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J L Blumer

Publications and source records attributed to J L Blumer.

At least 55 records · Page 3Linked to original sources
PubMed1996

Analysis of the variability in the pharmacokinetics and pharmacodynamics of bumetanide in critically ill infants.

OBJECTIVES: Account for the interindividual variability in the pharmacokinetics and pharmacodynamics of bumetanide after intravenous administration of single doses to critically ill infants. METHODS: This prospective open-label study was carried out in the pediatric intensive care unit of a university-based children's hospital. Fifty-three volume-overloaded critically ill infants (age range, 4 days to 6 months) were divided into two groups: those with heart disease (31 infants) and those with lung disease (22 infants). Each patient received a single intravenous bolus dose of bumetanide. Doses, selected in sequential order, ranged from 0.005 to 0.100 mg/kg. Age was used as a continuous variable to determine its effects on the variability in the pharmacokinetics and pharmacodynamics of bumetanide. Hierarchical multiple regression analyses were used to assess the effects of age, disease, and other drugs on the variability in the effects of bumetanide. RESULTS: Total clearance, renal clearance, and nonrenal clearance of bumetanide all increased with age (p < 0.05), but the ratio of renal clearance to total clearance remained constant at about 0.4. Half-life and mean residence time decreased markedly in the first month of life (p < 0.05). Bumetanide excretion rate normalized for dose also increased with increasing age. Patients with lung disease exhibited a significantly greater clearance and shorter half-life (p < 0.05) than those with heart disease, whereas volume of distribution was similar in both groups. The primary determinant of bumetanide excretion rate was the administered dose (73%). Dose-response curves for urine flow rate and electrolyte excretion were similar between disease groups. The time course of the effect of bumetanide excretion rate on pharmacodynamics responses was similar between disease groups, as was the duration of the diuretic effect. CONCLUSIONS: The pharmacokinetics of bumetanide were influenced significantly by age and disease. Differences in pharmacokinetics between patients with lung and heart disease were primarily due to differences in total clearance. The administered dose of bumetanide and age were positive determinants of bumetanide excretion rate and pharmacodynamic responses. Pharmacodynamic responses as a function of bumetanide excretion rate were not significantly different between disease groups.

Aging↗
PubMed1996

Dose-ranging evaluation of bumetanide pharmacodynamics in critically ill infants.

OBJECTIVES: Determine the diuretic effects of single intravenous doses of bumetanide in volume-overloaded critically ill infants. METHODS: A prospective, open-label study was carried out in 56 infants aged 0 to 6 months who required diuretic therapy. Each patient received a single intravenous dose of bumetanide. Doses selected in sequential order ranged from 0.005 to 0.10 mg/kg. Determinations of urine volume, electrolytes, creatinine levels, and osmolality were performed before (collected from -2 to -4 hours to time 0) and at 1, 2, 3, 4, 6, and 12 hours after bumetanide dosing. Serum samples collected at time 0 and at 5, 15, 30, 60, 120, 180, 240, 360, and 480 minutes and urine aliquots collected at time 0, 0 to 1, 1 to 2, 2 to 3, 3 to 4, 4 to 6, and 6 to 12 hours were analyzed for bumetanide concentration. Individual changes in urine flow rate and electrolyte excretion were plotted against corresponding bumetanide excretion rates, taken as the effective dose of the drug. RESULTS: Peak bumetanide excretion rates increased linearly with increasing doses of drug. Time course patterns for urine flow rate and electrolyte excretion were similar for all dosage groups. Urine flow rate and electrolyte excretion increased linearly up to a bumetanide excretion rate of approximately 7 micrograms/kg/hr and either plateaued (urine flow rate) or declined at a bumetanide excretion rate of > 10 micrograms/kg/hr. Diuretic efficiency of bumetanide was maximal at doses of 0.005 to 0.010 mg/kg but decreased at higher doses. CONCLUSIONS: Maximal diuretic responses occurred at a bumetanide excretion rate of about 7 micrograms/kg/hr, corresponding to doses of 0.035 to 0.040 mg/kg. Higher doses produced a proportionately higher bumetanide excretion rate but no increased diuretic effect. Lower doses of bumetanide had the greatest diuretic efficiency, suggesting that continuous infusion of low doses of bumetanide or intermittent low-dose boluses may produce optimal diuretic responses in critically ill infants.

