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Randomized comparison of general and regional anesthesia for cesarean delivery in pregnancies complicated by severe preeclampsia
Randomized Comparison of General and Regional Anesthesia for Cesarean Delivery in Pregnancies Complicated by Severe Preeclampsia DONALDH. WALLACE,MBBS,FFARCS, KENNETHl. LEVENO,MD, F. GARY CUNNINGHAM, MD, ADOLPH H. GIESECKE,MD, VANCE E. SHEARER,MD, AND J. ELAINE SIDA WI, MD Objective: To evaluate the maternal and fetal effects of three anesthetic methods used randomly in women with severe preeclampsia who required cesarean delivery. Methods: Eighty women with severe preeclampsia, who were to be delivered by cesarean, were randomized to general (26 women), epidural (27), or combined spinal• epidural (27) anesthesia. The mean preoperative blood pres• sure (BP) was approximately 170/110 mmHg, and all women had proteinuria. Anesthetic and obstetric management in• cluded antihypertensive drug therapy and limited intrave• nous (IV) fluid and drug therapy. Results: The mean gestational age at delivery was 34.8 weeks. All infants were born in good condition as assessed by Apgar scores and umbilical arterial blood gas determina• tions. Maternal hypotension resulting from regional anes• thesia was managed without excessive IV fluid administra• tion. Similarly, maternal BP was managed without severe hypertensive effects in women undergoing general anesthe• sia. There were no serious maternal or fetal complications attributable to any of the three anesthetic methods. Conclusion: General as well as regional anesthetic meth• ods are equally acceptable for cesarean delivery in pregnan• cies complicated by severe preeclampsia if steps are taken to ensure a careful approach to either method. (Obstet Gynecol 1995;86:193-9)
In the past, both spinal and epidural anesthesia were avoided in women with severe preeclampsia and eclampsia.! Physiologic changes leading to these con• cerns centered on the hypotension induced by sympa• thetic blockade and, in turn, on dangers from pressor From the Departments of Anesthesiology and Pain Management and Obstetrics and Gynecology, University of Texas Southwestern Medical School, Dallas, Texas.
VOL. 86, NO.2, AUGUST 1995
agents or large volumes of intravenous (IV) fluid used to correct iatrogenically induced hypotension. For ex• ample, rapid infusion of large volumes of crystalloid or colloid, given to counteract maternal hypovolemia caused by a variety of causes, including epidural anal• gesia, has been implicated as a cause of pulmonary edema. 2 There have also been concerns about fetal safety because sympathetic blockade-induced hypoten• sion can dangerously lower uteroplacental perfusion? Another concern is that attempts to restore blood pres• sure (BP) pharmacologically with vasopressors may be • hazardous because women with preeclampsia are ex• tremely sensitive to such agents.4 As regional techniques were improved during the past decade, epidural anesthesia was promoted by some proponents for women with severe preeclampsia to ameliorate vasospasm and lower BP. s Moreover, many who favored epidural blockade believed that general anesthesia was inadvisable because stimulation caused by tracheal intubation may result in sudden hypertension, which causes pulmonary edema, cerebral edema, or intracranial hemorrhage. 6 - Io These propo• nents also cited that tracheal intubation may be partic• ularly hazardous in women with edema of the airway due to preeclampsia. l l - I4 These differing perspectives on the advantages, dis• advantages, and safety of the anesthetic method used in the cesarean delivery of women with severe preeclamp• sia have evolved so that some authorities believe that epidural anesthesia is the preferred method,Is whereas others are more circumspect.4,16 We evaluated these important issues by conducting a randomized investi• gation in women with severe preeclampsia.
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193
Materials and Methods Women with severe preeclampsia who required deliv• ery by cesarean were asked to participate in a random• ized investigation approved by the Institutional Review Board. The study began on November 1, 1989, and ended June 30, 1992. The Division of Obstetrics at Parkland Hospital, a tax-supported institution, primar• ily serves indigent women. The nearly 100 anesthesiol• ogy and 60 obstetrics-gynecology house officers who rotate through the Labor and Delivery Unit are super• vised by the faculty members of these departments at the University of Texas Southwestern Medical School. Enrollment criteria for severe preeclampsia included the following: systolic BP 160 mmHg or greater and diastolic BP 110 mmHg or more (Korotkoff V phase) or proteinuria of 100 mg/dL (2+) or more. Women with thrombocytopenia, defined by a platelet count less than 100,000/mm3 , and those with eclampsia or medical complications (including heart disease, diabetes melli• tus, or chronic renal disease) were excluded. This study was also limited to pregnancies requiring cesarean delivery for indications other than nonreassuring fetal heart rate (FHR) patterns. For women who had labor, electronic fetal monitoring was used continuously. Obstetric management included magnesium sulfate for seizure prophylaxis, and intermittent IV hydrala• zine was given as needed to lower diastolic BP that reached 110 mmHg or greater. This management ap• proach has been described previously.4 In brief, mag• nesium sulfate (5 g, 50% solution) was administered intramuscularly every 4 hours throughout labor, cesar• ean delivery, and the first 24 hours of the puerperium. Hydralazine was administered IV in 5-, 10-, or 15-mg boluses, as needed, at 20-minute intervals during labor or the puerperium to reduce diastolic BP to approxi• mately 90 mmHg. Administration of fluid containing electrolytes was limited to 60 mL/hour. Women who gave written consent after the decision to perform cesarean was made were assigned according to a random-number table and numbered, sealed enve• lopes to receive general, epidural, or combined spinal• epidural anesthesia. Immediate anesthetic management for all three groups included 30 mL of sodium citrate, left uterine tilt, and administration of 100% oxygen by a clear face mask. They were monitored continuously using electrocardiography, pulse oximetry, and nonin• vasive brachial BP measurements (Space Labs 5120 Monitor; Space Labs Inc., Hillsboro, OR). Central hemo• dynamic monitoring was not used. Postoperatively, IV fluid infusion was limited to 60 mLlhour in all three study groups. On entry to the operating room, women randomized to general anesthesia were evaluated at 1-2-minute
194 Wallace et al
