Multimodal short acting sedation using NMDA antagonist and remifentanil in brain trauma patients: a prospective randomised study

Abstract

We hypothesize that using a multimodal short-acting sedation regimen based on remifentanil and NMDA-antagonist receptors such as ketamine, clonidine and magnesium will improve cerebral protection and make clinical patient examination easier without hemodynamic impairments. Methods Sixty-eight ventilated brain trauma patients (mean Glasgow Coma Scale: 5 � 3) with controlled invasive ventilation during 6.4 (� 4) days were prospectively randomized into two groups (G1 n = 32; G2 n = 36) using different sedation protocols to reach a mean hourly Ramsay Score of 4. Sedation in G1 was based on morphine (0.1 � 0.1 mg/kg/hour) and midazolam (0.4 � 0.4 mg/kg/hour); in G2 on remifentanil (0.25 � 0.25 �g/kg/min), magnesium (0.08 g/kg/day), ketamine (0.15 � 0.15 �g/kg/min), clonidine (0.001 � 0.001 �g/kg/min) and propofol (2 � 1.5 mg/kg/ hour). The cerebral parameters (mean intracranial continuous pressure (mICP); mean cerebral perfusion pressure (mCPP)) and the needs of norepinephrine (Ne) were evaluated hourly. Preloading was adapted by a continuous central venous pressure measurement before Ne adaptation requirements to keep the mCPP over 60 mmHg. For statistical analysis a ShapiroWilk test, a Wilcox test and a Student t test were used. Results Demographic data (age, gender, trauma severity score) were comparable in both groups. The waking time was significantly shorter in G2 (5 � 8 min) compared with G1 (35 � 20 min) (P < 0.05). The mICP was more stable in G2 (9 � 4 mmHg) compared with G1 (10 � 9 mmHg) (P = 0.02). The mCPP were comparable in G1 (62 � 10 mmHg) and in G2 (63 � 0.2 mmHg) but with a 24% swing in dose requirement adaptation of Ne in G1 compared with a 6% daily swing in G2 (P < 0.02). Conclusion By using a multimodal short-acting sedation protocol based on remifentanil and NMDA-antagonist receptors we were able to provide adequate sedation in brain trauma patients. Neurological parameters were respected with this regimen, avoiding the risk of secondary patient hemodynamic destabilisation during the waking periods.