TITLE: EFFECTS OF (S)-KETAMINE ON THE BRAIN IN A PORCINE MODEL OF CARDIOPULMONARY RESUSCITATION

AUTHORS: Christof Denz, MD¹, Christoph Janke¹, Michaela Weiss, MD¹, Peter Horn, MD², Klaus Ellinger, MD¹, Heiner Krieter, MD, DEAA¹
AFFILIATION: ¹Inst. of Anesthesiology, Faculty of Clinical Med. Mannheim, Univ. of Heidelberg, Mannheim, Germany; ²Dept. of Neurosurgery, Faculty of Clinical Med. Mannheim, Univ. of Heidelberg, Mannheim, Germany.

INTRODUCTION: The known neuroprotective effects of ketamine (1) are faced with sympathomimetic effects that might increase both, systemic blood pressure and intracranial pressure (ICP) (2) which, in turn, could result in the formation of brain edema. Therefore, this randomized experimental study was designed to investigate the impact of (S)-ketamine on ICP, mean arterial pressure (MAP), and brain edema in a porcine model of cardiopulmonary resuscitation.
METHODS: After approval by the federal animal care com- mittee 10 domestic pigs (body weight 28±2kg) were anesthetized (Piritramid, Pentobarbital) and mechanically ventilated. Cardiac arrest (VF) was induced by AC (60V, 50Hz, 5sec). Basic Life Support was begun 4 min after arrest (Ventilation: FiO2: 0.21). CPR was continued according to the ERC algorithm 5 min after arrest (3). Upon return of spontaneous circulation (ROSC) the animals randomly received an iv infusion of 125ml 0.9% NaCl (PLA: n=5) or 5mg/kg (S)-ketamine in 125ml 0.9% NaCl (KET: n=5) at a rate of 12.5ml/min. The ventilation was adjusted at a PaCO2 of 38-40mmHg. No buffer solution was applied at any time. MAP and ICP (Codman-probe) were documented at baseline, 5, 15, 30, 60, 120, and 240 min after ROSC. Samples of brain tissue were collected at the end of each experiment to measure the wet/dry ratio (W/T).
RESULTS: Baseline values were similar in both groups. The mean duration of CPR until ROSC was 9.4±4.2 min (PLA: 8±3.2 min vs. KET: 10.2±6.1 min; n.s.) At ROSC 5 a significant increase of MAP and CPP occurred in the ketamine treated group (MAP: PLA: 89±13 mmHg vs. KET: 116±15 mmHg; p<0,01/ CPP: PLA: 69±17 mmHg vs. KET: 95±23 mmHg). At ROSC 15 the MAP as well as the CPP were still higher in the KET-group. Neither the time course of the ICP (referred to the baseline) nor the the wet/dry ratio (PLA: 0,749 vs. KET: 0,747, n.s.) did reveal any significant differences between the PLA and KET groups.
DISCUSSION: The significant increases in MAP and CPP in ketamine treated pigs did neither result in marked changes of ICP nor in brain edema. Given the well documented neuroprotective effects of ketamine we will have to reconsider the use of this agent during CPR.
REFERENCES:

1.) Brain Research (1986) 380:186-190.

2.) Anesthesiology (1972) 36:174-176.

3.) Resuscitation (1998) 37: 81-90.