Objective
To determine whether severe preeclampsia is associated with increased maternal hypotension or fetal heart rate abnormalities after epidural anesthesia placement during labor.
Study Design
Retrospective cohort study of 100 women with severe preeclampsia and 100 normotensive controls who underwent epidural anesthesia during labor from May 2008 to July 2011. Blood pressures during 2-minute time intervals for 20 minutes postepidural were compared with baseline measurements. Fetal heart rate abnormalities and related interventions were evaluated according to study group.
Results
Severe preeclampsia was associated with a greater percent decrease in blood pressure across all intervals and more episodes of systolic and diastolic hypotension after dosing. Severely preeclamptic women received more intravenous pressor support and developed more Category II fetal heart rate tracings, minimal variability, and late decelerations after dosing.
Conclusion
Severe preeclampsia is associated with more frequent hypotension, need for pressor support, and fetal heart rate abnormalities after epidural anesthesia placement during labor.
Maternal hypotension, resulting from regional anesthesia-associated sympathectomy, complicates 5-17% of labor epidurals, and is an important potential cause of intrapartum fetal heart rate (FHR) abnormalities and emergent cesarean delivery.
Severe preeclampsia is characterized by maternal vasoconstriction and increased vascular permeability with resultant third-space fluid losses and intravascular volume depletion. Epidural anesthesia related sympathetic blockade has the potential to cause significant hypotension in women who are intravascularly depleted and vasoconstricted. The way in which the sympathetic blockade associated with regional anesthesia placement interacts with the vascular changes of severe preeclampsia has not been well studied. In small studies of women with severe preeclampsia, epidural anesthesia has been shown to improve intervillous blood flow and decrease uterine artery S/D ratios; however, no episodes of hypotension occurred in any of these studies, and they were not powered to detect this common complication. To our knowledge, previous studies of uterine perfusion in severely preeclamptic have not included cases complicated by maternal hypotension.
Our objective was to determine whether women with severe preeclampsia have more frequent epidural anesthesia-related hypotension and resultant FHR abnormalities than normotensive patients.
Materials and Methods
In this retrospective cohort study, women who had undergone epidural anesthesia placement during labor from May 2008 to July 2011 at an academic tertiary care center were identified using our computerized perinatal database. We then selected the next patient who met matching criteria but avoided matching patients who had delivered on the same day to avoid the potential bias that the occurrence of adverse events in one patient might directly influence the management of the subsequent patient. Women admitted for labor or induction who received epidural anesthesia were included. Women with multifetal deliveries, nonvertex presentations, major fetal anomalies, and fetal demise were excluded. Women with cervical dilation greater than 5 cm at time of epidural placement were excluded to minimize tracing abnormalities more common in the active phase of labor.
One hundred consecutive women with singleton pregnancies who met criteria for severe preeclampsia, as defined in the ACOG practice bulletin no. 33, were matched for maternal age, gestational age, race, and year of delivery to 100 normotensive women. Preeclampsia was diagnosed in a previously normotensive woman who had blood pressure of at least 140/90 mm Hg on 2 occasions after 20 weeks’ gestation in addition to 300 mg proteinuria in a 24-hour urine collection. Women were considered to have severe preeclampsia if they had over 5 g of protein in a 24-hour hour urine collection, oliguria of less than 500 mL urine output in 24 hours, cerebral or visual disturbances, pulmonary edema or cyanosis, epigastric or right upper quadrant pain, impaired liver function, thrombocytopenia, fetal growth restriction (<10 percentile on institutional growth curves), or met blood pressure criteria for severe hypertension (160/110 mm Hg on 2 occasions at least 6 hours apart) in the absence of severe hypertension before 20 weeks’ gestation. Criteria for HELLP syndrome were defined according to the Tennessee Classification system: increased LDH (≥600 U/L), increased AST (≥70 U/L), and low platelets (≤100,000 μL).
Women with severe preeclampsia superimposed on chronic hypertension were included in our cohort as these patients comprise a significant proportion of severe preeclamptic patients in our population. As chronic hypertensive women with superimposed severe preeclampsia may be at increased risk for adverse perinatal outcomes than those with isolated preeclampsia, we thought it important that these patients be represented in our cohort. To meet criteria for preeclampsia based on proteinuria, women with chronic hypertension had to demonstrate an acute increase in 24-hour urine protein excretion by over 300 mg in a 24-hour urine collection after a baseline value less than 150 mg in 24 hours before 20 weeks’ gestation. Women with chronic hypertension were considered to have superimposed severe preeclampsia if they developed any of the following: acutely worsening blood pressures of 160/110 mm Hg or above where they had previously been well controlled, new-onset severe proteinuria (24-hour urinary protein at least 5 g), or new onset of multiple end organ system involvement (by the criteria for severe preeclampsia as described above). After primary analysis of the study, a post hoc analysis was performed to evaluate the incidence of hypotension in the subgroup of women without preexisting chronic hypertension.
