Marcia L. Buck

Providing Patients with Written Medication Information

OBJECTIVE: To review the literature and provide recommendations for the development and dissemination of written medication information to patients and their care providers. DATA SOURCES: A MEDLINE search (1966–1997) of the English-language literature was performed to identify articles pertaining to the development or use of written medication information. A search of the Internet was conducted by using Yahoo as the guide and “medication information” as the search term. Additional resources were obtained through texts, bibliographies, and catalogs from medical publishers. DATA EXTRACTION: Reports documenting the creation and use of written medication information systems were reviewed, as well as studies of readability and reading skills assessment. Examples of materials available for purchase by laypeople and healthcare providers were also examined. DATA SYNTHESIS: Current statistics support the widespread availability of written medication information for patients and care providers. The goal set forth by the Food and Drug Administration of having 75% of patients receive written information by the year 2000 appears achievable. However, there are still many issues to address. Content is not standardized, and materials are frequently written at reading levels higher than that of the average patient. The development and use of resources requiring only minimal reading skills and an increase in the availability of materials written in Spanish are needed. CONCLUSIONS: Written medication information provides a useful addition to counseling by healthcare professionals. A wide variety of prepared materials is available, as well as resources for those interested in developing tools for a specific patient, population, or setting. Healthcare professionals should be aware of the limitations of some resources. Content and readability must be appropriate for the intended audience for these tools to serve a useful role in patient education.

Possible Anaphylaxis after Propofol in a Child with Food Allergy

OBJECTIVE: To report a case of anaphylaxis due to propofol in a child with allergies to egg and peanut oil. CASE SUMMARY: A 14-month-old boy with a history of reactive airway disease was hospitalized for treatment of respiratory symptoms. The patient had documented allergies to egg, peanut oil, and mold. Within the first few hours after admission, acute respiratory decompensation occurred, and arrangements were made to transfer the patient to our tertiary-care hospital. Prior to transfer, he was emergently intubated under sedation and paralysis with propofol and rocuronium. When emergency air transport arrived, the patient was hypotensive and tachycardic. His symptoms of anaphylaxis were managed throughout the flight and, upon arrival at our institution, the patient was admitted to the Pediatric Intensive Care Unit. He improved over a 5-day hospital course, and his caregivers were instructed to avoid propofol in the future. The patients anaphylactic reaction following propofol was rated as a possible adverse drug reaction using the Naranjo probability scale. DISCUSSION: The use of propofol in pediatric patients for procedural sedation has gained increased favor. Since the propofol formulation contains both egg lecithin and soybean oil, its use is contraindicated in patients with hypersensitivities to these components. Several other drugs have a food component, resulting in contraindications and warnings in product labeling. CONCLUSIONS: Propofol should be avoided in patients with allergies to egg and/or soybean oil, if possible. Clinicians should consider the potential for adverse drug events in patients with select food allergies.

Dopamine agonist therapy in low-response children following traumatic brain injury

The objective of this study was to determine whether a dopamine agonist could improve mental status among children in a low-response state following traumatic brain injury. In an 8-week, prospective, double-blind, randomized trial, 10 children and adolescents ages 8 to 21 years ( = 16.7 years) with traumatic brain injury sustained at least 1 month previously and remaining in a low-response state (Rancho Los Amigos Scale level ≤ 3) received pramipexole or amantadine. Medication dosage was increased over 4 weeks, weaned over 2 weeks, and then discontinued. At baseline and weekly during the study, subjects were evaluated with the Coma Near Coma Scale, Western NeuroSensory Stimulation Profile, and Disability Rating Scale. Scores improved significantly from baseline to the medication phase on the Coma Near Coma Scale, Western NeuroSensory Stimulation Profile, and Disability Rating Scale (P < .005). The weekly rate of change was significantly better for all three measures on medication than off medication (P < .05). Rancho Los Amigos Scale levels improved significantly on medication as well (P < .05). There was no difference in efficacy between amantadine and pramipexole. No unexpected or significant side effects were observed with either drug. This clinical trial supports the benefit of two dopamine agonists in the restoration of functional arousal, awareness, and communication. These drugs can be helpful in accelerating eligibility for acute rehabilitation among children and adolescents who have sustained significant brain injuries. (J Child Neurol 2006;21:879—885; DOI 10.2310/ 7010.2006.00203).

Use of Dexmedetomidine in the Pediatric Intensive Care Unit

Study Objective. To determine the safety, effectiveness, and dosing of dexmedetomidine in intensive care infants and children who require sedation, and the rationale for patient selection.

