Table of Contents  
ORIGINAL ARTICLE
Year : 2016  |  Volume : 9  |  Issue : 2  |  Page : 225-228

Comparative study between magnesium sulfate and phenytoin for prevention of eclampsia in severely pre-eclamptic patients with acute kidney injury


Department of Anesthesia, ICU and Pain Management, Faculty of Medicine, Ain Shams University, Cairo, Egypt

Date of Submission27-Apr-2015
Date of Acceptance16-Sep-2015
Date of Web Publication11-May-2016

Correspondence Address:
Aktham A shoukry
El Rehab City, Block 129, Building No 21, Post Code 11841
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/1687-7934.182262

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  Abstract 

Introduction
Pre-eclampsia is a pregnancy-specific, multisystem disorder that is characterized by the development of hypertension and proteinuria after 20 weeks of gestation. Acute kidney failure occurs in about 20% of patients with severe pre-eclampsia. Magnesium sulfate is the medication of choice for the prevention of eclamptic seizures in women with severe pre-eclampsia and for the treatment of women with eclamptic seizures. This medication is renally excreted and hence significant renal impairment can result in exaggerated toxicity. Phenytoin was specifically developed as an anticonvulsant and is the most widely prescribed drug for epilepsy worldwide. The aim of this study is to compare magnesium sulfate with phenytoin for prevention of eclampsia in severely pre-eclamptic patients with acute kidney injury.
Patients and methods
Forty pregnant women were enrolled in the study; all patients had American Society of Anesthesiologists (ASA) physical status of II or III and were proved to have severe pre-eclampsia with acute kidney injury. Patients were allocated randomly into one of two groups (20 patients each). Group A (magnesium sulfate group) included 20 patients who received magnesium sulfate for prophylaxis against eclampsia. Group B (phenytoin group) included 20 patients who received phenytoin for prophylaxis against eclampsia. For each patient, the following data were collected: age, gestational age, body weight, height, occurrence of magnesium or phenytoin toxicity, occurrence of fits, and fetal outcome.
Results
In terms of the occurrence of fits, we found a statistically significant difference between the magnesium group and the phenytoin group as five patients in the phenytoin group developed fits, whereas none of the patients in the magnesium group developed fits. In this study, we did not find a statistically significant difference between the magnesium group and the phenytoin group in the incidence of magnesium or phenytoin toxicity and fetal outcome.
Conclusion
The results of this study showed that prophylaxis against eclampsia in severely pre-eclamptic patients with acute kidney injury using magnesium sulfate (adjusted dose) resulted in no toxicity and no fetal effects besides fewer incidences of fits compared with phenytoin.

Keywords: magnesium sulfate, phenytoin, pre-eclampsia, renal


How to cite this article:
shoukry AA, Hennawy AA, Bassiony M, Sallam M, Mahrous RA. Comparative study between magnesium sulfate and phenytoin for prevention of eclampsia in severely pre-eclamptic patients with acute kidney injury. Ain-Shams J Anaesthesiol 2016;9:225-8

How to cite this URL:
shoukry AA, Hennawy AA, Bassiony M, Sallam M, Mahrous RA. Comparative study between magnesium sulfate and phenytoin for prevention of eclampsia in severely pre-eclamptic patients with acute kidney injury. Ain-Shams J Anaesthesiol [serial online] 2016 [cited 2021 Oct 25];9:225-8. Available from: http://www.asja.eg.net/text.asp?2016/9/2/225/182262


  Introduction Top


Pre-eclampsia is a pregnancy-specific, multisystem disorder that is characterized by the development of hypertension and proteinuria after 20 weeks of gestation. The disorder complicates ∼5-7% of pregnancies and is one of the leading causes of maternal and fetal morbidity and mortality [1].

Acute kidney failure occurs in about 20% of patients with severe pre-eclampsia. Hypertension, proteinuria, and renal function resolve to normal over an average period of about 35 days [2].

Magnesium sulfate is the medication of choice for the prevention of eclamptic seizures in women with severe pre-eclampsia and for the treatment of women with eclamptic seizures [3]. This medication is renally excreted and hence significant renal impairment can result in exaggerated toxicity. Hence, close monitoring of serum magnesium level is warranted with appropriate titration as indicated [4].

Phenytoin was specifically developed as an anticonvulsant and is the most widely prescribed drug for epilepsy worldwide. Because of the empirical success of magnesium sulfate in obstetrical practice, phenytoin treatment has been evaluated only in small studies and reports on its efficacy in preventing eclampsia are not conclusive [5].

