Corticosteroids for HELLP (haemolysis, elevated liver enzymes, low platelets) syndrome
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《英国医生杂志》
1 Uniformed Services University of Health Sciences, F Edward Hébert School of Medicine, Bethesda, MD, USA
Correspondence to: T L Clenney t_l_clenney@sar.med.navy.mil
Patient
Observational studies
We found six observational studies (one case report and five retrospective reviews) that assessed corticosteroids in women with HELLP syndrome (table 1).2-7 These studies showed improvement in laboratory variables such as platelet counts and aminotransferase levels and in some clinical measures such as urine output, mean arterial pressure, and length of hospital stay. Caution is needed in drawing conclusions based solely on retrospective studies, given their propensity for bias. Having considered the hierarchy of evidence (figure), we focused on prospective studies with the highest available evidence we could find.
Table 1 Observational studies of corticosteroids in patients with HELLP (haemolysis, elevated liver enzymes, low platelets) syndrome
Hierarchy of evidence8
Prospective studies
We assessed the three prospective studies on the basis of the method described by the Evidence Based Medicine Working Group.9 10 Table 2 details our assessment.
Table 2 Validity assessment of prospective studies
We identified one prospective randomised controlled trial of corticosteroids in women with HELLP syndrome antepartum. In this small study (25 participants) women given 10 mg dexamethasone every 12 hours had clinically and statistically significant increases in platelet counts and decreased levels of lactate dehydrogenase and alanine aminotransferase.11 Maternal oriented outcomes included improved urinary output. Investigators failed to note whether controls at 34 weeks' or less gestation received steroids for maturation of fetal lung. Any effect from this should have been minimised by the patients being randomised equally. However, because baseline platelet counts were significantly lower in the steroid group than in the control group (69.3 v 106.8, P = 0.034), the effectiveness of randomisation and allocation is uncertain.
Our search also identified two prospective randomised controlled studies that evaluated corticosteroids among women with HELLP syndrome post partum.12 13 In one of these studies 40 women were randomised to receive either two doses of dexamethasone 10 mg 12 hours apart followed by 5 mg at 24 and 36 hours (total 30 mg) or no corticosteroids.12 Women in the dexamethasone group had clinically and statistically significant increases in urine output and platelet counts. Likewise, lactate dehydrogenase and aspartate aminotransferase levels decreased significantly in this group. No mention is made of whether women at less than 34 weeks' gestation received dexamethasone for fetal indications. Randomisation should have minimised any effects.
In a more recent prospective randomised trial, 30 women with HELLP syndrome post partum also received two doses of dexamethasone 10 mg 12 hours apart followed by 5 mg at 24 and 36 hours or no corticosteroids.13 The dexamethasone group had meaningful improvements in several variables. At 48 hours post partum, women receiving dexamethasone had a significantly decreased mean arterial pressure (115 mm Hg v 94 mm Hg; P < 0.05) and mean asparatate aminotransferase level (100 IU/l v 50 IU/l; P < 0.05). During this time they also showed improvements in urine output (60 ml/h v 40 ml/h; P < 0.05) and mean platelet count (115 000 v 70 000; P < 0.05). The authors concluded that their findings supported high dose corticosteroid treatment of women with HELLP syndrome for 36 hours after delivery. They also noted that although three patients (one control) had infectious complications, there were no statistically significant differences in morbidity.
Outcome
Matchaba P, Moodley J. Corticosteroids for HELLP syndrome in pregnancy. Cochrane Database Syst Rev 2004;(1): CD002076.
Schlembach D, Munz W, Fischer T. Effect of corticosteroids on HELLP syndrome: a case report. J Perinatal Med 2000;28: 502-5.
Crane JM, Tabarsi B, Hutchens D. The maternal benefits of corticosteroids with HELLP (hemolysis, elevated liver enzymes, and low platelet count) syndrome. J Obstet Gynaecol Canada 2003;25: 650-5.
O'Brien JM, Milligan DA, Barton JR. Impact of high-dose corticosteroid therapy for patients with HELLP (hemolysis, elevated liver enzymes, and low platelet count) syndrome. Am J Obstet Gynecol 2000;183: 921-4.
Martin JN, Thigpen BD, Rose CH, Cushman J, Moore A, May WL. Maternal benefit of high-dose intravenous corticosteroid therapy for HELLP syndrome. Am J Obstet Gynecol 2003;189: 830-4.
Vigil-De Gracia P, Garcia-Caceres E. Dexamethasone in the post-partum treatment of HELLP syndrome. Int J Gynaecol Obstet 1997;59: 217-21.
