CASE REPORT

Saúl Alvarez Robles, MD^*. Germán Darío Álvarez Villamizar, MD^**

* Médico anestesiólogo. Profesor asistente Posgrado en Anestesiología y Reanimación, Universidad Industrial de Santander, Bucaramanga-Colombia. Hospital Universitario de Santander, Departamento de Cirugía. E-mail: salvarob@uis.edu.co.

** Médico residente de tercer año, posgrado en Anestesiología y Reanimación, Universidad Industrial de Santander.

Recibido: Noviembre 11/2009 Aceptado: Diciembre 11/2009

This case deals with a 25-year-old patient, G1P0, who was admitted already undergoing preterm labour (33 weeks) and in treatment for urinary infection caused by Proteus mirabilis. She had a background of myasthenia gravis which had been diagnosed five years before and had suffered annual relapses. 15 months ago she had presented a myasthenic crisis which required tracheostomy and ventilatory support in an ICU, as well as thymectomy 10 months before being admitted. She was currently receiving 60 mg pyridostigmine bromide every six hours.

Her weight was 50 Kg during the physical exam. She was in good physical state: 31cm uterine height, 3 cm dilatation and 70% shortening. There were no signs of respiratory insufficiency.

Uterine activity persisted up to the third day after being admitted, meaning that corticoids were applied for inducing pulmonary maturation; likewise, peridural analgesia was ordered for labour. As labour did not progress, it was decided to perform a caesarean section, this being done under peridural anaesthesia, without complications.

The newborn was in a good state, scoring 8 on the APGAR scale without signs of respiratory difficulty, having good tone and a somewhat superficial respiratory pattern. Paediatrics were managed with 50mg IM pyridostigmine and the newborn was taken to the ICU due to the risk of neonatal myasthenia. The patient evolved satisfactorily.

The mother began to present respiratory difficulty and hypoxaemia during the immediate puerperium; it was thus considered that she was surfing a myasthenic crisis. Because of this she was intubated and transferred to the ICU. Ventilatory support was administered there, consisting of 10 mg EV methylprednisolone c/6h and 60mg IV pyridostigmine every 6 hours. It was decided to apply 0.2 gr /Kg day immunoglobulin at 48 hours for the next five days. She was discharged from the ICU after 72 hours with suitable oxygenation indices and without consequences.

Myasthenia gravis (MG), described for the first time by the physiologist Thomas Willis (17th century), is an alteration of the neuromuscular plate which could be acquired or be autoimmune. It is characterised by muscular weakness affecting a muscular a group, but may also be generalised, having a calculated incidence of around 85/100,000 (1) or 50 to 142 cases per million(2) It affects females more frequently (2:1 ratio), especially during the second and third decades of life, this being a time when there is a greater probability of becoming pregnant(3-4) There is another peak of incidence between the sixth and seventh decade, but this time mainly affecting males.

Even though MG has been recognised as being a disease for more than 300 years, the use of oral and parenteral neostigmine was only discovered by neurologists Walter and Everts in 1935. The first case of MG during pregnancy to be treated with neostigmine was reported by Tabachnick in 1938(5)

75% of patients follow a course with thymic alterations (85% hyperplasia, 10%-15% thymomas) and 85% with high acetylcholine receptor antibodies. The entity may occur via one of the three following mechanisms(6)

• Accelerated degradation of acetylcholine receptors;
  
• Blocking antibody-mediated receptors; and
  
• Secondary damage to the neuromuscular junction.

Osserman and Genkis classified MG as follows( 7)

• Class 1: just ocular myasthenia, with ptosis and diplopia
  
• Class 2A: generalised moderate weakness
  
• Class 2B:generalised moderate weakness and/ or bulbar dysfunction
  
• Class 3: acute fulminant presentation and/or respiratory dysfunction
  
• Class 4: late severe generalised compromise

It has been shown that pregnancy frequently triggers myasthenia gravis: 126 pregnancies were reported in 87 patients affected by this entity between 1938 and 1962 in the literature published in English.

Djelmis et al., reviewed 69 cases of females suffering from MG and pregnancy, finding a 15% deterioration in clinical state and 16% during peripartum, whilst 17% terminated in caesarean; however, only one had an exacerbated indication of MG.3 Plauché(8) found that 31% of pregnant females with MG did not present changes in their clinical course, 28% improved and the condition of 40% worsened during the immediate postpartum period. It thus follows that the effects of gestation on MG are not so relevant during pregnancy as during the postpartum period, where greater complications become evident. The case cited here confirms this.

