Ann Thorac Surg 2001;72:845-849
© 2001 The Society of Thoracic Surgeons
Original article: cardiovascular
Can hypocapnia reduce cerebral embolization during cardiopulmonary bypass?
Walter Plöchl, MDa,
Claus G. Krenn, MDa,
David J. Cook, MDb,
Eva Gollob, PhDc,
Thomas Pezawas, MDa,
Heinz Schima, PhDc,
Osman Ipsiroglu, MDd,
Gregor Wollenek, MDc,
Georg Grubhofer, MDa
a Department of Cardiothoracic and Vascular Anesthesiology and Intensive Care, University of Vienna, Vienna, Austria
b Department of Anesthesiology, Mayo Clinic, Rochester, Minnesota, USA
c Department of Cardiothoracic Surgery and Ludwig-Boltzmann-Institut For Cardiosurgical Research, University of Vienna, Vienna, Austria
d Department of Pediatrics, University of Vienna, Vienna, Austria
Accepted for publication May 9, 2001.
Address reprint requests to Dr Plöchl, Department of Cardiothoracic and Vascular Anesthesiology and Intensive Care, General Hospital of Vienna, Währinger Gürtel 18-20, A-1090 Vienna, Austria
e-mail: walter.ploechl{at}univie.ac.at
 |
Abstract
|
|---|
Background. Cerebral embolization is a major cause of central nervous dysfunction after cardiopulmonary bypass. Experimental studies demonstrate that reductions in arterial carbon dioxide tension (PaCO2) can reduce cerebral embolization during cardiopulmonary bypass. This study examined the effects of brief PaCO2 manipulations on cerebral embolization in patients undergoing cardiac valve procedures.
Methods. Patients were prospectively randomized to either hypocapnia (PaCO2 = 30 to 32 mm Hg, n = 30) or normocapnia (PaCO2 = 40 to 42 mm Hg, n = 31) before aortic cross-clamp removal. With removal of the aortic cross-clamp embolic signals were recorded by transcranial Doppler ultrasonography for the next 15 minutes.
Results. Despite significant differences in PaCO2, groups did not differ statistically in total cerebral emboli counts. The mean number of embolic events was 107 ± 100 (median, 80) in the hypocapnic group and 135 ± 115 (median, 96) in the normocapnic group, respectively (p = 0.315).
Conclusions. Due to the high between-patient variability in embolization, reductions in PaCO2 did not result in a statistically significant decrease in cerebral emboli. In contrast to experimental studies, the beneficial effect of hypocapnia on cerebral embolization could not be demonstrated in humans.
|
Introduction
|
|---|
Neurologic morbidity after cardiopulmonary bypass (CPB) is of critical importance and can manifest as stroke, encephalopathy, or cognitive dysfunction [1, 2]. Transcranial Doppler (TCD) [3, 4], echocardiographic [5, 6], retinal angiographic [7], pathologic [8] and radiographic [9] information indicate that postcardiac surgical brain injury is in part a function of cerebral embolic events during CPB. During CPB, emboli may be detected in virtually all patients [7] and cerebral embolization as measured by TCD is a predictor of brain injury after cardiac operations [3, 4]. Importantly, cerebral embolization is associated with specific CPB surgical events [4–6, 10, 11]. Most embolization occurs with aortic cannulation, the onset of CPB, and after release of the aortic clamp and during the early phases of ventricular ejection [4–6, 10, 11]. It has been suggested that increases in cerebral blood flow (CBF) as with pH-stat management [12, 13] or normothermic CPB [14] may result in a higher incidence of cerebral embolization. One might also predict that simple physiologic interventions to reduce CBF during periods of embolic risk might reduce cerebral embolization. One practical intervention to reduce CBF during periods of embolic risk would be to acutely lower arterial carbon dioxide tension (PaCO2). Recently, we demonstrated in an animal model that acute manipulations of PaCO2 significantly reduced cerebral embolization during normothermic [15] and hypothermic CPB [16]. However, the clinical practicality and efficacy of this intervention remains to be tested. The aim of the present study was to determine under clinical conditions the effects of brief PaCO2 manipulations on cerebral embolization after cross-clamp release in patients undergoing CPB.
