Skip to content

Restrictive Fluid Therapy in Severe Preeclampsia

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

Status
Completed
Phases
NA
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT02214186
Enrollment
46
Registered
2014-08-12
Start date
2014-01-31
Completion date
2015-05-31
Last updated
2017-03-07

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Pre-Eclampsia

Keywords

Pre-Eclampsia, Acute Kidney Injury, Fluid Therapy, Anesthesia, Spinal

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.

Interventions

The intervention in this randomized clinical trial is fluid restriction during cesarean section. The restricted group will receive 250 mL of crystalloid during surgery.

Sponsors

University of Sao Paulo General Hospital
Lead SponsorOTHER

Study design

Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
SUPPORTIVE_CARE
Masking
NONE

Eligibility

Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No

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

Design outcomes

Primary

MeasureTime frameDescription
Postoperative Renal Dysfunction Evaluated by the Acute Kidney Injury Network (AKIN) IndexPostoperative renal dysfunctionRenal 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
Renal Function in Severe Preeclampsia With Restrictive Fluid Therapypreoperative, first and second day postoperativeRenal function evaluated through creatinine levels in three moments: preoperative, first and second postoperative days.

Secondary

MeasureTime frameDescription
Cystatin C as New Marker of Renal Injury in Preeclampsiapreoperative, first and second day postoperativeEvaluate 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.
Proteinuria in Severe Pre-eclampsia Submitted to Cesarean Section Under Different Regimes of HydrationProteinuria in severe pre-eclampsia in in pre-operative and post-operative periodProteinuria in severe pre-eclampsia submitted to cesarean section under different regimes of hydration. Analyses in pre-operative and post-operative period.
International Normalized Ratio (INR) of Prothrombin Time (PT) in Restrictive Fluid Management of Severe Preeclampsia During Cesarean Sectionpreoperative, first and second day postoperativeCompare 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.
Activated Partial Thromboplastin Time in Restrictive Fluid Management of Severe Preeclampsia During Cesarean Sectionpreoperative, first and second day postoperativeCompare 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.
Platelets in Restrictive Fluid Management of Severe Preeclampsiapreoperative, first and second day postoperativeCompare platelets count in the restrictive and liberal groups during the first and second post-operative days.
Neutrophil Gelatinase-associated Lipocalin (NGAL) as New Marker of Renal Injury in Preeclampsiapreoperative, first and second day postoperativeEvaluate 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.

Other

MeasureTime frameDescription
Urine Output During Cesarean Section in Severe Pre-eclampsiaurine output during cesarean section (an average of 60 minutes)Urine output during cesarean section in severe pre-eclampsia under two different regimes of hydration (restrictive and liberal)

Countries

Brazil

Participant flow

Pre-assignment details

We calculated the total sample size from a pilot study. Assuming a power of 80% and 95% confidence, the sample necessary to conduct the study was 21 patients in each group of interest. As we considered 10% as maximum margin of loss during follow-up, there were 23 patients enrolled in each group.

Participants by arm

ArmCount
Liberal Fluid Therapy
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.
23
Restrictive Fluid Therapy
The restrictive group will receive 250 mL of crystalloid solution during cesarean section. Restrictive Fluid Therapy: The intervention in this randomized clinical trial is fluid restriction during cesarean section. The restricted group will receive 250 mL of crystalloid during surgery.
23
Total46

Withdrawals & dropouts

PeriodReasonFG000FG001
Overall StudyLost to Follow-up11
Overall StudyProtocol Violation11

