EPILEPSY AND PREGNANCY
to Buccheri La Ferla
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Vincenzo Lanza
Servizio di Anestesia e Rianimazione Ospedale
Buccheri La Ferla FATEBENEFRATELLI
Via M. Marine 197, 90123 PALERMO - ITALY
E.MAIL. LANZA@MBOX.UNIPA.IT
Epilepsy is a disease presenting with different kinds of symptoms
going from the generalized seizures to an impairment of consciousness
of a few seconds.
In pregnancy , the most important clinical presentation for the anesthetist is the epilepsy with convulsive symptoms.
In the following work we will examine:
1.1 Etiology
Epilepsy is a disorder affecting 2% of population when in association with other encefalopathic form and about 0.5% referring with the simple disease.The latter concerns with subjects with normal coefficient intellective without any other mental problem except for the psychological one. In the anamnesis of these patients is often possible to find high temperature the first time convulsive disorders appear while temperature disappearing in the following episodes. Generally "febrile seizures" are considered normal until the age of 6 years because of immaturity of cerebral structures, but they are considered as epileptic disease after the age of 6 years . A differential diagnosis can be made with the EEG : subjects with a pathological EEG without fever surely will have in puberty epilepsy also without clinical crisis.Different features of epilepsy (absence seizures, convulsive seizures etc.) can coexist or replace one another in the same patient. In tab.1 the International Classification of Epileptic Seizures is shown.
| A. Simple partial seizures consciousness not impaired | |
| 1. With motor symptoms
2. With somatosensory or special sensory symptoms | 3. With autonomic symptoms
4. With psychic symptoms |
| B. Complex partial seizures with impairment of consciousness | |
| 1. Beginning as simple partial seizures and progressing to impairment of consciousness | |
| a. With no other features
b. With features in I.A.I-I.A.4 | c. With automatisms |
| 2. With impairment of consciousness at onset | |
| a. With no other features
b. With features as in I.A.I-I.A.4 | c. With automatisms |
| C. Partial seizures evolving to secondarily generalized seizures | |
| 1. Simple partial seizures evolving to generalized seizures
2. Complex partial seizures evolving to generalized seizures | 3. Simple partial seizures evolving to complex partial seizures to generalized seizures |
| A. Absence seizures | |
| 1. Absence seizures | 2. Atypical absence seizures |
| B. Myoclonic seizures | C . Clonic seizures |
| D. Tonic seizures | E. Tonic-clonic seizures |
| F. Atonic seizures jastatic seizures! | |
| Includes all seizures that cannot be classified because of inadequate or incomplete data and some that defy classification in hitherto described categories. | This includes some neonatal seizures leg, rhythmic eye movements, chewing, and swimming movements. |
Pregnancy seems not to be an etiopathological factor of epilepsy. As a matter of fact epilepsy disorders frequently occur approaching the delivery and not during the pregnancy [2].
We can find very few reports (50/100.000 pregnant women) of patients with no previous history of epilepsy that present the appearance of a chronic epileptic disease during pregnancy.
Knight et al. reports 16 cases of primigravidas
patients with symptoms of epilepsy disappearing one or two months
after delivery. No case was reported from 1989 to 1995 in 16000
deliveries at Buccheri La Ferla Hospital.
2.2 Complications of epilepsy during pregnancy
Several statistics point out an increase of epileptic crisis frequency. The incidence ranges from 40 to 50%. The causes have to be investigated in the physiological changes of pregnancy:
* Reduction of functional residual capacity with hypocapnia and possible reduction of cerebral flow.
* Retention of fluids with consequent cerebral edema.
*The typical "nitrogen sparing" of pregnant woman with consequent change of the amino acids pattern.
*The increased metabolism and excretion of hidantoyn (100% more) that may reduce plasma concentration to subtherapeutic levels.
* The typical hormonal variations of
pregnancy
2.3 Risks of epilepsy during pregnancy
The epileptic patient shows a greater incidence of neonatal disease. This is likely to be due to toxic effects of anticonvulsant drugs [3] and to epileptic seizures.
2.3.1 Effects of epileptic seizures:
6-10% of epileptic patients in pregnancy shows tonic-clonic seizures. During the seizures, a trauma to mother and fetus, abruptio placental, fetal intra-cranial hemorrhage, miscarriage, fetal neonatal and prenatal death may occur.
