preeclampsia-eclampsia admitted to critical care unit

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678432AUTHOR’S QUERY SHEET

Author(s): J. Rojas-Suarez and P. Vigil-De Gracia Article title: Pre-eclampsia-eclampsia admitted to critical care unitArticle no: DJMF 678432Enclosures: 1) Query sheet 2) Article proofs 3) Track changes manuscript showing language editing

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RID Given Names Surname Suffix1. José Rojas-Suarez2. Paulino Vigil-De Gracia

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Journal of Maternal-Fetal and Neonatal Medicine, 2012; Early Online: 1–4© 2012 Informa UK, Ltd.ISSN 1476-7058 print/ISSN 1476-4954 onlineDOI: 10.3109/14767058.2012.678432

Objective: To evaluate women with hypertensive disorder admitted to critical care unit. Methods: This study was carried out in Cartagena, Colombia, between January 2006 and December 2009. Patients were divided into 4 groups; severe pre-eclampsia, eclampsia, HELLP syndrome and HELLP with eclampsia (HEEH). Result: A total of 217 cases were admitted. The admitting diag-noses were severe pre-eclampsia without HELLP syndrome (39.2%), HELLP syndrome without eclampsia (33.6%), eclampsia without HELLP syndrome (20.3%) and Eclampsia with HELLP syndrome or HEEH (6.9%). Groups were similar with respect to parity (p = 0.25), gestational age (p = 0.11), cesarean section (p = 0.58), mechanical ventilation (p = 0.54), level of systolic (p = 0.48) and diastolic blood pressure (p = 0.15) and inotropic support (p = 0.32). Average total duration of hospitalization was significantly different among groups, more time in women with HEEH (p = 0.001). Multiple organ dysfunctions was diag-nosed > 70% of all women admitted to intensive care, but was significantly more frequent in patients with HELLP syndrome and HEEH (p = 0.001). There were 5 maternal deaths (2.3%). Causes of maternal death were intracranial hemorrhage (3), intra-abdominal bleeding (1) and pulmonary complications (1). Conclusion: Women with HELLP syndrome with or without eclampsia are associated with major morbidity and mortality. Therefore, the maternal outcome in eclampsia is influenced for HELLP syndrome.

Keywords: Maternal Mortality, Eclampsia, HELLP syndrome, critical care unit pre-eclampsia-eclampsia

IntroductionHypertensive disorders of pregnancy affect about 10% of all preg-nant women around the world [1].

Hypertension in pregnancy is the first-leading cause of morbidity and mortality in Latin America and Caribbean [2], and is a major risk factor for fetal morbidity and mortality [3]. About 63,000 women worldwide die every year because of eclampsia and pre-eclampsia [4], with 99% of these deaths occurring in low income countries.

The HELLP syndrome represents a severe form of pre-eclampsia-eclampsia, and is characterized by hemolysis, elevated liver enzymes and low platelets [5]. Eclampsia is defined as the occurrence in a woman with pre-eclampsia of seizures that cannot be attributed to other causes [3] and HELLP/Eclampsia or Eclampsia/HELLP (HE/EH) is defined as the presence of eclampsia more HELLP syndrome in the same woman [6]. Like eclampsia, HELLP syndrome can cause significant morbidity and

mortality for both mother and fetus. Either one by itself consti-tutes an obstetric emergency. However, both at the same time could be fatal [6].

Worldwide, it has been considered that eclampsia is the final expression of pre-eclampsia and that represents the worst prog-nosis for these women. Thus, for decades magnesium sulphate have been given to women with pre-eclampsia, in the belief that they reduce the risk of seizure, and so improve outcome. There is evidence to support that reduce the fits, and maternal mortality although the differences were not significant [7]. A recent review of published cases [6] suggests that in maternal mortality by eclampsia, the management to avoid seizures in women with pre-eclampsia syndrome is not the main goal, except in patients with HELLP syndrome.

The present study was carried out to find the trends of maternal complications and deaths due to severe pre-eclampsia, eclampsia, HELLP syndrome and concurrent HELLP with eclampsia in women admitted to critical care unit.

Material and methodsThis is a retrospective study that included 217 consecutive cases. This study was carried out in the intensive care unit from the Clínica de Maternidad Rafael Calvo, Cartagena, Colombia, between January 2006 and December 2009. The local Ethic Committee approve this study. We included only women admitted to the critical care unit. Patients were divided into 4 groups:

A-Severe pre-eclampsia without HELLP syndrome.B-Eclampsia without HELLP syndrome.C-HELLP syndrome without eclampsia.D-Eclampsia more HELLP syndrome (HE/EH complication).

Severe pre-eclampsia was defined as elevated blood pressure (at least 140/90 mm Hg) with proteinuria (a dipstick reading of 2+ or more) in association with one o more of the following: headache, visual disturbances, epigastric pain, pulmonary edema, acute renal insufficiency [3,8]. A blood pressure of 160/110 mmHg or higher with proteinuria in the absence of any of the other features was also classified as severe pre-eclampsia [3,8].

Eclampsia was defined as the report of convulsion or seizures during pregnancy or postpartum in a woman with pre-eclampsia that cannot be attributed to other causes [3,8].

HELLP syndrome was determined by the presence pre-eclampsia in association with thrombocytopenia

ORIGINAL ARTICLE

Pre-eclampsia-eclampsia admitted to critical care unitJosé Rojas-Suarez1 & Paulino Vigil-De Gracia2

1Critical Care Unit, Clínica de Maternidad Rafael Calvo. Grupo de Investigación en Cuidados Intensivos y Obstetricia, Universidad de Cartagena, Cartagena, Colombia and 2Critical Care Unit, department of Obstetrics and Gynecology, Caja de Seguro Social, Panama

AQ1

Correspondence: Paulino Vigil-De Gracia, Critical Care Unit, department of Obstetrics and Gynecology, Caja de Seguro Social, Apartado Postal: 0823-03828, Panama. Phone: 507 66143240. E-mail: [email protected]

(Received 21 October 2011; revised 12 December 2011; accepted 13 March 2012)

Journal of Maternal-Fetal and Neonatal Medicine

2012

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© 2012 Informa UK, Ltd.

