Eclampsia-The most common cause of generalized tonic clonic seizures in pregnancy

 When generalized tonic clonic seizures ( convulsions) and / or unexplained coma develops during  pregnancy or postpartum in patients with signs and symptoms of pre-eclampsia, in the absence of other neurological conditions that condition is called eclampsia.

Incidence :

• Incidence in developed countries is 1 in 2000 deliveries.
• In developing countries around 1 in 100 to 1 in 1700 cases.
• More common in primigravidae women with low socioeconomic status.
• Peak incidence  is  in teenage pregnancies , in early 20s& in women  older than 35 yrs.

§  Even though  incidence decreased  due to better antenatal care ,  maternal and fetal mortality and morbidity  are significant.

§  The incidence of antepartum eclampsia is 35 – 45%, incidence of intrapartum eclmpsia is 15- 20% and the incidence of postpartum eclampsia is 35 – 45%. Eclampsia is common in third trimister  compared with first and second trimisters.

• Late postpartum eclmpsia:  is eclampsia which occurs  beyond 48 hrs but within 4 weeks postpartum.

Pathophisiology of Eclampsia:

             severe hypertension          

                            I                                    

          Cerebral vasoconstiction                    

              /                                    \

Ischemic cytotoxic               failure of regulatory

 edema &infarction                   mechanisms

                                                         I

                                          dilatation of vessels

                                                           I

                                             hyper perfussion &

                                             vasogenic edema

                              \                         /

                Infarctions

               Hemmorrhage

               Vascular damage                                                                                                                                                                                              

                                              \                             

                Triggering of electrical activity

                                            I

                                                  seizures        

Symptoms and signs of impending eclampsia:

• Head ache:  persistent occipital or frontal headaches may occur.
• Visual disturbance: blurred vision or photophobia may be noted.
• Restlessness and agitation: may occur before convulsions.
• Epigastric or /and right upper quadrant pain can  be seen in some patients .
• Nausea and vomiting can be seen.
• Oliguria occurs when renal blood supply got affected.

Clinical features:

• One or more generalised tonic-clonic convulsions and / or coma in pre-eclamptic women.
• Hypertension
• Proteinuria
• Oedema

Generalised convulsions :

• Premonitory stage -   twichings of muscles of face, tongue and limbs, this stage  lasts for 30 sec.
• Tonic stage – whole body goes into a tonic spasm, trunk opisthotonus, limbs flexed, hands clenched, tongue protrudes between teeth, this stage lasts for 30 sec.
• Clonic stage -Suddenly the jaw and other facial muscles contract and relax alternatively, then whole body involved.  Biting of tongue occurs, this stage last for 1 minute.

• Throughout the seizure the diaphragm has been fixed , with respiration halted.
• Women appears as dying of respiratory arrest but breathing resumes.
• One or two convulsions in mild cases, status epilepticus can occur in untreated severe cases.
• Stage of coma-After seizures coma ensures with loss of memory of events immediately before and after, overtime these memories return.
• After arousal semiconscious   combative state may ensue.
• After convulsions respiratory rate  increases.
• Due to hypercarbia from lacticacidemia, varying intensities of hypoxia occurs.
• Cyanosis  is seen in severe cases.
• High fever as a consequence of CNS hemorrhage can occur.

Hypertension:

• BP will be usually very high.
• But convulsions can occur with DBP of 90 to 100 mm of hg, or even with normal BP.
• BP returns to normal within a few days to 2 weeks after delivery.
• Persistent elevation of blood pressure may occur as a  consequence of chronic vascular disease. 

Proteinuria:

• Almost always present & frequently pronounced.
• May reach as much as 15 – 20 g/day.
• Urine output is  likely to be diminished, occasionally anuria develops.
• Hemogilbinuria is common but hemoglobinemia is rare.
• After delivery increase in urinary output is seen it is usually early sign of improvement.

                Edema :

• Edema is pronounced , at times massive may present with anasarca. But may be also be absent.
• Proteinuria and edema usually disappear within a week.

• Visual disturbances including blindness  due to retinal detachment or occipital lobe lesions
• Most often reversible.