2.3.2 Toxic effects of anticonvulsant therapy
Treatment of epilepsy often consists of more than one drug administration to prevent the toxic effects of a drug alone. The side-effects of these drugs are often unacceptable in pregnancy, but discontinuation of one or more drugs as well as the physiologic and metabolic changes associated with pregnancy, can trigger a cluster of seizures that can lead to a dangerous status epilepticus.
The side-effects of anticonvulsant drugs in pregnancy are:
* An increased incidence of fetal malformations (from 2-3% in healthy pregnant to 4-6% in epileptic pregnant).
* Fetal malformation of the fingers and face occurs in 5-30% up to 40% in untreated patients. These malformations are more frequent in epileptic patients who lack of folates.
* Haemorrhagic syndrome produced by a reduction of vit.K-dependent clotting factors.
* The treatment with valproic acid may
produce an increased incidence (1%) of neural tube defects as
spina bifida aperta that raises up to 5% during carbamazepine
treatment.
[Contents]
In the late stage of pregnancy, epilepsy is often observed in Eclampsia-related syndromes:
- Pre-eclampsia
- HELLP syndrome (Hemolysis, Elevated liver function tests, low Platelets)
- Eclampsia
Eclampsia is clinically associated with seizures (tab. 2).
| TABLE 2 - Features of pregnancy diseases susceptible to induce seizures | |||
| H.E.L.L.P. Syndrome: | Eclampsia | ||
| CLINIC | Hypertension, proteinuria, and peripheral edema onset after twenty weeks gestational age. | Hemolysis (on peripheral smear, or increased haptoglobin)
Elevated Liver function tests T.Bil>1.2, LDH>600 SGOT>70 Low Platelets :<100000 | Pre-eclampsia with addition of seizures. |
| Incidence | 2.6% of all pregnancies; recurs in 20% | 4-12% of all pre-eclamptics | 0.056% of all pregnancies. |
| Risk factors | Age between 25-34, Primip/multip 6.8/1, Twin/single 5/1. | ||
| FINDINGS IN SEVERE SINDROME | Blood pression Systolic > 160
Diastolic > 110, proteinuria 2 g/die oliguria < 400 ml/die creatinine 1.2 headache visual disturbances, pulmonary edema, intrauterine growth retardation increased liver function tests or thrombocytopenia | pulmonary edema
fetal death hemorrhagic shock liver insuff. Seizures | |
In these patients seizures often occur
during labor, thus representing a relevant therapeutic problem;
differential diagnosis should consider brain tumor . We observed
40 y patient, hospitalized for a bigeminal pregnancy, who developed
seizures because of brain tuberculosis. Pre-eclampsia incidence
in our hospital and patient outcome are shown in tab.3
[Contents]
| Tab.3 ICU admittance of obstetric patients (January 1993-JUNE 1996 ) | ||||
| Health Pregnancy | ||||
| NUMBER OF PATIENTS | ||||
| PATIENTS WITH SEIZURES * | ||||
| PATIENTS IN ICU | ||||
| DAYS IN ICU (MEAN) | ||||
| OUTCOME | ||||
| *PRE-ECLAMPSIA + SEIZURES = ECLAMPSIA | ||||
3.1 Diagnosis and prevention of pregnancy epilepsy
Patients already known as epileptic
do not present problems for diagnosis. Instead, diagnosis can
be difficult in patients suffering from absences, often hidden
for shame, who develop generalized seizures. Therefore patients
who do not have epileptic disease but present risk factors represent
the more problematic group. These patients often begin a single
seizure and then quickly organize an epilepticus status. In our
experience on about 16000 deliveries, just one patient with these
characteristics has occurred.
[Contents]
3.1.1 Seizure prevention in epileptic patients
To avoid toxic risks shown in the point 2.3.2. ,epilepsy treatment with more than one drug has to be stopped. Phenytoin is the drug more commonly used alone. The drug already used by patient should be preferred. The switch to an alternative drug should be early made to avoid the occurrence of seizures.
Sometimes this therapeutic approach is problematic to be applied, as patients a favorable therapeutic balance is achieved after many clinical attempts in the clinical setting. In cases of "drug-resistant" epilepsy a single drug treatment may be ineffective and intravenous Phenytoin i.v. may be tried.
3.1.2 Prevention of seizures in pregnant women at risk not affected by epilepsy.
- Patients with pre-eclampsia symptoms require seizure prevention. A weekly EEG monitoring is recommended throughout the two months before delivery. The appearance of EEG changes as delta rhythm (fig.1) suggests to start Magnesium or Phenytoin therapy. (tab.4)
- The development of seizures does not seem to be related to patients blood pressure.
