Sheila Jacobson

Prospective multicentre study of pregnancy outcome after lithium exposure during first trimester

Lithium carbonate is an effective drug for prophylaxis and treatment of major affective disorders. In-utero exposure to lithium during the first trimester of pregnancy might be associated with an increased risk of cardiac malformations, especially the rare Ebsteins anomaly. We prospectively recruited and followed 148 women (mean age 30 years, SD 5 range 15-40) using lithium during the first trimester of pregnancy, who consulted four teratogen information centres in the USA and Canada. Pregnancy outcome was compared with that of controls matched for maternal age. We had complete follow-up of pregnancy outcome in 138 of 148 patients recruited. In the other 10, fetal echocardiograms were available but postnatal follow-up was not done. Mean daily dose of lithium was 927 mg (SD 340). Rates of major congenital malformations did not differ between the lithium (2.8%) and control (2.4%) groups. 1 patient in the lithium group chose to terminate pregnancy after Ebsteins anomaly was detected by a prenatal echocardiogram. There was 1 ventricular septal defect in the controls. Birthweight was significantly higher in the lithium-exposed infants than in the controls despite identical gestational ages (3475 [660] g vs 3383 [566] g, p = 0.02). The true difference in birthweight might have been even larger, since significantly more women using lithium than controls were cigarette smokers (31.8% vs 15.5%, p = 0.002). These results indicate that lithium is not an important human teratogen. Women with major affective disorders who wish to have children may continue lithium therapy, provided that adequate screening tests, including level II ultrasound and fetal echocardiography, are done.

A Comparison of Nebulized Budesonide, Intramuscular Dexamethasone, and Placebo for Moderately Severe Croup

BACKGROUND In children with croup, treatment with nebulized budesonide decreases symptoms, but it is uncertain how budesonide compares with dexamethasone, the conventional therapy for croup, and whether either reduces the rate of hospitalization. METHODS We performed a double-blind, randomized trial involving 144 children with moderately severe croup. The children were treated with racepinephrine and a single dose of 4 mg of nebulized budesonide (48 children), 0.6 mg of intramuscular dexamethasone per kilogram of body weight (47 children), or placebo (49 children). The children were assessed before treatment and then hourly for five hours after treatment. Physicians who were unaware of the treatment assignments determined the childrens need for further treatment and hospitalization. RESULTS The characteristics of the groups were similar at base line, including the types of viruses identified, the types of croup, and the clinical severity of the illness. The overall rates of hospitalization were 71 percent in the placebo group (35 of 49 children), 38 percent in the budesonide group (18 of 48 children), and 23 percent in the dexamethasone group (11 of 47 children) (unadjusted P=0.001 for the comparison of budesonide with placebo, P<0.001 for the comparison of dexamethasone with placebo, and P=0.18 for the comparison of budesonide with dexamethasone). Children treated with budesonide or dexamethasone had a greater improvement in croup scores than those given placebo (P=0.03 and P<0.001, respectively), and those treated with dexamethasone had a greater improvement than those treated with budesonide (P=0.003). CONCLUSIONS In children with moderately severe croup, treatment with intramuscular dexamethasone or nebulized budesonide resulted in more rapid clinical improvement than did the administration of placebo, with dexamethasone offering the greatest improvement. Treatment with either glucocorticoid resulted in fewer hospitalizations.

Tissue plasminogen activator for the treatment of thromboembolism in infants and children

We report our experience with the use of tissue plasminogen activator to treat 12 infants and children with various thromboembolic states after conventional thrombolytic agents had failed. The dosage range was between 0.1 to 0.5 mg/kg per hour. Complete clot dissolution occurred in seven cases after 2 hours to 3 days of therapy. Partial clot dissolution and clinical improvement were noted in another four patients. Bleeding complications were noted in 6 of the 12 patients and included bruising, oozing from various venipuncture sites, and bleeding; these complications were controlled by clinically available means. In all cases with bleeding the dose rate was in the higher range (0.46 to 0.50 mg/kg per hour). In one patient, restlessness, agitation, and screaming were noted during administration of tissue plasminogen activator and when it was reinstituted. We conclude that tissue plasminogen activator is effective in inducing clot lysis in children. Because the effective dose appears to overlap with those causing bleeding, we recommend that a dose of 0.1 mg/kg per hour be started and increased gradually if clot dissolution does not occur, with close monitoring for bleeding.

