Anesth Analg 1999;88:357
© 1999 International Anesthesia Research Society
OBSTETRIC ANESTHESIA
Changes in Maternal Middle Cerebral Artery Blood Flow Velocity Associated with General Anesthesia in Severe Preeclampsia
Jaya Ramanathan, MD*,
,
John J. Angel, MD*,
Andrew J. Bush, PhD
,
Phyllis Lawson, RN, CCRC*, and
Baha Sibai, MD
Departments of
*Anesthesiology,
Obstetrics and Gynecology, and
Preventive Medicine, University of Tennessee College of Medicine, Memphis, Tennessee
Address correspondence and reprint requests to Jaya Ramanathan, MD, Department of Anesthesiology, University of Tennessee, Memphis 800 Madison Ave., Memphis, TN 38163.
 |
Abstract
|
|---|
In women with severe preeclampsia, significant increases in mean arterial pressures (MAP) are common after rapid induction of general anesthesia (GA) and tracheal intubation. The objectives of this prospective study were to assess the effects of the rapid induction-intubation technique on middle cerebral artery (MCA) flow velocity in severe preeclampsia and to examine the correlation between mean MCA flow velocity (Vm) and MAP. Eight women with severe preeclampsia (study group) and six normotensive women at term (control group) scheduled to undergo cesarean section under GA were studied. Before induction, patients in the study group received IV labetalol in divided doses to lower diastolic pressures to <100 mm Hg. Anesthesia was induced with pentothal 4–5 mg/kg, followed by succinylcholine 1.5 mg/kg to facilitate tracheal intubation. A transcranial Doppler was used to measure Vm. Both Vm and MAP were recorded before induction and every minute for 6 min after intubation. In the study group, after the administration of labetalol, MAP decreased from 129 ± 9 to 113 ± 9 mm Hg (P < 0.05), and Vm decreased from 59 ± 11 to 54 ± 10 cm/s (P < 0.05). After intubation, MAP increased from 113 ± 9 to 134 ± 5 mm Hg (P < 0.001), and Vm increased from 54 ± 10 to 70 ± 10 cm/s (P < 0.001). In the control group, while MAP increased significantly from 89 ± 6 to 96 ± 4 mm Hg (P < 0.05) after intubation, the concurrent increase in Vm from 49 ± 5 to 54 ± 7 cm/s was not significant. There was a significant positive pooled correlation between Vm and MAP (r = 0.5, P < 0.0006) in the study group but not in the control group (r = 0.24). After induction and intubation, both Vm and MAP values were significantly increased in the study group patients at all observation points compared with the control group patients. The findings indicate that Vm increases significantly after rapid-sequence induction of GA and tracheal intubation in women with severe preeclampsia, and there seems to be a direct relationship between MAP and Vm.
Implications: In women with severe preeclampsia, rapid-sequence induction of general anesthesia and tracheal intubation can cause severe hypertension. Our results indicate that the increase in blood pressure is associated with a significant increase in maternal cerebral blood flow velocity and that there is a significant correlation between these two variables.
|
Introduction
|
|---|
In women with severe preeclampsia, significant increases in blood pressure are common after rapid-sequence induction of general anesthesia (GA) and tracheal intubation (1,2). The abrupt increase in mean arterial pressure (MAP), although transient, can be quite dramatic and may lead to cerebral edema and hemorrhage (1,3). Women with severe preeclampsia exhibit neurologic symptoms and signs such as headache, visual disturbances, and hyperreflexia, presumably because of pathophysiologic changes affecting cerebral circulation. Although earlier studies found diffuse cerebral vasospasm and ischemia in severe preeclampsia and eclampsia (4,5), recent studies showed a forced overdistension of the small intracranial arteries and vasogenic edema probably caused by impaired cerebral autoregulation (6,7).