Bumetanide↗
PubMed1996

A pharmacokinetically based propofol dosing strategy for sedation of the critically ill, mechanically ventilated pediatric patient.

OBJECTIVE: To assess the pharmacokinetics and pharmacodynamics of propofol sedation of critically ill, mechanically ventilated infants and children. DESIGN: A prospective clinical study. SETTING: A pediatric intensive care unit (ICU) in a university hospital. PATIENTS: Clinically stable, mechanically ventilated pediatric patients were enrolled into our study after residual sedative effects from previous sedative therapy dissipated and the need for continued sedation therapy was defined. Patients were generally enrolled just before extubation. INTERVENTIONS: A stepwise propofol dose escalation scheme was used to determine the steady-state propofol dose necessary to achieve optimal sedation, as defined by the COMFORT scale, a validated scoring system which reliably and reproducibly quantifies a pediatric patient's level of distress. When in need of continued sedation, study patients received an initial propofol loading dose of 2.5 mg/kg and were immediately started on a continuous propofol infusion of 2.5 mg/kg/hr. The propofol infusion rate was adjusted and repeat loading doses were administered, if needed, using a coordinated dosing scheme to maintain optimal sedation for a 4-hr steady-state period. After 4 hrs of optimal sedation, the propofol infusion was discontinued and simultaneous blood sampling and COMFORT scores were obtained until the patient recovered. Additional blood samples were obtained up to 24 hrs after stopping the infusion and analyzed for propofol concentration by high-performance liquid chromatography. MEASUREMENTS AND MAIN RESULTS: Twenty-nine patients were enrolled into this study. One patient was withdrawn from this study because of an acute decrease in blood pressure occurring with the first propofol loading dose; 28 patients completed the study. All patients were sedated immediately after the first 2.5-mg/kg propofol loading dose. Eight patients were adequately sedated with the starting propofol dose regimen, whereas five patients required downward dose adjustment and 11 patients required dosage increases to achieve optimal sedation. Four patients failed to achieve adequate sedation after five dose escalations and the drug was stopped. Recovery from sedation (COMFORT score of > or = 27) after stopping the propofol infusion was rapid, averaging 15.5 mins in 23 of 24 evaluable patients. In 13 patients who were extubated after stopping the propofol infusion, the time to extubation was also rapid, averaging 44.5 mins. Determination of the blood propofol concentration at the time of recovery from propofol sedation was possible in 15 patients. The blood propofol concentration was variable, ranging between 0.262 to 2.638 mg/L but < or = 1 mg/L in 13 of 15 patients. Similarly, tremendous variation was observed in propofol pharmacokinetics. Propofol disposition was best characterized by a three-compartment model with initial rapid distribution into a small central compartment, V1, and two larger compartments, V2 and V3, which are two-and 20-fold greater in volume, respectively, than V1. Redistribution from V2 and V3 into V1 was much slower than ingress, underscoring the importance of the propofol concentration in V1 as reflective of the drug's sedative effect. Propofol was well tolerated. Two patients experienced an acute decrease in blood pressure which resolved without treatment. CONCLUSIONS: We conclude that a descending propofol dosing strategy, which maintains the propofol concentration constant in the central compartment (V1) while drug accumulates in V2 and V3 to intercompartmental steady-state, is necessary for effective propofol sedation in the pediatric ICU. Our proposed dosing scheme to achieve and maintain the blood propofol concentration of 1 mg/L would appear effective for sedation of most clinically stable, mechanically ventilated pediatric patients.

Adolescent↗
PubMed1996

Problems with resistance in pediatric intensive care.