Randomised trial of oral morphine for painful episodes of sickle-cell disease in children

BACKGROUND Oral controlled-release morphine can provide effective analgesia through a non-invasive route and may facilitate outpatient management of severe episodes of sickle-cell pain. We compared the clinical efficacy and safety of oral morphine with continuous intravenous morphine in children with severe episodes of sickle-cell pain, by a double-blind, randomised, parallel-group design. METHODS 56 children aged 5-17 years received loading doses of intravenous morphine of up to 0.15 mg/kg, followed by randomly assigned oral morphine 1.9 mg/kg every 12 h plus intravenous placebo (saline), or intravenous morphine 0.04 mg kg-1 h-1, plus placebo tablet. Breakthrough pain was treated with oral, immediate-release morphine 0.4 mg/kg every 2-3 h as required. Pain was assessed daily at 0900 h, 1300 h, 1700 h, and 2100 h with a picture face scale, a pictorial scale (Oucher), a behavioural-observational scale (CHEOPS), and by an investigator. FINDINGS 50 children completed the study (28 boys, 22 girls; mean age 11.2 years [SD 3.5]; mean oral morphine dose 2.99 mg/kg daily [0.75]; mean intravenous morphine dose, 0.81 mg/kg daily [0.30]). Mean overall pain scores were similar for oral and intravenous morphine (CHEOPS, 6.3 [1.5] vs 6.4 [1.4], p = 0.8; Oucher, 31.5 [25.4] vs 39.2 [21.7], p = 0.3; Faces, 2.2 [1.4] vs 2.4 [1.3], p = 0.6; clinical rating, 1.7 [0.7] vs 1.9 [0.5], p = 0.3). Opioid analgesia was required for a mean of 4.2 days (1.7) and 5.4 days (2.6), respectively (p = 0.0591). Pain scores from all scales correlated significantly (r = 0.5865-0.8980, p = 0.0001). Frequency of rescue analgesia did not differ significantly between the oral and intravenous morphine groups (0.7 [0.8] vs 0.9 [0.7] doses daily, p = 0.2). Frequency and severity of adverse events did not differ significantly. INTERPRETATION Oral, controlled-release morphine is a reliable, non-invasive alternative to continuous intravenous morphine for the management of painful episodes of sickle-cell disease in children.

Systemic Exposure to Morphine and the Risk of Acute Chest Syndrome in Sickle Cell Disease

The etiology of acute chest syndrome, the most severe complication of the sickle cell crisis, is unknown.

Safety and pharmacokinetics of EMLA in the treatment of postburn pruritus in pediatric patients: a pilot study.

The purpose of this study was to determine the safety and pharmacokinetics of a eutectic mixture of local anesthetics (EMLA) used to ameliorate postburn pruritus after application onto newly formed, intact skin in children. EMLA was applied once to an itchy site where healed skin had formed. Serial blood samples were collected to measure lidocaine, prilocaine, o-toluidine, and methemoglobin. Maximal plasma concentration, minimal plasma concentration, time to achieve the maximal plasma concentration, elimination half-life, and area under the concentration-time curve were calculated. Vital signs, oxygen saturation, clinical signs of hypoxia, and itch intensity were measured. Five children had 15.7 +/- 2.54 g (+/- SD) of EMLA applied to a skin surface area of 93.0 +/- 37.0 cm2. Lidocaine and prilocaine concentrations were below toxic levels; o-toluidine was not detected. Methemoglobin remained between 1 and 3%; patients did not exhibit any clinical signs of hypoxia. Mean oxygen saturation was 98.9 +/- 0.01%. The mean number of pruritic episodes and antihistamine breakthrough doses were greater in the 2 prestudy control days compared with study day 3 (P = 0.01 and P = 0.03, respectively). Skin at the site of EMLA application remained anesthetized for 12 to 13 hours. In this small pilot study, EMLA seems to be a safe, novel treatment for postburn pruritus in burned children when applied to newly healed, intact skin.

Mercury Intoxication: It Still Exists

Abstract:  A 3‐year‐old boy presented to the Hospital for Sick Children with systemic symptoms and oropharyngeal and peripheral extremity changes suggestive of Kawasaki disease. He was found to have severe hypertension. Investigation for a catecholamine‐secreting tumor was negative. Toxins were considered when the patients 20‐month‐old brother presented with similar symptoms, and the boys were subsequently diagnosed with elemental mercury poisoning. We review the literature on mercury intoxication and discuss the historical context, clinical syndrome (acrodynia), treatment, and radiologic findings of this unusual diagnosis.

