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Biomedical subjects

R E Kauffman

Publications and source records attributed to R E Kauffman.

At least 37 records · Page 2Linked to original sources
PubMed1992

Antipyretic efficacy of ibuprofen vs acetaminophen.

OBJECTIVE: To compare the antipyretic efficacy of ibuprofen, placebo, and acetaminophen. DESIGN: Double-dummy, double-blind, randomized, placebo-controlled trial. SETTING: Emergency department and inpatient units of a large, metropolitan, university-based, children's hospital in Michigan. PARTICIPANTS: 37 otherwise healthy children aged 2 to 12 years with acute, intercurrent, febrile illness. INTERVENTIONS: Each child was randomly assigned to receive a single dose of acetaminophen (10 mg/kg), ibuprofen (7.5 or 10 mg/kg), or placebo. MEASUREMENTS/MAIN RESULTS: Oral temperature was measured before dosing, 30 minutes after dosing, and hourly thereafter for 8 hours after the dose. Patients were monitored for adverse effects during the study and 24 hours after administration of the assigned drug. All three active treatments produced significant antipyresis compared with placebo. Ibuprofen provided greater temperature decrement and longer duration of antipyresis than acetaminophen when the two drugs were administered in approximately equal doses. No adverse effects were observed in any treatment group. CONCLUSION: Ibuprofen is a potent antipyretic agent and is a safe alternative for the selected febrile child who may benefit from antipyretic medication but who either cannot take or does not achieve satisfactory antipyresis with acetaminophen.

Acetaminophen↗
PubMed1992

Effect of age on ibuprofen pharmacokinetics and antipyretic response.

The effect of age on ibuprofen pharmacokinetics and antipyretic effect was studied in 49 infants and children aged 3 months to 10.4 years. The relationship of plasma concentration to antipyretic effect was examined in 38 of the children by using an iterative least squares technique that allows estimation of drug concentration with time in a theoretical effect compartment and rate constant for elimination of drug from the effect compartment. There was a delay of 1 to 3 hours between peak ibuprofen plasma concentration and peak temperature decrement. The mean elimination rate constant from the effect compartment was 0.6 hour-1, corresponding to a half-life of drug in the effect compartment of 1.1 hours. The mean slope of the effect compartment concentration versus temperature regression line was -0.242 degrees C/mg per liter. Age did not significantly influence the rate of absorption of ibuprofen, its plasma concentration, its rate of elimination, or the time course of ibuprofen concentration in the effect compartment. However, in younger children the onset of antipyresis was earlier, maximum antipyretic effect was greater, and the area under the curve of the percentage of change in temperature from baseline versus time was greater than in older children. We conclude that the greater relative body surface area in younger children may allow more efficient dissipation of heat in response to antipyretic-induced lowering of the temperature "set point" in the hypothalamus.

Acute Disease↗
PubMed1992

Pharmacokinetic studies in paediatric patients. Clinical and ethical considerations.

Important advances in paediatric clinical pharmacology have been made over the past 2 decades. However, there remains a reluctance to pursue pharmacodynamic and pharmacokinetic studies in children and, consequently, many important therapeutic agents have not been adequately studied in this population. Age-related pharmacokinetic/pharmacodynamic studies are not only essential to provide optimal drug therapy for children, but are quite feasible. Usually, paediatric pharmacokinetic studies are conducted in children receiving treatment for a specific medical condition. The approach to soliciting participation of paediatric subjects requires special sensitivity to the fears and anxieties of the child and the parents. Factors influencing subject enrollment and suggestions to enhance enrollment into study protocols are discussed. Pharmacokinetic/pharmacodynamic studies require repeated measurements over time and often entail obtaining multiple blood and urine samples. Techniques for reducing sample volume and number of necessary samples while minimising the discomfort and fear associated with obtaining multiple samples include the development of highly sensitive analytical methods to measure drug concentrations in small volume samples. The number of samples obtained from individual subjects can be minimised by using pharmacokinetic analytical approaches such as the nonlinear mixed effect model (NONMEM) which allows estimation of pharmacokinetic characteristics of a population using limited data from each subject. In addition, less invasive methods to measure drug metabolism/elimination such as salivary sampling, transcutaneous collection and breath analysis have been applied to the study of certain drugs. Children are a particularly vulnerable population because of their limited cognitive abilities and dependence on adults. Thus, they must be afforded greater protection from exploitation as research subjects than that provided to adults.