At our institution laboring patients routinely receive a 500-mL bolus of intravenous crystalloid for volume expansion before epidural catheter placement and there is not a specific protocol for preepidural fluid administration for women with preeclampsia. If women are receiving pitocin before epidural catheter placement at a steady infusion rate that was tolerated by the fetus before epidural placement, the practice at our institution is to continue the pitocin during placement of the epidural catheter. After epidural placement and administration of a test dose, a bolus dose of 2-6 mL of a bupivicaine 0.125%, fentanyl 7.5 mcg/mL, and epinephrine 5 mcg/mL solution is administered. If the initial dose produces insufficient analgesia, then further anesthetic boluses are given. The attending anesthesiologist determines the amount of initial epidural anesthetic bolus, whether to rebolus, and whether to give intravenous pressor support. Phenylephrine is the first-line intravenous pressor medication used for maternal hypotension. For this study, baseline blood pressure was defined as the value recorded immediately before epidural catheter dosing. Systolic and diastolic blood pressures are recorded at 2-minute intervals for the first 20 minutes after epidural placement.
We defined “systolic hypotension” as a 20% decrease in systolic blood pressure and “diastolic hypotension” as a 20% decrease in diastolic blood pressure. We evaluated systolic and diastolic pressures separately. Although there is no widely accepted definition for epidural related hypotension, systolic hypotension has more commonly been reported. However, we thought that diastolic hypotension might have potential clinical significance in the obstetric population, as our previous work has suggested that diastolic blood pressure may maintain uteroplacental perfusion more than systolic blood pressure.
We defined “transient hypotension” as at least 20% decrease in blood pressure from baseline over 1-3 intervals (lasting 2-6 minutes) over the 20 minutes studied. We defined “persistent hypotension” as at least 20% decrease in blood pressure from baseline over 4-10 intervals (lasting 8-20 minutes) during the 20 minutes studied. Percent change in blood pressure at each interval as well as the frequency of systolic and diastolic hypotension across intervals was evaluated within and between study groups.
FHR patterns for 20 minutes before and after epidural anesthetic bolus were classified according to the 2008 NICHD Electronic Fetal Monitoring guidelines by a single reviewer who was masked to study group and vital signs during tracing evaluation. The pre- and postepidural FHR patterns were classified as Category I (normal), Category II (indeterminant), or Category III (abnormal). Findings not present before epidural dosing were considered new changes. New findings of minimal variability, recurrent variable decelerations, recurrent late decelerations, and prolonged decelerations for more than 2 minutes constituted “abnormal” FHR patterns that would necessitate an obstetric intervention to return the pattern to a Category I FHR pattern or necessitate delivery. As late and prolonged decelerations are the FHR abnormalities associated with uteroplacental insufficiency from epidural-associated hypotension, these were evaluated individually.
Statistical analysis
The institutional review board at MetroHealth Medical Center approved this retrospective chart review. Statistical analyses were performed using commercially available software (SPSS version 18.0; SPSS Inc, Chicago, IL). We used the Student t test for continuous variables and the Mann-Whitney U and Fisher exact tests for categorical variables. P values < .05 were considered significant. Individual maternal and anesthesia records were evaluated. Electronic FHR patterns were reviewed by a single investigator (L.V.). Baseline maternal characteristics, anesthesia outcomes, hemodynamic parameters, and delivery outcomes were compared between groups. The primary outcome measure was the occurrence of hypotension (systolic or diastolic) within 20 minutes of epidural placement. Secondary outcome measures included new onset of FHR pattern abnormalities within 20 minutes of epidural catheter placement.
A 5% incidence of hypotension has been previously reported when intravenous preloading is given before epidural catheter placement for labor. With an a priori alpha of .05 and a beta of .2, 100 women would be needed in each group to detect a 3-fold increase in hypotension in women with severe preeclampsia.
Results
One hundred consecutive women with severe preeclampsia who met our inclusion criteria were matched for age, race, and gestational age with 100 normotensive controls in a 1:1 ratio. The 2 groups were similar regarding insurance status and frequency of medical complications (asthma, diabetes), ( Table 1 ). The gestational ages of women meeting criteria for inclusion ranged from 28 to 40 weeks. Normotensive women had a lower mean body mass index (30 kg/m 2 ), and greater parity. Delivery indications for the normotensive controls were term or preterm labor (65%), preterm premature rupture of membranes (18%), placental abruption (6%), cholestasis of pregnancy (3%), oligohydramnios (2%), intrauterine growth restriction (5%), and maternal cancer (1%).
