitoring
Future Directions: Integrate pharmacogenomics (planned GWAS), model-based dosing algorithms, and validation in procedural sedation and diverse surgical contexts.
BACKGROUND: Propofol is a commonly used intravenous sedative and general anesthetic, with rapid onset and short duration of action. It has a narrow therapeutic index and significant interindividual variability in dosing requirements, which may elevate risks of its use, particularly in children. AIMS: We aimed to quantify the doses required to induce loss of consciousness and apnea in children by age and sex to contribute to tailored propofol dosing recommendations for improved safety and efficacy in pediatric anesthesia. METHODS: In this stratified- and purposive-sampling study, we enrolled children in six groups based on sex and age (3- to 5-year-olds, 6- to 10-year-olds, 11- to 18-year-olds), targeting 60 participants per group. For induction of anesthesia, we administered propofol at a constant rate until apnea was reached (absence of end-tidal CO RESULTS: Data were available for 318 participants, with 162 females and a median (interquartile range) age of 8.1 (5.3-12.9) years. The mean (SD) propofol dose to LOER was 2.65 (0.69) mg/kg with no effect of sex (-0.10 mg/kg for male, 95% confidence interval (CI) -0.26 to 0.05, p = 0.183) or age (0.0 mg/kg per year, 95% CI -0.02 to 0.02, p = 0.876). The mean (SD) propofol dose to apnea was 6.82 (1.64) mg/kg, with significant effects of both sex (+0.67 mg/kg for male, 95% CI 0.30 to 1.03, p < 0.001) and age (-0.14 mg/kg per year, 95% CI -0.19 to -0.1, p < 0.001). Apnea was not reached in 62 participants. CONCLUSIONS: Older and female children exhibited narrower therapeutic indices for the margin between LOER and apnea. This requires heightened vigilance, especially when maintaining spontaneous respiration. A planned genome-wide association study may identify pharmacogenetic-pharmacodynamic relationships and correlations with genetic ancestry. TRIAL REGISTRATION: The trial was registered on clinicaltrials.gov before enrolment (NCT04164264; date of registration 2019-11-15).