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Eclampsia and HELLP syndrome in critical care

J. Rojas-Suarez and P. Vigil-De Gracia

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2 J. Rojas-Suarez and P. Vigil-De Gracia


(<150,000 cells/µl), hemolysis, and hepatic dysfunction (elevated transaminases and lactic dehydrogenase activities).

HELLP/Eclampsia or Eclampsia/HELLP (HE/EH) was defined as the presence of eclampsia and HELLP syndrome in a woman.

Demographic data included maternal age, parity, gestational age, and associated medical conditions. Records were reviewed for presenting symptoms, laboratory findings, maternal compli-cations and perinatal deaths.

Acute renal insufficiency was diagnosed in the presence of oliguria-anuria in association with severe reduction in renal func-tion (serum creatinine ≥ 1.2 mg/dl and reduced creatinine clear-ance). Pulmonary edema was diagnosed according to the presence of clinical and radiographic findings; and congestive heart failure was diagnosed with the previous signs and symptoms and respiratory difficulty as new onset of difficulty breathing, as evidenced by tachy-pnea, or dyspnea or low peripheral oxygen saturation. Coagulopathy was defined as clinically abnormal bleeding or a laboratory diagnosis of a coagulation abnormality. Multiple organ dysfunctions were defined as at least two organ systems dysfunction (cardiovascular, respiratory, neurological, hematological, renal, metabolic, hepatic).

Laboratory evaluation included serial measurement of liver function tests, complete blood cell count, coagulation profile, and renal function tests. All women received intensive monitoring of blood pressure, cardiac and general status.

Management of severe pre-eclampsia, eclampsia, and HELLP syndrome included bed rest; to prevent or avoid seizure, all women initially received magnesium sulfate as a 4 g intravenous

loading dose followed by 1 g intravenous per hour before delivery, intrapartum and for 24 h postpartum. Labetalol and Nifedipine were used as antihypertensives in these patients, some cases required sodium nitroprusside or nitroglycerin in low dose.

A plasma volume expansion with saline solution was used in all women studied to maintain adequate intravascular volume. In the presence of oliguria one or two fluid boluses of 300–500 ml are administered.

All statistical analysis was performed with the use of EPI-Info (version 3.5.1, 2008). The two groups were compared with use of analysis of variance, the Mann–Whitney/Wilconxon test, Fisher’s exact test, the χ2-test as appropriate. Each category was compared among the different groups. All significance tests were two-tailed, with an α level of 0.05.

ResultsDuring the study period there are 51,084 births and 217 (0.42%) women with pre-eclampsia-eclampsia were admitted to critical care unit. The admitting diagnoses were severe pre-eclampsia without HELLP syndrome (39.2%), HELLP syndrome without eclampsia (33.6%), eclampsia without HELLP syndrome (20.3%) and Eclampsia with HELLP syndrome or HEEH (6.9%). Groups were similar with respect to parity, gestational age, cesarean section, mechanical ventilation, level of blood pressure and inotropic support (Tables I and II). One hundred seventy-four women in total were delivered by caesarean section (80.2%).

Table I. General characteristics.N Group 1 (85) Group 2 (44) Group 33) Group 4 (15) pAge year (SD) 26 (7) 22.2 (8.2) 25.1 (6.4) 21.5 (6.8) 0.01Parity (SD) 1.9 (1.5) 1.4 (1) 1.9 (1.4) 1.6 (0.7) 0.25Women with pregnancy at ICU* N (%) 21 (24.7) 6 (13.6) 7 (9.6) 0 (0) 0.01Week’s Gestation (SD) 32.8 (5.4) 35.2 (3.8) 33.4 (6.3) 34.7 (4.1) 0.11Cesarean (%) 81 84 75 87 0.58SBP (SD) 159 (22) 153 (22) 154 (20) 158 (28) 0.48DBP (SD) 109 (15) 105 (16) 109 (14) 114 (20) 0.15Hemoglobin (SD) 10 (2.3) 10.9 (1.8) 9.3 (2.5) 10.3 (2,4) 0.01Platelets 215,000 265,000 79,000 86,000 0.001Perinatal Deaths N (%) 16(18.8) 5(11.4) 14(19.1) 1(6.7) 0.42Group 1: Severe pre-eclampsia without HELLP syndrome.Group 2: Eclampsia without HELLP syndrome.Group 3: HELLP syndrome without eclampsia.Group 4: HELLP syndrome with eclampsia or HEEH.*Admitted before delivery to intensive critical unit.SBP, Systolic blood pressure, mmHg; DBP, diastolic blood pressure.

Table II. Interventions in the intensive care unit.Group 1 (85) Group 2 (44) Group 3 (73) Group 4 (15) p

Stay ICU days (SD) 4.4 (6.8) 3.3 (2.2) 4.8 (3.2) 6.9 (6) 0.001Mechanical Ventilation N (%) 10 (11.8) 9 (20.5) 10 (13.7) 3 (20.0) 0.54Inotropic support N (%) 3 (3.5) 1 (2.3) 4 (5.5) 2 (13.3) 0.32Total blood transfusion (%) 15 (18) 3 (7) 37 (51) 7 (47) 0.001Platelets transfusion (%) 3 (3.5) 0 (0) 14 (19) 2 (13.3) 0.001Red cells transfusion (%) 15 (17.6) 3 (7) 32 (44) 7 (47) 0.001MOF (%) 60 (71) 31 (70) 71 (97) 14 (93) 0.001≥3 OF % 30 (35) 18 (41) 42 (57) 12 (80) 0.001Deaths N (%) 1 (1.1) 1 (2.2) 2 (2.7) 1 (6.7) 0.6Group 1: Severe pre-eclampsia without HELLP syndrome.Group 2: Eclampsia without HELLP syndrome.Group 3: HELLP syndrome without eclampsia.Group 4: HELLP syndrome with eclampsia or HEEH.ICU, Intensive care unit; MOF, multiple organic failure (≥2 organic failure); OF, organic failure.

