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A review of myasthenia gravis in cardiac surgery

Marzia Cottini

Department of Heart and Vessels, Cardiac Surgery Unit and Heart Transplantation Center, S. Camillo-Forlanini Hospital, Italy

E-mail : marzia.cottini@hotmail.it

Marco Picichè

Department of Heart and Vessels, Cardiac Surgery Unit and Heart Transplantation Center, S. Camillo-Forlanini Hospital, Italy

AmedeoPergolini

Department of Heart and Vessels, Cardiac Surgery Unit and Heart Transplantation Center, S. Camillo-Forlanini Hospital, Italy

Tania Dominici

Department Heart and Vessels A.Reale, Policlinico Umberto I, La Sapienza, Italy

Francesco Musumeci

Department of Heart and Vessels, Cardiac Surgery Unit and Heart Transplantation Center, S. Camillo-Forlanini Hospital, Italy

DOI: 10.15761/JIC.1000145

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Abstract

Thymomatous Myasthenia G (T-MG) is an uncommon acquired, neuromuscular and autoimmune disorder characterized by weakness of skeletal muscles presented with episodes of remission and exacerbation due to action of antibodies against acetylcholine receptors. What is the best surgical and anesthesiologist management of T-MG patients? Morbidity and mortality depend on integrated cardiac, neurological and respiratory management. The onset of respiratory and immunological complications represent the main obstacles to a successful outcome.

Keywords

myasthenia gravis, neurological disease in cardiac surgery, neuromuscular disease, surgical management of myasthenia gravis

Introduction

Myasthenia Gravis (MG) is a neuromuscular autoimmune disorder that affects neuromuscular transmission leading to generalized or localized muscle weakness. Most frequently it is due to the binding of autoantibodies against acetylcholine receptors in the postsynaptic motor end-plate (AChR antibodies) [1, 2].AChR antibodies specific to skeletal muscles do not bind to heart muscle [3] and the 48% of all MG cases have antibodies towards heart muscle [4]. The annual incidence of MG is 1-2/100.000 with an estimated prevalence of 5-15/100.000, in twenty-one percent of the patient the disease onset after 60 years [5].MG crisis is characterized by worsening muscle weakness, resulting in respiratory failure that may require intubation and mechanical ventilation. In postsurgical patients, exacerbation of muscle weakness may cause a delayed prolonged intubation. MG crisis is a very important, serious, and reversible neurological emergency that affect 20/30% of the MG patients, usually within the first year of illness.Most patients have a predisposing factor that trigger the crisis, generally surgical stress or infection of respiratory tract.

Materials and methods

The search strategy consisted of a search of Medline, Pubmed, Cochrane database of systematic reviews, from 2000 to 2015, with the following keywords "myasthenia gravis and cardiac surgery", "myasthenia gravis preoperative management" and "myasthenia and surgery".

References were analyzed for additional relevant studies to be included in the reviews. Suitable article were independently reviewed by 2 authors and further revised by the principal investigator.

The studies that were eligible for the analysis consisted of case series describing patients with T-MG underwent to cardiac surgery. Inclusion or exclusion criteria for patients undergoing cardiac surgery were not standardized between different study centre. Single case report, series of less than 5 patients, and published abstracts from oral presentation were included.The primary outcome is the best management of T-MG patients undergoing cardiac surgery. Secondary outcomes included procedural success rate.

Case report

A 61-year-old male with a history of thymectomy thirty years earlier and residual thymomatous-myasthenia gravis (Table 1), presented to the hospital suffering from shortness of breath and chest pain. He was admitted for inferior ST elevation myocardial infarction. TransThoracic Echocardiography (TTE) revealed a moderate mitral valve regurgitation (regurgitation volume 45 cc, EROA 0.3 cmq) and mild left ventricle hypokinesis of the infero-lateral wall. Coronary angiography showed significant critical stenosis on the Left Anterior Descending artery (LAD), obtuse marginal and posterior interventricular arteries. He was prepared with intravenous immunoglobulin (IVIG, 2g/Kg for two days) to cardiac surgery procedure.

Patient Characteristics

Cardiac Disease

CAD and Mitral Regurgitation

Age

61yrs

Sex

Male

Copathologies

Hypertension, Dyslipidemia, Thymomatous Myasthenia Gravis

Previous Anaesthesia

1. Thymectomy in full, sternotomy for Thymoma,( Masaoka III, WHO B1)

2. Repeated thymectomy in full sternotomy (Masaoka II, WHO B1)

Drugs

Steroids,  Pyridostigmine

 

 

Table 1:Baseline Patient characterists

He underwent triple coronary artery bypass surgery and mitral valve annuloplasty by standard cardiopulmonary bypass and through median sternotomy access. The patient was discharged without any perioperative or postoperative complications.