The use of dopamine enhancing medications with children in low response states following brain injury

Primary objective : The study examines the possible relationship between dopamine-enhancing medications and improvement of arousal and awareness in children during persistent low response states (Rancho Los Amigos Levels I, II and III). Research design : A retrospective review was conducted of 10 children enrolled in an existing clinical protocol. The Kluge Childrens Rehabilitation Center (KCRC) low response protocol provides a double baseline serial measure (A, A, B, B, B) design. Scores on the Western NeuroSensory Stimulation Profile (WNSSP) are the dependent variable. Methods and procedures : Ten children, mean age of 13.7 years low response state (30 days or more) who were treated with dopamine agonists. Co-morbid or iatrogenic influences were addressed or ruled out. Seven children had traumatic brain injury, one cerebral vascular accident, one anoxia and one encephalitis. Experimental intervention : On average, dopamine medications were started 52.9 days post-event. Main outcomes and results : Paired t -test of WNSSP scores before medications and on medications were significant at p = 0.03 (paired t -test). Also, the distributions of the slopes (rates of change of WNSSP scores over time) were significantly different in the pre-medication and medication phases (Paired T -test, p = 0.02). Random coefficient model comparison of individuals during pre- and medication phase response variability on WNSSP yielded F -test at p = 0.02. Conclusions : These results suggest a promising relationship between acceleration of recovery for some children in a low response state and administration of dopamine-enhancing medications.

Vancomycin Pharmacokinetics in Neonates Receiving Extracorporeal Membrane Oxygenation

Vancomycin is administered as both prophylaxis and treatment in neonates receiving extracorporeal membrane oxygenation (ECMO), typically after surgery. An open‐label, retrospective study was conducted to determine dosing strategies in all neonates who received vancomycin during ECMO and compare pharmacokinetic values with those of matched controls not receiving ECMO. Fifteen neonates receiving ECMO were given vancomycin infused into the circuit, with dosages based on weight and gestational age. Blood for serum concentrations was drawn around the third dose, for trough concentrations immediately before the dose, and for peak concentrations 1 hour after infusion. Samples were analyzed by fluorescence polarization immunoassay. The most frequent regimen for both groups (8 ECMO, 13 controls) was 10 mg/kg every 8 hours. It produced peak and trough concentrations of 27.5 ± 4.3 and 13.7 ± 2.7 μg/ml, and 23.0 ± 5.4 and 13.2 ± 4.5 μg/ml, respectively. Pharmacokinetic analysis using a one‐compartment model revealed volume of distribution of 0.45 ± 0.18 L/kg, half‐life of 8.29 ± 2.23 hours, and total body clearance of 0.65 ± 0.28 ml/min/kg in ECMO recipients. Volume of distribution and clearance were not significantly different in controls (0.39 ± 0.12 L/kg, 0.79 ± 0.41 ml/min/kg), but half‐life was shorter (6.53 ± 2.05 hrs, p = 0.02). Based on long volume of distribution in neonates receiving ECMO, we recommend that empiric vancomycin regimens incorporate a longer dosing interval than the 6–8 hours commonly recommended for term infants. The effects of severity of illness on drug elimination require additional study.

Traumatic Brain Injury in Children and Adolescents: Surveillance for Pituitary Dysfunction

Background. Children who sustain traumatic brain injury (TBI) are at risk for developing hypopituitarism, of which growth hormone deficiency (GHD) is the most common manifestation. Objective. To determine the prevalence of GHD and associated features following TBI among children and adolescents. Study design. A total of 32 children and adolescents were recruited from a pediatric TBI clinic. Participants were diagnosed with GHD based on insufficient growth hormone release during both spontaneous overnight testing and following arginine/glucagon administration. Results. GHD was diagnosed in 5/32 participants (16%). Those with GHD exhibited more rapid weight gain following injury than those without GHD and had lower levels of free thyroxine and follicle-stimulating hormone. Males with GHD had lower testosterone levels. Conclusions. GHD following TBI is common in children and adolescents, underscoring the importance of assessing for GHD, including evaluating height and weight velocities after TBI. Children and adolescents with GHD may further exhibit absence or intermediate function for other pituitary hormones.