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Eclampsia and HELLP syndrome in critical care 3

© Informa UK, Ltd.

The average maternal age was 24.6 ± 7 years; significantly the groups with eclampsia without HELLP syndrome were younger, Table I. Significantly, women with HELLP syndrome without eclampsia or eclampsia with HELLP syndrome were admitted post delivery at the critical care unit.

Average total duration of hospitalization at the critical care unit was significantly different among groups, less time to eclampsia without HELLP syndrome and more time to HEEH (eclampsia with HELLP syndrome), Table II.

The hemoglobin concentration was lower in women with HELLP syndrome, and the use of transfusion of blood compo-nents was statistically significant more frequent in the group with HELLP syndrome and HEEH (Table II). Multiple organ dysfunc-tions was diagnosed >70% of all women admitted to intensive care, but was significantly more frequent in patients with HELLP syndrome without eclampsia and HEEH. Three o more organ dysfunctions were statistically significant in the group with eclampsia more HELLP syndrome (HEEH), Table II.

The perinatal deaths were similar among groups, Table I.There were 5 maternal deaths (2.3%), Table II. Causes of

maternal death were: 3 cases with intracranial hemorrhage [eclampsia with HELLP syndrome (1), HELLP syndrome (1), and severe pre-eclampsia (1)], one case with intra-abdominal bleeding (HELLP syndrome) and one case with pulmonary complications secondary to bronco aspiration (eclampsia).

CommentsThis observational study shows that 0.4% of women (pregnancy/post partum) attended in our hospital are admitted to intensive care unit with pre-eclampsia-eclampsia. Furthermore, patients with HELLP syndrome with or without eclampsia represent the most important complication because were associated with major morbidity and mortality in women with pre-eclampsia-eclampsia.

There are statistically significant fewer women with HELLP syndrome admitted with pregnancy to intensive care unit, they were admitted mainly post delivery. This may be due to early referral of high-risk patients, rapid pregnancy termination and could explain our mortality rate relatively low. There is limited information available in the literature about maternal outcomes in pre-eclampsia-eclampsia-HELLP syndrome admitted at inten-sive care unit.

The term severe maternal morbidity, has been used to refer to complications occurring during pregnancy, delivery or puerperium that may be life-threatening if not treated with adequate medical care, this category include women admitted to an intensive care unit during pregnancy or puerperium who needs intensive life-saving treatment [9,10]. Pregnant patients account for a small but significant number of intensive care unit admissions. Thus, an indicator of pronounced maternal morbidity is obstetric transfer to the intensive care unit [11]. pre-eclampsia-eclampsia who develops pulmonary edema, oliguria or acute renal failure, hepatic hemorrhage, persistent hypertension, neurologic dysfunction or cerebral edema may require invasive hemodynamic monitoring and can benefit from being closely managed in the intensive care unit setting [11].

Eclampsia it is a common problem in developing countries because illiteracy, lack of health awareness and education, poverty, and superstitious beliefs prevent women from seeking medical advice during pregnancy. We therefore believe that the reduction in incidence of eclampsia in some countries has occurred because women with severe pre-eclampsia and HELLP syndrome are being managed better with quick birth and according to guidelines

including the pregnancy termination and are thus prevented from having an eclamptic fit. However, to manage women with HELLP syndrome the first step is the diagnosis and unfortunately in developing countries this diagnosis is made very late or not made. Then, it is possible that in developing countries a lot of death by eclampsia have HELLP syndrome. The present study found major morbidity and mortality in women with HELLP syndrome and less complication in women with eclampsia without HELLP syndrome; however when both complications are present in the same patient exist a major risk of maternal morbidity and mortality. Therefore, prevention or control of fits is very impor-tant in patients with severe pre-eclampsia, especially when exist the diagnosed of HELLP syndrome.

In the present study, 15% of patients received mechanical ventilation; this is comparable with some reports [12]. The median length of stay in the intensive care unit was 4 days; women with HELLP syndrome more eclampsia (HEEH) significantly stays more time in the intensive care unit. Patients with HELLP syndrome with or without eclampsia received significantly more blood products transfusions. Interestingly, eclampsia group received less packed red cell, platelets or transfusion of blood products than the other three groups. Furthermore, there were five maternal deaths in this study, representing a mortality rate of 2.3% and three deaths were in patients with HELLP syndrome.

In the evaluation of multiple organ failure with three or more organ failures, the cases with HELLP syndrome with or without eclampsia had significantly higher percentages. However, the major risk is for eclampsia with HELLP syndrome (HEEH). Then, according to our outcomeshigher multiple organ failure in women with HELLP syndrome and mainly in patients with HEEH confirms that the worst prognostic in women with pre-eclampsia-eclampsia is produced by HELLP syndrome not by eclampsia.

Studies analyzing MOF in pre-eclampsia-eclampsia patients are urgently needed in order to adopt more effective strategies for reducing maternal mortality in developing countries. Findings of the present study indicate that such strategies should be oriented particularly toward early treatment of pre-eclampsia-eclampsia by general doctor and obstetrician-gynecologist providing prenatal and delivery care.

