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Three Part Question

In [patients experiencing pain complicating Guillain Barre syndrome] do [anticonvulsants provide better analgesia than opiates] and [with fewer side effects]?

Clinical Scenario

A 9 year old girl is admitted to the Paediatric Intensive Care Unit (PICU) with a diagnosis of GBS. She has global motor weakness with a MRC power grade 3 and does not require mechanical ventilation. She has dysautonomia and remains on the PICU for respiratory and invasive arterial monitoring. During her admission she develops severe leg and back pain. Regular paracetamol and non-steroidal anti-inflammatories are ineffective. Your educational supervisor asks you whether anticonvulsants would be an effective analgesic, or whether the tried and tested opiates would be the best option.

Search Strategy

Cochrane Library and Medline database
Cochrane - Guillain Barre (MeSH – explode) and pain (explode). Medline - Guillain Barre (explode all fields) and pain (explode all fields). Limit LA = English

Search Outcome

Cochrane 13 hits - 1 relevant
Medline 21 hits - 2 relevant

Relevant Paper(s)

Author, date and country	Patient group	Study type (level of evidence)	Outcomes	Key results	Study Weaknesses
Pandey et al 2002 India	18 adults with GBS and pain >3 on scale 1-10 All mechanically ventilated Group 1 given gabapentin for 7 days then after 2 days washout, placebo for 7 days Group 2 given placebo for 7 days, 2 days washout, then gabapentin	Double blinded randomised controlled cross over trial. Period of treatment with gabapentin (PTG) versus period of treatment with placebo (PTP) were directly compared, not one group versus other, due to cross over nature of trial.	Improvement of pain scores	Pain scores during PTG fell from 7.22 + 0.83, day 0, to 2.06 + 0.63, day 7 (p<0.001). Pain scores during PTP fell from 7.83 + 0.78, day 0, to 5.67 + 0.91, day 7, (non sig)	Small numbers
			Use of rescue analgesia (2 mcg/kg fentanyl)	Rescue analgesia in PTG 211.11 + 21.38 mcg, day 1, fell to 65.55 + 16.17 mcg, day 7, (p< 0.001). In PTP 319.44 + 25.08 mcg fell to 316.67 + 24.25 mcg (non sig)
Tripathi and Kaushik 2000 India	12 adults with pain complicating GBS All mechanically ventilated Group 1 given placebo for 3 days, 1 day washout, then 3 days carbamazepine Group 2 carbamazepine then placebo	Prospective, double blinded, randomly controlled cross over trial	Pain scores on an ordinal scale 1 to 5	Group 1 pain scores 4.2 + 0.6 (control) fell to 3.5 + 0.6, day 3, (nsd); then fell to 1.5 + 0.6, day 7, (p< 0.001). Group 2 pain scores 4.7 + 0.5 (control) fell to 1.2 + 0.5, day 3, (p<0.001), then rose to 3.0 + 0, day 7 (nsd)	Small numbers Short treatment and washout time
			Use of rescue analgesia (pethidine requirements)	Rescue analgesia: Group 1 4.1 + 0.9 mg/kg/day fell to 4.5 + 0.4, day 3, (non sig), then fell to 0.5 + 0.6, day 7 (p<0.5). Group 2 3.9 + 1.0 mg/kg/day fell to 0.2 + 0.5, day 3, (p<0.5), then rose to 3.6 + 0.6, day 7 (nsd)

Comment(s)

The apparent success of carbamazepine, an anticonvulsant with an unknown mode of action, in the treatment of pain associated with GBS was documented as long ago as 1970 (2). Since then, anticonvulsants have been shown to be effective in neuropathic pain of differing origin (1). There have been only two trials conducted in a cohort of patients with GBS that have compared the use of anticonvulsants to placebo, with opiate rescue analgesia. The trials, using either gabapentin or carbamazepine, despite small numbers, have shown both a significant reduction in opiate requirements and in the subjective perception of pain, as assessed by pain scales. The advantages to reducing the opiate requirements are obvious. In both trials the sedation scores were significantly reduced in the groups receiving anticonvulsants at that time. Improved sedation scores can lead to improved respiratory function and less time weaning from mechanical ventilation. Side effects from the anticonvulsants were not apparent. Can we draw the conclusions above given that the data reviewed was obtained from adult patients? We believe that the data is applicable in this case. Guillain Barre syndrome is a disease that commonly affects adults and older children but can affect children as young as infants. Pain pathways in older children are similar to those of adults and there is growing evidence that pain pathways are fully functional in the newborn. In this age of evidence based medicine there is more adult data available than paediatric, possibly secondary to difficulties of ethics, recruitment and consent. To ignore all adult data and reproduce randomised trials in children would be time consuming, expensive and unethical, particularly in cases such as the one cited above where the underlying pathophysiology is very similar. Our conclusions from studying the adult data led us to apply the findings to our paediatric practice. We do endorse the need for seeking out critically appraised 'paediatric literature' where available, but to ignore all adult data is to do the child a disservice. We suggest that in circumstances similar to ours – where the pathophysiology of the disease is understood and similar to the mature state – adult data should be considered.

Clinical Bottom Line

Guillain Barre syndrome can be associated with pain in up to 55-80% of patients (3) This pain tends to be of two different types; musculoskeletal and neuropathic. Anticonvulsants are at least as effective as opiates in treating the neuropathic pain in GBS. They have the additional advantages of reducing the opiate requirements and consequently lessening sedation scores and opiate-related side effects.

References

1. Pandey CK, Bose N, Garg G, et al. Gabapentin for the treatment of pain in Guillain Barre syndrome: A double-blinded, placebo-controlled, crossover study. Anesth Analg 2002;95(6):1719-23.
2. Tripathi M, Kaushik S. Carbamazepine for pain management in Guillain Barre syndrome patients in the intensive care unit. Crit Care Med 2000;28(3):655-58.
3. Winspur I. Tegretol for pain in the Guillain Barre syndrome. Lancet 1970;1(7637):85.
4. Backonja MM. Use of anticonvulsants for treatment of neuropathic pain. Neurology 2002;59(5 Suppl 2):S14-7.
5. Pentland B, Donald S. Pain in the Guillain Barre syndrome: a clinical review. Pain 1994;59:169-64.