Economic implications of neonatal intensive care unit collaborative quality improvement.

OBJECTIVE: To make measurable improvements in the quality and cost of neonatal intensive care using a multidisciplinary collaborative quality improvement model. DESIGN: Interventional study. Data on treatment costs were collected for infants with birth weight 501 to 1500 g for the period of January 1, 1994 to December 31, 1997. Data on resources expended by hospitals to conduct this project were collected in a survey for the period January 1, 1995 to December 31, 1996. SETTING: Ten self-selected neonatal intensive care units (NICUs) received the intervention. They formed 2 subgroups (6 NICUs working on infection, 4 NICUs working on chronic lung disease). Nine other NICUs served as a contemporaneous comparison group. PATIENTS: Infants with birth weight 501 to 1500 g born at or admitted within 28 days of birth between 1994 and 1997 to the 6 study NICUs in the infection group (N = 2993) and the 9 comparison NICUs (N = 2203); infants with birth weight 501 to 1000 g at the 4 study NICUs in the chronic lung disease group (N = 663) and the 9 comparison NICUs (N = 1007). INTERVENTIONS: NICUs formed multidisciplinary teams which worked together to undertake a collaborative quality improvement effort between January 1995 and December 1996. They received instruction in quality improvement, reviewed performance data, identified common improvement goals, and implemented "potentially better practices" developed through analysis of the processes of care, literature review, and site visits. MAIN OUTCOME MEASURES: Treatment cost per infant is the primary economic outcome measure. In addition, the resources spent by hospitals in undertaking the collaborative quality improvement effort were determined. RESULTS: Between 1994 and 1996, the median treatment cost per infant with birth weight 501 to 1500 g at the 6 project NICUs in the infection group decreased from $57 606 to $46 674 (a statistical decline); at the 4 chronic lung disease hospitals, for infants with birth weights 501 to 1000 g, it decreased from $85 959 to $77 250. Treatment costs at hospitals in the control group rose over the same period. There was heterogeneity in the effects among the NICUs in both project groups. Cost savings were maintained in the year following the intervention. On average, hospitals spent $68 206 in resources to undertake the collaborative quality improvement effort between 1995 and 1996. Two thirds of these costs were incurred in the first year, with the remaining third in the second year. The average savings per hospital in patient care costs for very low birth weight infants in the infection group was $2.3 million in the post-intervention year (1996). There was considerable heterogeneity in the cost savings across hospitals associated with participation in the collaborative quality improvement project. CONCLUSION: Cost savings may be achieved as a result of collaborative quality improvement efforts and when they occur, they appear to be sustainable, at least in the short run. In high-cost patient populations, such as infants with very low birth weights, cost savings can quickly offset institutional expenditures for quality improvement efforts.

Pharmacokinetics and pharmacodynamics of heparin during hemodialysis: interpatient and intrapatient variability.

Heparin pharmacokinetics and pharmacodynamics were studied in 17 patients undergoing hemodialysis, once a week for 4 weeks in order to evaluate intrapatient variability over time. A single bolus injection of heparin was administered directly into the circulation immediately prior to the start of hemodialysis in doses ranging from 3000 to 12,000 U. Blood samples were obtained to determine activated coagulation times (ACT) and heparin concentrations (HC). Combined zero- and first-order elimination was seen in each of the 4 weeks. The half-life of heparin decreased from beginning to end of hemodialysis during each week, with the percentage of decrease from the start of dialysis ranging from 70-74%, indicating concentration-dependent elimination. Since the zero-order component did not appear to be clinically significant, first-order elimination was assumed. A linear decline in ACT over the time of the dialysis period was also seen during each week. A profile of ACT versus HC was generated for each patient as well as for the mean data to assess the relationship of HC to response. An excellent correlation was found for both individual patient data and mean data. In the third week the patients were randomized to receive standard treatment or an individualized dose. They were then crossed over to the opposite group in the fourth week to see if this relationship between ACT and HC would be useful in predicting heparin dose. These profiles were used to individualize the dose during either the third or fourth week of the study. No significant differences were noted between actual and predicted ACT. A significant degree of interpatient variability was demonstrated.(ABSTRACT TRUNCATED AT 250 WORDS)

Heparin pharmacokinetics during hemodialysis.

