Comparison of mannitol regimens in patients with severe head injury undergoing intracranial monitoring. The University of Toronto head injury treatment study: a prospective, randomized comparison of pentobarbital and mannitol. Isovolume hypertonic solutes (sodium chloride or mannitol) in the treatment of refractory posttraumatic intracranial hypertension: 2 mL/kg 7.5% saline is more effective than 2 mL/kg 20% mannitol. Out-of-hospital administration of mannitol to head-injured patients does not change systolic blood pressure.
Eighty patients sustaining head injuries and presenting with Glasgow Coma Scale scores of 8 or less were entered into a prospective randomized study to assess the benefit of intracranial pressure (ICP) monitoring with two regimens of mannitol administration. Group I was treated with mannitol for ICP elevations greater than 25 mm Hg, while Group II received empirical mannitol therapy irrespective of ICP readings. No statistically significant differences in mortality rate or neurological outcome were demonstrated between the two groups. These results are comparable to those of several published series of head-injured patients receiving similar treatment from 1977 to 1982. However, those series must be reassessed in light of recently published studies with treatment initiated at lower levels of ICP. Fifty-nine patients were treated in a prospective, randomized comparison of pentobarbital and mannitol for the control of intracranial hypertension resulting from head injury. Patients with elevated intracranial pressure (ICP) after evacuation of intracranial hematomas were randomized to one of two treatment groups; mannitol initially or pentobarbital initially, followed by the second drug as required by further elevation of ICP. Similarly, patients with raised ICP but without hematomas requiring evacuation were randomly assigned to two treatment groups in an identical paradigm. Those with ICP elevation and no hematoma treated with pentobarbital as initial therapy had a 77% mortality compared to a 41% mortality for those with mannitol as initial treatment. Patients with evacuated hematomas had mortalities of 40% and 43% (no significant difference) for pentobarbital and mannitol respectively. In both no-hematoma and hematoma streams pentobarbital was less effective than mannitol for control of raised ICP. Multivariable statistical analysis indicates that pentobarbital coma is not better than mannitol for the treatment of intracranial hypertension and may be harmful in no-hematoma patients with intracranial hypertension after head injury. To evaluate the clinical benefit of increasing the osmotic load of the hypertonic solution administered for the treatment of refractory intracranial hypertension episodes in patients with severe head injury.
                Prospective, randomized study.
                A trauma center in a university hospital.
                Twenty consecutive patients with head trauma and persistent coma who required infusions of an osmotic agent to treat episodes of intracranial hypertension resistant to well-conducted standard modes of therapy were studied. Intracranial hypertension was considered refractory when it persisted despite deep sedation, optimal hemodynamic status, and, in some patients, drainage of cerebral spinal fluid.
                Patients were randomly assigned to receive isovolume infusions of either 7.5% hypertonic saline solution (2400 mOsm/kg/H(2)O) or 20% mannitol (1160 mOsm/kg/H(2)O). The patients were given 2 mL/kg (body weight) of either solution, i.e., 361 +/- 13 mOsm of saline or 175 +/- 12 mOsm of mannitol per injection.
                The main variables studied were the number and the duration of episodes of intracranial hypertension per day during the study period, which was stopped after the last episode of intracranial hypertension was recorded from intracranial pressure monitoring or after the allocated treatment failure. Patients in the HHS group were monitored for 7 +/- 5 days and those in the mannitol group for 7 +/- 6 days (not significant). The rate of failure for each treatment was also evaluated. Failure was defined as the persistence of intracranial hypertension despite two successive infusions of the same osmotic agent. The mean number of osmotic solute infusions was 3.7 +/- 5.3 in the mannitol group and 3.3 +/- 4.1 in the hypertonic saline solution group (not significant). The mean number (6.9 +/- 5.6 vs. 13.3 +/- 14.6 episodes) of intracranial hypertension episodes per day and the daily duration (67 +/- 85 vs. 131 +/- 123 min) of intracranial hypertension episodes were significantly lower in the hypertonic saline solution group (p <.01). The rate of clinical failure was also significantly lower in the hypertonic saline solution group: 1 of 10 patients vs. 7 of 10 patients (p <.01).
                In this study, when a hypertonic solute was required for the treatment of refractory intracranial hypertension episodes in patients with severe head trauma, increasing the osmotic load by giving 2 mL/kg (body weight) of 7.5% saline (361 +/- 13 mOsm) was more effective than giving 2 mL/kg (body weight) of 20% mannitol (175 +/- 12 mOsm). Within the limitations of the present study, these data suggest that giving 2 mL/kg hypertonic saline solution (approximately 480 mOsm/70 kg body weight) is an effective and safe initial treatment for intracranial hypertension episodes in head-trauma patients when osmotherapy is indicated. To determine the effect of out-of-hospital mannitol administration on systolic blood pressure (BP) in the head-injured multiple-trauma patient.
                This was a prospective, randomized, double-blind, placebo-controlled clinical trial involving a university-based helicopter air medical service and level-1 trauma center hospital. Endotracheally intubated head-trauma victims with Glasgow Coma Scale (GCS) scores < 12 were enrolled from November 22, 1991, to November 20, 1992, if evaluated by the participating aeromedical transport team within 6 hours of injury. Patients were excluded if they were < 18 years old, had already received mannitol or another diuretic, were potentially pregnant, or were receiving CPR. All patients were intubated prior to study drug (mannitol [1 g/kg] or normal saline) use. Pulse and BP were measured every 15 minutes for 2 hours following study drug administration.
                A total of 44 patients were enrolled. After exclusion of 3 patients who did not meet all inclusion criteria, there were 20 patients in the mannitol group and 21 patients in the placebo group. The groups were similar at baseline in age, pulse, systolic BP (baseline mannitol: 124 +/- 47 mm Hg; placebo: 128 +/- 32 mm Hg), GCS score, and Injury Severity Scale score. Systolic BP did not change significantly throughout the observation period in either group. This study had 83% power to detect a mean systolic BP drop to < 90 mm Hg.
                Out-of-hospital administration of mannitol did not significantly change systolic BP in this group of head-injured multiple-trauma patients.
Mannitol therapy for raised ICP may have a beneficial effect on mortality when compared to pentobarbital treatment, but may have a detrimental effect on mortality when compared to hypertonic saline. ICP-directed treatment shows a small beneficial effect compared to treatment directed by neurological signs and physiological indicators. There are insufficient data on the effectiveness of pre-hospital administration of mannitol.