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Myasthenia gravis and pregnancy: anaesthetic management – a series of cases

Almeida, Carlos; Coutinho, Ester; Moreira, Daniela; Santos, Ernestina; Aguiar, José

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European Journal of Anaesthesiology: November 2010 - Volume 27 - Issue 11 - p 985-990
doi: 10.1097/EJA.0b013e32833e263f



Myasthenia gravis is an autoimmune disease characterised by weakness and fatigability of skeletal muscles, with improvement following rest.1–4 It may be referred to specific muscle groups or generalised. Myasthenia gravis is caused by a decrease in the number of postsynaptic acetylcholine receptors at the neuromuscular junction,1–5 which decreases the capacity of the neuromuscular end-plate to transmit the nerve signal.6 In myasthenia gravis, the number of activated postsynaptic receptors may be insufficient to trigger a muscle action potential.3 Further, with repeated stimulation, the decline in release of acetylcholine correlates with the characteristic fatigability.4

The estimated prevalence is 50–142 cases per million people.1 This disorder affects mostly young women, with a male: female ratio of 1: 3, and during the period in which pregnancy is likely to occur. This disorder does not have a major influence on prematurity, miscarriage or caesarean section rates, although the influence of pregnancy on myasthenia gravis is recognised and its course is unpredictable during this period.3,7,8

In order to control the disease before pregnancy and reduce exacerbations during this period, adequate management of the disease is needed and must involve anticholinesterasic drugs, corticosteroids, intravenous immunoglobulins, plasmapheresis and thymectomy.1–3,9

This disorder has well described anaesthetic implications in general anaesthesia in non-obstetric patients.3,7,10 The role of locoregional analgesia or anaesthesia in the peripartum period has been discussed in a small number of cases.10–13 The aim of this study was to analyse retrospectively the anaesthetic management of myasthenia gravis patients during vaginal delivery and caesarean section and to describe complications in both mother and newborn during the peripartum period.


Files from myasthenia gravis patients who delivered between 1985 and 2009 in Hospital Santo António, Portugal were examined. Then, we divided patients into three groups according to evolution of the disease during pregnancy. The first group included myasthenia gravis patients without exacerbations of the disease during pregnancy; the second group included myasthenia gravis patients with exacerbations of the disease during pregnancy; and the third group included patients without diagnosis of myasthenia gravis at delivery.

We collected data concerning age, parity, time since diagnosis, disease stage at delivery and treatment administered during pregnancy. Then, we described time of gestation, Osserman Classification (as modified by the Myasthenia Gravis Foundation of America; Table 1) at delivery, type of delivery, reasons for caesarean section, analgesic or anaesthetic technique used and complications in the peripartum period. Concerning the postpartum period, we described newborn complications, exacerbations of the disease or any alteration in the therapeutic regimen.

Table 1
Table 1:
Myasthenia Gravis Osserman Classification (modification by Myasthenia Gravis Foundation of America)


Seventeen myasthenia gravis patients delivered between 1985 and 2009 in Hospital Santo António. Two women were excluded from the study as they had a spontaneous abortion in the first trimester. General epidemiological and clinical data are described in Table 2. Concerning evolution of the disease during pregnancy, eight patients did not have exacerbations of the disease during pregnancy; four patients had exacerbations of the disease during pregnancy; and three patients presented mild symptoms, but without diagnosis of myasthenia gravis during pregnancy or at delivery.

Table 2
Table 2:
General epidemiological and clinical data

Concerning the first group (Table 3), pregnancy was brought to term in seven cases (87.5%); five women were submitted to non-urgent caesarean section because of obstetric causes (62.5%); three patients had vaginal delivery (37.5%); epidural block was performed in six patients (75%) and spinal block in two patients (25%). No complications occurred in these patients.

Table 3
Table 3:
Description of patients without aggravation of the disease during pregnancy

In the second group (Table 4), pregnancy was brought to term in three cases (75%); two women were submitted to non-urgent caesarean related to obstetric causes and one because of poor control of the disease (75%); one patient had vaginal delivery (25%); epidural block was performed in three patients (75%) and spinal block in one case (25%). Concerning complications, one patient was submitted to an uncomplicated thymectomy under general anaesthesia during pregnancy; in the postpartum period, there was a myasthenic crisis in one patient submitted to caesarean section under epidural block that required ventilatory support and admission to the intensive care unit.

