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Patients with Severe Preeclampsia Experience Less Hypotension During Spinal Anesthesia for Elective Cesarean Delivery than Healthy Parturients: A Prospective Cohort Comparison

Section Editor(s): Birnbach, David J. Section EditorAya, Antoine G. M. MD, PhD; Mangin, Roseline MD, MSc; Vialles, Nathalie MD; Ferrer, Jean-Michel MD; Robert, Colette MD; Ripart, Jacques MD, PhD; de La Coussaye, Jean-Emmanuel MD, PhD

doi: 10.1213/01.ANE.0000073610.23885.F2

In this prospective cohort study, we compared the incidence and severity of spinal anesthesia (SA)-associated hypotension in severely preeclamptic (n = 30) versus healthy (n = 30) parturients undergoing cesarean delivery. After the administration of IV fluids, SA was performed with hyperbaric 0.5% bupivacaine, sufentanil, and morphine. Blood pressure (BP) was recorded before and at 2-min intervals for 30 min after SA. Clinically significant hypotension was defined as the need for ephedrine (systolic BP decrease to <100 mm Hg in healthy parturients or 30% decrease in mean BP in both groups). Despite receiving a smaller fluid volume (1653 ± 331 mL versus 1895 ± 150 mL; P = 0.005) and a larger bupivacaine dose (10.5 ± 0.9 mg versus 10.0 ± 0.7 mg; P = 0.019), the severely preeclamptic patients had a less frequent incidence of clinically significant hypotension (16.6% versus 53.3%; P = 0.006), which was less severe and required less ephedrine. The risk of hypotension was almost six times less in severely preeclamptic patients (odds ratio, 0.17; 95% confidence interval, 0.05–0.58; P = 0.006) than that in healthy patients.

IMPLICATIONS: This prospective cohort study shows that the incidence and severity of hypotension are less in severely preeclamptic patients, as compared with healthy parturients, undergoing spinal anesthesia for cesarean delivery. However, larger studies are required to meaningfully document the safety of spinal anesthesia in this setting.

Division of Anesthesiology, Pain Management, Emergency and Critical Care Medicine, University Hospital, Nîmes, France

Accepted for April 3, 2003.

Address correspondence to Antoine G. M. Aya, MD, PhD, Fédération Anesthésie-Douleur-Urgences-Réanimation, CHU Gaston Doumergue, 5 rue Hoche, 30029 Nîmes Cedex 04, France. Address e-mail to Reprints will not be available from the author.

Many severely preeclamptic patients require cesarean delivery. Because of hazards related to management of the difficult airway and to the hemodynamic consequences of laryngoscopy and tracheal intubation (1,2), general anesthesia is usually chosen only when regional techniques are contraindicated. Epidural anesthesia is used in patients with severe preeclampsia. Although spinal anesthesia may be avoided in these patients because of the risk of severe hypotension, several studies have shown that the hemodynamic effects of spinal and epidural anesthesia are similar (3–5). This is especially true when a small-dose spinal anesthetic is used as part of a combined spinal-epidural technique (6). The aim of this study was to compare the hemodynamic effects of spinal anesthesia in patients with severe preeclampsia, as compared with healthy parturients, undergoing cesarean delivery.

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After institutional ethics committee approval and informed consent, consecutive severely preeclamptic patients cared for in our unit from May 2001 to July 2002 were enrolled in the case cohort. Severe preeclampsia was defined, according to the criteria of Davey and MacGillivray (7), as systolic blood pressure (SBP) ≥160 mm Hg, diastolic blood pressure (DBP) ≥110 mm Hg, or both. The pharmacologic treatment of hypertension before inclusion in the protocol was recommended when mean blood pressure (BP) was >130 mm Hg, with symptoms of end-organ involvement. To allow optimal management of hypertension, the antihypertensive drug was not standardized and was left to the choice of the treating anesthesiologist. However, regardless of the drug used, the goal of acute treatment was to reduce the mean BP by 20%. IV MgSO4 (4.5-g initial loading dose over 20–30 min followed by a 1–2 g/h continuous maintenance infusion) was given as seizure prophylaxis in patients with neuromuscular hyperexcitability. After each case enrollment, the next normotensive patient scheduled for cesarean delivery under spinal anesthesia was selected as a control. Patients in labor; those with chronic hypertension, multiple gestation, diabetes, or coagulopathy; or those given β-tocolytic drugs were not included in the study.