Clinical Trials as Topic↗
PubMed1991

Occult cocaine exposure in children.

We determined the prevalence of cocaine and cannabinoid exposure among young children presenting to an urban pediatric emergency department without signs or symptoms suggestive of the exposure. The study included 460 children between 1 and 60 months of age in whom urinalysis was required for investigation of routine pediatric complaints. Anonymously and without informed consent, an aliquot of urine was screened for cocaine metabolite (benzoylecgonine) and 11- or delta-9-tetrahydrocannabinol-9 carboxylic acid with the enzyme multiplied immunoassay technique. Positive specimens were rescreened with a radioimmunoassay and confirmed with gas chromatography/mass spectrometry, if a sufficient quantity of urine was available. Benzoylecgonine was identified in 25 patients (5.4%) by both screening techniques. Enough urine was available for confirmatory testing in eight patients, and all eight urine specimens contained benzoylecgonine. Neither 11- nor delta-9-tetrahydrocannabinol-9 carboxylic acid was detected in any patient. We documented the magnitude of the problem of occult passive cocaine exposure in young children living in an urban environment. Such exposure has serious implications for the assessment of outcomes in postnatal follow-up studies of prenatally exposed children as well as potential risks to children living in household environments where occult cocaine exposure occurs.

Adult↗
PubMed1991

Pharmacokinetic and pharmacodynamic study of midazolam in children during esophagogastroduodenoscopy.

We undertook a prospective study to evaluate the relationship between the onset and degree of sedation and the midazolam plasma concentration in children between 6 and 18 years of age during esophagogastroduodenoscopy. Thirteen boys and seven girls (median age 13.5 years) were studied. Midazolam was injected intravenously for 5 minutes, and the dose was titrated to sedation or a maximum dose of 0.1 mg/kg was given. Plasma midazolam concentration was determined just before and at 5, 10, 15, 30, 45, and 60 minutes after the start of midazolam injection. The patient's level of sedation was evaluated by an assistant at each blood sampling time. Clearance, volume of distribution, and terminal elimination (beta) half-life were estimated from a biexponential fit of the serial plasma midazolam concentrations. Mean beta half-life of midazolam was 47 +/- 26 minutes and mean clearance was 10.0 +/- 5.0 ml/min per kilogram of body weight. Maximum level of sedation occurred at 5 minutes after initiation of the injection and corresponded to a mean peak midazolam serum concentration of 229 +/- 39 micrograms/L. Thereafter, a decline of mean sedation scores paralleled the decrease in midazolam concentration. Mean oxygen saturation remained greater than 94% during the study. We conclude that children metabolize and excrete midazolam more rapidly than adults do and that sedation adequate for endoscopy is safely achieved in the majority of children with a midazolam dose of 0.05 to 0.1 mg/kg and a mean peak midazolam concentration greater than 200 microgram/L.

Adolescent↗
PubMed1990

Comparison of evaluation of gastroesophageal reflux in infants using different feedings during intraesophageal pH monitoring.

The effect of two different types of feedings on results of esophageal pH monitoring was prospectively studied in 49 infants undergoing evaluation for gastroesophageal reflux (GER). Infants were randomly assigned to receive either apple juice (AJ) or formula for the first feeding during extended pH monitoring (EPM). Each infant received the alternate liquid for the second feeding. During the rest of the monitoring period, infants received formula feedings. The percentage of time that esophageal pH was less than 4.0 following both types of feedings and the percentage of time that pH was lower than 5.0 following formula feedings were determined. Following AJ feeding, the mean percentage of time pH was less than 4.0 was 43.8% in contrast to 5.1% following formula feeding. However, following formula feeding, pH was less than 5.0 35.7% of time, similar to the percentage of time pH was less than 4.0 after AJ feeding. Ability to detect GER with short-term monitoring after the two feedings was compared to detection following extended monitoring. Detection of GER with short-term monitoring following AJ feeding correlated well with extended monitoring (r = 0.67; p less than 0.001). There was a weaker, although significant, correlation between short-term monitoring following formula feeding using pH less than 5.0 as the reflux criterion and extended monitoring (r = 0.3; p less than 0.01). We conclude that outpatient GER evaluation with intraesophageal pH monitoring during a feeding interval following an AJ feeding may serve as an acceptable substitute for extended pH monitoring when it is not practical or desirable to admit the patient to the hospital.

