Barbara J. Zarowitz

Predictability of creatinine clearance estimates in critically ill patients.

To evaluate the predictive ability of different creatinine clearance methods as compared with the criterion standard, inulin clearance; and b) to determine which of the predictive methods yields the most accurate estimation of creatinine clearance. Design:Prospective study. Setting:Medical intensive care unit (ICU) of a university-affiliated tertiary care hospital. Interventions:Glomerular filtration rate was measured by the criterion standard, inulin clearance. Patients:Twenty mechanically ventilated adults. Measurements:Renal function was assessed by the following procedures: inulin clearance using a standard protocol, 30-min creatinine clearance, 24-hr creatinine clearance, and creatinine clearance estimates by the Cockcroft-Gault equation. Ideal body weight, total body weight or lean body mass with actual serum creatinine or serum creatinine concentration corrected to 1 mg/dL (85 umol/L) in cachectic patients were sequentially incorporated into the Cockcroft-Gault equation. Results:The Cockcroft-Gault equation, using ideal body weight and the corrected serum creatinine concentration, was the best predictor of inulin clearance with the smallest bias (9.7 ± 8.6, 95% confidence interval 5.7 to 13.8). The bias encountered with the 30-min creatinine clearance was not different from that value with the 24-hr creatinine clearance (21.6 ± 33.0,95% confidence interval 6.2 to 37.1 vs. 25.4 ± 28.3, 95% confidence interval 11.8 to 42.9). Good correlations existed between inulin clearance and the Cockcroft-Gault equation, using ideal body weight and the corrected serum creatinine concentration (r2 = .81; p = .0001), as well as between inulin clearance and the Cockcroft-Gault equation, using the lower of ideal or total body weight and the higher of the actual serum creatinine concentration or corrected serum creatinine (r2 = .75; p = .0001). The 30-min creatinine clearance and the 24-hr creatinine clearance had poorer agreement with inulin clearance. The incorporation of a corrected serum creatinine value into the Cockcroft-Gault equation consistently led to better predictions and higher correlation coefficients. Conclusions:The utilization of the Cockcroft-Gault equation as used clinically (the lower of ideal or total body weight and the higher of actual serum creatinine or corrected serum creatinine concentration to 1 mg/dL [85 umol/L]) results in more accurate predictions of glomerular filtration rate in the medical, critically ill patient than urine creatinine clearance measures. If creatinine clearance measures are used, the 30-min collection provided results not different from those results obtained with 24-hr urinary collections. (Crit Care Med 1993; 21:1487–1495)

Is it time to reposition vasopressors and inotropes in sepsis

OBJECTIVES To review the literature on the current use of vasopressors and inotropes in patients with sepsis and sepsis syndrome with respect to the choice of agent, therapeutic end points, and safe and effective doses to be used. To examine the available evidence that supports or refutes goal-directed therapy toward supranormal oxygen transport in optimizing the outcome of critically ill sepsis syndrome patients. DATA SOURCES All pertinent English and French articles dealing with hemodynamic support with selected vasopressors and inotropic agents in human sepsis and sepsis syndrome retrieved from a computerized MEDLINE search from 1985 to 1994. STUDY SELECTION Clinical studies with norepinephrine, epinephrine, phenylephrine, dopamine, and dobutamine in sepsis syndrome were considered if goal-directed therapy with oxygen transport variables was utilized. Emphasis was placed on prospective, randomized, controlled comparative trials. However, open-label, observational, and comparative studies, or case series, were also evaluated when limited data were available. DATA EXTRACTION From the selected studies, information was obtained regarding patient population, dosing regimen, type of therapeutic goals or end points (hemodynamic, or normal vs. supranormal oxygen transport variables) and outcome data (e.g., achievement of goals, resolution of the episode, mortality rate, and development of end-organ dysfunction). DATA SYNTHESIS When used in larger than usual doses, epinephrine, norepinephrine, and phenylephrine uniformly increased hemodynamic values. Epinephrine may increase oxygen transport values more reliably than norepinephrine. Dobutamine doses in the range of 2.5 to 6 microgram/kg/min increase oxygen transport variables and hemodynamics to predetermined goals in only 30% to 70% of patients. Larger infusion rates offer no further benefits. CONCLUSIONS Insufficient evidence exists to support goal-directed therapy with vasopressors and inotropes in the treatment of sepsis syndrome. No definitive recommendations can be made about the superiority of a vasopressor or inotropic agent due to the lack of data. However, it may be that evaluation of vasopressors earlier in sepsis syndrome will yield more promising results. Large, comparative, controlled trials assessing mortality rate and development of multiple organ system dysfunction are needed.

Reduction of high-risk polypharmacy drug combinations in patients in a managed care setting.

Study Objectives. To enhance physician and patient awareness of polypharmacy; to decrease the risks, drug costs, and waste resulting from polypharmacy; and to make the business case for reducing misuse, overuse, and underuse of drugs by reducing polypharmacy.

Economic impact of prolonged motor weakness complicating neuromuscular blockade in the intensive care unit

OBJECTIVE We compared a case-series of ten patients who developed prolonged neuromuscular weakness after continuous, nondepolarizing, neuromuscular blockade with a group of controls without neuromuscular weakness to determine the economic impact of the neuromuscular weakness. DESIGN Frequency-matched case control trial. SETTING Medical and surgical intensive care units of a 937-bed tertiary care, university-affiliated teaching hospital. PATIENTS Ten patients developed prolonged neuromuscular weakness after continuous administration of nondepolarizing neuromuscular blockers. Ten patients from a 1994 drug utilization database who did not develop motor weakness after paralysis were identified to serve as controls. MEASUREMENTS AND MAIN RESULTS The medical and accounting records of the patients were retrospectively reviewed. Charge data were obtained from patient accounts. Institutional ratios to convert charges to full costs and marginal costs were obtained from the Hospital Finance Department of Henry Ford Hospital. The economic impact of the diagnosis and recovery of the motor weakness was estimated for the intensive care unit (ICU) and hospital stays and compared with those values for control patients. Median hospital charges (excluding rehabilitation), totaling

Estimation of Total Body and Extracellular Water Using Single-and Multiple-Frequency Bioimpedance

91,476, were attributed to the patients who developed neuromuscular weakness and included charges for neuromuscular blocking agents, continuous mechanical ventilation, ICU and hospital beds, neurologic studies, and physical therapy services. In the control patients, median charges were

Estimation of total body and extracellular water in post-coronary artery bypass graft surgical patients using single and multiple frequency bioimpedance.

22,191 (p = .001). The total median cost differential for a patient in the neuromuscular weakness group was in excess of

The Economic Impact of Irritable Bowel Syndrome in a Managed Care Setting

66,713 (95% confidence interval

Changing Perspectives of Stress Gastritis Prophylaxis

23,485 to

Prediction of Glomerular Filtration Rate Using Aminoglycoside Clearance in Critically Ill Medical Patients

189,214, p = .001). Significant differences were also found for patient charges, full costs, and marginal costs for mechanical ventilation (p = .002), neurologic studies (p = .014), as well as ICU (p = .002) and hospital (p = .001) stays. CONCLUSIONS The development of motor weakness was associated with an increase in ICU and hospital stays, continued mechanical ventilation, and disproportionate healthcare expenditures in excess of

Influence of Digoxin Immune Fab Therapy and Renal Dysfunction on the Disposition of Total and Free Digoxin

66,000 per patient. A prospective evaluation of the true prevalence of neuromuscular weakness after neuromuscular blockade and of the costs to the healthcare system is needed.