Discussion

Myasthenia gravis is an uncommon autoimmune disorder that affect postsynaptic acetylcholine receptors of voluntary muscle and results in weakness and fatigue of the affected muscle group [6,7] MG occurs in 3-7 people per 100.000 and is more frequent in females than males [4,6,8]. Of major clinical importance is the classification of myasthenia gravis developed by Osserman[9].In 1958, he proposed placing patients with myasthenia gravis in five groups: I – localized (ocular), II – generalized (mild or moderate), III – acute fulminating, IV – late severe, and V – muscle atrophy. Furthermore, Osserman divided group II into subgroup A (mild) and subgroup B (moderate) as follow. Various modified criteria have been suggested over the years by the Medical Scientific Advisory Board of the Myasthenia Gravis Foundation of America, MGFA [10].This classification allows to grade the disease and to assess the perioperative risk and possible complications [9,11](Table 2). Medical treatment for MG consists of anticholinesterase agents, steroids, immunosuppressive and plasmapheresis to reduce serum antibody concentration [7,11,12-15].Management of patients with clinical history of MG is complex because of the high risk of respiratory failure and disseminated intravascular coagulation [13,16-19]. Its management could be difficult from a decision-making standpoint, and treatment clearly needs to be tailored on single patients individualized [20-22] due to the individual reaction to analgesia and muscle relaxants [13,16,20]. Endo and Colleagues [7] use high dose of steroids (1 mg/Kg/day) to decrease the rate of postoperative respiratory insufficiency. OtherwiseZielinski and coworkers [23] suggest to not use steroids in types I and IIA patients for the negligible risk of crisis. In addition they usually start steroid at low doses (0.5 mg/Kg/day of prednisone), increasing the dose every second day until reaching the optimal dose of about 1 mg/Kg/day. Other authors suggested using preoperative prophylactic low dose of IVIG (10 g daily for 3 days) to reduce the incidence of allosensibilization and consequently the production of autoantibody that causes onset of crisis [24-26]. With regards to the use of preoperative and perioperative immunosuppressant agent, there is still not unanimous consensus.The anesthesiological management of MG patients requires a special considerations. Hayashidaet al.[17]reported a successful management of a patient with MG undergone to coronary artery bypass. The general anaesthesia was induced with fentanyl and midazolam, and vecuronium bromide was administered whilst a neuromuscular transmission monitor was applied. Agrifoglio and coworkers [27] described the successful case of a patient who underwent mitral valve repair and was found to have thymomatous MG without any particular differences (Table 3).

In our experience, the correct management of preoperative patient with MG stands on administration of IVIG (10g daily for 3 day) for any type of MG.

Classes

Characteristics

I

Ocular myasthenia

IIA

Mild generalized myasthenia with slow progression: no crises,

responsive to drugs

IIB

Moderately severe generalized myasthenia : severe skeletal

and bulbar involvement but no crises; drug response less than

satisfactory

III

Acute fulminating myasthenia, rapid progression of severe

IIIA: predominantly limb,

symptoms, with respiratory crises and poor drug response

axial or both

IIIB: predominantly

oropharyngeal and respiratory

IV

Late severe myasthenia, same as III but progression over 2

IVA: predominantly limb,

years from class I to II

axial or both

IVB: predominantly

oropharyngeal and respiratory

V

Intubation with or without ventilation

Table 2: Modified Osserman Classification (9) of myasthenia gravis characteristics depending of the grade of weakness and involved muscle group.

We suggest an oral premedication (for instances lorazepam or flunitrazepam). On arrival in the operating theatre, the general anaesthesia could be induced with fentanyl (20/50 mcg/kg/dose IV) and midazolam, and low-dose of atracurium (0.3 mg/Kg). In our patient, neuromuscular transmission was blocked with atracurium administered at fractional doses of 1 mg until the required degree of relaxation. The Nerve stimulation monitoring was useful and important, it could be performed by the Datex-Ohmeda, model Train of Four (TOF) and Bispectral Index of Monitoring (BIS). Maintenance doses of 1 mg (0.3 mg/kg body weight) were administered every 50 min [28-30]. The management described above resulted in excellent circulatory stabilization. We didn't start steroids in the perioperative period. We usually administer them after the 7 th postoperative day in order to decrease the risk of infection of the wound, pneumonia, coagulation and blood glucose disorders (Table 4).