To our knowledge, the changes in cerebral blood flow associated with rapid induction of GA and tracheal intubation in patients with severe preeclampsia has not been previously described. Transcranial Doppler (TCD) is a noninvasive technique for measuring the blood flow velocity in basal intracranial arteries, including the middle cerebral artery (MCA). TCD studies in patients with severe preeclampsia have shown that the mean MCA flow velocity (Vm) is increased in the peripartum period (8,9). Based on available information, we hypothesized that maternal Vm would increase significantly with the rapid induction-intubation technique. The objectives of our prospective study were to measure maternal Vm during rapid induction of GA and tracheal intubation in severely preeclamptic women undergoing cesarean sections; to examine the correlations between Vm and MAP; and to compare the findings with a control group of normotensive women undergoing cesarean sections under GA.
|
Methods
|
|---|
After obtaining institutional approval and written informed consent, eight women with severe preeclampsia (study group) and six normotensive women at term (control group) scheduled to undergo cesarean sections under GA were enrolled in this prospective study. Severe preeclampsia was defined as systolic blood pressure 
160 mm Hg or diastolic blood pressure 110 mm Hg and proteinuria 5g in 24 h (3+ or 4+ on dipstick). Women in labor; those with hemolysis, elevated liver enzymes, and low platelet count (HELLP) syndrome; eclampsia; coagulation abnormalities; major organ diseases; or morbid obesity and those with a history of drug abuse and cigarette smoking were excluded from the study. All patients with Mallampati class 3, short thick neck, receding jaw, and other evidence of anticipated difficult airway were also excluded. Patients in the study group received 6 g of magnesium sulfate IV over 20 min followed by 2 g/h as infusion for seizure prophylaxis. Preoperative blood samples were drawn for serum magnesium levels from all patients in the study group.
The right MCA flow velocity was monitored using a 2-MHz pulsed range-gated Doppler ultrasound probe (TC 2000; EME, Uberlingen, Germany). A transtemporal approach was used (9,10) The right MCA was insonated by placing the probe at the right temporal window above the zygomatic arch. The depth of insonation was initially increased to identify the bidirectional flow patterns at the bifurcation of the internal carotid artery into the MCA and anterior communicating artery. Thereafter, the depth of insonation was slowly decreased to obtain the signals from the proximal segment of MCA with the flow toward the probe. The ultrasound probe was positioned where the MCA waveforms were best identified (45–52 mm) by using a Muller-Moll probe holder and head strap (Nicolet Biomedical, EME, Uberlingen, Germany).
Preoperative medications consisted of a clear oral antacid. In the operating room, patients were positioned supine with left uterine displacement. Automatic blood pressure cuff, pulse oximetry, electrocardiogram leads, and skin thermistor probe were applied. End-tidal CO2 was monitored via a face mask during preoxygenation and via the tracheal tube at the Y-piece of the anesthetic circuit after intubation. Before induction, all women with preeclampsia received labetalol in 5- to 10-mg bolus doses IV to a total dose of 1 mg/kg to lower the diastolic arterial pressures to <100 mm Hg. After preoxygenation, anesthesia was rapidly induced with pentothal 4–5 mg/kg IV, followed immediately by 1.5 mg/kg succinylcholine to facilitate tracheal intubation. A size 3 Macintosh laryngoscope was used for direct laryngoscopy, and the trachea was intubated under direct vision with a 7-mm inner diameter endotracheal tube. Anesthesia was maintained with 50% N2O in O2 and isoflurane 0.5% inspired concentration with a fresh gas flow of 6 L/min.
All variables were measured before induction, after the administration of labetalol in the preeclamptic group, and at 1-min intervals for 6 min after tracheal intubation. The following variables were recorded: mean MCA flow velocity (Vm), systolic (Vs), and diastolic (Vd) flow velocities and pulsatility index (PI), which is calculated as PI = (Vs - Vd)/Vm. Systolic and diastolic blood pressures, MAP, heart rate, end-tidal CO2, oxygen saturation, and skin temperature were also recorded.
Data are expressed as mean ± SD. The differences in demographics and baseline values were examined by using independent t-tests. To determine within-group and between-group differences, a mixed design analysis of variance was used. Significant interaction effects were further analyzed by single degree of freedom contrasts testing group differences in change from baseline. Probability values for these contrasts were Bonferroni-adjusted to suppress inflation of the overall decision error rate. The within-group pooled correlations of MAP with Vm were estimated separately for the study and control groups using Snedecor and Cochran's method for simultaneously pooling data over time and over subjects and were tested for significance (11). Regression analysis of the percent changes in Vm and MAP from before induction to 1 min postintubation for the study and control groups, group slopes, and differences in slopes was performed and tested for significance by using traditional F-tests. P < 0.05 was regarded as significant.