The disposition of heparin was studied in 21 chronic hemodialysis patients. Heparin was administered as a bolus injection in doses of 3,000-12,000 U. Combined zero and first-order elimination was demonstrated, with heparin half-life declining by 74% over 3.5 h during dialysis. Assumption of a first-order pharmacokinetic model of elimination resulted in a mean difference of 0.001 U/ml between actual and predicted heparin concentrations. Mean first-order pharmacokinetic parameters were: half-life, 117 min; heparin volume of distribution (V), 68 ml/kg; clearance, 28 ml/min. A high degree of interpatient variability was also observed. A comparison of V and plasma volume (PV) revealed V to be significantly greater than PV (p less than 0.001), indicating distribution outside the plasma compartment. When compared to blood volume, there was no significant difference (p greater than 0.1), indicating that blood volume may be used to approximate V. The nonlinear component of the elimination process is not clinically significant within the range of therapeutic plasma concentrations used during hemodialysis, but the high degree of interpatient variability indicates that dosage individualization may be useful.

Genital necrosis secondary to warfarin therapy.

Several adverse dermatologic effects have been reported with the use of warfarin. Among these is the rare complication of drug-induced necrosis. Approximately 150 cases had been reported by 1976, and a review of the literature since 1943 revealed only 4 reported cases of penile necrosis. We present the fifth case of genital necrosis reported with coumarin anticoagulants and the third such case associated with warfarin.

Double-blind, placebo-controlled trial of twice-daily nifedipine as a step-2 agent in mild essential hypertension.

Nifedipine is a calcium-channel blocker that produces vasodilatation and decreased peripheral resistance in humans. Several clinical reports document blood-pressure-lowering effects of nifedipine with either acute or chronic administration. Little data are available to evaluate sustained-release nifedipine as a step-2 agent. We performed a multicenter double-blind, placebo-controlled trial of twice-daily nifedipine in the treatment of mild essential hypertension not controlled by diuretic alone. Seventy-one subjects completed 8 weeks of treatment with nifedipine or placebo in combination with a stable dose of diuretic. Treatment groups were comparable with respect to age, sex, race, duration of hypertension, and pretreatment weight. Baseline supine blood pressure was no different in the two treatment groups (144 +/- 15/98 +/- 6 mmHg in the nifedipine/diuretic-treated group and 145 +/- 16/98 +/- 6 mmHg in the placebo/diuretic-treated group). After 8 weeks of treatment, supine blood pressure was 132 +/- 11/88 +/- 6 mmHg in the nifedipine/diuretic-treated group and 140 +/- 16/92 +/- 8 mmHg in the placebo/diuretic-treated subjects (p less than 0.01 for both systolic and diastolic blood pressure when compared to placebo/diuretic). Nifedipine with diuretic had similar effects on standing blood pressure. Nifedipine/diuretic decreased blood pressure from baseline values within 1 week of treatment, and the effect persisted for 8 weeks. Heart rate increased in nifedipine/diuretic-treated subjects during the first 2 weeks of treatment but returned to baseline by 4 weeks. No laboratory abnormalities could be attributed to nifedipine/diuretic treatment. Side effects were mild and infrequent. In summary, nifedipine/diuretic is effective and well tolerated in the treatment of uncomplicated essential hypertension inadequately controlled with diuretic therapy alone.

Peritoneal transport of cefonicid.

The pharmacokinetic characteristics of cefonicid, a highly protein-bound expanded-spectrum cephalosporin, were examined in six noninfected, clinically stable patients undergoing continuous ambulatory peritoneal dialysis. After a 1.0-g intravenous dose of cefonicid, the mean concentrations in serum were 105 +/- 25 and 35.6 +/- 14.4 micrograms/ml at 3 and 72 h, respectively. Despite a prolonged half-life in serum of 49.7 +/- 18 h, the penetration into peritoneal fluid was low. The average concentration in dialysate over the 72-h study period was 2.7 micrograms/ml. The serum clearance was 2.6 +/- 1.0 ml/min, and the distribution volume was 0.14 +/- 0.02 liter/kg. Dosage recommendations and clinical considerations for cefonicid use in continuous ambulatory peritoneal dialysis patients are discussed.