Effects of rewarming with extracorporeal membrane oxygenation to restore oxygen transport and organ blood flow after hypothermic cardiac arrest in a porcine model
Abstract:We recently documented that cardiopulmonary resuscitation (CPR) generates the same level of cardiac output (CO) and mean arterial pressure (MAP) during both normothermia (38 °C) and hypothermia (27 °C). Furthermore, continuous CPR at 27 °C provides O2 delivery (ḊO2) to support aerobic metabolism throughout a 3-h period. The aim of the present study was to investigate the effects of extracorporeal membrane oxygenation (ECMO) rewarming to restore ḊO2 and organ blood flow after prolonged hypothermic cardiac arres… Show more
“…Based on promising clinical reports ( Ruttmann et al, 2007 ) the use of ECMO for rewarming from accidental hypothermia has been recommended as ECMO can also be continued after rewarming for cardio/respiratory support for days, if needed ( Ruttmann et al, 2007 ; Morita et al, 2011 ). Recently, we have demonstrated that by the use of the present model that rewarming with ECMO restored blood flow to the heart and brain and created a “shockable” cardiac rhythm after 3 h of continuous CPR at 27°C ( Nilsen et al, 2021 ).…”
IntroductionCooling by cardiopulmonary bypass (CPB) to deep hypothermic cardiac arrest (HCA) for cardiac surgical interventions, followed by CPB-rewarming is performed on a routine basis with relatively low mortality. In contrast, victims of deep accidental hypothermia rewarmed with CPB generally have a much worse prognosis. Thus, we have developed an intact pig model to compare effects on perfusion pressures and global oxygen delivery (DO2) during immersion cooling versus cooling by CPB. Further, we compared the effects of CPB-rewarming between groups, to restitute cardiovascular function, brain blood flow, and brain metabolism.Materials and MethodsTotal sixteen healthy, anesthetized juvenile (2–3 months) castrated male pigs were randomized in a prospective, open placebo-controlled experimental study to immersion cooling (IMMc, n = 8), or cooling by CPB (CPBc, n = 8). After 75 minutes of deep HCA in both groups, pigs were rewarmed by CPB. After weaning from CPB surviving animals were observed for 2 h before euthanasia.ResultsSurvival rates at 2 h after completed rewarming were 4 out of 8 in the IMMc group, and 8 out of 8 in the CPBc group. Compared with the CPBc-group, IMMc animals showed significant reduction in DO2, mean arterial pressure (MAP), cerebral perfusion pressure, and blood flow during cooling below 25°C as well as after weaning from CPB after rewarming. After rewarming, brain blood flow returned to control in CPBc animals only, and brain micro dialysate-data showed a significantly increase in the lactate/pyruvate ratio in IMMc vs. CPBc animals.ConclusionOur data indicate that, although global O2 consumption was independent of DO2, regional ischemic damage may have taken place during cooling in the brain of IMMc animals below 25°C. The need for prolonged extracorporeal membrane oxygenation (ECMO) should be considered in all victims of accidental hypothermic arrest that cannot be weaned from CPB immediately after rewarming.
