Biomedical subjects

B J Zarowitz

Publications and source records attributed to B J Zarowitz.

At least 73 records · Page 4Linked to original sources

PubMed1988

Variability in theophylline volume of distribution and clearance in patients with acute respiratory failure requiring mechanical ventilation.

This study examines the intrasubject variability in theophylline volume of distribution (V) and clearance (CL) in critically ill, mechanically ventilated adults. Fifteen patients received two intravenous doses of theophylline approximately ten hours apart. Although there was no statistical difference between the mean VI (first dose, 0.51 L/kg) and V2 (second dose, 0.47 L/kg), the absolute difference between measurements of 0.15 L/kg was statistically significant (p less than .05). Range of differences follows: between VI and V2, 3.8 to 72.4 percent (mean, 33.5 percent); between CL1 and CL2, 6.1 to 100 percent (mean, 32.2 percent). Absolute difference between clearances was 0.019 L/kg/hr. A comparative error analysis revealed an absolute difference for V of 27.9 percent and for CL of 37 percent. Considerable intra-subject variability was shown for theophylline V and CL in these critically ill adults. Variability in V was not significantly different than variability in CL, and may result in severe underdosing or overdosing.

Acute Disease↗

PubMed1987

Individualizing nutrition in patients with acute respiratory failure requiring mechanical ventilation.

Provision of adequate nutrition is recognized as a therapeutic necessity to maintain inspiratory muscle strength and prevent weaning failures in patients with acute respiratory failure requiring mechanical ventilation. Total caloric needs are empirically estimated by calculation of basal energy expenditure and modified by correction factors for concurrent levels of stress. Energy requirements can vary considerably from empiric estimations and may be better defined by indirect calorimetry that measures oxygen consumption and carbon dioxide production. Protein constituents are initiated empirically until patient-specific urea nitrogen excretion is available. The addition of fat emulsion as 20-50 percent of total daily calories limits lipogenesis, prevents excessive carbon dioxide production, and provides a volume-concentrated caloric source to fluid-restricted patients. Manipulation of nutrient composition can improve or impair ventilatory weaning and nutritional rehabilitation. The significance of substrate utilization is reviewed and recommendations for establishing nutritional regimens for mechanically ventilated adults with acute respiratory failure are provided.

Energy Metabolism↗

PubMed1987

A clinical pharmacy-oriented drug surveillance network: II. Results of a pilot project.

A nationwide network of clinical pharmacists has been organized for the purpose of collecting drug experience data generated during the routine clinical care of patients. In order to assess the utility of this network a pilot project was performed to obtain a cross-sectional view of antibiotic utilization in the U.S. and to identify potential problems with a more widespread implementation of this program. One hundred eleven pharmacists enrolled in the drug surveillance network participated in this survey and collected information on more than 2000 patients treated with antimicrobial agents over approximately a three-month period (February-April 1987). The most common sites of infection were the lung, genitourinary tract, skin and soft tissue, and the abdomen, and accounted for approximately 75 percent of infections. Overall, the aminoglycosides, the first-generation cephalosporins, and the aminopenicillins remain the most commonly used antibiotics and represent approximately 50 percent of antimicrobials used in the surveyed population. The results of this pilot project suggest that the use of a nationwide network of clinical pharmacists is a promising source of clinically relevant drug experience data. The ability to concurrently evaluate patients and link information regarding patient demographics, drug therapy regimens, diagnosis, and clinical outcomes fills an important gap in our knowledge of clinical drug utilization.

Adult↗

PubMed1987

Developing and implementing standards of practice for clinical pharmacy services.

The authors' department has attempted to bring more order to the provision and evaluation of clinical services through the development of "Clinical Standards of Practice." A pilot project was initially conducted on one satellite. Pharmacists were asked to prepare a list of minimum standards that could be agreed upon and that everyone believed were achievable even on the busiest days. After standards were developed and implemented, a procedure was established to evaluate compliance through review of pharmacy records and patient materials. Staff received feedback concerning the results of the review. As a result of the success with the pilot, Clinical Standards of Practice have been developed by staff and are in use throughout the department. Plans for the future include continuous revision of the standards to reflect changing departmental goals and directions and a change to a "pharmacist specific" rather than a current "nursing unit specific" monthly review format to facilitate performance review and staff development. Eleven standards are shown in the appendices.

