Using Natriuretic Peptide to Guide Fluid Management During Ventilator Weaning
Abstract & Commentary
By Eric C. Walter, MD, MSc, Pulmonary and Critical Care Medicine, Northwest Permanente and Kaiser Sunnyside Medical Center, Portland, is Associate Editor for Critical Care Alert.
Dr. Walter reports no financial relationships relevant to this field of study.
Synopsis: A protocol using daily natriuretic peptide measurements to guide fluid management during ventilator weaning led to a more negative fluid balance and earlier extubation.
Source: Dessap AM, et al. Natriuretic peptide-driven fluid management during ventilator weaning: A randomized controlled trial. Am J Respir Crit Care Med 2012;186:1256-1263.
This multicenter, randomized controlled trial compared daily B-type natriuretic peptide (BNP) measurements as a way to guide fluid management with usual care in patients undergoing weaning from mechanical ventilation. Patients mechanically ventilated for > 24 hours with SpO2 ≥ 90%, FiO2 ≤ 50%, and PEEP ≤ 8 cm H2O were included. Exclusion criteria were strict and aimed to maximize patient safety. Pregnancy, age < 18 years, allergy to study medications, tracheostomy, cerebral edema, acute hydrocephalus, and some neurologic illnesses were absolute exclusion criteria. Temporary exclusion criteria included acute right ventricular failure, renal insufficiency (renal replacement therapy, plasma urea > 25 mmol/L, plasma creatinine > 180 μmol/L, creatinine clearance < 30 mL/min, or > 25% increase in plasma creatinine over the past 24 hours), iodinated contrast injection within 6 hours, sodium > 150 mEq/L, potassium < 3.5 mEq/L, or arterial pH > 7.5. If temporary criteria were corrected, patients could then be enrolled. Weaning was performed in all patients via an automatic weaning system. A computerized system within the ventilator gradually decreased pressure support and performed a spontaneous breathing trial (SBT). When an SBT was passed, the computer sounded an alert. If patients also met other safety criteria for extubation (not overly sedated, no excessive secretions, etc.), they were immediately extubated.
At the start of weaning, all patients had a daily BNP measured. Patients in the intervention arm (n = 152) had fluid and diuretic management guided by BNP results. If BNP was ≥ 200 pg/mL, fluid intake was restricted and furosemide was administered with a goal urine output of 1.5 to 3 mL/kg/hour. BNP results for patients in the control arm (n = 152) were not available to the treatment team and fluid and diuretic management were at the treatment team’s discretion.
The primary endpoint was time from randomization to successful extubation (alive and without reintubation for 72 hours). Time to extubation was approximately 16 hours shorter in the BNP-guided group than the control group [median 42.4 (20.8-140.6) vs 58.6 (23.3-139.8); P = 0.034]. The BNP-guided group also had more ventilator-free days (9.7 vs 12.0) and a greater negative fluid balance during weaning (-2320 mL vs -180 mL). There were no significant differences in cardiovascular function, metabolic abnormalities, or renal function between groups. During weaning, fewer patients in the BNP-guided group had respiratory deterioration, ventilator-associated pneumonia, or needed continuous sedation than in the control group. A priori subgroup analyses suggested that the treatment effect was most pronounced among patients with left ventricular dysfunction and less so among patients with chronic obstructive pulmonary disease.
Strengths of this study include the multicenter design, excellent follow-up, and the use of a simple, once daily diagnostic test. Furthermore, the use of an automated weaning protocol should have helped to minimize differences in weaning techniques. This trial provides additional strong support for the idea that a negative fluid balance is helpful for ventilator weaning and extubation success. Previous studies have shown that a negative fluid balance shortens mechanical ventilation time,1 and a positive fluid balance is associated with extubation failure.2
It is unlikely that BNP itself is a biomarker specific to weaning success. Rather, the act of measuring BNP may have stimulated the treatment team to react to volume overload and aggressively diurese. Since more than two-thirds of patients in both groups had at least one BNP ≥ 200, most patients were in need of diuresis. Interestingly, the observed difference in ventilator-free days at day 28 (2.6 days) was nearly identical to that seen in the Fluids and Catheters Treatment Trial ([FACTT] 2.5 days).1 The advantage of BNP would seem to be the use of a single daily lab measurement vs the complex algorithm requiring invasive measurements described in FACTT. As in previous studies, aggressive diuresis was shown to be safe. Weaknesses of this study include the strict exclusion criteria, which may limit generalizability. Furthermore, since the study was not blinded, it is possible that the final decision to extubate was biased by knowledge of the patient’s study arm.
Avoiding fluid overload with aggressive diuresis leads to earlier extubation without significant adverse events. It appears this goal can be achieved with either invasive monitoring, or now, with measurement of BNP. Both appear to serve as reminders to clinicians of the importance of diuresis. In the future, it may be that neither is absolutely necessary as long as clinicians have a fundamental understanding of this concept and apply it to patient care.
- Wiedemann HP, et al. Comparison of two fluid-management strategies in acute lung injury. N Engl J Med 2006;354:2564-2575.
- Frutos-Vivar F, et al. Risk factors for extubation failure in patients following a successful spontaneous breathing trial. Chest 2006;130: 1664-1671.