Baseline characteristics

CharacteristicRestrictive Fluid TherapyTotalLiberal Fluid Therapy
Age, Continuous33 years
STANDARD_DEVIATION 5
32.07 years
STANDARD_DEVIATION 6.77
31 years
STANDARD_DEVIATION 8
Body mass index (kg/m2)31.98 kg/m2
STANDARD_DEVIATION 5.58
32.88 kg/m2
STANDARD_DEVIATION 6.37
33.78 kg/m2
STANDARD_DEVIATION 7.17
Chronic hypertension
no
14 participants26 participants12 participants
Chronic hypertension
yes
9 participants20 participants11 participants
Diabetes Mellitus
no
18 participants32 participants14 participants
Diabetes Mellitus
yes
5 participants14 participants9 participants
Diastolic blood pressure (mmHg)104.80 mmHg
STANDARD_DEVIATION 15.75
102.42 mmHg
STANDARD_DEVIATION 13.75
100.05 mmHg
STANDARD_DEVIATION 11.75
Gender
Female
23 Participants46 Participants23 Participants
Gender
Male
0 Participants0 Participants0 Participants
Gestational age (weeks)36.7 weeks36.8 weeks36.9 weeks
Previous preeclampsia
no
12 participants26 participants14 participants
Previous preeclampsia
yes
11 participants20 participants9 participants
Systolic blood pressure (mmHg)170 mmHg
STANDARD_DEVIATION 20
165.5 mmHg
STANDARD_DEVIATION 18.5
161 mmHg
STANDARD_DEVIATION 17
Twin pregnancy
no
20 participants38 participants21 participants
Twin pregnancy
yes
3 participants5 participants2 participants

Adverse events

Event typeEG000
affected / at risk
EG001
affected / at risk
deaths
Total, all-cause mortality
— / —— / —
other
Total, other adverse events
0 / 210 / 21
serious
Total, serious adverse events
0 / 210 / 21

Outcome results

Primary

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

Time frame: Postoperative renal dysfunction

ArmMeasureGroupValue (NUMBER)
Liberal Fluid TherapyPostoperative Renal Dysfunction Evaluated by the Acute Kidney Injury Network (AKIN) IndexAKIN stage I7 participants
Liberal Fluid TherapyPostoperative Renal Dysfunction Evaluated by the Acute Kidney Injury Network (AKIN) IndexAKIN stage II2 participants
Liberal Fluid TherapyPostoperative Renal Dysfunction Evaluated by the Acute Kidney Injury Network (AKIN) IndexAKIN stage III1 participants
Restrictive Fluid TherapyPostoperative Renal Dysfunction Evaluated by the Acute Kidney Injury Network (AKIN) IndexAKIN stage I6 participants
Restrictive Fluid TherapyPostoperative Renal Dysfunction Evaluated by the Acute Kidney Injury Network (AKIN) IndexAKIN stage II4 participants
Restrictive Fluid TherapyPostoperative Renal Dysfunction Evaluated by the Acute Kidney Injury Network (AKIN) IndexAKIN stage III0 participants
p-value: <0.05Wilcoxon (Mann-Whitney)
Primary

Renal Function in Severe Preeclampsia With Restrictive Fluid Therapy

Renal function evaluated through creatinine levels in three moments: preoperative, first and second postoperative days.

Time frame: preoperative, first and second day postoperative

Population: Were included in the analysis the patients who violated the protocol and lost follow-up (intention to treat analysis)

ArmMeasureGroupValue (MEDIAN)
Liberal Fluid TherapyRenal Function in Severe Preeclampsia With Restrictive Fluid TherapyCreatinine preoperative0.69 mg/dl
Liberal Fluid TherapyRenal Function in Severe Preeclampsia With Restrictive Fluid TherapyCreatinine 1st post-operative0.99 mg/dl
Liberal Fluid TherapyRenal Function in Severe Preeclampsia With Restrictive Fluid TherapyCreatinine 2nd post-operative0.96 mg/dl
Restrictive Fluid TherapyRenal Function in Severe Preeclampsia With Restrictive Fluid TherapyCreatinine preoperative0.73 mg/dl
Restrictive Fluid TherapyRenal Function in Severe Preeclampsia With Restrictive Fluid TherapyCreatinine 1st post-operative0.93 mg/dl
Restrictive Fluid TherapyRenal Function in Severe Preeclampsia With Restrictive Fluid TherapyCreatinine 2nd post-operative0.84 mg/dl
p-value: <0.05Wilcoxon (Mann-Whitney)
Secondary

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.

Time frame: preoperative, first and second day postoperative

Population: The values are expressed in seconds and presented as a ration (R) with control patients.