Table 4
Table 4:
Myasthenia gravis patients who presented aggravation of the disease during pregnancy

In the third group (Table 5), a woman presenting clinically appraised mild muscular weakness during pregnancy had vaginal delivery under epidural block, without complications during the peripartum period; another woman presenting blurred vision that appeared in the third trimester was submitted to a non-urgent caesarean section under spinal block (sensitive level T6) developing aggravation of blurred vision, ptosis, oculomotricity impairment, muscular weakness and respiratory failure after motor function recovery that required mechanical ventilation and ICU admission; and the last woman presenting discrete dyspnoea in the supine position that appeared in the third trimester was submitted to a non-urgent caesarean section under general anaesthesia that resulted in delayed emergence, muscular weakness and respiratory failure requiring ICU admission. Pregnancy was brought to term in all cases.

Table 5
Table 5:
Patients presenting myasthenia gravis symptoms but without diagnosis at partum


General considerations

This series of cases of female myasthenia gravis patients in the peripartum period is to our knowledge one of the largest retrospective series of cases describing the anaesthetic management in this population.3,14

No death was reported in our study, though there are descriptions of maternal mortality of up to 3.4% in the literature, mostly related to respiratory failure.3,15 The maternal mortality risk is inversely proportional to the duration of the disease with the highest risk being in the first year after diagnosis.8 An increased risk of preterm rupture has been reported in patients with other autoimmune disorders.1,16,17 The cause of the rupture is not clear; it might be an effect of medication, namely steroids, or be related to the disease process.1 Nevertheless, the fertility of myasthenia gravis women is probably normal and the risk of prematurity is not increased.3

In our study, two cases of myasthenia gravis patients have not been included in the analysis because spontaneous abortion occurred in the first trimester. Term pregnancy was frequent and no different from in the general population. These cases of non-term pregnancy had no apparent relationship with the course of myasthenia gravis.

Specific considerations about labour/vaginal delivery

A careful evaluation before labour analgesia in strict cooperation with the neurologist is crucial.1–3,10,11 The anaesthesiologist must observe carefully the presence of respiratory distress, bulbar symptoms and muscular weakness. In pregnant women, functional pulmonary examination is advisable if there is no remission of the disease prior to labour.2,18

An adequate control of labour pain is essential to reduce the number of caesarean sections and distocic vaginal delivery rates, as myasthenia gravis can affect the second stage of delivery because striate muscles are involved and fatigability can contribute to respiratory distress.2,3,10 In patients with controlled disease, vaginal delivery is the reference method. Planning the procedure can be very important and should allow for the presence of a multidisciplinary team. In our patients, there was a tendency to a higher rate of surgical delivery, but in only three cases was the cause related primarily to myasthenia gravis. This can be explained by reasons other than clinical, because the observed rate is unusually high. Regional anaesthesia is preferred for vaginal delivery when the disease is categorised as mild-to-moderate because it allows adequate anaesthesia if operative vaginal delivery is required to shorten the second stage of labour.8,19

Epidural analgesia has a fundamental role in delivery of myasthenia gravis women, mainly because it can prevent or reduce the administration of potentially respiratory depressant systemic analgesics, regularise breathing and reduce fatigability. The presence of the catheter is valuable as transition to surgical delivery may be necessary.3,20,21 Utilisation of low concentrations of local anaesthetic can prevent motor block3,10,13 and opioids are usually combined with local anaesthetics.2,8,10 In our series of cases, local anaesthetics were combined with the liposoluble narcotic, sufentanil, allowing the usage of low concentration of local anaesthetics. Anticholinesterase may impair the hydrolysis of the ester-type local anaesthetics; therefore, amide-type local anaesthetics are preferable for regional block in myasthenic patients.2,8 The surveillance of the motor block in labour analgesia is crucial; thus, ropivacaine is preferable because the differential block is more evident and less likely to produce motor block that can negatively influence the dynamic process of delivery.3,22 In our series, there was a transition from bupivacaine to ropivacaine in the last years. Both were used safely and effectively. In our study, it was not possible to observe the stage of labour at which analgesia was started. Early initiation of labour analgesia is preferable because stress, pain and fatigability may exacerbate symptoms, preventing vaginal delivery, or provoking an increase in the rate of dystocic deliveries as the expulsion stage depends on adequate striate muscle function.3,8,14

Specific considerations about caesarean section

Concerning the anaesthetic approach to caesarean section, an extension of anaesthetic block higher than the T4 dermatome can compromise the integrity of respiratory function and airway patency.3 This makes epidural block more suitable than spinal block in these patients. Nevertheless, epidural block requires a higher dose of local anaesthetic than spinal block.