To et al., however, only found 5 cases of MG in a total of 161 pregnant female patients suffering from neurological disorders;(9) even studies in ICU have shown that up to 50% of critical obstetric patients have neurological compromise(10)

The condition of around 30% to 41% of pregnant females suffering from MG worsens regarding gestation; this happens to half of them during the postpartum period(3-4-8-11)

When reviewing the literature in 1964, Plauché( 12) found that 57% of 87 MG patients in a series of 126 pregnancies presented postpartum exacerbations and only 14% improved during this period. Likewise, he described exacerbations during pregnancy in 16% of the patients, whilst 38% had remission of the disease and 46% did not present changes. The first and third trimesters were the most prone to exacerbations, generally being related to infectious diseases and emotional disturbances, even though cases were mentioned which were caused by summer heat. Caesarean section was necessary in 5.6% of the cases and forceps use was high. The puerperium was a critical period, the first 10 days postpartum being considered to have a high risk of exacerbations being presented(12) There was 2.4% mortality during this period. Postpartum haemorrhage incidence, however, was not a frequently occurring problem.

The risk of clinical deterioration has been seen to be greater in females who became pregnant during the first year that the disease was diagnosed( 3-4) Recurring infection during gestation or puerperium could lead to myasthenic crisis with reparatory parálisis.(3-11) Djelmis(3) saw that all females suffering puerperal infections developed exacerbations. Respiratory tract and urinary system infections were most associated with MG.

Anticholinesterasic medicaments, such as pyridostigmine, are continued during pregnancy; however, the dose should be increased due to reduced gastric emptying speed and poor intestinal absorption during gestation(13) these medicaments must be administered by intravenous route during birth, since oral absorption is unpredictable(13)

Anticholinesterase drugs may increase uterine tone and contractility, even though it has not been demonstrated that they increase the incidence of spontaneous abortion. Corticoids are also continued during pregnancy, in spite of the risk of cleft palate in the foetus (class B)(13) Azathioprine is used when there is no response to corticoids (this is a class D drug)(11-13) Cyclosporine A is also used, having similar results to azathioprine (class C).

Plasmapheresis is reserved for patients having severe bulbar symptoms or respiratory compromise requiring mechanical ventilation (myasthenic crisis)(3-11-13) Intravenously administered immunoglobulin is used when plasmapheresis cannot be used.

Therapeutic abortion is not useful when managing MG(3-11) and caesarean is only carried out following obstetric indications.

Even though preeclampsia may occur, Mg sulphate is not recommended because it increases muscular weakness; there are also drugs which can trigger a myasthenic crisis such as aminoglycosides and halogenates(11)

The foetal monitoring test is not reliable in MG patients. Other methods should be used instead for ensuring foetal wellbeing. On the other hand, some studies have suggested increased incidence of premature birth and perinatal death in MG patients(11-13) but duration of birth does not become altered(13) Possibly due to this musculature type not being affected by the pathology, labour does not become affected; however, increased incidence of forceps use has been shown due to the lack of expulsive force.

Around 10% to 20% of myasthenic mothers’ newborn develop the syndrome due to transplacentary transfer of antibodies against Ach receptors(3-11) Neonatal myasthenia was diagnosed in 30% of all newborn in Djelmis’ study( 3) and such incidence was inversely associated with the disease’s duration. Symptoms could appear after 12 hours, last up to three months and, sometimes, require mechanical ventilation(3-11-13) even though usually for short duration(14)

This syndrome is characterised by weakness, inability to suck, swallow and cry, having recurrent episodes of cyanosis. Diagnosis is confirmed by therapeutic test with anticholinesterasics; a patient’s improvement constitutes confirmation. It has been observed that thymectomised mothers’ newborn have shown low neonatal myasthenia rate compared to non-thymectomised mothers’ newborn.

