Advances in pediatric pharmacokinetics and therapeutics.
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Clinical Trials as Topic↗
Biomedical subjects
S J Phelps
Publications and source records attributed to S J Phelps.
A rapid, noninstrumented whole blood carbamazepine assay for pediatric patients.
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Adolescent↗
Inability of inline pressure monitoring to predict or detect infiltration of peripheral intravenous catheters in infants.
Monitoring of inline intravenous pressure as a method for predicting or detecting infiltration of peripheral catheter sites in infants was evaluated. Inline intravenous pressure was measured every 30 minutes in infants less than 12 months of age who had standardized peripheral catheters through which they were receiving a continuous infusion. Pressure was measured by an inline pressure transducer, and the signal was recorded by a strip chart recorder. Physical activities or manipulations of the patients were recorded simultaneously with each pressure reading. The catheter site was inspected hourly for clinical signs of infiltration. There was no significant difference in baseline or final pressure measurements between patients whose catheter sites became infiltrated (n = 20) and patients whose catheter sites did not (n = 22). Likewise, changes in pressure from baseline did not differ between the infiltrated and noninfiltrated groups. At 12 hours before the final reading, pressures for the infiltrated group did not differ significantly from pressures for the noninfiltrated group, nor did these values differ from the respective baseline values. Over the final 12 hours of catheterization, mean slopes (changes in pressure over time) for the two groups did not differ significantly from 0 or from each other. Intrapatient specificity and sensitivity of the method and the false-alarm rate were clinically unacceptable. Monitoring of inline intravenous pressure is not useful for predicting or detecting infiltration of peripheral catheter sites in infants.
Catheterization, Peripheral↗
Parenteral nutrition in the critically ill patient.
The metabolic alterations, nutritional and metabolic assessment, and nutritional requirements of critically ill patients are discussed, and parenteral nutrition support therapies are reviewed. Physiological alterations in the metabolism of the injured or septic patient are mediated through the interactions of neuroendocrine, cardiovascular, toxic, and starvation responses. These responses cause mobilization of nutritional substrates in an effort to maintain vital organ function and immune defenses. A patient's nutritional status can be determined from anthropometric measurements, creatinine excretion rate, and evaluations of protein stores and immune reserves and function; body weight is a poor indicator. Nitrogen-balance calculations are also useful for determining the adequacy of nutritional intake and the degree of metabolic stress. Early assessments of nutritional status may assist in identifying those patients for whom nutritional support interventions are needed. Nutritional requirements are altered by the metabolic responses to injury and sepsis. Studies suggest that use of nutrient solutions enriched for branched-chain amino acids may enhance nitrogen retention and that energy expenditures in injured or septic patients are only moderately elevated. Most nonprotein calories in parenteral nutrient solutions are provided as glucose, but lipids are an important source of energy in the critically ill patient who has high energy requirements or carbohydrate intolerance; however, clearance of lipids may be decreased. Fluid, electrolyte, and mineral status must be evaluated frequently. Critically ill patients have unique nutritional requirements, and parenteral nutrition support therapies for these patients are being investigated and refined.
Critical Care↗
The influence of gestational age and preeclampsia on the presence and magnitude of serum endogenous digoxin-like immunoreactive substance(s).
Digoxin-like immunoreactive substance(s) has been measured in serum during pregnancy. Because of its presence in pregnancy, investigators have suggested that digoxin-like immunoreactive substance may play an etiologic role in the development of preeclampsia. The objectives of this study were to evaluate the relationship between maternal digoxin-like immunoreactive substance and gestational age and compare digoxin-like immunoreactive substance concentrations in patients with and without preeclampsia who were in the third trimester. Two hundred twenty patients were studied during either the first (n = 53), second (n = 56), or third (n = 111) trimester of pregnancy. Digoxin-like immunoreactive substance was undetectable in the serum of patients during the first trimester; however, 11% of second-trimester and 96% of third-trimester patients had measurable levels of serum digoxin-like immunoreactive substance (p less than 0.05). The mean +/- SEM concentration of digoxin-like immunoreactive substance in serum in third-trimester patients was 0.29 +/- 0.01 ng/ml (range 0 to 0.58 ng/ml). Gestational age at delivery was significantly lower in patients with preeclampsia than in those without preeclampsia (36.3 +/- 0.6 versus 38.8 +/- 0.4 weeks; p less than 0.001). In addition, there was no statistical difference in mean +/- SEM concentration of digoxin-like immunoreactive substance between 27 patients without preeclampsia (0.32 +/- 0.02 ng/ml) and 27 patients with preeclampsia (0.30 +/- 0.02 ng/ml; p = 0.47) matched for gestational age. We conclude that (1) digoxin-like immunoreactive substance appearance and increasing serum concentration during pregnancy are correlated with increasing gestational age and (2) there is no difference in digoxin-like immunoreactive substance values between patients with and without preeclampsia, which may exclude digoxin-like immunoreactive substance as a predictor of preeclampsia.