All patients were given an IV infusion of 1500 to 2000 mL of lactated Ringer’s solution over 20 min before the anesthetic. The volume of fluids administered to severely preeclamptic patients was not decreased, because we expected that the intravascular volume contraction (8) could cause severe hypotension in the setting of sympathetic blockade-induced vasodilation. BP and heart rate (HR) were monitored continuously. The IV fluids were given with the patient in the supine position with a wedge placed under the right hip to obtain a 15°–20° left uterine displacement. Baseline BP and HR were obtained as the mean of three consecutive measurements taken 2 min apart. The patient was then placed in the sitting position, and spinal anesthesia was administered. After skin infiltration with lidocaine, a 25- or 27-gauge Whitacre needle was inserted at the L2-3 or L3-4 vertebral interspace, and hyperbaric 0.5% bupivacaine (8–12 mg at the discretion of the anesthesiologist), sufentanil (3–5 μg), and preservative-free morphine hydrochloride (100 μg) were injected intrathecally. The patient was then returned to the supine position with left uterine displacement. The upper sensory level was checked at 10 min after the spinal injection by using loss of cold sensation to ice, and a 10°–15° head down-tilt (Trendelenburg position) was initiated if a T4 sensory level was not achieved.

Maternal BP and HR were recorded at 2-min intervals from the spinal injection for 30 min and then at 5-min intervals until the end of the surgery. Hypotension was treated with IV ephedrine (6 mg every 2 min). Although hypotension in normotensive patients is usually defined as a 20% decrease in mean BP, given that a 20% decrease in mean BP is usually a therapeutic goal in severely hypertensive patients (9), we defined hypotension in both study groups as a decrease in mean BP to <70% of the baseline value over a 30-min period after the spinal injection. An additional definition of hypotension in healthy parturients was a decrease in SBP to <100 mm Hg. Therefore, for intergroup comparisons, we considered the incidence of ephedrine administration and the mean dosage of ephedrine given. The largest and smallest values of maternal HR and the incidence of 20% changes in HR from the baseline values were also compared. The other study variables included demographic data; gestational age; spinal puncture to skin incision, skin incision to skin closure, and uterine incision to delivery intervals; the upper sensory level at 10 min after the spinal injection; neonatal weight; and 1- and 5-min Apgar scores.

Data are presented as number, median and range, mean ± SD, or percentage, as appropriate. Fisher’s exact test was used for intergroup comparisons of the number of nulliparous parturients, the upper sensory level, the incidence of hypotension, and the incidence of 20% changes in HR. Odds ratios were calculated to estimate the relative risk of hypotension between the groups. Mean values of most quantitative study variables were compared by using the unpaired Student’s t-test. Kruskal-Wallis and Dunn tests were used to analyze the time course of mean BP and HR. In addition, the largest and smallest values of BP and HR were compared with corresponding baseline values in each study group by using the paired Student’s t-test. A P value of <0.05 was considered to indicate statistical significance.

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Thirty patients with severe preeclampsia and 30 controls were studied. Patient characteristics; spinal puncture to skin incision, skin incision to skin closure, and uterine incision to delivery intervals; and 5-min Apgar scores were similar between groups (Table 1). The severely preeclamptic group included more nullipara than the healthy parturients group. In addition, patients with severe preeclampsia had a younger gestational age, which was the likely etiology of the observed smaller birth weight and lower 1-min Apgar scores of their neonates. However, in each group, only one neonate had 1-min Apgar scores <7. The volume of IV fluid administered was smaller and the dose of bupivacaine larger in the severely preeclamptic group. The height of the spinal blockade was similar in both groups (Table 1), and all patients had effective anesthesia, allowing the cesarean delivery.

