Spontaneous recovery from neuromuscular block after a single dose of a muscle relaxant in pediatric patients: A systematic review using a network meta-analytic and meta-regression approach.

BACKGROUND: Age-related differences in the pharmacokinetics and pharmacodynamics of neuromuscular blocking agents (NMBAs) and the short duration of many surgical procedures put pediatric patients at risk of postoperative residual curarization (PORC). To date, the duration of neuromuscular blocking agent effect in children has not been analyzed in a quantitative review. The current meta-analysis aimed to compare spontaneous recovery following administration of various types and doses of neuromuscular blocking agents and to quantify the effect of prognostic variables associated with the recovery time in pediatric patients. METHOD: We searched for randomized controlled trials (RCTs) and controlled clinical trials (CCTs) that compared the time to 25% T1 (t25), from 25% to 75% T1 (RI25-75), and to ≥90% train-of-four (tTOF90) neuromuscular recovery between common neuromuscular blocking agent treatments administered as a single bolus to healthy pediatric participants. We compared spontaneous t25, RI25-75, and tTOF90 between (1) neuromuscular blocking agent treatments and (2) age groups receiving a given neuromuscular blocking agent intervention and anesthesia technique. Bayesian random-effects network and pairwise meta-analyses along with meta-regression were used to evaluate the results. RESULTS: We used data from 71 randomized controlled trials/controlled clinical trials including 4319 participants. Network meta-analysis allowed for the juxtaposition and ranking of spontaneous t25, RI25-75, and tTOF90 following common neuromuscular blocking agent interventions. For all neuromuscular blocking agents a log-linear relationship between dose and duration of action was found. With the neuromuscular blocking agent treatments studied, the average tTOF90 (mean[CrI95]) in children (>2-11 y) was 41.96 [14.35, 69.50] and 17.06 [5.99, 28.30] min shorter than in neonates (<28 d) and infants (28 d-12 M), respectively. We found a negative log-linear correlation between age and duration of neuromuscular blocking agent effect. The difference in the tTOF90 (mean[CrI95]) between children and other age groups increased by 21.66 [8.82, 34.53] min with the use of aminosteroid neuromuscular blocking agents and by 24.73 [7.92, 41.43] min with the addition of sevoflurane/isoflurane for anesthesia maintenance. CONCLUSIONS: The times to neuromuscular recovery are highly variable. These can decrease significantly with age and are prolonged when volatile anesthetics are administered. This variability, combined with the short duration of many pediatric surgical procedures, makes quantitative neuromuscular monitoring mandatory even after a single dose of neuromuscular blocking agent.

Development and validation of a model to calculate anesthetic agent consumption from inspired and end-expired concentrations, minute ventilation, fresh gas flow and dead space ventilation.

Anesthetic agent consumption is often calculated as the product of fresh gas flow (FGF) and vaporizer dial setting (FVAP). Because FVAP of conventional vaporizers is not registered in automated anesthesia records, retrospective agent consumption studies are hampered. The current study examines how FVAP can be retrospectively calculated from the agent's inspired (FIN) and end-expired concentration (FET), FGF, and minute ventilation (MV). Theoretical analysis of agent mass balances in the circle breathing reveals FVAP = [FIN - (dead space fraction * FIN + (1 - dead space fraction) * FET) * (1 - FGF/MV)]/(1-(1 - FGF/MV)). FIN, FET, FGF and MV are routinely monitored, but dead space fraction is unknown. Dead space fraction for sevoflurane, desflurane, and isoflurane was therefore determined empirically from an unpublished data set of 161 patient containing FVAP, FIN, FET, MV and FGF ranging from 0.25 to 8 L/min delivered via an ADU® (GE, Madison, WI, USA). Dead space fraction for each agent was determined empirically by having Excel's solver function calculate the value of dead space fraction that minimized the sum of the squared differences between dialed FVAP and predicted FVAP. With dead space fraction known, the model was then prospectively tested for sevoflurane in O2/air using data collected over the course of two weeks with one FLOW-i (Getinge, Solna, Sweden) and one Zeus workstation (Dräger, Lübeck, Germany). Because both workstations use an electronically controlled vaporizer/injector, the dialed FVAP were available to allow the calculation of median performance error (MDPE) and median absolute performance error (MDAPE). MDPE and MDAP are reported as median and interquartiles. The empirical dead space fraction for isoflurane, sevoflurane, and desflurane were 0.59, 0.49, and 0.66, respectively. For prospective testing, a total of 149.4 h of useful data were collected from 78 patient with the Zeus and Flow-i combined, with FGF ranging from 0.18 to 8 L/min. The model predicted dialed FVAP well, with a MDPE of -1 (-11, 6) % and MDAPE of 8 (4, 17) %. FVAP can be retrospectively calculated from FIN, FET, FGF, and MV plus an agent specific dead space fraction factor with a degree of error that we believe suffices for retrospective sevoflurane consumption analyses. Performance with other agents and N2O awaits further validation.