|
Results
|
|---|
Patient characteristics are given in Table 1. No significant differences were noted, other than lower gestational age among women with severe preeclampsia. Tracheal intubations were easily accomplished in all patients in both groups, and no patient required multiple attempts at laryngoscopy or intubation. End-tidal CO2 concentrations before induction and 1 min postintubation in the study group (32 ± 1 vs 34 ± 1 mm Hg) and in the control group (31 ± 1 vs 34 ± 1 mm Hg) showed no significant differences. Oxygen saturation values remained 98%–100% before and after intubation. Plasma magnesium concentrations in the study group were 5.2 ± 0. 6 mg/dL (range 4.7–6.2 mg/dL), which is within therapeutic range.
In the study group, MAP decreased from 129 ± 9 to 113 ± 9 mm Hg after the administration of labetalol (P < 0.05) (Fig. 1). After intubation, MAP increased from 113 ± 9 mm Hg, reaching a peak values of 134 ± 5 mm Hg (P < 0.001) 1 min after intubation, followed by a gradual decrease within the next 5–6 min (Fig. 1). Similarly, the control group showed an increase in MAP from 89 ± 6 to 96 ± 4 mm Hg (P < 0.05) after intubation, followed by a gradual decrease (Fig. 1). MAP values in the study group were significantly higher at all observation points compared with those in the control group (P < 0.05) (Fig. 1). In the study group, heart rate (HR) decreased from 114 ± 10 to 95 ± 8 bpm with the administration of labetalol (P < 0.05). After intubation, HR increased, reaching a maximum of 106 ± 10 bpm (P < 0.05). In the control group, HR increased from 84 ± 8 to 98 ± 9 bpm (P < 0.05) after intubation, followed by a gradual decrease.
View larger version (16K):
[in this window]
[in a new window]
|
Figure 1. Mean arterial pressure (MAP) in the study (preeclampsia) and control groups at baseline (Base); after the administration of labetalol and before induction in the study group (Labet); before induction in the control group (Preind); and 1–6 min after tracheal intubation. *Significantly different between groups (P < 0.05). Significantly different from baseline values (P < 0.05).
|
|
In the study group, there was a modest decrease in Vm after the administration of labetalol, from 59 ± 11 to 54 ± 10 cm/s (P < 0.05) (Fig. 2). One minute after intubation, Vm increased significantly above both the baseline and postlabetalol values, reaching a maximum of 70 ± 10 cm/s (P < 0.001) (Fig. 2). In the control group, the increase in Vm after intubation from 49 ± 5 to 53 ± 7 cm/s was not significant. After intubation, Vm remained significantly increased in the study group throughout the observation period (P < 0.05) (Fig. 2). The PI did not change after intubation in either group. In the study group, the PI values before and after intubation were 0.55 ± 0.1 and 0.63 ± 0.1, respectively. In the control group, the corresponding values were 0.53 ± 0.1 and 0.56 ± 0.1.
View larger version (16K):
[in this window]
[in a new window]
|
Figure 2. Mean middle cerebral artery flow velocity (Vm) in the study (preeclampsia) and control groups at baseline (Base); after the administration of labetalol and before induction in the study group (Labet); before induction in the control group (Preind); and 1–6 min after tracheal intubation. *Significantly different between groups (P < 0.05). Significantly different from baseline values (P < 0.05).
|
|
In the study group, there was a significant positive pooled within-group correlation between Vm and MAP (r = 0.5, P < 0.0006), whereas the correlation (r = 0.2) was not significant in the control group. Regression analysis of the percent changes in Vm and MAP from before induction to 1 min postintubation showed r2 = 0.74, P = 0.0006 (Fig. 3). The study group slope (1.37) was significant (P < 0.0007), but the control group slope (-0.53) was not significant.
View larger version (10K):
[in this window]
[in a new window]
|
Figure 3. Regression analysis of the percent change in flow velocity (Vm) and mean arterial pressure (MAP) from before induction to 1 min postintubation in both groups. The regression line and r2 value (P = 0.0006) are shown.
|
|
|
Discussion
|
|---|
Over the last several years, the topic of exaggerated sympathoadrenal reflex responses associated the rapid induction of GA and tracheal intubation in women with preeclampsia and the possible deleterious effects on maternal cerebral circulation has received some attention (1–3,12,13). In this study, our hypothesis proved to be correct, and we were able to demonstrate, for the first time, a significant increase in Vm associated with the rapid induction-intubation technique in women with severe preeclampsia. Furthermore, there was a significant positive correlation between MAP and Vm throughout the study period.