Esophagus↗
PubMed1990

Impaired oxidative metabolism of salicylate in Reye's syndrome.

Administration of salicylates during prodromal viral illness has been associated with the development of Reye's syndrome (RS). We studied salicylate biotransformation in RS patients and compared it with those on chronic salicylate therapy for juvenile rheumatoid arthritis (JRA). Urine of RS patients contained significantly more salicylic acid and less gentisic acid than that of JRA patients while the conjugated metabolites were not different between the two groups. These results suggest decreased salicylate microsomal oxidation in RS. The role of altered salicylate metabolism in the pathogenesis of RS is unclear.

Arthritis, Juvenile↗
PubMed1990

Therapeutic challenges. Prenatal and paediatric safety considerations.

Developmental changes make the fetus and child uniquely susceptible to drug toxicities which do not occur in mature individuals. Passive exposure to maternally administered drugs during fetal life introduces the potential risk of morphological or behavioural teratogenesis. Although animal studies are useful in identifying potential teratogens, they are poor predictors of human teratogenesis. Most drugs are excreted into breast milk in insufficient quantity to cause adverse effects in the nursing infant. However, there are several exceptions. Therefore, it is important to document the extent to which a drug appears in breast milk and is absorbed by the nursing infant prior to its use by the mother. Plasticity of growing tissues and changes in body composition, the rate of drug metabolism, drug metabolic pathways and elimination rates during growth and development may alter susceptibility to unique drug toxicities. This requires that drug safety and efficacy be established in children at different ages. Ethical and technical constraints inherent in drug studies in children introduce increased effort and cost. However, there is a moral imperative for academicians, government agencies and the pharmaceutical industry to work together to ensure that drugs intended for use in children are adequately tested in children.

Animals↗
PubMed1990

Randomized, double-blind trial of midazolam and diazepam for endoscopic sedation in children.

We performed a prospective, randomized, double-blind study of 41 children (6-18 years of age) who were undergoing esophagogastroduodenoscopy (EGD) to compare the efficacy of diazepam and midazolam with respect to quality of sedation and amnesia. The endoscopist assessed the patients for control of salivation, gag reflex, vomiting and cooperation after intravenous injection of either 0.1-0.15 mg/kg of midazolam or 0.2-0.4 mg/kg of diazepam. The patients answered a questionnaire at 1 and 24 h after the procedure to assess recall of procedure details, pain and/or discomfort, and their medication choice for future procedures. Vital signs were monitored for 1 h after injection. Although midazolam caused greater mean maximum increase in heart rate than diazepam (30 vs. 14/min), no difference was found between the two treatment groups with respect to other vital signs. There was also no difference in physician's assessment or patient recall of specific events during the procedure. However, significantly fewer patients recalled pain or discomfort with midazolam at both 1 and 24 h following the procedure (p = 0.02). In addition, more patients receiving midazolam indicated preference for the same sedation for future procedures. We conclude that midazolam may provide better amnesia in children undergoing endoscopic procedures.

Adolescent↗
PubMed1990

Lack of correlation between extended pH monitoring and scintigraphy in the evaluation of infants with gastroesophageal reflux.

Sixty-nine infants younger than 1 year of age, with symptoms of persistent vomiting, recurrent choking, apnea, persistent cough, or stridor, were evaluated for gastroesophageal reflux. All infants underwent extended intraesophageal pH monitoring for 16 to 24 hours as well as gastroesophageal scintigraphy with technetium 99m sulfur colloid to study the correlation between the two tests. Forty-eight infants exhibited reflux with extended pH monitoring whereas 46 infants showed reflux with scintigraphy. However, the diagnosis of reflux in individual patients by extended pH monitoring corresponded poorly with the diagnosis of reflux in the same patients by scintigraphy. Similarly, no correlation was observed between extended pH monitoring and scintigraphy results, whether expressed as percent gastric emptying or as gastroesophageal reflux ratio. We conclude that extended pH monitoring and scintigraphy measure different pathophysiologic phenomena and detect reflux under different conditions. The ability of these tests to detect reflux may be complementary and they may be of greatest value when used together to enhance the sensitivity and specificity of the diagnostic evaluation. Extended pH monitoring and scintigraphy should not be used interchangeably to monitor gastroesophageal reflux.