Induction of anesthesia with sevoflurane in children: Curiosities and controversies.

Inhalational inductions with sevoflurane (up to 8% inspired concentration) have been the standard for inducing anesthesia in children for over three decades. However, when sevoflurane was first introduced, clinicians reported isolated cases of unexpected myoclonic jerking movements during the induction in children without epilepsy. These cases raised concerns regarding the widespread use of sevoflurane particularly after reports of seizures and epileptiform electroencephalographic (EEG) discharges surfaced. The latter reports prompted recommendations to reduce the concentration of sevoflurane during induction of anesthesia. More recently, a shift away from the use of nitrous oxide has prompted some to question whether sevoflurane has a role as an induction agent in children. The preponderance of evidence supports the practice of safely inducing anesthesia with 8% sevoflurane with or without nitrous oxide in children but recommended strategies to mitigate against epileptiform discharges may be more harmful than beneficial.

Comparative evaluation of one-handed versus two-handed mask holding techniques in children during inhalational induction of anesthesia: A randomized crossover study.

BACKGROUND: We aimed to evaluate if two-handed mask airway is superior to one-handed mask airway during inhalational induction of anesthesia in children. METHODS: A randomized, two period, crossover study was performed on 60 children aged 1-8 years, with obstructive sleep apnea due to adenotonsillar hypertrophy, scheduled for adenotonsillectomy. Children were assigned to two study sequences and one control sequence of 20 subjects each. A control sequence was added to evaluate the effect of anesthetic depth. Sequence 1: One-handed followed by two-handed airway, 30 seconds each; Sequence 2: two-handed followed by one-handed airway, 30 seconds each and Sequence 3: two-handed airway, for 60 seconds. The work of breathing indices, phase angle, and labored breathing index were recorded using respiratory inductance plethysmography. Additional outcome measures were tidal volume, minute ventilation, and respiratory rate. A straight comparison and a crossover analysis was performed. RESULTS: The initial comparison revealed that one-handed airway had greater phase angle (mean diff. 17.4; 95% confidence interval [CI] 1.07-33.68; P = .034), greater labored breathing index (mean diff. 0.56; 95% CI 0.16-1.04; P = .004),lower minute ventilation (mean diff. -1567; 95% CI -2695 to -5.4; P = .004),and lower tidal volume (mean diff. -39; 95% CI -2.7 to -5.4; P = .02) than two-handed airway. On crossover analysis, within-subject difference in the phase angle was greater during one-handed than two-handed airway (34.3; 95% CI 8.46-60.14; P = .01) as was labored breathing index (mean diff. 1.2; 95% CI 0.39-2.00; P < .0046).Minute ventilation was lower during one-handed than two-handed airway (mean diff. -3359; 95% CI -4363 to -2355, P < 0.0001) as was tidal volume(mean diff. -78; 95% CI -110.4 to -45.8; P < .0001). CONCLUSION: In children with obstructive sleep apnea due to adenotonsillar hypertrophy, two-handed airway provides superior airway patency that was not influenced by the anesthetic depth.