|
Material and methods
|
|---|
After institutional review board approval and written informed consent, patients undergoing aortic or mitral valve operations with/without coronary bypass grafting were enrolled in the study. Patients with preexisting neurologic dysfunction were excluded. On the day before operation patients were examined to determine whether an acceptable signal of the right middle cerebral artery could be obtained. Sixty-four patients, in whom the artery could be identified, were prospectively randomized to one of the following groups. In the hypocapnic group (n = 32), the PaCO2 was adjusted to 30 to 32 mm Hg before aortic cross-clamp removal, whereas in the normocapnic group (n = 32), the PaCO2 was maintained at 40 to 42 mm Hg. Patients were premedicated with midazolam 1 hour before operation. Anesthesia was induced intravenously with midazolam (0.1 to 0.2 mg/kg), fentanyl (5 to 10 µg/kg), and etomidate (0.2 to 0.3 mg/kg). Pancuronium (0.15 mg/kg) was used for neuromuscular blockade. After endotracheal intubation all patients were normoventilated using oxygen in air (fractional concentration of oxygen, 0.3 to 0.5). Anesthesia was maintained with boluses of fentanyl and midazolam as clinically required. Catheters were placed into one radial artery and internal jugular vein. Cardiopulmonary bypass was managed with membrane oxygenators, a 40-µm arterial line filter and nonpulsatile perfusion. Pump flow was maintained at 2.5 L · min-1 · m-2 and 
-stat blood gas management was used. Nasopharyngeal temperature was maintained between 32°C and 36°C. Phenylephrine was used to maintain a mean arterial blood pressure of 50 to 80 mm Hg. Red blood cells were infused to keep hemoglobin levels greater than or equal to 7.5 g/dL.
Approximately 15 minutes before cross-clamp removal an arterial blood gas was drawn and PaCO2 was adjusted by alterations of the fresh gas flow of the CPB circuit to reach the desired value at the time of clamp removal. In the hypocapnic group PaCO2 was decreased to 30 to 32 mm Hg and maintained at this level for 15 minutes after clamp release. In the normocapnic group PaCO2 was maintained at 40 to 42 mm Hg throughout the observation period. Nasopharyngeal temperature was targeted to be greater than or equal to 34.5°C before release of the aortic cross-clamp. The following procedures to remove air were routinely performed:
- The patient was placed in the head-down position.
- The lungs were ventilated to remove sequestered air from the pulmonary veins into the left atrium.
- With the open atrium under a pool of blood, the venous line was partially clamped and the lungs were ventilated so that the ventricle became filled with blood. The ventricle was then freed of air either by aspiration on a vent line or by apical needle aspiration while the heart was elevated and massaged.
- The atriotomy or vent insertion site was closed under a pool of blood.
- Air was evacuated from the proximal aorta either through the cardioplegia cannula or through a needle placed in the aorta.
- Transesophageal echocardiography was used in all patients to monitor the effectiveness of air removal.
With removal of the aortic cross-clamp embolic signals and CBF velocity (CBFV) were measured by transcranial Doppler ultrasonography for 15 minutes. The TCD (Multi-Dop X4, DWL Elektronische Systeme, Sipplingen, Germany) is a 2-MHz pulsed-wave transcranial Doppler probe with a 7.5-mm sample length gated at depths of 45 to 56 mm. In all patients the probe was placed over the right middle cerebral artery. Constant position of the ultrasound probe was ensured by use of a head frame probe holder. Embolic signals were recorded on-line beginning with cross-clamp release for the next 15 minutes using an automated counting system (TCD-8, version 8.20c, DWL Elektronische Systeme). Emboli counts were verified off-line by an observer blinded to study group using both audio and video methods. All patients underwent routine neurologic assessments in the intensive care unit and in the ward.
Statistical analysis
Systemic physiologic data at the time of aortic cross-clamp release, 5 minutes, and 15 minutes after clamp removal were analyzed using two-factor repeated measures analysis of variance. For these models the physiologic variable was the dependent variable, treatment group was the independent cross-classification factor, and time was the repeated factor. A two-sample t test was used to compare cerebral embolization between groups. All data are presented as the mean ± standard deviation. A p value less than 0.05 was considered significant.
|
Results
|
|---|
Of the total 64 patients enrolled in the study 3 had to be excluded. Two patients, one in each group, were excluded because of difficulties in weaning from CPB and another patient was excluded due to incomplete data acquisition. Therefore, 30 patients in the hypocapnic group and 31 in the normocapnic group were analyzed. Characteristics of these patients are presented in Table 1. Demographic and surgical data were similar between groups.
Approximately 15 minutes before cross-clamp removal the PaCO2 was 38 ± 6 mm Hg in the hypocapnic group and 39 ± 4 mm Hg in the normocapnic group. Nasopharyngeal temperatures at this time were 34.5°C ± 1.5°C and 34.9°C ± 1.7°C, respectively. Increases of the fresh gas flow of the CPB circuit decreased PaCO2 levels in the hypocapnic group and rewarming increased nasopahryngeal temperatures in both groups. As such the desired values could be reached at the time of aortic cross-clamp removal (Table 2).