Esophagus↗
PubMed1989

Randomized, prospective double-blind trial of metoclopramide and placebo for gastroesophageal reflux in infants.

The effect of metoclopramide on gastroesophageal reflux was studied in 30 infants less than 1 year of age. Gastroesophageal reflux was documented in all infants by extended pH monitoring before enrollment in the study. Patients were randomly assigned to receive metoclopramide 0.1 mg/kg or placebo four times a day, 1/2 hour before feeding for 1 week, followed by the alternate regimen for 1 week. The infants were reevaluated with extended pH monitoring and scintigraphy after 4 to 7 days of each treatment. A symptom score was derived by determining the average number of occurrences of all symptoms recorded daily by parents on a symptom checklist during pretreatment, placebo, and metoclopramide treatment periods. There was a difference between pretreatment evaluation and placebo periods with respect to daily symptom scores (p less than 0.005), reflecting a significant placebo response. However, no difference in scintigraphic study was found between placebo and metoclopramide periods. A significant difference between placebo and metoclopramide periods was noted in the percentage of time esophageal pH was less than 4.0 (p less than 0.001). However, although metoclopramide decreased the proportion of time esophageal pH was less than 4.0, pH remained less than 4.0 for more than 5% of the time in most patients. Substratification of the total group into infants younger and older than 3 months revealed that older infants had greater average daily weight gain during the metoclopramide treatment period (34.3 gm/day) than in the placebo treatment period (6.6 gm/day, p = 0.05). We conclude that metoclopramide in the dosage 0.1 mg/kg four times daily reduces reflux in infants and may be useful for infants with poor weight gain and other serious complications of gastroesophageal reflux.

Body Weight↗
PubMed1988

Adverse drug reactions in children leading to hospital admission.

To provide information regarding pediatric hospital admissions prompted by adverse drug reactions, data were reviewed from an intensive drug surveillance program in which 10,297 patients admitted to diverse pediatric wards at four teaching and three community hospitals were systematically monitored. Among 3,026 neonatal intensive care unit admissions, 0.2% were prompted by adverse drug reactions; among 725 children with cancer, 22% of admissions were prompted by adverse drug reactions. Among 6,546 children with other conditions monitored on general medical and specialty wards at two teaching hospitals and on general pediatric wards at three community hospitals, 2% (131) of admissions were prompted by adverse drug reactions. Two patients (0.03%) died because of their reactions. The proportion of admissions prompted by drug reactions increased between infancy and 5 years of age and tended to be relatively stable thereafter. The drugs most commonly implicated in the admissions were phenobarbital, aspirin, phenytoin, ampicillin/amoxicillin, theophylline/aminophylline, trimethoprim-sulfamethoxazole, and diphtheria-pertussis-tetanus vaccine. Similar proportions of admissions were prompted by adverse drug reactions in teaching hospitals (2.1%) and in community hospitals (1.8%), and the drug groups implicated in these admissions were generally similar in the two settings. In contrast to adult populations, children with adverse drug reactions account for a small proportion of hospital admissions. Findings from this large, systematic study of pediatric admissions to teaching and community hospitals may serve as a baseline to which other pediatric facilities can compare their experience.

Adolescent↗
PubMed1986

Pharmacokinetic basis for antenatal dosing of phenobarbital for the prevention of neonatal intracerebral hemorrhage.

The transplacental and elimination pharmacokinetics of phenobarbital administered antenatally was analyzed in both mothers and infants as part of a study evaluating the efficacy of antenatally administered phenobarbital in the prevention of neonatal intracerebral hemorrhage. Twenty-five pregnant women in labor less than 35 weeks' gestation received 500 mg phenobarbital administered intravenously. The maternal serum phenobarbital level at delivery was 8.76 +/- 1.99 micrograms/ml and cord serum phenobarbital level was 9.0 +/- 1.75 micrograms/ml (all values are mean +/- SD). There was no correlation between the time from phenobarbital administration to delivery (5.6 +/- 4.6 h) and the cord:maternal serum phenobarbital ratio (1.05 +/- 0.21) (r = -0.03; p greater than 0.05). The mean apparent half-life of phenobarbital estimated in 11 infants was 175.5 +/- 45.6 h. The present study documents the ability to predict serum levels in the fetus and neonate from the serum concentrations achieved in the mother.

Cerebral Hemorrhage↗