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Obstetric Implications of Antepartum Corticosteroid Therapy for HELLP Syndrome

Carl H. Rose, MD^*, Brad D. Thigpen, DO^*, James A. Bofill, MD^*, Julie Cushman, RN^*, Warren L. May, PhD and James N. Martin, Jr, MD^*

From the Departments of *Departments of Obstetrics and Gynecology and Preventive Medicine, University of Mississippi Medical Center, Jackson, Mississippi.

	ABSTRACT

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OBJECTIVE: We reviewed the impact of intravenous high-dose corticosteroid administration for preterm hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome on vaginal delivery rate and degree of clinically significant thrombocytopenia.

METHODS: Retrospective analysis of 1991–2000 HELLP syndrome (platelets < 100,000/uL, lactate dehydrogenase > 600 IU/L, aspartate aminotransferase and/or alanine aminotransferase > 70 IU/L) data focusing on labor inductions for gestations of less than 34 weeks and increase in platelet count sufficient to permit regional anesthetic techniques.

RESULTS: Antepartum high-dose corticosteroid use increased from 32% (1991–1995) to 67% (1996–2000) for 350 patients studied (n = 199, < 34 weeks; n = 151, > 34 weeks). Corresponding vaginal delivery rates were 32% for gestations of less than 30 weeks, 61% at 30–31 weeks, and 62% at 32–33 weeks. Similarly, 27% of patients with a platelet count of less than 75,000/uL and 52% with a platelet count of less than 100,000/uL who received high-dose corticosteroids during the study interval subsequently achieved a 100,000/uL threshold in time to perform regional anesthesia for delivery.

CONCLUSION: Administration of intravenous high-dose corticosteroids for preterm HELLP syndrome increases probability of successful labor induction and candidacy for regional anesthesia.

LEVEL OF EVIDENCE: II-3

Theoretically, high-dose corticosteroids should confer 2 major obstetric advantages: 1) brief temporization of maternal clinical status to attempt induction of labor, and 2) elevation of the platelet count to conventional thresholds to permit regional anesthesia for either vaginal or abdominal delivery. This project was undertaken to ascertain if either benefit was realized in the last decade of patient care in our maternal–perinatal unit.

	MATERIALS AND METHODS

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All patients in whom HELLP syndrome was diagnosed who were admitted to the University of Mississippi Medical Center/Wiser Hospital for Women and Infants in Jackson between January 1981 and December 2000 were reviewed for inclusion in the Mississippi HELLP Syndrome Database. For the purpose of the present investigation, only patients who satisfied criteria for antepartum class 1 or 2 HELLP syndrome between January 1991 and December 2000 were included in the analysis. Patients in whom HELLP syndrome developed after delivery were not considered for this study. As described previously, patients with class 1 HELLP exhibited severe thrombocytopenia with a perinatal platelet nadir below 50,000/uL, a total serum lactate dehydrogenase of more than 600 IU/L, and a serum transaminase level of more than 70 IU/L as aspartate aminotransferase or alanine aminotransferase. Patients with class 2 HELLP had similar laboratory criteria except for less profound thrombocytopenia (perinatal platelet nadir between > 50,000 and < 100,000 IU/L). All patients also demonstrated signs, symptoms, and laboratory findings consistent with a diagnosis of preeclampsia/eclampsia during their antepartum and postpartum course.⁴ The high-dose corticosteroid regimen consisted of 10 mg of dexamethasone administered intravenously every 12 hours until delivery followed by 2 postpartum taper of 10 mg intravenously every 12 hours 2 times and then 5 mg intravenously every 12 hours 2 times. Detailed reviews of this protocol and its use have been described elsewhere.⁵ A small number of patients (n = 19, 7.7%) received 2 supplemental dosages of 12 mg betamethasone intramuscularly every 24 hours to accelerate fetal lung maturation.

Two analyses were performed with the data from the selected patient population. For the first stage, aspects relevant to mode of delivery were considered. Previously published vaginal delivery rates for 189 women with class 1 or 2 HELLP syndrome managed from 1980–1991 were compared with the 1991–2000 interval. Additionally, intrinsic comparisons were made between patients who did or did not receive high-dose corticosteroids for the treatment of HELLP syndrome before delivery. Patients who underwent repeat or primary cesarean delivery for maternal or fetal reason within 12 hours of hospital admission, presented with an intrauterine fetal demise, or were at gestational age of less than 26 weeks were excluded from the analysis. This retrospective review was approved by the Institutional Review Board at the University of Mississippi Medical Center.