| Characterisitic | Normotensive controls | Severe preeclampsia | P value |
|---|---|---|---|
| n | 100 | 100 | |
| Age, y | 25 ± 6 | 25 ± 7 | .9 |
| Gestational age, wks | 36 ± 2 | 36 ± 2 | .8 |
| Body mass index, kg/m 2 | 30 ± 7 | 35 ± 7 | < .0001 |
| Parity | 1.5 ± 2.2 | 0.8 ± 1.2 | .004 |
| Nulliparity, % | 41 | 61 | .007 |
| Race, % | |||
| African American | 54 | 59 | .8 |
| Hispanic | 8 | 7 | |
| White | 38 | 34 | |
| Insurance, % | |||
| Public | 89 | 79 | .1 |
| Private | 11 | 21 | |
| Chronic hypertension, % | 0 | 38 | < .0001 |
| Asthma, % | 12 | 12 | > .99 |
| Diabetes (pregestational), % | 2 | 6 | .3 |
| Diabetes (gestational), % | 5 | 11 | .2 |
Women with severe preeclampsia had a higher mean body mass index (35 kg/m 2 ) than controls, and a 38% incidence of chronic hypertension; women with chronic hypertension were excluded from the control group. Of the 38 women with severe preeclampsia with underlying chronic hypertension, 18 (47%) had required antihypertensive medications during pregnancy. Thirty percent of women with severe preeclampsia required intravenous antihypertensive medications in labor and delivery for acute blood pressure control. Preeclamptic women met criteria for severe disease as follows: blood pressure criteria (90%), proteinuria over 5 g in 24 hours (7%), neurologic symptoms (47%), pulmonary edema or cyanosis (2%), epigastric or right upper quadrant pain (10%), elevated transaminases (7%), oliguria (1%), thrombocytopenia (5%), and intrauterine growth restriction (37%).
Regarding delivery and anesthesia outcomes, women with severe preeclampsia had more frequent rates of induction and cesarean delivery than normotensive controls. Birthweight was similar between groups, however, women with severe preeclampsia had more frequent small for gestational age (SGA) infants. They had more frequent emergent deliveries (operative vaginal or cesarean), and more emergent deliveries attributed to epidural-related hypotension and FHR abnormalities by their physician; however, these differences were not significant ( Table 2 ). The groups received similar intravenous crystalloid volume preloading and epidural anesthetic bolus dosages. The frequency of intravenous pressor support was not statistically different between groups. However, the mean dose of intravenous pressor support administered was significantly greater among the severely preeclamptic group.
| Variable | Normotensive controls | Severe preeclampsia | P value |
|---|---|---|---|
| Birthweight, g | 2690 ± 580 | 2580 ± 650 | .2 |
| SGA infant <10 percentile, (%) | 18 | 37 | .004 |
| Apgar scores | |||
| 1 min | 9 (9-9) | 9 (7-9) | |
| 5 min | 9 (9-9) | 9 (9-9) | |
| Anesthesia outcomes | |||
| Bupivicaine dose, mL | 4.7 ± 1.4 | 4.6 ± 1.7 | .6 |
| IV preload bolus volume, mL | 512 ± 160 | 472 ± 222 | .1 |
| Phenylephrine, mg | 17 ± 70 | 80 ± 292 | .04 |
| Any phenylephrine given, % | 6 | 15 | .06 |
| Admission blood pressure, mm Hg | |||
| Systolic | 121 ± 11 | 151 ± 15 | < .0001 |
| Diastolic | 77 ± 49 | 93 ± 14 | .003 |
| Baseline blood pressure, mm Hg | |||
| Systolic | 122 ± 11 | 145 ± 17 | < .0001 |
| Diastolic | 73 ± 11 | 87 ± 15 | < .0001 |
| Systolic hypotension, % | |||
| 0 episodes | 56 | 12 | < .0001 |
| Transient (1-3) | 42 | 54 | |
| Persistent (4-10) | 2 | 34 | |
| Diastolic hypotension, % | |||
| 0 episodes | 26 | 7 | < .0001 |
| Transient (1-3) | 39 | 19 | |
| Persistent (4-10) | 35 | 74 | |
| New onset fetal heart rate patterns, % | |||
| Change from category I to II | 6 | 27 | < .0001 |
| Category II or III | 9 | 33 | < .0001 |
| Minimal variability | 0 | 23 | < .0001 |
| Late decelerations | 7 | 22 | .004 |
| Prolonged decelerations | 4 | 10 | .2 |
| Tachysystole | 3 | 9 | .1 |
| Delivery outcomes, % | |||
| Induction | 35 | 87 | < .0001 |
| Spontaneous vaginal | 90 | 77 | .02 |
| Operative vaginal | 5 | 4 | > .99 |
| Cesarean section | 5 | 19 | .004 |
| Emergent (cesarean/operative vaginal) | 6 | 11 | .3 |
| Hypotension-related | 1 | 2 | > .99 |
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