Pre-Eclampsia
Conditions
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
Study design
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Postoperative Renal Dysfunction Evaluated by the Acute Kidney Injury Network (AKIN) Index | Postoperative renal dysfunction | 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 |
| Renal Function in Severe Preeclampsia With Restrictive Fluid Therapy | preoperative, first and second day postoperative | Renal function evaluated through creatinine levels in three moments: preoperative, first and second postoperative days. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cystatin C as New Marker of Renal Injury in Preeclampsia | preoperative, first and second day postoperative | 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. |
| Proteinuria in Severe Pre-eclampsia Submitted to Cesarean Section Under Different Regimes of Hydration | Proteinuria in severe pre-eclampsia in in pre-operative and post-operative period | Proteinuria 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 Section | preoperative, first and second day postoperative | 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. |
| Activated Partial Thromboplastin Time in Restrictive Fluid Management of Severe Preeclampsia During Cesarean Section | preoperative, first and second day postoperative | 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. |
| Platelets in Restrictive Fluid Management of Severe Preeclampsia | preoperative, first and second day postoperative | Compare 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 Preeclampsia | preoperative, first and second day postoperative | 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Urine Output During Cesarean Section in Severe Pre-eclampsia | urine 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
| Arm | Count |
|---|---|
| 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 |
| Total | 46 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 1 | 1 |
| Overall Study | Protocol Violation | 1 | 1 |
Baseline characteristics
| Characteristic | Restrictive Fluid Therapy | Total | Liberal Fluid Therapy |
|---|---|---|---|
| Age, Continuous | 33 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 participants | 26 participants | 12 participants |
| Chronic hypertension yes | 9 participants | 20 participants | 11 participants |
| Diabetes Mellitus no | 18 participants | 32 participants | 14 participants |
| Diabetes Mellitus yes | 5 participants | 14 participants | 9 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 Participants | 46 Participants | 23 Participants |
| Gender Male | 0 Participants | 0 Participants | 0 Participants |
| Gestational age (weeks) | 36.7 weeks | 36.8 weeks | 36.9 weeks |
| Previous preeclampsia no | 12 participants | 26 participants | 14 participants |
| Previous preeclampsia yes | 11 participants | 20 participants | 9 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 participants | 38 participants | 21 participants |
| Twin pregnancy yes | 3 participants | 5 participants | 2 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 21 | 0 / 21 |
| serious Total, serious adverse events | 0 / 21 | 0 / 21 |
Outcome results
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
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Liberal Fluid Therapy | Postoperative Renal Dysfunction Evaluated by the Acute Kidney Injury Network (AKIN) Index | AKIN stage I | 7 participants |
| Liberal Fluid Therapy | Postoperative Renal Dysfunction Evaluated by the Acute Kidney Injury Network (AKIN) Index | AKIN stage II | 2 participants |
| Liberal Fluid Therapy | Postoperative Renal Dysfunction Evaluated by the Acute Kidney Injury Network (AKIN) Index | AKIN stage III | 1 participants |
| Restrictive Fluid Therapy | Postoperative Renal Dysfunction Evaluated by the Acute Kidney Injury Network (AKIN) Index | AKIN stage I | 6 participants |
| Restrictive Fluid Therapy | Postoperative Renal Dysfunction Evaluated by the Acute Kidney Injury Network (AKIN) Index | AKIN stage II | 4 participants |
| Restrictive Fluid Therapy | Postoperative Renal Dysfunction Evaluated by the Acute Kidney Injury Network (AKIN) Index | AKIN stage III | 0 participants |
