European Journal of Cardiovascular Medicine

Because to hypoproteinemia, hunger, and inadequate obstetric facilities, the incidence of hypertensive diseases of pregnancy, including PE and eclampsia, is high in developing nations. The Pritchard regimen is the most often used regimen, and MgSO4 is the cornerstone of treatment for preeclampsia and eclampsia.¹ However, MgSO4's use in the community is restricted due to healthcare professionals' concerns about its safety. The underutilization of MgSO4 is caused by a low doctor-to-patient ratio, inadequate provider knowledge and training, and fear due to a lack of ventilator assistance in the event of respiratory depression.² As a result of MgSO4 IV, in particular, appearing unsettling to be administered at primary health centres, cases of severe preeclampsia or eclampsia are frequently sent from remote locations and have convulsions that threaten the life of the mother. The goal of the current study was to assess a reduced loading dosage of MgSO4 without the IV component so that women might receive it before being referred.

In Africa and Asia, preeclampsia and eclampsia cause around 9% of maternal deaths, but in Latin America and the Caribbean, they cause nearly 25%³. Eclampsia causes about one-third of maternal deaths in some regions of northern Nigeria⁴.

The liver, kidneys, coagulation system, or brain may also be affected by severe preeclampsia. Another factor that may be impacted is the placenta, which could raise the risk of placental abruption, poor growth, and preterm labour. During the second half of pregnancy or the first few weeks following delivery, these medical issues, which can happen at any time and relentlessly damage all the organs, can happen at any time. Only 5% or less of mothers after delivery present for the first time⁵.

Eclampsia accounts for roughly 12% of maternal deaths worldwide, placing it as the third most common cause of maternal mortality. This fact was mentioned in recent institutional reports from underdeveloped nations, where eclampsia was the cause of 5.3% and 11.6% of deaths⁶.

While in eclamptic patients, the goal is to treat and prevent recurring seizures, the goal of treatment in preeclampsia is to prevent eclamptic seizures and the associated morbidity. Despite extensive experience, there is debate surrounding the use of magnesium sulphate (MgSO4) in obstetrics. In Germany, Horn employed intrathecal injections of magnesium sulphate to treat eclamptic seizures for the first time in 1906. Women with eclampsia were treated with an injectable regimen to avoid repeated seizures in 1926, and the medication was administered intravenously to these same women in 1933⁷.

Confusion was also caused by differences of opinion regarding the kind and length of preventive dose schedules. In 5070 preeclampsia women who underwent the multicentre Magpie trial's preventive dosing schedules for 24 hours after delivery, either an intramuscular (Pritchard) or intravenous (Zuspan) regimen was used⁸. These recommendations struck the professionals as being blatantly generic, vague, and unreasonable in length in the clinical settings. Thus, despite consensus on the logic of administering prophylactic magnesium sulphate to preeclampsia women in order to prevent initial fits, discussions continue to surround the optimal candidates, ideal dosage, and duration of prophylactic magnesium sulphate therapy. The significance of this study is found in this.

This was a prospective study, conducted in department of obstetrics and gynaecology, Military hospital, Meerut conducted over a period of four years from August 2017 to July 2021.

All consecutive women admitted in the department with eclampsia/severe PE were enrolled in the study after taking informed consent.

Hypertension was managed with IV labetalol if systolic blood   pressure   was ≥160   mmHg   or   diastolic   blood pressure   was   110   mmHg   and   subsequently   by   oral labetalol and nifedipine accordingly, only if they were fit enough for oral intake.

Patients  with  other  causes  of  convulsions  like  epilepsy, cerebrovascular accidents, ruptured aneurysm, meningitis, encephalitis,  cerebral  tumors,metabolic  abnormalities, womenalready treated outside with MgSO4were excluded from the study.

Sample size:

Cases  were  further  divided  into  two  groups:  group  A (study  group/receiving  modified  dose  MgSO4as  given below); group B (receiving standard Pritchard’s regime of MgSO4).

Group A was given only 10 gm IM MgSO4 (5gm in each buttock) loading dose followed by maintenance dose 5 gm IM  in  alternate  buttock  every  4  hours  for  12  hours  after delivery/last convulsion whichever was later.

