Gastric ulcer perforation associated with the use of injectable ketorolac.

OBJECTIVE: To report a case of a perforated gastric ulcer associated with the use of injectable ketorolac tromethamine. DATA SYNTHESIS: A 77-year-old woman with no previous history of peptic ulcer disease developed a perforated gastric ulcer after four days of treatment with ketorolac. To date, six other cases of gastrointestinal (GI) perforation associated with the use of ketorolac have been reported to the manufacturer. CONCLUSIONS: Although ketorolac is an effective analgesic, it is a nonsteroidal antiinflammatory agent and thus has the propensity for causing GI ulceration. Caution should be used when administering this drug and patients should be monitored for GI adverse effects.

Oxygen homeostasis: theory, measurement, and therapeutic implications.

The ultimate goal of therapeutic intervention in a critically ill patient is to maintain oxygen homeostasis where delivery of oxygen to the cells is greater than, or at least equal to, the oxygen demand of the cells. Oxygen demand varies from organ to organ. Total body oxygen demand is the sum of all oxygen required by all tissues and organs for aerobic cellular function. Oxygen consumption (VO2) is the quantity of oxygen actually used by the cells. VO2 may be calculated if the values of cardiac output (CO), hemoglobin concentration, and arterial and venous oxygen saturations (SaO2 and SvO2, respectively) are known. Under normal circumstances, the quantities of oxygen demanded and oxygen consumed are equal, but in situations of inadequate oxygen delivery, oxygen demand may not be satisfied and the quantity of oxygen actually consumed will be governed by the quantity delivered. This then may result in an oxygen deficit and, ultimately, cellular death. This article discusses the principles of oxygen homeostasis, techniques for measuring VO2, CO, and SvO2, and the relevance of these principles and techniques to clinical practice.

Prospective surveillance of intravenous amphotericin B use patterns.

Information on amphotericin B use patterns and infusion-related adverse events were prospectively collected from 397 hospitalized adults. The methods of initiating amphotericin B varied greatly, with the majority of patients being gradually titrated to a full maintenance dose over 1-5 days. Overall, 71% of patients experienced at least one episode of an infusion-related adverse event (IRAE) during the first week of therapy. Fever and chills were most commonly observed, with peak frequency on days 1-3, followed by a subsequent decline. A wide variety of pretreatment medications were used to minimize IRAE; the most common regimens included some combination of diphenhydramine, acetaminophen, and corticosteroids, with or without heparin. The majority of patients (84.7%) received a test dose, and although none experienced a severe allergic reaction, one patient subsequently had an anaphylactic episode on the third day of amphotericin B therapy. The use of a test dose and the titration process are attempts to avoid the IRAE frequency associated with large initial doses of amphotericin B, but we observed that they provided little or no benefit. In addition, our study suggests that pretreatment regimens are frequently used in conjunction with the test dose. If the intent of the test dose is to identify patients sensitive to amphotericin B, pretreatment drugs may minimize these adverse events and prevent a complete evaluation of response to the test dose.

Intrapatient variation of aminoglycoside pharmacokinetics in critically ill surgery patients.

Intrapatient variation in aminoglycoside pharmacokinetics was studied in 100 critically ill surgery patients, and the relationships between aminoglycoside pharmacokinetics and physiological variables were evaluated. A one-compartment model and the DataMed Clinical Support Service System were used to calculate pharmacokinetic values from serum concentration-time data and to provide individualized dosage regimens. A total of 323 pharmacokinetic analyses (2 to 9 per patient) were performed. There were significant intrapatient differences in clearance (CL) between analyses, and there was a downward trend in elimination rate constant (k) and an upward trend in half-life (t1/2) with time. There were no significant differences in mean volume of distribution (V) between analyses and no strong correlations of V, k, and CL between analyses. The total daily dosage necessary to provide the desired serum aminoglycoside concentration decreased with time, while the dosing interval increased. The mean absolute changes in t1/2, V, and CL between analyses were 3.2 hr, 7.1 L, and 15.7 mL/min, respectively. Dosing regimen changes were required in 90% of the patients, regardless of the time between analyses, including 75% (24/32) of the patients with analyses on consecutive days. There were weak correlations between changes in serum creatinine concentration and changes in dosing interval and between changes in weight and changes in V. Changes in calculated creatinine clearance, BUN, pulmonary capillary wedge pressure, central venous pressure, systemic vascular resistance, cardiac index, input minus output, and maximum temperature did not result in strong correlations with k, t1/2, V, and CL by univariate or multivariate regression analyses.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of infusion pump fill-stroke flow interruption on response to sodium nitroprusside in surgical patients.

