Intensive Care for Guillain-Barre Syndrome

The CICM examiners love GBS. Their love is probably proportional to the importance of this condition for the intensivist, as a GBS patient often makes the ICU their home for some considerable number of weeks. Some of the GBS-flavoured questions from the exam in recent past have included the following:

• Question 27 from the second paper of 2020
• Question 10 from the first paper of 2013
• Question 22 from the first paper of 2020

Not only does GBS appear in SAQs but it inevitably finds its way into the hot cases. If there's a GBS at the hospital where the exam is being held, you bet your arse they're going in front of the candidates. Locally, chapters of interest include Approach to the ICU patient with generalised weakness and Features that distinguish Guillain-Barre syndrome from critical illness polyneuromyopathy. Distally, a LITFL article on GBS offers an extensive and well-referenced revision resource. 

Diagnosis of GBS

From Shahrizaila et al (2021): 

• Required criteria:
  • Bilateral and flaccid weakness of limbs
  • Decreased or absent deep tendon reflexes
  • Absence of alternative diagnosis
• Supportive clinical features:
  • Monophasic course (i.e. "just keeps getting worse")
  • Time between onset to plateau 12 h to 28 days
  • Symmetry of features
  • Sensory sparing (usually, no sensory loss- only paraesthesia)
  • Cranial nerve involvement (the Miller Fisher variant - classically, ataxia areflexia and ophthalmoplegia)
  • Autonomic dysfunction
  • Absence of fever at onset

Laboratory findings

• CSF protein is elevated, and monocytes and lymphocytes are present in the CSF
•  
• Blood IgG may be elevated
• The Miller Fisher variant may have GQ1b antiganglioside antibodies and the axonal forms may have antiganglioside GM1 antibodies

Electrolphysiology

• Nerve conduction studies: reduced conduction velocity and prolonged distal latencies are the cardinal findings
• LITFL lists the following NCS features:
  • Reduced conduction velocity
  • Multifocal conduction blocks
  • Abnormal temporal dispersion of compound muscle action potentials
  • Prolonged distal latencies
  • Prolonged F-waves

Imaging

• A contrast MRI may demonstrate enhancement and thickening of anterior nerve roots, but this is not diagnostic. Radiopedia has a thing about it.
• MRI probably has greater value in ruling out other causes of ascending weakness (eg. a stinking huge epidural abscess).

Features suggestive of poor prognosis in GBS:

• Age over 60
• Rapid progression in less than 7 days
• Mechanical ventilation
• A preceding diarrhoeal illness

Overall, the mortality in GBS patients admitted to ICU is around 25% according to Oh's Manual

Sensitising infections

• Campylobacter jejuni
• CMV
• Influenza A
• Parainfluenza,
• Varicella-zoster
• Epstein–Barr virus
• HIV
• Mycoplasma

Important staging investigations

These patients are often referred to the ICU for "monitoring in case of deterioration". Of course, the same could be said of all the patients in the hospital (they could all deteriorate!) and it would be unusual for the intensivist to admit the patient to the ICU just because a diagnosis of GBS has been established. Of the total number of GBS patients admitted to hospital, there is a large proportion who never require ICU admission. For example,  Barnes & Herkes (2019) reported a 13% ICU admission rate in a cohort from Concord Hospital in Sydney, which is a mixed ICU/HDU environment, i.e. it would be unexpected for them to be especially reluctant to accept "soft" patients. They would not have allowed borderline cases to languish in the general medical wards.

So, what criteria can you use to decided whether a patient needs to come to the ICU for ongoing monitoring? This is a decision which is not made on the basis of deteriorating lung function alone, but deteriorating lung function certainly seems to have become the focus of attention. Specifically, spirometry data has somehow risen into a position of prominence. The "20/30/40 rule" is often quoted, which consists of:

• FVC less than 20ml/kg (i.e. 1400ml for a normal 70kg male)
• Maximim inspiratory pressure (MIP) less than 30cmH₂O
• Maximum expiratory pressure (MEP) less than 40cmH₂O

This 20/30/40 rule, which everybody seems to uncritically apply, has come from a paper by Lawn et al (2001), which was a single centre retrospective study reporting on a historical period spanning from 1976 to 1996. It has already been publically dismembered by Josh Farkas, and nothing else about it can be usefully said, other than it should not be used as the sole trigger for intubation in GBS. However, to abandon the mindless application of this rule does not mean to completely ignore spirometry data. One should make their decision on the basis of a multifaceted assessment which takes into account all of the angles of this complex situation.