The second stage examined platelet counts at times of admission and delivery to determine if the high-dose corticosteroid protocol produced an increase to either of 2 thresholds (> 75,000/µL or > 100,000/µL) sufficient to permit regional anesthetic techniques. Patients of all gestational ages from 1991–2000 were included.

Categorical results were summarized using proportions and comparisons made using the ² test when appropriate; otherwise, Fisher exact P values are reported. Continuous variables were summarized using either medians or means plus or minus 1 standard deviation; distributional assumptions were assessed using normal probability plots and histograms. For statistical analysis, the 2 groups of patients were compared, with a P value of less than .05 considered significant.

	RESULTS

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During the 1991–2000 interval, 350 patients with antepartum class 1 (n = 119) or class 2 (n = 231) HELLP syndrome were identified for inclusion in the HELLP Syndrome Database; 199 had gestations of less than 34 weeks and 151 were beyond 34 weeks. Demographic details are depicted in Table 1. High-dose corticosteroid use for patients with HELLP syndrome at all gestational ages increased from 32% (1991–1995) to 67% (1996–2000) as the high-dose corticosteroid protocol was more consistently incorporated into routine management. Attending physician preference dictated high-dose corticosteroid administration during the early years, becoming much more prevalent in the latter half of the decade.

Induction of labor was attempted in 247 patients and was successful in 145 (59%). As shown in Table 2, vaginal delivery rates for high-dose corticosteroid–treated patents increased progressively from 32% before 30 weeks to 62% at or beyond 32 weeks (P = .005). In contrast, during the 1980–1991 era, before glucocorticoid use was routine, only 15% of patients at less than 30 weeks and only 47% between 30–34 weeks gestation delivered vaginally.² Focusing on specific gestational ages, Table 3 shows comparative cesarean delivery rates. Individual groupings are not statistically significant because of small sample sizes, but in aggregate show a 28% increase in cesarean delivery rates when dexamethasone was not administered (P = .02).

The impact of antepartum high-dose corticosteroid administration on intrapartum platelet count in patients with class 1 or 2 HELLP syndrome is shown in Table 4. Between 1991–2000, approximately 74% and 45% of patients at all gestational ages had platelet counts at delivery below 100,000/uL and 75,000/uL, respectively, 2 thresholds typically considered appropriate by anesthesiologists for regional techniques. For patients with less than 75,000/uL platelets before delivery, 54% received high-dose corticosteroids: 29% achieved the 75,000/uL platelet threshold at delivery compared with only 12% who were untreated (P = .06). Additionally, 27% of the high-dose corticosteroid–treated group and 10% of the untreated group went on to exceed 100,000/uL platelets at delivery (P = .01). For patients with less than 100,000/uL platelets at time of admission, 56% received antepartum high-dose corticosteroids, with 52% exceeding 100,000/µL by time of delivery. Spontaneous improvement to a count of more than 100,000/µL was noted in 39% of the untreated group (P = .10).

	DISCUSSION

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Incorporation of high-dose corticosteroids into our obstetric management of class 1 or class 2 HELLP syndrome has become increasingly routine since the early 1990s. We also occasionally use this regimen for the infrequent patient with class 3 HELLP syndrome (platelets 100–150,000/uL, lactate dehydrogenase > 600 IU/L, aspartate aminotransferase, and/or alanine aminotransferase > 40 IU/L) presenting with epigastric pain, eclampsia, severe hypertension, or rapidly deteriorating laboratory values suggestive of imminent class 2 HELLP syndrome.⁶ Previous work from our institution has shown reduced requirements for blood product transfusion, more prompt postpartum platelet recovery, and less maternal morbidity with the high-dose corticosteroid protocol.⁵

Antepartum high-dose corticosteroid use in patients with HELLP syndrome is associated with a higher rate of vaginal delivery. We hypothesize this is due to temporary stabilization of maternal status sufficient to attempt labor induction rather than perform immediate cesarean delivery in patients not actively laboring. As shown also in the study undertaken during the 1980–1991 era (when corticosteroids to enhance fetal lung maturation were rarely used), gestational age remains the most important predictor of successful labor induction. The addition of high-dose corticosteroids increases the likelihood of vaginal delivery, with a collective 37% success rate before 28 weeks.

Increasingly efficient methods of cervical ripening probably contribute to improvement on the dismal 15% rate of the 1980–1991 era. Misoprostol and dinoprostone both produce a shorter induction-to-delivery interval when compared with oxytocin; combination with a mechanical method (ie, Foley catheter) may optimize the likelihood of induction success.⁷ This can profoundly influence the clinical decision whether to attempt labor induction when confronted with a deteriorating preterm patient with HELLP syndrome. However, despite these advances, current vaginal delivery rates remain below 50% for gestations of less than 30 weeks.