The influence of the piston-cassette pump fill stroke on the pharmacodynamic response to sodium nitroprusside was evaluated prospectively in 10 adult patients in the surgical intensive-care unit. Simultaneous analog recordings of blood pressure and fill stroke were made over three complete pump fill cycles in each patient. Sodium nitroprusside flow rates and concentrations were recorded throughout the data-collection period. Analysis was based on the maximum pressure obtained during the two-minute baseline period before a fill stroke (Pmax baseline), the pressure at the initiation of the fill stroke (P initial), and the maximum pressure obtained during the two-minute period after the fill stroke (Pmax postfill). The maximum systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean blood pressure (MBP) during the baseline and post-fill-stroke periods were significantly different. The mean (+/- S.D.) variability in pressure between the time periods Pmax baseline and Pmax postfill was 3.9 +/- 5.8 mm Hg for SBP (range, -8 to +16), 3.5 +/- 5.7 mm Hg for DBP (range, -7 to +13), and 3.6 +/- 5.6 mm Hg for MBP (range, -7 to +14). The likelihood of a pharmacodynamic change was inconsistent both between and within patients. Within patients the difference between cycles for the variability between time periods ranged from a minimum of 2 mm Hg to a maximum of 16 mm Hg for SBP, 2 mm Hg to 17 mm Hg for DBP, and 1 mm Hg to 17 mm Hg for MBP. The variability within the baseline period (Pmax baseline - P initial) in SBP was significantly greater than the variability between the time periods, while the differences for DBP and MBP were not significant.(ABSTRACT TRUNCATED AT 250 WORDS)

Altered aminoglycoside pharmacokinetics in critically ill patients with sepsis.

The pharmacokinetic disposition of aminoglycosides in critically ill patients with sepsis was studied. In an open-label study of the disposition of gentamicin and tobramycin, individualized pharmacokinetic values of 100 critically ill patients in the surgical intensive-care unit were compared with those of a concurrently monitored group of 100 surgery patients who were not critically ill. The a priori computer-predicted dosage requirements of the critically ill patients were also compared with the dosages derived from their individualized pharmacokinetic values, and intrapatient variation in the critically ill patients was studied. Serum concentration-time data were analyzed using a one-compartment model and the DataMed Clinical Support Services system to provide individualized dosage requirements. Initial dosing guidelines were also generated for the critically ill patients using the a priori model of the DataMed Clinical Support Services program and patient demographic information. The critically ill patients were significantly older, had higher serum creatinine concentrations (SCr), and had lower elimination rate constants (k) and total body clearances (CL) than the surgery patients who were not critically ill. The volume of distribution (V) was not significantly different. The a priori computer predictions for the critically ill patients were significantly lower than the individualized values for V, CL, dose, and amount of drug per 24 hours. The dosing regimen from the a priori model was the same as the individualized regimen in only 2/100 patients. In the 76 critically ill patients who had a second pharmacokinetic analysis performed, there was a significant decrease in k and CL from the first analysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Decreased hepatic clearance of clindamycin in critically ill patients with sepsis.

Clindamycin pharmacokinetics was compared in critically ill patients with sepsis and healthy volunteers, and the relationship between pharmacokinetic values and physiological measurements obtained from the critically ill patients was characterized. Pharmacokinetic evaluations were performed on 10 patients with sepsis who were receiving clindamycin phosphate 900 mg i.v. every eight hours and on 6 previously studied healthy men receiving the same dosage regimen. Physiological variables measured included age, weight, cardiac index, systemic vascular resistance, central venous pressure, liver-function tests, alpha 1-acid glycoprotein concentration, and APACHE II score. Clindamycin was administered to the critically ill patients via a central venous catheter over 30 minutes; the healthy volunteers received their infusions via a peripheral venous catheter over 30 minutes. Blood samples were obtained at five minutes before and at various intervals after drug administration. Serum clindamycin concentrations were determined by a gas-liquid chromatographic method. Serum concentration data were analyzed using noncompartmental methods based on statistical moment theory, and the a priori level of significance was 0.05. The critically ill patients had significantly increased values for area under the curve (AUC), area under the moment curve (AUMC), mean residence time (MRT), and average concentration at steady state (Css), while total body clearance (TBC) was less than half that in the healthy volunteers. TBC in three of the critically ill patients was not different from that in the healthy volunteers. The apparent volume of distribution at steady state (Vss) was not significantly different between the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute renal failure.

Acute renal failure (ARF) is common among critically ill patients and renal dysfunction is often associated with the multisystem organ failure syndrome. The mortality of ARF remains high but animal data indicate that prevention and early treatment may decrease the morbidity and mortality. This review defines ARF based on urine volume, laboratory parameters, and clinical presentation. The pathophysiology of prerenal, postrenal, and intrinsic ART are differentiated and diagnostic criteria provided. Preventive therapy, supportive care, and proposed treatments are outlined. Studies examining the prevention and treatment of ARF in animal models and trials in humans are evaluated. Mannitol 0.5-1 g/kg, furosemide 0.5-1 mg/kg initially, and dopamine 1-5 micrograms/kg/min are effective in preventing or decreasing the severity of ARF in animal models. In humans these drugs are effective at maintaining urine output in various clinical situations and converting oliguria to nonoliguria in some patients; however, increased survival has not been adequately proven as of yet. Dialysis and experimental therapy are briefly discussed.