So, in summary, the following factors would need to be considered: 

• Patient factors:
  • Frailty, i.e. physiological reserve, age, baseline function, and whether ICU admission and aggressive treatment are appropriate
  • History of chronic respiratory illness and other comorbidities
  • New acute respiratory complications, eg. hospital-acquired pneumonia
  • Clinical features suggesting worsening respiratory function, such as:
    • Deteriorating peak flow (eg. a PEF rate less than 250 L/min)
    • Falling FVC (say, below 20ml/kg, or a decrease of 50% from FVC predicted by age/height/gender)
    • Falling MIP (say, under 30 cmH₂O)
    • Falling MEP (say, under 40 cmH₂O)
    • Poor cough
    • Increasing PaCO₂
• Disease factors:
  • Time course of progression: i.e. rapid deterioration over recent days
  • Type of disease, eg. "vanilla" GBS vs Miller-Fisher
  • Involvement of the autonomic nervous system (it can produce the sort of haemodynamic instability that could make the ward staff very nervous)
  • Whether appropriate treatment has been started, and how long ago
• Environmental factors:
  • Evidence that the patient is not being monitored with sufficiently attentive diligence, eg. missing FVC data from previous days
  • Level of skill of ward staff where the patient remains
  • Monitoring capacity of the environment where the patient remains, eg. availability of continuous cardiac monitoring or oximetry
  • Capacity of the ICU or hospital to care for the patient with GBS (eg. availability of immunoglobulin or plasmapheresis  in a small regional hospital)

Specific management

• Corticosteroids are counterproductive. Or rather, it appears the positive effect of dampening the autoimmune demyelination is offset by the negative effect of melting away the muscles. The net effect is zero effect, at least in terms of measurable patient-centred outcomes. For example, Hughes et al (2016) found that the steroids had no effect on mortality or the level of disability.
• Plasmapheresis works: 4 exchanges of 1-2 plasma volumes, over 1-2 weeks.
  Plasma exchange for Guillain-Barre syndrome aims to clear the aetiological autoantibody from the bloodstream. In essence, we say "we have no idea which antibody is causing the demyelination, so we will get rid of all of them". The evidence seems to support a 5-treatment regimen; it seems that six treatments are no better than four. Because there is no missing proteins to replace, the exchanged plasma can be FFP or albumin - it does not seem to matter to the resolution of disease. However, because FFP has a slightly higher risk of transfusion reactions, so in general albumin is the recommended replacement solution, unless there are specific reasons to replace blood proteins.
• IV immunoglobulin is at least as effective as plasmapheresis. Dose is 2g/kg. The college answer to Question 20 from the first paper of 2016 mentions a Cochrane review, probably referring to Hughes et al (2014) who demonstrated that in severe disease IVIG within the first 2 weeks "hastens recovery as much as plasma exchange".

Early vs. late tracheostomy

When do we offer them a tracheostomy? Nobody knows, is the short answer, but it appears as if there is no point in rushing into anything.

Some experts hold that if the pulmonary function tests fail to improve with treatment and two weeks of intubation has passed without change, a tracheostomy should be offered. Patients showing subtle improvement might be able to wait for another week. This is consistent with observational data which suggest that most patients with GBS seem to get a tracheostomy after about 12 days of ventilation, which is roughly the period of time required to trial plasmapheresis or immunoglobulin and to become disappointed with their effects. By twelve days, the intensivist will have come to the conclusion that we are in this for the long haul, and a tracheostomy is inevitable.

