Christian Zaarour

Development of Acute Opioid Tolerance During Infusion of Remifentanil for Pediatric Scoliosis Surgery

We tested the hypothesis that continuous intraoperative infusion of remifentanil is associated with the development of clinically relevant acute opioid tolerance in adolescents undergoing scoliosis surgery. Thirty adolescents were randomly assigned to receive an intraoperative analgesic regimen consisting of continuous remifentanil infusion or intermittent morphine alone. Postoperative analgesic consumption was assessed with a patient-controlled analgesia device that was used to self-administer morphine. Cumulative postoperative morphine consumption, pain scores, and sedation scores were recorded by a blinded investigator every hour for the first 4 h postoperatively and then every 4 h for a total of 24 h. Cumulative morphine consumption in the remifentanil group was significantly more than that in the morphine group at each time point in the initial 24 h after surgery (P < 0.0001). At 24 h after surgery, cumulative morphine consumption was 30% greater in the remifentanil group (1.65 ± 0.41 mg/kg) than in the morphine group (1.27 ± 0.32 mg/kg) (95% confidence interval for the difference, 0.11 to 0.65 mg/kg). Differences in pain and sedation scores were not statistically significant. These data suggest that intraoperative infusion of remifentanil is associated with the development of clinically relevant acute opioid tolerance in adolescents undergoing scoliosis surgery.

Intraoperative low-dose ketamine does not prevent a remifentanil-induced increase in morphine requirement after pediatric scoliosis surgery.

BACKGROUND: Remifentanil-based anesthesia is commonly used to facilitate neurophysiologic monitoring during pediatric scoliosis surgery. Acute opioid tolerance and/or hyperalgesia resulting from remifentanil-based anesthesia may involve activation of N-methyl-d-aspartate systems. We hypothesized that low-dose intraoperative infusion of the N-methyl-d-aspartate antagonist ketamine would suppress the development of tolerance and thereby decrease postoperative morphine consumption in children receiving remifentanil-based anesthesia for scoliosis surgery. METHODS: Thirty-four adolescents aged 12–18 yr scheduled for scoliosis surgery were randomly assigned to receive intraoperative low-dose ketamine (bolus dose of 0.5 mg/kg followed by continuous infusion of 4 &mgr;g · kg−1 · min−1) or an equal volume of saline during propofol/remifentanil anesthesia. Cumulative morphine consumption was assessed using a patient-controlled analgesia device for 72 h after surgery. Postoperative morphine consumption, pain scores at rest and during cough, and sedation scores were recorded by a blinded investigator every hour for the first 4 h, every 4 hours for 20 h, and then every 12 hours for 72 h. RESULTS: Cumulative morphine consumption at 24, 48, and 72 h after surgery did not differ significantly between groups (ketamine group: 1.57 ± 0.56, 3.05 ± 1.14, and 4.46 ± 1.53 mg/kg; saline group: 1.60 ± 0.53, 2.87 ± 1.05, and 4.11 ± 1.71 mg/kg, respectively). No differences in pain or sedation scores were found. The duration of anesthesia was similar in the two groups. CONCLUSIONS: These data do not support the use of intraoperative low-dose ketamine to prevent the development of remifentanil-induced acute opioid tolerance and/or hyperalgesia during pediatric scoliosis surgery.

Neurophysiological changes in deformity correction of adolescent idiopathic scoliosis with intraoperative skull-femoral traction.

Study Design. Retrospective review of 36 consecutive patients undergoing coronal plane deformity correction with intraoperative skull-femoral traction between 2005 and 2008 with motor evoked potential (MEP)/somatosensory evoked potential monitoring. Objective. To determine the prevalence and significance of neurophysiological changes with intraoperative skull-femoral traction in adolescent idiopathic scoliosis. Summary of Background Data. Intraoperative skeletal traction can be associated with spinal cord stretching and ischemia with resultant electrophysiological changes. The prevalence and risks of such changes and their clinical significance is unknown. Methods. Thirty-seven procedures involving 36 patients (27 females and 9 males) with a mean age of 14.8 (12–18) years were divided into two groups on the basis of the presence (group 1, n = 18 procedures) or absence (group 2, n = 19) of significant MEP changes with surgery. They were compared with patients undergoing correction without traction (group 3). Results. Significant differences among the groups were observed in mean preoperative Cobb angle (86° vs. 70° vs. 59°), mean intraoperative posttraction Cobb angle (50.0° vs. 34.6°), traction index (0.41 vs. 0.50), flexibility index (0.14 vs. 0.27 vs. 0.25), and presence of primary lumbar curves (0% vs. 32% vs. 14%). Initial onset of MEP amplitude loss (group 1) occurred at a mean of 94 (1–257) minutes from the onset of surgery, was bilateral in 13 procedures, and improved at a mean of 5.5 (1–29) minutes after decreasing or removing the traction. At closure, complete bilateral recovery to baseline was observed in 10 procedures, recovery to >50% baseline in five, and recovery to <50% baseline in three procedures. There were no neurologic deficits in this series. Conclusion. Intraoperative traction is associated with frequent changes in MEP monitoring. The thoracic location of the major curve, increasing Cobb angle, and rigidity of major curve are significant risk factors for changes in MEP with traction. The presence of any MEP recordings irrespective of its amplitude at closure was associated with normal neurological function. Somatosensory evoked potential monitoring did not correlate with the traction induced MEP amplitude changes.