Antibiotic resistance in the neonatal and pediatric intensive care environments has not been rigorously investigated. There is reason to believe that the epidemiology of antibiotic resistance in these settings may be different from that in other hospital settings because the patients' preadmission health status, the maturity of their immune systems, and their outpatient exposure to antibiotics are different from those seen in adults. At the present time, the areas of greatest concern are the outbreaks of infection caused by methicillin-resistant Staphylococcus aureus in the neonatal ICUs and the emergence of antibiotic-resistant Gram-negative bacteria in pediatric intensive care units (PICU). In the former, colonization and transmission by nursery personnel remains one of the great challenges in infection control. In the latter, new information is emerging which challenges the notion that antibiotic-restriction policies might be an effective means for modulating the emergence of antibiotic-resistant Gram-negative pathogens in the pediatric intensive care environment. It appears that these organisms are largely imported into the ICU from the community and are not a result of antibiotic practices within the unit itself. This observation requires that strategies to control these organisms in the PICU be reassessed.

Critical Care↗
PubMed1995

Pharmacokinetic-based ticarcillin/clavulanic acid dose recommendations for infants and children.

The pharmacokinetic characteristics of ticarcillin and clavulanic acid were determined after the first dose (n = 22) and again under steady-state conditions (n = 16) in a group of infants and children. Study subjects ranged in age from 1 month to 9.3 years; all but 3 study patients were 6 months of age or older. Each patient received 50 mg of ticarcillin and 1.7 mg of clavulanic acid (30:1 ratio) per kg of body weight given intravenously every 4 hours. Elimination half-life, steady-state volume of distribution, and body clearance averaged 1.1 hours, 0.22 L/kg, and 2.7 mL/min/kg, respectively, for ticarcillin, and 0.9 hours, 0.4 L/kg, and 6.2 mL/min/kg, respectively, for clavulanic acid. A total of 71% of the ticarcillin and 50% of the clavulanic acid dose were excreted unchanged in the urine over the 4-hour sampling period. Corresponding renal clearances averaged 2.1 and 3.2 mL/min/kg for ticarcillin and clavulanic acid, respectively. No differences were observed between first dose and steady-state evaluations in the pharmacokinetic behavior of either agent. In contrast, the pharmacokinetic behavior of clavulanic acid was significantly different from that observed for ticarcillin. These pharmacokinetic data combined with known in vitro susceptibilities of important clinical pathogens support a dose of 80 mg of ticarcillin and 2.7 mg/kg clavulanic acid per kg body weight given as a fixed dose combination every 8 hours for the treatment of most systemic infections that occur outside the central nervous system.

Child↗
PubMed1995

Antibiotic-resistant gram-negative bacteria in the critical care setting.

Gram-negative bacilli that are resistant to commonly used antibiotics are a growing problem in seriously ill, hospitalized patients. Numerous outbreaks involving these organisms have been reported in intensive care nurseries and among critically ill adults. In endemic situations, the major reservoir for these pathogens is the patient; occasionally, transmission from patient to patient occurs through the hands of caregivers. Although the degree of antibiotic use probably plays some role in the emergence of antibiotic-resistant gram-negative bacilli, this relationship has not been uniformly demonstrated, and other factors intrinsic to the organisms themselves and to the critically ill patient may play an important role.

Adult↗
PubMed1995

The pharmacokinetics of meropenem in infants and children: a population analysis.

Plasma meropenem concentration versus time data collected during a single dose, pharmacokinetic study in infants and children were analysed using the population pharmacokinetics program NONMEM. A total of 300 meropenem concentrations was obtained from 65 patients ranging from 2 months to 12 years of age; weighing between 3.7 and 46 kg. A two-compartment open pharmacokinetic model with a zero-order infusion over 30 min was fitted to the data. The most important determinant of meropenem clearance was the creatinine clearance but an additional improvement occurred when a nonlinear dependence upon age was included. The most important determinant of the volume of distribution in the central and peripheral compartments was the body weight. The distributional clearance showed a nonlinear dependence on body weight. Demographic factors other than weight and age were not found to be influential in the model. Both clearance and distributional clearance were markedly different in the younger (< 2 years) or lighter (< 10 kg) patients, respectively. Thereafter the parameter values slowly approached those found in adults. In this study, a mean of 4.6 samples per patient was used to provide information on the pharmacokinetics and the determinants of the pharmacokinetic variability in infants and children. The findings in the younger, lighter patients, if generally applicable, might have significance for the dosage recommendations for drugs with narrow therapeutic indices.