- Hydration status has to be carefully considered because pre-eclampsia is associated with dehydration : seizures may occur if blood osmolarity raises up 310 mOsm/l.
These prophylactic measures should be
added to vitamin K administration 3-4 weeks before delivery to
reduce the incidence of neonatal hemorrhage
[Contents]
| tab.4 Drugs used in the treatment of the eclampsia related syndrome | ||||
| Drug | Loading Dose | Maintenance | Therapeutic Effects | Side Effects |
| Magnesium (MgSO4 50%) | 12 ml (= 6 g) in 100 ml NaCl 0.9% I.V. (15 mins) | 2 g/Hr infusion
(25 g MgSO4 / 300 ml NaCl 0.9%) 25ml/Hr | Seizure control
Therapeutical 2 - 4 mmol/l | Plasma level 5 mmol/l : loss of tendon reactions
7.5 mmol/l : cardial conduction defect, cessation of breathing > 10 mmol/l : cardiac arrest treatment CaCL2 10 % 5 - 10 ml iv , O2 with a mask |
| Phenytoin (aurantin 150mg/f) | 2ff IV (5mins) | 200-400mg | Seizure control
Therapeutical 10-20mg/l | |
| Hydralazine | 5-10mg increments | Hypertension | crosses placenta- neonatal hypotension. | |
| Labetelol | 1 mg/kg | Hypertension | no neonatal effects | |
| Nitroprusside | 0.25-0.5 ug/kg/Min. | Hypertension | no evidence of fetal cyanide accumulation | |
| Nifedipine | 40-120 mg/gtt./nasal | Hypertension | less fetal distress | |
The anesthesiologist is involved in
the treatment of epileptic symptoms at delivery and rarely deals
with epileptic patients during pregnancy. The seizure presentation
is more complex in pre-eclampsia or HELLP-syndrome, as cesarean
section and seizures treatment are simultaneously present as problems
to face [7]. The anesthesiologist has to give anesthesia to a
pregnant woman just reaching the hospital on succeeding tonic-clonic
attacks. In these conditions patients present a high anesthetic
risk. General anesthesia is not always recommended: the propofol
administration to stop the attacks can be followed by spinal anesthesia.
4.1 Anesthesia for epileptic patients delivery
When the epileptic patient is well controlled by therapy during pregnancy, it is not usually necessary a special treatment at the delivery. However it is possible that the anesthesiologist is asked to treat epileptic symptoms occurring during labor. If no convulsions are present, a continuous epidural anesthesia throughout labor is preferred. This technique decreases seizure occurrence because 1) it suppresses labor pain, 2) maintains a constant anesthetic plasma concentration producing an anticonvulsant effect. It is important to do not overdosing local anesthetics: bupivacaine 0.25%, 6ml/hour should be indicated.
- For patients in advanced labor or near delivery propofol administration (1% 3-4ml in repeatable bolus) should be attempted. If this treatment is effective, the woman may have a normal delivery or a low forcep application with an acceptable level of consciousness. After delivery diazepam 10mg should be given.
- For cesarean delivery it is possible
to control seizures by propofol and decide about general or spinal
anesthesia after evaluating fetal conditions. In our experience
good results are achieved by spinal anesthesia (see Tab.5). During
surgery a propofol infusion at rate 10-15 ml/h is administered.
After delivery diazepam 10 mg is usually given. Other drugs other
than their routine therapy are not necessary by using this protocol.
In any case thiopental and general anesthesia may also be used
with good results, the most known approach, the best one. An effective
support is done by Magnesium administration (see Tab.4).
[Contents]
4.2 Anesthesia for delivery of non epileptic patients presenting seizures
This group is usually represented by
patients suffering from eclampsia or the related syndrome, as
the HELLP syndrome. The treatment is similar to that for seizure
occurrence (more frequently in eclampsia than in HELLP), that
is prompt delivery. However, in eclampsia syndrome there is a
severe hypertension while in HELLP syndrome there are clotting
abnormalities.