Adolescent↗
Treatment of severe digitalis intoxication with digoxin-specific antibody fragments: a clinical review.
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Animals↗
Parenteral nutrition in pediatric patients.
Protein, calorie, fluid, fat, and micronutrient requirements of pediatric patients are reviewed, as are methods of nutritional assessment and complications associated with the use of parenteral nutrition in these patients. In general, preterm infants and neonates require greater per-kilogram amounts of protein, calories, fluid, and micronutrients than older children. In addition, preterm infants and neonates have deficiencies in enzymes that metabolize certain amino acids, making otherwise nonessential amino acids essential. These unique protein needs have been addressed in amino acid formulations designed specifically for this group of patients. Supplying the neonate with the calcium and phosphorus needed for bone growth can be difficult because of solubility limitations in parenteral nutrient solutions. The use of intravenous fat emulsion in infants with hyperbilirubinemia or pulmonary complications is controversial. However, only rarely does fat emulsion have to be completely withheld. Complications associated with parenteral nutrition in pediatric patients include infection, metabolic disorders (cholestasis, bone demineralization), and mechanical problems. Cholestasis induced by parenteral nutrition has been shown to be more common in low-birth-weight infants; however, the precise etiology is unknown and may be multifactorial. Basic requirements necessary to promote growth while pediatric patients are receiving parenteral nutrition have been determined. However, current studies are challenging what were thought to be standards of pediatric parenteral nutrition therapy.
Child↗
Rocky Mountain spotted fever.
The epidemiology, pathogenesis, clinical features, and treatment of Rocky Mountain spotted fever are reviewed. Rocky Mountain spotted fever is a severe infection caused by Rickettsia rickettsii transmitted to man by various species of ticks. High-incidence areas exist in the southeast and south central United States. Only 60-70% of patients with the disease report a history of tick bite or exposure to tick-infested areas. The disease is initially characterized by fever, headache, gastrointestinal complaints, myalgia, and a generalized rash. In several days generalized vasculitis may lead to periorbital edema and nonpitting edema of the face and extremities. Central nervous system involvement is common. Because signs and symptoms associated with the disease are nonspecific, the diagnosis is often delayed or missed. Traditionally diagnostic confirmation relied on serologic testing, but an indirect fluorescent antibody assay will soon be commercially available. Rocky Mountain spotted fever is usually treated with the rickettsiostatic agents chloramphenicol or tetracycline, but few comparative data on these agents in patients with the disease are available. For patients who cannot tolerate oral medications, intravenous chloramphenicol sodium succinate is the preferred treatment; chloramphenicol is also the drug of choice for children less than eight years of age. Otherwise, oral tetracycline hydrochloride is the drug of choice. Antibiotic therapy should be continued for 7-10 days or until the patient is afebrile for two to five days. All cases of Rocky Mountain spotted fever must be reported to the Centers for Disease Control. The best ways to decrease the morbidity and mortality of the disease are to increase awareness of its signs and symptoms and to prevent exposure to ticks.
Humans↗
Digoxin-like immunoreactive substance in pregnancy.
Our aims were to determine the potential usefulness of digoxin-like immunoreactive substances in the prediction of preeclampsia, to study the relationship between fetal production of these substances and maternal serum levels, and to evaluate the association between digoxin-like immunoreactive substances and plasma volume findings in preeclamptic pregnancies. Serum digoxin-like immunoreactive substance concentrations were measured in normotensive and preeclamptic pregnant women and in umbilical artery and vein blood samples. None of the patients in the first trimester (n = 53) and 11% of those in the second (n = 56) had detectable levels of this substance. However, 91% of the patients in the third trimester (n = 161) had positive results. The concentrations of digoxin-like immunoreactive substances in the preeclamptic group (n = 78) were significantly (p less than 0.005) lower than those of third-trimester (n = 83) normotensive patients (0.22 +/- 0.12 versus 0.32 +/- 0.15 ng/ml). However, there were no significant differences between the two groups regarding digoxin-like immunoreactive substance concentrations when matched for gestational age (41 patients in each group). Digoxin-like immunoreactive substance concentrations in umbilical vessels were significantly higher (p less than 0.001) than the corresponding maternal levels. Umbilical vessel digoxin-like immunoreactive substance levels demonstrated good correlation with fetal gestational age and birth weight in both normotensive and preeclamptic pregnancies. On the other hand, there was a poor (r = 0.02; p = 0.91) correlation between plasma volume findings and digoxin-like immunoreactive substance concentration. We conclude that the digoxin-like immunoreactive substance level may be of very little value in the prediction of preeclampsia. The presence of digoxin-like immunoreactive substance at greater concentrations in the umbilical cord blood samples suggests the possibility of the fetus as the source of this substance. Digoxin-like immunoreactive substances may not play a major role in plasma volume expansion during pregnancy.