ArmMeasureGroupValue (MEAN)Dispersion
Liberal Fluid TherapyActivated Partial Thromboplastin Time in Restrictive Fluid Management of Severe Preeclampsia During Cesarean SectionAPPT/R preoperative0.98 ratioStandard Deviation 0.13
Liberal Fluid TherapyActivated Partial Thromboplastin Time in Restrictive Fluid Management of Severe Preeclampsia During Cesarean SectionAPPT/R 1st post-operative day1.07 ratioStandard Deviation 0.1
Liberal Fluid TherapyActivated Partial Thromboplastin Time in Restrictive Fluid Management of Severe Preeclampsia During Cesarean SectionAPPT/R 2nd post-operative day1.07 ratioStandard Deviation 0.13
Restrictive Fluid TherapyActivated Partial Thromboplastin Time in Restrictive Fluid Management of Severe Preeclampsia During Cesarean SectionAPPT/R preoperative1.01 ratioStandard Deviation 0.08
Restrictive Fluid TherapyActivated Partial Thromboplastin Time in Restrictive Fluid Management of Severe Preeclampsia During Cesarean SectionAPPT/R 1st post-operative day1.03 ratioStandard Deviation 0.1
Restrictive Fluid TherapyActivated Partial Thromboplastin Time in Restrictive Fluid Management of Severe Preeclampsia During Cesarean SectionAPPT/R 2nd post-operative day1.01 ratioStandard Deviation 0.07
p-value: <0.05ANOVA
Secondary

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.

Time frame: preoperative, first and second day postoperative

ArmMeasureGroupValue (MEAN)Dispersion
Liberal Fluid TherapyCystatin C as New Marker of Renal Injury in PreeclampsiaCyst C preoperative1.73 mg/LStandard Deviation 0.6
Liberal Fluid TherapyCystatin C as New Marker of Renal Injury in PreeclampsiaCyst C 1st postoperative day1.93 mg/LStandard Deviation 0.8
Liberal Fluid TherapyCystatin C as New Marker of Renal Injury in PreeclampsiaCyst C 2nd postoperative day1.64 mg/LStandard Deviation 0.5
Restrictive Fluid TherapyCystatin C as New Marker of Renal Injury in PreeclampsiaCyst C preoperative1.99 mg/LStandard Deviation 0.61
Restrictive Fluid TherapyCystatin C as New Marker of Renal Injury in PreeclampsiaCyst C 1st postoperative day2.03 mg/LStandard Deviation 0.66
Restrictive Fluid TherapyCystatin C as New Marker of Renal Injury in PreeclampsiaCyst C 2nd postoperative day1.72 mg/LStandard Deviation 0.43
p-value: <0.05ANOVA
Secondary

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.

Time frame: preoperative, first and second day postoperative

Population: The values are expressed in seconds and presented as a ration (INR) with control patients.

ArmMeasureGroupValue (MEDIAN)
Liberal Fluid TherapyInternational Normalized Ratio (INR) of Prothrombin Time (PT) in Restrictive Fluid Management of Severe Preeclampsia During Cesarean SectionPT/INR preoperative1.00 ratio
Liberal Fluid TherapyInternational Normalized Ratio (INR) of Prothrombin Time (PT) in Restrictive Fluid Management of Severe Preeclampsia During Cesarean SectionPT/INR first post-operative day1.03 ratio
Liberal Fluid TherapyInternational Normalized Ratio (INR) of Prothrombin Time (PT) in Restrictive Fluid Management of Severe Preeclampsia During Cesarean SectionPT/INR seconde post-operative day1.0 ratio
Restrictive Fluid TherapyInternational Normalized Ratio (INR) of Prothrombin Time (PT) in Restrictive Fluid Management of Severe Preeclampsia During Cesarean SectionPT/INR preoperative0.95 ratio
Restrictive Fluid TherapyInternational Normalized Ratio (INR) of Prothrombin Time (PT) in Restrictive Fluid Management of Severe Preeclampsia During Cesarean SectionPT/INR first post-operative day0.95 ratio
Restrictive Fluid TherapyInternational Normalized Ratio (INR) of Prothrombin Time (PT) in Restrictive Fluid Management of Severe Preeclampsia During Cesarean SectionPT/INR seconde post-operative day0.95 ratio
p-value: <0.05Wilcoxon (Mann-Whitney)
Secondary

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.

