Randy Prescilla

Efficacy of Tranexamic Acid in Pediatric Craniosynostosis Surgery: A Double-blind, Placebo-controlled Trial

Background:Extensive blood loss is common in pediatric craniosynostosis reconstruction surgery. Tranexamic acid (TXA) is increasingly used to reduce perioperative blood loss in various settings, but data on its efficacy are limited in children. The purpose of this randomized, double-blind, placebo-controlled, parallel trial was to evaluate the efficacy of TXA in pediatric craniosynostosis correction surgery. The primary and secondary outcome variables were reduction in perioperative blood loss and reduction in blood transfusion, respectively. Methods:Forty-three children, ages 2 months to 6 yr, received either placebo or TXA in a loading dose of 50 mg·kg−1, followed by an infusion of 5 mg·kg−1·h−1 during surgery. TXA plasma concentrations were measured. Results:The TXA group had significantly lower perioperative mean blood loss (65 vs. 119 ml·kg−1, P < 0.001) and lower perioperative mean blood transfusion (33 vs. 56 ml· kg−1, P = 0.006) compared to the placebo group. The mean difference between the TXA and placebo groups for total blood loss was 54 ml·kg−1 (95% CI for the difference, 23–84 ml·kg−1) and for packed erythrocytes transfused was 23 ml·kg−1 (95% CI for the difference, 7–39 ml·kg−1). TXA administration also significantly diminished (by two thirds) the perioperative exposure of patients to transfused blood (median, 1 unit vs. 3 units; P < 0.001). TXA plasma concentrations were maintained above the in vitro thresholds reported for inhibition of fibrinolysis (10 &mgr;g·ml−1) and plasmin-induced platelet activation (16 &mgr;g·ml−1) throughout the infusion. Conclusions:TXA is effective in reducing perioperative blood loss and transfusion requirement in children undergoing craniosynostosis reconstruction surgery.

Prevalence of fetal exposure to environmental toxins as determined by meconium analysis.

OBJECTIVE The primary objective was to determine whether environmental pollutants, specifically lead (Pb), cadmium (Cd), mercury (Hg), arsenic (As) and organochlorine and organophosphate pesticides can be detected in meconium. STUDY DESIGN Prospective, cohort study. Infants were randomly recruited from the nurseries of five hospitals in Manila, Philippines. Their stools (meconium) were collected and analyzed for heavy metals by atomic absorption spectrophotometry and for pesticides by gas chromatography/mass spectrometry (GCMS). RESULTS A total of 426 infants were studied. The exposure rate (based on meconium analysis) and the median concentration of the pollutants in the positive samples were as follows: lead (26.5%; 35.77 microg/ml), cadmium (8.5%; 13.37 microg/ml), mercury (83.9%; 3.17 ng/ml), chlordane (12.7%; 22.48 microg/ml), chlorpyrifos (11.0%; 8.26 microg/ml), diazinon (34.3%; 12.96 microg/ml), DDT (26.5%; 12.56 microg/ml), lindane (73.5%; 2.0 microg/ml), malathion (53.0; 6.80 microg/ml), parathion (32.0%; 2.30 microg/ml) and pentachlorphenol (16.1%; 90.00 microg/ml). Some maternal and neonatal factors that were significantly associated with the presence of environmental toxins in meconium included multi-gravidity, multiparity, multiple gestation, meconium stained fluid, smoking, gestational age, low birth weight and infant gender. CONCLUSION Meconium analysis is a new and sensitive tool to detect fetal exposure to environmental toxins and its clinical use awaits further investigation.

Hemodynamic effects of dexmedetomidine sedation for CT imaging studies

Background:  Dexmedetomidine sedation for radiological imaging studies is a relatively recent application for this drug. Previous studies have demonstrated some haemodynamic effects of dexmedetomidine, however, the effects remain poorly described in children. The aim of this study was to better define the effect of age on heart rate (HR) and blood pressure changes in children sedated for CT imaging with dexmedetomidine.

Incidence and predictors of hypertension during high-dose dexmedetomidine sedation for pediatric MRI

This study reviewed the hypertensive response of a large population of children to high‐dose dexmedetomidine sedation with the aim of determining the incidence and predictors of hypertension.

