A randomized multicenter study of remifentanil compared with halothane in neonates and infants undergoing pyloromyotomy. I. Emergence and recovery profiles.

UNLABELLED: Pyloric stenosis is sometimes associated with hemodynamic instability and postoperative apnea. In this multicenter study we examined the hemodynamic response and recovery profile of remifentanil and compared it with that of halothane in infants undergoing pyloromyotomy. After atropine, propofol, and succinylcholine administration and tracheal intubation, patients were randomized (2:1 ratio) to receive either remifentanil with nitrous oxide and oxygen or halothane with nitrous oxide and oxygen as the maintenance anesthetic. Pre- and postoperative pneumograms were done and evaluated by an observer blinded to the study. Intraoperative hemodynamic data and postanesthesia care unit (PACU) discharge times, PACU recovery scores, pain medications, and adverse events (vomiting, bradycardia, dysrhythmia, and hypoxemia) were recorded by the study's research nurse. There were no significant differences in patient age or weight between the two groups. There were no significant differences in hemodynamic values between the two groups at the various intraoperative stress points. The extubation times, PACU discharge times, pain medications, and adverse events were similar for both groups. No patient anesthetized with remifentanil who had a normal preoperative pneumogram had an abnormal postoperative pneumogram, whereas three patients with a normal preoperative pneumogram who were anesthetized with halothane had abnormal pneumograms after. IMPLICATIONS: The use of ultra-short-acting opioids may be an appropriate technique for infants less than 2 mo old when tracheal extubation after surgery is anticipated.

A randomized multicenter study of remifentanil compared with halothane in neonates and infants undergoing pyloromyotomy. II. Perioperative breathing patterns in neonates and infants with pyloric stenosis.

UNLABELLED: Although former preterm birth infants are at risk for postoperative apnea after surgery, it is unclear whether the same is true of full-term birth infants. We evaluated the incidence of apnea in 60 full-term neonates and infants undergoing pyloromyotomy both before and after anesthesia. All subjects were randomized to a remifentanil- or halothane-based anesthetic. Apnea was defined by the presence of prolonged apnea (>15 s) or frequent brief apnea, as observed on the pneumocardiogram. Apnea occurred before surgery in 27% of subjects and after surgery in 16% of subjects, with no significant difference between subjects randomized to remifentanil or halothane anesthesia. This apnea was primarily central in origin, occurred throughout the recording epochs, and was associated with severe desaturation in some instances. Of the subjects with normal preoperative pneumocardiograms, new onset postoperative apnea occurred in 3 (23%) of 13 subjects who received halothane-based anesthetics versus 0 (0%) of 22 subjects who received remifentanil-based anesthetics (P = 0.04). Thus, postoperative apnea can follow anesthesia in otherwise healthy full-term infants after pyloromyotomy and is occasionally severe with desaturation. New-onset postoperative apnea was not seen with a remifentanil-based anesthetic. IMPLICATIONS: Abnormal breathing patterns can follow anesthesia in infants after surgical repair of pyloric stenosis. Occasionally, these patterns can be associated with desaturation. New-onset postoperative apnea was not seen with a remifentanil-based anesthetic.

Pharmacokinetics of remifentanil in anesthetized pediatric patients undergoing elective surgery or diagnostic procedures.

UNLABELLED: Remifentanil hydrochloride is an ultra-short-acting opioid that undergoes rapid metabolism by tissue and plasma esterases. We aimed to characterize the pharmacokinetics and determine the hemodynamic profile of remifentanil after a single-bolus dose in children aged 0 to 18 yr. Forty-two children undergoing elective surgical procedures received remifentanil 5 microg/kg infused over 1 min. Patients were divided into age groups as follows: young infants (< or =2 mo), older infants (> 2 mo to < 2 yr), young children (2 to < 7 yr), older children (7 to < 13 yr), adolescents (13 to < 16 yr), and young adults (16 to < 18 yr). Arterial blood samples were collected and analyzed by mass spectroscopy to determine remifentanil pharmacokinetic profiles. Hemodynamic measurements for remifentanil's effect were made after the infusion. Methods of statistical analysis included analysis of variance and linear regression, with significance at P < or = 0.05. Complete remifentanil pharmacokinetic data were obtained from 34 patients. The volume of distribution was largest in the infants < 2 mo (mean, 452 mL/kg) and decreased to means of 223 to 308 mL/kg in the older patients. There was a more rapid clearance in the infants < 2 mo of age (90 mL. kg(-1). min(-1)) and infants 2 mo to 2 yr (92 mL. kg(-1). min(-1)) than in the other groups (means, 46 to 76 mL. kg(-1). min(-1)). The half-life was similar in all age groups, with means of 3.4 to 5.7 min. Seven subjects (17%) developed hypotension related to the remifentanil bolus. Remifentanil showed an extremely rapid elimination similar to that in adults. The fast clearance rates observed in neonates and infants, as well as the lack of age-related changes in half-life, are in sharp contrast to the pharmacokinetic profile of other opioids. Remifentanil in a bolus dose of 5 microg/kg may cause hypotension in anesthetized children. IMPLICATIONS: The pharmacokinetics of remifentanil were studied in children from birth to 18 yr. Remifentanil was found to have age-related changes in clearance and volume of distribution, but not half-life. The increased clearance observed in young infants is in contrast to other opioids.