Group  B  was  given  standard  Pritchard  regime,4  gm  IV and 10gm IM of MgSO4(5 gm in each but stock) loading dose  followed  by5  g  maintenance  dose  4  hourly  in alternate   buttock   for   24   hours   after   delivery   or   last convulsion whichever was later.

If the patient in the study or control group had convulsionafter  administration  of  loading  dose  then  2  g  IV  MgSO4was   given.   This   additional   dose   was   given   upto   a maximum of 2 times and if they had recurrent convulsions then   other   regimen   was   given   as   per   protocol.   The additional doses, when given, were given after one hour of the loading dose in all the cases, so the additional doses of MgSO4did  not  have  impact  on  the  serum  magnesium levels which were seen at 15 minutes and then at one hour after  the  loading  dose.  Number of cases requiring this additional dose in the two groups was compared.

Statistical Analysis:

For statistical analysis data were entered into a Microsoft excel spreadsheet and then analyzed by SPSS 27.0.and GraphPad Prism Version 5. Data had been summarized as mean and standard deviation for numerical variables and count and percentages for categorical variables. Two-sample t-tests for a difference in mean involved independent samples or unpaired samples.  Unpaired proportions were compared by Chi-square test or Fischer’s exact test, as appropriate. P-value ≤ 0.05 was considered for statistically significant.

Table 1: Distribution of cases according to various parameters

Table 2: Comparison of recurrence of convulsions in cases of antepartum eclampsia in two groups

Table 3: Comparison of timing of recurrence of convulsions among cases of antepartum eclampsia in the two groups

Table 4: Comparison of recurrent convulsions and maternal mortality in different studies in women of antepartum eclampsia

Educational status

In Group – A, 26 (52%) patients were Illiterate and24 (48%) patients were Literate (>standard 8)

In Group – B, 38 (76%) patients were Illiterate and 12 (24%) patients were Literate (>standard 8)

Association of Educational status with Group was statistically significant (p=0.0124).

Number of antenatal care visits

In Group – A, 21 (42%) patients were ≤4 times visited (un-booked) and 29(58%) patients were >4 times visited (booked).

In Group – B, 19 (38%) patients were ≤4 times visited (un-booked) and 31 (62%) patients were >4 times visited (booked).

Association of Number of antenatal care visits with Group was   not statistically significant (p=0.6831).

Parity

In Group – A, 9 (18%) patients had Parity 0, 13 (26%) patients had Parity 1, 17 (34%) patients had Parity 2 and 11 (22%) patients had Parity ≥3.

In Group – B, 14 (28%) patients had Parity 0, 19 (38%) patients had Parity 1, 8 (16%) patients had Parity 2 and 9 (18%) patients had Parity ≥3.

Association of Parity with Group was   not statistically significant (p=0.1298).

History of hypertension/PE/ eclampsia

In Group – A, 30 (60%) patients had History of hypertension/PE/ eclampsia.

In Group – B, 29 (58%) patients had History of hypertension/PE/ eclampsia.

Association of History of hypertension/PE/ eclampsia with Group was   not statistically significant (p=0.8388).

Mode of delivery

In Group – A, Delivery mode of 16 (32%) patients were vaginal, Delivery mode of 11 (22%) patients were LSCS and Delivery mode of 15 (30%) patients were Live.

In Group – B, Delivery mode of  20 (40%) patients were vaginal, Delivery mode of  15 (30%) patients were LSCS and Delivery mode of  6 (12%) patients were Live.

Association of Mode of delivery with Group was   not statistically significant (p=0.1735).

Perinatal outcomes

In Group – A, 15 (30%) patients had given stillborn birth and 35 (70%) patients had given improved birth.

In Group – A, 26 (52%) patients had given stillborn birth and 24 (48%) patients had given improved birth.

Association of Perinatal outcomes with Group was statistically significant (p=0.0253).

Maternal outcomes

In Group – A, 40 (80%) Patients were maternal outcomes improved and 10 (20%) Patients were maternal outcomes expired.

In Group – B, 37 (74%) Patients were maternal outcomes improved and 13 (26%) Patients were maternal outcomes expired.

Association of Maternal outcomes with Group was not statistically significant (p=0.4759).In Group – A, 26 (52%) patients had no repeated episodes after treatment, 24 (48%) patients had repeated episodes after treatment.

In Group – B, 20 (40%) patients had no repeated episodes after treatment, 30 (60%) patients had repeated episodes after treatment.

