L Chelluri, MD FCCP; Jonathan Warre...

L Chelluri, MD FCCP; Jonathan Warren, MD FCCP; and Michael s Jastremski, M.D.

We evaluated the pharmacokinetics and adequacy of gentamicin or tobramycin after administration of a loading dose of 3 mg/kg corpse weight in 14 critically ill patients with presum sepsis. Therapeutic vital current levels after loading dose were obtained in 13 of the 14 patients. Measured body of distribution, serum half-life, and elimination rate constant were significantly different from values calculated by dint of using standard formulae. All the patients tolerated the dose well without significant deterioration in renal function. Based onward the present study, we deduce that administration of 3 mg/kg corpse weight loading dose of getamicin or tobramycin in critically ill patients with sepsis would outcome in earlier therapeutic drug levels

(Chest 1989; 95:1295-97)

Gram-negative pneumonia and/or sepsis cause significant morbidity and mortality. Kreger et al[1] have shown that 50 percent of deaths secondary to Gram-negative bacteremia present itself in the initial 24 to 48 hours. Craven et al[2] demonstrated a significantly decreased survival for mechanically ventilated patients with the adult respiratory distress syndrome when Gram-negative pneumonia disentangleed The mainstay of therapy for Gram-negative sepsis includes fluid resuscitation, early and adequate antibiotic therapy, and removal of the focus of infection, if possible. It is recognized that achieving early and adequate horizontals of aminoglycoside in patients with Gram-negative infections positively influences outcome[3-5] Evidence also recommends that the volume of distribution for these unsalable articles is increased in most critically ill patients.[6-8] Therefore, standard loading doses and dosing schedules oftentimes result in subtherapeutic levels.[9] We have previously shown that a 2 mg/kg corpse weight amino-glycoside loading dose fails to achieve therapeutic flushs in critically ill patients,[10] and we now routinely utilize a 3 mg/kg aminoglycoside loading dose in these patients. This report summarizes the pharmacokinetic data observ after a 3 mg/kg dead body weight loading dose of gentamicin or tobramycin in a form into groups of critically ill patients with presum Gram-negative infection.

MATERIALS AND METHODS

Fourteen consecutive patients in our general medical/surgical ICU with presum Gram-negative sepsis are described in this summary. The diagnosis of sepsis required the appearance of hyperthermia (T>38.5 degrees C) or hypothermia (T<35 orders C), tachycardia, evidence of hypoperfusion, and an identifiable focus of infection. In all cases, standard resuscitation measures were occupyed and broad spectrum antibiotic therapy was begun empirically after obtaining appropriate agricultures All patients received a gentamicin or tobramycin loading dose of 3 mg/kg adjusted dead body weight intravenously over one-half hour as a continuous infusion. Using a modification of the orders of Ng,[11] estimates of body of distribution (Vd), half-life (T/12) and elimination rate constant (Ke) were derived for each patient. These were, in use used to calculate a maintenance dose and dosing interval as it is that the expected peak and between the sides of serum drug levels were 8 [unkeyable]g/ml and 1 [unkeyable]g/ml, respectively. Additional antibiotics were administered at different times in such a manner as to avoid potential interaction with aminoglycoside.

Three children levels of aminoglycoside were obtained after administration of the loading dose (30 minutes postinfusing, midcycle, and trough) for the calculation of "measured" Vd T1/2 and Ke using a mathematical reconstruction of the exponential elimination bend as described by Sawchuk and Zaske.[12] Aminoglycoside horizontals were measured by flourescence polarization immunoassay. The coefficient of variation for tobramycin was 43 percent with a reign over value of 4 [unkeyable]g/dl, and for gentamicin was 28 percent with a sway value of 4 [unkeyable]g/dl.

clear fluid balance as compared to hospital admission was determined for the sum of two units day period prior to administration of the loading dose, when available. Deterioration in renal function was defined as an increase in serum creatinine of 05 mg/dl if the initial value was 3 mg/dl or greater. Renal function was monitored until death or hospital discharge.

All data are showed as mean [+ or -] SD The two-tailed Student's t-test for paired samples was used for comparing estimated and measured values; p<005 was considered statistically significant.

RESULTS

General patient characteristics are summarized in Table 1 Lung with or without other sites, was the suspected site of infection in 12 patients, with abdomen and kidney suspected in the other sum of two units patients. Accurate fluid balance was obtained in eight of 14 patients. Seven were in positive fluid balance (mean 43 L) and undivided patient was in negative fluid balance (-08 L) Creatinine clearance calculated at the time of enrry into the application of mind using the method of Cockroft and Gault,[13] varied from 20 to 91 ml/min. Peak aminoglycoside serum plains obtained after the loading dose were within the therapeutic range in 13 of 14 patients (98 [+ or -] 28 [unkeyable]g/ml, range 44 to 15 [unkeyable]g/ml). long tray levels obtained prior to the first maintenance dose were well within the safe range (106 [+ or -] 044 [unkeyable]g/ml, range 05 to 16 [unkeyable]g/ml). No deterioration in renal function was noted in any patient come intoed into this study prior to death or hospital discharge. [TABULAR DATA OMITTED]