The magnitude and nature of changes in cerebral blood flow in women with severe preeclampsia are still under investigation. The use of TCD has gained popularity in obstetrics because it is noninvasive, reproducible, and easy to perform at bedside. However, the TCD technique has its limitations because it does not measure the actual blood flow. Vm increases with vasospasm of MCA or from reflex vasoconstriction of the distal resistance vessels, the precapillary arterioles. Vm also increases with increased blood flow. Several investigators have attempted to clarify this issue. Although some authors (14) showed poor correlation between flow velocity measured by TCD and regional cerebral blood flow, others (15,16) found excellent correlations between the two variables under various pathophysiologic conditions and pharmacologic challenges. In general, the large basal intracerebral vessels, such as the MCA, are considered conductance vessels, and acute changes in flow veloicty are thought to be reflective of changes in blood flow (10).
In previous TCD studies in women with preeclampsia and eclampsia, Vm increased significantly in the peripartum period (8,9). Additionally, Zunker et al. (17) found significant positive correlations between Vm and MAP in women with preeclampsia during pregnancy, a finding similar to our study. Such correlations were also present in another study involving the infusion of angiotensin II to experimentally increase blood pressures in a group of normotensive pregnant women (18). There was a significant increase in blood pressure in all of their subjects, with a simultaneous increase in MCA Vm (18).
Cerebral blood flow velocity can be influenced by factors other than the changes in MAP. All the women in our study group received magnesium sulfate for prophylaxis against seizures. The plasma magnesium concentrations were in the therapeutic range. In addition, all patients in the study group received labetalol to lower MAP before induction. Our intent was to collect data from patients with preeclampsia normally encountered in our daily practice who received the standard treatment for severe preeclampsia and a standard anesthetic technique for cesarean delivery.
The effects of magnesium on cerebral blood flow velocity are well documented. Belfort et al. (19) showed that magnesium sulfate causes vasodilation of the smaller-diameter vessels distal to the MCA. Other studies concur with these findings (20). The PI decreased significantly in these studies (19,20). PI partially reflects cerebral vascular resistance mediated by precapillary arterioles distal to the MCA. Baseline PI values in our study group were comparable to the values previously reported in patients receiving magnesium sulfate (19,20). We speculate that the absence of changes in PI after intubation in our patients may be due to lack of changes in the caliber of the MCA or distal vessels perfused by the MCA. The modest reduction in Vm after the administration of labetalol was probably secondary to a direct vasodilatory effect on intracranial arteries. Thus, magnesium prophylaxis, together with labetalol given just before induction, could have modified the increase in both Vm and MAP in our patients with preeclampsia.
Vm is also exquisitely sensitive to CO2 concentrations. In this study, the end-tidal CO2 levels after tracheal intubation were not significantly higher than those at baseline; therefore, they could have had only minimal effects, if any, on our results. Other investigators have reported similar findings (21,22). Other factors such as oxygen saturation did not change appreciably during the study period.
All induction and inhaled drugs can affect Vm. Pentothal in doses of 5 mg/kg decreases Vm 1 min after injection, but before tracheal intubation, in nonpregnant subjects (21,22). We could not detect this effect in our patients because of the rapid induction-intubation technique in our study, as opposed to the routine induction used in other studies. Nevertheless, it is reasonable to assume that pentothal did affect the Vm in our patients. Although isoflurane in low concentrations (<1% in this study) has virtually no effect on Vm, the addition of nitrous oxide causes an increase (23,24). Thus, we cannot exclude the effects of nitrous oxide on Vm changes our study.
The exact mechanism of the significant increase in Vm in our patients with severe preeclampsia is unclear. The increase in Vm in our study may be the result of a complex interaction of several simultaneously occurring factors, such as the exaggerated hypertensive response, the effects of anesthetics on cerebral blood flow, the enhanced vascular reactivity of preeclampsia (25), and the increase in catecholamine concentrations in response to tracheal intubation (2). The lack of a significant increase in Vm and the correlation between Vm and MAP in the control group were probably due to the lack of severe hemodynamic fluctuations in this group.
