Forskningsprosjekt


EFFECT OF OPIOIDS AND/OR KETAMINE ON SURVIVAL AND NEUROLOGICAL OUTCOME AFTER CARDIAC ARREST

Vitenskapelig tittel:
EFFECT OF OPIOIDS AND/OR KETAMINE ON SURVIVAL AND NEUROLOGICAL OUTCOME AFTER CARDIAC ARREST

Prosjektbeskrivelse:
Animal studies have shown that exposure to untreated repetitive pain and stress results in prolonged firing of C-fibers, causing glutamate-induced N-methyl-D-aspartate (NMDA) receptor activation. This may augment hypoxia-induced glutamate release, an important mechanism which contributes to neuronal injury or death. Morphine, fentanyl and ketamine are widely administered to critically ill patients in an effort to reduce pain and stress. The antinociceptive effects of opioid analgesics are mediated through a combined presynaptic and postsynaptic hyperpolarization, leading to reductions in the release of and sensitivity to endogenous mediators such as glutamate. These data suggest that opioids might confer neuroprotection by decreasing excitotoxicity through reduction in glutamate release, leading to greater overall reduction in neurological damage. Cell culture studies indicate that both endogenous and exogenous opioids can protect cortical neurons from hypoxia-induced cell death and induce ischemic tolerance in cerebellar Purkinje cells that are subjected to ischemia-reperfusion conditions. Opioid receptor agonists have been shown to increase tissue preservation and survival time of organs before their use in transplantation surgery and to increase survival time during severe and acute hypoxia in animals. Ketamine, because of its capacity to antagonize the NMDA receptor, may be useful for “preemptive analgesia” to decrease facilitation (wind up) of spinal neurons. However, ketamine binds not only to NMDA receptors but also to opioid receptors, with a distinct preference for  - receptors. In two case reports, administration of opioids before sudden cardiac arrest (SCA) apparently contributed to survival of the patients and full neurological recovery despite cardiopulmonary resuscitation (CPR) was abandoned. Despite extensive methodological research and development of modern CPR, survival rates and positive neurological outcome following SCA remain disappointingly low. The reasons for this low rate remain unknown. Thus, it should be investigated in a population of patients fulfilling the criteria of SCA, if increased targeted treatment of pain with different opioid receptor agonists, and blockade of glutamate-induced N-methyl-D-aspartate (NMDA) receptor activation, might affect survival rate and neurological outcome following resuscitation from cardiac arrest.
(Prosjektleders prosjektbeskrivelse)

Ref. nr.: 2009/925 Prosjektstart: 24.08.2009 Prosjektslutt: 30.09.2009

Behandlingsstatus: Under behandling
Prosjektleder: Vladimir Kuklin
Forskningsansvarlig(e):  UNN
Initiativtaker: Bidragsforskning

Forskningsdata: Registerdata
Utvalg: Allmennbefolkning
Forskningsmetode:: Fortolkende (kvalitative) analysemetoder

Behandlet i REK
DatoREK
03.09.2009 REK nord