Restrictive Fluid Therapy in Severe Preeclampsia

Pre-Eclampsia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02214186
• Other study ID #: CAPPesq 675.011
• Status: Completed
• Phase: N/A
• First received: July 16, 2014
• Last updated: September 8, 2015
• Start date: January 2014
• Est. completion date: May 2015

Study information

• Verified date: July 2014
• Source: University of Sao Paulo General Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: Brazil: Ethics Committee
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 42
• Est. completion date: May 2015
• Est. primary completion date: March 2015
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Supportive Care

Related Conditions & MeSH terms

• Eclampsia
• Pre-Eclampsia

Intervention

Other:
• 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.

Locations

Country	Name	City	State
Brazil	Hospital das Clínicas da Faculdade de Medicina da USP	São Paulo	SP

Sponsors (1)

Lead Sponsor	Collaborator
University of Sao Paulo General Hospital

Country where clinical trial is conducted

Brazil, 

References & Publications (13)

Aya AG, Mangin R, Vialles N, Ferrer JM, Robert C, Ripart J, de La Coussaye JE. Patients with severe preeclampsia experience less hypotension during spinal anesthesia for elective cesarean delivery than healthy parturients: a prospective cohort comparison. Anesth Analg. 2003 Sep;97(3):867-72. — View Citation

Aya AG, Vialles N, Ripart J. [Anesthesia and preeclampsia]. Ann Fr Anesth Reanim. 2010 May;29(5):e141-7. doi: 10.1016/j.annfar.2010.03.014. Epub 2010 May 15. French. — View Citation

Dennis AT, Solnordal CB. Acute pulmonary oedema in pregnant women. Anaesthesia. 2012 Jun;67(6):646-59. doi: 10.1111/j.1365-2044.2012.07055.x. Epub 2012 Mar 15. Review. — View Citation

Dyer RA, Piercy JL, Reed AR, Lombard CJ, Schoeman LK, James MF. Hemodynamic changes associated with spinal anesthesia for cesarean delivery in severe preeclampsia. Anesthesiology. 2008 May;108(5):802-11. doi: 10.1097/01.anes.0000311153.84687.c7. — View Citation

Mabie WC, Ratts TE, Sibai BM. The central hemodynamics of severe preeclampsia. Am J Obstet Gynecol. 1989 Dec;161(6 Pt 1):1443-8. — View Citation

Mårtensson J, Martling CR, Oldner A, Bell M. Impact of sepsis on levels of plasma cystatin C in AKI and non-AKI patients. Nephrol Dial Transplant. 2012 Feb;27(2):576-81. doi: 10.1093/ndt/gfr358. Epub 2011 Sep 12. — View Citation

Mehta RL, Kellum JA, Shah SV, Molitoris BA, Ronco C, Warnock DG, Levin A; Acute Kidney Injury Network. Acute Kidney Injury Network: report of an initiative to improve outcomes in acute kidney injury. Crit Care. 2007;11(2):R31. — View Citation

Pan PH, D'Angelo R. Anesthetic and analgesic management of mitral stenosis during pregnancy. Reg Anesth Pain Med. 2004 Nov-Dec;29(6):610-5. Review. — View Citation

Sibai B, Dekker G, Kupferminc M. Pre-eclampsia. Lancet. 2005 Feb 26-Mar 4;365(9461):785-99. Review. — View Citation

Sibai BM, Mabie WC. Hemodynamics of preeclampsia. Clin Perinatol. 1991 Dec;18(4):727-47. Review. — View Citation

Urbschat A, Obermüller N, Haferkamp A. Biomarkers of kidney injury. Biomarkers. 2011 Jul;16 Suppl 1:S22-30. doi: 10.3109/1354750X.2011.587129. Review. — View Citation

Vikse BE, Irgens LM, Leivestad T, Skjaerven R, Iversen BM. Preeclampsia and the risk of end-stage renal disease. N Engl J Med. 2008 Aug 21;359(8):800-9. doi: 10.1056/NEJMoa0706790. — View Citation

Xin C, Yulong X, Yu C, Changchun C, Feng Z, Xinwei M. Urine neutrophil gelatinase-associated lipocalin and interleukin-18 predict acute kidney injury after cardiac surgery. Ren Fail. 2008;30(9):904-13. doi: 10.1080/08860220802359089. — View Citation

* Note: There are 13 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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)	urine output during cesarean section (an average of 60 minutes)	Yes
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.	preoperative, first and second day postoperative	Yes
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	Postoperative renal dysfunction	Yes
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.	preoperative, first and second day postoperative	Yes
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.	preoperative, first and second day postoperative	Yes
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.	Proteinuria in severe pre-eclampsia in in pre-operative and post-operative period	Yes
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.	preoperative, first and second day postoperative	Yes
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.	preoperative, first and second day postoperative	Yes
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.	preoperative, first and second day postoperative	Yes