4.2.1 Seizure treatment in eclamptic patient
Convulsions are only a part of this severe syndrome, due to the severe hemodynamic impairment: blood pressure is often over 200mmHg . In Tab.4 the therapeutic procedures are described . If it is possible, seizure treatment should include prophylactic magnesium or phenytoin because both the drugs are able to stabilize an epileptic patient. However the acute treatment is based on the use of propofol or thiopental as diazepam produces neonatal hypotonia and respiratory depression and cannot be used, except after delivery. The antihypertensive therapy is very important: the drug of choice is hydralazine or, in alternative, labetelol and nitroprusside. Good results are achieved by nifedipine nasal drops [8]. This procedure is of value in an unconscious patient without a venous line. The effect is constant and the dosage ranges 20-80mg . The choice of the anesthesiological technique depends on anesthesiologist experience (see tab.5). During the general anesthesia EEG monitoring is suggested; if the monitoring system does not have any EEG module, an electroencephalograph should be used for the EEG recording that to detect an eventual perioperative status epilepticus. This practice requires specific knowledge. In fact it is difficult to make diagnosis of seizures on curarized patient and the sparing use of hypnotic drugs may be ineffective in switching off a epileptic focus. Skilled professionals should be immediately available to look after the newborn. In his absence the anesthetist has to start neonatal resuscitation and to decide newborn ICU admission. As regards as postoperative treatment, convulsions are prevalent on general anesthesia awakening : diazepam should be given after the delivery and repeated one hour after. The neurologic status has to be carefully assessed. If an hour after the end of the anesthesia the patient is still unconscious, cerebral edema should be suspected and a brain TC scan and patient admission in ICU should be planned (fig.1)
4.2.2 Seizures treatment in HELLP syndrome
The treatment is similar to that of eclampsia (see tab.4)
In the HELLP syndrome typical severe clotting abnormality and related bleeding, are the most important findings. Therefore a central venous line, large amounts of blood, plasma and platelets should be available before cesarean section. To gain a central access , a long catheter from an antecubital vein should be advanced to reach the atrium, as significant venous bleeding is frequently observed. Hemothorax by subclavian vein and important neck and thight hematoma by jugular or femoral attempts are the most troublesome complications. In these patients there is a high incidence of myocardial infarction and brain haemorrhage.
A brain TC scan is necessary in all
patients suffering from HELLP syndrome and seizures. General anesthesia
is the technique of choice for cesarean section because clotting
abnormalities contraindicate the regional anesthesia. Caution
has to be used for intubation to avoid oropharyngeal bleeding.
Postoperative management should be careful in the evaluation of
hepatic and coagulation function. Patients suffering from severe
forms have to be admitted in ICU (fig.2)
 |
| figure 2 |
| Tab.5 guidelines for cesarean section in the eclampsia related syndrome | |||
| Mild Pre-eclampsia | Severe Pre-eclampsia | HELLP | |
| Monitoring | Routine monitors (ECG,non invasive blood pressure, pulse oximeter, (capnography or transcutaneus PCO2 in regional anesthesia), stethoscope | Routine monitors + plus an arterial line, central venous or pulmonary artery catheter+ EEG monitoring | Routine monitors + plus an arterial line, central venous (control the coagulation tests) + EEG monitoring |
| Spinal anesthesia | Whitacre or Sprotte needle, Bupivacaine 1% hyperbaric
10-15mg according to height: < 150 cm 8mg, > 150 cm 10mg, > 160 cm 12mg, > 180 cm 15mg.L1-2 level | General anesthesia if seizure. | General anesthesia if seizure or clotting abnormality. |
| Epidural anesthesia | Specially Indicated after a epidural analgesia labor..10 ml of plan Bupivacaine 0.5% to have analgesia for surgery. Risk of not completed analgesia | General anesthesia if seizure. | General anesthesia if seizure or clotting abnormality. |
| General anesthesia | Clear antacid, metoclopramide IV.Left or right uterine displacement, pre-oxygenate at least 3-4 min.
Induction: Rapid sequence: Propofol 100-150 mg or Thiopental 4 mg/kg using cricoid pressure, Succinylcholine 1 mg/kg. Maintenance: Short acting curare 1) 50% N2O until delivery, then add fentanyl, isoflurane. Or 2) Propofol infusion +N2O 50% until delivery then add fentanyl Accurate decurarization (Hypertension ) | ||
[Contents]
Epileptic pregnant women have to be
carefully evaluated and a polytherapy should be changed in a monotherapy
to avoid toxic fetal effects. The occurrence of seizures in non
epileptic patients should suggest an eclamptic syndrome. In this
case the delivery is the treatment more effective for seizures.
Drugs of choice in seizures therapy are magnesium, propofol, thiopental
and phenytoin.
visitors n.
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