N° of

Cardiac

Preoperative

Anesthesia

Postoperative

patients of

management of

Authors

Year

Surgery

management

management of

MG

MG

Procedure

of MG

MG

considered

Hayashida et

2000

1

CABG

Premedication:

Fentanyl

/

al (17)

Flunitrazepam

Midazolam

Vecuronium

Harooun-

2003

1

CABG

/

Low dose

/

Bizri et al

cisatracurium

(31)

NMT monitoring

hypothermia

Suzuki et al

2004

1

Pericardiectomy

(32)

Asai et al

2004

1

CABG

/

/

Steroids

(33)

Grigolia et al

2006

1

CABG

/

No use of any

/

(34)

myorelaxants,

restriction of

opioids, use an

inhalation

anaesthetics and

propofol

Waitande et

2007

57

Thymectomy

/

/

Pyridostigmine

al (6)

(sternotomy)

PYR+Azathioprine

Pyr + steroids

None (70.2%)

Agrifoglio et

2009

1

MVr

Standard

Standard

/

al (27)

Narin et al

2009

1

MVr

/

Sufentanil

/

(35)

Propofol

No any muscle

relaxant agent

Rafiq et al

2011

1

TAVR

Azatioprine

(36)

Wang et al

2011

1

AVR, MVR, TVR

(37)

and thymectomy

Komoda et al

2013

1

AVR

/

/

/

(38)

Cheng et al

2013

141

ETT

/

/

Corticosteroids

(39)

treatment:

independent

negative predictor

Marulli et al

2013

100

Robotic

IVIg (12%)

/

Cholinesterase

(40)

Tymecthomy

Prednisone(56%)

inhibitors

No steroids or low

dose

Argiriou et al

2013

1

AVR, MVR

/

Cisatracurium, no

/

(41)

muscle relaxants

Demir et al

2014

1

CABG

/

Reduced doses of

/

(42)

muscle relaxants

HasanZaidi

2014

1

CABG

Prednisolone

/

Plasmapheresis

et al (43)

Pyridostigmine

Prednisolone

Pyridostigmine

Kowalczyk et

2015

2

CABG

/

Cisatracurium

/

al (44)

Table 3:  Perioperative, postoperative baseline characteristics in the management of MG patient undergoing cardiac surgery procedures.A prospective evaluation of the scientific literature. CABG= coronary artery bypass graft, MVr= mitral valve repair, ETT= Extended transthoracic thymectomy, AVR= aortic valve replacement, MVR= mitral valve replacement, TAVR= transcatheter aortic valve replacement, TVR= tricuspid valve replacement, NMT= neuromuscular transmission[45]

Preoperative Management

Operative Management

Postoperative management

●   IVIG (10g daily for 3 day)

●   Fentanyl (20/50 mcg/kg/dose IV)

NO MG CRISIS:

●   Premedication  (lorazepam

●   Midazolam

AChR antibodies dosing

or flunitrazepam)

●   Low-dose of atracurium (0.3

Restart Azathioprine

mg/Kg)

Restart Cyclosporine

●   Atracurium (fractional doses of 1

Restart Cholinesterase inhibitors

mg until the required degree of

No steroids

relaxation)

o    Restart low dose of

●   Monitoring (TOF and BIS)

oral steroids after

7th/10th postoperative

day

IF MG CRISIS:

●   iv steroids → low dose of

Prednisolone

Plasma exchange therapy

IVIg therapy

Table 4:  Suggestion for a good management of MG patient undergoing cardiac surgery procedure. IV=intravenous, IVIg= intravenous immunoglobulin.

Conclusion

The presented case confirmed the difficulty of decision-making standpoint in management of respiratory and immunological settings due to the individual reaction to analgesia and muscle relaxants. We prepared the patient with intravenous immunoglobulin and the general anaesthesia was managed with fentanyl, midazolam and low dose of atracurium.

The best way of preparing a patient for a surgical procedure is to recognize both the underlying medical condition and coexisting diseases. Proper awareness of these makes it possible to arrange individual pre-, peri- and postoperative management. Each stage of perioperative care could be thoroughly analysed and planned. Currently used neuromuscular transmission blockers are considered safe, with the recovery of normal muscle function occurring after a period specific to each drug. Acetylcholinesterase inhibitors are used to accelerate the recovery of normal neuromuscular transmission following administration of nondepolarizing neuromuscular blockers. On the contrary, the late use of steroids could decrease the spreading of infection, iatrogenic diabetes mellitus and modification of coagulation onset.

References

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Editorial Information

Editor-in-Chief

Massimo Fioranelli
Guglielmo Marconi University

Article Type

Research Article

Publication history

Received: December 01, 2015
Accepted: December 15, 2015
Published: December 18, 2015

Copyright

©2015 Cottini M. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Citation

Cottini M, Picichè M, Pergolini A, Dominici T, Musumeci F (2015) A review of myasthenia gravis in cardiac surgery. J Integr Cardiol, 2: DOI: 10.15761/JIC.1000145

Corresponding author

Marzia Cottini

Department of Heart and Vessels, Cardiac Surgery Unit, S. Camillo-Forlanini Hospital, 00149 Rome, Italy, Tel: +39-347-3245331, Fax: +39-06-58704511.