We therefore designed a randomized study to compare magnesium sulfate with phenytoin for the prevention of eclampsia in severely pre-eclamptic patients with acute kidney injury.


  Patients and methods Top


This study was carried out at Obstetric ICU of Ain Shams University Hospitals during the period from October 2013 to March 2014. The study protocol was approved by the 'research and ethics committee' of the Anesthesia and Intensive Care Department, Ain Shams University. Informed consent was obtained from all patients or their legal guardians before enrollment in the study.

The sample size was calculated using PS (version 3.0.43; Department of Biostatistics, Vanderbilt University, Nashville, Tennessee, USA) with the following parameters: incidence of occurrence of fits used as the primary goal, where the power of the study was 80%, SD was ± 2, mean was 20, and error was 0.05.

Forty pregnant women were enrolled in the study; they ranged in age between 20 and 40 years. All patients had American Society of Anesthesiologists physical status of II or III and were proved to have severe pre-eclampsia with acute kidney injury. Severely pre-eclamptic patients were defined as patients who had hypertension [defined as hypertension (at least systolic blood pressure 160 mmHg and/or diastolic at least 110 mmHg)] accompanied by proteinuria first detected after 20 weeks of gestation. Proteinuria was defined as at least 300 mg protein in 24 h urine collection [or ≥1+ dipstick (30 mg/dl) in a single urine sample] [6]. Acute kidney injury was defined by the RIFLE classification (when plasma creatinine increased to two-fold or glomerular filtration rate decreased >50% or urine output <0.5 ml/kg/h for 12 h) [7]. Here, we used the urine output criteria. Exclusion criteria for the study included the following: patient refusal to provide consent (absolute), hypersensitivity to magnesium sulfate or phenytoin, hepatic coma, myasthenia gravis, HELLP syndrome, elevated liver enzymes, eclamptic patients, convulsions because of other causes such as epilepsy, meningitis, intracranial space-occupying lesions, patients with sinus bradycardia, sinoatrial block, second-degree and third-degree A-V block, and patients with Adams Stokes syndrome and myocardial damage.

On arrival to the ICU, all patients were monitored continuously with ECG, noninvasive blood pressure, and pulse oximetry; a urinary catheter was inserted if not already present. A central venous line was inserted to measure central venous pressure.

After completion of the baseline lab work (complete blood picture, bleeding time, prothrombin time, international normalized ratio, liver, and kidney function and electrolytes), patients were allocated randomly to one of two groups (20 patients each) using the closed sealed envelope method of randomization.

Group A (magnesium sulfate group)

Severely pre-eclamptic patients with acute kidney injury received conventional treatment according to the Obstetric ICU protocol in Ain Shams University Hospitals: by strict fluid balance, control of blood pressure (by hydralazine 5-10 mg intravenously initially, followed by 5-10 mg every 20-30 min when necessary, but on administering up to 20 mg if there was no response, we used another antihypertensive drug, intravenous nitrates 0.5-5 mg/kg/min, or sodium nitroprusside 0.5-5 mg/kg/min), avoidance of nephrotoxic drugs with renal adjusted dose for the drugs, and then administration of a loading dose of 4 g magnesium sulfate in 200 ml of saline intravenously over 20-30 min, followed by 0.5 g of magnesium sulfate by an hourly infusion for 24 h postpartum if fits developed (supporting the airway, intravenous midazolam 2-5 mg, and magnesium sulfate reloading dose 2 g plus 200 ml saline over 20-30 min).

Group B (phenytoin group)

Severely pre-eclamptic patients with acute kidney injury were treated by the same protocol of treatment, followed by a loading dose of 15 mg/kg of phenytoin in 200 ml of normal saline intravenously over 1 h of infusion, and maintenance dose after 10 h of a loading dose in the form of 100 mg of phenytoin diluted to 8 ml normal saline and administered slowly intravenously every 6 h, continued for 24 h postpartum, in case of development of fits (supporting the airway, intravenous midazolam 2-5 mg, and magnesium sulfate loading dose 6 g plus 200 ml saline over 20-30 min and a maintenance dose of 0.5 g/h).

Endpoints

Magnesium sulfate was stopped if there was diminished patellar reflex, respiratory rate became below 14 breaths/min, urine output was less than 0.3 ml/kg/h, or serum magnesium level greater than 3.5 mmol/l.

