Efficacy of prolonged cardiopulmonary resuscitation during accidental cold water hypothermia

Effects of cardio-pulmonary resuscitation (CPR) in patients with hypothermia-induced cardiac standstill, and rewarming by heart-lung machine (HLM). The project idea was to explore effects of prolonged CPR in accidental hypothermia patients and effects of rewarming by HLM. While normothermic cardiac arrest patients seldom can be resuscitated if spontaneous circulation has not been achieved within the first 30 min, hypothermic patients may survive ongoing CPR for up to 6 hours CPR before being successfully rewarmed by HLM. By using an animal model (porcine) cooled to 27°C, before inducing cardiac standstill, the effects of CPR on global oxygen transport and organ blood flow to vital organs (brain, heart, kidneys, liver, and gut) was measured. For comparisons, the same experimental procedures and the same measurements were done in this animal model at 37°C. During the first 20 min of CPR in animals kept at 37°C, oxygen transport was reproduced up to 30% of the value measured during spontaneous circulation, but oxygen transport vanished after 45 min of CPR. However, in the hypothermic animals (27°C) CPR reproduced up to 80% of oxygen transport (compared to during spontaneous circulation at the same temperature) during 3h. In addition, an apparent preference of blood flow to the brain was observed. These findings indicate that in accidental hypothermia patients with cardiac standstill, if standard procedure CPR is immediately started close to normal oxygen transport to vital organs can be provided. For rewarming, the circulatory system of the animals was connected to a HLM after 3h CPR. The blood was continuously drained from the venous system of the animal via the pump on the HLM, oxygenated, heated, and thereafter returned to the main artery. The same measurements were repeated as during CPR. The animals were rewarmed to normal core temperature within 60-90 min on HLM, and results show that oxygen transport to all vital organs monitored was close to restored after 3h CPR and 60-90 min rewarming. Spontaneous heart activity took place in all animals during rewarming at about 30°C. These findings collected from our experiments show that CPR performed at low core temperature restitute oxygen transport to vital organs by 80%, when compared to oxygen transport during spontaneous circulation at the same temperature. Further, we show that this oxygen transport was provided throughout 3h at this temperature. Finally, we saw that rewarming to 37C by HLM was achieved within 60 - 90 min with restitution of blood flow and oxygen transport to all vital organs. These findings support the recommendations in our recently published national guidelines for treatment of accidental hypothermia patients: Immediate start of CPR in accidental hypothermia patients in cardiac arrest must be continued during transport to in hospital rewarming by HLM.

Due to the financial support from the Research Council of Norway of our research project:"220810 - Efficacy of prolonged cardiopulmonary resuscitation during accidental cold water hypothermia" our research group, both nationally and internationally, has managed to conduct numerous researc protocols. So far results from these protocols have been published as 8 original articles in international peer review Journals. These articles, in addition to manuscripts from these projects not yet published, are all included in 4 PhD thesis works, one at The Mayo Clinic, USA, and 3 at UiT - The arctic university of Norway. Further, results from these experimental hypothermia works are also included in our National Guidelines for Treatment of Accidental Hypothermia, released in 2017.

Accidental hypothermia is always a potential threat to humans exposed to circumpolar environments. If not immediately rescued body core tp. of immersion hypothermia victims will eventually drop. As a consequence of muscular rigidity and mental confusion t hey are unable to swim or move properly at core tp. close to 33ºC. Below 28ºC cardiac arrest and thus cold ischemia takes place. Theoretically, global ischemia at low tp. is ameliorated by protective effects on organ survival by primarily reducing cellula r metabolism (Q10) and subsequently O2 demand. As an example; at 25ºC brain tissue will survive ischemia > 30 min in contrast to < 5 min at 37ºC. These beneficial effects of hypothermia to buy time with respect to organ survival during rescue have been do cumented in our case reports showing successful rewarming after immersion to core tp. to 13.7°C on admission following 3- 5hs continuous pre-hospital cardiopulmonary resuscitation (CPR) before hospital rewarming by use of heart-lung machine. This indicate s that in hypothermic patients, in essential contrast to normothermic patients, CPR provides sufficient organ O2 transport to prolong organ survival for 3-4hs. Our published data show that mechanisms facilitating O2 extraction are functioning during hypot hermia; during maintained spontaneous cardiac activity for 4h at 15ºC, despite a temperature dependent decrease in cardiac output (50%) and blood pressure (70%), we documented adequate O2 supply at these low tp. In addition to Q10 reduction, also dissolve d O2 content is increased at low tp. which will elevate blood O2 transport. Our established porcine accidental hypothermia model will be used in the present project and equipped with an automatic, hydraulic chest compression/ decompression CPR device. Thi s model is equipped to provide mandatory new data on organ (heart and brain) O2 consumption and metabolic function during CPR. Post mortem organ examination on molecular and morphologic patency will also be done.