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)
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Liberal Fluid Therapy | Renal Function in Severe Preeclampsia With Restrictive Fluid Therapy | Creatinine preoperative | 0.69 mg/dl |
| Liberal Fluid Therapy | Renal Function in Severe Preeclampsia With Restrictive Fluid Therapy | Creatinine 1st post-operative | 0.99 mg/dl |
| Liberal Fluid Therapy | Renal Function in Severe Preeclampsia With Restrictive Fluid Therapy | Creatinine 2nd post-operative | 0.96 mg/dl |
| Restrictive Fluid Therapy | Renal Function in Severe Preeclampsia With Restrictive Fluid Therapy | Creatinine preoperative | 0.73 mg/dl |
| Restrictive Fluid Therapy | Renal Function in Severe Preeclampsia With Restrictive Fluid Therapy | Creatinine 1st post-operative | 0.93 mg/dl |
| Restrictive Fluid Therapy | Renal Function in Severe Preeclampsia With Restrictive Fluid Therapy | Creatinine 2nd post-operative | 0.84 mg/dl |
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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Liberal Fluid Therapy | Activated Partial Thromboplastin Time in Restrictive Fluid Management of Severe Preeclampsia During Cesarean Section | APPT/R preoperative | 0.98 ratio | Standard Deviation 0.13 |
| Liberal Fluid Therapy | Activated Partial Thromboplastin Time in Restrictive Fluid Management of Severe Preeclampsia During Cesarean Section | APPT/R 1st post-operative day | 1.07 ratio | Standard Deviation 0.1 |
| Liberal Fluid Therapy | Activated Partial Thromboplastin Time in Restrictive Fluid Management of Severe Preeclampsia During Cesarean Section | APPT/R 2nd post-operative day | 1.07 ratio | Standard Deviation 0.13 |
| Restrictive Fluid Therapy | Activated Partial Thromboplastin Time in Restrictive Fluid Management of Severe Preeclampsia During Cesarean Section | APPT/R preoperative | 1.01 ratio | Standard Deviation 0.08 |
| Restrictive Fluid Therapy | Activated Partial Thromboplastin Time in Restrictive Fluid Management of Severe Preeclampsia During Cesarean Section | APPT/R 1st post-operative day | 1.03 ratio | Standard Deviation 0.1 |
| Restrictive Fluid Therapy | Activated Partial Thromboplastin Time in Restrictive Fluid Management of Severe Preeclampsia During Cesarean Section | APPT/R 2nd post-operative day | 1.01 ratio | Standard Deviation 0.07 |
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
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Liberal Fluid Therapy | Cystatin C as New Marker of Renal Injury in Preeclampsia | Cyst C preoperative | 1.73 mg/L | Standard Deviation 0.6 |
| Liberal Fluid Therapy | Cystatin C as New Marker of Renal Injury in Preeclampsia | Cyst C 1st postoperative day | 1.93 mg/L | Standard Deviation 0.8 |
| Liberal Fluid Therapy | Cystatin C as New Marker of Renal Injury in Preeclampsia | Cyst C 2nd postoperative day | 1.64 mg/L | Standard Deviation 0.5 |
| Restrictive Fluid Therapy | Cystatin C as New Marker of Renal Injury in Preeclampsia | Cyst C preoperative | 1.99 mg/L | Standard Deviation 0.61 |
| Restrictive Fluid Therapy | Cystatin C as New Marker of Renal Injury in Preeclampsia | Cyst C 1st postoperative day | 2.03 mg/L | Standard Deviation 0.66 |
| Restrictive Fluid Therapy | Cystatin C as New Marker of Renal Injury in Preeclampsia | Cyst C 2nd postoperative day | 1.72 mg/L | Standard Deviation 0.43 |
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.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Liberal Fluid Therapy | International Normalized Ratio (INR) of Prothrombin Time (PT) in Restrictive Fluid Management of Severe Preeclampsia During Cesarean Section | PT/INR preoperative | 1.00 ratio |
| Liberal Fluid Therapy | International Normalized Ratio (INR) of Prothrombin Time (PT) in Restrictive Fluid Management of Severe Preeclampsia During Cesarean Section | PT/INR first post-operative day | 1.03 ratio |
| Liberal Fluid Therapy | International Normalized Ratio (INR) of Prothrombin Time (PT) in Restrictive Fluid Management of Severe Preeclampsia During Cesarean Section | PT/INR seconde post-operative day | 1.0 ratio |
| Restrictive Fluid Therapy | International Normalized Ratio (INR) of Prothrombin Time (PT) in Restrictive Fluid Management of Severe Preeclampsia During Cesarean Section | PT/INR preoperative | 0.95 ratio |