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intervals for BP control. Intravenous hydralazine was given in 5-mg intermittent doses to maintain diastolic BP at about 100 mmHg before intubation. To prevent hypertension from tracheal stimulation, lidocaine 0.5 mg/kg) and nitroglycerin (50-/-Lg boluses, maximum dose 200 /-Lg) were also administered imme• diately before intubation. These patients received rapid sequence induction using pentothal (4-5 mg/kg) and succinylcholine 0.5 mg/kg) with cricoesophageal com• pression until tracheal intubation was confirmed by capnography and auscultation. We controlled ventila• tion and maintained anesthesia using mass spectrome• try (SARA System; PPG Biomedical Systems, Lenexa, KS) measurements of end-tidal nitrous oxide, oxygen, and isoflurane concentrations (50, 50, and 0.7%, respec• tively). Neuromuscular blockade was maintained with atracurium or vecuronium and monitored using pe• ripheral nerve stimulation. Fentanyl (l00 /-Lg) and mor• phine (l0-15 mg) were administered IV shortly after delivery. Neuromuscular blockade was reversed using glycopyrrolate and neostigmine. These women were observed closely in the recovery room for a minimum of 12 hours. For epidural anesthesia, acute hydration with 1000 mL of Ringer's lactate solution was accomplished on arrival to the operating room. A lumbar epidural catheter was placed through a 17-gauge Tuohy needle and a 5-mL test dose of 2% lidocaine or 3% cWoropro• caine was administered. Repeated 3-5-mL doses were given (total dosage 18-23 mL) until loss of sensation to cold (ice test) to a T4 sensory level was achieved. Ringer's lactate infusions and ephedrine in 5-mg IV doses were given to treat hypotension diagnosed when systolic BP reached 100 mmHg. After delivery, 50 /-Lg of fentanyl and 3.5 mg of preservative-free morphine were administered via the epidural catheter. These women were then monitored closely in the recovery room for respiratory depression for at least 12 hours after sur• gery. For combined spinal-epidural anesthesia, acute hy• dration with 1000 mL of Ringer's lactate solution was accomplished on arrival to the operating room. A 17-gauge Tuohy needle was placed into the lumbar epidural space. Dural puncture by a long, 25-gauge Quincke needle passed through the Tuohy needle was confirmed by free flow of cerebrospinal fluid. Premixed hyperbaric bupivacaine, 1.5 mL of a 0.75% solution, was injected into the subarachnoid space. The long 25-gauge needle was withdrawn, an epidural catheter was placed, and the woman was immediately positioned supine, with her shoulders and neck elevated and in slight flexion to limit cephalad migration of the anes• thetic agent to the T4 level. Supplemental epidural anesthetic included additional 3-mL boluses of 0.5%
Obstetrics & Gynecology
bupivacaine. Maintenance of BP was accomplished as described for epidural anesthesia. Similarly, epidural fentanyl and morphine were given after delivery, and patients were observed in the recovery room for at least 12 hours. We recorded demographic data, duration of labor and oxytocin use, and indications for cesarean. The highest and lowest systolic and diastolic maternal BPs in the labor room were also recorded. Logistical data included intervals of preparation for anesthesia and time posts of anesthetic and surgical events. Maternal BPs on entry to the operating room were measured as described previously at 1-2 minute intervals through• out the preoperative preparation, induction of anesthe• sia, and intraoperatively. We also recorded IV fluid volumes administered and urine output. Infant, outcomes in relation to the type of anesthesia included gestational age at delivery, birth weight, Ap• gar scores, umbilical artery blood gas and acid-base status, admission to special care nursery, and incidence of small for gestational age infants, those with respira• tory distress requiring mechanical ventilation, or those with intracranial hemorrhage. Statistical analyses used Fisher exact test and analysis of variance. Repeated measures analysis of variance was used for maternal weight, urine output, and mean arterial pressures across key time posts. Bonferroni multiple comparison procedures were used to refine the results of the analyses of variance. P < .05 (two-tailed) was considered significant.
Results Eighty women were assigned to general (26 women), epidural (27), or combined spinal-epidural (27) anesthe• sia. Six women who were identified as possible study participants changed their minds when asked to pro• vide written consent. Another subject was excluded from this study because she was randomized to epi• dural anesthesia, which failed, and general anesthesia was administered. All anesthetics were supervised by one investigator (DHW). None of the women were given labor epidural analgesia. The most common indications for cesarean delivery were dystocia and abnormal fetal presentation. One-third of the women received oxytocin for labor stimulation. All had proteinuria, and 64 (80%) had 100 mg/dL (2 +) or greater. Those with less intense protein• uria were diagnosed as having severe preeclampsia because their diastolic BP exceeded 110 mmHg. None of the women were predicted to have a difficult airway for intubation, and there were no difficult intubations. None developed eclampsia or pulmonary edema. The demographics of these women were similar to
VOL. 86, NO.2, AUGUST 1995
Table 1. Intervals for Surgical Events Type of anesthesia Epidural (n = 27)
Spinalepidural (n = 27)
24 ± 4
20 ± 2
2.6 ± O.S-
36.0 ± 2.4-
23.9 ± 1.3-
5.5 ± O.4 t
8.9 ± 0.7
8.6 ± 1.2
1.3 ± 0.1
1.4 ± 0.1
1.7 ± 0.2
40 ± 2
47± 3
47 ± 3
General (n = 26) Operating room to anesthesia induction (min) Anesthesia induction to skin incision (min) Skin incision to delivery (min) Uterine incision to delivery (min) Surgery duration (skin to skin) (min)
22 ± 2
Data are presented as mean ± standard error of the mean. - P < .001 for all groups. t P = .004 for general anesthesia compared with both regional techniques.
those of the general obstetric population for Parkland Hospital and did not differ significantly among the three anesthetic study groups. Approximately half were nulliparous, 35% were Hispanic, 35% were African• American, and 30% were white. The mean maternal age (± standard error of the mean [SEM]) was 25.4 ± 0.6 years. Table 1 shows some of the logistics of providing these three types of anesthesia. General anesthesia was asso• ciated with significantly shorter anesthesia induction to skin incision times and a shorter skin incision to deliv• ery interval. The incision was made within 3 minutes of the initiation of general anesthesia, compared with 25-35 minutes when either regional technique was used. The skin incision to delivery interval for the infant was about 3 minutes shorter when general anesthesia was used. Table 2 summarizes maternal BPs before and during cesarean delivery and in relation to the type of anesthe• sia used. The mean highest systolic and diastolic BP before arrival to the operating room was approximately 170/110 mmHg; there were no preoperative differences among the anesthesia study groups. Table 2 also shows the mean highest and lowest BPs observed at any point in the operating room. There were no significant differ• ences in average highest or lowest BPs among the three anesthesia groups. Hypotension requiring treatment with fluid boluses and ephedrine occurred in both regional anesthesia groups. Preoperative and postoper• ative hematocrits (first postoperative morning) were not significantly different between the anesthetic groups, and none of the women required blood trans• fusion. The mean preoperative hematocrit (± SEM) for all study groups was 36 ± 0.4%, and the postoperative value was 34 ± 0.5%.
Wallace et al
Anesthesia and Preeclampsia
195
Table 2. Maternal Blood Pressures Before and During Cesarean Delivery
Table 3. Intravenous Fluid Volumes, Urine Output, and Maternal Weight
Type of anesthesia Epidural (n = 27)
General (n = 26) Blood pressure in labor room (mmHg) Highest systolic Highest diastolic Blood pressure in operating room (on arrival) (mmHg) Highest systolic Highest diastolic Lowest systolic Lowest diastolic Ephedrine for hypotension·
Type of anesthesia
Spinal• Epidural (n = 27)
169:!: 3 111 :!: 2
178:!: 4 113:!: 3
165:!: 3 110:!:2
170 :!: 3 108 :!: 2 112:!: 3 6O:!: 2 0
163 :!: 3 103 :!: 3 lID:!: 3 59:!: 2 8 (30%)
158 :!: 3 102 :!: 2 lID:!: 3 61 :!: 2 6 (22%)
Pre-induction IV fluid (mL) Total intraoperative IV fluid (mL) Urine flow (mL/kg/h) Before surgery During surgeryt 24 h after surgery Maternal weight (kg) Before surgery 24 h after surgery Discharge
Data are presented as mean:!: standard error of the mean or n (%). • P = .009 (ephedrine use was different between the anesthetic groups).
•
..-....