Age Factors↗
PubMed1995

Multinational multicenter controlled trial comparing ceftibuten with cefaclor for the treatment of acute otitis media. Members of the Ceftibuten Otitis Media International Study Group.

A randomized, controlled, single blind clinical trial was conducted in children with acute otitis media to evaluate the safety and efficacy of a 10-day course of therapy with ceftibuten 9 mg/kg taken as a single daily dose, up to a maximum daily dose of 400 mg, compared with cefaclor 40 mg/kg/day in three divided doses, up to a maximum of 1 g/day. Patients were evaluated any time from 1 to 3 days after completion of therapy (posttreatment follow-up). A total of 154 patients (106 ceftibuten, 48 cefaclor) were evaluable for efficacy. Clinical success as determined by resolution (cure) or improvement of signs and symptoms of infection were seen in 89 and 88% of patients treated with ceftibuten and cefaclor, respectively, at the posttreatment follow-up visit. At the extended follow-up visit (any time from 2 to 4 weeks after completion of therapy), clinical success was sustained in 88 and 82% of the ceftibuten-treated and cefaclor-treated patients, respectively. A total of 391 patients (264 ceftibuten, 127 cefaclor) were included in the safety analysis. Treatment-related adverse experiences occurred in 8% of ceftibuten-treated patients and 14% of cefaclor-treated patients. All were mild or moderate and the majority were gastrointestinal. There were no deaths or serious adverse events. The results of this study suggest that ceftibuten is an effective and well-tolerated alternative to other antibiotic therapies for the treatment of children with acute otitis media.

Acute Disease↗
PubMed1995

Sequential, single-dose pharmacokinetic evaluation of meropenem in hospitalized infants and children.

Meropenem is a new carbapenem antibiotic which possesses a broad spectrum of antibacterial activity against many of the pathogens responsible for pediatric bacterial infections. In order to define meropenem dosing guidelines for children, an escalating, single-dose, pharmacokinetic study at 10, 20, and 40 mg/kg of body weight was performed. A total of 73 infants and children in four age groups were enrolled in the study: 2 to 5 months, 6 to 23 months, 2 to 5 years, and 6 to 12 years. The first patients enrolled were those in the oldest age group, who received the lowest dose. Subsequent enrollment was determined by decreasing age and increasing dose. Complete studies were performed on 63 patients. No age- or dose-dependent effects on pharmacokinetic parameter estimates were noted. Mean pharmacokinetic parameter estimates were as follows: half-life, 1.13 +/- 0.15 h; volume of distribution at steady state, 0.43 +/- 0.06 liters/kg; mean residence time, 1.57 +/- 0.11 h; clearance, 5.63 +/- 0.75 ml/min/kg; and renal clearance, 2.53 +/- 0.50 ml/min/liters kg. Approximately 55% of the administered dose was recovered as unchanged drug in the urine during the 12 h after dosing. No significant side effects were reported in any patients. By using the derived pharmacokinetic parameter estimates, a dose of 20 mg/kg given every 8 h will maintain plasma meropenem concentrations above the MIC that inhibits 90% of strains tested for virtually all potentially susceptible bacterial pathogens.

Aging↗
PubMed1995

Slow component of O2 uptake during heavy exercise: adaptation to endurance training.

