Aminoglycoside dosing considerations in intensive care unit patients.

OBJECTIVE: Factors affecting aminoglycoside dosing requirements in critically ill adult patients were reviewed. DATA SOURCES: A literature search was performed from 1979 to 1992 and articles pertaining to aminoglycoside dosing were obtained. STUDY SELECTION: Only studies appearing in peer-reviewed journals were selected. Topics selected included: bactericidal kill kinetics, once-daily dosing regimens, critical illness, toxicity, aminoglycosides, intensive care unit, and lung penetration. CONCLUSIONS: Studies suggest that larger initial aminoglycoside doses are necessary in critically ill patients (tobramycin/gentamicin 3 mg/kg or amikacin 9 mg/kg) to achieve adequate peak serum concentrations. Current studies have not shown an increase in the incidence of aminoglycoside toxicity when using these larger initial doses. Follow-up monitoring is dependent upon the patient's physiology and risk factors for aminoglycoside-induced toxicity.

Population pharmacokinetics: development of a medical intensive care unit-specific gentamicin dosing nomogram.

OBJECTIVE: This study was designed to develop a population-specific dosing nomogram for gentamicin in medical intensive care unit (MICU) patients using the population pharmacokinetic program nonparametric expectation maximization (NPEM). DESIGN: Observational clinical gentamicin dosing data were collected, entered into the USC*PACK database program PASTRX, and downloaded into the population pharmacokinetic program NPEM. NPEM generated population pharmacokinetic parameter values that were used to develop a gentamicin dosing nomogram. The nomogram was tested in the next 15 patients admitted to MICU to determine accuracy. Doses given per the MICU and the Hull-Sarubbi nomograms were compared with doses based on actual patient-specific pharmacokinetic parameter values. Reliability coefficients (intraclass correlation coefficients) were calculated to assess the agreement between observations. SETTING: Data were gathered from patients receiving gentamicin therapy in the MICU, Presbyterian University Hospital, Pittsburgh. PATIENTS: Baseline population pharmacokinetic parameter values were determined in 36 MICU patients receiving gentamicin therapy. Patients with renal failure receiving hemodialysis or another mechanical method of blood clearance or fluid removal were excluded. The population parameter values in the form of a dosing nomogram were then used prospectively to dose gentamicin in 15 patients. RESULTS: NPEM generated population parameter values similar to those previously published using the Sawchuk-Zaske method in ICU patients. The mean volume of distribution generated using NPEM was 0.34 +/- 0.12 L/kg. The relationship between creatinine clearance (Clcr) and elimination rate constant (Ke) was: Ke = 0.00218 x Clcr + 0.007. The nomogram-derived doses correlated with doses determined by using actual patient-specific pharmacokinetic values (p < 0.05). The Hull-Sarubbi derived doses, however, did not correlate with patient-specific doses (p > 0.05). Only one patient had a peak concentration < 6 mg/L. Two of 15 patients had trough concentrations prior to the first maintenance dose > 2 mg/L. CONCLUSIONS: The use of NPEM to generate population-specific pharmacokinetic parameter values has been previously described. Application of population-specific dosing nomograms can improve initial dosing regimens such that conventional therapeutic concentrations can be achieved early in therapy. This nomogram, however, does not preclude follow-up patient-specific pharmacokinetic analysis.

Verapamil overdose: case report and review of the literature.

OBJECTIVE: To report the presentation and controversies regarding therapy of an 18-year-old man following a life-threatening ingestion of verapamil. CASE SUMMARY: An 18-year-old man ingested large quantities of dipyridamole, trimethoprim/sulfamethoxazole, amoxicillin, and verapamil. He presented to an outlying hospital and was initially conscious. Soon thereafter, the patient had a seizure; he required intubation, developed cardiac conduction abnormalities, and became hypotensive. The patient required pharmacologic pressors and a pacemaker for transfer to our institution. At our institution, vigorous fluid resuscitation, cardiac pacing, and careful attention to acid/base and electrolyte management provided the basis of therapy. The patient recovered without deficit and was discharged from the intensive care unit five days later. DISCUSSION: Current controversies regarding the management of verapamil overdose are reviewed. Removal of the drug by gastric lavage is a mainstay of therapy. Administration of syrup of ipecac is contraindicated. Although specific recommendations for calcium dosing in the overdose situation have not been rigorously studied, maintenance of a normal serum ionized calcium concentration is suggested. An exogenous catecholamine, rather than dopamine, may be the drug of choice for treating hypotension. Cardiopulmonary bypass provides a method for drug removal in cases of severe toxicity; however, this invasive method requires further study. Management of fluid/electrolyte, acid/base, and ventilation abnormalities is required to treat large ingestions of verapamil. Treatment guidelines for critical care clinicians are provided.