Meta Analysis Plasma exchange for Guillain-Barre syndrome
This review may be edited
Summary
Posted By:	Gordon S. Doig
E-Mail:	Gordon.Doig@EvidenceBased.net
Posted Date:	13 Aug 2002
Title:	Plasma exchange for Guillain-Barre syndrome
Authors:	Raphael JC, Chevret S, Hughes RAC and Annane D.
Reference:	Cochrane Database of Systematic Reviews 2002;Volume(Issue 2):no page #
Link:	Click here for a direct link to the paper. A password may be required for access to fulltext.
Abstract:	Background: Guillain-Barre syndrome is an acute symmetric, usually ascending and usually paralysing illness, due to inflammation of peripheral nerves. It is thought to be caused by autoimmune factors, such as antibodies. Plasma exchange removes antibodies and other potentially injurious factors from the blood stream. It involves connecting the patient's blood circulation to a machine which exchanges the plasma for a substitute solution, usually albumin. Several studies have evaluated plasma exchange for Guillain-Barre syndrome. Objectives: To systematically review the evidence concerning the efficacy of plasma exchange for treating Guillain-Barre syndrome. Search strategy: Search of the Cochrane Neuromuscular Disease Trial Register for randomised trials concerning plasma exchange in Guillain-Barre syndrome, search of the bibliographies of identified papers and enquiry from the authors of the papers. Selection criteria: Randomised and quasi-randomised trials of plasma exchange versus sham exchange or supportive treatment. Data collection and analysis: Potentially relevant papers were scrutinised by two reviewers and the selection of eligible studies was agreed by them and a third reviewer. Data were extracted by one reviewer and checked by a second reviewer. Some missing data were obtained from the authors of studies. Main results: Six eligible trials concerning 649 patients were identified, all comparing plasma exchange versus supportive treatment alone. Primary outcome measures Time to recover walking with aid In the only two trials for which this measure was reported, the median time to recover this ability was faster in the plasma exchange than the control group. Time to onset of motor recovery in mildly affected patients In the one trial for which this measure was available, the time was significantly shortened in the plasma exchange group. Secondary outcome measures Improvement in disability grade at four weeks In five trials, there were significantly more patients who had improved by one disability grade or more in the plasma exchange group as compared to the control group. Patients treated with plasma exchange fared significantly better in the following secondary outcome measures: time to recover walking without aid, percentage of patients requiring artificial ventilation, duration of ventilation, full muscle strength recovery after one year, and severe sequelae after one year. There were less patients with infectious events and cardiac arrhythmias in the plasma exchange than the control group. Subgroup analyses Plasma exchange was beneficial in patients with mild, moderate and severe (needing ventilation) Guillain-Barre syndrome. It was beneficial in patients with a disease duration of seven or less days and also in those with disease lasting more than seven days. However, in the only trial that enrolled patients up to 30 days from disease onset, the benefit of plasma exchange in patients treated after seven days was less apparent. Type of treatment Single studies showed that two plasma exchanges were significantly superior to none for mild Guillain-Barre syndrome and four to two for moderate Guillain-Barre syndrome, but that six were not superior to four for severe Guillain-Barre syndrome requiring ventilation. One study suggested that continuous flow plasma exchange was significantly superior to intermittent flow. Another study found no significant difference between the two techniques. The same study found a significantly higher rate of adverse events with fresh frozen plasma as the replacement fluid than albumin. Plasma exchange compared with cerebrospinal fluid filtration A single trial comparing these two treatments did not show any difference in outcomes but was too small to demonstrate equivalence. Conclusions: Plasma exchange is the first and only treatment that has been proven to be superior to supportive treatment alone in Guillain-Barre syndrome. Consequently, plasma exchange should be regarded as the treatment against which new treatments, such as intravenous immunoglobulin, should be judged. In mild Guillain-Barre syndrome two sessions of plasma exchange are superior to none. In moderate Guillain-Barre syndrome four sessions are superior to two. In severe Guillain-Barre syndrome six sessions are no better than four. Continuous flow plasma exchange machines may be superior to intermittent flow machines and albumin to fresh frozen plasma as the exchange fluid. Plasma exchange is more beneficial when started within seven days after disease onset rather than later, but was still beneficial in patients treated up to 30 days after disease onset. The value of plasma exchange in children less than 12 years old is not known. There is insufficient evidence to determine whether cerebrospinal fluid filtration is equivalent to plasma exchange.
Are the Results Valid?
1. Did the overview address a focused clinical question?
	Yes. The authors state that the objective of the review is to examine the efficacy of plasma exchange in hastening recovery and reducing the long term morbidigy from Guillian-Barre syndrome (GBS).
