Augmented renal clearance in traumatic brain injury

Introduction

Use of hypertonic saline and/or vasopressor infusion to achieve a desired cerebral perfusion pressure (CPP) in traumatic brain injury (TBI) is common. We hypothesised that the use of such therapies would significantly augment creatinine clearances (CrCl) in this population.

Methods

Head-injured patients requiring hyperosmolar therapy using 3% or 20% saline solutions and/or norepinephrine infusion for the maintenance of a CPP >60 mmHg were recruited into the study. Additional management was consistent with local practice and in line with the Brain Trauma Foundation guidelines [1]. An 8-hour CrCl, physiological variables, fluid balance, and medications were recorded daily during active management of CPP. A further CrCl was collected just prior to discharge (off CPP therapy), and if this was elevated, was repeated on the ward. Augmented renal clearance (ARC) was defined as a CrCl >160 ml/minute/1.73 m² for males and >150 ml/minute/1.73 m² for females [2].

Results

Twenty consecutive patients were enrolled. The average ICU length of stay was 15 days (CI 95% 11 to 18), and time to study entry averaged 2.3 days (CI 95% 1.7 to 2.8). All patients received norepinephrine (n = 20), 85% (n = 17) received hypertonic saline, and therapy lasted on average 7.6 days (CI 95% 5.6 to 9.5). ARC was demonstrated in 17 (85%) patients at any point during active management of CPP. The mean maximum CrCl was 179 ml/minute/1.73 m² while on CPP therapy (CI 95% 159 to 198) returning to a mean CrCl of 111 ml/minute/1.73 m² (CI 95% 91 to 131, P < 0.001) when measured in the ward. The mean CrCl in the ICU while not receiving CPP therapy was 150 ml/minute/1.73 m² (CI 95% 134 to 167, P = 0.03). The mean time to reach peak CrCl while on active treatment was 4.7 days (CI 95% 3.0 to 6.4). Norepinephrine use, saline loading, mean arterial pressure, and central venous pressure, predicted CrCl on the day of measurement.

Conclusions

ARC is common in head-injured patients receiving active management of CPP and persists even after ceasing such therapy. This has significant implications for appropriate dosing of renally excreted drugs in this setting.