TAOK3, a novel genome-wide association study locus associated with morphine requirement and postoperative pain in a retrospective pediatric day surgery population.

Candidate gene studies have revealed limited genetic bases for opioid analgesic response variability. Genome-wide association studies facilitate impartial queries of common genetic variants, allowing identification of novel genetic contributions to drug effect. Illumina (Illumina Inc, San Diego, CA, USA) single nucleotide polymorphism (SNP) arrays were used to investigate SNP associations with total morphine requirement as a quantitative trait locus and with postoperative pain in a retrospective population of opioid-naïve children ages 4-18years who had undergone day surgery tonsillectomy and adenoidectomy. In an independent replication cohort, significant genome-wide association studies-identified SNPs were assayed using TaqMan probes. Among 617 comprehensively phenotyped children, the 277 subjects of European Caucasian (EC) ancestry demonstrated nominal association between morphine dose and a series of novel SNPs (top rs795484, P=1.01 × 10(-6) and rs1277441, P=2.77 × 10(-6)) at the TAOK3 locus. Age, body mass index, and physical status were included covariates. Morphine requirement averaged 132.4 µg/kg (SD 40.9). Each minor allele at rs795484 (guanine [G]>adenine [A]) contributed +17.6 µg/kg (95% confidence interval [CI] 10.7-24.4) to dose. Effect direction and magnitude were replicated in an independent cohort of 75 EC children (P<0.05). No association with morphine dose was detected in African Americans (AA) (n=241). Postoperative pain scores ≥ 7/10 were associated with rs795484 (G>A) in the EC cohort (odds ratio 2.35, 95% CI 1.56-3.52, P<0.00005) and this association replicated in AA children (odds ratio 1.76, 95% CI 1.14-2.71, P<0.01). Variants in TAOK3 encoding the serine/threonine-protein kinase, TAO3, are associated with increased morphine requirement in children of EC ancestry and with increased acute postoperative pain in both EC and AA subjects.

Evaluation of central venous pressure monitoring in children undergoing craniofacial reconstruction surgery.

BACKGROUND: Massive hemorrhage during craniofacial surgery is common and often results in hypovolemia and hypotension. We conducted this study to assess the effect of the addition of routine central venous pressure (CVP) monitoring on the incidence of intraoperative hypotension and to evaluate the relationship between CVP and hypotension in this population. METHODS: Data from our prospective craniofacial perioperative registry for children 6 to 24 months of age undergoing cranial vault reconstruction with CVP monitoring were compared with data from a historical cohort without CVP monitoring. The incidence and duration of hypotension in the 2 cohorts were compared. In the cohort of subjects with CVP monitoring who experienced hypotension, CVP at the onset of hypotension (T0) was compared with CVP 5 minutes before (T-5) and 5 minutes after (T+5) the onset of hypotension and with the baseline CVP. The amount of time spent at various CVP levels below the baseline, and the associated incidence of hypotension were also determined. RESULTS: Data from 57 registry subjects were compared with data from 115 historical cohort subjects. The median total duration of hypotension in subjects experiencing hypotension was 278 seconds in the CVP cohort versus 165 seconds in the historical cohort; the median difference was 98 seconds (95% confidence interval [CI], -45 to 345 seconds). The incidence of hypotension was 18% in the CVP cohort versus 21% in the historical cohort; the difference in the incidence of hypotension was -3% (95% CI, -10% to 15%). Analysis using a linear mixed effects model showed a significant decrease in CVP from T-5 to T0 (95% CI, -0.9 to -2.2 mm Hg), a significant increase in CVP from T0 to T+5 (95% CI, 1.0-2.4 mm Hg), no significant difference in CVP between T-5 and T+5 (95% CI, -0.9 to 0.9 mm Hg), and a significant decrease in CVP from baseline to T0 (95% CI, -3.4 to -2.1 mm Hg). CVP at T0 was less than the baseline CVP in 97% of hypotensive episodes. When all cases were examined, CVP was ≥3 mm Hg below the baseline for 16% of the total time studied, with an associated incidence of hypotension of 2%. CONCLUSIONS: The implementation of routine CVP monitoring was not associated with a decreased incidence and likely was not associated with a decreased duration of hypotension in this population experiencing massive hemorrhage. Hypotension was associated with a decrease in CVP, and resolution of hypotension was associated with an increase in CVP to prehypotensive levels. However, significant decreases in CVP below the baseline were common and usually not associated with hypotension. The routine use of CVP monitoring in these children is of questionable utility as a means to decrease the incidence and duration of hypotension.

Absence of tachycardia during hypotension in children undergoing craniofacial reconstruction surgery.