The clinical relevance of the transient but significant increases in Vm in our study group, in terms of adverse consequences such as cerebral edema, is unclear. Some authors speculate that the increase in Vm associated with tracheal intubation reflects a transient state of increased cerebral blood flow because the cerebral autoregulatory mechanisms are not instantaneously initiated in response to acute hypertension (22,26). The same mechanism may have been partly responsible for the increase in Vm in our patients. Although abundant evidence suggests diffuse vasoconstriction of cerebral vasculature in severe preeclampsia (4,5,8,9), an alternate mechanism of neurologic changes in these patients may be impaired autoregulation with forced overdistension of intracranial arteries and cerebral edema (6,7). Regardless of the nature of the pathophysiologic changes in cerebral vasculature, any additional insult resulting from acute variations in cerebral blood flow may be deleterious in patients with severe preeclampsia.
It is not known whether further lowering of MAP with larger doses of labetalol or other antihypertensives would minimize the increase in Vm in patients with severe preeclampsia. Deepening the level of anesthesia before tracheal intubation with narcotics (e.g., fentanyl), larger doses of pentothal, or other drugs, such as propofol, may modify the increase in MAP and, possibly, Vm. Additional studies are required in this area. It is tempting to speculate that, with regional anesthesia, the increase in Vm may be minimized or completely avoided. The changes in cerebral hemodynamics associated with regional anesthesia have yet to be defined.
In conclusion, our results indicate that maternal Vm increases significantly after rapid-sequence induction of GA and tracheal intubation in women with severe preeclampsia. In our study, there was also a significant positive correlation between the maternal Vm and the changes in maternal MAP in response to tracheal intubation.
|
Footnotes
|
|---|
Presented in part at the annual meeting of American Society of Anesthesiology, San Diego, CA, October 1997.
|
References
|
|---|
-
Gutsche BB, Cheek TG. Anesthetic considerations in preeclampsia-eclampsia. In: Shnider SM, Levinson G, eds. Anesthesia for obstetrics. Baltimore:Williams & Wilkins, 1993:305–36.
-
Ramanathan J, Coleman P, Sibai BM. Anesthetic modifications of hemodynamic and neuroendocrine stress responses to cesarean delivery in women with severe preeclampsia. Anesth Analg 1991;73:772–9.[Abstract/Free Full Text]
-
Hawkins JL. Anesthesia and preeclampsia/eclampsia. In: Norris MC, ed. Obstetric anesthesia. Philadelphia:JB Lippincott, 1993:501–27.
-
Digre KB, Varner MW, Osborn AG, Crawford S. Cranial magnetic resonance imaging in severe preeclampsia vs. eclampsia. Arch Neurol 1993;50:399–406.[Abstract/Free Full Text]
-
Lewis LK, Hinshaw DB, Will AD, et al. CT and angiographic correlation of severe neurological disease in toxemia of pregnancy. Neuroradiology 1988;30:59–64.[Web of Science][Medline]
-
Viegen JH, Muskens E, Keunen RW, et al. Abnormal cerebral hemodynamics in pregnancy-related hypertensive encephalopathy. Eur J Obstet Gynecol Reprod Biol 1993;49:198–200.[Web of Science][Medline]
-
Morriss CM, Twickler DM, Hatab MR, et al. Cerebral blood flow and cranial magnetic resonance imaging in eclampsia and severe preeclampsia. Obstet Gynecol 1997;89:561–8.[Web of Science][Medline]
-
Williams KP, McLean C. Peripartum changes in maternal cerebral blood flow velocity in normotensive and preeclamptic patients. Obstet Gynecol 1993;82:334–7.[Web of Science][Medline]
-
Hansen WF, Burnham SJ, Svendsen TO, et al. Transcranial doppler findings of cerebral vasospasm in preeclampsia. J Matern Fetal Med 1996;5:194–200.[Medline]
-
Trindell MR, Dodson BA, Rampill IJ. Effects of fentanyl versus sufentanil in equianesthetic doses on middle cerebral artery blood flow velocity. Anesthesiology 1993;78:454–60.[Web of Science][Medline]
-
Snedecor GW, Cochran WG. Statistical methods. 6th ed.Ames, IA:The Iowa University Press, 1967:186–8.
