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Management of Guillain-Barré syndrome with plasmapheresis or

immunoglobulin: Our experience from a tertiary care institute in South India

Article  in  Renal Failure · March 2014

DOI: 10.3109/0886022X.2014.890859 · Source: PubMed

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! 2014 Informa Healthcare USA, Inc. DOI: 10.3109/0886022X.2014.890859

CLINICAL STUDY

Management of Guillain–Barré syndrome with plasmapheresis or

immunoglobulin: our experience from a tertiary care institute in
South India
C. Krishna Kishore1, J. Vijayabhaskar2, R. Vishnu Vardhan3, V.V. Sainaresh1, P. Sriramnaveen1, A.V.S.S.N. Sridhar1,
B. Varalaxmi1, P. Sandeep1, R. Ram1, B. Vengamma2, and V. Siva Kumar1
1
Department of Nephrology, Sri Venkateswara Institute of Medical Sciences, Tirupati, AP, India, 2Department of Neurology, Sri Venkateswara
Institute of Medical Sciences, Tirupati, AP, India, and 3Department of Statisitcs, Ramanujan School of Mathematical Sciences, Pondicherry
University, Kalapet, Puducherry, India
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Abstract Keywords
Guillain–Barré syndrome (GBS), an acute inflammatory demyelinating polyneuropathy is the Developing country, disability, Guillain–Barre
most common generalized paralytic disorder. The objective was to study the outcome of syndrome, immunoglobulin,
disability grade in two groups of GBS treated with plasmapheresis alone and treated with IVIg plasmapheresis
alone. A retrospective analysis of all consecutive patients with GBS, admitted in our intensive
care unit during the period of 3 years, 2009–2012 were included in the study. All patients of GBS History
who were to be treated with plasmapheresis or IVIg, the modality of management were always
decided at their preference and consent after explaining the modalities to patient/family. Received 1 October 2013
For personal use only.

The plasma exchange done was 200–250 mL of plasma per kilogram weight in five sessions Revised 1 January 2014
(40–50 mL/kg per session) within 7–14 days. The replacement fluid contained 100 mL of 20% Accepted 26 January 2014
albumin diluted in 1000 mL of normal saline and 1000 mL of fresh frozen plasma. IVIg was Published online 28 February 2014
administered as 0.4 g/kg body weight daily for 5 days. Our observations brought out the
following, both the plasmapheresis and IVIg treatments were effective in reducing the disability
grade amongst all time points, i.e., at presentation, immediate post-therapy and after 4 weeks.
There was a marginal superiority in plasmapheresis over IVIg effect. However, whether the
delay in presentation as noted in our study probably would have contributed to this effect was
conjectural.

Introduction 2–5% die. The likelihood of permanent disability increases

with severity and duration of disease and patients may
Guillain–Barré syndrome (GBS), an acute inflammatory
require prolonged stays in the hospital.3,4 Therefore,
demyelinating polyneuropathy is the most common general-
keeping the disability and prognosis in view, the disease
ized paralytic disorder with an approximate incidence of
needs specific treatment. Oral and intravenous steroids were
two cases per 100,000 population. The disorder usually
proved to be ineffective.5,6 The rationale for plasmapheresis
presents with acute motor deficits and sensory symptoms
is the existence of a circulating factor that reproduces
involving peripheral nerves. GBS is believed to be an
in vitro, the electrophysiological and histological patterns of
autoimmune process due to the finding of complement
demyelination.7 Subsequently, several large randomized
binding IgM antibodies directed against peripheral nerve
trials were taken up to study the effect of plasmapheresis
myelin.1,2 Although many patients with GBS recover
in the treatment of GBS. The North American GBS study
spontaneously, 10–23% require mechanical ventilation,
group,3 the French study group,8,9 the English study
7–22% are left with some disability, 3–10% relapse and
group,10 and the Swedish study group,11 have all shown
comparable benefit with plasmapheresis. They found
plasmapheresis was beneficial when applied within first 4
weeks of onset, but largest effect was seen when started
early (with in first 2 weeks). A review of literature revealed
that the intravenous immunoglobulin (IVIg) had comparable
efficacy with the plasmapheresis in the management of
Address correspondence to Ram R, MD DM, Associate Professor, GBS. The objective was to study the outcome of disability
Department of Nephrology, Sri Venkateswara Institute of Medical
Sciences, Tirupati, AP, India. Tel: +91-9848246364; E-mail: grade in two groups of GBS treated with plasmapheresis
[email protected] alone and treated with IVIg alone.
 2 C.K. Kishore et al. Ren Fail, Early Online: 1–5