Seven untrained male subjects [age 25.6 +/- 1.5 (SE) yr, peak O2 uptake (VO2) 3.20 +/- 0.19 l/min] trained on a cycle ergometer 4 days/wk for 6 wk, with the absolute training workload held constant for the duration of training. Before and at the end of each week of training, the subjects performed 20 min of constant-power exercise at a power designed to elicit a pronounced slow component of VO2 (end-exercise VO2-VO2 at minute 3 of exercise) in the pretraining session. An additional 20-min exercise bout was performed after training at this same absolute power output during which epinephrine (Epi) was infused at a rate of 100 ng.kg-1.min-1 between minutes 10 and 20. After 2 wk of training, significant decreases in VO2 slow component, end-exercise VO2, blood lactate ([La-] and glucose concentrations, plasma Epi ([Epi]) and norepinephrine concentrations, ventilation (VE), and heart rate (HR) were observed (P < 0.05). Although the rapid attenuation of the VO2 slow component coincided temporally with reductions in plasma [Epi], blood [La-], and VE, the infusion of Epi after training significantly increased plasma [Epi] (delta 2.22 ng/ml), blood [La-] (delta 2.4 mmol/l) and VE (delta 10.0 l/min) without any change in exercise VO2. We therefore conclude that diminution of the VO2 slow component with training is attributable to factors other than the reduction in plasma [Epi], blood [La-] and VE.

Adaptation, Physiological↗
PubMed1995

Carbapenems in paediatrics.

Serious infections in paediatric patients pose some unique challenges to clinicians. Children represent a dynamic group of patients in whom there are age-related changes as well as age-related alterations in the biodisposition of various antimicrobial agents. In infants and children with serious infections multidrug therapy is generally employed. This occurs because most antibiotic therapy in these patients is initiated and continued on an empiric basis and few, if any, of the currently available agents may be employed confidently as monotherapy. When the agents currently available are compared on a pharmacokinetic and pharmacodynamic basis the carbapenems emerge as close to ideal for the treatment of serious infections in infants and children. Imipenem is the only member of this group currently available. It lacks paediatric labelling in the USA and its efficacy has not been compared directly with that of antibiotic regimens commonly employed in children. Meropenem is a new carbapenem currently under evaluation of the treatment of moderate to severe infections in children and adults. In 2 multicentre, randomised evaluations of the treatment of a variety of infections including lower respiratory tract infections, urinary tract infections, intra-abdominal infections, infections of the skin and skin structures, and septicaemia, the efficacy and safety of meropenem monotherapy were compared with those of cefotaxime-based regimens. Meropenem had an overall clinical efficacy rate of 98% compared with a rate of 95% for cefotaxime-based regimens. Neither regimen was associated with any significant clinical or laboratory adverse events. The carbapenem, meropenem, appears to be a reasonable choice for empiric therapy in infants and children with serious infections. Meropenem monotherapy has been evaluated and has been found to be as well tolerated and as effective as cefotaxime-based regimens in these patients.

Bacterial Infections↗
PubMed1994

Effective short-course treatment of acute group A beta-hemolytic streptococcal tonsillopharyngitis. Ten days of penicillin V vs 5 days or 10 days of cefpodoxime therapy in children.

OBJECTIVE: To compare bacteriologic and clinical efficacy and safety of 10 vs 5 days of cefpodoxime proxetil vs 10 days of penicillin V potassium for the treatment of acute group A beta-hemolytic streptococcal tonsillopharyngitis in children. DESIGN: Prospective, randomized, observer-blind, multicenter study. PATIENTS/INTERVENTIONS: Four hundred eighty-four children (age range, 2 to 17 years) with signs and symptoms of acute tonsillopharyngitis were enrolled; 377 had a positive throat culture for group A beta-hemolytic streptococci and were fully evaluable. One hundred twenty-one patients received cefpodoxime once a day for 10 days, 126 received cefpodoxime twice a day for 5 days, and 130 received penicillin V three times a day for 10 days. RESULTS: Cefpodoxime for 10 days vs cefpodoxime for 5 days vs penicillin V for 10 days produced bacteriologic eradication at the end of therapy in 95%, 90%, and 78% of the patients, respectively. The 10- and 5-day cefpodoxime treatment regimens were more efficacious than penicillin V (P = .003 and P = .02, respectively). The cumulative bacteriologic failure rate among assessable patients by the 32- to 38-day posttreatment visit was 20 (17%) of 121 patients who were treated with cefpodoxime for 10 days, 24 (19%) of 125 patients who were treated with cefpodoxime for 5 days, and 45 (35%) of 130 patients who were treated with penicillin V for 10 days (P = .001 and P = .005, respectively). Clinical cure or improvement was observed at the end of therapy in 96%, 94%, and 91% of the patients, respectively (P = not significant). Adverse events were infrequent and similar in all three treatment groups, with minor gastrointestinal side effects predominating. CONCLUSIONS: Five days of treatment with cefpodoxime is as efficacious in bacteriologic eradication and clinical response (cure plus improvement) as 10 days of cefpodoxime therapy, and both cefpodoxime regimens produced superior bacteriologic efficacy compared with a 10-day regimen of penicillin V in the treatment of group A beta-hemolytic streptococcal tonsillopharyngitis in children.