Volatiles or TIVA: Which is the standard of care for pediatric airway procedures? A pro-con discussion.

Anesthesia for pediatric airway procedures constitutes a true art form that requires training and experience. Communication between anesthetist and surgeon to establish procedure goals is essential in determining the most appropriate anesthetic management. But does the mode of anesthesia have an impact? Traditionally, inhalational anesthesia was the most common anesthesia technique used during airway surgery. Introduction of agents used for total intravenous anesthesia (TIVA) such as propofol, short-acting opioids, midazolam, and dexmedetomidine has driven change in practice. Ongoing debates abound as to the advantages and disadvantages of volatile-based anesthesia versus TIVA. This pro-con discussion examines both volatiles and TIVA, from the perspective of effectiveness, safety, cost, and environmental impact, in an endeavor to justify which technique is the best specifically for pediatric airway procedures.

The effect of fresh gas flow during induction of anaesthesia on sevoflurane usage: a quality improvement study.

Reducing fresh gas flow during inhalational anaesthesia results in cost savings and decreases environmental impact. We are interested in the influence of fresh gas flow on the early (induction) phase of overall fresh gas flow and vapour consumption. This stage is often excluded in studies of fresh gas flow. Data were collected from 3199 sevoflurane anaesthetics over an 11-month period in four operating theatres. We determined fresh gas flow at different stages of anaesthesia, and developed an explanatory model for the influence of the 'induction' period. Following a three-month collection of baseline data we emphasised the importance of the early phase to our department repeatedly over a two-week period. We explored the relationship between fresh gas flow and total vapour usage, and used a simple mathematical model to explore the effect of changes in the fresh gas flow and duration of the 'induction' phase. Mean fresh gas flow was 1.15 l.min-1 in the baseline period and 0.91 l.min-1 in the two months following our educational effort (p = 0.0005). In the following six months, mean fresh gas flow was 1.17 l.min-1 (p = 0.7726 compared with baseline). These results were driven by changes in both fresh gas flow and duration of the initial high-flow period. We found some correlation (R2  = 0.85) between overall fresh gas flow and vapour consumption; a 1 l.min-1 increase in fresh gas flow consumes an additional 18 ml.hr-1 of liquid sevoflurane. This preliminary study demonstrates that an episode of high fresh gas flow at the start of anaesthesia has a large and modifiable effect on overall fresh gas flow and vapour consumption. We also confirmed the linear relationship between fresh gas flow and vapour usage.

How David Hatch became a professor of pediatric anesthesia.

This is an account of an interview with David John Hatch who was one of the first Professors of Pediatric Anesthesia in the world. He began his anesthesia career as a medical student administering chloroform and ended it 40 years later as a Consultant at Great Ormond Street Hospital where he developed and led a world renowned research team measuring and assessing lung function in infants and children. These productive years earned him his chair at the Institute of Child Health in London (part of University College London) funded by Portex (currently, a branch of Smiths Medical). His academic achievements include over 110 journal publications, two textbooks and having many honors and awards. Yet he does not think of himself as an academic. In his words "I wanted to be a hard working clinician with an interest in research, and not just academic".

Toxicity of inhaled agents after prolonged administration.

Inhaled anesthetics have been utilized mostly for general anesthesia in the operating room and oftentimes for sedation and for treatment of refractory status epilepticus and status asthmaticus in the intensive care unit. These contexts in the ICU setting are related to potential for prolonged administration wherein potential organ toxicity is a concern. Over the last decade, several clinical and animal studies of neurotoxicity attributable to inhaled anesthetics have been emerging, particularly in extremes of age. This review overviews potential for and potential mechanisms of neurotoxicity and systemic toxicity of prolonged inhaled anesthesia and clinical scenarios where inhaled anesthesia has been used in order to assess safety of possible prolonged use for sedation. High dose inhaled agents are associated with postoperative cognitive dysfunction (POCD) and other situations. However, thus far no strong indication of problematic neuro or organ toxicity has been demonstrated after prolonged use of low dose volatile anesthesia.