Influence of goldenseal root on the pharmacokinetics of indinavir

Goldenseal root was identified as the most potent inhibitor of CYP3A4 in a study that tested 21 popular herbal products for in vitro inhibitory activity. The purpose of this investigation was to examine the influence of goldenseal root on the disposition of the CYP3A4 substrate indinavir in humans. Using a crossover study design, the pharmacokinetics of indinavir were characterized in 10 healthy volunteers before and after 14 days of treatment with goldenseal root (1140 mg twice daily). Indinavir was given as a single 800‐mg oral dose, and blood samples were collected for 8 hours following the dose. No statistically significant differences in peak concentration (11.6 vs. 11.9 mg/L) or oral clearance (26.8 vs. 23.9 mg•mDh/L) were observed following treatment with goldenseal root. Half‐life and time to reach peak concentration were also unchanged by goldenseal. These results suggest that patients being treated with indinavir can safely take goldenseal root and that interactions with other drugs metabolized by CYP3A4 in the liver are unlikely.

Pediatric CT sedation: comparison of dexmedetomidine and pentobarbital.

OBJECTIVE Our institution replaced pentobarbital with dexmedetomidine for pediatric CT sedation. The purpose of this study was to compare the efficacy, incidence of adverse events, and cardiovascular and respiratory profiles of these two sedatives. MATERIALS AND METHODS Quality assurance data were accessed for a review of demographics, outcome parameters, and adverse events among all children who received either pentobarbital or dexmedetomidine. RESULTS From January 2004 through June 2009 there were 388 pentobarbital sedations and 1,274 dexmedetomidine sedations. Age, sex, weight, and duration of imaging study were similar in the two groups. Average time to achieve sedation was 12 ± 4 minutes with dexmedetomidine and 6 ± 3 minutes with pentobarbital (p < 0.001). Recovery time was 32 ± 18 minutes with dexmedetomidine and 95 ± 28 minutes with pentobarbital (p < 0.001). There were no differences between groups in incidence of oxygen desaturation and need for brief positive pressure ventilation. The odds of needing additional sedative agents to complete the study were significantly higher with pentobarbital than with dexmedetomidine (odds ratio, 4.0; 95% CI, 2.0-8.4; p < 0.001). There was a significantly lower incidence of agitation and rage with dexmedetomidine (p < 0.01) but higher risk of hypotension (p < 0.01). There was one failed sedation in each group (p = 0.99). CONCLUSION Dexmedetomidine is a safe and effective alternative to pentobarbital for pediatric CT, being associated with a much shorter recovery time and less need for adjuvant sedatives.

Dexmedetomidine Offers an Option for Safe and Effective Sedation for Nuclear Medicine Imaging in Children

PURPOSE To determine the safety, efficacy, and outcomes of bradycardia, hypotension, and hypertension with dexmedetomidine (DEX), a recently approved sedative used for procedural sedation that has not been described previously for pediatric nuclear medicine imaging. MATERIALS AND METHODS Between March 2005 and August 2011, 669 patients (mean age, 5.7 years ± 4.5 [standard deviation]; median age, 4.5 years; age range, 0.1-22.5 years) received DEX in this HIPAA-compliant study. Sedation was administered with DEX, an α-2 adrenergic agonist, as an intravenous bolus (2 μg per kilogram of body weight) over a 10-minute period; this was followed by continuous infusion at a rate of 1 μg/kg/h until imaging was complete. The bolus could be repeated up to two times, if needed, to achieve the targeted level of a Ramsay sedation score of 4. After institutional review board approval, collected quality assurance data were reviewed. RESULTS Adequate sedation was achieved within 8.6 minutes ± 4.6 (median, 8.0 minutes; range, 1.0-40.0 minutes) on average in studies that averaged 41.3 minutes ± 25.5 (median, 31.5 minutes; range, 9.0-183.0 minutes). Of 669 studies, 667 (99.7%) were completed successfully. Six children (0.9%) had brief periods of oxygen desaturation below 95%, none of which required airway intervention. Hypotension, hypertension, and bradycardia (all defined as deviations of more than 20% from age-adjusted awake norms), occurred in 58.7% (n = 393), 2.1% (n = 14), and 4.3% (n = 29) of patients, respectively. Both hypotension and bradycardia were related to age (P = .033 and P = .002, respectively); older children tended to experience more of these events. None of these fluctuations required pharmacologic therapy. Discharge criteria (modified Aldrete score ≥ 9) were met, on average, within 41.4 minutes ± 27.9 (median, 36.0 minutes; range, 1.0-220.0 minutes). CONCLUSION DEX offers advantages for pediatric sedation for nuclear medicine imaging. DEX produces a condition similar to natural sleep, with no detrimental effect on respiration. The hemodynamic variability anticipated with DEX did not require pharmacologic treatment, and the drug was well tolerated.