“…Based on promising clinical reports ( Ruttmann et al, 2007 ) the use of ECMO for rewarming from accidental hypothermia has been recommended as ECMO can also be continued after rewarming for cardio/respiratory support for days, if needed ( Ruttmann et al, 2007 ; Morita et al, 2011 ). Recently, we have demonstrated that by the use of the present model that rewarming with ECMO restored blood flow to the heart and brain and created a “shockable” cardiac rhythm after 3 h of continuous CPR at 27°C ( Nilsen et al, 2021 ).…”
IntroductionCooling by cardiopulmonary bypass (CPB) to deep hypothermic cardiac arrest (HCA) for cardiac surgical interventions, followed by CPB-rewarming is performed on a routine basis with relatively low mortality. In contrast, victims of deep accidental hypothermia rewarmed with CPB generally have a much worse prognosis. Thus, we have developed an intact pig model to compare effects on perfusion pressures and global oxygen delivery (DO2) during immersion cooling versus cooling by CPB. Further, we compared the effects of CPB-rewarming between groups, to restitute cardiovascular function, brain blood flow, and brain metabolism.Materials and MethodsTotal sixteen healthy, anesthetized juvenile (2–3 months) castrated male pigs were randomized in a prospective, open placebo-controlled experimental study to immersion cooling (IMMc, n = 8), or cooling by CPB (CPBc, n = 8). After 75 minutes of deep HCA in both groups, pigs were rewarmed by CPB. After weaning from CPB surviving animals were observed for 2 h before euthanasia.ResultsSurvival rates at 2 h after completed rewarming were 4 out of 8 in the IMMc group, and 8 out of 8 in the CPBc group. Compared with the CPBc-group, IMMc animals showed significant reduction in DO2, mean arterial pressure (MAP), cerebral perfusion pressure, and blood flow during cooling below 25°C as well as after weaning from CPB after rewarming. After rewarming, brain blood flow returned to control in CPBc animals only, and brain micro dialysate-data showed a significantly increase in the lactate/pyruvate ratio in IMMc vs. CPBc animals.ConclusionOur data indicate that, although global O2 consumption was independent of DO2, regional ischemic damage may have taken place during cooling in the brain of IMMc animals below 25°C. The need for prolonged extracorporeal membrane oxygenation (ECMO) should be considered in all victims of accidental hypothermic arrest that cannot be weaned from CPB immediately after rewarming.
“…The femoral artery was the preferred vessel for arterial access in 19 studies (95%), with the right femoral artery being the most commonly used site (50%). 34 ECMO flow rate, reported in 18 studies (90%), varied from 30-100 ml/kg/min. 95% (19/20) of studies reported an ECMO duration time with a median of 60 minutes (IQR = 30–360).…”
“…We, therefore, added rewarming using extracorporal membrane oxygenation following 3-h continuous cardiopulmonary resuscitation to our model. Results showed sustained lower levels of cardiac output and blood pressure, maintained aerobic metabolism, restoration of blood flow to the heart and brain, and this rewarming method created a "shockable" cardiac rhythm (134). Due to the appearance of hypothermia-induced cardiac dysfunction in our animals after rewarming, extracorporeal circulation for cardio/respiratory support must be continued for days, if needed, similar to the accidental hypothermia patients rewarmed with this technique (128,160), in order to reestablish a perfusing rhythm.…”
Hypothermia is defined as a core body temperature of < 35°C, and as body temperature is reduced the impact on physiological processes can be beneficial or detrimental. The beneficial effect of hypothermia enables circulation of cooled experimental animals to be interrupted for 1-2 h without creating harmful effects, while tolerance of circulation arrest in normothermia is between 4 and 5 min. This striking difference has attracted so many investigators, experimental as well as clinical, to this field, and this discovery was fundamental for introducing therapeutic hypothermia in modern clinical medicine in the 1950's. Together with the introduction of cardiopulmonary bypass, therapeutic hypothermia has been the cornerstone in the development of modern cardiac surgery. Therapeutic hypothermia also has an undisputed role as a protective agent in organ transplantation and as a therapeutic adjuvant for cerebral protection in neonatal encephalopathy. However, the introduction of therapeutic hypothermia for organ protection during neurosurgical procedures or as a scavenger after brain and spinal trauma has been less successful. In general, the best neuroprotection seems to be obtained by avoiding hyperthermia in injured patients. Accidental hypothermia occurs when endogenous temperature control mechanisms are incapable of maintaining core body temperature within physiologic limits and core temperature becomes dependent on ambient temperature. During hypothermia spontaneous circulation is considerably reduced and with deep and/or prolonged cooling, circulatory failure may occur, which may limit safe survival of the cooled patient. Challenges that limit safe rewarming of accidental hypothermia patients include cardiac arrhythmias, uncontrolled bleeding, and "rewarming shock".
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