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(Stroke. 1997;28:1569-1573.)
© 1997 American Heart Association, Inc.

Articles

Cerebrovascular Reactivity in Comatose Patients Resuscitated From a Cardiac Arrest

Gerba Buunk, MD; Johannes G. van der Hoeven, MD, PhD Arend E. Meinders, MD, PhD

From the Department of General Internal Medicine (Medical Intensive Care Unit), University Hospital Leiden, the Netherlands.

Correspondence to Gerba Buunk, MD, Medical Intensive Care Unit, C6-Q, Albinusdreef 2, PO Box 9600, 2333 ZA Leiden, Netherlands. E-mail snoeken{at}worldonline.nl

	Abstract

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Background and Purpose Cerebral blood flow after cardiac arrest is reduced during the delayed hypoperfusion phase, while cerebral metabolic rate of oxygen returns to baseline values. Hypocapnia can induce cerebral ischemia in neurosurgical patients who already have reduced cerebral blood flow. The purpose of the present study was to determine whether comatose patients resuscitated from a cardiac arrest have a normal cerebrovascular reactivity to changes in Paco₂ and whether hypocapnia causes cerebral ischemia.

Methods We measured mean flow velocity (MFV) and pulsatility index (PI) in the middle cerebral artery, jugular bulb oxygen saturation (SjbO₂), and arterial-jugular lactate difference (AJLD) during normo-, hypo-, and hyperventilation in 10 comatose patients resuscitated from a cardiac arrest. The first measurements were made within 6 hours after cardiac arrest and repeated 6, 12, and 24 hours later.

Results During hypoventilation we observed a significant decrease in PI and an increase in MFV and SjbO₂. During hyperventilation PI and MFV did not change, but SjbO₂ showed a significant decrease. This was accompanied by an increase in AJLD, suggesting cerebral ischemia. In four patients the SjbO₂ decreased below the ischemic threshold of 55%.

Conclusions The cerebrovascular reactivity to changes in arterial carbon dioxide tension is preserved in comatose patients resuscitated from a cardiac arrest. Hyperventilation may induce cerebral ischemia in the postresuscitation period.

Key Words: cardiac arrest • cerebral blood flow • carbon dioxide tension

	Introduction

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Changes in PaCO₂ have a profound effect on CBF. A decrease of 0.15 kPa in the PaCO₂ results in a 5% decrease in CBF.¹ Hypocapnia can induce cerebral ischemia in neurosurgical patients who already have reduced CBF.^{2 3} Multiple episodes of ischemia are significantly associated with a poor neurological outcome.⁴

Hyperventilation is still recommended in the postresuscitation care of comatose patients after cardiac arrest. It is assumed that areas with intact CO₂ responsiveness will constrict during hyperventilation and shunt blood to the more damaged areas where CO₂-responsiveness is lost.⁵ However, there is no evidence that this reverse-steal phenomenon improves neurological outcome.

CBF after cardiac arrest is reduced to about 50% of normal, while the cerebral metabolic rate of oxygen increases to normal or supranormal levels.^{6 7 8} This may result in a mismatch between cerebral oxygen delivery and oxygen consumption. A further reduction in CBF caused by hypocapnia might induce or enhance cerebral ischemia. This decrease in CBF is evident from 2 to 12 hours after cardiac arrest and is called the delayed hypoperfusion phase. The pathogenesis is unclear; vasospasm,⁹ edema,^{10 11} and blood cell aggregates¹² are all suggested possibilities. In a previous study¹³ we found evidence for increased cerebrovascular resistance caused by an imbalance between local vasodilators and vasoconstrictors.

Data from animal experiments show that cerebrovascular reactivity to changes in PaCO₂ is severely impaired¹⁴ or variable¹⁵ after global ischemia. Data in humans are not available. The purpose of the present study was to determine the cerebrovascular reactivity to changes in PaCO₂ in comatose patients resuscitated from a cardiac arrest.

	Materials and Methods

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After approval of the study by the hospital ethics committee, we studied 10 comatose patients (Glasgow Coma Score 6) successfully resuscitated from an out-of-hospital cardiac arrest. Written informed consent was obtained from the nearest relative.

Immediately after restoration of spontaneous circulation, patients were transferred from the emergency department to the medical intensive care unit. All patients were intubated and mechanically ventilated. For hemodynamic monitoring a 7.5F flow-directed pulmonary artery catheter was introduced through the right jugular vein, and thermodilution cardiac output was measured by standard methods. The radial or femoral artery was cannulated for monitoring of blood pressure and sampling of arterial blood. A 5.5F oximetry thermodilution catheter (Baxter Healthcare Corporation) was introduced into the left jugular bulb according to the method described by Goetting and Preston.¹⁶ In the literature there is controversy regarding the venous drainage of the brain.^{17 18} In patients with head injury the jugular bulb catheter is usually inserted into the jugular vein causing the largest increase in intracranial pressure on unilateral compression. However, Stocchetti et al¹⁹ were not able to identify the most appropriate side for monitoring SjbO₂ in patients with head injury. Therefore, in the absence of an intracranial pressure monitor we chose for reasons of convenience to cannulate the left jugular bulb. SjbO₂ was continuously measured with the SAT-2 oximetry computer (Baxter Healthcare Corporation).

