A moderate dose of propofol and rapidly induced mild hypothermia with extracorporeal lung and heart assist (ECLHA) improve the neurological outcome after prolonged cardiac arrest in dogs.
OBJECTIVE
Propofol has been shown to protect against neuronal damage induced by brain ischaemia in small animal models. We reported previously that mild hypothermia (33 degrees C) in combination with extracorporeal lung and heart assist (ECLHA) improved the neurological outcome in dogs with cardiac arrest (CA) of 15 min induced during normothermia. In the present study, we investigated the neuroprotective effect of propofol infusion under mild hypothermia with ECLHA in this model.


METHODS
Twenty-one female dogs (15 mongrel dogs and 6 beagles) were divided into three groups: Midazolam 0.1 mg/(kg h) infusion group (M, n=7), Propofol 2 mg/(kg h) infusion group (P2, n=7), Propofol 4 mg/(kg h) infusion group (P4, n=7). Normothermic ventricular fibrillation (VF) was induced in all dogs for 15 min, followed by brief ECLHA and 168 h of intensive care. The drug infusion was initiated at a constant rate after the restoration of spontaneous circulation (ROSC) to 24 h. Mild hypothermia (33 degrees C) was maintained for 20 h. Neurological deficit scores (NDS: 0%=normal, 100%=brain death) were evaluated for neurological function from 33 to 168 h.


RESULTS
One dog in the M group died, and the remaining dogs survived for 168 h. The P4 group showed better neurological recovery compared with the M group (48 h, 21+/-16% versus 32+/-15%; 72 h, 7+/-6% versus 25+/-11%; 96 h, 6+/-6% versus 21+/-6%; 120 h, 5+/-5% versus 20+/-6%; 144 h, 4+/-4% versus 20+/-6%; 168 h, 4+/-4% versus 20+/-6%, p<0.05). One dog in the P2 and three dogs in the P4 group achieved full neurological recovery (NDS: 0%). The number of intact pyramidal cells in the hippocampal CA1 was greater in the propofol groups than midazolam group (p<0.05).


CONCLUSIONS
The combination of propofol infusion at a rate of 4 mg/(kg h), 24h and rapidly induced mild hypothermia (33 degrees C) with ECLHA might provide a successful means of cerebral resuscitation from CA.
Ichinose
Keisuke
K
Department of Anesthesiology, Faculty of Medical and Pharmaceutical Sciences, Kumamoto University, and Kumamoto Rehabiliation Hospital, Japan. ichikei1234@yahoo.co.jp
Okamoto
Taisuke
T
Tanimoto
Hironari
H
Taguchi
Hiroyuki
H
Tashiro
Masafumi
M
Sugita
Michiko
M
Takeya
Motohiro
M
Terasaki
Hidenori
H
D018686:Anesthetics, Intravenous / Q000008:administration & dosage*; D000818:Animals; D001927:Brain Diseases / Q000209:etiology* / Q000517:prevention & control*; D004285:Dogs; D005260:Female; D006323:Heart Arrest / Q000150:complications* / Q000628:therapy*; D006353:Heart-Assist Devices; D007036:Hypothermia, Induced / Q000379:methods*; D008874:Midazolam / Q000008:administration & dosage*; D015742:Propofol / Q000008:administration & dosage*; D012121:Respiration, Artificial; D013997:Time Factors
D018686:Anesthetics, Intravenous; D008874:Midazolam; D015742:Propofol