A randomized, double-blinded study of remifentanil versus fentanyl for tonsillectomy and adenoidectomy surgery in pediatric ambulatory surgical patients.

UNLABELLED: We compared, in a double-blinded manner, the anesthetic maintenance and recovery properties of remifentanil with a clinically comparable fentanyl-based anesthetic technique in pediatric ambulatory surgical patients. Anesthesia was induced with either halothane or sevoflurane and nitrous oxide and oxygen. Patients were randomized (computer generated) to receive either remifentanil or fentanyl in a blinded syringe with nitrous oxide and oxygen in one of four possibilities: halothane/remifentanil, halothane/fentanyl, sevoflurane/remifentanil or sevoflurane/fentanyl. In patients receiving remifentanil, a placebo bolus was administered, and a continuous infusion (0.25 microg. kg(-1). min(-1)) was begun. In patients receiving fentanyl, a bolus (2 microg/kg) was administered followed by a placebo continuous infusion. The time from discontinuation of the anesthetic to extubation, discharge from the postanesthesia care unit (PACU), and discharge to home, as well as pain scores, were assessed by a blinded nurse observer. Systolic blood pressure and heart rate were noted at selected times, and adverse events were recorded. Remifentanil provided faster extubation times and higher pain-discomfort scores. PACU and hospital discharge times were similar. There were no statistical differences among the groups for adverse events. There were statistically, but not clinically, significant differences in hemodynamic variables. We noted that continuous infusions of remifentanil were intraoperatively as effective as bolus fentanyl. Although patients could be tracheally extubated earlier with remifentanil, this did not translate to earlier PACU or hospital discharge times. In addition, remifentanil was associated with higher postoperative pain scores. The frequent incidence of postoperative pain observed in the postoperative recovery room suggests that better intraoperative prophylactic analgesic regimens for postoperative pain control are necessary to optimize remifentanil's use as an anesthetic for children. IMPLICATIONS: This is a study designed to examine the efficacy and safety of a short-acting opioid, remifentanil, when used in pediatric patients. The frequent incidence of postoperative pain observed in the postoperative recovery room suggests that better intraoperative prophylactic analgesic regimens for postoperative pain control are necessary to optimize remifentanil's use as an anesthetic for children.

The role of psychopathology in the parenting of drug-dependent women.

This paper explores the parenting of drug-dependent women and the contributions of comorbid psychopathology to their parenting. A sample of 32 children whose mothers were dependent on opioid drugs during pregnancy and 37 children whose mothers were not drug users were followed from birth to middle childhood. Multivariate regression analyses were conducted contrasting whether maternal substance abuse or psychopathology was more closely linked to parenting behaviors and continuity in parenting over time. Maternal drug dependence was related to whether mothers were able to remain primary caregivers for their children over time, even after controlling for psychopathology. Maternal drug use was related to unresponsive and negative parenting behavior during mother-infant interaction, but this relation was largely accounted for by the effects of comorbid maternal psychopathology on parenting, particularly symptoms of antisocial and related personality disorders. For those children whose mothers continued to care for them into middle childhood, perceptions of their mothers as rejecting were related to maternal antisocial personality and maternal depression. Substance-abuse treatment for women should be integrated with interventions addressing their mental health and parenting needs.

A randomized multicenter study of remifentanil compared with alfentanil, isoflurane, or propofol in anesthetized pediatric patients undergoing elective strabismus surgery.