Pre-treatment with morphine does not prevent the development of remifentanil-induced hyperalgesia

Purpose: Remifentanil, an ultra short-acting opioid commonly used to supplement general anesthesia, is associated with the development of hyperalgesia that manifests clinically as an increase in postoperative analgesic requirement. This study involving adolescents undergoing scoliosis surgery evaluated whether pre-treatment with morphine prior to commencing remifentanil infusion would decrease the initial 24-hr morphine consumption and pain scores.Methods: Forty ASA 1–11 pediatric patients undergoing surgical correction of idiopathic scoliosis were recruited in a prospective, randomized, double-blind fashion to receive 150µg·kg−1 morphine or an equal volume saline prior to commencing remifentanil by infusion. The primary outcome was the initial 24-hr postoperative morphine consumption. Numeric rating scale (NRS) pain scores at rest and on coughing were recorded, as were scores for nausea, vomiting, and sedation and incidences of pruritus.Results: The groups were demographically similar. No differences were observed between groups vis-à-vis the initial 24-hr morphine consumption, NRS pain scores, sedation, nausea, or vomiting.Conclusion: Pre-treatment with 150µg·kg−1 morphine did not decrease the initial 24-hr morphine consumption in adolescents who received remifentanil by infusion for surgical correction of idiopathic scoliosis.RésuméObjectif: Le rémifentanil est un opioïde à action extra-courte couramment utilisé comme adjuvant à une anesthésie générate. II est associé à l’apparition d’hyperalgéesie, laquelle prend la forme clinique d’une augmentation des besoins analgésiques postopératoires. Cette étude portait sur des adolescents subissant une chirurgie de correction de scoliose. Son objectif était de déterminer si un prétraitement à la morphine avant la perfusion de rémifentanil diminuerait la consommation de morphine et l’intensite de la douleur dans les 24 premières heures suivant l’opération.Méthode: Quarante adolescents ASA 1–11 subissant une chirurgie corrective pour une scoliose idiopathique ont été recrutés de façon prospective, randomisée et à double insu, à recevoir de la morphine 150 µg·kg−1 ou un volume équivalent de sérum physiologique avant le début d’une perfusion de rémifentanil. La consommation de morphine durant les 24 premières heures postopératoires était l’objectif primaire. Les scores de douleur sur l’échelle d’évaluation numérique (EEN) au repos et en toussant ont été notes, de même que les scores concernant les nausées, les vomissements, la sédation et l’aptparition de prurit.Résultats: Les groupes étaient semblables d’un point de vue démographique. Aucune différence n’a été observée entre les groupes quant à la consommation de morphine des 24 premières heures, les scores de douleur EEN, la sédation, les nausées ou les vomissements.Conclusion: Le prétraitement avec 150µ·kg−1 de morphine n’a pas diminué la consommation de morphine durant les 24 premières heures postopératoires chez des adolescents recevant une perfusion de rémifentanil pour une chirurgie corrective d’une scoliose idiopathique.

Dose-dependent suppression of the electrically elicited stapedius reflex by general anesthetics in children undergoing cochlear implant surgery.

BACKGROUND: Cochlear implants stimulate the auditory nerve to enable hearing. Determining appropriate upper and lower limits of stimulation is essential for successful cochlear implantation. The intraoperative evoked stapedius reflex threshold (ESRT) and evoked compound action potential (ECAP) are commonly used to determine the limits of implant stimulation. In this study, we evaluated the dose-related effects of sevoflurane, desflurane, isoflurane, and propofol on the intraoperative ESRT and ECAP. METHODS: Forty-four children aged 6 mo to 17 yr undergoing cochlear implantation were recruited. Each child was randomly assigned to receive sevoflurane, desflurane, isoflurane, or propofol. Evoked responses were measured by a blinded investigator at end-tidal anesthetic concentrations corresponding to 0, 0.75, and 1.5 age-adjusted minimum alveolar concentration administered in random sequence and at targeted blood concentrations of propofol of 0, 1.5, and 3.0 &mgr;g/mL. Data were analyzed using one-way repeated-measures analysis of variance. P < 0.05 was considered statistically significant. RESULTS: The ESRT increased dose dependently with increasing volatile anesthetic concentration (P < 0.01). The stapedius reflex was completely abolished by volatile anesthesia in more than half of children. Propofol minimally affected the ESRT. In contrast, the ECAP was unaffected by anesthesia. CONCLUSIONS: Volatile anesthetics suppress the stapedius reflex in a dose-dependent manner, suggesting that ESRT measurements acquired during volatile anesthesia will overestimate the maximum comfort level, which may cause discomfort postoperatively and adversely affect the child’s adaptation to the implant. We advise against the use of volatile anesthetics for measurement of the stapedius reflex threshold during cochlear implant surgery.

