Safety and Efficacy of an Auto-Titrating Diuretic Protocol: A Pilot

Introduction In general, clinicians round on patients hospitalized with heart failure (HF) once per day. Additionally, the metrics commonly used to determine response to diuretics, such as fluid and weight loss, are often not recorded after each diuretic dose. Given these limitations, diuretics are generally titrated at best daily. In patients with diuretic resistance, this can translate to lost hospital days with ineffective doses of diuretics. To address this issue, we designed a protocol (herein referred to as the Yale Diuretic Pathway or YDP) to allow for rapid and safe loop diuretic escalation. Hypothesis The nurse driven auto-titrating YDP will lead to rapid dose escalation, without an excessive incidence of hypokalemia, worsening renal function, or hypotension. Methods Advanced heart failure physicians selected 51 patients, largely those who were failing traditional diuretic therapy, for this non-randomized pilot of the YDP. The provider could select the starting dose of diuretic (though the default was 2 mg of bumetanide). Additionally, providers would select safety parameters such as lowest tolerable blood pressure (default was a systolic reading of 90 mmHg or less) and largest allowable increase in creatinine (0.5 mg/dL). Diuretics were titrated based on predicted sodium excretion after each dose, which was predicted using an equation based on a spot urine sample taken 2 h after administration. Based on the predicted sodium output diuretic doses were either held, kept constant, or increased. Patients could receive up to 3 doses daily and a maximum of 12.5 mg bumetanide, equivalent to 500 mg of furosemide per dose and 1500 mg of furosemide per day. Signals for safety such as hypotension, electrolyte abnormalities, and changes in renal function were examined. Results Patients were on the YDP for an average of 3 ± 1.3 days, and the median starting dose was 80 mg of furosemide equivalents (IQR 80-160 mg). The majority of patients required the maximum daily dose of furosemide equivalents over this period (median = 1500mg, IQR 980 to 1500mg) and they reached their peak dose within 1.9 ± 0.7 days. Despite this degree of diuretic resistance, YDP still resulted in a weight loss of 4.0± 3.3 kgs total and fluid output of 9.4L ± 5.1L over the average 3 days of the protocol. With respect to safety, the average rise in creatinine was 0.1 mg/dL. No patients experienced a serum potassium below 3.0 mg/dL and only 3 patients had a serum magnesium below 1.5 mg/dL. Discontinuation of YDP for issues such as a rise in creatinine (10%) and reduction in systolic blood pressure (8%) were relatively uncommon. Conclusion The YDP lead to safe and rapid loop diuretic titration in a population comprised largely of diuretic resistant HF patients. Randomized studies are needed better characterize the safety and efficacy of the YDP.