Randomized, controlled trial on the effect of a 20% mannitol solution and a 7.5% saline/6% dextran solution on increased intracranial pressure after brain injury.

Crit Care Med 2005;33:196-202

Introduction

Intracranial hypertension is an important cause of secondary cerebral damage after severe traumatic brain injury. Both mannitol and hypertonic saline are effective in reducing intracranial pressure. The current study is a randomized controlled trial comparing the effects of 20% mannitol with 7.5% saline/6% dextran-70 (HSD) in patients with increased ICP.

Study

The study was a prospective, non-blinded, randomized crossover pilot trial. A patient was recruited to the trial if the ICP was > 20 mm Hg for more than 5 minutes after exclusion of easy treatable external factors. A total of 9 patients were recruited (6 after severe TBI and 3 after SAB). CPP was maintained at > 70 mm Hg. A treatment consisted of an equimolar infusion of either 200 ml 20% mannitol or 100 ml HSD. Each patient received four treatments, two of mannitol and two of HSD. The order of the first/second and the third/fourth treatment was randomized.

Although both mannitol and HSD reduced the minimum ICP, the effect of HSD was significantly stronger (difference -5 mm Hg, 95% CI -10.8 to -3.0; p = 0.014). The duration of the ICP lowering effect was also significantly longer for HSD than mannitol (p = 0.044). HSD resulted in a significant decrease in the minimal mean arterial pressure and increased the maximal CPP. Mannitol both decreased the minimal CPP and increased the maximal CPP. Minimal CPP was significantly higher after HSD than mannitol. Mannitol caused a significant decrease in serum sodium levels while HSD resulted in a significant increase in serum sodium levels. Both mannitol and HSD showed comparable increases in serum osmolality. Urine sodium levels were significantly higher after HSD while urine volumes appeared to be higher after mannitol.

Discussion

This is a small non-blinded pilot trial suggesting that HSD is more effective than mannitol in lowering increased ICP. Furthermore, minimal CPP was significantly higher after HSD and both findings may be clinically important. Unfortunately, the trial included only 9 patients (six after severe TBI and 3 after SAB) and some of the required data are missing. This trial was non-blinded and concomitant treatment (sedatives, hyperventilation) should have been described more precisely. As the most important clinical outcome parameters were not considered (neurological outcome, mortality) an adequately powered trial in a homogenous patient group is necessary to answer these questions. In the meanwhile both mannitol and HSD appear to be suitable treatment options for patients with increased ICP.

A. Salet, Fellow Intensive Care
J.G. van der Hoeven, Intensivist