Phenytoin was stopped if there was ataxia, blurring of vision, slurred speech, diplopia, or serum level more than 20 mg/ml.

Follow-up included the following:

Monitoring of level of consciousness (occurrence of fits) hourly.

Assessment of magnesium sulfate level every 4 h (in group A).

Assessment of phenytoin level 4 h after the loading dose (in group B).

Assessment of fetal outcome.


  Results Top


Demographic data

In terms of age, gestational age (weeks), and body weight of patients (kg), there were no statistically significant differences between both groups (P > 0.05) [Table 1].
Table 1 Demographic data

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Occurrence of fits

There was a statistically significant difference (P = 0.05) between the magnesium group and the phenytoin group as five patients in the phenytoin group developed fits, whereas none of the patients in the magnesium group developed fits.

Occurrence of magnesium and phenytoin toxicity

For group A (magnesium group), there was no attenuation of the patellar reflex, respiratory rate did not decrease below 14 breaths/min, and serum magnesium level did not exceed 3.5 mmol/l.

In group B (phenytoin group), there was no ataxia, blurring of vision, slurred speech, or diplopia, and serum phenytoin level did not exceed 20 mg/ml.

No drug toxicity occurred in the two groups and there was no statistically significant difference between both groups.

Infant outcome

In terms of birth weight, live birth, and stillbirth, there were no statistically significant differences between both groups (P > 0.05) [Table 2].
Table 2 Fetal outcome

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  Discussion Top


Affecting up to 8% of pregnancies, pre-eclampsia is, in fact, the most common glomerular-based kidney disease worldwide and remains a leading cause of infant and maternal morbidity and mortality [1].

Various studies have been carried out to compare seizure prevention and control in patients with pre-eclampsia and eclampsia managed with magnesium sulfate and phenytoin. In our study, 40 patients with severe pre-eclampsia and acute kidney injury were admitted in the Obstetric ICU of Ain Shams University Hospitals; 20 patients received magnesium sulfate (magnesium group) and the other 20 patients were treated by phenytoin (phenytoin group).

The dose of magnesium sulfate is adjusted for patients with acute kidney injury and administered as a loading dose of 2 g magnesium sulfate in 200 ml of saline intravenously over 20-30 min, followed by 0.5 g of magnesium sulfate by an hourly infusion for 24 h postpartum. Leveno et al.[8] recommended this dose adjustment for prophylaxis of eclampsia in severely pre-eclamptic patients with acute kidney injury, whereas Brown et al. [9] reported that in any patient with renal insufficiency, the loading dose will be the same as that for individuals with normal renal function; however, the continuous drip rate will be dependent on renal function and urine output.

In terms of the occurrence of fits, we found a significant difference between the magnesium group and the phenytoin group as five patients in the phenytoin group developed fits, whereas none of the patients in the magnesium group developed fits as shown in [Table 3]. This is in agreement with the study carried out by Sawhney and Sawhney [10], who reported recurrence of seizures in 10 out of 25 eclamptic patients (40%) treated with phenytoin and in two out of 25 eclamptic patients (8%) treated with magnesium sulfate, indicating the better efficacy of magnesium sulfate as an anticonvulsant.
Table 3 Occurrence of fi ts

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Chein [11] carried out a systematic quantitative overview of controlled clinical trials. An online search of the Medline database between 1966 and 1995 showed that compared with phenytoin, magnesium sulfate is superior in preventing the recurrence of seizures in eclampsia and in seizure prophylaxis in pre-eclampsia.

In terms of the occurrence of magnesium and phenytoin toxicity, in group A (magnesium group), there was no attenuation of the patellar reflex, the respiratory rate did not decrease below 14 breaths/minute, and the serum magnesium level did not exceed 3.5 mmol/l. In group B (phenytoin group), there was no ataxia, blurring of vision, slurred speech, or diplopia, and the serum phenytoin level did not exceed 20 mg/ml; no drug toxicity occurred in the two groups and there was no statistically significant difference between both groups.

Fetal outcome

In this study, we did not find a significant difference between the magnesium and the phenytoin group.

In a review by Druzin et al. [12], evidence suggested that treatment of severe hypertension and seizure prophylaxis with magnesium sulfate and management by experienced healthcare professionals will improve maternal, fetal, and neonatal outcomes.