Eclampsia is a potentially fatal disorder of pregnant women that has been prevalent since the Hippocrates, but the preva-lence varies widely [13]. It is a common problem in developing countries. In those countries most pre-eclampsia with HELLP syndrome cases remains unrecognized until severe complica-tions, such as eclampsia, occur.

HELLP syndrome is an enigmatic condition, and its etiopatho-genesis is not completely understood and can be responsible for a multiplicity of adverse outcomes including cerebral hemorrhage/stroke, cardiopulmonary compromise/failure, renal failure, liver hematoma or rupture, placental abruption, preterm delivery and death of the mother [14,15]. The risk of serious morbidity correlates usually with increasingly severe signs, symptoms, and laboratory abnormalities, especially the platelets count [16,17]. Maternal morbidity is greatest and maternal mortality most likely when HELLP syndrome deteriorates to a class 1 (50,000 or less platelets [5,18]),. Delivery is the cornerstone of therapy, however in some cases the diagnosis of HELLP syndrome is made post eclampsia or after any complications.

Optimal maternal and fetal outcomes are dependent on prompt recognition and treatment of HELLP syndrome. In women with pre-eclampsia is very important diagnose HELLP syndrome and the pregnancy termination can be the better treatment in this

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4 J. Rojas-Suarez and P. Vigil-De Gracia


group of patients. Patients with suspected HELLP syndrome should be hospitalized immediately and observed in a labor and delivery unit. This is a very important step to reduce eclampsia and maybe deaths by pre-eclampsia-eclampsia.

Of the limitations of this study, the first is that is an obser-vational study, not a clinical trial study; then the outcomes can be interpreted with caution. A second limitation is that relevant cases may have been not admitted to critical care unit. Finally, the great of this study is that there are few studies about this topic; the number of cases is large enough to be able to find differences among the classification groups, furthermore the methodology is comprehensive and reproducible.

A team of obstetricians and other specialists such as, nephrologists, intensivists and neurologists, an anesthetist, and nurses with interest and experience are needed in an intensive care unit to protect preeclamptic-eclamptic mothers from death. Eclampsia, HELLP syndrome and special HEEH are very high-risk patients and require intensive monitoring, thorough investigation, and prompt and rational treatment whenever necessary. It is time that doctors took a new look at this major obstetric problem.

Declaration of interest: The authors report no declaration of interest.

References 1. WHO recommendations for prevention and treatment of pre-eclampsia

and eclampsia. World Health Organization 2011. 2. Khan KS, Wojdyla D, Say L, Gülmezoglu AM, Van Look PF. WHO

analysis of causes of maternal death: a systematic review. Lancet 2006;367:1066–1074.

3. Report of the National High Blood Pressure Education Program Working Group on High Blood Pressure in Pregnancy. Am J Obstet Gynecol 2000;183:S1–S22.

4. Langer A, Villar J, Tell K, Kim T, Kennedy S. Reducing eclampsia-related deaths–a call to action. Lancet 2008;371:705–706.

5. Isler CM, Rinehart BK, Terrone DA, Martin RW, Magann EF, Martin JN Jr. Maternal mortality associated with HELLP (hemolysis, elevated liver enzymes, and low platelets) syndrome. Am J Obstet Gynecol 1999;181:924–928.

6. Vigil-De Gracia P. Maternal deaths due to eclampsia and HELLP syndrome. Int J Gynecol Obstet 2009;104:90–94.

7. Magpie Trial Collaboration Group. 2002. Do Women with pre-eclampsia, and their babies, benefit from magnesium sulphate? The Magpie Trial: a randomized placebo-controlled trial. Lancet 359:1877–1890.

8. Brown MA, Lindheimer MD, de Swiet M, Van Assche A, Moutquin JM. The classification and diagnosis of the hypertensive disorders of pregnancy: statement from the International Society for the Study of Hypertension in Pregnancy (ISSHP). Hypertens Pregnancy 2001;20:IX–XIV.

9. Murphy DJ, Charlett P. Cohort study of near-miss maternal mortality and subsequent reproductive outcome. Eur J Obstet Gynecol Reprod Biol 2002;102:173–178.

10. Karnad DR, Guntupalli KK. Critical illness and pregnancy: review of a global problem. Crit Care Clin 2004;20:555–76, vii.

11. Collop NA, Sahn SA. Critical illness in pregnancy. An analysis of 20 patients admitted to a medical intensive care unit. Chest 1993;103:1548–1552.

12. Lataifeh I, Amarin Z, Zayed F, Al-Mehaisen L, Alchalabi H, Khader Y. Indications and outcome for obstetric patients’ admission to intensive care unit: a 7-year review. J Obstet Gynaecol 2010;30:378–382.

13. Leitch CR, Cameron AD, Walker JJ. The changing pattern of eclampsia over a 60-year period. Br J Obstet Gynaecol 1997;104:917–922.

14. Martin JN Jr, Rose CH, Briery CM. Understanding and managing HELLP syndrome: the integral role of aggressive glucocorticoids for mother and child. Am J Obstet Gynecol 2006; 195:914–934.

15. Keiser SD, Owens MY, Parrish MR et al. HELLP syndrome with and without eclampsia. Am J Perinatol In press.

16. Cavkaytar S, Ugurlu EN, Karaer A, Tapisiz OL, Danisman N. Are clinical symptoms more predictive than laboratory parameters for adverse maternal outcome in HELLP syndrome? Acta Obstet Gynecol Scand 2007;86:648–651.

17. Osmanagaoglu MA, Osmanagaoglu S, Ulusoy H, Bozkaya H. Maternal outcome in HELLP syndrome requiring intensive care management in a Turkish hospital. Sao Paulo Med J 2006;124:85–89.