Physiologic variables at the time of aortic cross-clamp release and for the next 15 minutes are shown in Table 2. With exception of the controlled variable, PaCO2, physiologic variables did not differ between groups. PaCO2 was significantly lower in the hypocapnic group than in the normocapnic group (p < 0.0001). The CBFV showed a tendency to lower levels in the hypocapnic group, but this was not statistically significant (p = 0.069). Groups did not differ in the total number of cerebral embolic signals (Fig 1). The mean embolic count was 107 ± 100 (median, 80; range, 2 to 459) in the hypocapnic group and 135 ± 115 (median, 96; range, 4 to 441) in the normocapnic group, respectively (p = 0.315). In 3 hypocapnic group patients and in 2 normocapnic group patients CPB was terminated within 15 minutes after cross-clamp release. (In these patients, like in all other patients TCD data acquisition was continued for exactly 15 minutes after cross-clamp removal.) One patient of each group showed postoperative cerebral dysfunction, manifesting as confusion and somnolence. No patient showed a focal neurologic deficit.
View larger version (15K):
[in this window]
[in a new window]
|
Fig 1. The bars represent the mean ± standard deviation of cerebral embolic signals of both groups detected by transcranial Doppler for 15 minutes after removal of the aortic cross-clamp. Although a modest reduction in PaCO2 decreased cerebral emboli by 21% in the hypocapnic group, this difference did not reach statistical significance. (ns = not significant.)
|
|
|
Comment
|
|---|
Cerebral embolization is a major cause of neurologic injury after cardiac operation. During CPB hundreds of cerebral embolic events occur and their number is associated with postoperative neurologic outcome. A variety of intraoperative interventions may reduce embolic risk. Increased surgical attention to the atherosclerotic aorta, echocardiographic assessment of air removal, and technical interventions, such as membrane oxygenators and arterial in-line filters should improve patient outcomes. Theoretically, simple physiologic interventions might also be used to reduce cerebral embolization, as has been demonstrated in experimental studies [15, 16]. In those investigations animals underwent normothermic [15] or hypothermic [16] CPB and a defined number of emboli were injected into the aortic inflow line of the CPB circuit. The embolic load consisted of 120,000 67-µm fluorescent microspheres injected within 5 minutes. At the time of embolization PaCO2 was 50 to 55 mm Hg in hypercapnic animals and 25 to 30 mm Hg in hypocapnic animals. Under normothermic [15] as well as hypothermic [16] conditions, reductions in PaCO2 at the time of embolization significantly decreased the number of emboli detected in the brain. This clinical report differs from those laboratory investigations because the 21% reduction in TCD-detected embolization with mild hypocapnia did not reach statistical significance. There are technical and physiologic reasons for the differences in results.
Technically, TCD studies demonstrate a huge variability in the number of embolic signals detected during bypass. Brækken and colleagues [17] reported a mean of 1,389 ± 1,264 cerebral embolic signals in patients undergoing valve replacement. The severity of aortic atheroma [5] and the technique of air removal in open heart operations [10] are important factors in determining the number of aortic emboli, and these factors can vary widely between patients. Because of the huge variability in the number of emboli entering the aorta, TCD data also shows a wide variability in cerebral emboli counts. This is in contrast to experimental studies, where a known embolic load is injected into the aorta and the effect of an intervention is readily detected.
There are also technical limitations related to TCD for emboli detection. Specificity for TCD has not been well defined and there can be important between-observer and between-instrument variability in embolic counts [18]. More important, in contrast to laboratory studies, TCD sensitivity is uncharacterized. In the laboratory technical reproducibility is mandatory and the sensitivity of the technique used in the animal studies, spectrofluorometry, is sufficient to detect as few as three 67-µm fluorescent microspheres per gram of tissue [15].
The most important physiologic difference between this study and the prior animal report is that the PaCO2 group difference in this clinical investigation (9 mm Hg) was much lower than in the animal studies (25 mm Hg). Because a change of 1 mm Hg in PaCO2 results in a change in CBF of approximately 3% [19, 20] we would predict that CBF and embolization should have been approximately 25% less in the hypocapnic group than in the normocapnic group. Our clinical result was quite close to the predicted value, with cerebral emboli counts reduced by 21% and CBFV by 15% in the mild hypocapnia group. As such, the modest differences in PaCO2 between groups might have been too small to show a difference in emboli counts given the large between-patient variability. In spite of the inability to achieve statistical significance, it can be rationally argued that mild-to-moderate hypocapnia during periods of high embolic risk remains clinically justifiable. A 9-mm Hg reduction in PaCO2 might reduce cerebral embolization in a patient from 400 to 320 (a 20% reduction), and in another from 50 to 40. Although a group composed of a pool of these patients might not show a statistical difference from a similarly pooled control group, this intervention may be of clinical value in improving outcomes.