Martin JN, Perry KG, Blake PG, May WA, Moore A, Roninette L. Better maternal outcomes are achieved with dexamethasone therapy for postpartum HELLP (hemolysis, elevated liver enzymes, and thrombocytopenia) syndrome. Am J Obstet Gynecol 1997;177: 1011-7.
Ebell MH, Siwek J, Weiss BD, et al. Strength of recommendation taxonomy (SORT): a patient-centered approach to grading evidence in the medical literature. J Fam Pract 2003;53: 111-20.
Guyatt GH, Sackett DL, Cook DJ. Users' guides to the medical literature: II. How to use an article about therapy or prevention: A. Are the results of the study valid? JAMA 1993;270: 2598-601.
Guyatt G, Cook D, Devereaux PJ, Meade M, Straus S. Therapy. In: Guyatt G, Rennie D, eds. Users' guide to the medical literature. Chicago: American Medical Association Press, 2002: 55-79.
Magann EF, Bass D, Chauhan SP, Sullivan DL, Martin RW, Martin JN Jr. Antepartum corticosteroids: disease stabilization in patients with the syndrome of hemolysis, elevated liver enzymes, and low platelets (HELLP). Am J Obstet Gynecol 1994;171: 1148-53.
Magann EF, Perry KG Jr, Meydrech EF, Harris RL, Chauhan SP, Martin JN Jr. Postpartum corticosteroids: accelerated recovery from the syndrome of hemolysis, elevated liver enzymes, and low platelets (HELLP). Am J Obstet Gynecol 1994;171: 1154-8.
Yalcin OT, Sener T, Hassa H, Ozalp S, Okur A. Effects of postpartum corticosteroids in patients with HELLP syndrome. Int J Gyn Obstet 1998:61: 141-8.
Novy MJ. Adverse effects of repeated administration of antenatal corticosteroids in nonhuman primates. Am J Obstet Gynecol 2001;185: 1276-7.
Aghajafari F, Murphy K, Willan A, Ohlsson A, Amankwali K, Matthews S, et al. Multiple courses of antenatal corticosteroids: a systematic review and meta-analysis. Am J Obset Gynecol 2001;185: 1073-80.
Thorp JA, Jones AM, Hunt C, Clark R. The effect of multidose antenatal betamethasone on maternal and infant outcomes. Am J Obstet Gynecol 2001;184; 196-202.(Timothy L Clenney, assist)
Correspondence to: T L Clenney t_l_clenney@sar.med.navy.mil
Patient
Observational studies
We found six observational studies (one case report and five retrospective reviews) that assessed corticosteroids in women with HELLP syndrome (table 1).2-7 These studies showed improvement in laboratory variables such as platelet counts and aminotransferase levels and in some clinical measures such as urine output, mean arterial pressure, and length of hospital stay. Caution is needed in drawing conclusions based solely on retrospective studies, given their propensity for bias. Having considered the hierarchy of evidence (figure), we focused on prospective studies with the highest available evidence we could find.
Table 1 Observational studies of corticosteroids in patients with HELLP (haemolysis, elevated liver enzymes, low platelets) syndrome
Hierarchy of evidence8
Prospective studies
We assessed the three prospective studies on the basis of the method described by the Evidence Based Medicine Working Group.9 10 Table 2 details our assessment.
Table 2 Validity assessment of prospective studies
We identified one prospective randomised controlled trial of corticosteroids in women with HELLP syndrome antepartum. In this small study (25 participants) women given 10 mg dexamethasone every 12 hours had clinically and statistically significant increases in platelet counts and decreased levels of lactate dehydrogenase and alanine aminotransferase.11 Maternal oriented outcomes included improved urinary output. Investigators failed to note whether controls at 34 weeks' or less gestation received steroids for maturation of fetal lung. Any effect from this should have been minimised by the patients being randomised equally. However, because baseline platelet counts were significantly lower in the steroid group than in the control group (69.3 v 106.8, P = 0.034), the effectiveness of randomisation and allocation is uncertain.
Our search also identified two prospective randomised controlled studies that evaluated corticosteroids among women with HELLP syndrome post partum.12 13 In one of these studies 40 women were randomised to receive either two doses of dexamethasone 10 mg 12 hours apart followed by 5 mg at 24 and 36 hours (total 30 mg) or no corticosteroids.12 Women in the dexamethasone group had clinically and statistically significant increases in urine output and platelet counts. Likewise, lactate dehydrogenase and aspartate aminotransferase levels decreased significantly in this group. No mention is made of whether women at less than 34 weeks' gestation received dexamethasone for fetal indications. Randomisation should have minimised any effects.