E-mail : marzia.cottini@hotmail.it

Patient Characteristics

Cardiac Disease

CAD and Mitral Regurgitation

Age

61yrs

Sex

Male

Copathologies

Hypertension, Dyslipidemia, Thymomatous Myasthenia Gravis

Previous Anaesthesia

1. Thymectomy in full, sternotomy for Thymoma,( Masaoka III, WHO B1)

2. Repeated thymectomy in full sternotomy (Masaoka II, WHO B1)

Drugs

Steroids,  Pyridostigmine

 

 

Table 1:Baseline Patient characterists

Classes

Characteristics

I

Ocular myasthenia

IIA

Mild generalized myasthenia with slow progression: no crises,

responsive to drugs

IIB

Moderately severe generalized myasthenia : severe skeletal

and bulbar involvement but no crises; drug response less than

satisfactory

III

Acute fulminating myasthenia, rapid progression of severe

IIIA: predominantly limb,

symptoms, with respiratory crises and poor drug response

axial or both

IIIB: predominantly

oropharyngeal and respiratory

IV

Late severe myasthenia, same as III but progression over 2

IVA: predominantly limb,

years from class I to II

axial or both

IVB: predominantly

oropharyngeal and respiratory

V

Intubation with or without ventilation

Table 2: Modified Osserman Classification (9) of myasthenia gravis characteristics depending of the grade of weakness and involved muscle group.

N° of

Cardiac

Preoperative

Anesthesia

Postoperative

patients of

management of

Authors

Year

Surgery

management

management of

MG

MG

Procedure

of MG

MG

considered

Hayashida et

2000

1

CABG

Premedication:

Fentanyl

/

al (17)

Flunitrazepam

Midazolam

Vecuronium

Harooun-

2003

1

CABG

/

Low dose

/

Bizri et al

cisatracurium

(31)

NMT monitoring

hypothermia

Suzuki et al

2004

1

Pericardiectomy

(32)

Asai et al

2004

1

CABG

/

/

Steroids

(33)

Grigolia et al

2006

1

CABG

/

No use of any

/

(34)

myorelaxants,

restriction of

opioids, use an

inhalation

anaesthetics and

propofol

Waitande et

2007

57

Thymectomy

/

/

Pyridostigmine

al (6)

(sternotomy)

PYR+Azathioprine

Pyr + steroids

None (70.2%)

Agrifoglio et

2009

1

MVr

Standard

Standard

/

al (27)

Narin et al

2009

1

MVr

/

Sufentanil

/

(35)

Propofol

No any muscle

relaxant agent

Rafiq et al

2011

1

TAVR

Azatioprine

(36)

Wang et al

2011

1

AVR, MVR, TVR

(37)

and thymectomy

Komoda et al

2013

1

AVR

/

/

/

(38)

Cheng et al

2013

141

ETT

/

/

Corticosteroids

(39)

treatment:

independent

negative predictor

Marulli et al

2013

100

Robotic

IVIg (12%)

/

Cholinesterase

(40)

Tymecthomy

Prednisone(56%)

inhibitors

No steroids or low

dose

Argiriou et al

2013

1

AVR, MVR

/

Cisatracurium, no

/

(41)

muscle relaxants

Demir et al

2014

1

CABG

/

Reduced doses of

/

(42)

muscle relaxants

HasanZaidi

2014

1

CABG

Prednisolone

/

Plasmapheresis

et al (43)

Pyridostigmine

Prednisolone

Pyridostigmine

Kowalczyk et

2015

2

CABG

/

Cisatracurium

/

al (44)

Table 3:  Perioperative, postoperative baseline characteristics in the management of MG patient undergoing cardiac surgery procedures.A prospective evaluation of the scientific literature. CABG= coronary artery bypass graft, MVr= mitral valve repair, ETT= Extended transthoracic thymectomy, AVR= aortic valve replacement, MVR= mitral valve replacement, TAVR= transcatheter aortic valve replacement, TVR= tricuspid valve replacement, NMT= neuromuscular transmission[45]

Preoperative Management

Operative Management

Postoperative management

●   IVIG (10g daily for 3 day)

●   Fentanyl (20/50 mcg/kg/dose IV)

NO MG CRISIS:

●   Premedication  (lorazepam

●   Midazolam

AChR antibodies dosing

or flunitrazepam)

●   Low-dose of atracurium (0.3

Restart Azathioprine

mg/Kg)

Restart Cyclosporine

●   Atracurium (fractional doses of 1

Restart Cholinesterase inhibitors

mg until the required degree of

No steroids

relaxation)

o    Restart low dose of

●   Monitoring (TOF and BIS)

oral steroids after

7th/10th postoperative

day

IF MG CRISIS:

●   iv steroids → low dose of

Prednisolone

Plasma exchange therapy

IVIg therapy

Table 4:  Suggestion for a good management of MG patient undergoing cardiac surgery procedure. IV=intravenous, IVIg= intravenous immunoglobulin.