Cerebral complications and neuropsychologic deficits after cardiac operations are related to the number of microemboli delivered during the procedure [3, 4]. Therefore, simple, cost-effective maneuvers for decreasing cerebral embolization are indicated. Ultrasonography scanning of the ascending aorta and alterations in the sites of aortic cannulation and clamping, as well as meticulous removal of air in the heart can be important tools to decrease the embolic load. Shifting of emboli away from the cerebral circulation by CBF manipulations during periods of risk is probably another tool that is simple and cost effective. However, it could be argued that increases in gas flow of the CPB circuit increases the number of gaseous emboli generated by the oxygenator [21]. Although this might be a concern with bubble oxygenators, formation of gaseous emboli are much less with membrane oxygenators [22, 23]. During periods of embolic risk increases in gas flow to achieve moderate hypocapnia and to reduce cerebral embolization are probably justified, if the number of emboli which are shifted away from the cerebral circulation will exceed those who hypothetically could be generated by the oxygenator through gas flow increases.
A variety of methodologic reasons explains why we were unable to reproduce the results of the experimental studies in humans. However, the underlying physiologic principle, decreasing PaCO2 can reduce the number of cerebral emboli, is clear and has been adequately demonstrated in experimental work. As such the absence of a positive result in this report is not an indictment of the intervention, but rather speaks to large clinical variability and the limitations of current detection techniques. We would argue that these brief periods of induced hypocapnia should be considered during high-risk periods in any patient undergoing CPB.
|
Acknowledgments
|
|---|
We thank the Cardiac Perfusion Department for assistance in the study. The study was supported in part by a research grant ("Jubiläumsfonds") from the Austrian Nationalbank, Vienna, Austria.
|
References
|
|---|
-
Shaw P.J., Bates D., Cartlidge N.E.F., Heaviside D., Julian D.G., Shaw D.A. Early neurological complications of coronary artery bypass surgery. Br Med J 1985;291:1384-1387.
-
Roach G.W., Kanchuger M., Mangano C.M., et al. Adverse cerebral outcomes after coronary bypass surgery. Multicenter Study of Perioperative Ischemia Research Group and the Ischemia Research and Education Foundation Investigators. N Engl J Med 1996;335:1857-1863.[Abstract/Free Full Text]
-
Pugsley W., Klinger L., Paschalis C., Treasure T., Harrison M., Newman S. The impact of microemboli during cardiopulmonary bypass on neuropsychological functioning. Stroke 1994;25:1393-1399.[Abstract]
-
Clark R.E., Brillman J., Davis D.A., Lovell M.R., Price T.R.P., Magovern G.J. Microemboli during coronary artery bypass grafting. Genesis and effect on outcome. J Thorac Cardiovasc Surg 1995;109:249-258.[Abstract/Free Full Text]
-
Barbut D., Yao F.S., Hager D.N., Kavanaugh P., Trifiletti R.R., Gold J.P. Comparison of transcranial Doppler ultrasonography and transesophageal echocardiography to monitor emboli during coronary artery bypass surgery. Stroke 1996;27:87-90.[Abstract/Free Full Text]
-
Barbut D., Yao F.S.F., Lo Y.W., et al. Determination of size of aortic emboli and embolic load during coronary artery bypass grafting. Ann Thorac Surg 1997;63:1262-1267.[Abstract/Free Full Text]
-
Blauth C.I., Arnold J.V., Schulenberg W.E., McCartney A.C., Taylor K.M., Loop F.D. Cerebral microembolism during cardiopulmonary bypass. Retinal microvascular studies in vivo with fluorescein angiography. J Thorac Cardiovasc Surg 1988;95:668-676.[Abstract]
-
Brown W.R., Moody D.M., Challa V.R., Stump D.A., Hammon J.W. Longer duration of cardiopulmonary bypass is associated with greater numbers of cerebral microemboli. Stroke 2000;31:707-713.[Abstract/Free Full Text]
-
