Dose response of alcuronium and d-tubocurarine in infants, children and adolescents

Seventy neonatal to adolescent general surgical patients were studied to create an individual dose-response curve for the long-acting neuromuscular blocking agents, alcuronium and d-tubocurarine. The mean (SEM) ED95 of alcuronium was 196 (9), 271 (13) and 243 (8) micrograms/kg in infants, children and adolescents, respectively (P less than 0.01). d-tubocurarine showed a similar age dependent dose-response relationship. ED95 doses were 414 (40), 499 (41) and 445 (31) micrograms/kg, respectively. The onset time (time from intravenous administration to maximal effect) following equipotent dosages was 40-50% shorter in infants than in children or adolescents (1.5 vs 2.7 minutes, P less than 0.05).     

Topical anaesthesia in neonates, infants and children

Editor—While we share the interest of Long and colleagues¹in topical anaesthesia for procedural pain in neonates and applaudtheir initiative to evaluate a potential new agent, some oftheir statements are incorrect or outdated. When commentingon one case of methaemoglobinaemia reported in 1995 after injectionof prilocaine for circumcision in a neonate,² Long and colleagueswrite ‘this means that EMLA cream is contraindicated ininfants of less than 3 months     

Dose-response characteristics of pancuronium in neonates, infants and children

This paper presents pharmacodynamic data for pancuronium in neonates, infants, children and adolescents during N2O-O2-fentanyl anaesthesia. Neuromuscular block (NMB) was evaluated by the adductor pollicis electromyogram. Dose-response curves of pancuronium were parallel in all age-groups. ED95 was greatest in children and least in infants (93 vs. 66 micrograms/kg, P less than 0.05). The rate of spontaneous recovery following 95% NMB was comparable in all age-groups, as was the maintenance requirement of pancuronium when related to ED-values. The hourly requirement to maintain NMB greater than 85% was 60-68% of the individual ED95 dose. When administered on this basis, pancuronium is an equally long-acting neuromuscular blocking agent in patients of all ages.     

The hemodynamic effects of phenoxybenzamine in neonates, infants, and children

STUDY OBJECTIVES: To evaluate the hemodynamic effects of the long-acting, alpha-adrenergic blocker, phenoxybenzamine, in children of different age groups. DESIGN: Retrospective chart review. SETTING: Tertiary-care, congenital cardiac surgery center. MEASUREMENTS: The data of 75 pediatric patients who received phenoxybenzamine while undergoing surgical repair of congenital heart defects on cardiopulmonary bypass (CPB) were studied. Patients were selected in three age groups: younger than one month (n = 25), one to 12 months (n = 25), and one to 5 years (n = 25). All patients received a full dose of phenoxybenzamine 1 mg/kg. Demographics, CPB duration, mean arterial pressure on CPB, mean flow on CPB (normalized to body surface area), and central-to-peripheral temperature gradients were recorded. Systemic vascular resistance index (SVRI) was calculated. MAIN RESULTS: Cardiopulmonary bypass duration was significantly longer in the age group of younger than 1 mo than in the older groups. Mean CPB flow/body surface area was similar in all children (3.45 +/- 0.9, 3.74 +/- 0.69, and 3.48 +/- 0.59 L/min/m2, respectively; P < 0.28). However, mean SVRI was significantly lower in children younger than 1 mo (997.3 +/- 233, 1196.9 +/- 394, and 1168.83 +/- 227 dynes/cm2m5; P < 0.04). Temperature gradient was significantly narrower in patients younger than one month than those who were one to 12 months and one to 5 years at the end of cooling (0.90 degrees C +/- 0.1 degrees C, 1.04 degrees C +/- 3.61 degrees C, 1.4 degrees C +/- 3.07 degrees C; P < 0.001) at end-rewarming and termination of CPB (4.58 degrees C +/- 2.36 degrees C, 6.23 degrees C +/- 4.17 degrees C, 7.32 degrees C +/- 3.46 degrees C; P < 0.02). Multivariate analysis showed that patient age was a significant variable affecting response to phenoxybenzamine, after adjusting for duration of CPB (P = 0.31), mean hematocrit on CPB (P = 0.86), and core cooling temperature (P = 0.34). CONCLUSION: The effect of phenoxybenzamine on SVRI, cooling, and rewarming on CPB varies with age as shown by more profound vasodilatation and narrower temperature gradients.     