120
0'>
:r:
E E
~
110
~
,/,..1.----•--
-------------
100
401 :!: 81·
1024:!: 59
987:!: 55
1537:!: 101·
2387:!: 110
2255 :!: 102
1.1 :!: 0.1 1.3 :!: 0.2 1.0 :!: 0.1
1.1 :!: 0.1 1.9 :!: 0.5 1.4 :!: 0.2
0.9:!: 0.1 1.4:!: 0.3 1.0:!: 0.1
80:!: 4 77:!: 3 73:!: 3
80:!: 4 77:!: 3 73:!: 3
84:!: 5 81 :!: 5 77:!: 5
Spina I-e p id u ra I
....----
Epidural General
T -----~
'.
T
T
90
Spinalepidural (n = 27)
with 2387 ± 110 and 2255 ± 102 ml in women managed with epidural and spinal-epidural anesthesia, respec• tively (P < .00l) (Table 3). Consistent with our standard approach, IV fluids were carefully restricted dUring the first 24 hours postpartum.4 The mean infusion volumes were approximately 1100-1300 ml, with no significant differences between study groups. Urine flow significantly increased in women in all groups (Table 3). These flow rates were generally sus• tained during the immediate puerperium, with no significant tendency for augmented flow in women
.1\
n. 4:
T
Epidural (n = 27)
IV = intravenous. Data are presented as mean :!: standard error of the mean. • P < .001 compared with epidural or spinal-epidural anesthesia. t P = .022 for each group compared with urine flow before surgery. There were no significant differences between anesthetic groups.
We also analyzed mean arterial pressure profiles across the three anesthesia groups at key time posts (Figure 1). Blood pressure significantly declined over time in all three groups. When anesthetic methods were compared, BP was significantly lower only with either method of regional anesthesia at the time of skin incision compared with general anesthesia (P = .003). Women assigned to either regional anesthesia tech• nique were given significantly more IV fluids in the operating room before induction and during surgery, compared with those given general anesthesia. Specifi• cally, the mean infusate volume (± SEM) was 1537 ± 101 ml in women given general anesthesia, compared
T
General (n = 26)
. t.', ,
=-..--........~. . . T SK1
To
T SKC
. . . . .1
Figure 1. The profiles of average mean arterial pressure (MAP) were significantly different over the five common time posts (P < .00l). However, only at skin incision does the general group differ from the two regional groups (P = .003). TOR = time into operating room; TIN = time of induction; TSKI = time of skin incision; To = time of delivery; TsKc = time of skin closure; TT = time of intubation; To = time of extubation. Regional groups: TINS = time of induction + 5 minutes; TINIO = time of induction + 10 minutes; TIN20 = time of induction + 20 min• utes.
TIME POSTS
196 Wallace et al
Anesthesia and Preeclampsia
Obstetrics & Gynecology
Table 4. Infant Outcomes in Relation to Type of Anesthesia Type of anesthesia
Infants (n) Gestation at delivery (wk) Birth weight (g) 500-1500 (%) 1501-2500 (%) ~2501 (%)
Apgar scores ~6 at 1 min (%) ~6 at 5 min (%) Umbilical artery blood pH Special care nurseryt (%) Small for gestational age* (%) Respiratory distress§
General
Epidural
Spinalepidural
26 34::t 0.8
31' 34::t 0.7
27 36 ::t 0.5
2138::t 180 8 (30%) 9(35%) 9(35%)
2158::t 132 6 (19%) 16 (52%) 9(29%)
2589::t 159 3(11%) 9(33%) 15 (56%)
5 (19%) 2 (8%) 7.30 ± 0.01
3 (10%) 0 7.26 ± 0.01
5 (19%) 1 (4%)
16 (59%)
22 (71%)
6(22%)
6(22%)
6 (22%)
7(26%)
7 (26%)
4 (13%)
2(7%)
2(7%)
1 (4%)
0
7.27 ± 0.01
(%)
Intracranial hemorrhage
Data are presented as n, mean ± standard error of the mean, or n (%).
, Includes four twin gestations. t p < .001 Fisher exact test. *Tenth percentile or less for gestational age. § Respiratory distress-mechanical ventilation required.
given larger fluid volumes. Oliguria-defined as 0.5 mL/kg per hour-did not develop in any of the women. The average maternal weight loss from deliv• ery to discharge was 5-7 kg, with no significant differ• ences among anesthesia groups (Table 3). There were four twin gestations, all in the epidural anesthesia group. There were 84 live-born infants and no neonatal deaths. Table 4 shows selected infant out• comes in relation to the type of anesthesia. The infants were typically 34-36 weeks' gestation at delivery, but the range was large because all infants were between 26-41 weeks. The mean birth weights ranged from about 2200-2500 g among the three study groups. When the neonates were stratified based on their birth weight groupings, women randomized to spinal-epi• dural anesthesia more often delivered larger and more mature infants. This asymmetry of birth weight group• ing, which favors the spinal-epidural group, accounts for the infrequent occurrence of neonatal morbidity due to respiratory distress or intracranial hemorrhage in this group. The type of anesthesia did not affect such neonatal morbidities when only those infants weighing less than 1500 g at birth were analyzed in each group. Infant condition at birth, measured by Apgar scores, was not affected by the type of anesthetic used (Table 4). Similarly, none of the infants were depressed at 5
VOL. 86, NO.2, AUGUST 1995
minutes of age because none had Apgar scores of 3 or less. Umbilical artery blood was obtained from each infant using a doubly clamped cord segment. The omnibus test of mean cord pH was not significant (P = .051), and there were no pairwise group differences large enough to be clinically significant. Our study of three groups had more than adequate (greater than 80%) power for a mean pH difference of 0.05 with a 0.05 standard deviation, based on an analysis of variance at the P < .05 level of significance. Additional power analysis, with fetal acidosis defined as pH 7.19 or less, shows that to have adequate power to find a significant difference in acidemia based on a rate of acidemia in the spinal and epidural groups at 23.4% compared with 7.8% in the general group (a threefold difference) would require a total of 291 patients (97 per group) based on a Jt test at the P < .05 level of significance. We chose to report results based on 80 patients, as opposed to attempting a study of four times as many patients, based on the rate of acidemia.