Midline posterior glossectomy and lingual tonsillectomy in obese and nonobese children with down syndrome: Biomarkers for success

To examine outcomes following midline posterior glossectomy (MPG) plus lingual tonsillectomy (LT) for the treatment of significant obstructive sleep apnea (OSA) in children with Down syndrome (DS).

Effect of low-dose ketamine on voltage requirement for transcranial electrical motor evoked potentials in children.

Study Design. Randomized controlled trial. Objective. To determine the effect of low-dose ketamine on the voltage needed to elicit maximal amplitude of the motor-evoked response to transcranial electrical stimulation during propofol/remifentanil anesthesia in children undergoing scoliosis surgery. Summary of Background Data. Motor-evoked potentials (MEPs) are increasingly used to assess the integrity of motor pathways during surgery. Whereas most general anesthetics depress MEP amplitude, the effect of ketamine has been variable, ranging from little or no reduction to an increase in amplitude, suggesting that ketamine may be useful as an agent to facilitate MEP monitoring. We tested the hypothesis that low-dose ketamine would reduce the voltage required to elicit maximal amplitude of the motor-evoked response to transcranial electrical stimulation during propofol/remifentanil anesthesia. Methods. Thirty-four patients 12 to 16 years of age undergoing posterior instrumentation for correction of idiopathic scoliosis were randomly assigned to receive low-dose ketamine (0.5 mg/kg bolus, followed by 4 &mgr;g/kg/min infusion) or an equal volume of saline. Anesthesia was maintained using a mixture of 30% oxygen in air, continuous infusion of propofol at a rate of 100 to 150 &mgr;g/kg per min, and continuous infusion of remifentanil. Myogenic motor-evoked responses to transcranial electrical stimulation of the motor cortex were recorded. The minimum voltage required to elicit maximal amplitude of the MEP response was determined. Voltage requirements were compared using the Mann-Whitney U rank sum test. P < 0.05 was considered statistically significant. Results. No significant difference was found in the minimal voltage needed to elicit maximum amplitude of the MEP response. Median (range) voltage requirements in the ketamine and control groups were 227 V (range, 160–350 V) and 215 V (range, 150–300 V), respectively. Conclusion. Addition of low-dose ketamine to propofol/remifentanil anesthesia does not significantly reduce the voltage needed to elicit maximum amplitude of the motor-evoked response to transcranial electrical stimulation.

Pediatric reference intervals for lymphocyte vitamin C (ascorbic acid)

OBJECTIVE To establish pediatric reference intervals for lymphocyte vitamin C. DESIGN AND METHODS This was a prospective study of 194 well children aged 0-7 years old of mixed ethnicity who had blood drawn for the purpose of this study. Blood was collected during elective surgery under general anesthesia and lymphocytes isolated and stored as frozen ascorbic acid lymphocyte lysates for later HPLC analysis by previously described methodology. Reference intervals were established according to the Clinical and Laboratory Standards Institute (CLSI) and the International Federation of Clinical Chemistry (IFCC) guidelines (C28-A3). Horn-Pesce robust method was used to estimate the 95% confidence interval and 95% reference interval. RESULTS Reference intervals were independent of age or gender and shown to be 12.9-52.8 μg/10(8) cells (lymphocytes). CONCLUSION We have defined pediatric reference ranges for lymphocyte vitamin C in healthy, fasted children at a relevant age group (0-7 years). The new reference interval can now be used to more reliably explore possible implications of variation of vitamin C levels on bleeding and other clinical signs.

Does remifentanil-based anesthesia cause acute opioid tolerance?

INTRODUCTION: The development of acute opioid tolerance with potent short-acting opioids such as remifentanil is described in animal studies, but the results of clinical studies are controversial. Remifentanil-based anesthesia is commonly used at our hospital to facilitate neurophysiologic monitoring during scoliosis surgery. We compared postoperative morphine consumption and visual analogue pain scores in children receiving remifentanil/propofol or morphine/propofol anesthesia for scoliosis surgery.