Table 1

Table 1

Twelve patients with severe preeclampsia were treated with MgSO4 (1.4 ± 0.5 g/h), which was discontinued just before initiation of the spinal block in 3. Thirteen patients had antihypertensive therapy: nicardipine (2.0 ± 1.2 mg/h) in 11 and urapidil (22.5 ± 3.5 mg/h) in 2. Hypotensive drugs were discontinued at the time of spinal anesthesia in three patients. Eight patients had both MgSO4 and nicardipine. BP and HR values of severely preeclamptic and healthy parturients are shown in Table 2. Mean baseline values of SBP, DBP, and mean BP were larger in the severely preeclamptic group. These three variables decreased significantly in both groups after the spinal block (Kruskal-Wallis and Dunn tests). The magnitude of the decrease in DBP and mean BP was significantly smaller in patients with severe preeclampsia, whereas the decrease in SBP was similar in both groups (Table 2). However, the incidence of clinically relevant hypotension leading to ephedrine treatment was 16.6% in the severely preeclamptic group and 53.3% in the normotensive group (P = 0.006). All healthy parturients given ephedrine fitted the 2 definitions of hypotension planned in the protocol, so that no patient received ephedrine because of a decrease in SBP to <100 mm Hg with <30% decrease in mean BP. The SBP and mean BP in this subgroup were approximately 89.2 ± 13.6 mm Hg and 59.0 ± 9.8 mm Hg, respectively. All but one patient in each study group had symptoms such as nausea, vomiting, or dizziness at the time of hypotension, which disappeared after effective treatment with ephedrine. Power analysis showed that the observed difference of incidence in hypotension between groups was detected with a power of 85% at the 5% significance level. Odds ratio calculation suggested that the risk of hypotension was almost six times less in patients with severe preeclampsia (odds ratio, 0.175; 95% confidence interval, 0.052–0.580; P = 0.006). Mean BP tended to decrease more in healthy parturients and was partially restored by ephedrine treatment (Fig. 1). In severely preeclamptic patients, mean BP decreased more slowly and remained at a significantly lower level at the end of the study period as compared with baseline. In both groups, the decrease in mean BP was significant starting 8 min after injection of the spinal anesthetic. In addition, the time interval to the nadir of mean BP was 17.0 ± 9.0 min in the preeclamptic group versus 13.3 ± 5.4 min in the control group (P = 0.094). Baseline mean BP values were similar in untreated severely preeclamptic patients and those given antihypertensive drugs (125.7 ± 10.0 mm Hg versus 127.4 ± 11.8 mm Hg, respectively; P = 0.726), as was the decrease in mean BP (−24% ± 12% versus −19% ± 9%, respectively; P = 0.228). Baseline values of HR were similar in the two groups. The incidence of HR changes ≥20% was also similar between the groups. However, the increase in HR was of larger magnitude in healthy parturients. Nevertheless, although some patients in each group had HR changes of at least 20%, the mean values of HR in both groups did not change significantly throughout the study period (Kruskal-Wallis and Dunn tests). The time courses of HR are shown in Figure 2.

Table 2

Table 2

Figure 1

Figure 1

Figure 2

Figure 2

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This study shows that the incidence of significant hypotension leading to ephedrine treatment is less in patients with severe preeclampsia undergoing spinal anesthesia for cesarean delivery as compared with healthy parturients. The magnitude of the decrease in SBP was similar in both groups, whereas DBP and mean BP decreased less in severely preeclamptic patients. These findings were observed despite the use of a smaller volume of IV fluid and a larger dose of intrathecal bupivacaine in severely preeclamptic patients. However, given the small variability of the bupivacaine dose in both groups and the small efficacy of crystalloids in preventing spinal-induced hypotension, the clinical relevance of the differences in IV fluid and bupivacaine doses is poor, because these differences are not sufficient to affect the incidence of hypotension.

Although SBP is used to determine hypotension in normotensive patients, we chose to consider mean BP as the primary study variable because its time course reflects changes in both SBP and DBP and because it is usually used in the study of patients with severe preeclampsia, at least in studies designed to evaluate the effects of regional anesthetic techniques on BP in these patients (3–6). However, although SBP is often used (10), it has not been shown whether SBP or mean BP should be considered more accurate in the appreciation of the effect of hypotension on uteroplacental blood flow. Therefore, although we were specifically considering changes in mean BP, special attention was given to the decrease in SBP in healthy parturients to give ephedrine when SBP was <100 mm Hg.

Sympathetic blockade-induced hypotension may occur in up to 64%–100% of pregnant women given spinal anesthesia for cesarean delivery, especially when hyperbaric solutions are used (11–14). Severely preeclamptic patients were previously believed to be at high risk of severe hypotension, with maternal and fetal consequences (15) because of reduced plasma volume (8) and because of the need to limit IV fluids to avoid iatrogenic pulmonary edema (16). Therefore, spinal anesthesia is avoided in preference to an epidural technique.

Currently, several retrospective and prospective studies show that epidural and spinal anesthesia induce a similar incidence and severity of hypotension in patients with severe preeclampsia (3–5). No study has compared the incidence and severity of hypotension in severely preeclamptic versus healthy parturients. In this study, spinal anesthesia was safely administered to patients with severe preeclampsia. Furthermore, the incidence and the severity of hypotension were less in severely preeclamptic patients. Several factors might have contributed to this finding. An obvious factor is the large difference in gestational age and birth weight between the study groups. Indeed, healthy parturients carrying a larger fetus may be at increased risk of aortocaval compression. In addition, by dilating epidural blood vessels, the aortocaval compression could facilitate the cephalad spread of local anesthetics, leading to a higher upper level of spinal blockade in healthy parturients. Although the upper sensory levels were similar in both groups, the aortocaval compression may, at least partly, account for the increased incidence and severity of hypotension in the healthy parturients in our study.

