No abstract

Aim Large interindividual variability in morphine disposition could contribute to unpredictable variability in morphine analgesia and adverse events. Caucasian children have more adverse effects and slower morphine clearance than African–American children. To study variations in intravenous morphine pharmacokinetics in children, we examined the influence of genetic polymorphisms in OCT1 Methods In 146 children undergoing adenotonsillectomy, 146 concentration–time profiles (2–4 measurements per patient) were available. Population pharmacokinetic ana lysis characterized the profiles in NONMEM® and tested OCT1 variants as covariates. Results Allometrically scaled post hoc Bayesian morphine clearance in homozygotes of loss-of-function OCT1 variants (n = 9, OCT1*2–*5/*2–*5 was significantly lower (20%) than in wild-type (n = 85, OCT1*1/*1) and heterozygotes (n = 52, OCT1*1/*2–*5; p < 0.05). Conclusion Besides bodyweight, OCT1 genotypes play a significant role in intravenous morphine pharmacokinetics. Relatively high allelic frequencies of defective OCT1 variants among Caucasians may explain their lower morphine clearance and possibly higher frequencies of adverse events compared with African–American children.

OIRD is an important, albeit mostly preventable, complication of opioid therapy in children. Naloxone use can be used as a measure to track opioid safety in children, identify contributing factors, and formulate preventive strategies to reduce the risk for OIRD.

Background General anesthesia during infancy is associated with neurocognitive abnormalities. Potential mechanisms include anesthetic neurotoxicity, surgical disease, and cerebral hypoxia–ischemia. This study aimed to determine the incidence of low cerebral oxygenation and associated factors during general anesthesia in infants. Methods This multicenter study enrolled 453 infants aged less than 6 months having general anesthesia for 30 min or more. Regional cerebral oxygenation was measured by near-infrared spectroscopy. We defined events (more than 3 min) for low cerebral oxygenation as mild (60 to 69% or 11 to 20% below baseline), moderate (50 to 59% or 21 to 30% below baseline), or severe (less than 50% or more than 30% below baseline); for low mean arterial pressure as mild (36 to 45 mmHg), moderate (26 to 35 mmHg), or severe (less than 25 mmHg); and low pulse oximetry saturation as mild (80 to 89%), moderate (70 to 79%), or severe (less than 70%). Results The incidences of mild, moderate, and severe low cerebral oxygenation were 43%, 11%, and 2%, respectively; mild, moderate, and severe low mean arterial pressure were 62%, 36%, and 13%, respectively; and mild, moderate, and severe low arterial saturation were 15%, 4%, and 2%, respectively. Severe low oxygen saturation measured by pulse oximetry was associated with mild and moderate cerebral desaturation; American Society of Anesthesiology Physical Status III or IV versus I was associated with moderate cerebral desaturation. Severe low cerebral saturation events were too infrequent to analyze. Conclusions Mild and moderate low cerebral saturation occurred frequently, whereas severe low cerebral saturation was uncommon. Low mean arterial pressure was common and not well associated with low cerebral saturation. Unrecognized severe desaturation lasting 3 min or longer in infants seems unlikely to explain the subsequent development of neurocognitive abnormalities.

Background Effective perioperative analgesia is lacking for children owing to interindividual variations and underdosing of opioids caused by fear of adverse effects. We investigated the role of COMT SNPs on postoperative pain management in children. Methods One hundred and forty nine children undergoing adenotonsillectomy were enrolled. The associations of four COMT SNPs (rs6269, rs4633, rs4818 and rs4680) with postoperative pain were analyzed and outcome measures included maximum pain scores, need for postoperative opioid interventions and postoperative morphine requirements. Results We detected an association of postoperative opioid intervention need with all four COMT SNPs. Minor allele carriers of COMT SNPs were approximately three-times more likely to require analgesic interventions than homozygotes of major alleles (p-value range: 0.0031–0.0127; odds ratio range: 2.6–3.1). In addition, significant association was detected between maximum Face, Leg, Activity, Consolability, Cry (FLACC) pain scores and three COMT SNPs (rs6269, rs4633 and rs4680). Haplotype 1 (ATCA: 51.3%) and Haplotype 2 (GCGG: 36.2%) are more frequent. Haplotype 2 was associated with higher odds of intravenous analgesic intervention need in postanesthesia recovery unit with an odds ratio of 2.6 (95% CI: 1.2–5.4; p-value = 0.022). Conclusion COMT SNPs may play a significant role in interindividual variation in postoperative pain perception and postoperative morphine requirements in children.

This study demonstrates that child's sex influences morphine's dose response and adverse effects. White girls have an unequal burden with higher incidences of PONV, RD, and prolonged PACU stays following tonsillectomy from PONV and RD as total morphine doses are increased.

SAH during pregnancy results from a range of etiologies, and is less likely to be because of a cerebral aneurysm than SAH occurring in the nonpregnant patient. Peripartum SAH frequently occurs in the setting of hypertensive disorders.

Background Intraoperative isoelectric electroencephalography (EEG) has been associated with hypotension and postoperative delirium in adults. This international prospective observational study sought to determine the prevalence of isoelectric EEG in young children during anesthesia. We hypothesized that the prevalence of isoelectric events would be common worldwide and associated with certain anesthetic practices and intraoperative hypotension. Methods. Fifteen hospitals enrolled patients age ≤ 36 months for surgery using sevoflurane or propofol anesthetic. Frontal 4-channel EEG was recorded for isoelectric events. Demographics, anesthetic, emergence behavior, and Pediatric Quality of Life (PedsQL) variables were analyzed for association with isoelectric events. Results. Isoelectric events occurred in 32% (206/648) of patients, varied significantly among sites (9-88%), and were most prevalent during pre-incision (117/628, 19%) and surgical maintenance (117/643, 18%). Isoelectric events were more likely with [odds ratio-OR (95% confidence interval-CI)] infants &lt; 3 months [4.4 (2.57-7.4) p&lt;0.001], endotracheal tube use [1.78 (1.16-2.73) p=0.008], propofol bolus for airway placement after sevoflurane induction [2.92 (1.78-4.8) p&lt;0.001], and less likely with use of muscle relaxant for intubation [0.67 (0.46-0.99) p=0.046]. Expired sevoflurane was higher in patients with isoelectric events [mean difference (95% CI)] during pre-incision [0.2% (0.1, 0.4) p=0.005] and surgical maintenance [0.2% (0.1, 0.3) p=0.002]. Isoelectric events were associated with moderate (8/12, 67%) and severe hypotension (11/18, 61%) during pre-incision [OR: 4.6 (1.30-16.1) p=0.018; 3.54 (1.27, 9.9) p=0.015] and surgical maintenance [OR: 3.64 (1.71-7.8) p=0.001; 7.1 (1.78- 28.1) p=0.005], and lower PedsQL scores [median of differences (95% CI)] at baseline in patients 0-12 [-3.5 (-6.2, -0.7) p=0.008] and 25-36 months [-6.3 (-10.4, -2.1) p=0.003] and 30-day follow-up in 0-12 months [-2.8 (-4.9, 0) p=0.036]. Isoelectric events were not associated with emergence behavior or anesthetic (sevoflurane vs propofol). Conclusions. Isoelectric events were common worldwide in young children during anesthesia and associated with age, specific anesthetic practices, and intraoperative hypotension.