In a more recent prospective randomised trial, 30 women with HELLP syndrome post partum also received two doses of dexamethasone 10 mg 12 hours apart followed by 5 mg at 24 and 36 hours or no corticosteroids.13 The dexamethasone group had meaningful improvements in several variables. At 48 hours post partum, women receiving dexamethasone had a significantly decreased mean arterial pressure (115 mm Hg v 94 mm Hg; P < 0.05) and mean asparatate aminotransferase level (100 IU/l v 50 IU/l; P < 0.05). During this time they also showed improvements in urine output (60 ml/h v 40 ml/h; P < 0.05) and mean platelet count (115 000 v 70 000; P < 0.05). The authors concluded that their findings supported high dose corticosteroid treatment of women with HELLP syndrome for 36 hours after delivery. They also noted that although three patients (one control) had infectious complications, there were no statistically significant differences in morbidity.
Outcome
Matchaba P, Moodley J. Corticosteroids for HELLP syndrome in pregnancy. Cochrane Database Syst Rev 2004;(1): CD002076.
Schlembach D, Munz W, Fischer T. Effect of corticosteroids on HELLP syndrome: a case report. J Perinatal Med 2000;28: 502-5.
Crane JM, Tabarsi B, Hutchens D. The maternal benefits of corticosteroids with HELLP (hemolysis, elevated liver enzymes, and low platelet count) syndrome. J Obstet Gynaecol Canada 2003;25: 650-5.
O'Brien JM, Milligan DA, Barton JR. Impact of high-dose corticosteroid therapy for patients with HELLP (hemolysis, elevated liver enzymes, and low platelet count) syndrome. Am J Obstet Gynecol 2000;183: 921-4.
Martin JN, Thigpen BD, Rose CH, Cushman J, Moore A, May WL. Maternal benefit of high-dose intravenous corticosteroid therapy for HELLP syndrome. Am J Obstet Gynecol 2003;189: 830-4.
Vigil-De Gracia P, Garcia-Caceres E. Dexamethasone in the post-partum treatment of HELLP syndrome. Int J Gynaecol Obstet 1997;59: 217-21.
Martin JN, Perry KG, Blake PG, May WA, Moore A, Roninette L. Better maternal outcomes are achieved with dexamethasone therapy for postpartum HELLP (hemolysis, elevated liver enzymes, and thrombocytopenia) syndrome. Am J Obstet Gynecol 1997;177: 1011-7.
Ebell MH, Siwek J, Weiss BD, et al. Strength of recommendation taxonomy (SORT): a patient-centered approach to grading evidence in the medical literature. J Fam Pract 2003;53: 111-20.
Guyatt GH, Sackett DL, Cook DJ. Users' guides to the medical literature: II. How to use an article about therapy or prevention: A. Are the results of the study valid? JAMA 1993;270: 2598-601.
Guyatt G, Cook D, Devereaux PJ, Meade M, Straus S. Therapy. In: Guyatt G, Rennie D, eds. Users' guide to the medical literature. Chicago: American Medical Association Press, 2002: 55-79.
Magann EF, Bass D, Chauhan SP, Sullivan DL, Martin RW, Martin JN Jr. Antepartum corticosteroids: disease stabilization in patients with the syndrome of hemolysis, elevated liver enzymes, and low platelets (HELLP). Am J Obstet Gynecol 1994;171: 1148-53.
Magann EF, Perry KG Jr, Meydrech EF, Harris RL, Chauhan SP, Martin JN Jr. Postpartum corticosteroids: accelerated recovery from the syndrome of hemolysis, elevated liver enzymes, and low platelets (HELLP). Am J Obstet Gynecol 1994;171: 1154-8.
Yalcin OT, Sener T, Hassa H, Ozalp S, Okur A. Effects of postpartum corticosteroids in patients with HELLP syndrome. Int J Gyn Obstet 1998:61: 141-8.
Novy MJ. Adverse effects of repeated administration of antenatal corticosteroids in nonhuman primates. Am J Obstet Gynecol 2001;185: 1276-7.
Aghajafari F, Murphy K, Willan A, Ohlsson A, Amankwali K, Matthews S, et al. Multiple courses of antenatal corticosteroids: a systematic review and meta-analysis. Am J Obset Gynecol 2001;185: 1073-80.
Thorp JA, Jones AM, Hunt C, Clark R. The effect of multidose antenatal betamethasone on maternal and infant outcomes. Am J Obstet Gynecol 2001;184; 196-202.(Timothy L Clenney, assist)