Discussion None of the women with severe preeclampsia suffered serious complications resulting from any of the three anesthetic methods used. Specifically, there were no serious fetal effects from maternal circulatory changes induced by sympathetic blockade. A number of poten• tial maternal complications have been described. laryn• geal edema with difficult intubation associated with aspiration results in hypoxemia of rapid onset and causes serious morbidity and mortality.17,18 In addition, laryngeal edema has resulted in respiratory arrest in the recovery room. 19 Maternal hypotension caused by re• gional anesthesia was manageable without excessive IV fluids, and there was not a dangerous response to pressors when such agents were necessary. Impor• tantly, we observed that maternal BP control was not enhanced appreciably by regional anesthesia when compared with conventional antihypertensive treat• ment with intermittent IV hydralazine. Tracheal intu• bation did not stimulate uncontrolled maternal hyper• tension when BP was carefully managed immediately before induction of general anesthesia. Not unexpect• edly, the choice of anesthetic had logistic implications because preparation time for cesarean delivery was 25-35 minutes longer when one of the regional tech• niques was used. Our decision to include spinal-epidural anesthesia in this study may be challenged by many clinicians. Some anesthesiologists and obstetricians consider spinal an• esthesia contraindicated in preeclampsia because of the risk of rapid onset of severe hypotension. However, we considered that the potential advantage of spinal anes-
Wallace et al
Anesthesia and Preeclampsia
197
thesia-rapid achievement of surgical anesthesia and resultant earlier delivery of the infant-warranted re• appraisal of this anesthetic method for cesarean deliv• ery in women with preeclampsia. Indeed, others have also concluded that use of spinal anesthesia in cases of severe preeclampsia should be reconsidered. 20 We were somewhat surprised that none of the advan• tages or disadvantages frequently cited for any of the anesthetic methods used for these women with severe preeclampsia were confirmed in our investigation. There are certain caveats that likely explain our failure to find outcomes that indict or prohibit use of any of these methods of anesthesia. For example, we excluded women with a platelet count less than 100,000/mm3 to avoid the risk of epidural hematoma?1 We also ex• cluded women whose cesarean was performed for nonreassuring FHR patterns because the immediacy of such births typically mandates the use of general anes• thesia. These exclusions were deliberate to avoid con• founding variables that could obscure interpretation of the BP effects of regional anesthesia. For example, if cesareans for nonreassuring FHR patterns had been included, depressed infant condition at birth could not be attributed to placental hypoperfusion because of sympathetic blockade as opposed to intrinsic fetal com• promise. There were no women in whom intubation would be predicted as difficult, nor did we encounter unpredictable failed tracheal intubations.u-14 The sample size selected for this investigation was unavoidably arbitrary because of the rarity of several maternal or fetal outcome measures that precluded estimates of power analysis. For example, maternal cerebral damage complicating preeclampsia occurs in only one to two per 1000 women? If the null hypothesis were based on an assumption of 0.2% overall, and we assumed a tripling of the rate of intracranial hemor• rhage, we would examine the hypothesis of 0.36% (general) versus 0.12% (spinal and epidural groups). For a tripling, the overall sample size is estimated to be 5013 or 1671 per group, which we considered to be unrealistic. Similarly, if fetal acidemia, defined as pH 7.19 or less, had been selected as an outcome measure, then for an 80% power, our study would have required approximately 100 pregnancies in each arm, and this would have extended our study from about 3 years to as many as 12, which is also unrealistic. These statistical realities precluded us from designing our study based on ad hoc or post hoc power analyses. In 1988, a group of interested obstetricians and anes• thetists collaborated to produce a protocol for the management of severe preeclampsia. 22 It was recog• nized that there was a major clinical need to codify the management of women with severe preeclampsia, and the derived protocol is reported to be used in four
198 Wallace et al
Anesthesia and Preeclampsia
United Kingdom teaching hospitals. The Newcastle protocol included limited fluid administration without the theoretical but unproven benefits of central venous pressure measurements. 22 Similarly, we believe that our adherence to a simple, albeit different, codified com• bined anesthetic and obstetric management approach was pivotal to the success of our study. Specifically, anesthesia principles that included careful and re• stricted IV fluid administration and a specified and limited selection of pharmacologic agents for BP control was added to a previously well-described obstetric protocol for management of severe hypertensive dis• ease in pregnancy.1,4,16 Moreover, this codified com• bined anesthesia and obstetric protocol permitted us to manage these women successfully without the risk of invasive hemodynamic monitoring, similar to the re• ported experience at Newcastle Upon Tyne. 15,16,23-26 Given the caveats described, general anesthesia is not contraindicated nor is regional anesthesia indicated exclusively in women with severe preeclampsia.
References 1. Pritchard JA, Cunningham FG, Pritchard SA. The Parkland Me• morial Hospital protocol for treatment of eclampsia: Evaluation of 245 cases. Am J Obstet GynecoI1984;148:951-63. 2. Sibai BM, Mabie Be, Harvey q, Gonzalez AR. Pulmonary edema in severe preeclampsia: Analysis of 37 consecutive cases. Am J Obstet GynecoI1987;156:1174-9. 3. Montau S, Ingemarsson I. Intrapartum fetal heart rate patterns in pregnancies complicated by hypertension. Am J Obstet Gynecol 1989;160:283--8. 4. Hypertensive disorders in pregnancy. In: Cunningham FG, Mac• Donald PC, Gant NF, Leveno KJ, Gilstrap III LC, eds. Williams obstetrics. 19th ed. Norwalk, Connecticut: Appleton & Lange, 1993:800-1. 5. Gutsche BB, Cheek TG. Anesthesia considerations in preeclamp• sia-eclampsia. In: Shnider SM, Levinson G, eds. Anesthesia for obstetrics. 3rd ed. Baltimore: Williams & Wilkins, 1993:321. 6. Lopez-Liera M. Complicated eclampsia: Fifteen years experience in a referral medical center. Am J Obstet GynecoI1982;142:18-35. 7. Hibbard LT. Maternal mortality due to acute toxemia. Obstet GynecoI1973;42:263-70. 8. Fox EJ, Sklargs Hill CH, Villanueva R, King BD. Complications related to the pressor response to endotracheal intubation. Anes• thesiology 1977;47:524-5. 9. Lavies NG, Meiklejohn BH, May AE, Achola KJ, Fell D. Hyperten• sive and catecholamine response to tracheal intubation in patients with pregnancy-induced hypertension. Br J Anaesth 1989;63:429• 34. 10. Hodgkinson R, Husai FJ, Hayashi RH. Systemic and pulmonary blood pressure during cesarean section in parturients with gesta• tional hypertension. Can Anaesth Soc J 1980;27:389-94. 11. Morgan M. Anaesthetic contribution to maternal mortality. Br J Anaesth 1987;59:842-55. 12. Chadwick HS, Posner K, Caplan RA, Ward RJ, Cheney FW. A comparison of obstetric and nonobstetric anesthesia malpractice claims. Anesthesiology 1991;74:242-9. 13. Marx GF, Berman JA. Anesthesia-related maternal mortality. Bull NY Acad Med 1985;61:323-30.
Obstetrics & Gynecology
14. Turnbull A, Tindall VR, Beard RW, et a1. Report on confidential enquiries into maternal deaths in England and Wales 1982-84. London: Her Majesty's Stationary Office, 1989. 15. Cheek TG, Samuels P. Pregnancy-induced hypertension. In: Datta S, ed. Anesthetic and obstetric management of high-risk preg• nancy. St. Louis: Mosby-Year Book Inc., 1991:441. 16. Cunningham FG, Lindheimer MD. Hypertension in pregnancy. N Engl J Med 1992;326:927-32. 17. Brimacomb J. Acute pharyngeal oedema and pre-eclampsia. An• aesth Intens Care 1992;20:97-8. 18. Rocke DA, Scoones GP. Rapidly progressive laryngeal oedema associated with pregnancy-aggravated hypertension. Anaesthesia 1992;47:141-3. 19. Hein HAT. Cardiorespiratory arrest with laryngeal oedema in pregnancy-induced hypertension. Can Anaesth Soc J 1984;31: 210-2. 20. Writer D. Hypertensive disorders. In: Chestnut D, ed. Obstetric anesthesia principles and practice. St. Louis: Mosby Yearbook Inc., 1994:871-2. 21. Rasmus KT, Rottman RL, Kotelko DM, Wright WC, Stone JJ, Rosenblatt RM. Unrecognized thrombocytopenia and regional anesthesia in parturients: A retrospective review. Obstet Gynecol 1989;73:943-6. 22. Robson SC, Redfern N, Walkinshaw SA. A protocol for the intrapartum management of severe preeclampsia. Int J Obstet Anesth 1992;1:222-9. 23. American College of Obstetricians and Gynecologists. Invasive hemodynamic monitoring in obstetrics and gynecology. ACOG
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technical bulletin no. 128. Washington, DC: American College of Obstetricians and Gynecologists, 1988. 24. Clark SL, Cotton DB. Clinical indications for pulmonary artery catheterization in the patient with severe preeclampsia. Am J Obstet Gynecol 1988;158:453-8. 25. Robin ED. Death by pulmonary flow-directed catheter: Time for a moratorium? Chest 1987;92:727-31. 26. Visser W, Wallenburg HCS. Central hemodynamic observations in untreated preeclamptic patients. Hypertension 1991;17:1072-7.
