Effects of intravenous loxapine on systemic and brain hemodynamics

Introduction

Intravenous loxapine is an injectable neuroleptic that can be used as a sedative drug in intensive care. Its effects in patients with severe head trauma are still unknown. The effects of intravenous loxapine on intracranial pressure, cerebral hemodynamics and EEG were studied 11 ± 5 days after trauma (mean ± SD) in seven severe brain-injured patients sedated with continuous infusions of sufentanil and midazolam and mechanically ventilated (age = 37 ± 11 years, initial Glasgow coma scale = 7 ± 3, mortality = 0%).

Methods

Loxapine (10 mg) was injected IV at a constant flow during a period of 10 min; mean arterial pressure (MAP), end tidal CO₂ (ETCO₂), intracranial pressure (ICP), heart rate (HR), mean flow velocity (MFV) and pulsatility index (IP) of the middle cerebral artery (transcranial Doppler WAKI™), left and right spectral edge frequency (SEFl, SEFr) of continuous EEG recording (Philips^© technologies) were simultaneously recorded and digitalized at a frequency rate of 50 Hz (AcqKnowledge™ software) before, during and after loxapine. Statistical analysis was performed by Student t test. P < 0.05 was considered significant.

Results

Before loxapine injection: MAP = 99 ± 11 mmHg, ICP = 14 ± 5 mmHg, MFV = 53 ± 16 cm/s, IP = 0.96 ± 0.26 mmHg, SEFl = 3.1 ± 1.4 Hz, SEFr = 2.5 ± 1.2 Hz. Loxapine did not induce any significant change on these parameters: MAP = 98 ± 12 mmHg (P = 0.7), ICP = 13 ± 4 mmHg (P = 0.1), MFV = 53 ± 16 cm/s (P = 0.9), IP = 1.00 ± 0.20 (P = 0.5), SEFl = 2.4 ± 0.9 Hz (P = 0.06), SEFr = 2.2 ± 0.7 Hz (P = 0.56). ETCO₂ and the dose of vasopressors did not change during the recording.

Discussion

Deep sedation is necessary to control ICP but should not induce a decrease in cerebral perfusion pressure or a direct vasoconstrictor effect. The use of loxapine is safe in terms of cerebral mechanics and hemodynamics and might permit a reduction of benzodiazepine's consumption.

Conclusion

A 10 mg IV injection of loxapine does not induce any change in intracranial pressure, cerebral blood flow or brain electrical activity in patients with severe head trauma.