BACKGROUND: Tachycardia is a baroreceptor-mediated response to hypotension. Heart rate (HR) behavior in the setting of hypotension in anesthetized children is not well characterized. We conducted this study to assess the relationship between HR and hypotension in a population of anesthetized children experiencing massive blood loss. Our primary hypothesis was that HR would be increased with the onset of hypotension associated with hypovolemia in comparison with time points without hypotension. METHODS: We performed a query of our prospective craniofacial perioperative registry for children younger than 24 months who underwent cranial vault reconstruction surgery. Demographic and perioperative data were extracted, and the intraoperative blood loss was calculated. Vital signs were extracted from our computerized anesthesia record and analyzed. Hypotension was defined as a mean arterial blood pressure <40 mm Hg for at least 3 computerized anesthesia record entries (captured every 15 seconds). The preoperative HR, the average HR over the entire intraoperative period, the HR at the onset of hypotension, and the HR 5 minutes before and 5 minutes after the hypotensive episode were compared. RESULTS: The registry query yielded data from 57 procedures. There were 29 episodes of hypotension occurring in 10 subjects. There was no significant difference in HR at the onset of hypotension (when mean arterial blood pressure decreased below 40 mm Hg) in comparison with the preoperative HR, the average intraoperative HR, or in comparison with 5 minutes before and 5 minutes after the episode of hypotension. CONCLUSIONS: In this study of anesthetized children younger than 24 months undergoing surgery with massive blood loss, hypotension was not associated with an increased HR. HR does not appear to be a useful indicator of hypovolemia in this population.

Perioperative morbidity in posterior cranial vault expansion: distraction osteogenesis versus conventional osteotomy.

BACKGROUND: The treatment of multisuture syndromic craniosynostosis is in evolution, with an increasing prevalence of reports on posterior vault expansion with distraction osteogenesis over conventional osteotomy. The purported benefits of distraction osteogenesis include less perioperative morbidity. The authors conducted this preliminary study to compare the perioperative course in children undergoing posterior cranial vault expansion with distraction osteogenesis versus conventional osteotomy. METHODS: A query was performed of the authors' institutional review board-approved, prospective, craniofacial registry for posterior cranial expansion between 2008 and 2011. Data collected included age, weight, diagnosis, surgical procedure and duration, perioperative laboratory data, number of perioperative blood donor exposures, length of intensive care unit and hospital stay, and intraoperative and postoperative complications. Data for conventional osteotomy and distraction osteogenesis were then compared. RESULTS: The registry query returned data from 25 subjects (16 with conventional osteotomy and nine with distraction osteogenesis). There were no significant differences in age or weight between the two groups. Mean total surgery time for conventional osteotomy was 239 ± 48 minutes versus 200 ± 70 minutes for distraction osteogenesis (p = 0.11). Intensive care unit stay was a median of 3.5 days with conventional osteotomy versus 4.0 days for distraction osteogenesis (p = 0.10). There was no statistically significant difference in median hospital length of stay, calculated blood loss in blood volumes, total perioperative blood donor exposures, intraoperative complications, or postoperative complications. CONCLUSIONS: The results from this review of the authors' early experience with posterior vault distraction osteogenesis suggest that distraction osteogenesis and conventional osteotomy have similar perioperative safety and morbidity profiles. These data may seem counterintuitive, and the perioperative course of children undergoing distraction osteogenesis is likely to improve as experience with distraction osteogenesis increases. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, II.

A prospective randomized equivalence trial of the GlideScope Cobalt® video laryngoscope to traditional direct laryngoscopy in neonates and infants.

BACKGROUND: Intubation in children is increasingly performed using video laryngoscopes. Many pediatric studies examine novice laryngoscopists or describe single patient experiences. This prospective randomized nonblinded equivalence trial compares intubation time for the GlideScope Cobalt® video laryngoscope (GCV, Verathon Medical, Bothell, WA) with direct laryngoscopy with a Miller blade (DL, Heine, Dover, NH) in anatomically normal neonates and infants. The primary hypothesis was that intubation times with GCV would be noninferior to DL. METHODS: Sixty subjects presenting for elective surgery were randomly assigned to intubation using GCV or DL. Intubation time, time to best view, percentage of glottic opening score, and intubation success were documented. We defined an intubation time difference of less than 10 s as clinically insignificant. RESULTS: There was no difference in intubation time between the groups (GCV median = 22.6 s; DL median = 21.4 s; P = 0.24). The 95% one-sided CI for mean difference between the groups was less than 8.3 s. GCV yielded faster time to best view (median = 8.1 s; DL 9.9 s; P = 0.03). Endotracheal tube passage time was longer for GCV (median = 14.3 s; DL 8.5 s; P = 0.007). The percentage of glottic opening score was improved with GCV (median 100; DL 80; P < 0.0001). CONCLUSIONS: Similar intubation times and success rates were achieved in anatomically normal neonates and infants with the GCV as with DL. The GCV yielded faster time to best view and better views but longer tube passage times than DL.