Clinical Experience with Ketorolac in Children

OBJECTIVE: To describe the use of parenteral ketorolac in a large population of children, focusing on dosing patterns, efficacy, and safety. DESIGN: Observational, prospective study conducted over a four-month period. SETTING: A 122-bed childrens medical center located within an academic medical center hospital. PARTICIPANTS: Children receiving ketorolac during their hospitalization. MAIN OUTCOME PARAMETERS: Indications for treatment, dose, dosing interval, use of a loading dose, length of therapy, efficacy (subjective response and use of concomitant therapy), and adverse effects (bleeding, gastrointestinal ulceration or vomiting, and renal dysfunction). RESULTS: Of 112 children evaluated, 110 received ketorolac for analgesia, and 2 were given ketorolac as an antipyretic. The children ranged in age from 6 months to 19 years. Doses of 0.5 mg/kg q6h were used for most children (range 0.17–1.0). The average length of therapy was 3.4 days (range 1–12). The most frequent reason for discontinuing ketorolac therapy was a change to oral therapy. Therapy was discontinued because of a lack of efficacy in only 2 children. Adverse reactions were unusual, with only 2 patients having bleeding potentially associated with ketorolac use. CONCLUSIONS: Ketorolac appears to be a safe and effective therapy for children when given in appropriate doses for a limited duration.

Phenobarbital Dosing and Pharmacokinetics in a Neonate Receiving Extracorporeal Membrane Oxygenation

OBJECTIVE: To describe the dosing and pharmacokinetics of phenobarbital in a neonate receiving extracorporeal membrane oxygenation (ECMO). CASE SUMMARY: The treatment of a 2.6 kg, 38-week gestational age boy with congenital diaphragmatic hernia who developed seizures while receiving ECMO support is described. A loading dose of 20 mg/kg resulted in concentrations of 16.4 and 12.9 μg/mL at 3 and 24 hours, respectively. A maintenance dose of 5 mg/kg/d provided a peak concentration of 19.7 μg/mL and trough concentration of 16.7 μg/mL after four doses. The calculated volume of distribution was 1.2 L/kg and the estimated elimination half-life was 92 hours. Serum concentrations decreased after circuit changes unless the new circuit was redosed. DISCUSSION: The reported incidence of seizures in neonates while receiving ECMO support is 18%. Despite this frequency, there are no clinical reports describing anticonvulsant use in this population. This case demonstrates the use of standard phenobarbital doses to achieve low, but therapeutic, serum concentrations. Pharmacokinetic analysis revealed a volume of distribution slightly larger than expected in neonates and an elimination half-life similar to published values. Altering circulating blood volumes resulted in significant reductions in serum concentrations. CONCLUSIONS: Neonates on ECMO may have a larger volume of distribution than neonates not receiving ECMO and may require larger phenobarbital doses to achieve desired serum concentrations. This may result from the presence of large exogenous blood volumes for priming, as well as loss of drug during circuit changes, extraction by the circuit, or hemofiltration. Further work is needed to better define the pharmacokinetics and pharmacodynamics of phenobarbital in the neonatal ECMO population.

Anticoagulation with Warfarin in Infants and Children

OBJECTIVE: TO provide a comprehensive review of warfarin use in infants and children, including recommendations for appropriate dosage and monitoring parameters. DATA SOURCES: A MEDLINE search (1966-1995) was used to identify pertinent English-language articles in the medical literature. The key search term was warfarin. Additional material was obtained from references cited in articles retrieved through MEDLINE. STUDY SELECTION: All articles involving children younger than 18 years were evaluated. In addition, articles on the pharmacokinetics and pharmacodynamics in adults, adverse effects, and drug interactions were included. DATA EXTRACTION: Material selected for review included clinical trials, case reports, and surveys of practice. DATA SYNTHESIS: Warfarin has been used as prophylactic therapy in children with prosthetic cardiac valves as well as for prevention of thromboembolic complications associated with autoimmune disorders and protein C or protein S deficiency. Warfarin also has been used to prevent embolization in children with deep-vein thrombosis or clots in central venous catheters. According to the literature, an initial dosage of 0.1 mg/kg/d should provide anticoagulation without significant adverse effects. As in adults, dosing should be adjusted to achieve a target international normalized ratio (INR). Although the target range in children is not well established, INR values of 1.5–3 are recommended for most patients. Higher values have been used in children with prosthetic cardiac valves and hereditary clotting disorders. CONCLUSIONS: Due to its infrequent use, there is limited information on the effects of warfarin in children. Basic guidelines for initiating and monitoring warfarin were developed by using data gathered from clinical trials, retrospective reviews, case series, and surveys of practice.