Complications:

• Injuries: can occur while falling during convulsios, tongue bite etc can occur.
• Placental abruption :may occur due to fall or due to thrombosis of vessels.
• Neurological deficits: due to injury to blood vessels in central nervous system.
• Aspiration pneumonia: while convulsing due to loss of consciousness.
•  Pulmonary edema : due to aspiration of contents.
• Cadio pulmonary arrest: due to severe spasm of blood vessels, and continued convulsions leading to respiratory arrest.
• Acute renal failure : due to hampered blood supply to the kidney.
• Hepatic necrosis: thrombosis and vasospasm leading to necrosis of vessels.
• DIC:  dissiminated intra vascular coagulation can occur due to consumption of coagulation factors.
• HELLP syndrome: hemolysis, elevated liver enzymes, low platelet count can occur.
• Maternal death can occur in severe cases where proper care is not taken.
• Poor outcome for the fetus unless seizures controlled quickly  due to profound hypoxia and lactic acedemia
• Fetal bradycardia occurs  but may recover in  3 to 5 minutes.
• If persists for more than 10 min another cause as placental abruption to be looked and immediate delivery to be considered.
• IUD and neonatal mortality rate is high due to intrauterine anoxia, cerebral hemorrhage,
• IUGR or prematurity can develop in survived patients.

Management of impending eclampsia:

• To prevent seizures, careful monitoring of patient blood pressure levels and general condition to be done. Anti hypertensives to be taken properly.
• If at home, patient to be  kept in bed, sedated and transferred to hospital as soon as gently as possible.

In hospital:

• Patient should be nursed in a quiet, darkened room.
• Sedated if required.
• Anti-hypertensive therapy  to be initiated
• Loading dose of alpha- methyldopa (500-1000mg) followed by 250-500 mg thrice a day may be given.
• Though nifedipine is preferred due to quicker onset of action.
• Intravenous access for intravenous antihypertensive or prophylactic anticonvulsant therapy if required.
• BP, fluid balance, protenuria and degree of restlessness to be monitored
• Once condition stabilizes the pregnancy should be terminated by induction or caesarean section.
• If condition fails to improve, head ache, visual disturbances or restlessness persists prophylactic anticonvulsant therapy  is recommended.
• The anticonvulsant of choice for prevention is magnesium sulphate.
• Intially 4 g to be  infused intravenousely in a 20% solution over 5 minutes.
• Followed by 10 g initial dose in a 50 % solution intramuscularly ( 5 g in each buttocks)
• Followed by 5 g every 4 hrs in alternate buttocks.
• Morphine, pethidine, chlorpromazine can also be used but maternal or fetal respiratory depression can occur.

Investigations:

Routine:

•   Urine investigations: albumin, sugar, deposits
•   Blood investigations: Hb%, blood grouping and typing, blood surar.

Specific:

•  BT, CT, CRT, Platelet count
•  Renal function tests: blood urea, serum creatinine
•  Liver function tests: SGOT, SGPT, serum bilurubin etc.
• Ultrasonography:  to visualize the status of baby and placenta.

Management of eclampsia:

• Priority is to avoid maternal injury and immediate attention to the airways.
• Patient to be nursed in left lateral position.
• Any secretions   or vomitus to be suctioned to avoid aspiration.
• A padded tongue blade or airway   inserted in between teeth to avoid tongue bite and maintain airway.
• Oxygen by mask at 8 to 10 l/min to correct maternal and fetal hypoxia.
• Oxygen saturation monitored by trans cutaneous  pulse oximeter.
• Arterial blood gas analysis is needed if saturation is <92%.
• Then Intravenous access to prevent recurrence of seizures and control blood pressure.
• Once patient is stable and not restless, foley  catheterization and vaginal examination to be done to know the cervical status. 
• Followed by 5g of 50% solution  of magnesium sulphate every 4 hrs in alternate buttocks , only after ensuring of , presence of patellar reflex,  respirations are not depressed and  urine out put in previous 4 hrs  is > 100ml.
• Intermittent IV or oral administration of anti hypertensives  can be given to control blood pressure.