An additional (although speculative) contributing factor related to the regulation of BP is also possible. BP is regulated via vascular tone by sympathetic and endothelial pathways. Sympathetic activity increases the vascular tone. Because sympathetic hyperactivity was shown in preeclampsia (17), this could contribute to hypertension. The sympathetic outflow to vessels may be altered by spinal anesthesia in both preeclamptic and healthy parturients. Concerning the endothelial pathway, the endothelium regulates the vascular tone via endothelium-related vasodilator systems that are altered in preeclampsia, decreasing the physiologic role of endothelial-dependent relaxation of small resistance vessels (18–20). In addition, preeclampsia is characterized by an increased production of numerous circulating factors with a potent pressor effect on one hand and by an increased sensitivity of blood vessels to pressor drugs because of endothelial damage on the other hand. These two phenomena contribute to the widespread vasoconstriction observed in preeclampsia (21), are not altered by spinal anesthesia, and could maintain a high vascular tone that, finally, contributes to limit the decrease in BP during spinal block in preeclamptic patients. This might explain why, among parturients given ephedrine in this study, mean BP decreased by 32% to 39% in severely preeclamptic patients, versus 33% to 60% in healthy parturients.

Some other study variables may also have contributed to our findings. First, the volume of administered crystalloids was smaller in severely preeclamptic patients despite the fact that we did not recommend reducing it in these patients. Despite its poor efficacy in the prevention of spinal anesthesia-induced hypotension (12,22), preload is important in preeclamptic patients because of the hypovolemia and vasospasm present in this pathologic condition. In addition, it has been previously reported that acute preload stimulates the release of atrial natriuretic peptide, which has natriuretic, diuretic, and vasodilator effects (23). However, although no pulmonary edema occurred in severely preeclamptic patients in this study, we believe that preload should be limited in patients with severe preeclampsia, probably to 10 mL/kg given over 10–15 minutes at the time of spinal block (24). The usefulness and the safety of this needs to be evaluated on a larger scale. Similarly, the influence of the long-term preoperative fluid supply on the incidence of spinal hypotension remains to be evaluated in patients with severe preeclampsia. Second, healthy parturients were given more ephedrine than severely preeclamptic patients as treatment for hypotension. As previously stated, this could be explained by the increased sensitivity of blood vessels to pressor drugs in preeclampsia (20), so that BP could be easily restored to baseline with smaller doses of ephedrine. In addition, in healthy parturients, a 30% decrease in mean BP can result in unacceptably low BP with adverse fetal consequences, leading to the use of large doses of ephedrine to restore BP.

In this study, healthy parturients given ephedrine had an SBP and mean BP of approximately 89.2 ± 13.6 mm Hg and 59.0 ± 9.8 mm Hg, respectively. Nevertheless, although the fetal condition was not monitored at the time of hypotension, the fetal effect of the decrease in BP was probably small, even in the healthy parturients group, as evaluated by Apgar scores. Indeed, although mean BP decreased more in healthy parturients, five-minute Apgar scores were similar in both groups. This could be explained by the fact that hypotension was short lasting, so uteroplacental blood flow was not significantly impaired. Therefore, because all but one baby in each group had one-minute Apgar scores more than 7, the cause of the lower median one-minute Apgar scores in newborns from severely preeclamptic women may be that they were younger and had less body weight.

The conclusions of our study are limited by the small sample size of the study groups. Thus, although the odds ratio was 0.17, the confidence interval was very wide, indicating the influence of the variability of several uncontrolled factors. Similarly, despite the satisfactory power for detecting a difference in the incidence of spinal-induced hypotension, the sample size was too small to draw conclusions regarding the safety of the preload and the technique in severely preeclamptic patients or to determine the effect of hypotensive treatments on this incidence.

In summary, this prospective cohort study showed that the incidence of hypotension, as defined by a 30% decrease in mean BP, is less in patients with severe preeclampsia undergoing spinal anesthesia for cesarean delivery, as compared with healthy parturients. In addition, the magnitude of the decrease in mean BP is smaller in severely preeclamptic patients. These findings suggest that the incidence and severity of spinal hypotension in preeclamptic patients with severe hypertension may be less than previously believed. However, larger studies are required to determine the safety of spinal anesthesia in this setting.

The authors thank Margaret Manson for editorial assistance.

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