| Restrictive Fluid Therapy | International Normalized Ratio (INR) of Prothrombin Time (PT) in Restrictive Fluid Management of Severe Preeclampsia During Cesarean Section | PT/INR first post-operative day | 0.95 ratio |
| Restrictive Fluid Therapy | International Normalized Ratio (INR) of Prothrombin Time (PT) in Restrictive Fluid Management of Severe Preeclampsia During Cesarean Section | PT/INR seconde post-operative day | 0.95 ratio |
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
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Liberal Fluid Therapy | Neutrophil Gelatinase-associated Lipocalin (NGAL) as New Marker of Renal Injury in Preeclampsia | NGAL 2nd post-operative day | 0.15 mg/L |
| Liberal Fluid Therapy | Neutrophil Gelatinase-associated Lipocalin (NGAL) as New Marker of Renal Injury in Preeclampsia | NGAL preoperative | 0.16 mg/L |
| Liberal Fluid Therapy | Neutrophil Gelatinase-associated Lipocalin (NGAL) as New Marker of Renal Injury in Preeclampsia | NGAL 1st post-operative day | 0.18 mg/L |
| Restrictive Fluid Therapy | Neutrophil Gelatinase-associated Lipocalin (NGAL) as New Marker of Renal Injury in Preeclampsia | NGAL 2nd post-operative day | 0.15 mg/L |
| Restrictive Fluid Therapy | Neutrophil Gelatinase-associated Lipocalin (NGAL) as New Marker of Renal Injury in Preeclampsia | NGAL preoperative | 0.15 mg/L |
| Restrictive Fluid Therapy | Neutrophil Gelatinase-associated Lipocalin (NGAL) as New Marker of Renal Injury in Preeclampsia | NGAL 1st post-operative day | 0.21 mg/L |
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
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Liberal Fluid Therapy | Platelets in Restrictive Fluid Management of Severe Preeclampsia | Platelets preoperative | 194400 thrombocytes/mm3 | Standard Deviation 77867 |
| Liberal Fluid Therapy | Platelets in Restrictive Fluid Management of Severe Preeclampsia | Platelets 1st postoperative day | 183250 thrombocytes/mm3 | Standard Deviation 83234 |
| Liberal Fluid Therapy | Platelets in Restrictive Fluid Management of Severe Preeclampsia | Platelets 2nd postoperative day | 192850 thrombocytes/mm3 | Standard Deviation 80692 |
| Restrictive Fluid Therapy | Platelets in Restrictive Fluid Management of Severe Preeclampsia | Platelets preoperative | 207941 thrombocytes/mm3 | Standard Deviation 71371 |
| Restrictive Fluid Therapy | Platelets in Restrictive Fluid Management of Severe Preeclampsia | Platelets 1st postoperative day | 201118 thrombocytes/mm3 | Standard Deviation 61687 |
| Restrictive Fluid Therapy | Platelets in Restrictive Fluid Management of Severe Preeclampsia | Platelets 2nd postoperative day | 221824 thrombocytes/mm3 | Standard Deviation 62925 |
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
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Liberal Fluid Therapy | Proteinuria in Severe Pre-eclampsia Submitted to Cesarean Section Under Different Regimes of Hydration | Proteinuria 1st post-operative day | 0.15 g/dl |
| Liberal Fluid Therapy | Proteinuria in Severe Pre-eclampsia Submitted to Cesarean Section Under Different Regimes of Hydration | Proteinuria pre-operative | 0.46 g/dl |
| Liberal Fluid Therapy | Proteinuria in Severe Pre-eclampsia Submitted to Cesarean Section Under Different Regimes of Hydration | Proteinuria 2nd post-operative day | 0.20 g/dl |
| Restrictive Fluid Therapy | Proteinuria in Severe Pre-eclampsia Submitted to Cesarean Section Under Different Regimes of Hydration | Proteinuria pre-operative | 2.62 g/dl |
| Restrictive Fluid Therapy | Proteinuria in Severe Pre-eclampsia Submitted to Cesarean Section Under Different Regimes of Hydration | Proteinuria 1st post-operative day | 0.40 g/dl |
| Restrictive Fluid Therapy | Proteinuria in Severe Pre-eclampsia Submitted to Cesarean Section Under Different Regimes of Hydration | Proteinuria 2nd post-operative day | 0.45 g/dl |
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)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Liberal Fluid Therapy | Urine Output During Cesarean Section in Severe Pre-eclampsia | 116 ml/h |
| Restrictive Fluid Therapy | Urine Output During Cesarean Section in Severe Pre-eclampsia | 80 ml/h |