Association of after treatment with Group was not statistically significant (p=0.2286).

In Group – A, 12 (24%) patients had taken time of recurrent convulsion within 5 min, 22 (44%) patients had taken time of recurrent convulsion within 15 min, 9 (18%) patients had taken Time of recurrent convulsion within 1 hour and 7 (14%) patients had taken Time of recurrent convulsion within 4 hour.

In Group – A, 21 (42%) patients had taken time of recurrent convulsion within 5 min, 15 (30%) patients had taken time of recurrent convulsion within 15 min, 6 (12%) patients had taken Time of recurrent convulsion within 1 hour and 8 (16%) patients had taken Time of recurrent convulsion within 4 hour.

Association of Time of recurrent convulsion (interval after loading dose) with Group was not statistically significant (p=0.2172).

Recurrence of convulsions

In Group – A, 33 (66%) patients were in control group and 17 (34%) patients were in study group.

In Group – B, 22 (44%) patients were in control group and 28 (56%) patients were in study group.

Association of Recurrence of convulsions with Group was statistically significant (p=0.027).

Maternal mortality

In Group – A, 18 (36%) patients were in control group and 32 (64%) patients were in study group.

In Group – B, 31 (62%) patients were in control group and 19 (38%) patients were in study group.

Association of Maternal mortality with Group was statistically significant (p=0.0093).

Group A - Study group/receiving modified dose MgSO4

Group B - Receiving standard Pritchard’s regime of MgSO4

Our study showed that, most of patients had Severe PE in Group - B [35 (70.0%)] compared to Group - A [27 (54.0%)] but this was not statistically significant (p=0.0993).

In our study, out of 200 patients most of the patients were ≤20 years old [38 (38.0%)] but this was statistically significant (p=0.0021).

Our study showed that, most of patients were Hindu in Group - A [39 (78.0%)] compared to Group - B [31(62.0%)] but this was not statistically significant (p=0.0808).

We observed that, higher number of patients were belonging from Urban area in Group - A [30 (60.0%)] compared to Group – B [25 (50.0%)] but which was statistically not significant (p=0.3148).

It was found that, more number of patients were Illiterate in Group – B [38 (76.0%)] compared to Group – A [26 (52.0%)] but this was statistically significant (p=0.0124).

We examined that, more number of patients had antenatal care >4 visits (booked) in Group - B [31 (62.0%)] compared to Group - A [25 (50.0%)] which was not statistically significant (p=0.6831).

Our study showed that, most of patients had Parity – I in Group - B [19 (38.0%)] compared to Group - A [13 (26.0%)] but this was not statistically significant (p=0.1298).

We observed that, higher number of patients had History of hypertension/PE/ eclampsia in Group - A [30 (60.0%)] compared to Group – B [29 (58.0%)] but which was statistically not significant (p=0.8388).

It was found that, more number of patients delivery mode was Vaginal in Group – B [20 (40.0%)] compared to Group – A [16 (32.0%)] but this was not statistically significant (p=0.1735).

Our study showed that, most of patients Perinatal outcomes was Improved in Group - A [35 (70.0%)] compared to Group - B [24(48.0%)] but this was statistically significant (p=0.0253).

We observed that, higher number of patients Maternal outcomes was Improved in Group - A [40 (80.0%)] compared to Group – B [37 (74.0%)] but this was statistically not significant (p=0.4759).

Our study showed that, higher number of patients had repeated episodes in Group - B [30 (60.0%)] compared to Group – A [24 (48.0%)] but which was statistically not significant (p=0.2286).

Our study showed that, most of patient’s Time of recurrent convulsion within 15 min in Group - A [22 (44.0%)] compared to Group - B [15 (30.0%)] but this was not statistically significant (p=0.2172).

We observed that, Recurrence of convulsions (p=0.0271) and Maternal mortality (p=0.0093) with Group was statistically not significant.