Blood Proteins↗
Effect of age and serum creatinine on endogenous digoxin-like substances in infants and children.
An apparent digoxin-like immunoreactive substance(s) (DLIS) was evaluated in 374 pediatric patients, 0 to 72 months of age, not receiving digoxin. The relationship between DLIS presence or concentration and age, weight, gender, race, and serum creatinine was investigated. Twenty-seven percent of patients had a positive apparent DLIS concentration (greater than or equal to 0.2 ng/ml). The mean +/- SD concentration of DLIS in the positive group was 0.39 +/- 0.18 ng/ml (range 0.2 to 1.37 ng/ml). Patients in the DLIS-positive group were younger than those in the negative group (P less than 0.01). Although a greater percentage of infants younger than 6 months of age had measurable DLIS, the mean DLIS concentrations, when present, were not significantly different for all age groups (P greater than 0.05). No significant relationship was found between race or gender and DLIS. A weakly positive correlation between serum creatinine concentration and DLIS was noted (r = 0.22, P less than 0.03), but elevated serum creatinine measurements (greater than 0.6 mg/dL) did not correlate with DLIS concentration. These results support the hypothesis that the presence of DLIS is age related, but DLIS appears to be present in a much larger and older population of pediatric patients than previously reported.
Aging↗
Risk factors affecting infiltration of peripheral venous lines in infants.
The influence of 11 variables on the infiltration of peripheral venous lines (PVLs) was evaluated during 151 infusions in patients younger than 1 year of age. Infusions were followed from the time of cannula placement to discontinuation. Fifty-eight percent of PVLs were infiltrated by 36.30 +/- 33.53 hours (mean +/- SD; median 40 hours, range 10 to 187 hours). No difference between infiltrated and noninfiltrated PVLs was noted with regard to patient age, gender, weight, cannula type, cannula gauge, cannula site, infusion device, potassium or dextrose concentration, medications, or rate of solution administration (P greater than 0.05). Infiltration was observed more often in black than in white infants (P = 0.03) and in patients with lower controller solution head heights (P = 0.01). The time to infiltration was decreased significantly for steel verus Teflon cannulas (P = 0.02), for administration of intravenous medication versus no administration of medication (P = 0.03), for peripheral parenteral nutrition solutions compared with 5% or 10% dextrose solutions (P = 0.014), and with increasing cannula gauge (P = 0.05). The time to infiltration did not differ significantly for gravity-controlled versus positive-pressure infusion device delivery (P = 0.51) or for potassium concentrations less than or equal to 20 mEq/L versus greater than 20 mEq/L (P = 0.13). Infusion device occlusion alarms were associated with only 19% of infiltrations. No sloughing of skin or necrosis of tissue occurred related to infiltration.
Black or African American↗
Chloramphenicol-induced cardiovascular collapse in an anephric patient.
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Adult↗
Interference with digoxin immunoassays.
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Blood Proteins↗
Comparison of a noninstrumented immunoassay for carbamazepine to high performance liquid chromatography and fluorescence polarization immunoassay.
The accuracy, precision, and potential clinical utility of a new whole blood, noninstrumented immunochromatographic assay (AccuLevel) for carbamazepine (CBZ) was evaluated in a multicenter trial including 100 pediatric and 205 adult patients. The AccuLevel assay, a fluorescence polarization immunoassay (FPIA), and high-performance liquid chromatography (HPLC) were used to determine CBZ concentration in samples from 111 female and 194 male patients aged 2-72 years (median 25 years). Mean +/- SD plasma CBZ concentrations in all patients were 7.4 +/- 3.0 micrograms/ml with the AccuLevel assay and 7.5 +/- 2.9 micrograms/ml with FPIA. In 204 patients, the mean concentration determined by the HPLC assay was 7.7 +/- 3.0 micrograms/ml, whereas concentrations determined by the AccuLevel and FPIA assays were 8.0 +/- 3.1 and 8.1 +/- 3.1 micrograms/ml, respectively. Concentrations determined by the AccuLevel and FPIA assays were significantly higher than those quantified by HPLC (p less than 0.05), but not different from each other. In addition, the AccuLevel assay was highly correlated with FPIA (r = 0.97) and HPLC (r = 0.98). Coefficients of variation for the AccuLevel assay at 8 micrograms/ml ranged from 6.8 to 7.5% for the three institutions. We conclude that the AccuLevel assay is a simple, reliable method for determining CBZ concentration in a small volume of whole blood and is an acceptable alternative for assessment of CBZ therapy and individualization of CBZ dosage in the physician's office or emergency room.