18. Vigil-De Gracia P. 2001. Pregnancy complicated by pre-eclampsia-eclampsia with HELLP syndrome. Int J Gynaecol Obstet 72:17–23.

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ORIGINAL PAPER

Eclampsia and HELLP syndrome in critical care

José J. Rojas-Suarez, and Paulino P. Vigil-De Gracia

Pre-eclampsia-eclampsia admitted to critical care unit

José Rojas-Suarez1, & Paulino Vigil-De Gracia2

1Critical Care Unit, Clínica de Maternidad Rafael Calvo. Grupo de Investigación

en Cuidados Intensivos y Obstetricia, Universidad de Cartagena. , Cartagena,

Colombia and 2Critical Care Unit, department of Obstetrics and Gynecology. ,

Caja de Seguro Social, Panama, Panama

*Corresponding Authorence: Adress: Paulino Vigil-De Gracia, Critical Care Unit, department of Obstetrics and Gynecology, Caja de Seguro Social, Apartado Postal: 0823-03828, Panama, Panama. Phone: 507 66143240, . E-mail: [email protected]

Keywords: Maternal Mortality, Eclampsia, HELLP syndrome, critical care unit preeclampsia-eclampsia.

Objective: To evaluate women with hypertensive disorder admitted to critical care unit. Methods: This study was carried out in Cartagena, Colombia, between January 2006 and December 2009. Patients were divided into 4 groups; severe pre-eclampsiapreeclampsia, eclampsia, HELLP syndrome and HELLP with eclampsia (HEEH).

Result: A total of 217 cases were admitted. The admitting diagnoses were severe eclampsiapreeclampsia without HELLP syndrome (39.2%), HELLP syndrome eclampsia (33.6%), eclampsia without HELLP syndrome (20.3%) and Eclampsia HELLP syndrome or HEEH (6.9%). Groups were similar with respect to parity (p gestational age (pp = 0.11), cesarean section (pp = 0.58), mechanical ventilation level of systolic (pp = 0.48) and diastolic blood pressure (pp = 0.15) and inotropic

- 2 -

(pp = 0.32). Average total duration of hospitalization was significantly different groups, more time in women with HEEH (pp = 0.001). Multiple organ diagnosed > 70% of all women admitted to intensive care, but was significantly frequent in patients with HELLP syndrome and HEEH (pp = 0.001). There were 5 deaths (2.3%). Causes of maternal death were intracranial hemorrhage (3), intra-bleeding (1) and pulmonary complications (1).

Conclusion: Women with HELLP syndrome with or without eclampsia are major morbidity and mortality. Therefore, the maternal outcome in eclampsia is for HELLP syndrome.

Keywords: Maternal Mortality, Eclampsia, HELLP syndrome, critical care unit eclampsia-eclampsia

Introduction

Hypertensive disorders of pregnancy affect about 10% of all pregnant women

around the world [1].

Hypertension in pregnancy is the first-leading cause of morbidity and mortality in

Latin America and Caribbean [2], and is a major risk factor for fetal morbidity

and mortality [3]. About 63,000 women worldwide die every year because of

eclampsia and pre-eclampsia [4]preeclampsia, with 99% of these deaths occurring

in low income countries.

The HELLP syndrome represents a severe form of pre-eclampsiapreeclampsia-eclampsia, and is characterized by hemolysis, elevated liver enzymes and low Eclampsia is defined as the occurrence in a woman with pre-

seizures that cannot be attributed to other causes [3] and HELLP/Eclampsia or

Eclampsia/HELLP (HE/EH) is defined as the presence of eclampsia more HELLP

in the same woman [6]. Like eclampsia, HELLP syndrome can cause significant

Formatted: Font: 12 pt, Italic, Font color:Gray-80%

Formatted: Font: 12 pt, English (U.K.)

Formatted: Font: 12 pt, Font color: Auto






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and mortality for both mother and fetus. Either one by itself constitutes an

emergency. However, both at the same time could be fatal [6].

Worldwide, it has been considered that eclampsia is the final expression of pre-eclampsiapreeclampsia and that represents the worst prognosis for these women. Thus, for decades magnesium sulphate have been given to women with pre-eclampsiapreeclampsia, in the belief that they reduce the risk of seizure, and so improve outcome. There is evidence to support that reduce the fits, and maternal

mortality although the differences were not significant [7]. A recent review of

published cases [6] suggests that in maternal mortality by eclampsia, the

management to avoid seizures in women with pre-eclampsiapreeclampsia syndrome is not the main goal, except in patients with HELLP syndrome.

The present study was carried out to find the trends of maternal complications and deaths due to severe pre-eclampsiapreeclampsia, eclampsia, HELLP syndrome and concurrent HELLP with eclampsia in women admitted to critical care unit.

Material and methods

This is a retrospective study that included 217 consecutive cases. This study was carried out in the intensive care unit from the Clínica de Maternidad Rafael Calvo, Cartagena, Colombia, between January 2006 and December 2009. The local Ethic Committee approve this study. We included only women admitted to the critical care unit. Patients were divided into 4 groups:

A- Severe pre-eclampsiapreeclampsia without HELLP syndrome.

B- Eclampsia without HELLP syndrome.

C- HELLP syndrome without eclampsia.

D- Eclampsia more HELLP syndrome (HE/EH complication).

Severe pre-eclampsiapreeclampsia was defined as elevated blood pressure (at mm Hg) with proteinuria (a dipstick reading of 2+ or more) in association with

Formatted: Font: 12 pt, Font color: Auto,English (U.S.), Border: : (No border)

- 4 -

the following: headache, visual disturbances, epigastric pain, pulmonary edema,

insufficiency [3,8]. A blood pressure of 160/110 mmHg or higher with proteinuria

absence of any of the other features was also classified as severe pre-eclampsia

[3,8]preeclampsia.