Clinical Competence↗

PubMed1987

Evaluation of gentamicin premixed admixtures: cost and clinical utility.

An objective of this study was to evaluate the cost effectiveness of employing gentamicin premixed admixtures compared to using exact, individualized compounded doses. Gentamicin use and waste data were collected over a 2-month period. Annualized institutional savings (300 beds) were projected to be $8,802. A second objective was to compare predicted to measured peak and trough serum gentamicin concentrations when premixed admixtures are used (rounding off computer generated doses to the nearest 10 mg) and when individually compounded exact doses are delivered. Twenty adults were randomized to receive premixed or compounded doses. Blood levels drawn at steady state were compared to predicted levels for the delivered dose. Differences between measured and predicted levels were not significant by performance of an independent t test on the mean square prediction errors. We conclude that it is cost effective and clinically valid to employ premixed intravenous admixtures in a large teaching hospital.

Adult↗

PubMed1987

Work group design in pharmacy: the pharmacist-technician team.

The contemporary pharmacy practice manager faces the challenge of designing pharmacy service programs that not only satisfy the needs of the patient, but at the same time satisfy and motivate the pharmacists and technicians who sustain the programs. This research examined the team design, which has been recommended but not fully described in the literature. This application did not explore the full potential of the team design in the hospital pharmacy setting. More study is needed in this area to assess the impact of work group design on the expansion of clinical programs, employee turnover rates, quality and quantity of work produced, and, most important, the impact on job satisfaction enjoyed by pharmacists and technicians.

Data Collection↗

PubMed1986

Evaluation of premixed intravenous theophylline loading doses.

We evaluated the use of a standard protocol utilizing premixed theophylline containers in comparison to traditional intravenous aminophylline loading doses in 19 critically ill adults. Blood samples were obtained immediately before and after 30-minute infusions of aminophylline and theophylline bags. Aminophylline loading doses were calculated to the exact mg/kg and were delivered as such. Calculation of the theophylline loading dose used a simplified protocol that uses doses rounded to the nearest 100 mg. Comparison of the relative performance of the two loading dose methods was evaluated by computing mean squared prediction errors and root mean squared errors. The two methods were not statistically different when evaluated by a matched pair t-test. We conclude that use of a standard protocol that rounds theophylline doses to the nearest 100mg results in peak theophylline concentrations not significantly different from those predicted.

Aged↗

PubMed1985

Pharmacist competency certification in aminoglycoside dosing.

A pharmacist competency-certification program was developed to train and evaluate newly hired pharmacists, provide continuing education and skills development for staff pharmacists, and standardize clinical pharmacy practice at a 940-bed teaching hospital. A pretest, self-teaching module, and written final examination were developed; the total program can be completed in approximately one month. The self-teaching module contains 37 pages of factual material on the pharmacology, pharmacokinetics, antimicrobial spectra, cost, relative toxicities, and dosing and monitoring techniques for aminoglycoside antibiotics. The pretest and final examination consist of 20 multiple-choice questions based on actual patient cases. Following its initial implementation, 21 of 49 staff pharmacists elected to complete the program. There was an equal representation of pharmacist trainees, novice pharmacists, and experienced clinical pharmacists. All three groups demonstrated improvement over pretest scores. The trainees and novice pharmacists showed the greatest improvement. This program defines a standard of practice and provides a continuing-education tool. Because of its success, the program has been mandated in the orientation of all clinical pharmacists.

Aminoglycosides↗

PubMed1984

The pharmacokinetics and metabolism of cimetidine in neonates.