Accelerated onset and delayed recovery of d-tubocurarine blockade with pancuronium in infants and children

The effect of age on the onset and duration of action of a d-tubocurarine (DTC) neuromuscular blockade with and without pancuronium priming in children was examined. Sixty ASA physical status I or II patients in three age ranges (0-1 yr, 1-3 yr and 3-10 yr) were anaesthetized with thiopentone, halothane and nitrous oxide. Each patient received either a single paralyzing dose of DTC 0.4 mg.kg-1, or DTC 0.36 mg.kg-1 preceded three minutes earlier by pancuronium 0.007 mg.kg-1. Evoked force of contraction of the adductor pollicis was measured using train-of-four stimulation applied every 12 sec. Time to 90 per cent first twitch depression after a single dose of DTC increased with increasing age (r = 0.65, p less than 0.01), and was 1.6 min (SEM +/- 0.3) in the 0-1 yr group, 1.9 +/- 0.3 min (1-3 yr), and 5.2 +/- 1.2 min (3-10 yr). Time to ten per cent spontaneous recovery after single dose DTC was shorter in older individuals (r = 0.40, p less than 0.05), being 36.4 +/- 5.1 min in infants 0-1 yr, 30.6 +/- 4.6 min (1-3 yr), and 24.0 +/- 2.7 min (3-10 yr). Priming with pancuronium accelerated the onset significantly in all age groups with 90 per cent T1 depression occurring at 0.7 +/- 0.1 min (0-1 yr), 0.9 +/- 0.1 min (1-3 yr), and 2.1 +/- 0.6 min (3-10 yr). However, priming delayed recovery, especially in infants.(ABSTRACT TRUNCATED AT 250 WORDS)     

Plasma concentrations of fentanyl in infants,children and adults

To evaluate whether there are age-related differences in the plasma concentration-vs-time course of fentanyl, the authors administered fentanyl to seven infants (3-10 months), seven children (1-9 years) and seven adults (18-41 years). Anaesthesia was induced with thiopentone, nitrous oxide, and pancuronium; following tracheal intubation, fentanyl (approximately 30 micrograms X kg-1 for infants and children, 20 micrograms X kg-1 for adults) was administered as a 2-min IV infusion. Anaesthesia was maintained with nitrous oxide, pancuronium, and morphine sulphate as clinically indicated. Plasma samples were obtained for 4 h and fentanyl concentrations determined by radioimmunoassay. Plasma concentrations per microgram X kg-1 fentanyl administered were lowest in infants 4-10 and 60-240 min after the start of the 2-min infusion; values for children were lower than those for adults 4, 180 and 210 min after the start of the 2-min infusion. These findings are consistent with the authors' clinical observation that infants tolerate larger doses of fentanyl than do adults.     

Rocuronium in infants, children and adults during balanced anaesthesia

We studied 20 infants, 20 children and 20 adults during balanced anaesthesia to compare the neuromuscular blocking effects of rocuronium in these age groups. Neuromuscular function was recorded by adductor pollicis emg and a cumulative log-probit dose-response curve of rocuronium was established. Thereafter, full spontaneous recovery of the neuromuscular function was recorded. Onset time of the first dose of rocuronium was shorter in children than in infants or adults. The potency of rocuronium was greatest in infants and least in children; the ED₅₀ doses (mean ± SD) being 149 ± 36 μg˙kg^?1 in infants, 205 ± 52 μg˙kg^?1 in children and 169 ± 47 μg˙kg^?1 in adults (P<0.05 between infants and children) and the ED₉₅ doses being 251 ± 73 μg˙kg^?1, 409 ± 71 μg˙kg^?1 and 350 ± 77 μg˙kg^?1, respectively (P<0.05 between all groups). The emg recovery following an average 94.5 ± 4.8% neuromuscular blockade established by rocuronium was roughly similar in all study groups. Thus, one ED₉₅ dose of rocuronium, unlike vecuronium, acts as an intermediate-acting agent in all age groups.     