General anaesthesia is recommended for caesarean section in myasthenic patients with significant bulbar or respiratory involvement to better control airway, oxygenation and secretions.2,3,8,19

In general anaesthesia, neuromuscular block drugs are frequently avoided as adequate block can be achieved with inhalation agents and non-depolarising agents are difficult to titrate: their effects are more profound and last longer. Neuromuscular block reversion can produce a cholinergic crisis provoked by an excessive amount of acetylcholine in the motor plaque.2,3,8,10

In recent years, sugammadex in combination with rocuronium has led to a change in practice in some centres. It has been used successfully to reverse rocuronium-induced neuromuscular blockade in patients with myasthenia gravis, thereby avoiding the need for reversal with acetylcholinesterase inhibitors.23,24

Myasthenic patients are relatively resistant to succinylcholine, therefore necessitating larger doses, though this is more prone to provoke a phase II block.8 Narcotics should be used with caution because respiratory depression can supervene.2,3,8,19

We hypothesised that the myasthenic crisis in the women with de-novo myasthenia gravis reported after caesarean section under general anaesthesia could be explained by the modifying aspect of the delivery in myasthenia gravis, emotional or surgical stress, pain, fatigability, perioperative administration of neuromuscular block or cholinergic crisis.

These reasons make locoregional anaesthesia ideal to avoid postoperative respiratory complications in myasthenia gravis.

Specific considerations about patients who presented aggravation of disease during pregnancy

During the first 3 months postpartum, the risk of relapse may be as high as 30%. In our patients, exacerbations were controlled by increasing the daily doses of anticholinesterase or corticosteroid drugs or by initiating immunoglobulins in some patients. The anticholinesterasics are oxytocics but cross the placenta only poorly.3,20

Currently, the majority of authors consider that corticosteroid drugs must be used at the lowest possible dose. Immunosuppressor drugs are teratogenic and are contraindicated.3,7,10,25 Plasma exchange may be necessary to control symptoms.2

In these patients, magnesium sulphate is especially contraindicated as it can interfere in neuromuscular transmission and provoke an exacerbation of myasthenia gravis.3,10,21

The major exacerbations occurred during the second and third trimester and puerperium, though in the literature they are described more frequently in the first trimester.8,26

There was a tendency to a higher Osserman stage at delivery in this group. One patient presented myasthenic crises in puerperium, beginning on the 2nd day postpartum and 1 week later required therapeutic optimisation, several plasma exchange sessions and periods of mechanical ventilation in the ICU.

In our opinion, a higher Osserman stage at delivery and aggravation of the disease during pregnancy may be associated with a higher rate or more severe complications in the peripartum period. To support this hypothesis, further studies are necessary. No complication in mother or newborn in patients without aggravation of the disease was reported.

Specific considerations about patients presenting symptoms during pregnancy but without myasthenia gravis diagnosis at partum

Three patients presented undiagnosed mild myasthenia gravis symptoms in the last trimester. Two women submitted to caesarean section under spinal block or general anaesthesia developed respiratory insufficiency associated with neurological symptoms (ocular or bulbar symptoms together with muscular weakness) not explained by residual effect of local anaesthetics or intravenous drugs. Diagnosis was established on the 3rd postoperative day in both cases.

From the anaesthesiologist point of view, we think that myasthenia gravis must be considered as a differential diagnosis if respiratory insufficiency associated with neurological symptoms occurs in the peripartum period. The reasons to consider this condition are that this syndrome is not frequent, pregnant women are young, pregnancy can modify or precipitate the disease, the therapeutic approach is specific and life-threatening complications are more likely to occur during the first year after diagnosis.1–3 This presentation can occur after locoregional or general anaesthesia, as it was observed in this study.

Specific considerations about newborns

Newborns must be kept under strict surveillance because a myasthenic crisis may occur in 20–30% according to some studies.2,8 In the majority of cases, the newborn myasthenic crisis occurs during the first 24 h postpartum.7–11,27,28 This syndrome is caused by maternal transfer of antibodies and is characterised by muscular weakness (inadequate cry and suction, facial neutrality and respiratory failure can be present). It generally lasts 3 weeks after delivery.1–3,7,11 We found no complications in the newborns.

Limitations of the study

As a retrospective series of cases, our records were limited to the data registered in the clinical files. Some data were missing or not systematically described such as sensitive level of the neuroaxial block and time from beginning of labour analgesia to delivery.


Myasthenia gravis can interfere slightly in pregnancy and partum, although exacerbations of the disease frequently occur. Strict surveillance and therapeutic optimisation are crucial. In women with controlled disease, caesarean section should be carried out only if there are obstetric reasons. Locoregional anaesthesia is preferred, mainly epidural block. Good multidisciplinary cooperation, specific precautions and surveillance can certainly contribute to improved outcome in myasthenia gravis patients during the peripartum period.


The authors have not received any external assistance, financial support or sponsorship to perform this study and the authors have no conflicts of interest to report.


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