Anaesthetic management

The pathology’s severity and the treatment regime must be reviewed in all patients suffering MG during pregnancy who require surgery. It is important to evaluate muscular strength for respiration. A patient’s ability to maintain and protect the postoperative airway may become impaired if there is preoperative bulbar compromise. If a patient (in spite of treatment) is poorly controlled, a course of plasmapheresis could be beneficial before programmed surgery (13)

Patients having the disease are particularly sensitive to non-depolarising relaxant action, which could become manifest in patients having minimum compromise (e.g. in single-eye compromise (15) patients having remission of symptoms (16) or non-diagnosed subclinical cases),( 17) meaning that the impregnation dose for preventing fasciculation must not be used as this could lead to loss of airway protection. SD95 for these medicaments ranges from 40% to 55% of normal control (18-19) Elimination is not affected(18) SD95 for vecuronium ranges from 40% (17 μg/Kg cf 24μg/Kg)18 to 55% (20 μg/Kg cf 36 μg/Kg)(19) compared to normal controls.

Increased sensitivity for mivacurium has also been reported.(20) Recovery was prolonged (25%-75% index for 20.5 minute T1 cf 11.9 minutes) in patients who have been receiving pyridostigmine;( 21) this inhibits mivacurium metabolism, thereby increasing recovery time. A drug such as atracurium is thus preferable in these patients,(22) even though broad variability (58% DE95) has been observed with it (0.14 mg/Kg cf 0.24 mg/Kg) compared to normal controls. These patients are also sensitive to cisatracurium, as seen by faster onset of action and longer blocking- action compared to controls.

On the other hand, SD95 for depolarised MNB is 2.6 times greater than normal control (0.8 cf 0.3 mg/Kg)(23) A 1.5 to 2 mg/Kg dose is suggested for rapid-sequence induction.(24) MG patients are more likely to present phase II block with repeated doses. Metabolism may also become affected due to reduced cholinesción terase when a patient is given plasmapheresis, or when receiving anticholinesterasics. Neuromuscular transmission monitoring must always be used.

Some authors recommend that anticholinesterasics not be applied on the day of surgery for reducing neuromuscular relaxant requirements, whilst others suggest continuing them for maintaining psychological support.

Inhaled anaesthetics cause muscular relaxation in healthy patients and their sensitivity is greater in myasthenics; however, it is difficult make a comparison since response is very individual (24-25) It has been shown that 2.5% sevoflurane depresses T1/T control response to 47% and T4/T1 to 57% (26) Sevoflurane and isoflurane seem to depress neuromuscular function at the same level, but their sensitivity in myasthenic patients is greater by up to 85% T1 suppression.

Corticoids have been shown to reduce nondepolarised MNB requirements in MG.(27) Likewise, the most tolerated short-term endovenous aesthetics are ones such as propofol (28) which also does not have effects on the neuromuscular plate.

Opioids in analgesic plasma concentrations do not depress neuromuscular transmission in these patients.(29-30) Due to its short-action, remiphentanyl offers advantages, but its dependence on metabolism by ester hydrolysis is affected by anticholinesterasic use, thereby prolonging its action (31)

Subarachnoideal regional anaesthesia has proved to be safe in MG patients; however, precaution must be taken with the anaesthetic level so as not to block intercostal muscular innervation and avoid respiratory compromise(13) likewise, chlorprocaine must not be used as it has been shown that it causes weakness in MG patients. Problems may also be encountered with ester-type anaesthetics in patients taking anticholinesterasics as these are metabolised by cholinesterase, meaning that they should be avoided.

POP pain control has been shown to be greater with regional anaesthesia, without increased respiratory depression and better vital capacity.( 32)

It is essential to predict that patients may need mechanical ventilation during the postoperative period. Previous work has identified factors predicting the need for mechanical POP ventilation, such as: 1) > 6 years MG duration, 2) chronic respiratory disease, 3) > 750 mg pyridostigmine dose and 4) < 2.9 Lt CV.^33-34

Recent studies have identified: 1) being female, 2) < 3.3 Lt. / sec FEF 25 – 75 and < 85% predicted value, 3) < 2.6 Lt CVF and < 78% predicted value and 4) < 3.9 Lt/sec FEM and < 80% predicted value.(33-35-36)

Particular attention must thus be paid to the final phases of pregnancy in MG patients since they have an increased risk of presenting a myasthenic crisis during this period. Likewise, it is important to considerer the different responses observed with anaesthetic drugs so that safe attention is ensured for this type of patient.

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