There is a dearth of evidence in both the obstetric and anesthesia literature regarding evidence-based platelet thresholds appropriate for regional anesthesia. Many anesthesiologists consider a platelet count of less than 100,000/uL a contraindication to spinal or epidural placement irrespective of etiology. The 1993 Shnider and Levinson anesthesia text is often cited, but the 2002 revision suggests that regional techniques are permissible in the absence of overt coagulopathy.^8,9 Development of paraspinal hematoma is an extremely rare complication, with only 8 cases reported to date in obstetric patients.¹⁰ In a retrospective review of regional anesthesia administered before determination of platelet count, Rasmus et al¹¹ found a 1% incidence of peripartum thrombocytopenia. Similarly, Beilin et al¹² reviewed epidural placement in 52 obstetric patients with platelet counts below 100,000/uL. No maternal sequelae were noted in either study. Both authors concluded regional anesthesia to be a reasonable option in patients with platelet counts of less than 100,000/uL, commenting that the minimum safe value has not been established. Particularly when confronted with a potentially difficult airway, early placement of an epidural catheter may be the more prudent anesthetic choice.

Only 5% of patients with HELLP syndrome demonstrate laboratory evidence of impaired clotting function, and spontaneous hemorrhage is uncommon until the platelet count falls below 40,000/uL.⁶ The American College of Obstetricians and Gynecologists’ guidelines consider epidural or spinal to be the preferred anesthetic for patients with preeclampsia.¹³ O'Brien et al¹⁴ noted that corticosteroid use improved maternal platelet counts sufficiently to increase the epidural rate for patients with HELLP syndrome from 0% to 57%. Depending on which of the 2 thresholds is considered adequate, between 45% and 70% of patients with class 1 or 2 HELLP syndrome who receive high-dose corticosteroids are potential candidates. Our data suggest a benefit primarily to those patients presenting with platelet counts of less than 75,000/µL. Such treatment can substantially affect the eligibility of a patient to receive either epidural or spinal anesthesia for delivery.

Patients with HELLP syndrome who have rapidly falling platelet counts present a further anesthetic challenge. Some authorities recommend against combined spinal–epidural techniques, opining that the rapid onset of analgesia provided by the spinal medication may conceal initial signs of epidural hematoma formation. Catheter placement early during the course of labor (while platelet counts are still relatively high), and saline infusion until analgesia is required may present a reasonable alternative. Postpartum catheter removal is deferred until platelet count has begun to recover.

Interestingly, a small proportion of untreated patients in the study group showed spontaneous increases in platelet counts. We find this puzzling and cannot offer a consistent explanation for this phenomenon, except that perhaps initiation of supportive therapy—in the form of magnesium sulfate prophylaxis and antihypertensive medications—may have transiently stabilized the evolving disease pathophysiology and accordingly improved laboratory parameters.

This study is limited by use of historical controls. Retrospective analysis intrinsically lacks the definitive nature of a randomized control trial, although this would be difficult to envision for the anesthetic aspects. Preterm antepartum corticosteroid use for fetal indication has become almost universally prevalent. Obstetric practice has evolved over the past 2 decades as increasing experience with HELLP syndrome and attendant complications has accrued. Recognizing the limitations of the current study, the high-dose corticosteroid protocol for HELLP syndrome appears effective in reducing cesarean delivery rates and potentially improving candidacy for regional anesthesia in class 1 and 2 disease.

	Footnotes

 
Received February 26, 2004. Received in revised form July 4, 2004. Accepted July 8, 2004.

Reprint are not available. Address correspondence to: Carl H. Rose, MD, Department of Obstetrics and Gynecology, University of Mississippi Medical Center, 2500 North State Street, Jackson, MS 39216–4505; e-mail: crose{at}ob-gyn.umsmed.edu.

Supported in part by the Vicksburg Hospital Medical Foundation, Vicksburg, Mississippi.

doi:10.1097/01.AOG.0000143262.85124.e8

	REFERENCES

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8. Gutsche BB, Cheek TG. Anesthetic considerations in preeclampsia-eclampsia. In: Shnider, Levinson, editors. Anesthesia for obstetrics. 3rd ed. Philadelphia (PA): Lippincott Williams and Wilkins; 1993. p. 305–36.

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This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Rose, C. H. Articles by Martin, J. N. Search for Related Content PubMed PubMed Citation Articles by Rose, C. H. Articles by Martin, J. N., Jr Related Collections Hypertension and PIH