Adolescent↗
Effect of the continuous administration of fat emulsion on the infiltration of intravenous lines in infants receiving peripheral parenteral nutrition solutions.
Animal data and anecdotal human experience suggest that vascular damage induced by the infusion of dextrose/amino acid solutions may be ameliorated by the concomitant administration of fat emulsion. We prospectively evaluated the effect of the continuous infusion of peripheral nutrition solutions with and without fat emulsion on the incidence of, probability of, and time to infiltration of peripheral venous lines in infants (median age: 1.0 month; range 1 day-11.9 months). Ninety-seven peripheral venous lines were studied in 53 infants who received 10% dextrose (n = 34), 10% dextrose/2% amino acids (n = 30), or 10% dextrose/2% amino acids/fat emulsion (n = 33). Solutions were administered by positive pressure infusion devices through Teflon catheters with similar gauge. Dextrose, amino acid, electrolyte, and mineral content was standardized for the dextrose/amino acid and dextrose/amino acid/fat emulsion groups. The three groups were similar with respect to age, race, gender, weight, administration of intravenous medications, and catheter site (p greater than 0.05). Patients receiving dextrose/amino acid or dextrose/amino acid/fat emulsion had greater rates of solution administration than those receiving dextrose alone (p less than 0.002). Infiltration occurred in 71% of dextrose, 66% of dextrose/amino acid, and 67% of dextrose/amino acid/fat emulsion solutions (p greater than 0.05). The probability of infiltration was greater for infants receiving dextrose/amino acid than for those receiving either dextrose or dextrose/amino acid/fat emulsion (p = 0.01). The mean +/- SEM length of time the intravenous sites were viable was significantly shorter for the dextrose/amino acid solutions (26.3 +/- 3.3 hr) compared to the dextrose (54.9 +/- 7.8 hr) and dextrose/amino acid/fat emulsion (43.6 +/- 4.2 hr) groups. No site complications were associated with the infiltration of any solution. We conclude that the incidence of infiltration among the three solution groups studied is not different. However, the time to infiltration is prolonged and the probability of infiltration is decreased following the infusion of either dextrose alone or dextrose/amino acid/fat emulsion solutions when compared to the administration of dextrose/amino acid solutions without concomitant fat emulsion infusion.
Amino Acids↗
Hemodynamic response to intentionally altered flow continuity of dobutamine and dopamine by an infusion pump in infants.
STUDY OBJECTIVE: To evaluate the effect of an intentional alteration in infusion pump flow continuity on the hemodynamic stability of infants receiving either dobutamine or dopamine. DESIGN: Prospective, open-label study. SETTING: A university-affiliated children's hospital. PATIENTS: Ten hemodynamically stable infants (age 2 wks-10 mo) in intensive care receiving dobutamine (5) or dopamine (5). Three patients received both agents and were studied at independent times. INTERVENTIONS: Dobutamine and dopamine were administered using the Flo-Gard VP pump that delivers an intentional alteration of flow continuity (rate pulse). Heart rate and mean arterial pressure (MAP) were recorded every second. Analysis was based on the measurements obtained from the first 5 minutes on the study pump and the 2 minutes before and after the rate pulse. MEASUREMENTS AND MAIN RESULTS: Although hemodynamic changes in pre- and post-rate pulses were statistically significant (p < 0.05) in some individuals, only one infant had a greater that 10% change in MAP 2 minutes after the rate pulse. Alterations in hemodynamics were not consistent among or within patients. CONCLUSION: In infants requiring dobutamine or dopamine, no clinically significant pharmacodynamic effects were associated with alteration in continuity of drug delivery caused by the single positive rate pulse. Therefore, we conclude there is no contraindication to the use of this infusion pump in hemodynamically stable infants receiving these drugs.
Cardiotonic Agents↗