Address reprint requests to: Donald H. Wallace, MBBS, FFARCS
Anesthesiology and Pain Management Texas Southwestern Medical Center 5323 Harry Hines Boulevard Dallas, TX 75235-9068
Received December 27, 1994. Received in revised form March 27, 1995. Accepted May 1, 1995. Copyright © 1995 by The American College of Obstetricians and Gynecologists.
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In the past, both spinal and epidural anesthesia were avoided in women with severe preeclampsia and eclampsia.! Physiologic changes leading to these con• cerns centered on the hypotension induced by sympa• thetic blockade and, in turn, on dangers from pressor From the Departments of Anesthesiology and Pain Management and Obstetrics and Gynecology, University of Texas Southwestern Medical School, Dallas, Texas.
VOL. 86, NO.2, AUGUST 1995
agents or large volumes of intravenous (IV) fluid used to correct iatrogenically induced hypotension. For ex• ample, rapid infusion of large volumes of crystalloid or colloid, given to counteract maternal hypovolemia caused by a variety of causes, including epidural anal• gesia, has been implicated as a cause of pulmonary edema. 2 There have also been concerns about fetal safety because sympathetic blockade-induced hypoten• sion can dangerously lower uteroplacental perfusion? Another concern is that attempts to restore blood pres• sure (BP) pharmacologically with vasopressors may be • hazardous because women with preeclampsia are ex• tremely sensitive to such agents.4 As regional techniques were improved during the past decade, epidural anesthesia was promoted by some proponents for women with severe preeclampsia to ameliorate vasospasm and lower BP. s Moreover, many who favored epidural blockade believed that general anesthesia was inadvisable because stimulation caused by tracheal intubation may result in sudden hypertension, which causes pulmonary edema, cerebral edema, or intracranial hemorrhage. 6 - Io These propo• nents also cited that tracheal intubation may be partic• ularly hazardous in women with edema of the airway due to preeclampsia. l l - I4 These differing perspectives on the advantages, dis• advantages, and safety of the anesthetic method used in the cesarean delivery of women with severe preeclamp• sia have evolved so that some authorities believe that epidural anesthesia is the preferred method,Is whereas others are more circumspect.4,16 We evaluated these important issues by conducting a randomized investi• gation in women with severe preeclampsia.
0029-7844/95/$9.50
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193
Materials and Methods Women with severe preeclampsia who required deliv• ery by cesarean were asked to participate in a random• ized investigation approved by the Institutional Review Board. The study began on November 1, 1989, and ended June 30, 1992. The Division of Obstetrics at Parkland Hospital, a tax-supported institution, primar• ily serves indigent women. The nearly 100 anesthesiol• ogy and 60 obstetrics-gynecology house officers who rotate through the Labor and Delivery Unit are super• vised by the faculty members of these departments at the University of Texas Southwestern Medical School. Enrollment criteria for severe preeclampsia included the following: systolic BP 160 mmHg or greater and diastolic BP 110 mmHg or more (Korotkoff V phase) or proteinuria of 100 mg/dL (2+) or more. Women with thrombocytopenia, defined by a platelet count less than 100,000/mm3 , and those with eclampsia or medical complications (including heart disease, diabetes melli• tus, or chronic renal disease) were excluded. This study was also limited to pregnancies requiring cesarean delivery for indications other than nonreassuring fetal heart rate (FHR) patterns. For women who had labor, electronic fetal monitoring was used continuously. Obstetric management included magnesium sulfate for seizure prophylaxis, and intermittent IV hydrala• zine was given as needed to lower diastolic BP that reached 110 mmHg or greater. This management ap• proach has been described previously.4 In brief, mag• nesium sulfate (5 g, 50% solution) was administered intramuscularly every 4 hours throughout labor, cesar• ean delivery, and the first 24 hours of the puerperium. Hydralazine was administered IV in 5-, 10-, or 15-mg boluses, as needed, at 20-minute intervals during labor or the puerperium to reduce diastolic BP to approxi• mately 90 mmHg. Administration of fluid containing electrolytes was limited to 60 mL/hour. Women who gave written consent after the decision to perform cesarean was made were assigned according to a random-number table and numbered, sealed enve• lopes to receive general, epidural, or combined spinal• epidural anesthesia. Immediate anesthetic management for all three groups included 30 mL of sodium citrate, left uterine tilt, and administration of 100% oxygen by a clear face mask. They were monitored continuously using electrocardiography, pulse oximetry, and nonin• vasive brachial BP measurements (Space Labs 5120 Monitor; Space Labs Inc., Hillsboro, OR). Central hemo• dynamic monitoring was not used. Postoperatively, IV fluid infusion was limited to 60 mLlhour in all three study groups. On entry to the operating room, women randomized to general anesthesia were evaluated at 1-2-minute
194 Wallace et al
Anesthesia and Preeclampsia
intervals for BP control. Intravenous hydralazine was given in 5-mg intermittent doses to maintain diastolic BP at about 100 mmHg before intubation. To prevent hypertension from tracheal stimulation, lidocaine 0.5 mg/kg) and nitroglycerin (50-/-Lg boluses, maximum dose 200 /-Lg) were also administered imme• diately before intubation. These patients received rapid sequence induction using pentothal (4-5 mg/kg) and succinylcholine 0.5 mg/kg) with cricoesophageal com• pression until tracheal intubation was confirmed by capnography and auscultation. We controlled ventila• tion and maintained anesthesia using mass spectrome• try (SARA System; PPG Biomedical Systems, Lenexa, KS) measurements of end-tidal nitrous oxide, oxygen, and isoflurane concentrations (50, 50, and 0.7%, respec• tively). Neuromuscular blockade was maintained with atracurium or vecuronium and monitored using pe• ripheral nerve stimulation. Fentanyl (l00 /-Lg) and mor• phine (l0-15 mg) were administered IV shortly after delivery. Neuromuscular blockade was reversed using glycopyrrolate and neostigmine. These women were observed closely in the recovery room for a minimum of 12 hours. For epidural anesthesia, acute hydration with 1000 mL of Ringer's lactate solution was accomplished on arrival to the operating room. A lumbar epidural catheter was placed through a 17-gauge Tuohy needle and a 5-mL test dose of 2% lidocaine or 3% cWoropro• caine was administered. Repeated 3-5-mL doses were given (total dosage 18-23 mL) until loss of sensation to cold (ice test) to a T4 sensory level was achieved. Ringer's lactate infusions and ephedrine in 5-mg IV doses were given to treat hypotension diagnosed when systolic BP reached 100 mmHg. After delivery, 50 /-Lg of fentanyl and 3.5 mg of preservative-free morphine were administered via the epidural catheter. These women were then monitored closely in the recovery room for respiratory depression for at least 12 hours after sur• gery. For combined spinal-epidural anesthesia, acute hy• dration with 1000 mL of Ringer's lactate solution was accomplished on arrival to the operating room. A 17-gauge Tuohy needle was placed into the lumbar epidural space. Dural puncture by a long, 25-gauge Quincke needle passed through the Tuohy needle was confirmed by free flow of cerebrospinal fluid. Premixed hyperbaric bupivacaine, 1.5 mL of a 0.75% solution, was injected into the subarachnoid space. The long 25-gauge needle was withdrawn, an epidural catheter was placed, and the woman was immediately positioned supine, with her shoulders and neck elevated and in slight flexion to limit cephalad migration of the anes• thetic agent to the T4 level. Supplemental epidural anesthetic included additional 3-mL boluses of 0.5%
Obstetrics & Gynecology
bupivacaine. Maintenance of BP was accomplished as described for epidural anesthesia. Similarly, epidural fentanyl and morphine were given after delivery, and patients were observed in the recovery room for at least 12 hours. We recorded demographic data, duration of labor and oxytocin use, and indications for cesarean. The highest and lowest systolic and diastolic maternal BPs in the labor room were also recorded. Logistical data included intervals of preparation for anesthesia and time posts of anesthetic and surgical events. Maternal BPs on entry to the operating room were measured as described previously at 1-2 minute intervals through• out the preoperative preparation, induction of anesthe• sia, and intraoperatively. We also recorded IV fluid volumes administered and urine output. Infant, outcomes in relation to the type of anesthesia included gestational age at delivery, birth weight, Ap• gar scores, umbilical artery blood gas and acid-base status, admission to special care nursery, and incidence of small for gestational age infants, those with respira• tory distress requiring mechanical ventilation, or those with intracranial hemorrhage. Statistical analyses used Fisher exact test and analysis of variance. Repeated measures analysis of variance was used for maternal weight, urine output, and mean arterial pressures across key time posts. Bonferroni multiple comparison procedures were used to refine the results of the analyses of variance. P < .05 (two-tailed) was considered significant.
