Physiologic response of stress and aminoglycoside clearance in critically ill patients.

OBJECTIVE: To examine the relationships between aminoglycoside clearance and physiologic parameters associated with the physiologic response to injury. DESIGN: Cross-sectional study of surgical patients receiving aminoglycoside pharmacokinetic monitoring and parenteral nutritional support. SETTING: An adult surgical ICU. PATIENTS: Fifty-four surgical/trauma patients who had Gram-negative sepsis. INTERVENTIONS: Measurements of the physiologic stress response to injury were associated with aminoglycoside clearance in 54 surgical/trauma patients who had Gram-negative sepsis. Measurements used to estimate the magnitude of the stress response included a 24-hr urinary urea nitrogen excretion, blood urea nitrogen, peak temperature, serum albumin, bilirubin, and transferrin concentrations. MEASUREMENTS AND MAIN RESULTS: Mean drug clearance rate (4.4 +/- 2.5 [SD] L/hr) was related to the physiologic measurements using correlation and regression techniques. Collectively, all physiologic indices (utilized) explained 59% of the variance in drug clearance (p < .001), an amount similar to the variance explained by creatinine clearance alone (53%). When all six physiologic measurements were included into a multiple regression model that included creatinine clearance, the total variance explained increased to 73%. CONCLUSIONS: Along with renal function estimates, the physiologic response to stress should be considered when treating critically ill patients with aminoglycosides and other, similar, renally eliminated drugs.

Thermal injury effects on drug disposition: a prospective study with piperacillin.

The disposition of piperacillin was prospectively evaluated in nine severely burned patients who had normal renal and hepatic function. Wide interpatient variations were demonstrated in the drug's distribution volume, half-life, and clearance, with mean (+/- SD) values of 55.0 (+/- 44.2) liters, 3.6 (+/- 5.2) hours, and 14.9 (+/- 6.3) liters/hour, respectively. Piperacillin clearance was best explained by patient factors other than age, renal function, and the percentage of body surface area burns. Piperacillin disposition was related to the patients' serum albumin, total bilirubin, blood urea nitrogen, and the amount of urea nitrogen excreted daily in urine. Altered piperacillin disposition thus appeared to occur secondary to changes in the patients' physiologic and metabolic state caused by injury-related stress and fluid therapy. The patient's physiologic and metabolic response to injury, along with age and renal function, should be considered when instituting treatment with piperacillin or other agents cleared from the body in a similar manner.

Effects of treatment and the metabolic response to injury on drug clearance: a prospective study with piperacillin.

The disposition of piperacillin was prospectively evaluated in 11 critically ill surgical patients who had no evidence of pre-existing renal and hepatic disease. Interpatient variations were demonstrated in the drug's half-life, distribution volume, and clearance, with values of 1.50 +/- 2.05 (SD) h, 25.0 +/- 17.2 L, and 23.8 +/- 17.2 L/h, respectively. Variations in piperacillin disposition were best explained by serum concentrations of albumin, total protein, and bilirubin, and the amount of urea nitrogen excreted daily in urine. Age and renal function were moderately associated with piperacillin elimination rate and clearance. Altered piperacillin disposition thus appeared to occur as secondary to changes in the patients' physiologic and metabolic state caused by injury-related stress and fluid/colloid therapy. These alterations may necessitate dosage modifications to achieve optimal patient response when treating patients with piperacillin as well as with other similar drugs eliminated via renal and nonrenal routes.

Protamine sulfate and fatal anaphylactoid shock.

A 73-year-old male underwent uneventful three-vessel coronary artery bypass grafting after which he received iv protamine sulfate for reversal of systemic heparinization. Shortly thereafter, the patient developed and succumbed to an anaphylactoid reaction attributed to protamine. The patient had none of the previously reported risk factors for hypersensitivity to the drug and was therefore not considered at high risk for such a severe adverse reaction. Although uncommon, the fatal outcome of this low-risk patient seriously addresses the need for alternative measures for heparin reversal.

Pseudomonas aeruginosa susceptibility in a university hospital: recognition and treatment.

Pseudomonas aeruginosa continues to be a leading cause of nosocomial bacteremia and other serious, often life-threatening infections. The incidence of P. aeruginosa infection appears to be increasing. The resilience of Pseudomonas in the hospital environment, its endogenous virulence factors, and its current level of resistance to antimicrobials make it a formidable pathogen, particularly in a compromised host. Despite the availability of several effective antipseudomonal antibiotics, infections caused by this pathogen are still associated with significant morbidity and mortality. Early recognition and prompt intervention with appropriate antimicrobial agents are vital to successful management. Combination therapy with an aminoglycoside and an extended-spectrum penicillin or cephalosporin is recommended in the initial management of suspected or documented P. aeruginosa infections.

The clinical utility of a published nomogram to predict aminoglycoside nephrotoxicity.

Moore and colleagues recently published a nomogram for predicting the risk of aminoglycoside nephrotoxicity. This study was undertaken to evaluate the clinical usefulness of this nomogram. The nephrotoxicity risk scores of 61 patients were determined using parameters suggested by Moore et al. Thirteen patients (21%) could not be scored because their initial creatinine clearances exceeded the upper limit of the nomogram. Six patients (9.8%) developed nephrotoxicity (defined as a greater than or equal to 50% decrease in creatinine clearance). In five of these patients in whom risk scores could be determined, the scores were estimated at 14% or less. Twenty patients had risk scores of 10% or more (four patients, greater than or equal to 50%) without developing nephrotoxicity. These results demonstrate that this nomogram may have limited clinical application in predicting patients likely to develop aminoglycoside nephrotoxicity.