Clinical trial NCT02214186: Restrictive Fluid Therapy in Severe Preeclampsia
Official title: Impact of Restrictive Fluid Therapy on Renal Function in Severe Preeclamptic Women Submitted to Cesarean Section Under Spinal Anesthesia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Pre-Eclampsia
Keywords: Pre-Eclampsia
Acute Kidney Injury
Fluid Therapy
Anesthesia, Spinal
Lead sponsor: University of Sao Paulo General Hospital
Sponsor class: OTHER
First posted: 2014-08-12
Enrollment: 46
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: SUPPORTIVE_CARE

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Renal Function in Severe Preeclampsia With Restrictive Fluid Therapy
timeFrame: preoperative, first and second day postoperative
measure: Postoperative Renal Dysfunction Evaluated by the Acute Kidney Injury Network (AKIN) Index
timeFrame: Postoperative renal dysfunction
Secondary outcomes:
measure: Neutrophil Gelatinase-associated Lipocalin (NGAL) as New Marker of Renal Injury in Preeclampsia
timeFrame: preoperative, first and second day postoperative
measure: Cystatin C as New Marker of Renal Injury in Preeclampsia
timeFrame: preoperative, first and second day postoperative
measure: Proteinuria in Severe Pre-eclampsia Submitted to Cesarean Section Under Different Regimes of Hydration
timeFrame: Proteinuria in severe pre-eclampsia in in pre-operative and post-operative period
measure: Platelets in Restrictive Fluid Management of Severe Preeclampsia
timeFrame: preoperative, first and second day postoperative
measure: International Normalized Ratio (INR) of Prothrombin Time (PT) in Restrictive Fluid Management of Severe Preeclampsia During Cesarean Section
timeFrame: preoperative, first and second day postoperative
measure: Activated Partial Thromboplastin Time in Restrictive Fluid Management of Severe Preeclampsia During Cesarean Section
timeFrame: preoperative, first and second day postoperative
Other outcomes:
measure: Urine Output During Cesarean Section in Severe Pre-eclampsia
timeFrame: urine output during cesarean section (an average of 60 minutes)
Locations:
city: São Paulo
country: Brazil
facility: Hospital das Clínicas da Faculdade de Medicina da USP
state: SP
Study officials:
affiliation: Hospital das Clínicas da Faculdade de Medicina da USP
name: Wallace A Da Silva, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Hospital das Clínicas da Faculdade de Medicina da USP
name: Fernando Bliacheriene, PHD
role: STUDY_CHAIR
affiliation: Hospital das Clínicas da Faculdade de Medicina da USP
name: Maria José C Carmona, PHD
role: STUDY_DIRECTOR
affiliation: Hospital das Clínicas da Faculdade de Medicina da USP
name: Carlo Victor A Varela, MD
role: STUDY_CHAIR
affiliation: Hospital das Clínicas da Faculdade de Medicina da USP
name: Paula C Scherer, MD
role: STUDY_CHAIR
affiliation: Hospital das Clínicas da Faculdade de Medicina da USP
name: Marcelo Luis A Torres, PHD
role: STUDY_DIRECTOR
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