Results Eighty women were assigned to general (26 women), epidural (27), or combined spinal-epidural (27) anesthe• sia. Six women who were identified as possible study participants changed their minds when asked to pro• vide written consent. Another subject was excluded from this study because she was randomized to epi• dural anesthesia, which failed, and general anesthesia was administered. All anesthetics were supervised by one investigator (DHW). None of the women were given labor epidural analgesia. The most common indications for cesarean delivery were dystocia and abnormal fetal presentation. One-third of the women received oxytocin for labor stimulation. All had proteinuria, and 64 (80%) had 100 mg/dL (2 +) or greater. Those with less intense protein• uria were diagnosed as having severe preeclampsia because their diastolic BP exceeded 110 mmHg. None of the women were predicted to have a difficult airway for intubation, and there were no difficult intubations. None developed eclampsia or pulmonary edema. The demographics of these women were similar to
VOL. 86, NO.2, AUGUST 1995
Table 1. Intervals for Surgical Events Type of anesthesia Epidural (n = 27)
Spinalepidural (n = 27)
24 ± 4
20 ± 2
2.6 ± O.S-
36.0 ± 2.4-
23.9 ± 1.3-
5.5 ± O.4 t
8.9 ± 0.7
8.6 ± 1.2
1.3 ± 0.1
1.4 ± 0.1
1.7 ± 0.2
40 ± 2
47± 3
47 ± 3
General (n = 26) Operating room to anesthesia induction (min) Anesthesia induction to skin incision (min) Skin incision to delivery (min) Uterine incision to delivery (min) Surgery duration (skin to skin) (min)
22 ± 2
Data are presented as mean ± standard error of the mean. - P < .001 for all groups. t P = .004 for general anesthesia compared with both regional techniques.
those of the general obstetric population for Parkland Hospital and did not differ significantly among the three anesthetic study groups. Approximately half were nulliparous, 35% were Hispanic, 35% were African• American, and 30% were white. The mean maternal age (± standard error of the mean [SEM]) was 25.4 ± 0.6 years. Table 1 shows some of the logistics of providing these three types of anesthesia. General anesthesia was asso• ciated with significantly shorter anesthesia induction to skin incision times and a shorter skin incision to deliv• ery interval. The incision was made within 3 minutes of the initiation of general anesthesia, compared with 25-35 minutes when either regional technique was used. The skin incision to delivery interval for the infant was about 3 minutes shorter when general anesthesia was used. Table 2 summarizes maternal BPs before and during cesarean delivery and in relation to the type of anesthe• sia used. The mean highest systolic and diastolic BP before arrival to the operating room was approximately 170/110 mmHg; there were no preoperative differences among the anesthesia study groups. Table 2 also shows the mean highest and lowest BPs observed at any point in the operating room. There were no significant differ• ences in average highest or lowest BPs among the three anesthesia groups. Hypotension requiring treatment with fluid boluses and ephedrine occurred in both regional anesthesia groups. Preoperative and postoper• ative hematocrits (first postoperative morning) were not significantly different between the anesthetic groups, and none of the women required blood trans• fusion. The mean preoperative hematocrit (± SEM) for all study groups was 36 ± 0.4%, and the postoperative value was 34 ± 0.5%.
Wallace et al
Anesthesia and Preeclampsia
195
Table 2. Maternal Blood Pressures Before and During Cesarean Delivery
Table 3. Intravenous Fluid Volumes, Urine Output, and Maternal Weight
Type of anesthesia Epidural (n = 27)
General (n = 26) Blood pressure in labor room (mmHg) Highest systolic Highest diastolic Blood pressure in operating room (on arrival) (mmHg) Highest systolic Highest diastolic Lowest systolic Lowest diastolic Ephedrine for hypotension·
Type of anesthesia
Spinal• Epidural (n = 27)
169:!: 3 111 :!: 2
178:!: 4 113:!: 3
165:!: 3 110:!:2
170 :!: 3 108 :!: 2 112:!: 3 6O:!: 2 0
163 :!: 3 103 :!: 3 lID:!: 3 59:!: 2 8 (30%)
158 :!: 3 102 :!: 2 lID:!: 3 61 :!: 2 6 (22%)
Pre-induction IV fluid (mL) Total intraoperative IV fluid (mL) Urine flow (mL/kg/h) Before surgery During surgeryt 24 h after surgery Maternal weight (kg) Before surgery 24 h after surgery Discharge
Data are presented as mean:!: standard error of the mean or n (%). • P = .009 (ephedrine use was different between the anesthetic groups).
•
..-....
120
0'>
:r:
E E
~
110
~
,/,..1.----•--
-------------
100
401 :!: 81·
1024:!: 59
987:!: 55
1537:!: 101·
2387:!: 110
2255 :!: 102
1.1 :!: 0.1 1.3 :!: 0.2 1.0 :!: 0.1
1.1 :!: 0.1 1.9 :!: 0.5 1.4 :!: 0.2
0.9:!: 0.1 1.4:!: 0.3 1.0:!: 0.1
80:!: 4 77:!: 3 73:!: 3
80:!: 4 77:!: 3 73:!: 3
84:!: 5 81 :!: 5 77:!: 5
Spina I-e p id u ra I
....----
Epidural General
T -----~
'.
T
T
90
Spinalepidural (n = 27)
with 2387 ± 110 and 2255 ± 102 ml in women managed with epidural and spinal-epidural anesthesia, respec• tively (P < .00l) (Table 3). Consistent with our standard approach, IV fluids were carefully restricted dUring the first 24 hours postpartum.4 The mean infusion volumes were approximately 1100-1300 ml, with no significant differences between study groups. Urine flow significantly increased in women in all groups (Table 3). These flow rates were generally sus• tained during the immediate puerperium, with no significant tendency for augmented flow in women
.1\
n. 4:
T
Epidural (n = 27)
IV = intravenous. Data are presented as mean :!: standard error of the mean. • P < .001 compared with epidural or spinal-epidural anesthesia. t P = .022 for each group compared with urine flow before surgery. There were no significant differences between anesthetic groups.