Office-Based Randomized Controlled Trial to Reduce Screen Time in Preschool Children

OBJECTIVE: To determine if an intervention for preschool-aged children in primary care is effective in reducing screen time, meals in front of the television, and BMI. METHODS: A randomized controlled trial was conducted at a primary care pediatric group practice in Toronto, Canada. Three-year-old children and their parents were randomly assigned to receive a short behavioral counseling intervention on strategies to decrease screen time. The primary outcome 1 year later was parent reported screen time. Secondary outcomes included television in the child’s bedroom, number of meals in front of the television, and BMI. RESULTS: In the intention-to-treat analysis at 1 year, there were no significant differences in mean total weekday minutes of screen time (60, interquartile range [IQR]: 35–120 vs 65, IQR: 35–120; P = .68) or mean total weekend day minutes of screen time (80, IQR: 45–130 vs 90, IQR: 60–120; P = .33) between the intervention and control group. Adjusting for baseline BMI, there was a reduction in the number of weekday meals in front of the television (1.6 ± 1.0 vs 1.9 ± 1.2; P = .03) but no differences in BMI or number of televisions in the bedroom. CONCLUSIONS: This pragmatic trial was not effective in reducing screen time or BMI but was effective in reducing meals in front of the screen. Short interventions focused solely on reducing screen time implemented in the primary care practice setting may not be effective in this age group.

Correlation of morphine sulfate in blood plasma and saliva in pediatric patients

This study sought to determine whether saliva concentrations of morphine correlate with plasma levels of morphine in pediatric patients receiving morphine analgesia for severe pain, and to evaluate whether the measurement of saliva morphine concentrations would be a useful, noninvasive, clinical tool to diagnose systemic exposure to morphine. Fifteen pediatric patients were enrolled; for the control group, 18 adult volunteers were recruited. Patients received continuous morphine drips to ameliorate pain caused by a sickle cell vasoocclusive crisis (range, 10-40 micrograms/kg.h). Control subjects were randomized into those receiving acetaminophen with either 8 mg (n = 13) or 30 mg (n = 5) of codeine. All participants fasted at least 2 hours before sample collection. Blood and saliva samples were collected simultaneously. All samples were analyzed by radioimmunoassay for morphine. There was no correlation between saliva and plasma morphine concentrations in either the patients receiving intravenous morphine (r = 0.04, P = 0.89) or in the controls receiving codeine (r = 0.43, P = 0.08). There was no observed difference in the mean counts per minute (CPM) for saliva samples in the pH range 3.96 to 8.06. Saliva concentrations of morphine cannot be used to predict the plasma concentration of morphine in children or adults. However, the concentration of morphine in saliva may be used as a qualitative indicator of systemic exposure to morphine in a subject.

Office-Based Intervention to Reduce Bottle Use Among Toddlers: TARGet Kids! Pragmatic, Randomized Trial

OBJECTIVE: The goal was to determine whether an office-based, educational intervention for parents of 9-month-old children could reduce bottle use and iron depletion at 2 years of age. METHODS: Between January 2006 and 2007, 251 healthy, 9-month-old infants attending a routine health maintenance visit were assigned randomly to intervention or control groups. Parents in the intervention group were introduced to a 1-week protocol to wean their children from the bottle. Iron depletion (ferritin levels of <10 μg/L) and bottle use at 2 years were assessed. RESULTS: A total of 201 children were monitored to 2 years of age (follow-up rate: 81%). Rates of iron depletion (10 [10%] of 102 children vs 13 [13%] of 99 children; P = .42) and milk consumption of >16 oz (16 [16%] of 102 children vs 17 [17%] of 99 children; P = .7) were not significantly different between the 2 groups at 2 years of age. However, children in the intervention group started using a cup 3 months earlier (9 vs 12 months; P = .001), were weaned from the bottle 4 months earlier (12 vs 16 months; P = .004), and were more than one-half as likely to be using a bottle at 2 years of age (15 [15%] of 102 children vs 39 [40%] of 99 children; P = .0004). CONCLUSIONS: This simple intervention administered during a health maintenance visit did not result in a decrease in iron depletion at 2 years of age but did result in a 60% reduction in prolonged bottle use.