(Stroke. 1997;28:1569-1573.)
© 1997 American Heart Association, Inc.
Articles |
Cerebrovascular Reactivity in Comatose Patients Resuscitated From a Cardiac Arrest
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
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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
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Introduction |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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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.
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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
(Vsystolic–Vdiastolic)/Vmean.
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.
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Results |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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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.
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Discussion |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
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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.
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Selected Abbreviations and Acronyms |
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Received January 14, 1997; revision received May 12, 1997; accepted May 13, 1997.
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References |
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