Early tracheostomy, on the other hand, does not seem to have much of a mortality benefit. One might expect to find it, as many GBS patients cannot be successfully extubated; for example in one small but representative study of 44 patients, Nguyen et al (2006) were only able to successfully extubate 14. Surely, one might say, it is pointless to wait, as most of these people cannot be weaned quickly. Yes, this may be true, but an early tracheostomy ritual does not seem to ward against major complications of ICU stay, and does not seem to improve mortality. Early small-scale studies seemed to suggest that a late tracheostomy was associated with more chances of a ventilator associated pneumonia (Ali et al, 2006), but the larger the studies get, the smaller this effect seems to become.  In their observational study of 654 tracheostomised GBS patients, Naoki et al (2020) were not able to find any outcome difference between patients who had a tracheostomy within the first 7 days of their stay, vs. those who had a tracheostomy after the obligatory two-week wait.

In summary:

• There is no mortality benefit from early tracheostomy in GBS
• It may not protect them from VAP
• Some patients with GBS may get extubated normally without requiring a tracheostomy
• Ergo, it is better to wait.

Supportive management

Question 22 from the first paper of 2020 specifically asked about the different factors which predispose these patients to frequent infections, and how you would go about minimising that risk. The answer to that question is duplicated here to facilitate revision:

Factors which Contribute to the Increased Risk of Nosocomial Infection among Patients with Guillain-Barre Syndrome

Infectious consequences	Contributing factors
VAP	Prolonged intubation Gram-negative colonisation of the lower airway Poor oral hygiene (with intubation) Weak cough
Sinusitis	Prolonged NGT dwell-time
Hospital-acquired pneumonia	Weak cough Impaired airway defence reflexes Prostration and basal atelectasis
Pressure area infections	Prolonged immobility
Line-related sepsis	Prolonged need for parenteral medications
Urinary tract infection	Long term IDC
Increased predisposition to infection	Immunosuppressant therapies Malnutrition
Resistant organisms	Multiple courses of antibiotics Prolonged hospital stay, and therefore increased risk of cross-contamination

With this exercise behind us, we can easily recombine the contributing factors into a structured list of interventions designed to address them:

Strategies for the Prevention of Nosocomial Infection
in Patients with Guillain-Barre

Factor	Intervention
Prolonged intubation	An early tracheostomy could prevent VAP, on the basis of older smaller studies (Ali et al, 2006)
Gram-negative colonisation of the lower airway	Consider SDD Upright (30 degrees head up) position Discontinue PPI to maintain lower GI tract acidity Promote gastro-oesophageal sphincter competence by removing NGT when able
Poor oral hygiene	Extubate early to give the nurses access Educate nursing staff re. importance of oral hygiene, and promote internal audits of compliance
Weak cough	Chest physiotherapy to assist cough Postural drainage Longer suction catheters
Prolonged NGT dwell-time	If prolonged swallowing dysfunction is anticipated, a PEG may be a better option
Impaired airway defence reflexes	Prevent aspiration by the methods recommended in the VAP prevention section above (eg. head up position, etc) If feeding orally, ensure the fluids are thickened and the diet is puree.
Prostration and basal atelectasis	Ensure daily physiotherapy engagement and encourage early passive mobilisation (eg. placing the patient into a chair-like position i bed)
Prolonged immobility	Realistically, this is GBS and you can't do much about this. Anecdotally, it appears that larger and earlier doses of IVIG tend to produce a more rapid improvement, but this is really not the topic of discussion here.
Prolonged need for parenteral medications	Rationalise IV medications (eg. can't that paracetamol be oral?) Rationalise IV antibiotics Rationalise central access (if it has to be parenteral, can it be peripherally parentral?) If central access is imperative, transition to PICCs
Long term IDC	Unless the patient has specific urinary retention problems, the IDC may be superfluous in the later stages of disease
Immunosuppressant therapies	Corticosteroids have no role to play and so you shouldn't be using them anyway
Malnutrition	Optimal nutrition (including protein intake) may require specialist dietitian consultation and a means of delivering the nutrients safely (eg. PEG)
Resistant organisms	Antibiotic stewardship should be practiced
Cross-contamination with MROs	Single room with handwashing basin and alcohol handrub for staff Standard contact precautions for all visitors