Eclampsia was defined as the report of convulsion or seizures during pregnancy or postpartum in a woman with pre-eclampsiapreeclampsia that cannot be

attributed to other causes [3,8].

HELLP syndrome was determined by the presence pre-eclampsiapreeclampsia in association with thrombocytopenia (< 150 ,000 cells/µl), hemolysis, and hepatic dysfunction (elevated transaminases and lactic dehydrogenase activities).

HELLP/Eclampsia or Eclampsia/HELLP (HE/EH) was defined as the presence of eclampsia and HELLP syndrome in a woman.

Demographic data included maternal age, parity, gestational age, and associated medical conditions. Records were reviewed for presenting symptoms, laboratory findings, maternal complications and perinatal deaths.

Acute renal insufficiency was diagnosed in the presence of oliguria-anuria in association with severe reduction in renal function (serum creatinine ≥ 1.2 mg/dl and reduced creatinine clearance). Pulmonary edema was diagnosed according to the presence of clinical and radiographic findings; and congestive heart failure was diagnosed with the previous signs and symptoms and respiratory difficulty as new onset of difficulty breathing, as evidenced by tachypnea, or dyspnea or low peripheral oxygen saturation. Coagulopathy was defined as clinically abnormal bleeding or a laboratory diagnosis of a coagulation abnormality. Multiple organ dysfunctions were defined as at least two organ systems dysfunction (cardiovascular, respiratory, neurological, hematological, renal, metabolic, hepatic).

Laboratory evaluation included serial measurement of liver function tests, complete blood cell count, coagulation profile, and renal function tests. All

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women received intensive monitoring of blood pressure, cardiac and general status. Management of severe pre-eclampsiapreeclampsia, eclampsia, and HELLP syndrome included bed rest; to prevent or avoid seizure, all women initially received magnesium sulfate as a 4 gm intravenous loading dose followed by 1 gm intravenous per hour before delivery, intrapartum and for 24 hours postpartum. Labetalol and Nifedipine were used as antihypertensives in these patients, some cases required sodium nitroprusside or nitroglycerin in low dose.

A plasma volume expansion with saline solution was used in all women studied to maintain adequate intravascular volume. In the presence of oliguria one or two fluid boluses of 300– – 500 ml are administered.

All statistical analysis was performed with the use of EPI-Info (version 3.5.1, The two groups were compared with use of analysis of variance, the Mann–-Whitney/Wilconxon test, Fisher’s exact test, the χchi-square2 -test as appropriate. was compared among the different groups. All significance tests were two-tailed, αalpha level of 0.05.

Results

During the study period there are 51 51,084 births and 217 (0.42%) women with eclampsiapreeclampsia-eclampsia were admitted to critical care unit. The diagnoses were severe pre-eclampsiapreeclampsia without HELLP syndrome HELLP syndrome without eclampsia (33.6%), eclampsia without HELLP and Eclampsia with HELLP syndrome or HEEH (6.9%). Groups were similar parity, gestational age, cesarean section, mechanical ventilation, level of blood

inotropic support (Tables 1 I and II2). One hundred seventy-four women in total

were delivered by caesarean section (80.2%).

The average maternal age was 24.6 ± 7 years; significantly the groups with

without HELLP syndrome were younger, table Table I1. Significantly, women

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syndrome without eclampsia or eclampsia with HELLP syndrome were admitted post delivery at the critical care unit. Average total duration of hospitalization at the critical care unit was significantly different among groups, less time to eclampsia without HELLP syndrome and

HEEH (eclampsia with HELLP syndrome), table Table II2.

The haemoglobin concentration was lower in women with HELLP syndrome, and use of transfusion of blood components was statistically significant more frequent

group with HELLP syndrome and HEEH (table Table II2). Multiple organ

diagnosed > 70% of all women admitted to intensive care, but was significantly frequent in patients with HELLP syndrome without eclampsia and HEEH. Three organ dysfunctions were statistically significant in the group with eclampsia more

syndrome (HEEH), table Table II2.

The perinatal deaths were similar among groups, table Table I1.

There were 5 maternal deaths (2.3%), table Table II2. Causes of maternal death

3 cases with intracranial hemorrhage [eclampsia with HELLP syndrome (1), syndrome (1), and severe pre-eclampsiapreeclampsia (1)], one case with intra-bleeding (HELLP syndrome) and one case with pulmonary complications bronco aspiration (eclampsia).

Comments

This observational study shows that 0.4% of women (pregnancy/post partum) attended in our hospital are admitted to intensive care unit with pre-eclampsiapreeclampsia-eclampsia. Furthermore, patients with HELLP syndrome with or without eclampsia represent the most important complication because were associated with major morbidity and mortality in women with pre-eclampsiapreeclampsia-eclampsia. There are statistically significant fewer women with HELLP syndrome admitted pregnancy to intensive care unit, they were admitted mainly post delivery. This early referral of high-risk patients, rapid pregnancy termination and could explain mortality rate relatively low. There is limited information available in the











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maternal outcomes in pre-eclampsiapreeclampsia-eclampsia-HELLP syndrome admitted at intensive care unit. The term severe maternal morbidity, has been used to refer to complications occurring during pregnancy, delivery or puerperium that may be life-threatening if not treated with adequate medical care, this category include women admitted to an intensive care unit during pregnancy or puerperium who needs intensive life-

saving treatment [9,10]. Pregnant patients account for a small but significant

number of intensive care unit admissions. Thus, an indicator of pronounced

maternal morbidity is obstetric transfer to the intensive care unit [11]. pre-

eclampsiaPreeclampsia-eclampsia who develops pulmonary edema, oliguria or acute renal failure, hepatic hemorrhage, persistent hypertension, neurologic dysfunction or cerebral edema may require invasive hemodynamic monitoring

and can benefit from being closely managed in the intensive care unit setting [11].