Steinberg G.K., De La Paz R., Mitchell R.S., Bell T.E., Albers G.W. MR and cerebrospinal fluid enzymes as sensitive indicators of subclinical cerebral injury after open-heart valve replacement surgery. Am J Neuroradiol 1996;17:205-212.[Abstract]
-
Van der Linden J., Casimir-Ahn H. When do cerebral emboli appear during open heart operations? A transcranial Doppler study. Ann Thorac Surg 1991;51:237-241.[Abstract]
-
O’Brien J.J., Butterworth J., Hammon J.W., Morris K.J., Phipps J.M., Stump D.A. Cerebral emboli during cardiac surgery in children. Anesthesiology 1997;87:1063-1069.[Medline]
-
Patel R.L., Turtle M.R., Chambers D.J., James D.N., Newman S., Venn G.E. Alpha-stat acid-base regulation during cardiopulmonary bypass improves neuropsychologic outcome in patients undergoing coronary artery bypass grafting. J Thorac Cardiovasc Surg 1996;111:1267-1279.[Abstract/Free Full Text]
-
Venn G.E., Patel R.H., Chambers D.J. Cardiopulmonary bypass: perioperative cerebral blood flow and postoperative cognitive deficit. Ann Thorac Surg 1995;59:1331-1335.[Abstract/Free Full Text]
-
Craver J.M., Bufkin B.L., Weintraub W.S., Guyton R.A. Neurologic events after coronary bypass grafting: further observations with warm cardioplegia. Ann Thorac Surg 1995;59:1429-1434.[Abstract/Free Full Text]
-
Plöchl W., Cook D.J. Quantification and distribution of cerebral emboli during cardipulmonary bypass in the swine: the impact of PaCO2. Anesthesiology 1999;90:183-190.[Medline]
-
Cook D.J., Plöchl W., Orszulak T.A. Effect of temperature and PaCO2 on cerebral embolization during cardiopulmonary bypass in swine. Ann Thorac Surg 2000;69:415-420.[Abstract/Free Full Text]
-
Brækken S.K., Russell D., Brucher R., Abdelnoor M., Svennevig J.L. Cerebral microembolic signals during cardiopulmonary bypass surgery. Frequency, time of occurrence, and association with patient and surgical characteristics. Stroke 1997;28:1988-1992.[Abstract/Free Full Text]
-
Markus H.S., Molloy J. Use of a decibel threshold in detecting Doppler embolic signals. Stroke 1997;28:692-695.[Abstract/Free Full Text]
-
Johnsson P., Messeter K., Ryding E., Kugelberg J., St
hl E. Cerebral vasoreactivity to carbon dioxide during cardiopulmonary perfusion at normothermia and hypothermia. Ann Thorac Surg 1989;48:769-775.[Abstract]
-
Reivich M. Arterial PCO2 and cerebral hemodynamics. Am J Physiol 1964;206:25-35.[Abstract/Free Full Text]
-
Padayachee T.S., Parsons S., Theobold R., Gosling R.G., Deverall P.B. The effect of arterial filtration on reduction of gaseous microemboli in the middle cerebral artery during cardiopulmonary bypass. Ann Thorac Surg 1988;45:647-649.[Abstract]
-
Padayachee T.S., Parsons S., Theobold R., Linley J., Gosling R.G., Deverall P.B. The detection of microemboli in the middle cerebral artery during cardiopulmonary bypass: a transcranial Doppler ultrasound investigation using membrane and bubble oxygenators. Ann Thorac Surg 1987;44:298-302.[Abstract]
-
Blauth C.I., Smith P.L., Arnold J.V., Jagoe J.R., Wootton R., Taylor K.M. Influence of oxygenator type on the prevalence and extent of microembolic retinal ischemia during cardiopulmonary bypass. Assessment by digital image analysis. J Thorac Cardiovasc Surg 1990;99:61-69.[Abstract]
Related Article
-
Invited commentary
- Christopher I. Blauth
Ann. Thorac. Surg. 2001 72: 849.
[Extract]
[Full Text]
[PDF]
This article has been cited by other articles:
|
|
|
|
 
M. Kurusz and B. D Butler
Bubbles and bypass: an update
Perfusion,
January 1, 2004;
19(1_suppl):
S49 - S55.
[Abstract]
[PDF]
|
|
|
|
|
|
|
M. Dworschak, M. Czerny, M. Grimm, G. Grubhofer, and W. Plochl
The impact of asymptomatic carotid artery disease on the intraoperative course of coronary artery bypass surgery
Perfusion,
January 1, 2003;
18(1):
15 - 18.
[Abstract]
[PDF]
|
|
|
|
|
|
|
D C Whitaker, J Stygall, and S P Newman
Neuroprotection during cardiac surgery: strategies to reduce cognitive decline
Perfusion,
March 1, 2002;
17(2_suppl):
69 - 75.
[Abstract]
[PDF]
|
|
|
Top
Abstract
Introduction