Time frame: preoperative, first and second day postoperative

ArmMeasureGroupValue (MEDIAN)
Liberal Fluid TherapyNeutrophil Gelatinase-associated Lipocalin (NGAL) as New Marker of Renal Injury in PreeclampsiaNGAL 2nd post-operative day0.15 mg/L
Liberal Fluid TherapyNeutrophil Gelatinase-associated Lipocalin (NGAL) as New Marker of Renal Injury in PreeclampsiaNGAL preoperative0.16 mg/L
Liberal Fluid TherapyNeutrophil Gelatinase-associated Lipocalin (NGAL) as New Marker of Renal Injury in PreeclampsiaNGAL 1st post-operative day0.18 mg/L
Restrictive Fluid TherapyNeutrophil Gelatinase-associated Lipocalin (NGAL) as New Marker of Renal Injury in PreeclampsiaNGAL 2nd post-operative day0.15 mg/L
Restrictive Fluid TherapyNeutrophil Gelatinase-associated Lipocalin (NGAL) as New Marker of Renal Injury in PreeclampsiaNGAL preoperative0.15 mg/L
Restrictive Fluid TherapyNeutrophil Gelatinase-associated Lipocalin (NGAL) as New Marker of Renal Injury in PreeclampsiaNGAL 1st post-operative day0.21 mg/L
p-value: <0.05Wilcoxon (Mann-Whitney)
Secondary

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.

Time frame: preoperative, first and second day postoperative

ArmMeasureGroupValue (MEAN)Dispersion
Liberal Fluid TherapyPlatelets in Restrictive Fluid Management of Severe PreeclampsiaPlatelets preoperative194400 thrombocytes/mm3Standard Deviation 77867
Liberal Fluid TherapyPlatelets in Restrictive Fluid Management of Severe PreeclampsiaPlatelets 1st postoperative day183250 thrombocytes/mm3Standard Deviation 83234
Liberal Fluid TherapyPlatelets in Restrictive Fluid Management of Severe PreeclampsiaPlatelets 2nd postoperative day192850 thrombocytes/mm3Standard Deviation 80692
Restrictive Fluid TherapyPlatelets in Restrictive Fluid Management of Severe PreeclampsiaPlatelets preoperative207941 thrombocytes/mm3Standard Deviation 71371
Restrictive Fluid TherapyPlatelets in Restrictive Fluid Management of Severe PreeclampsiaPlatelets 1st postoperative day201118 thrombocytes/mm3Standard Deviation 61687
Restrictive Fluid TherapyPlatelets in Restrictive Fluid Management of Severe PreeclampsiaPlatelets 2nd postoperative day221824 thrombocytes/mm3Standard Deviation 62925
p-value: >0.05ANOVA
Secondary

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.

Time frame: Proteinuria in severe pre-eclampsia in in pre-operative and post-operative period

ArmMeasureGroupValue (MEDIAN)
Liberal Fluid TherapyProteinuria in Severe Pre-eclampsia Submitted to Cesarean Section Under Different Regimes of HydrationProteinuria 1st post-operative day0.15 g/dl
Liberal Fluid TherapyProteinuria in Severe Pre-eclampsia Submitted to Cesarean Section Under Different Regimes of HydrationProteinuria pre-operative0.46 g/dl
Liberal Fluid TherapyProteinuria in Severe Pre-eclampsia Submitted to Cesarean Section Under Different Regimes of HydrationProteinuria 2nd post-operative day0.20 g/dl
Restrictive Fluid TherapyProteinuria in Severe Pre-eclampsia Submitted to Cesarean Section Under Different Regimes of HydrationProteinuria pre-operative2.62 g/dl
Restrictive Fluid TherapyProteinuria in Severe Pre-eclampsia Submitted to Cesarean Section Under Different Regimes of HydrationProteinuria 1st post-operative day0.40 g/dl
Restrictive Fluid TherapyProteinuria in Severe Pre-eclampsia Submitted to Cesarean Section Under Different Regimes of HydrationProteinuria 2nd post-operative day0.45 g/dl
p-value: <0.05Wilcoxon (Mann-Whitney)
Other Pre-specified

Urine Output During Cesarean Section in Severe Pre-eclampsia

Urine output during cesarean section in severe pre-eclampsia under two different regimes of hydration (restrictive and liberal)

Time frame: urine output during cesarean section (an average of 60 minutes)

ArmMeasureValue (MEDIAN)
Liberal Fluid TherapyUrine Output During Cesarean Section in Severe Pre-eclampsia116 ml/h
Restrictive Fluid TherapyUrine Output During Cesarean Section in Severe Pre-eclampsia80 ml/h
p-value: <0.05Wilcoxon (Mann-Whitney)

Source: ClinicalTrials.gov · Data processed: Feb 26, 2026