Multicenter clinical trial of recombinant human insulin-like growth factor I in patients with acute renal failure

Multicenter clinical trial of recombinant human insulin-like growth factor I in patients with acute renal failure.BackgroundPatients with acute renal failure (ARF) have high morbidity and mortality rates, particularly if they have serious comorbid conditions. Several studies indicate that in rats with ARF caused by ischemia or certain nephrotoxins, insulin-like growth factor-I (IGF-I) enhances the recovery of renal function and suppresses protein catabolism.MethodsOur objective was to determine whether injections of recombinant human IGF-I (rhIGF-I) would enhance the recovery of renal function and is safe in patients with ARF. The study was designed as a randomized, double-blind, placebo-controlled trial in intensive care units in 20 teaching hospitals. Seventy-two patients with ARF were randomized to receive rhIGF-I (35 patients) or placebo (37 patients). The most common causes of ARF in the rhIGF-I and placebo groups were, respectively, sepsis (37 and 35% of patients) and hypotension or hemodynamic shock (42 and 27% of patients). At baseline, the mean (± sd) APACHE II scores in the rhIGF-I and placebo-treated groups were 24 ± 5 and 25 ± 8, respectively. In the rhIGF-I and placebo groups, the mean (median) urine volume and urinary iothalamate clearances (glomerular filtration rate) were 1116 ± 1037 (887) and 1402 ± 1183 (1430)ml/24hr and 6.4 ± 5.9 (4.3) and 8.7 ± 7.2 (4.4)ml/min and did not differ between the two groups. Patients were injected subcutaneously every 12hours with rhIGF-I, 100 μg/kg desirable body weight, or placebo for up to 14days. Injections were started within six days of the onset of ARF. The primary end-point was a change in glomerular filtration rate from baseline. Other end points included changes from baseline in urine volume, creatinine clearance and serum urea, creatinine, albumin and transferrin, frequency of hemodialysis or ultrafiltration, and mortality rate.ResultsDuring the treatment period, which averaged 10.7 ± 4.1 and 10.6 ± 4.5days in the rhIGF-I and placebo groups, there were no differences in the changes from baseline values of the glomerular filtration rate, creatinine clearance, daily urine volume, or serum urea nitrogen, creatinine, albumin or transferrin. In patients who did not receive renal replacement therapy, there was also no significant difference in serum creatinine and urea between the two groups. Twenty patients in the rhIGF-I group and 17 placebo-treated patients underwent dialysis or ultrafiltration. Twelve rhIGF-I–treated patients and 12 placebo-treated patients died during the 28days after the onset of treatment.ConclusionsrhIGF-I does not accelerate the recovery of renal function in ARF patients with substantial comorbidity

Impact of Fluconazole Prophylaxis on Cortisol Levels in Critically Ill Surgical Patients

Fluconazole is widely used in the intensive care unit for prevention and treatment of fungal infections. Case reports have described an association between fluconazole and adrenal dysfunction, an important cause of morbidity and mortality in critically ill patients. We sought to determine whether 400 mg of fluconazole per day administered to critically ill surgical patients was associated with a reduction in cortisol levels. Cortisol levels were measured in stored plasma specimens drawn from 154 critically ill surgical patients randomized in 1998-1999 to receive fluconazole or placebo for the prevention of candidiasis. The primary outcome measure was the median plasma cortisol level ≥1 day after study drug initiation (MPCL). Secondary outcomes were adrenal dysfunction, defined as an MPCL of <15 μg/dl, changes in cortisol levels over time, and mortality. The median MPCL was 15.75 μg/dl (interquartile range [IQR], 11.65 to 21.33 μg/dl) in 79 patients randomized to fluconazole and 16.71 μg/dl (IQR, 11.67 to 23.00 μg/dl) in 75 patients randomized to placebo (P = 0.52). Patients randomized to fluconazole did not have significantly increased odds of adrenal dysfunction compared to patients randomized to placebo (odds ratio, 0.98; 95% confidence interval, 0.48 to 2.01). Randomization to fluconazole was not associated with a significant difference in cortisol level changes over time. Mortality was not different between patients with and without adrenal dysfunction, nor was it different between patients with adrenal dysfunction who were randomized to fluconazole and those randomized to placebo. Fluconazole prophylaxis in this population of critically ill surgical patients did not result in significant adrenal dysfunction

Effective Clinical Practice Intensive Care Unit Nurse Staffing and the Risk for Complications after Abdominal Aortic Surgery

Context. We previously found that length of stay in the intensive care unit (ICU) after abdominal aortic surgery increased when fewer ICU nurses were available per patient. We hypothesized that having fewer nurses increases the risk for medical complications. Objective. To evaluate the association between nurse-to-patient ratio in the ICU and risk for medical and surgical complications after abdominal aortic surgery. Design. Observational study. Setting. All nonfederal acute care hospitals in Maryland. Data Sources. Information about patients came from hospital discharge data on all patients in Maryland with a principal procedure code for abdominal aortic surgery from 1994 through 1996 (n = 2606). The organizational characteristics of ICUs were obtained by surveying ICU medical and nursing directors in 1996 at the 46 Maryland hospitals that performed abdominal aortic surgery. Thirty-nine of the ICU directors (85%) completed the survey. Exposure. Surgery in hospitals with fewer ICU nurses (in which each nurse cared for three or four patients) compared with hospitals with more ICU nurses (in which each nurse cared for one or two patients). Outcome. Proportion of patients who developed postoperative complications. Results. Seven hospitals with 478 patients had fewer ICU nurses, and 31 hospitals with 212