Zuspan regimen:

• 4 g of  20% solution of Mg So₄   over 5-10 min, followed by 1-2 gms /hr IV infusion

Sibai regimen:

• 6 g of 20% solution  over 20 min followed by 2gms/ hr IV infusion.

• Magnesium sulphate is almost totally cleared by renal excretion.
• Levels to be maintained at 4 to 7 meq/l.
• Patellar reflex disappears when plasma Mg level reaches 10 meq/l,  may be because of curariform action –sign of impending magnesium toxicity.
• At the level of >/ 10 meq/l respiratory depression develops
• And at the level of >/ 12 meq/l respiratory paralysis and arrest follows.

Treatment  of magnesium toxicity:

• Withholding Mgso_4,
•  10% of 10 ml calcium gluconate to be given , in 3 min  intravenously slowly.
• Prompt tracheal intubation and mechanical ventilation if needed.

     Control of seizures:

     Pritchard regimen:

• Magnesium sulphate,  is the drug of choice.
• Total loading dose is 14g.
• 4g of 20% solution as intravenous infusion over 4 to 5 min.
• 5g of 50% solution  intramuscularly in upper outer quadrant of each buttock, through 3 inch long, 20 gauge needle.
• In persistence of convulsions , 2g IV 20% solution at a rate of < 1g/min.

Lean regimen:

• Diazepam: is highly effective in arresting immediate convulsion.
• IV bolus of 10 mg to be given to abort convulsion.
• To prevent recurrence , IV infusion with 80 mg in 1 liter of 5% dextrose for 24 hrs to be given,  depending on the patient condition.
• Neonatal depression, floppy neonate with intractable hypothermia are the complications with this regimen.
• No antidote is there for this regimen.

Phenytoin:

• IV loading dose of 15 – 18 mg/ kg body weight can be given.
• Followed by intravenous  dose 100 mg every 8 hrs to prevent recurrence.
• No significant maternal or fetal side effects.

Lytic cocktail regimen:

• Introduced by  Menon.
• 25 mg of chlorpromazine and 100 mg of pethidine should be given  IV.
• And 50 mg of chlorpromazine and 25 mg of promethazine IM.
• Followed by 50 mg of chlorpromazine and 25 mg of promethazine IM at 4 hrs interval, simultaneous pethidine drip 100 mg in 500 ml of dextrose  IV.
• Pethidine dose should not be more than 300mg in  24 hrs.
• Side effects:
• Respiratory depression in mother and neonate can occur, which is reversible with  naloxone.

Control of blood pressure:

• Persistent and severe BP should be treated.

Hydralazine :

• 5 mg IV can be given every 20 to 30 min, maximum of 30 mg.
• If BP not decreased in 3 doses, 50 mg in 50ml of NS , infusion rate of 10ml/hr can be given, rate increased  by 5 ml/hr after every 15 min until BP gets controlled.
• Side effects: tachycardia, anxiety, restlessness, hyper reflexia
• Fetal heart rate abnormalities may occur.

Labetalol:

• 20 mg IV initially, doubling the dose every 10 min, till cumulative dose of 300 mg reached.
• Onset of action within 5 min, peak effect at 10 to 20 min.

Nifidipine:

• Calcium channel blocker.
• 5 to 10 mg orally, onset of action in 10 to 15 min.
• Dose can be repeated every 30 to 60 min until adequate response achieved.
• Side effects: palpitations, flushing, headache, nausea rarely sudden hypotension, myocardial infarction, synergistic effect with magnesium can occur.

Sodium nitroprusside:

• Short acting vasodilator of arterial and venous smooth muscles.
• IV infusion of 0.25 microgms/kg/min , maximum of 8 microgms/kg/min can be given.
• Onset is in 1 min, and duration is 1 to 3min.
• Side effect : cyanide toxicity.

Delivery:

• Delivery is the definitive treatment,  irrespective of the gestational age for the maternal benifit.
• Cervical status, fetal condition, position and gestational age to be considered before determining the most appropriate route of delivery.
• Vaginal delivery is preferred due to low maternal mortality rates.
• Cervical ripening agents can be used but prolong inductions should be avoided