A sixty year old man was admitted to the ITU with respiratory failure. He initially presented with a week long history of limb weakness that started in his legs. CSF sampling showed elevated protein levels and a diagnosis of Guillain-Barré Syndrome (GBS) was made. Symptoms progressed to weakness in coughing and deep breathing. Serial vital capacity measurements progressively deteriorated. His vital capacity on referral to ITU was 1.2L (roughly 15ml/kg), he was having difficulty expectorating and had an acute respiratory acidosis with hypercapnia. Treatment was commenced with intravenous immunoglobulin. He was initially treated with non-invasive ventilation but he continued to deteriorate largely because of sputum retention. He was sedated, intubated and invasively ventilated and after 7 days he underwent percutaneous tracheostomy to facilitate bronchial toilet and weaning. His respiratory function improved slowly and he was decannulated after 22 days of invasive ventilation. He was discharged back to neurology services for rehabilitation after a further 9 days on ITU. He remained profoundly weak on discharge and was unable to mobilise or transfer without assistance.
What are the clinical features of Guillain-Barré Syndrome and how is it managed on the ICU?
David Hepburn
Guillain-Barré Syndrome (GBS) is an autoimmune mediated acute inflammatory demyelinated polyneuropathy. It is due to autoimmune attack on Schwann cells (1). It is classically described as an acute, ascending polyneuropathy, commencing in the peripheries and moving to involve the trunk, chest and bulbar muscles. It has an incidence of 1:100,000 population, affecting men 1.5 times more frequently than women. The majority of cases have no obvious precipitating cause but there is an association with antecedent Influenza and Campylobacter jejuni (2) infection.
The disease is diagnosed on clinical history and either nerve conduction studies or CSF analysis as in this case. CSF findings are characteristic of albumino-cytological dissociation. Elevated protein levels are seen in the absence of increased CSF cell count, differentiating this condition from infectious ones where an elevated CSF protein is accompanied by increased cell load. Nerve conduction studies show conduction slowing and block as well as prolonged distal latencies. The natural history of GBS is that 80% of patients will recover, with onset of resolution after an average of 4 weeks. 5-10% will recover with severe residual disability secondary to severe motor and sensory axonal damage, in particular to proximal neurons. Mortality is 2-3% and this has not altered since the advent of ITU. (3) Deaths are commonly due to complications of prolonged immobility and treatment: pneumonias, nosocomial infections and stress ulceration. Deaths from thromboembolic complications as in this patient’s case are increasingly rare with modern approaches to thromboprophylaxis such as heparins and sequential compression devices but do still occur.
Treatment is largely based on symptomatic relief and organ support. Patients may require vasopressors for autonomic instability and ventilatory therapies for respiratory failure. Invasive ventilation is considered for patients with a >20% deterioration in vital capacity (VC) or VC of less than 20ml/kg. Bronchial toilet can be problematic if bulbar muscles are involved as well as accessory respiratory musculature as patients cannot expectorate effectively, leading to retention of secretions. A proactive approach with regard to pre-empting complications should be adopted.
In terms of specific treatments the most evidence is for the use of intravenous immunoglobulins (IVIG) and plasmapheresis. Plasmapheresis acts by removing circulating pathologic substances such as autoantibodies, immune complexes, and cytokines. The predominant mechanism by which IVIG exerts its action in GBS appears to be a combined effect on complement inactivation, neutralisation of idiotypic antibodies and cytokine inhibition (4).
Evidence has shown that plasmapheresis is effective in reducing severity and recovery times in GBS (5) but it is invasive, time consuming and can be prone to complications related to vascular access and circulatory disruption as it necessitates extracorporeal circulation and anticoagulation. A Cochrane collaboration review (6) examined trials comparing plasmapheresis with intravenous human immunoglobulin. They looked at seven trials that compared IVIG with plasmapheresis in 623 “severely affected” patients. They found that the mean difference change in a disability scale after four weeks was not significantly different between the two treatments, concluding that IVIG treatment is as effective as plasmapheresis. No trials comparing IVIG with placebo have been performed, perhaps because plasmapheresis has been established therapy for some time, has been proven superior to placebo in past studies and thus equipoise over not using it is unlikely. The cost to treat a patient with both modalities is debated in the literature with some groups declaring IVIG the more cost effective (7) and others finding plasmapheresis a more economical option (8), but the “hassle factor” with IVIG is probably reduced, and it can be performed in a ward setting more easily than can plasmapheresis.
Lessons Learnt
Guillain-Barré Syndrome is a potentially life-altering disease that still carries a significant mortality and risk of disability despite advances in intensive care medicine and respiratory and circulatory support. Sufferers may have a protracted illness course, as in this case. IVIG is currently the premier specific therapy for this condition and should be commenced as early as possible in order to have maximum effect. The evidence base is not huge and a large-scale placebo controlled crossover trial would be warranted if equipoise issues could be overcome. It has however been adopted into mainstream ICM practice doctrine and so this may be difficult.
References
1. Hughes RA, Cornblath DR. Guillain-Barre syndrome. Lancet. 2005;366:1653-1666.
ICM Case Summaries 