Preserved Metabolic Coupling and Cerebrovascular Reactivity During Mild Hypothermia After Cardiac Arrest
Bisschops LLA, Hoedemaekers CWE, Simons KS, van der Hoeven JG.
Crit Care Med 2010; 38: 1542-1547
Reviewer: Mojca Remskar Konia, MD
University of Minnesota, Minneapolis, MN
Bisschops et al present data from their observational study in patients treated with mild hypothermia following out-of-hospital cardiac arrest. Their primary foci of interest were measurements of cerebral blood flow and cerebral oxygen extraction during the first 48 hours following out-of-hospital cardiac arrest. They further investigated the preservation of cerebrovascular reactivity to changes in the partial pressure of carbon dioxide.
The study included 10 comatose patients admitted to the intensive care unit following cardiac arrest. All of them were treated for 24 hours with mild hypothermia (32 -34 °C) with initiation of cooling within 139 +/- 34.6 minutes after collapse. Following the 24-hour period the body temperature was returned to normothermia with passive re-warming. All patients were mechanically ventilated during the test period and PaCO2 was kept between 34 and 41 mmHg. Mean flow velocity of middle cerebral artery and pulsatility index were measured with cranial Doppler on admission and at 3, 6, 9, 12, 18, 24, 48 hours. Jugular bulb oxygenation was also measured at the same time-points by sampling of blood from the jugular bulb catheter. Cerebrovascular reactivity to carbon dioxide was studied by a temporary decrease/increase of minute ventilation by 20% to achieve an increase/decrease of PaCO2 to 46.5+/-7.2 mmHg/31.4+/-5.6 mmHg on admission to the ICU and at 6, 12, 18 and 24 hours.
The results of the study showed a decreased mean flow velocity (30.3+/-9.5 cm/sec) in the middle cerebral artery during the period of hypothermia, which increased following the normalization of body temperature (67.5+/-33 cm/sec). Jugular bulb oxygenation was normal at the start 66.2+/-8.5% and increased to 82.9+/-4.9% at 48 hours. Changes in carbon dioxide correlated with changes in mean flow velocity (p<0.001) and jugular bulb oxygenation (p<0.001) indicating preserved cerebrovascular reactivity to carbon dioxide.
The survival rate for out-of-hospital and in-hospital cardiac arrest remains disappointingly low at 5-35%. One of the causes of poor outcomes in these patients is the initial insult caused by the absence of body perfusion followed by post-cardiac arrest syndrome, which includes brain injury, myocardial dysfunction, systemic ischemia/reperfusion response and persistent disease state that lead to cardiac arrest. Several actions have been demonstrated to improve neurologic outcome in post-cardiac arrest patients: restoration of myocardial perfusion with percutaneous coronary intervention or fibrinolysis, maintenance of high normal blood pressure 80-100 mmHg, controlled re-oxygenation with minimum necessary fraction of oxygen to maintain SaO2 between 94 and 98, glucose control to moderate glucose levels of 108-144 mg/dL, and mild hypothermia.
This latter area was the focus of this study and an increasing number of studies demonstrate a survival benefit of mild hypothermia initiated up to six hours after return of spontaneous circulation following cardiac arrest. Mild hypothermia following cardiac arrest causes decreases metabolic rate, decreases apoptosis, the inhibition of neuro-excitatory mediator release, decreases levels of pro-inflammatory cytokines, decreases free-radical production and decreases vascular permeability which may all lead to improved survival.
Cardiovascular changes observed during mild hypothermia include: a decreased cardiac index, increased systemic vascular resistance and intravascular hypovolemia due to diuresis, which may all lead to hypotension.
Cerebrovascular changes described in hypothermic patients include reduced cerebral blood flow and oxygen extraction and impaired cerebrovascular reactivity during re-warming phase to more than 37°C. It is obvious that hypotension in conjunction with impaired metabolic coupling and impaired cerebrovascular reactivity may have detrimental consequences.
Even though the presented study is limited by a small number of patients and its observational nature, it does increase the information available about cerebrovascular changes during hypothermia. The study suggests that metabolic coupling in the brain of mildly hypothermic patients is preserved. This is an important finding since decreased cerebral blood flow has been shown to be the result of induced hypothermia. They further demonstrated that cerebro-vascular reactivity to carbon dioxide is preserved during hypothermia.
In conclusion, mild hypothermia in cardiac arrest patients is beneficial for patient survival. Since cerebrovascular reactivity to carbon dioxide is preserved during mild hypothermia, special attention should be paid to PaCO2 levels in these patients.