Cimetidine pharmacokinetics and metabolism were studied in 2 full-term and 1 premature neonates. All infants demonstrated the capacity to eliminate cimetidine via both metabolic and renal routes. The half-life of cimetidine ranged from 3.4 to 2.1 h, and decreased as total body clearance increased. These alterations in pharmacokinetics were felt to represent developmental and maturational differences, primarily in renal function. In contrast to the 60% routinely seen in adults, approximately 90% of the administered dose was recovered in the urine of the full-term infants as cimetidine and its known metabolites. Cimetidine sulfoxide and hydroxymethyl cimetidine were detected in the serum and urine of 2 patients, and the elimination half-life of these metabolites was two- to threefold longer than values seen for cimetidine. During multiple dosing of cimetidine, significant accumulation of cimetidine metabolites may be expected. The reported dose of 15-20 mg/kg/day is adequate in full-term neonates, however, it appears that premature infants and those with renal dysfunction may require lower dosing rates.

Biotransformation↗

PubMed1982

High gentamicin trough concentrations in neonates of less than 28 weeks gestational age.

77 newborns, ranging from 25.5 to 43 weeks gestational age (GA) and receiving gentamicin, were studied prospectively over 4 months. Peak and trough serum concentrations were obtained on days 1, 3, and 5 of therapy. Gentamicin, 2.5 mg/kg/dose, was given at intervals according to GA. 63% of newborns of less than 28 weeks on doses of gentamicin of 2.5 mg/kg every 24 h (q24h), 75% of less than 28 weeks on gentamicin q18h, 90% of newborns of 23-34 weeks (on q18h), and 82% of those of greater than 34 weeks GA (on q12h) had serum gentamicin trough concentrations less than or equal to 2.0 micrograms/ml on day 1. By day 3, 5/5 newborns of less than 28 weeks (q18h) had trough concentrations greater than 2.0 micrograms/ml, whereas only 20% of those on the q24h regimen had high trough concentrations (p less than 0.05). Possible risk factors associated with altered gentamicin disposition in neonates are discussed.

Bacterial Infections↗

PubMed1981

Effect of erythromycin base on theophylline kinetics.

Because of several recent reports describing altered theophylline elimination in the presence of salts of erythromycin, the effect of a 10-day course of erythromycin base on theophylline kinetics was studied in eight healthy adult men. Theophylline (4 mg/kg) was given on four separate study days: (1) prior to starting erythromycin, (2) on the third day of erythromycin administration, (3) on the tenth day of erythromycin administration, and (4) 2 weeks after the course of erythromycin was completed. Mean theophylline kinetic parameter values on each of the 4 study days were: apparent volume of distribution (Vd), 0.466, 0.466, 0.472, and 0.470 1/kg; elimination half-life (t1/2), 7.4, 7.8, 8.5, and 7.0 hr; and total body clearance (ClB), 0.747, 0.723, 0.683, and 0.821 ml/min/kg. A maximum decrease of 20.7% in theophylline ClB was noted by the third study day. Two weeks after erythromycin was discontinued, the greatest increase in ClB observed was 45.7%. Differences in t1/2 and ClB between the third and fourth study days were statistically significant (p less than 0.05).

Adult↗

PubMedDate not supplied

Continuous arteriovenous hemofiltration of aminoglycoside antibiotics in critically ill patients.

The effect of continuous arteriovenous hemofiltration on the clearance of either tobramycin or gentamicin (mean dose, 1.65 +/- 0.36 mg/kg) was studied in eight critically ill patients. Mean aminoglycoside clearance by hemofiltration was 3.47 +/- 1.93 mL/min and total body clearance was 11.92 +/- 3.51 mL/min. Hemofiltration clearance (HFCL) was directly correlated with hemofiltration flow rate (HFQR): HFCL (mL/min) = 1.03 HFQR (mL/min)-0.88 (R = .89). Mean volume of distribution was 0.31 +/- 0.08 L/kg, and the elimination rate constant was 0.020 +/- 0.01 hr-1. Continuous arteriovenous hemofiltration was responsible for the removal of between 3% and 36% of each aminoglycoside dose in 24 hours. In critically ill patients with changing hemofiltration flow rates, measurement of multiple serum aminoglycoside concentrations is necessary to accurately assess dosing requirements and avoid ototoxicity and nephrotoxicity.