Hypertensive  disorders  of  pregnancy  including  PE  and eclampsia   complicate   around   5-10%   of   pregnancies worldwide and together they were a member of the deadly triad, along with hemorrhage and infection that contributed to maternal morbidity and mortality.4,5The incidence was high  in  developing  countries  due  to  hypoproteinemia, malnutrition and poor obstetric facilities. Overall, 10-15% of maternal deaths were directly associated with PE and eclampsia.2

The  collaborative  eclamptic  trials  in  1995  conclusively proved  that  MgSO4was  the  drug  of  choice  for  the anticonvulsant   management   of   eclampsia   rather   than diazepam  or  phenytoin.6 The  use  of  this  drug  reduced maternal deaths from 7% to 4% and the recurrence rate of convulsion was reduced by 52% and 67% when compared with diazepam and phenytoin respectively.7,8

Since the introduction of Pritchard’s regimen of MgSO4there had been a constant discussion regarding the dose of MgSO4and therapeutic serum magnesium levels.

Phuapradit  et  al  and  Witlin  in  their  study,  observed  that MgSO4 dosing should vary according to women’s weight or  body  mass  index.9,10Based  on  these  observations various low dose regimens have been introduced in Asian countries.

The present study was a comparison between modified low dose  regime  of  MgSO4(10gm  only  IM  loading  dose omitting IV dose and continuing maintenance dose for 12 hours after delivery/last convulsion whichever was later as compared  to  24  hours  in  Pritchard  regime)  and  standard Pritchard regime of MgSO4(4gm IV+10gm IM of MgSO4loading  dose),  in  terms  of  occurrence  of  convulsion  in severe  PE,  recurrence  of  convulsion  in  eclampsia  and serum levels of magnesium.

The relevance of our study lied in the fact that MgSO4was not an innocuous drug.  It was  necessary  to  monitor  the patients  who were  receiving  the  medication  to  prevent serious  side-effects.  It was recommended that frequent monitoring (every 5-10min) should be undertaken during the first 2 hour of therapy when the intravenous regimen was being used. Where the number of patients was high in relation   to   attending   doctor   and   health   care   workers frequent monitoring was sometimes difficult. MgSO4 particularly IV appeared scary to be given at all places considering this; IM regime appeared to be most suitable.

As mentioned in literature serum magnesium levels of 2.0 to 3.5 mmol/lor 4.8 to 8.4 mg/dl or 4 to 7 mEq/l had been suggested   for   treatment   and   prevention   of   eclamptic convulsions.11

In present study serum magnesium levels were measured prior, after 15 min and 1 hour of loading dose of MgSO4, which showed low level of serum magnesium (but still in therapeutic range) in study group as compared to control group. In severe PE women, therapeutic serum magnesium levels  were  not  reached  after  15  min  of  loading  dose administration but were in therapeutic range at 1 hour post loading dose. In eclampsia women serum magnesium level were within therapeutic range after 15 min and 1 hour both in study group and control group.

On comparing with another study in 2015 by Savitha et al assessed the effectiveness of low dose MgSO4regime for the  prevention of convulsion in severe PE and eclampsia and compared the therapeutic levels of serum magnesium at  1  hour,  6  hour  and  12  hours  after  administration  of loading dose.12In study group, low dose MgSO4,loading dose 4gm IV, maintenance dose 2gm/4hr IV infusion and in control group loading dose 4gm IV, maintenance dose of 2gm/hr IV infusion was given serum magnesium levels prior  to  loading  dose  were  not  measured  either  in  study group   or   in   control   group.   There   was   statistically significant difference between serum magnesium levels at 1  hour,  6  hour  and  12  hour  between  the  two  groups (p=0.02)  but  levels  in  both  groups  were  in  therapeutic range at all time intervals at which they were measured.

Recurrence of convulsions in eclampsia

In   present   study,   recurrence   of   convulsions   among antepartum eclampsia (APE) women was 60.0% in group B  and  48.0%  in  group  A;  this  was  in  variance  to  the results   described   in   standard   literature   of   western population.   This   can   be   explained   by   poor   health awareness among Indian women leading to late arrival at heath care centres. So that by the time they arrive they have already had many convulsions (7.510±3.60) in group A and 5.81± 2.10 in group Bin women who did not have repeat convulsions  and  6.95±3.62  in group  A  and  6.81± 4.24  in group Bin women who had repeat convulsions) and were in a low condition.

In  their  study,  Samoriski  et  al observed that  generalized clonic  seizures resulted in a  progressive  decrease  in both the generalized seizure threshold and caused hypoxic brain injury.13So  it was  postulated  that  the  high  number  of seizures  prior  to  admission  resulted  in  lower  seizure threshold and hypoxic brain injury accounting for the high incidence of recurrent seizures after MgSO4loading dose in both groups.

