Clinical paperEffect of moderate hyperventilation and induced hypertension on cerebral tissue oxygenation after cardiac arrest and therapeutic hypothermia☆
Introduction
After global brain ischemia and return of spontaneous circulation (ROSC) cerebral blood flow (CBF) may be inadequate to meet increased cerebral energy demand, mainly because of reperfusion injury-related disorders of macro- and micro-circulation.1, 2, 3 Increasing mean arterial pressure (MAP) with vasopressors may improve CBF4 and neurological recovery5 after cardiac arrest (CA) in animals. Main determinants of CBF are the arterial partial pressure of carbon dioxide (PaCO2) and MAP/cerebral perfusion pressure. When autoregulation is preserved, a reduction in PaCO2 results in brain vasoconstriction that may decrease CBF to ischemic levels.6 If cerebrovascular reactivity is normal, CBF remains constant over a wide range of MAP. In contrast, when autoregulatory capacities are impaired – as it may occur after acute brain injury – CBF becomes increasingly dependent on MAP and higher levels of MAP are necessary to avoid secondary ischemic brain insults.7 These mechanisms have been largely explored in patients with a variety of acute cerebral conditions, namely head trauma and ischemic/haemorrhagic stroke,8, 9 however little is known for patients with global brain ischemia following CA. Furthermore, although the importance of avoiding low MAP levels <60 mmHg is recognized,10 no precise recommendations are given on how to optimize CBF and what threshold of MAP and PaCO2 should be used in post-resuscitation care of comatose CA patients.11
Two clinical studies previous to the introduction of therapeutic hypothermia (TH) examined cerebral autoregulation using transcranial Doppler (TCD). Buunk and colleagues found that moderate hyperventilation could be detrimental by inducing secondary ischemia.12 Sundgreen and colleagues investigated the relationship of CBF velocities to spontaneous changes of MAP (static autoregulation) and found a linear relationship between MAP and CBF was frequent resulting in impaired cerebrovascular reactivity and a shift of the cerebral autoregulatory curve to the right, thereby suggesting higher MAP levels to prevent cerebral ischemia in these patients.7 Part of hypothermia-mediated neuroprotection is by preserving cerebral autoregulation.13 Only one clinical study – using TCD and jugular bulb saturation – examined cerebral autoregulation in 10 hypothermic comatose CA patients and found that CO2 and cerebrovascular reactivity was preserved, suggesting that increasing MAP levels may not improve CBF, at least during TH.14
The issue appears still controversial. In addition, none of these studies tested the dynamic response of CBF to changes in MAP. Near-infrared spectroscopy (NIRS) is increasingly used in critical care to monitor cerebral tissue oxygen saturation (SctO2) non-invasively.15, 16 SctO2 reflects oxygen extraction fraction of the brain, i.e. the balance between oxygen supply and oxygen consumption and can be used as a surrogate marker of CBF and its main clinical application in neurocritical care is to assess cerebral autoregulation in patients with acute brain injury.17, 18 The advantage of NIRS is that it is non-invasive and not operator-dependent thus it is a potentially attractive tool to test dynamic cerebral autoregulation in patients with CA.
The aim of this study was to examine the effect of moderate hyperventilation and induced hypertension on SctO2 in patients with coma after CA treated with TH.
Section snippets
Patients
A prospective pilot study was performed in 10 consecutive comatose patients who were admitted to the medical/surgical intensive care unit (ICU) of the Lausanne University Hospital, Switzerland, following out-of-hospital CA and were treated with TH. Approval for the study was obtained by the local Institutional Review Board. Patients were excluded from the study if they presented haemodynamic instability requiring increasing dose of vasopressors and/or inotropic agents, or hypoxaemia defined as
Patient characteristics
Patients’ baseline characteristics are summarized in Table 1. From May to October 2012, 10 patients were studied. Median patient age was 69 (range 52–87) and median time to return to ROSC was 19 (5–50). All patients had a cardiac cause of CA and were treated with TH and NIRS was applied as soon as the patient was into a stable TH maintenance phase; no patients were excluded due to failure of detecting NIRS signal. At 3 months, 3 patients died and 7 survived with a good outcome.
SctO2 changes to moderate hyperventilation
Mean temperature
Discussion
This is the first study to examine the dynamic response of cerebral tissue oxygenation to changes in PaCO2 and MAP during TH in comatose CA patients, using NIRS. We found moderate hyperventilation (PaCO2 ∼ 30 mmHg) was associated with a significant and clinically relevant reduction in SctO2, while induced hypertension (MAP ∼ 90 mmHg) had no effect on cerebral tissue oxygenation. Our data using NIRS suggest that CO2 and cerebrovascular reactivity are preserved during the hypothermic phase after CA.
Conclusions
Our pilot single-centre prospective study cohort indicates that CO2 and cerebrovascular reactivity seem to be preserved during therapeutic hypothermia in comatose CA patients. As a consequence, moderate hyperventilation (PaCO2 ∼ 30 mmHg) – but not induced hypertension (MAP ∼ 90 mmHg) – was associated with a significant and clinically relevant reduction of NIRS-derived cerebral tissue oxygenation (SctO2) and an increase in oxygen extraction fraction. Our data suggest that hyperventilation might induce
Funding
MO is supported by Grants from the Swiss National Science Foundation (FN 320030_138191) and the European Critical Care Research Network (ECCRN). PB is supported by grants from the “Gueules Cassées” Foundation, France.
Conflict of interest statement
None.
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A Spanish translated version of the abstract of this article appears as Appendix in the final online version at http://dx.doi.org/10.1016/j.resuscitation.2013.05.014.