Airway management and anesthesia in neonates, infants and children during endolaryngotracheal surgery

BACKGROUND: Endolaryngotracheal surgery in neonates, infants and children poses a big challenge for both anesthesiologist and surgeon. The narrowness of the airways and the great variability of the pathological lesions necessitate close collaboration between the surgical and the anesthesia team to provide optimal operating conditions and ensure adequate ventilation and oxygenation. METHODS: Sixty-two anesthetic records of endolaryngotracheal surgical procedures in neonates, infants and children with ASA physical status 1-3 were analyzed retrospectively. Anesthesia was administered as total intravenous anesthesia; propofol supplemented with remifentanil. Ventilation was performed as supraglottic, superimposed high-frequency jet ventilation via jet laryngoscope with integrated jet nozzles. RESULTS: Age was 58.93 (SD 35.40) months, range 3 weeks to 14 years; body weight 17.83 (SD 8.79) kg, range 2.4-50 kg. The capillary pCO(2) 5 min after the start of the surgical procedure (n = 62) was 40.01 (SD 7.71) mmHg and after 20 min (n = 24) 41.77 (SD 7.12) mmHg. No hypoxemia (oxygen saturation <90%) developed. All patients were hemodynamically stable during jet ventilation. Barotrauma or gas insufflation in the stomach did not occur. No perioperative tracheostomy was necessary. Laryngospasm occurred in one child during emergence from anesthesia. Four infants received postoperative conventional respirator therapy in the ICU overnight. CONCLUSIONS: Supraglottic superimposed high-/low-frequency jet ventilation via jet laryngoscopes with integrated jet nozzles is a minimally invasive ventilation technique for neonates, infants and children in endolaryngotracheal surgery, which allows an unimpaired operating field for the surgeon especially in LASER surgery.     

Complications of circumcision in male neonates, infants and children: a systematic review

Background

Approximately one in three men are circumcised globally, but there are relatively few data on the safety of the procedure. The aim of this paper is to summarize the literature on frequency of adverse events following pediatric circumcision, with a focus on developing countries.

Methods

PubMed and other databasess were searched with keywords and MeSH terms including infant/newborn/pediatric/child, circumcision, complications and adverse events. Searches included all available years and were conducted on November 6^th 2007 and updated on February 14th 2009. Additional searches of the Arabic literature included searches of relevant databases and University libraries for research theses on male circumcision. Studies were included if they contained data to estimate frequency of adverse events following neonatal, infant and child circumcision. There was no language restriction. A total of 1349 published papers were identified, of which 52 studies from 21 countries met the inclusion criteria. The Arabic literature searches identified 46 potentially relevant papers, of which six were included.

Results

Sixteen prospective studies evaluated complications following neonatal and infant circumcision. Most studies reported no severe adverse events (SAE), but two studies reported SAE frequency of 2%. The median frequency of any complication was 1.5% (range 0-16%). Child circumcision by medical providers tended to be associated with more complications (median frequency 6%; range 2-14%) than for neonates and infants. Traditional circumcision as a rite of passage is associated with substantially greater risks, more severe complications than medical circumcision or traditional circumcision among neonates.

Conclusions

Studies report few severe complications following circumcision. However, mild or moderate complications are seen, especially when circumcision is undertaken at older ages, by inexperienced providers or in non-sterile conditions. Pediatric circumcision will continue to be practiced for cultural, medical and as a long-term HIV/STI prevention strategy. Risk-reduction strategies including improved training of providers, and provision of appropriate sterile equipment, are urgently needed.     

Minimum alveolar concentration of desflurane and hemodynamic responses in neonates, infants, and children.