Eclampsia it is a common problem in developing countries because illiteracy, lack health awareness and education, poverty, and superstitious beliefs prevent women seeking medical advice during pregnancy. We therefore believe that the reduction incidence of eclampsia in some countries has occurred because women with eclampsiapreeclampsia and HELLP syndrome are being managed better with quick birth and according to guidelines including the pregnancy termination and are thus prevented from having an eclamptic fit. However, to manage women with HELLP syndrome the first step is the diagnosis and unfortunately in developing countries this diagnosis is made very late or not made. Then, it is possible that in developing countries a lot of death by eclampsia have HELLP syndrome. The present study found major morbidity and mortality in women with HELLP syndrome and less complication in women with eclampsia without HELLP syndrome; however when both complications are present in the same patient exist risk of maternal morbidity and mortality. Therefore, prevention or control of fits important in patients with severe pre-eclampsiapreeclampsia, especially when diagnosed of HELLP syndrome.

In the present study, fifteen 15%percent of patients received mechanical

this is comparable with some reports [12]. The median length of stay in the

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unit was 4 days; women with HELLP syndrome more eclampsia (HEEH) significantly stays more time in the intensive care unit. Patients with HELLP syndrome with or without eclampsia received significantly more blood products transfusions. Interestingly, eclampsia group received less packed red cell, platelets or transfusion of blood products than the other three groups. Furthermore, there were five maternal deaths in this study, representing a mortality rate of 2.3% and three deaths were in patients with HELLP syndrome. In the evaluation of multiple organ failure with three or more organ failures, the cases with HELLP syndrome with or without eclampsia had significantly higher percentages. However, the major risk is for eclampsia with HELLP syndrome or (HEEH). Then, according to our outcomeshigher multiple organ failure in women with HELLP syndrome and mainly in patients with HEEH confirms that the worst prognostic in women with pre-eclampsiapreeclampsia-eclampsia is produced by HELLP syndrome not by eclampsia.

Studies analyzing MOF in pre-eclampsiapreeclampsia-eclampsia patients are urgently needed in order to adopt more effective strategies for reducing maternal mortality in developing countries. Findings of the present study indicate that such strategies should be oriented particularly toward early treatment of pre-eclampsiapreeclampsia-eclampsia by general doctor and obstetrician-gynecologist providing prenatal and delivery care. Eclampsia is a potentially fatal disorder of pregnant women that has been

prevalent since the Hippocrates, but the prevalence varies widely [13]. It is a

common problem in developing countries. In those countries most pre-eclampsiapreeclampsia with HELLP syndrome cases remains unrecognized until severe complications, such as eclampsia, occur.

HELLP syndrome is an enigmatic condition, and its etiopathogenesis is not completely understood and can be responsible for a multiplicity of adverse including cerebral hemorrhage/stroke, cardiopulmonary compromise/failure, renal liver hematoma or rupture, placental abruption, preterm delivery and death of the

[14,15]. The risk of serious morbidity correlates usually with increasingly severe

symptoms, and laboratory abnormalities, especially the platelets count [16,17].

morbidity is greatest and maternal mortality most likely when HELLP syndrome

to a class 1 (50 50,000 or less platelets [5,18]),. Delivery is the cornerstone of

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however in some cases the diagnosis of HELLP syndrome is made post eclampsia or after any complications. Optimal maternal and fetal outcomes are dependent on prompt recognition and treatment of HELLP syndrome. In women with pre-eclampsiapreeclampsia is diagnose HELLP syndrome and the pregnancy termination can be the better group of patients. Patients with suspected HELLP syndrome should be immediately and observed in a labor and delivery unit. This is a very important eclampsia and maybe deaths by pre-eclampsiapreeclampsia-eclampsia.

Of the limitations of this study, the first is that is an observational study, not a clinical trial study; then the outcomes can be interpreted with caution. A second limitation is that relevant cases may have been not admitted to critical care unit. Finally, the great of this study is that there are few studies about this topic; the number of cases is large enough to be able to find differences among the classification groups, furthermore the methodology is comprehensive and reproducible. A team of obstetricians and other specialists such as, nephrologists, intensivists and neurologists, an anesthetist, and nurses with interest and experience are needed in an intensive care unit to protect preeclamptic-eclamptic mothers from death. Eclampsia, HELLP syndrome and special HEEH are very high-risk patients and require intensive monitoring, thorough investigation, and prompt and rational treatment whenever necessary. It is time that doctors took a new look at this major obstetric problem.

Declaration of interest:

The authors report no declaration of interest.

References

1-. WHO recommendations for prevention and treatment of pre-eclampsia and World Health Organization 2011.

2. Khan KS, Wojdyla D, Say L, Gülmezoglu AM, Van Look PF. WHO analysis of causes of maternal death: a systematic review. Lancet 2006;367:1066–1074.




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3-. Report of the National High Blood Pressure Education Program Working Group on High Blood Pressure in Pregnancy. Am J Obstet Gynecol 2000;183:S1-–S22. 4. Langer A, Villar J, Tell K, Kim T, Kennedy S. Reducing eclampsia-related deaths–a call to action. Lancet 2008;371:705–706.

5. Isler CM, Rinehart BK, Terrone DA, Martin RW, Magann EF, Martin JN Jr. Maternal mortality associated with HELLP (hemolysis, elevated liver enzymes, and low platelets) syndrome. Am J Obstet Gynecol 1999;181:924–928. 6-. Vigil-De Gracia P. Maternal deaths due to eclampsia and HELLP Gynecol Obstet 2009;104:90-–94.