Patients were treated according to our resuscitation protocol. The goal was to keep PaO₂ >10 kPa, PaCO₂ between 4.0 and 4.5 kPa, mean arterial blood pressure between 90 and 110 mm Hg, and the cardiac index >3.0 L · min^–1 · m^–2. If necessary, patients were treated by volume infusion, dobutamine, and occasionally noradrenaline.

Cerebrovascular reactivity to changes in PaCO₂ was studied with a combination of transcranial Doppler ultrasound and jugular bulb oximetry. The following measurements were performed: systemic artery– and pulmonary artery–derived hemodynamic parameters and arterial and jugular bulb blood gas analyses and lactate. Kety and Schmidt²⁰ reported a normal range of SjbO₂ between 55% and 75%. Mean blood flow velocity and PI in the MCA were measured using transcranial Doppler ultrasonography.

After obtaining baseline measurements, ventilator settings were changed and hypocapnia was achieved by increasing the minute ventilation by 20% over 20 minutes. After obtaining the hypocapnic measurements, the minute ventilation was changed to baseline setting. After 20 minutes the minute ventilation was decreased by 20% over 20 minutes, and hypercapnic data were obtained. Patients were treated with pancuronium 0.1 mg/kg to avoid breathing efforts. The first measurements were made immediately after hemodynamic stabilization, always within 6 hours after cardiac arrest, and repeated 6, 12, and 24 hours later.

Blood Gases/Lactate
Blood gas measurements were performed using a BGE analyzer (Instrumentation Laboratory). Lactate was measured on a DuPont ACA.

Transcranial Doppler Ultrasonography
The MCA was chosen for the examination because this vessel perfuses about 80% of the cerebral hemisphere and because of its ease and reproducible accessibility for transcranial Doppler ultrasonography. Blood flow velocity measurements in the MCA were performed with a range-gated Doppler device with 2 MHz emission frequency (TC2-64; Eden Medical Electronics) according to the method developed by Aaslid et al.²¹ We measured mean flow velocities; the time-mean of the spectral outline was averaged over at least 5 cardiac cycles. The temporal acoustic window and Doppler depth giving the highest velocities were used for all measurements. To minimize interobserver variability all measurements were done by two investigators (G. Buunk and J.G. van der Hoeven). Normal mean MCA velocity varies from 41±7 to 94±10 cm/s. Most of this variation can be explained by age differences; mean MCA velocity gradually declines with age.²² The PI was calculated as (V_systolic–V_diastolic)/V_mean. Normal PI in the MCA varies between 0.69±0.10 at 55 mm and 0.71±0.13 at 30 mm.²³

Statistical analysis was performed using a commercial software package (Excel for Windows). Data are expressed as mean±SD and analyzed with Student's t test for paired samples. The cerebrovascular reactivity, expressed as % change in MFV per kPa, was analyzed by ANOVA. A value of P.05 was considered statistically significant. To describe the relation between changes in PaCO₂ on the one hand and changes in SjbO₂, MCA velocity, and PI on the other, we performed a linear regression analysis and calculated the Pearson correlation coefficient.

	Results

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We studied 10 consecutive comatose patients successfully resuscitated from an out-of-hospital cardiac arrest. There were 2 women and 8 men, with a mean age of 60.5±21.5 years (range, 24 to 83 years). The clinical diagnosis and outcome are shown in Table 1. Hemodynamic data obtained before the change in minute ventilation are shown in Table 2. The MFV, PI in the MCA, and the SjbO₂ (as measured before the change in minute ventilation) did not change significantly during the 24 hours of our study. Hypoventilation (ie, hypercapnia) was followed by a significant increase in MFV, a decrease in PI, and an increase in PjbO₂ and SjbO₂ (Table 3). Hyperventilation (ie, hypocapnia) did not change the MFV and PI of the MCA. However, there was a significant decrease in PjbO₂ and SjbO₂ (Table 4). The SjbO₂ decreased below the potential ischemic threshold of 55% in 4 patients. The PaCO₂ in these patients varied between 3.0 and 4.0 kPa, with a SjbO₂ between 33% and 51%. We found a significant correlation between PaCO₂ and PI (r=.61, P<.0001) (Figure, panel a), PaCO₂ and MFV (r=.78, P<.0001) (Figure, panel b), and PaCO₂ and SjbO₂ (r=.58, P<.0001) (Figure, panel c). The increase in PaCO₂ was accompanied by a significant increase in blood pressure, from 93.9±21.9 mm Hg to 99.8±21.2 mm Hg (P=.009). The decrease in PaCO₂ was accompanied by a slight, nonsignificant decrease in blood pressure, from 91.6±17.8 mm Hg to 90.3±15.5 mm Hg (P=.472). Regression analysis showed that the MFV and SjbO₂ were significantly correlated with the change in PaCO₂ (P<.0001) but not with the change in mean arterial pressure (P=.75). When we analyzed the hypo- and hyperventilation data separately we also could not find a significant correlation between the change in mean arterial blood pressure and the MFV and SjbO₂. The cerebrovascular reactivity expressed as % change in MCA velocity per kPa change in PaCO₂ was significantly different during hypo- and hyperventilation (P<.0001) but did not change significantly during the 24 hours of our study (Tables 3 and 4). However, the change in SjbO₂ per kPa change in PaCO₂ was not different during hypo- and hyperventilation. This parameter also did not change during the study period (Tables 3 and 4). During the first measurements, hyperventilation induced a significant increase in the arterial-jugular lactate difference and hypoventilation induced a significant decrease in the arterial-jugular lactate difference. No differences between survivors and nonsurvivors were found. Neither did we find an age- or sex-related difference in response.