¿Existe relación entre la concentración de inducción anestésica de sevofluorano y la incidencia de agitación postanestésica en niños? / Is there a relationship between the concentration of sevofluoran anesthetic induction and the incidence of post-anesthetic agitation in children?

Introducción. La inducción anestésica con sevofluorano se asocia con agitación postanestésica (APA) en niños. Concentraciones de sevofluorano mayores a 6% producen actividad cerebral epileptiforme, la que podría estar relacionada a APA. El propósito de este estudio fue comparar el efecto de dos diferentes concentraciones de inducción anestésica con sevofluorano sobre la incidencia de APA, en niños sometidos a cirugía infraumbilical. Método. Estudio prospectivo y doble ciego, en pacientes de 2 a 7 años, operados de fimosis o hernia inguinal con anestesia general y bloqueo epidural caudal. Los pacientes fueron aleatorizados para recibir sevofluorano 5 por ciento (grupo S5) o sevofluorano 8 por ciento (grupo S8). Se registraron variables demográficas, signos vitales, profundidad anestésica utilizando índice biespectral (BIS) y respuesta motora durante distintos momentos de la anestesia. Se evaluó la presencia de agitación en pabellón y recuperación utilizando la escala de APA pediátrica (PAED). Análisis estadístico: t-test o Mann-Whitney y test Chi-cuadrado o Fisher, p < 0,05 considerada significativa. Resultados. Se reclutaron 33 pacientes, 16 en el grupo S5 y 17 en el grupo S8. Ambos grupos fueron comparables en cuanto a variables demográficas, signos vitales, respuesta motora y valores de BIS. No hubo diferencias significativas en la incidencia de APA en pabellón (S5: 31,3 por ciento y S8: 35,3 por ciento) y en recuperación (S5: 43,8 por ciento y S8: 41,2 por ciento), entre los grupos. Conclusión. No habría relación entre la concentración de inducción anestésica de sevofluorano y la incidencia de APA en niños sometidos a cirugía infraumbilical con anestesia general y bloqueo caudal. (AU)

Introduction. Induction of anesthesia with sevoflurane is associated with post-anesthetic agitation (PAA) in children. Sevoflurane concentration greater than 6% produces epileptiform brain activity, which could be related to PAA. The aim of this study was to compare the effect of two different sevoflurane concentrations for anesthesia induction on the incidence of PAA in children undergoing infraumbilical surgery. Method. Prospective, double blind study, performed in patients 2 to 7 years of age, undergoing circumcision or inguinal hernia repair under general anesthesia and epidural caudal block. Patients were randomized to receive sevoflurane 5 percent (S5 group) or sevoflurane 8 percent (S8 group), during anesthesia induction. Demographic variables, vital parameters, anesthesia depth using bispectral index (BIS) and motor responses during different moments of anesthesia were recorded. The presence of agitation in the operating room and recovery room were determined using the pediatric PAA scale (PAED). Statistical analysis: t-test or Mann-Whitney, and Chi-square or Fisher test, p < 0.05 considered significant. Results. Thirty-three patients were enrolled, 16 in the S5 group and 17 in the S8 group. Demographic variables, vital parameters, motor responses and BIS values were comparable between both groups. There were no significant differences in the incidence of PAA in the operating room (S5: 31.3 percent percent and S8: 35.3 percent) or in the recovery room (S5: 43,8 percent and S8: 41.2 percent), between both groups. Conclusion. Sevoflurane concentration used for induction of anesthesia would not be related to the incidence of PAA in children undergoing infraumbilical surgery under general anesthesia and epidural caudal block. (AU)