Remifentanil hydrochloride is a new, ultrashort-acting opioid metabolized by nonspecific plasma and tissue esterases. We conducted this multicenter study to examine the hemodynamic response and recovery profile of premedicated children undergoing strabismus repair who were randomly assigned to receive one of four treatment drugs (remifentanil, alfentanil, isoflurane, or propofol) along with nitrous oxide and oxygen for maintenance of anesthesia. Induction of anesthesia was by nitrous oxide, oxygen, and halothane or nitrous oxide, oxygen, and propofol. Anesthesia was then maintained with remifentanil 1.0 microgram/kg over 30-60 s, followed by a constant infusion of 1.0 microgram.kg-1.min-1, alfentanil 100 micrograms/kg bolus followed by a constant infusion of 2.5 micrograms.kg-1.min-1, propofol 2.5 mg/kg bolus followed by a constant infusion of 200 micrograms.kg-1.min-1, or isoflurane 1.0 minimum alveolar anesthetic concentration. The infusions of the anesthetics and the administration of the inhaled gases were adjusted clinically by predetermined protocols. Elapsed time intervals from the end of surgery to the time the patients were tracheally extubated and displayed purposeful movement, as well as the time the patients met the postanesthesia care unit (PACU) and hospital discharge times, were recorded. Heart rate and systolic and diastolic blood pressure were measured at fixed intervals. In addition, cardiovascular side effects (bradycardia, hypotension, and hypertension) as well as vomiting, pruritus, agitation, and postoperative hypoxemia were also noted. There were no significant differences in patient demographics among the treatment groups. There was no difference in the early recovery variables (times to extubation and purposeful movement) or the times to PACU and hospital discharge among groups. There were significant differences in side effects among the groups. Patients who received remifentanil had higher PACU objective pain-discomfort scores than those who received alfentanil and propofol. Patients anesthetized with alfentanil had a greater incidence in the use of naloxone and a greater incidence of postoperative hypoxemia compared with those anesthetized with remifentanil. The incidence of postoperative hypoxemia was the same for remifentanil, propofol, and isoflurane groups. There were no significant differences in the incidence of emesis among the four groups, and all four groups had similar hemodynamic profiles. We conclude that remifentanil appears to be an effective drug for anesthesia. Its hemodynamic and recovery profile appear similar to other comparable drugs. Based on previous pharmacokinetic studies, the 1.0 microgram.kg-1.min-1 infusion may be twice the 50% effective dose observed in adults. In this study, the relative "overdose" of remifentanil was well tolerated and did not prolong recovery.

Naloxone-induced and spontaneous reversal of depressed ventilatory responses to hypoxia during and after continuous infusion of remifentanil or alfentanil.

Remifentanil is a new mu opioid analgesic of the synthetic phenylpiperidine class. It has an extremely short half-life (10-20 min) due to its breakdown by nonspecific estrases. We studied the effects of continuous infusion of remifentanil, compared with alfentanil, on the respiratory response to hypoxia. In addition, we examined the efficacy of naloxone to reverse remifentanil-mediated depression of respiration. Spontaneous recovery after the end of the infusion was also assessed. Twelve adult males participated in the study. On three sessions, separated by 7 to 14 days, the participants received continuous infusion over 240 min of alfentanil (0.5 microgram/kg/min), remifentanil (0.025 microgram/kg/min) or remifentanil (0.1 microgram/kg/min). Naloxone (6 micrograms/kg) was given at 95 min. On a fourth session, remifentanil (0.1 microgram/kg/min) was infused and placebo was given instead of naloxone. Base-line hypoxic challenge was induced at 30 min before starting the infusion. Eight hypoxic challenges were conducted at 10 min after starting the infusion and half-hourly thereafter. Two postinfusion challenges were performed at 250 and 280 min. The slope (liter/min/SPO2) of the ventilatory response and the predicted ventilation at SPO2 of 80% (VE80) (liter/min) significantly decreased during the infusion with remifentanil and alfentanil. A significant difference was noted between the two doses of remifentanil. Naloxone administration was associated with reversal of the depressed hypoxic responses during the infusion of alfentanil and the low dose of remifentanil. Termination of remifentanil infusion was associated with a prompt spontaneous recovery of the blunted hypoxic responses that was not detected with alfentanil.(ABSTRACT TRUNCATED AT 250 WORDS)