Baricitinib in adult patients with moderate-to-severe atopic dermatitis: a phase 2 parallel, double-blinded, randomized placebo-controlled multiple-dose study

Background: Baricitinib, an oral selective inhibitor of Janus kinase 1 and Janus kinase 2, modulates proinflammatory cytokine signaling. Objectives: The efficacy and safety of baricitinib were evaluated in patients with moderate‐to‐severe atopic dermatitis (AD). Methods: In this phase 2, randomized, double‐blind, placebo‐controlled study, 124 patients with moderate‐to‐severe AD applied topical corticosteroids (TCSs) for 4 weeks before randomization to once‐daily placebo, 2 mg of baricitinib, or 4 mg of baricitinib for 16 weeks. Use of TCSs was permitted during the study. The primary outcome was the proportion of patients achieving at least a 50% reduction in the Eczema Area and Severity Index (EASI‐50) compared with placebo. Results: Significantly more patients who received baricitinib, 4 mg, achieved EASI‐50 than did patients receiving placebo (61% vs 37% [P = .027]) at 16 weeks. The difference between the proportion of patients receiving baricitinib, 2 or 4 mg, who achieved EASI‐50 and the proportion of patients receiving placebo and achieving EASI‐50 was significant as early as week 4. Baricitinib also improved pruritus and sleep loss. Treatment‐emergent adverse events were reported in 24 of the patients receiving placebo (49%), 17 of those receiving 2 mg of baricitinib (46%), and 27 of those receiving 4 mg of baricitinib (71%). Limitations: A TCS standardization period before randomization reduced disease severity, limiting the ability to compare results with those of baricitinib monotherapy. Longer studies are required to confirm baricitinibs efficacy and safety in patients with AD. Conclusions: Baricitinib used with TCSs reduced inflammation and pruritus in patients with moderate‐to‐severe AD.

Feasibility of measuring memory response to increasing dexmedetomidine sedation in children

Background. The memory effect of dexmedetomidine has not been prospectively evaluated in children. We evaluated the feasibility of measuring memory and sedation responses in children during dexmedetomidine sedation for non-painful radiological imaging studies. Secondarily, we quantified changes in memory in relation to the onset of sedation. Methods. A 10 min bolus of dexmedetomidine (2 mcg kg-1) was given to children as they named simple line drawings every five s. The absence of sedation was identified as any verbal response, regardless of correctness. After recovery, recognition memory was tested with correct Yes/No recognitions (50% novel pictures) and was matched to sedation responses during the bolus period (subsequent memory paradigm). Results. Of 64 accruals, 30 children (mean [SD]6.1 (1.2) yr, eight male) received dexmedetomidine and completed all study tasks. Individual responses were able to be modelled successfully in the 30 children completing all the study tasks, demonstrating feasibility of this approach. Children had 50% probability of verbal response at five min 40 s after infusion start, whereas 50% probability of subsequent recognition memory occurred sooner at four min five s. Conclusions. Quantifying memory and sedation effects during dexmedetomidine infusion in verbal children was possible and demonstrated that memory function was present until shortly before verbal unresponsiveness occurred. This is the first study to investigate the effect of dexmedetomidine on memory in children. Clinical trial registration. NCT 02354378.

Pharmacokinetics of rofecoxib in children with sickle cell hemoglobinopathy.

Summary:Rofecoxib is a selective cyclooxygenase-2 (COX-2) inhibitor approved for the treatment of pain and arthritis in adults. It is available as a suspension, but there are no published pediatric pharmacokinetic data. This study characterized the disposition of rofecoxib in children with sickle cell hemoglobinopathy in a single-oral-dose, intensive pharmacokinetic study. Eight subjects aged 3 to 14 years (mean 8.9 years, 5 boys and 3 girls) received a single oral dose of rofecoxib (1 mg/kg, maximum 50 mg) as a suspension. Blood samples were collected over 72 hours following drug administration and plasma was assayed for rofecoxib using high-performance liquid chromatography (HPLC). Pharmacokinetic parameters (peak concentration [Cmax], time to reach peak concentration [tmax], area under the curve [AUC], oral clearance [Cl/F], elimination half-life [t½]) were calculated using standard noncompartmental methods. The mean dose was 35.6 mg (range 15–50 mg). Cmax averaged 582 ± 129 ng/mL, with a median tmax of 4.0 hours. Secondary peaks were observed in two subjects. Two subjects were discharged at 12 hours, preventing characterization of elimination. In the remaining six subjects, Cl/F averaged 1.34 ± 0.32 mL/min/kg, with a t½ of 14.8 ± 4.5 hours. No significant adverse events were observed. The disposition of rofecoxib in children appears to be similar to that in adults, with comparable values for Cmax, tmax, t½, and Cl/F.