We sought to determine the minimum alveolar concentration (MAC) and hemodynamic responses to desflurane in 72 fasting and unpremedicated full-term neonates, infants, and children up to 12 yr of age. The patients were divided into six groups (n = 12) according to age. After awake tracheal intubation, neonates were anesthetized with desflurane in oxygen and air. Infants greater than 1 month of age and all older children were anesthetized with desflurane in 100% oxygen, and their tracheas were intubated without muscle relaxation. MAC was determined using the "up-and-down technique" and logistic regression. Heart rate and systolic arterial pressure were recorded awake, at approximately 1 MAC desflurane before skin incision and at approximately 1 MAC during the peak hemodynamic responses to skin incision. We found that the relationship between MAC (mean +/- standard deviation) as determined by the up-and-down technique and age was quadratic, reaching a maximum value in infants 6-12 months of age: in neonates 0-1 month MAC was 9.16 +/- 0.02%, in infants 1-6 months 9.42 +/- 0.06%, in infants 6-12 months 9.92 +/- 0.44%, in children 1-3 yr 8.72 +/- 0.59%, in children 3-5 yr 8.62 +/- 0.45%, and in children 5-12 yr 7.98 +/- 0.43%. MAC values obtained using logistic regression were similar. Heart rate decreased an average of 16% before skin incision in infants 6-12 months of age and children 1-3 and 3-5 yr of age when compared to awake values (P less than 0.025) but did not change significantly in the remaining three groups.(ABSTRACT TRUNCATED AT 250 WORDS)     

Carbon dioxide elimination during total cardiopulmonary bypass in infants and children

The authors measured the rate of carbon dioxide elimination (VCO2) in 25 pediatric patients (age 2 days to 9 yr) during total cardiopulmonary bypass at average venous blood temperatures ranging from 19.5 to 35.9 degrees C. A multiplexed mass spectrometer was connected to the gas inlet and exhaust ports of the bubble oxygenator, and the gas-phase Fick principle was used to determine VCO2. A curvilinear relationship was found between log VCO2 and venous blood temperature, and a quadratic regression equation (r2 = 0.74) was fit to the data. Q10 (the ratio of VCO2 before and after a 10 degree C temperature change) was estimated to be 2.7 or 3.0, depending on the analytic method used. Venous blood temperature as a predictor variable explained a greater proportion of the variability of log VCO2 than did nasopharyngeal or rectal temperatures. Analysis of covariance revealed that total circulatory arrest during bypass (utilized in 10 patients for 34 +/- 4 min, mean +/- SEM) affected the relationship of venous blood temperature with log VCO2, by increasing the y-intercept (P = .008) but not the slope. These data, with associated 95% prediction intervals, define the expected CO2 elimination rates at various temperatures during standard bypass conditions in our patients. Real-time measurement of VCO2 using mass spectrometry can be a useful routine monitor during CPB that may help to assess patient metabolic function, adequacy of perfusion, and oxygenator performance.     

Experience with a total muscle-sparing approach for thoracotomies in neonates, infants, and children.

We have adopted a total muscle-sparing technique for thoracotomies in infants and children. The technique preserves the latissimus dorsi and serratus anterior muscles and provides excellent exposure for most thoracic and mediastinal operations. Thirty-two such procedures have been performed with only one complication, a small wound seroma. Use of this technique may not only decrease postoperative pain and splinting, but may decrease the incidence of scoliosis and muscle dysfunction found in children having undergone thoracotomies as infants.     

Uptake and elimination of isoflurane and halothane by children and adults

The rate of increase of alveolar concentrations (FA/FI) of isoflurane and halothane was studied in children and adults during general anaesthesia and controlled ventilation. After 30 min of body equilibrium, elimination curves of the volatile anaesthetics were determined by measurement of alveolar (FA/FA0; infrared technique) and venous concentrations (gas chromatography). The distribution and elimination half-times (t1/2 alpha, t1/2 beta), clearance (Cl), volume of central and peripheral compartment (V1, Vz) and the volume of distribution at steady state (Vss) were calculated from the intercepts and slopes of a two-compartment model. During the uptake of anaesthetic concentrations of isoflurane and halothane, the FA/FI ratio of each gas was found to rise significantly faster in children than in adults. The reason for the more rapid approach to equilibrium in children seems to be related to physiological differences. Irrespective of age, uptake of isoflurane was more rapid than that of halothane, as it is less soluble. Similarly, isoflurane was eliminated from the lung or blood faster than halothane. Moreover, anaesthetic wash-out in children differed from that in adults. In the paediatric age group t1/2 beta under isoflurane was shorter than in adults, whereas halothane excretion took longer in children. This could be accounted for by the larger volumes of distribution Vz and Vss in the young, due to higher organ affinity of halothane. From our data we conclude that age significantly affects uptake and elimination of volatile anaesthetics and the control of anaesthesia is easiest with isoflurane in paediatric patients.