Omu et al.[13] evaluated the use of magnesium sulfate therapy in women with severe pre-eclampsia and concluded that magnesium sulfate was effective in preventing recurrence of eclamptic fits. As each eclamptic seizure results in significant cerebral anoxia and brain damage, magnesium sulfate, which leads to low occurrences and recurrences of seizures, is a better anticonvulsant than phenytoin in severe pre-eclampsia and eclampsia and our study corroborates the evidence.


  Conclusion Top


The results of the present study suggest that magnesium sulfate with a renal adjusted dose is better than phenytoin for prophylaxis against eclampsia in severely pre-eclamptic patients with acute kidney injury.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
  References Top

1.
Duley L. The global impact of preeclampsia and eclampsia. Semin Perinatol 2009; 33:130-137.  Back to cited text no. 1
    
2.
J Prakash, R Vohra, LK Pandey, SS Niwas, SK Behura, U Singh. Spectrum of kidney diseases in patients with preeclampsia-eclampsia. JAPI 2010; 58:543-546.  Back to cited text no. 2
    
3.
Magpie Trial Collaboration Group. Do women with pre-eclampsia, and their babies, benefit from magnesium sulphate? The Magpie Trial: a randomised placebo-controlled trial. Lancet 2002; 359:1877-1890.  Back to cited text no. 3
    
4.
Dildy GA, Belfort MA, Saade GR, Phelan JP, Hankins GD, Clark SL. Do women with pre-eclampsia, and their babies, benefit from magnesium sulphate?. Acta Obstetricia et Gynecologica Scandinavica 2004; 83:240-245.  Back to cited text no. 4
    
5.
Robson SC, Redfern N, Seviour J, Campbell M, Walkinshaw S, Rodeck C, de Swiet M. Phenytoin prophylaxis in severe preeclampsia and eclampsia. Br J Obstet Gynaecol 1993; 100:623-628.  Back to cited text no. 5
    
6.
ACOG (American College of Obstetricians and Gynecologists) Committee on Obstetric Practice. Diagnosis and management of preeclampsia and eclampsia. Number 33, January. Obstet Gynecol 2002; 99:159-167.  Back to cited text no. 6
    
7.
Bell M, Liljestam E, Granath F, Fryckstedt J, Ekbom A, Martling CR. Optimal follow-up after continuous renal replacement therapy in actual renal failure patients stratified with the RIFLE criteria. Nephrol Dial Transplant 2005; 20:354-360.  Back to cited text no. 7
    
8.
Leveno KJ, Cunningham FG, Gant NF, Norman F. Gant, Gilstrap, John C, Katharine D. Wenstrom, et al. Gestational hypertension and pre-eclampsia-eclampsia: William's manual of obstetrics (21sted), USA, McGrew Hill components, 2003: p. 339.  Back to cited text no. 8
    
9.
Brown MA, Lindheimer MD, de Swiet M, Van Assche A, Moutquin JM. The classification and diagnosis of the hypertensive disorders of pregnancy: statement from the International Society for the Study of Hypertension in Pregnancy (ISSHP). Hypertens Pregnancy 2001; 20:IX-XIV.  Back to cited text no. 9
    
10.
Sawhney H, Sawhney IM. Efficacy of magnesium sulphate and phenytoin in the management of eclampsia. J Obstet Gynaecol Res 1999; 25:333-338.  Back to cited text no. 10
    
11.
P Chein. Magnesium sulphate in the treatment of eclampsia and pre-eclampsia: an overview of the evidence from randomised trials. Br J Obstet Gynaecol 1996; 103:1085-1091.  Back to cited text no. 11
    
12.
Druzin MD, Maurice L, Laurence E, Shields MD, NL Peterson. Preeclampsia toolkit: improving health care response to preeclampsia (California Maternal Quality Care Collaborative Toolkit to Transform Maternity Care) Developed under contract #11-10006 with the California Department of Public Health; Maternal, Child and Adolescent Health Division; Published by the California Maternal Quality Care Collaborative, November 2013  Back to cited text no. 12
    
13.
Omu AE, Al-Harmi J, Vedi HL, Mlechkova L, Sayed AF, Al-Ragum NS. Magnesium sulphate therapy in women with pre-eclampsia and eclampsia in Kuwait. Med Princ Pract 2008; 17:227-232.  Back to cited text no. 13
    



 
 
    Tables

  [Table 1], [Table 2], [Table 3]



 

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