Acute Disease↗
PubMed1994

Therapeutic drug monitoring in the pediatric intensive care unit.

Drugs are administered in the pediatric intensive care unit using either a target-effect or a target-concentration strategy. In the former, drug dose is escalated until the predetermined target-effect is achieved, no further pharmacologic effect is obtained with incremental increases in dose, or toxicity supervenes. When the target-concentration strategy is used, drug therapy is adjusted to achieve serum/plasma drug concentrations within an accepted therapeutic range. This strategy does not recognize interindividual differences in drug responsiveness. Therapeutic drug monitoring in the pediatric intensive care unit is further confounded by the limited data available concerning the effects of the other technologies used on drug disposition and the paucity of information related to therapeutic agents in pediatric patients. Clearly therapeutic drug monitoring in the pediatric intensive care unit is a daunting challenge.

Adolescent↗
PubMed1994

Optimal sedation of mechanically ventilated pediatric critical care patients.

OBJECTIVE: To derive a target range of optimal sedation for the COMFORT Scale and to prospectively test that target range against intensivist assessment of adequacy of sedation. DESIGN: Serial prospective agreement cohort studies. SETTING: Twelve-bed pediatric intensive care unit in an urban academic teaching hospital. PATIENTS: Eighty-five mechanically ventilated children (aged 0 to 102 months). INTERVENTIONS: Three serial prospective studies comparing simultaneous, independent ratings conducted by trained observers using an objective scale and intensive care physicians using global assessment. The initial study was designed to derive the target range. The second study was conducted to verify that target range in a second population. The third study was added to evaluate relative variability in methods used in the second study. MEASUREMENTS AND MAIN RESULTS: Adequacy of sedation using visual analog scale and descriptive ratings or the COMFORT Scale (a previously validated behaviorally anchored scale to rate eight behavioral or physiologic dimensions of distress). The first study comprised 100 observations. Groups of patients described by the intensivist as inadequately sedated, optimally sedated, and excessively sedated had different mean COMFORT scores (30.5 +/- 0.7 vs. 22.9 +/- 5.8 vs. 14.3 +/- 0.7, respectively, p < .05). The target range of optimal sedation was defined as COMFORT scores of 17 to 26. The second study verified the target range prospectively in a second group of 96 observations. The COMFORT score was strongly associated with the sedation adequacy rating by the intensivist (p < .001; r2 = .662). COMFORT scores accurately predicted the patient assignment to adequacy of sedation categories by the intensivist in 66.1% of observations. Discrepancy between physicians occurred in 38.5% of 16 paired physician ratings in the second study. In the third study, 120 observations comparing paired COMFORT scores to paired physician ratings of the same subjects demonstrated significantly less variability in COMFORT assessment of adequacy of sedation. COMFORT scores were similarly unbiased (1.1% vs. 0.22%) but more precise (8.0% vs. 16.7%) than intensivist ratings (p < .025). CONCLUSION: Adequacy of sedation is measured more consistently by observers using the COMFORT Scale than by intensivist global assessment.

Child↗