7-. Magpie Trial Collaboration Group. 2002. Do Women with pre-eclampsia, babies, benefit from magnesium sulphate? The Magpie Trial: a randomized controlled trial. Lancet 359:1877-–1890.

8. Brown MA, Lindheimer MD, de Swiet M, Van Assche A, Moutquin JM. The classification and diagnosis of the hypertensive disorders of pregnancy: statement from the International Society for the Study of Hypertension in Pregnancy (ISSHP). Hypertens Pregnancy 2001;20:IX–XIV.

9. Murphy DJ, Charlett P. Cohort study of near-miss maternal mortality and subsequent reproductive outcome. Eur J Obstet Gynecol Reprod Biol 2002;102:173–178.

10. Karnad DR, Guntupalli KK. Critical illness and pregnancy: review of a global problem. Crit Care Clin 2004;20:555–76, vii.

11. Collop NA, Sahn SA. Critical illness in pregnancy. An analysis of 20 patients admitted to a medical intensive care unit. Chest 1993;103:1548–1552. 12. Lataifeh I, Amarin Z, Zayed F, Al-Mehaisen L, Alchalabi H, Khader Y. Indications and outcome for obstetric patients’ admission to intensive care unit: a 7-year review. J Obstet Gynaecol 2010;30:378–382. 13. Leitch CR, Cameron AD, Walker JJ. The changing pattern of eclampsia over a 60-year period. Br J Obstet Gynaecol 1997;104:917–922.


























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14. Martin JN Jr, Rose CH, Briery CM. Understanding and managing HELLP syndrome: the integral role of aggressive glucocorticoids for mother and child. Am J Obstet Gynecol 2006;195:914–934. 15-. Keiser SD, Owens MY, Parrish MR et al. In press. HELLP syndrome with

without eclampsia. Am J Perinatol In press.http://dx.doi.org/10.1055/s-0030–

16. Cavkaytar S, Ugurlu EN, Karaer A, Tapisiz OL, Danisman N. Are clinical symptoms more predictive than laboratory parameters for adverse maternal outcome in HELLP syndrome? Acta Obstet Gynecol Scand 2007;86:648–651.

17. Osmanagaoglu MA, Osmanagaoglu S, Ulusoy H, Bozkaya H. Maternal outcome in HELLP syndrome requiring intensive care management in a Turkish hospital. Sao Paulo Med J 2006;124:85–89.

18-. Vigil-De Gracia P. 2001. Int J Gynaecol Obstet. 2001. Pregnancy eclampsia-eclampsia with HELLP syndrome. Int J Gynaecol Obstet 72(1):17–23.

Table I1. General characteristics.

(N) Group 1 (85) Group 2 (44) Group 3 (73) Group 4 (15) pP

Age year (SD) 26 (7) 22.2 (8.2) 25.1 (6.4) 21.5 ((6.8) 0.01

Parity (SD) 1.9 (1.5) 1.4 ((1) 1.9 ((1.4) 1.6 ((0.7) 0.25

Women with pregnancy at ICU* N ((%)

21 ((24.7) 6 ((13.6) 7 ((9.6) 0 ((0) 0.01

Week´s Gestation (SD)

32.8 ((5.4) 35.2 ((3.8) 33.4 ((6.3) 34.7 ((4.1) 0.11

Cesarean

(%)

81 84 75 87 0.58

SBP (SD) 159 ((22) 153 ((22) 154 ((20) 158 ((28) 0.48

DBP (SD) 109 ((15) 105 (16) 109 ((14) 114 ((20) 0.15

Hemoglobin (SD) 10 ((2.3) 10.9 ((1.8) 9.3 ((2.5) 10.3 ((2,4) 0.01

Platelets 215000 265000 79000 86000 0.001

Perinatal Deaths N ((%)

16(18.8) 5(11.4) 14(19.1) 1(6.7) 0.42

Group 1: Severe pre-eclampsiapreeclampsia without HELLP syndrome.























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Group 2: Eclampsia without HELLP syndrome.

Group 3: HELLP syndrome without eclampsia.

Group 4: HELLP syndrome with eclampsia or HEEH.

*Admitted before delivery to intensive critical unit.

SBP, = Systolic blood pressure, mmHg; DBP, = diastolic blood pressure.

Table II2. Interventions in the intensive care unit.

Group 1 (85)

Group 2 (44)

Group 3

(73)

Group 4 (15)

pP

Stay ICU days (SD) 4.4 (6.8) 3.3 (2.2) 4.8 (3.2) 6.9 (6) 0.001

Mechanical Ventilation N (%)

10 (11.8) 9 (20.5) 10 (13.7) 3 (20.0) 0.54

Inotropic support N (%)

3 (3.5) 1 (2.3) 4 (5.5) 2 (13.3) 0.32

Total blood

transfusion (%)

15 (18) 3 (7) 37 (51) 7 (47) 0.001

Platelets transfusion (%)

3 (3.5) 0 (0) 14 (19) 2 (13.3) 0.001

Red cells transfusion (%)

15 (17.6) 3 (7) 32 (44) 7 (47) 0.001

MOF (%) 60 (71) 31 (70) 71 (97) 14 (93) 0.001

≥ 3 OF % 30 (35) 18 (41) 42 (57) 12 (80) 0.001

Deaths N (%) 1 (1.1) 1 (2.2) 2 (2.7) 1 (6.7) 0.6

Group 1: Severe pre-eclampsiapreeclampsia without HELLP syndrome.

Group 2: Eclampsia without HELLP syndrome.

Group 3: HELLP syndrome without eclampsia.

Group 4: HELLP syndrome with eclampsia or HEEH.

ICU, = intensive care unit; MOF, = multiple organic failure (≥ 2 organic failure); OF, = organic failure.


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preeclampsia-eclampsia admitted to critical care unit

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