Adult↗

PubMedDate not supplied

Electrophysiologic and proarrhythmic effects of intravenous inotropic agents.

Intravenous inotropic agents promote increased myocardial contractility via elevation of myocyte calcium concentrations, a mechanism that is also known to promote the development of cardiac arrhythmias. The purpose of this article is to review the electrophysiologic effects and relative potential for proarrhythmia associated with dobutamine, dopamine, and the phosphodiesterase inhibitors amrinone and milrinone. Dobutamine increases sinoatrial node automaticity and decreases atrial and atrioventricular (AV) node refractoriness and AV nodal conduction time. The drug also decreases ventricular refractoriness in both healthy and ischemic myocardium. Dobutamine has been shown to increase heart rate in a dose-related fashion in animals and in humans. In humans, dobutamine has been reported to induce ventricular ectopic activity (VEA) in 3% to 15% of patients, although VEAs are often asymptomatic, requiring no intervention. Ventricular tachycardia (VT) associated with dobutamine appears to occur rarely. Patients with underlying arrhythmias or heart failure or those receiving excessive doses of dobutamine are at greatest risk for proarrhythmia. Dopamine increases automaticity in Purkinje fibers and has a biphasic effect on action potential duration. Dopamine has been reported to induce atrial or ventricular arrhythmias in animals. In humans, dopamine may be associated with dose-related sinus tachycardia but has also been reported to cause VEA, which is usually asymptomatic. Dopamine-associated VT appears to occur rarely. Dopamine produces greater elevations in heart rate or frequency of ventricular premature beats at a given value of cardiac index than does dobutamine. The phosphodiesterase inhibitors amrinone and milrinone increase conduction through the AV node and decrease atrial refractoriness. Intravenous administration of these drugs may result in sinus tachycardia in some patients and has been reported to cause VEA, which is often asymptomatic, in up to 17% of patients. VT has also been reported in association with short-term use of intravenous phosphodiesterase inhibitors. In summary, intravenous inotropic agents may be associated with proarrhythmic effects in some patients. The primary arrhythmias reported are sinus tachycardia and VEA, although other supraventricular or ventricular arrhythmias have been reported less commonly. However, clinically significant proarrhythmic effects associated with these agents appear to occur rarely, and, at conventional doses, intravenous inotropic agents are relatively safe with respect to proarrhythmic effects.

Adolescent↗

PubMedDate not supplied

Bioelectrical impedance in clinical practice.

Bioelectrical impedance (BI) relies on the conduction of a low-voltage alternating current through the body. Lean tissue and fluids containing electrolytes conduct the current and cell membranes serve as capacitors and account for capacitive resistance. Fat and bone are poor conductors. Measurement of the voltage drop of the applied current yields resistance (R) and reactance (Xc). R and Xc are used with height, weight, age, and gender in a number of multiple regression relationships to predict body composition compartments such as fat-free mass, lean body mass, extracellular mass, and body cell mass. The technique has been compared with and validated against traditional measures of body composition analysis. In clinical practice, BI has been used to monitor fluid status in burn and dialysis patients, assess changes of body cell mass with nutritional repletion, and predict pharmacokinetic parameters and dose of theophylline and aminoglycoside antibiotics. BI is a noninvasive, safe, rapid, and reproducible technique with exciting potential in clinical practice.

Body Composition↗

PubMedDate not supplied

Human monoclonal antibody against endotoxin.