View this table: [in this window] [in a new window]   Table 1. Demographic Data

View this table: [in this window] [in a new window]   Table 2. Hemodynamic Data During Normoventilation

View this table: [in this window] [in a new window]   Table 3. Results of Hypoventilation

View this table: [in this window] [in a new window]   Table 4. Results of Hyperventilation

View larger version (14K): [in this window] [in a new window]   Figure 1. Change in PaCO2 vs changes in PI (panel a), MFV (panel b), and SjbO2 (panel c).

	Discussion

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Several methods are available to assess cerebrovascular CO₂ reactivity.^{24 25 26} Transcranial Doppler ultrasonography is a frequently used noninvasive method.^{27 28} Changes in the MFV in the MCA are very well correlated with changes in CBF during changes in PaCO₂,²⁹ and the PI is a reliable indicator of cerebrovascular resistance during hypercapnic challenge.³⁰ To detect hypoperfusion we measured SjbO₂ and the arterial-jugular lactate difference.

Heretofore, the cerebrovascular CO₂ reactivity had not been studied in comatose patients resuscitated from a cardiac arrest. The increase in MFV and decrease in PI during hypercapnia, accompanied by an increase in SjbO₂, indicate that the cerebrovascular CO₂ reactivity is preserved in comatose patients within 24 hours after cardiac arrest. The MFV and PI did not change during hyperventilation. However, the decrease in SjbO₂ and increase in arterial-jugular lactate difference suggest that the slight but significant decrease in PaCO₂ did alter CBF. An explanation for this discrepancy could be that cerebral vessels may constrict early after hyperventilation and dilate later on because of local ischemia and lactate accumulation. We measured MFV and PI only after 20 minutes and may have missed an early transitory drop in MFV. Regression analysis showed that the changes in MFV and SjbO₂ were not correlated with the change in mean arterial pressure. Obviously the changes in MFV and SjbO₂ were the result of the local effect of a change in PaCO₂. Furthermore, the fact that the change in SjbO₂ per kPa change in PaCO₂ was strikingly similar for hypo- and hyperventilation supports our hypothesis that cerebrovascular reactivity is preserved after cardiac arrest.

We found a decrease in SjbO₂ below the potential ischemic threshold of 55% in 4 of 10 patients. Furthermore, we observed a significant increase in arterial-jugular lactate difference, suggesting cerebral ischemia. Ebmeyer et al³¹ showed in a pilot study in dogs that the very low sagittal sinus PO₂ during hypocapnia could be normalized by normocapnia. Therefore, Safar et al³² used in their most recent study normoventilation instead of hyperventilation in the postresuscitation care of dogs. Data on the effect of normocapnia or hypocapnia on the neurological outcome of animals or comatose patients resuscitated from a cardiac arrest are not available.

We conclude from our data that the cerebrovascular CO₂ reactivity is preserved in comatose patients resuscitated from a cardiac arrest. Hypocapnia induced a decrease in SjbO₂ and an increase in arterial-jugular lactate difference, suggesting cerebral ischemia. Gopinath et al⁴ demonstrated in head-injured patients that the incidence of jugular venous desaturations significantly correlated with adverse neurological outcomes at 3 and 6 months. Sheinberg et al³³ found that hyperventilation was the second most frequent cause of jugular venous oxygen desaturation. Although there is no evidence that hyperventilation in comatose patients resuscitated from a cardiac arrest causes progressive neurological damage, our data indicate that hyperventilation may induce ischemia and therefore should be avoided in the postresuscitation period. Monitoring of SjbO₂ could be useful to adjust mechanical ventilation.

	Selected Abbreviations and Acronyms

 

CBF = cerebral blood flow MCA = middle cerebral artery MFV = mean flow velocity PI = pulsatility index PjbO2 = jugular bulb oxygen tension SjbO2 = jugular bulb oxygen saturation

View this table: [in this window] [in a new window]   Table 5. Arterial-Jugular Lactate Difference (mEq/L)

Received January 14, 1997; revision received May 12, 1997; accepted May 13, 1997.

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This Article Abstract Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Buunk, G. Articles by Meinders, A. E. Search for Related Content PubMed PubMed Citation Articles by Buunk, G. Articles by Meinders, A. E. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB LACTIC ACID OXYGEN