Is the pleth variability index a surrogate for pulse pressure variation in a pediatric population undergoing spine fusion?

OBJECTIVE: To compare simultaneous measurements of pulse pressure variation (PPV) and pleth variability index (PVI) in patients undergoing spinal fusion. AIMS: To determine if PVI can be used as a surrogate for PPV and also the influence of the prone position on these measurements. BACKGROUND: Spine fusion is an involved surgical procedure requiring attention to fluid administration. Dynamic indices for assessing fluid responsiveness like PPV have proven useful to guide fluid administration. Plethysmographic waveform variation like PVI is an appealing surrogate for measurements like PPV that require invasive arterial pressure measurement. Spine fusion patients are unique and the potential of either PPV or PVI to guide fluid therapy has not been studied. METHODS: Patients undergoing spine fusion for scoliosis were studied. In addition to the usual monitors including direct arterial pressure measurement, a multi-wavelength pulse co-oximeter was applied to measure PVI. Paired measurements of PPV and PVI were obtained and limits of agreement determined using the method of Bland and Altman. PPV and PVI in prone and supine positions were compared by paired t-test. RESULTS: The bias between PVI and PPV measurements was -0.56% with 95% limits of agreement of +21.67% to -20.55%. There was no significant difference between the prone and supine measurements at the P = 0.05 level (Table 1). CONCLUSIONS: Our data indicate that PVI is not a surrogate for PPV. PVI measurements were not influenced by changing from the supine to prone position and therefore may prove useful for patients undergoing spine surgery.

Reconstituted blood reduces blood donor exposures in children undergoing craniofacial reconstruction surgery.

OBJECTIVE/AIMS: To assess the effect of prophylactic administration of fresh-frozen plasma (FFP) in the form of reconstituted blood in children undergoing craniofacial reconstruction. The outcomes of interest included immediate postoperative coagulation laboratory test results, postoperative surgical drain output, and the number of unique blood donor exposures incurred. BACKGROUND: We recently changed our intraoperative transfusion strategy in children undergoing craniofacial reconstruction surgery to one in which blood loss is replaced with donor-matched reconstituted blood rather than traditional blood component therapy. METHODS: We performed a query of our prospective craniofacial surgery perioperative registry for children who underwent fronto-orbital advancement or posterior cranial vault reconstruction. Registry data from this query were compared to data from a historical cohort. RESULTS: Data for 46 registry cases were compared to 150 historical cohort cases. The median number of unique donor exposures for the reconstituted blood group was 2 vs 3 in the historical cohort (P=0.004). The reconstituted blood group had a decreased incidence of postoperative derangements in soluble clotting factor tests (fibrinogen, PT, or aPTT; 2% vs 24%, P=0.001), while there was no evidence for a difference in the incidence of thrombocytopenia. There was no evidence for differences in postoperative surgical drain output in the reconstituted blood group and historical cohort over the first 12, 24, and 48 h. CONCLUSIONS: Prophylactic administration of FFP in the form of donor-matched reconstituted blood in children undergoing craniofacial reconstruction was associated with improved postoperative coagulation parameters, reduced blood donor exposures, and unchanged postoperative surgical drain output.

Bradycardia during induction of anesthesia with sevoflurane in children with Down syndrome.

BACKGROUND: Bradycardia is a complication associated with inhaled induction of anesthesia with halothane in children with Down syndrome. Although bradycardia has been reported after anesthetic induction with sevoflurane in these children, the incidence is unknown. OBJECTIVES: In this study we compared the incidence and characteristics of bradycardia after induction of anesthesia with sevoflurane in children with Down syndrome to healthy controls. METHODS: We reviewed electronic anesthetic records of 209 children with Down syndrome and 268 healthy control patients who had inhaled induction of anesthesia with sevoflurane over an 8-year period. Data extracted from the medical record included demographics, history of congenital heart disease, heart rate, oxyhemoglobin saturation, expired sevoflurane concentrations, arterial blood pressure, and any treatment of bradycardia during the first 360 seconds after the start of induction of anesthesia. Bradycardia and hypotension were defined as heart rate and arterial blood pressure below the critical limits recommended for activating a pediatric rapid response team to the bedside of a hospitalized child for quick intervention. Factors associated with bradycardia were identified in a univariate analysis. A step-wise backward multiple logistic regression model was used to identify independent factors. Differences between the 2 groups were computed using Fisher's exact test or χ(2) tests for categorical data and t tests for continuous data. RESULTS: Univariate analysis demonstrated that Down syndrome, low ASA physical status, congenital heart disease, and mean sevoflurane concentrations were factors associated with bradycardia. However, multivariate analysis showed that only Down syndrome and low ASA physical status remained as independent factors associated with bradycardia. CONCLUSION: Bradycardia during anesthetic induction with sevoflurane was common in children with Down syndrome, with and without a history of congenital heart disease.