We also analyzed mean arterial pressure profiles across the three anesthesia groups at key time posts (Figure 1). Blood pressure significantly declined over time in all three groups. When anesthetic methods were compared, BP was significantly lower only with either method of regional anesthesia at the time of skin incision compared with general anesthesia (P = .003). Women assigned to either regional anesthesia tech• nique were given significantly more IV fluids in the operating room before induction and during surgery, compared with those given general anesthesia. Specifi• cally, the mean infusate volume (± SEM) was 1537 ± 101 ml in women given general anesthesia, compared
T
General (n = 26)
. t.', ,
=-..--........~. . . T SK1
To
T SKC
. . . . .1
Figure 1. The profiles of average mean arterial pressure (MAP) were significantly different over the five common time posts (P < .00l). However, only at skin incision does the general group differ from the two regional groups (P = .003). TOR = time into operating room; TIN = time of induction; TSKI = time of skin incision; To = time of delivery; TsKc = time of skin closure; TT = time of intubation; To = time of extubation. Regional groups: TINS = time of induction + 5 minutes; TINIO = time of induction + 10 minutes; TIN20 = time of induction + 20 min• utes.
TIME POSTS
196 Wallace et al
Anesthesia and Preeclampsia
Obstetrics & Gynecology
Table 4. Infant Outcomes in Relation to Type of Anesthesia Type of anesthesia
Infants (n) Gestation at delivery (wk) Birth weight (g) 500-1500 (%) 1501-2500 (%) ~2501 (%)
Apgar scores ~6 at 1 min (%) ~6 at 5 min (%) Umbilical artery blood pH Special care nurseryt (%) Small for gestational age* (%) Respiratory distress§
General
Epidural
Spinalepidural
26 34::t 0.8
31' 34::t 0.7
27 36 ::t 0.5
2138::t 180 8 (30%) 9(35%) 9(35%)
2158::t 132 6 (19%) 16 (52%) 9(29%)
2589::t 159 3(11%) 9(33%) 15 (56%)
5 (19%) 2 (8%) 7.30 ± 0.01
3 (10%) 0 7.26 ± 0.01
5 (19%) 1 (4%)
16 (59%)
22 (71%)
6(22%)
6(22%)
6 (22%)
7(26%)
7 (26%)
4 (13%)
2(7%)
2(7%)
1 (4%)
0
7.27 ± 0.01
(%)
Intracranial hemorrhage
Data are presented as n, mean ± standard error of the mean, or n (%).
, Includes four twin gestations. t p < .001 Fisher exact test. *Tenth percentile or less for gestational age. § Respiratory distress-mechanical ventilation required.
given larger fluid volumes. Oliguria-defined as 0.5 mL/kg per hour-did not develop in any of the women. The average maternal weight loss from deliv• ery to discharge was 5-7 kg, with no significant differ• ences among anesthesia groups (Table 3). There were four twin gestations, all in the epidural anesthesia group. There were 84 live-born infants and no neonatal deaths. Table 4 shows selected infant out• comes in relation to the type of anesthesia. The infants were typically 34-36 weeks' gestation at delivery, but the range was large because all infants were between 26-41 weeks. The mean birth weights ranged from about 2200-2500 g among the three study groups. When the neonates were stratified based on their birth weight groupings, women randomized to spinal-epi• dural anesthesia more often delivered larger and more mature infants. This asymmetry of birth weight group• ing, which favors the spinal-epidural group, accounts for the infrequent occurrence of neonatal morbidity due to respiratory distress or intracranial hemorrhage in this group. The type of anesthesia did not affect such neonatal morbidities when only those infants weighing less than 1500 g at birth were analyzed in each group. Infant condition at birth, measured by Apgar scores, was not affected by the type of anesthetic used (Table 4). Similarly, none of the infants were depressed at 5
VOL. 86, NO.2, AUGUST 1995
minutes of age because none had Apgar scores of 3 or less. Umbilical artery blood was obtained from each infant using a doubly clamped cord segment. The omnibus test of mean cord pH was not significant (P = .051), and there were no pairwise group differences large enough to be clinically significant. Our study of three groups had more than adequate (greater than 80%) power for a mean pH difference of 0.05 with a 0.05 standard deviation, based on an analysis of variance at the P < .05 level of significance. Additional power analysis, with fetal acidosis defined as pH 7.19 or less, shows that to have adequate power to find a significant difference in acidemia based on a rate of acidemia in the spinal and epidural groups at 23.4% compared with 7.8% in the general group (a threefold difference) would require a total of 291 patients (97 per group) based on a Jt test at the P < .05 level of significance. We chose to report results based on 80 patients, as opposed to attempting a study of four times as many patients, based on the rate of acidemia.
Discussion None of the women with severe preeclampsia suffered serious complications resulting from any of the three anesthetic methods used. Specifically, there were no serious fetal effects from maternal circulatory changes induced by sympathetic blockade. A number of poten• tial maternal complications have been described. laryn• geal edema with difficult intubation associated with aspiration results in hypoxemia of rapid onset and causes serious morbidity and mortality.17,18 In addition, laryngeal edema has resulted in respiratory arrest in the recovery room. 19 Maternal hypotension caused by re• gional anesthesia was manageable without excessive IV fluids, and there was not a dangerous response to pressors when such agents were necessary. Impor• tantly, we observed that maternal BP control was not enhanced appreciably by regional anesthesia when compared with conventional antihypertensive treat• ment with intermittent IV hydralazine. Tracheal intu• bation did not stimulate uncontrolled maternal hyper• tension when BP was carefully managed immediately before induction of general anesthesia. Not unexpect• edly, the choice of anesthetic had logistic implications because preparation time for cesarean delivery was 25-35 minutes longer when one of the regional tech• niques was used. Our decision to include spinal-epidural anesthesia in this study may be challenged by many clinicians. Some anesthesiologists and obstetricians consider spinal an• esthesia contraindicated in preeclampsia because of the risk of rapid onset of severe hypotension. However, we considered that the potential advantage of spinal anes-
Wallace et al
Anesthesia and Preeclampsia
197