Little progress has been made over the past several years in the treatment of gram-negative bacteremia and septic shock. Advances in biotechnology have led to the development of human monoclonal antibody against endotoxin (HA-1A), a toxic mediator of the septic response. HA-1A is an immunoglobulin M antibody to the lipid A component of the endotoxin molecule. It distributes into an apparent volume of distribution 10-20 percent larger than plasma volume and has a circulating half-life of 16.0 hours. In a major, multicenter, double-blind trial of HA-1A 100 mg administered intravenously versus placebo, mortality was greatly reduced in HA-1A recipients with gram-negative bacteremia. Increased survival was noted early and was sustained throughout the 28-day study period in patients with and without shock at the time of enrollment. HA-1A has an excellent safety profile; thus far only two minor hypersensitivity reactions and no drug interactions have been reported. Based on currently available information, the release of HA-1A as adjunct therapy for patients with gram-negative bacteremia with or without shock represents a significant therapeutic advance. Investigations are underway to define the optimal dose of HA-1A and its duration of action. Comparative trials between HA-1A and competitive products are necessary.

Antibodies, Monoclonal↗

PubMedDate not supplied

Characterization of drug disposition and dosing using bioelectrical impedance.

Bioelectrical impedance analysis (BIA) yields accurate, safe and non-invasive estimates of body composition in humans. Pharmacokinetic characterization of drugs represents the body as a series of non-physiologic compartments. We evaluated the utility of BIA in the pharmacokinetic characterization and dosing of water soluble drugs. Serial serum concentrations of gentamicin (G) in 30 hospitalized adults, and theophylline (T), in 15 normal adult males were obtained over a dosing interval after an 8h fast, and analyzed in duplicate by enzyme-mediated immunoassay technique. BIA was performed serially in duplicate during the same time period using a fixed frequency (50kHz, 800 microA) current-injection 4-electrode plethysmograph. Multiple regression techniques were used to develop descriptive models of pharmacokinetic parameters which yielded equations with p-values < 0.03 and coefficients of variation < 20% accounting for > 85% of the pharmacokinetic variability. The G models were then tested in 20 critically ill adults at steady state by serum concentration measurement (criterion standard) and BIA. BIA predictive equations yielded pharmacokinetic parameters not different (by paired t-tests) than those derived by serum concentration measurement. While BIA is an innovative approach to the non-invasive characterization water soluble drugs, further testing with variable frequency BIA under perturbed conditions is warranted.

Adult↗

PubMedDate not supplied

Pharmacotherapy specialty certification examination. IV. 1992 results and process modifications, including recertification. The 1992 Specialty Council on Pharmacotherapy, Board of Pharmaceutical Specialties.

Certification of pharmacotherapy specialists is proceeding smoothly. Modifications to the examination process, which include reapportioning domains, offering the examination at several sites, and establishing the recertification process, have occurred. The guidelines for petitioners and structure of specialization continue to receive the attention and interest of prospective candidates, pharmacy organizations, and the BPS. To date, 674 specialists have been certified in the approved specialties: 175 nuclear pharmacists, 236 nutrition pharmacists, and 263 pharmacotherapy specialists.

Certification↗

PubMedDate not supplied

Bar code documentation of pharmacotherapy services in intensive care units.

Bar code technology has been used for 5 years to improve the efficiency of identifying and documenting clinical pharmacy services at our institution. Data for an entire year (1993) were analyzed to quantify the nature and magnitude of pharmacy services provided for critically ill patients in intensive care units (ICU). Patients in the medical (MICU), respiratory (RICU), intermediate (IMU), and surgical (SICU) units (3234/3743 patients, 86%) were reviewed. Clinical interventions and expected outcomes were documented by pharmacists using an automated bar code system. There were 11,628 pharmacotherapy interventions, 3.6/patient; 12/pharmacist work day. Of patients whose drug therapy was reviewed at least once, 50% (1610/3234) received at least one intervention. The mean number of interventions/patient was 7.2 in the MICU, 6.1 in RICU, 3.4 in IMU, and 2.4 in the SICU, corresponding to APACHE III scores of 71.2, 66.2, 42.8, and 43.3, respectively. The majority of interventions were to modify dosages of antimicrobial agents, and were performed to achieve optimum efficacy (42%) and to minimize toxicity (46.2%). These data support the necessity for pharmacists to provide individualized care to critically ill patients.

Drug Therapy, Computer-Assisted↗