Restrictive Fluid Therapy in Severe Preeclampsia

Study Overview
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Brief Summary
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Introduction: Pre-eclampsia is a multifactorial syndrome which occurs in hypertension and proteinuria in pregnant women over 20 weeks gestation. It is the leading cause of maternal complications such as pulmonary edema, which occurs in about 3% of severe preeclamptic having as one of the causes volume overload. Anesthetic procedures are frequent in this population, with replacement with crystalloid of the duct during cesarean section under spinal anesthesia for combat hypotension and hypovolemia manifested by oliguria. However, as water therapy have antagonistic effects on cardiopulmonary and renal systems is no doubt as to the benefits compared to conventional or restrictive pattern of fluid therapy on renal function. Objective: To compare the renal function of patients with severe preeclampsia who received restrictive fluid therapy during caesarean section, as well as evaluating the use of cystatin C and Neutrophil gelatinase-associated lipocalin (NGAL) as a predictor of renal damage in this population. Hypothesis: Intraoperative fluid restriction did not influence renal function of patients with severe preeclampsia undergoing cesarean section under spinal anesthesia.

Detailed Description
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Preeclampsia (PE) is the leading cause of morbidity and mortality worldwide during pregnancy. Fluid therapy for PE women during cesarean section is a controversial issue among medical specialists. The replacement with crystalloid fluids tool is traditionally used by anesthesiologists during cesarean section under spinal anesthesia for combat hypotension and hypovolemia manifested by oliguria. However, as crystalloid infusion has antagonistic effects on cardiopulmonary and renal systems, there is controversy regarding benefits over conventional and restrictive fluid therapy. Therefore, due to cardiovascular changes in severe PE, restrictive fluid therapy could possibly be beneficial, avoiding complications such as acute pulmonary edema. Currently, volume replacement during cesarean section in these patients is performed with volumes of about 1500 ml of crystalloid to decrease the chance of developing kidney injury or aggravating previous injury. However, it is not known in the literature whether the renal lesions that appear after birth in patients with PE are just due to the course of the disease itself or can be modified by fluid restriction during the conduct of anesthesia cesarean. Moreover, intraoperative fluid restriction (250 ml crystalloid) appears as an alternative to handling the patient with PEG, as already safely used in cardiac patients, such as patients with mitral valve stenosis. The security of fluid restriction in patients with PE comes from the fact that pre-eclamptic suffer fewer episodes of hypotension during cesarean section under spinal anesthesia, requiring less fluid input for this purpose. In addition, the pathophysiology of this disease points to a relative hypovolemia, once the delivery performed, with removal of the placenta, fluids kidnapped in excess to third space (tissue edema) will be redirected to the intravascular compartment, restoring homeostasis. Cystatin C and NGAL (Neutrophil gelatinase-associated lipocalin) arise as valid tools to predict the degree of renal injury. These molecules arise before the onset of renal injury, providing diagnostic and therapeutic actions that can reduce morbidity and mortality related to kidney failure, since some studies have shown that women in first pregnancy with PE are more likely to develop chronic kidney disease that pregnant women without PE.

Official Title
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Impact of Restrictive Fluid Therapy on Renal Function in Severe Preeclamptic Women Submitted to Cesarean Section Under Spinal Anesthesia

Conditions
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Pre-Eclampsia

Intervention / Treatment
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* Other: Restrictive Fluid Therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Severe PE was defined as at least one of the following criteria: systolic pressure ≥160 mmHg or diastolic pressure ≥110 mmHg, severe proteinuria (>5 g/24 h), oliguria (<500 ml/24 h), cerebral or visual disturbances, pulmonary edema, epigastric pain, hepatic rupture, impaired liver function, thrombocytopenia, hemolysis, elevated liver enzymes and low platelet count (HELLP) syndrome and evidence of fetal compromise. Exclusion Criteria: previous serum creatinine levels >1 mg/dl previous kidney disease contraindication to spinal anesthesia

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Supportive Care
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Liberal Fluid therapy<br>The liberal group will receive 1500 mL of crystalloid solution during the cesarean section. This is the non-intervention arm once that 1500 ml of crystalloid is the amount usually used during caesarean. | |
| Active Comparator: Restrictive Fluid Therapy<br>The restrictive group will receive 250 mL of crystalloid solution during cesarean section. | Other: Restrictive Fluid Therapy<br>* The intervention in this randomized clinical trial is fluid restriction during cesarean section. The restricted group will receive 250 mL of crystalloid during surgery.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Renal Function in Severe Preeclampsia With Restrictive Fluid Therapy | Renal function evaluated through creatinine levels in three moments: preoperative, first and second postoperative days. | preoperative, first and second day postoperative | 
| Postoperative Renal Dysfunction Evaluated by the Acute Kidney Injury Network (AKIN) Index | Renal dysfunction was stratified by the Acute Kidney Injury Network (AKIN) index in three stages, in terms of creatinine increase from baseline: stage 1 included an interval of 150-200%, stage 2 200%-300%, and stage 3 more than 300% or hemodialysis | Postoperative renal dysfunction | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Neutrophil Gelatinase-associated Lipocalin (NGAL) as New Marker of Renal Injury in Preeclampsia | Evaluate new marker of renal injury (NGAL) in the specific population of patients with severe preeclampsia, comparing the values of first and second postoperative days to baseline. | preoperative, first and second day postoperative | 
| Cystatin C as New Marker of Renal Injury in Preeclampsia | Evaluate new marker of renal injury (Cystatin C) in the specific population of patients with severe preeclampsia, comparing the values of first and second postoperative days to baseline. | preoperative, first and second day postoperative | 
| Proteinuria in Severe Pre-eclampsia Submitted to Cesarean Section Under Different Regimes of Hydration | Proteinuria in severe pre-eclampsia submitted to cesarean section under different regimes of hydration. Analyses in pre-operative and post-operative period. | Proteinuria in severe pre-eclampsia in in pre-operative and post-operative period | 
| Platelets in Restrictive Fluid Management of Severe Preeclampsia | Compare platelets count in the restrictive and liberal groups during the first and second post-operative days. | preoperative, first and second day postoperative | 
| International Normalized Ratio (INR) of Prothrombin Time (PT) in Restrictive Fluid Management of Severe Preeclampsia During Cesarean Section | Compare International Normalized Ratio (INR) of Prothrombin Time (PT) in the restrictive and liberal groups in preoperative, first and second day postoperative. PT is expressed in seconds and the entered values represented the INR of PT among study participants and a control population. | preoperative, first and second day postoperative | 
| Activated Partial Thromboplastin Time in Restrictive Fluid Management of Severe Preeclampsia During Cesarean Section | Compare activated partial thromboplastin time (APPT) and relation with control (R) in the restrictive and liberal groups. APPT is a laboratory test that evaluates the efficiency of the intrinsic pathway of coagulation. The unit of measure is seconds and the results are presented as relation (R) with control. | preoperative, first and second day postoperative | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Fluid Therapy, Pre-Eclampsia, Acute Kidney Injury, Anesthesia, Spinal