Effect of pharmacokinetic sampling methods on aminoglycoside dosing in critically ill surgery patients.

We compared pharmacokinetic parameters derived from three aminoglycoside serum concentration sampling methods and evaluated their effects on recommended aminoglycoside dosing regimens in 60 critically ill surgery patients. Patients had presumed or documented gram-negative sepsis, and had at least 4 aminoglycoside serum concentrations measured. We used a one-compartment model for peak and trough, 3-point series, and 4-point series sampling methods. Dosing regimens were calculated for each patient based on values derived from each method. We found differences in regimens for nearly 50% of patients if either 4- or 3-point series sampling was used to calculate the recommended dosage rather than peak and trough sampling. However, the 3-point method required a clinically significant change in regimen in only 12% of patients compared with 4-point sampling. The variability of all values derived from 3-point sampling were well accounted for by the 4-point method (r2 > 0.80). In addition, we noted significantly greater relative precision for 3-point sampling than peak and trough sampling for estimates of clearance, elimination rate, recommended daily dosage, and recommended dosing frequency. We recommend three optimally timed samples be drawn instead of peak and trough levels in dosing aminoglycosides in critically ill surgery patients.

Comparison of the effect of intermittent administration and continuous infusion of famotidine on gastric pH in critically ill patients: results of a prospective, randomized, crossover study.

OBJECTIVES: To compare the effects of intermittent intravenous administration and continuous intravenous infusion of famotidine on gastric pH in critically ill patients. DESIGN: A prospective, randomized, crossover study of continuous infusion and bolus administration of famotidine in critically ill patients. SETTING: A 14-bed medical intensive care unit (ICU) of a 500-bed county hospital. PATIENTS: Medical ICU patients requiring stress ulcer prophylaxis. INTERVENTIONS: Patients were randomized to receive an equivalent dose of famotidine by continuous infusion or intravenous bolus for 24 hrs, and then were crossed over to the other arm of the study. MEASUREMENTS AND MAIN RESULTS: Critically ill patients who met the inclusion criteria were randomly assigned to receive famotidine 20 mg i.v. over 10 mins, every 12 hrs or a continuous infusion of 1.7 mg/hr for 24 hrs. After a 16-hr washout period, patients crossed over to the other arm of the study. Gastric pH was monitored continuously for 24 hrs. A total of 710 gastric pH measurements were obtained for each phase of the study. The mean area under the pH-time curve for a 24-hr period was higher for continuous infusion than bolus administration (p = .05). Continuous infusion of famotidine maintained a gastric pH of > or = 4 over a longer time period than bolus administration (20.8 hrs vs. 12.6 hrs, respectively; p < .01). Onset of therapeutic gastric pH for continuous infusion was slightly delayed as compared with bolus administration. CONCLUSIONS: Continuous infusion of famotidine is more effective than an equivalent dose given by intermittent bolus in maintaining the appropriate gastric pH necessary for prevention of stress ulceration. Delayed onset of effect may warrant a priming dose when famotidine is given by continuous infusion.

Equivalence of litmus paper and intragastric pH probes for intragastric pH monitoring in the intensive care unit.

OBJECTIVE: To compare the accuracy of litmus paper-determined gastric pH to a nasogastric graphite antimony pH probe. DESIGN: A prospective clinical trial of gastric pH determination in patients enrolled in a study of histamine-2-receptor (H2) antagonists. SETTING: The medical intensive care unit (ICU) of a 450-bed county hospital. PATIENTS: Critically ill ICU patients requiring stress ulcer prophylaxis. INTERVENTIONS: Using a crossover design, the patients were randomized to initially receive an H2 antagonist by continuous infusion or intravenous bolus, and subsequently were crossed over to the other limb of the study. MEASUREMENTS AND MAIN RESULTS: Gastric pH was determined using pH-sensitive litmus paper at the initiation of each limb of the study and at 1, 2, 4, and 8 hrs after the initiation of H2 receptor antagonist therapy. In addition, gastric pH was continuously determined over the same time period utilizing a graphite antimony pH probe. Gastric pH measurements determined with litmus paper and intragastric pH probes demonstrated an excellent correlation (r2 = .93, p < .001). McNemar's test of correlated proportions could not demonstrate a significant difference between the two monitoring methods (chi-square = 0.5, p > .47), and the kappa statistic (0.95, p < .001) demonstrated excellent concordance. Bias measurement was 0.01 (95% confidence interval = -0.155 to 0.176). CONCLUSIONS: Measurement of intragastric pH, using pH-sensitive litmus paper, is both sensitive and specific when utilizing a graphite antimony nasogastric pH probe as a reference standard. Litmus paper-determined gastric pH testing is both easy to perform and inexpensive. Therefore, based on the current data, we believe this technique (i.e., litmus paper determined gastric pH testing) to be the method of choice for determination of intragastric pH in patients at risk for stress gastric ulcers in the medical ICU.