2. Were the criteria used to select articles for inclusion appropriate?
	Yes. The authors explicitly state their criteria for article selection. They selected papers including children and adults where GBS was diagnosed according to internationally accepted diagnostic criteria. The authors also state that they considered randomized and pseudo-randomized trials.
3. Is it unlikely that important, relevant studies were missed?
	The Cochrane Neuromuscular Disease Review Group registry was searched combined with a review of bibliographies retrieved. Experts and industry were also contacted. Due to the nature of the content, it is unlikely that important trials were missed however confidence in the process could have been increased by cross-validating the search against primary Medline and EMBASE search strategies.
4. Was the validity of the included studies appraised?
	YEs, validity was appraised. It is interesting to note that none of the studies reviewed were blinded. The reviewers report that "Sham apheresis would have been the only method for patient blinding, and it was thought unethical by all authors." There are studies investigating plasma exchange in chronic inflammatory demyelinating polyneuropathy that have successfully employed a Sham aphoresis process to achieve blinding. This approach could have easily been employed in any study of acute inflammatory demyelinating polyneuropathy.
5. Were assessments of studies reproducible?
	No. The authors do not provide a measure of agreement between two independent reviewers with regards to study validity.
6. Were the results similar from study to study?
	Yes. There was no statistical heterogeneity. The Forrest Plots (aka Peto-grams) also demonstrate that results were similar from study to study.
What are the Results?
1. What are the overall results of the overview?
	Primary endpoints Time to recover walking with aid Overall, there were no significant differences with regards to time to recover walking with an aid. Time to onset of motor recovery Based on the results of only one trial, the median time to onset of motor recovery was significantly shorter in the plasma exchange (PE) group (6 vs. 10 days, p<0.0001) Secondary endpoints Improvement in disability grade 4 weeks after randomization Mean grade improvment was 1.1 in the PE group compared to 0.4 in the control (p<0.001). Time to recovery of walking without aid. Overall results were uninterpretable due to heterogeneity. Percentage of mechanically ventilated patients. Based on results from 5 studies, significantly fewer patients required ventilation 1 month after randomization to the PE group (RR = 0.53, 95%CI 0.39 to 0.74, p=0.0001). Time to weaning from the ventilator after randomization. Based on results from two studies, duration of ventilation was not signifcantly different. Percentage of patients with full muscle strength recovery at one year. Based on results from 5 trials, the chance of full muscle recovery after one year was significantly increased in the PE group (RR 1.24, 95%CI 1.07 to 1.45, p=0.005). Percentage of deaths at one year. There was no significant difference in mortality rates. Percentage of patients with severe sequalae at one year. There were significantly fewer patients with severe sequalae in the PE group (RR 0.65, 95%CI 0.44 to 0.96, p=0.03). Percentage of relapses at one year. Based on follow-up from 6 trials, there were significantly more relapses in the PE treated group (RR 2.89, 95%CI 1.05 to 7.93, p=0.04) Subgroup Analyses Younger and older There was no clear effect of age on outcome due to PE. More severly or less sevely affected Seperate data for less severly affected patients (defined as those able to walk at randomization) was not readily available. For more severly affected patients (defined as those requiring mechanical ventilation at randomization), studies demonstarte consistent benefit from PE. Number of plasma exchanges. 4 PEs have been demonstarted to be better than 2 PEs. Trials comparing 6 PEs to 4 PEs did not demonstrate any difference. Costs Fully costed studies comparing outcomes in GBS patients who could stand unaided at the start of the trial reported that the total cost of care in the PE arm was 20,876 Euros per patient compared to 38,877 Euros per patient in the control arm. For patients who could not stand, the total cost of care in the 4PE arm was estimated at 56,335 Euros per patient compared to 78,293 Euros per patient in the 2PE arm. In ventilated patients, the cost per patient in the 6PE arm was 55,983 Euros compared to 53,221 Euros in the 4PE arm.
2. How precise were the results?
	See above for 95% CIs.
Will the Results Help Me In Caring For My Patients?
1. Can the results be applied to my patient care
	Yes. The trials included in this review are fairly representative of the GBS patient who requires ICU care. Results are presented for GBS patients who required mechanical ventilation.
2. Were all clinically important outcomes considered?
	Yes. The authors conducted a very comprehensive review. The only outcome missing was a formal quality of life tool.
3. Are the benefits worth the harms and costs?
	Yes. The review suggests that PE improves patient outcomes AND reduces costs. Thus PE can be considered a 'dominant technology'. The increase in relapse rates should be monitored and investiagted in future studies.
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