thesia-rapid achievement of surgical anesthesia and resultant earlier delivery of the infant-warranted re• appraisal of this anesthetic method for cesarean deliv• ery in women with preeclampsia. Indeed, others have also concluded that use of spinal anesthesia in cases of severe preeclampsia should be reconsidered. 20 We were somewhat surprised that none of the advan• tages or disadvantages frequently cited for any of the anesthetic methods used for these women with severe preeclampsia were confirmed in our investigation. There are certain caveats that likely explain our failure to find outcomes that indict or prohibit use of any of these methods of anesthesia. For example, we excluded women with a platelet count less than 100,000/mm3 to avoid the risk of epidural hematoma?1 We also ex• cluded women whose cesarean was performed for nonreassuring FHR patterns because the immediacy of such births typically mandates the use of general anes• thesia. These exclusions were deliberate to avoid con• founding variables that could obscure interpretation of the BP effects of regional anesthesia. For example, if cesareans for nonreassuring FHR patterns had been included, depressed infant condition at birth could not be attributed to placental hypoperfusion because of sympathetic blockade as opposed to intrinsic fetal com• promise. There were no women in whom intubation would be predicted as difficult, nor did we encounter unpredictable failed tracheal intubations.u-14 The sample size selected for this investigation was unavoidably arbitrary because of the rarity of several maternal or fetal outcome measures that precluded estimates of power analysis. For example, maternal cerebral damage complicating preeclampsia occurs in only one to two per 1000 women? If the null hypothesis were based on an assumption of 0.2% overall, and we assumed a tripling of the rate of intracranial hemor• rhage, we would examine the hypothesis of 0.36% (general) versus 0.12% (spinal and epidural groups). For a tripling, the overall sample size is estimated to be 5013 or 1671 per group, which we considered to be unrealistic. Similarly, if fetal acidemia, defined as pH 7.19 or less, had been selected as an outcome measure, then for an 80% power, our study would have required approximately 100 pregnancies in each arm, and this would have extended our study from about 3 years to as many as 12, which is also unrealistic. These statistical realities precluded us from designing our study based on ad hoc or post hoc power analyses. In 1988, a group of interested obstetricians and anes• thetists collaborated to produce a protocol for the management of severe preeclampsia. 22 It was recog• nized that there was a major clinical need to codify the management of women with severe preeclampsia, and the derived protocol is reported to be used in four
198 Wallace et al
Anesthesia and Preeclampsia
United Kingdom teaching hospitals. The Newcastle protocol included limited fluid administration without the theoretical but unproven benefits of central venous pressure measurements. 22 Similarly, we believe that our adherence to a simple, albeit different, codified com• bined anesthetic and obstetric management approach was pivotal to the success of our study. Specifically, anesthesia principles that included careful and re• stricted IV fluid administration and a specified and limited selection of pharmacologic agents for BP control was added to a previously well-described obstetric protocol for management of severe hypertensive dis• ease in pregnancy.1,4,16 Moreover, this codified com• bined anesthesia and obstetric protocol permitted us to manage these women successfully without the risk of invasive hemodynamic monitoring, similar to the re• ported experience at Newcastle Upon Tyne. 15,16,23-26 Given the caveats described, general anesthesia is not contraindicated nor is regional anesthesia indicated exclusively in women with severe preeclampsia.
References 1. Pritchard JA, Cunningham FG, Pritchard SA. The Parkland Me• morial Hospital protocol for treatment of eclampsia: Evaluation of 245 cases. Am J Obstet GynecoI1984;148:951-63. 2. Sibai BM, Mabie Be, Harvey q, Gonzalez AR. Pulmonary edema in severe preeclampsia: Analysis of 37 consecutive cases. Am J Obstet GynecoI1987;156:1174-9. 3. Montau S, Ingemarsson I. Intrapartum fetal heart rate patterns in pregnancies complicated by hypertension. Am J Obstet Gynecol 1989;160:283--8. 4. Hypertensive disorders in pregnancy. In: Cunningham FG, Mac• Donald PC, Gant NF, Leveno KJ, Gilstrap III LC, eds. Williams obstetrics. 19th ed. Norwalk, Connecticut: Appleton & Lange, 1993:800-1. 5. Gutsche BB, Cheek TG. Anesthesia considerations in preeclamp• sia-eclampsia. In: Shnider SM, Levinson G, eds. Anesthesia for obstetrics. 3rd ed. Baltimore: Williams & Wilkins, 1993:321. 6. Lopez-Liera M. Complicated eclampsia: Fifteen years experience in a referral medical center. Am J Obstet GynecoI1982;142:18-35. 7. Hibbard LT. Maternal mortality due to acute toxemia. Obstet GynecoI1973;42:263-70. 8. Fox EJ, Sklargs Hill CH, Villanueva R, King BD. Complications related to the pressor response to endotracheal intubation. Anes• thesiology 1977;47:524-5. 9. Lavies NG, Meiklejohn BH, May AE, Achola KJ, Fell D. Hyperten• sive and catecholamine response to tracheal intubation in patients with pregnancy-induced hypertension. Br J Anaesth 1989;63:429• 34. 10. Hodgkinson R, Husai FJ, Hayashi RH. Systemic and pulmonary blood pressure during cesarean section in parturients with gesta• tional hypertension. Can Anaesth Soc J 1980;27:389-94. 11. Morgan M. Anaesthetic contribution to maternal mortality. Br J Anaesth 1987;59:842-55. 12. Chadwick HS, Posner K, Caplan RA, Ward RJ, Cheney FW. A comparison of obstetric and nonobstetric anesthesia malpractice claims. Anesthesiology 1991;74:242-9. 13. Marx GF, Berman JA. Anesthesia-related maternal mortality. Bull NY Acad Med 1985;61:323-30.
Obstetrics & Gynecology
14. Turnbull A, Tindall VR, Beard RW, et a1. Report on confidential enquiries into maternal deaths in England and Wales 1982-84. London: Her Majesty's Stationary Office, 1989. 15. Cheek TG, Samuels P. Pregnancy-induced hypertension. In: Datta S, ed. Anesthetic and obstetric management of high-risk preg• nancy. St. Louis: Mosby-Year Book Inc., 1991:441. 16. Cunningham FG, Lindheimer MD. Hypertension in pregnancy. N Engl J Med 1992;326:927-32. 17. Brimacomb J. Acute pharyngeal oedema and pre-eclampsia. An• aesth Intens Care 1992;20:97-8. 18. Rocke DA, Scoones GP. Rapidly progressive laryngeal oedema associated with pregnancy-aggravated hypertension. Anaesthesia 1992;47:141-3. 19. Hein HAT. Cardiorespiratory arrest with laryngeal oedema in pregnancy-induced hypertension. Can Anaesth Soc J 1984;31: 210-2. 20. Writer D. Hypertensive disorders. In: Chestnut D, ed. Obstetric anesthesia principles and practice. St. Louis: Mosby Yearbook Inc., 1994:871-2. 21. Rasmus KT, Rottman RL, Kotelko DM, Wright WC, Stone JJ, Rosenblatt RM. Unrecognized thrombocytopenia and regional anesthesia in parturients: A retrospective review. Obstet Gynecol 1989;73:943-6. 22. Robson SC, Redfern N, Walkinshaw SA. A protocol for the intrapartum management of severe preeclampsia. Int J Obstet Anesth 1992;1:222-9. 23. American College of Obstetricians and Gynecologists. Invasive hemodynamic monitoring in obstetrics and gynecology. ACOG
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technical bulletin no. 128. Washington, DC: American College of Obstetricians and Gynecologists, 1988. 24. Clark SL, Cotton DB. Clinical indications for pulmonary artery catheterization in the patient with severe preeclampsia. Am J Obstet Gynecol 1988;158:453-8. 25. Robin ED. Death by pulmonary flow-directed catheter: Time for a moratorium? Chest 1987;92:727-31. 26. Visser W, Wallenburg HCS. Central hemodynamic observations in untreated preeclamptic patients. Hypertension 1991;17:1072-7.
Address reprint requests to: Donald H. Wallace, MBBS, FFARCS
Anesthesiology and Pain Management Texas Southwestern Medical Center 5323 Harry Hines Boulevard Dallas, TX 75235-9068
Received December 27, 1994. Received in revised form March 27, 1995. Accepted May 1, 1995. Copyright © 1995 by The American College of Obstetricians and Gynecologists.
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