In present study it was found that  convulsions  did  not  occur  after  giving MgSO4in women  of  severe PE in  both  groups.  However, in APE repeated episodes of convulsions were observed in 22.53% and 35.4% women in group A and group B respectively and   the   difference   was   not   found   to   be   statistically significant (p=0.502).

In group  A,  recurrent  convulsions  occurred  in  24 women (20.68%) and in all of them serum magnesium levels were not  in  therapeutic  range.  In group  B,  30 women  had recurrent  convulsions  in  whom  18  women  had  serum magnesium levels in therapeutic range, in only 1 woman therapeutic  levels  were  not  reached  and  sample  of  one woman could not be sent as she expired within 15 min of admission.

Begum  et  al  2002  in  their  study,  used  only  loading  dose consisting of 4gmintravenously and 6 gm intramuscularly in each buttock in study group and 4gm intravenously and 6  gm  intramuscularly  as  loading  followed  by  2.5gm intramuscularly  every  4  hourly  in  each  alternate  buttock for  24  hourly  in  control  group  and  the  difference  in recurrence  rate  of  convulsion in  both  the  groups  was notsignificant.14So   they   concluded   that   only   a   reduced loading dose of 10 gm (4 gm IV+6 gm IM) was sufficient for   preventing   recurrent   convulsions   in   eclampsia   in Bangladeshi women.

Okusanya  et  al  2012 in their study, used loading dose  of 10  gm  MgSO4  via IM route  in  study  group  and  14  gm loading dose (10 gm IM and 4 gm IV) of Pritchard regimen was   given   to   control   group   in   women   with   severe PE/eclampsia  and  there  was  no  significant  difference  in rate of recurrent convulsion(p=0.1948).15

Maternal outcome

Present  study  showed that  maternal  outcome  of  majority of women was good with 101 women of each group being discharged  well  (97.58%  overall;  98.06% group  A  and 97.12% group  B).  Maternal death occurred in 2 women (1.94%) in group A and 3 women (2.88%) in group B. This difference was not found to be statistically significant (p=0.659).  Cause of death of 2 women of group A was pulmonary   edema   and   pulmonary   embolism   each.   3 women  expired  in  group  B  and  the  cause  of  death  of  3 women  in group  B  was  pulmonary  edema, pulmonary embolism  and  DIC  with  pulmonary  embolism  in  each case.

Table 6 shows that maternal deaths in present study were lower  as  compared  to  observations  by  Begum  et  al  and Okusanya et alin their studies.14,15

The reported maternal mortality ranged from 0.4% to 4% depending on the condition of the women on admission and hospital facilities.

The  present  study  indicates  that  a  reduced  loading  dose (only 10 gm IM) and shortened period of maintenance dose (12 hours after delivery/convulsion whichever is later) of MgSO4alone is as effective in controlling and preventing the  recurrence  of  convulsions  in  eclampsia  as  that  of Pritchard  regime  in  Indian  women.  It  also  has  the  added advantage  of  being  less  expensive  and  in  reducing  the number of painful IM injections. The introduction of only IM MgSO4 to primary   health   facilities   would   make available an evidence-based treatment at the first point of contact  for  women  with  eclampsia  as  in  present  study 44.34%  women  had  been  referred  without  being  given loading  dose  of  MgSO4.  This study suggests that many lives may be saved by this intervention and demonstrates the prospects for its use at this level of care. The adverse maternal  and  perinatal  outcome  in  this  study  is  still unacceptably high due to poor antenatal care received by the  patients;  however,  based  on  the  findings  from  this study, consideration should be given to the use of low dose MgSO4in  the  management  of  eclampsia  as  there  is  no significant difference between it and the standard Pritchard regime. The key issue in developing countries like India is transport and high patient to staff ratio, especially in rural areas. In   such situations,  the  intramuscular  regime  can  be  initiated  and then  they  can  be  transported  without  fear  of  convulsion during transit. The dose we propose is small and very easy to administer. A larger study, preferably a randomized control trial is recommended to further evaluate the   feasibility and efficacy of the use of only MgSO4 intramuscular loading dose in cases of eclampsia and severe preeclampsia.

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