-
Ramanathan J, Sibai BM, Mabie WC, et al. The use of labetalol for attenuation of the hypertensive response to endotracheal intubation in preeclampsia. Am J Obstet Gynecol 1988;159:650–4.[Web of Science][Medline]
-
Hood DD, Dewan DM, James FM III, et al. The use of nitroglycerin in preventing the hypertensive response to tracheal intubation in severe preeclampsia. Anesthesiology 1985;63:329–32.[Web of Science][Medline]
-
Bishop CCR, Powell S, Rutt D, Browse NL. Transcranial Doppler measurement of middle cerebral artery blood flow velocity: a validation study. Stroke 1986;17:913–5.[Abstract/Free Full Text]
-
Dahl A, Lindgaard KF, Russell D, et al. A comparison of transcranial Doppler and cerebral blood flow studies to assess cerebral vasoreactivity. Stroke 1992;23:15–9.[Abstract/Free Full Text]
-
Jansen C, Vriens EM, Eikelboom BC, et al. Carotid endarterectomy with transcranial Doppler and electroencephalographic monitoring. Stroke 1993;24:1025–32.[Abstract/Free Full Text]
-
Zunker P, Ley-Pozo J, Louwen F, et al. Cerebral hemodynamics in preeclampsia/eclampsia syndrome. Obstet Gynecol 1995;6:411–5.
-
Kyle PM, Swiet M, Buckley D, et al. Non-invasive assessment of the maternal cerebral circulation by transcranial doppler ultrasound during angiotensin II infusion. Br J Obstet Gynaecol 1993;100:85–91.[Web of Science][Medline]
-
Belfort MA, Moise KJ. Effect of magnesium sulfate on maternal brain blood flow in preeclampsia: a randomized placebo-controlled study. Am J Obstet Gynecol 1992;167:661–6.[Web of Science][Medline]
-
Naidu S, Payne AJ, Moodely J, et al. Randomized study assessing the effect of phenytoin and magnesium sulfate on maternal cerebral circulation in eclampsia using transcranial Doppler ultrasound. Obstet Gynaecol 1996;103:111–6.
-
Dong ML, Kofke A, Policare S, et al. Transcranial doppler ultrasonography in neurosurgery: effects of intracranial tumor on right middle cerebral artery flow velocity during induction of anesthesia. Ultrasound Med Biol 1996;22:1163–8.[Web of Science][Medline]
-
Thiel A, Zickmann B, Roth H, Hempelmann G. Effects of intravenous anesthetic agents on middle cerebral artery blood flow velocity during induction of general anesthesia. J Clin Monit 1995;11:92–8.[Web of Science][Medline]
-
Thiel A, Zickmann B, Zimmerman R, Hempelmann G. Transcranial doppler sonography: effects of halothane, enflurane and isoflurane on blood flow velocity in the middle cerebral artery. Br J Anaesth 1992;68:388–93.[Abstract/Free Full Text]
-
Strebel S, Kaufmann M, Anselmi L, Schaefer HG. Nitrous oxide is a potent cerebrovasodilator in humans when added to isoflurane: a transcranial doppler study. Acta Anaesthesiol Scand 1995;39:653–8.[Web of Science][Medline]
-
Royburt M, Seidman DS, Serr DM, Mashiach S. Neurologic involvement in hypertensive disease of pregnancy. Gynecol Surg 1991;46:656–64.
-
Moorthy SS, Greenspan CD, Dierdorf SF, Hillier SC. Increased cerebral and decreased femoral artery blood flow velocities during direct laryngoscopy and tracheal intubation. Anesth Analg 1994;78:1144–8.[Abstract/Free Full Text]
Accepted for publication November 10, 1998.
This article has been cited by other articles:
|
|
|
|
 
R. W. Sherman, R. A. Bowie, M. M. E. Henfrey, R. P. Mahajan, and D. Bogod
Cerebral haemodynamics in pregnancy and pre-eclampsia as assessed by transcranial Doppler ultrasonography
Br. J. Anaesth.,
November 1, 2002;
89(5):
687 - 692.
[Abstract]
[Full Text]
[PDF]
|
|
|
Top
Abstract
Introduction