Materials and methods The replacement fluid contained 100 mL of 20% albumin
diluted in 1000 mL of normal saline and 1000 mL of fresh
Study design and patients
frozen plasma. IVIg was administered as 0.4 g/kg body weight
A retrospective analysis of all consecutive patients with GBS, daily for 5 days. Patients received other supportive medication
admitted in our intensive care unit during the period of like prophylactic doses of heparin, antibiotics and proton
3 years, 2009–2012 were included in the study. The data were pump inhibitors. Neurorehabilitative care was also given. The
recorded on a ProForma. disability grade was studied measured at three different
periods, i.e., at presentation, immediately post-therapy and
Definitions after 4 weeks.
(1) Diagnosis of GBS: The diagnosis of GBS was done based
on National Institute of Neurological and Communicable Statistics
Disorders and Stroke (NINCDS) 1990 criteria.12 The statistical software used was PASW SPSS 18.0 version.
(2) Disability grade: The degree of motor function was For categorical data, chi-squared test has been used. Mann–
expressed on a seven-point functional scale used in Whitney U test was applied to compare the plasmapheresis
previous trials, on which 0 denotes healthy; 1, having and IVIg groups. Friedman test was used to compare the
minor symptoms and signs but fully capable of manual disability grading at different time points, i.e., at presentation,
work; 2, able to walk 10 m without assistance; 3, able to immediate post-therapy and after 4 weeks. p-Value50.05 was
walk 10 m with a walker or support; 4, bedridden or taken as significant.
chair bound (unable to walk 10 m with a walker or
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support); 5, requiring assisted ventilation for at least part Results

of the day; and 6, dead.3,10,13
The study included data from GBS patients treated in our
institute during 2009 and 2012. During the study period 90
Treatment modalities
patients of GBS were treated. Of them 29 patients were
All patients of GBS who were to be treated with plasma- treated with IVIg and 61 patients were treated with plasma-
pheresis or IVIg, the modality of management were always pheresis. The mean ages were 30.862 and 35.737 years,
decided at their preference and consent after explaining the respectively. The male to female ratio was 63.33%/36.67%
modalities to patient/family. The neurologist played an active
For personal use only.

and there was uniform distribution in both the groups (IVIg:

role in these discussions. 62.06%/37.93%; plasmapheresis: 63.93%/36.06%). There
Patients with vital capacity 515 mL/kg, partial pressure of were no statistically significant clinical differences between
oxygen of 570 mmHg or a partial pressure of carbon-dioxide the groups in age and duration before the treatment was
of 445 mmHg were placed on mechanical ventilator. initiated after the diagnosis of GBS (Table 1).
The plasma exchange (membrane based apheresis) done We observed on comparison using Friedman test, both
was 200–250 mL of plasma per kilogram weight in five modalities of treatments were found to be significant in
sessions (40–50 mL/kg per session) within 7–14 days. improving the patient disability grade (Table 2).

Table 1. Comparison of characteristics of patients in IVIg group and plasmapheresis.

All patients Respiratory (mechanical ventilation) patients

IVIg Plasmapheresis IVIg Plasmapheresis
Std. Std. t Value Std. Std. t Value
Mean Error Mean Mean Error Mean (p value) Mean Error Mean Mean Error Mean (p value)
Age (years) 30.8621 3.775 35.737 1.874 1.297 (0.198NS) 28.571 7.341 34.667 6.242 0.636 (0.535NS)
Duration (days) 8.4483 1.085 6.442 0.358 2.207 (0.030*) 6.571 1.020 6.667 1.000 0.066 (0.949NS)
Distal motor amplitude 1.272 0.2156 1.807 0.1353 2.171 (0.033*) 0.643 0.3939 1.089 0.3454 0.852 (0.409NS)
(mV)
Sex (M/F) 18/11 39/22 5/2 6/3
History of preceding 13/16 29/32 3/4 6/3
infection (present/no)

Notes: ‘‘*’’ represents significance and ‘‘NS’’ represents not significant. For sex and history of preceding infection, p values were not computed as they
are categorical variables.

Table 2. Comparison of the effect of treatments on the disability grade at different time points.

All patients Respiratory (mechanical ventilation)

I.V.Ig Plasmapheresis I.V.Ig Plasmapheresis
Duration Mean ± SE Mean ± SE Mean ± SE Mean ± SE
Disability grade at presentation 4.00 ± 0.131 4.02 ± 0.068 5.00 ± 0.000 5.00 ± 0.000
Disability grade at immediate post-therapy 3.31 ± 0.150 3.00 ± 0.096 3.86 ± 0.261 3.67 ± 0.167
Disability grade at after 4 weeks 2.28 ± 0.267 1.33 ± 0.161 3.14 ± 0.634 2.33 ± 0.441
 DOI: 10.3109/0886022X.2014.890859 Management of Guillain–Barré syndrome 3
Table 3. Superiority of plasmapheresis over IVIg in reducing the plasmapheresis or with IVIg. The number of patients in
disability grade.
plasmapheresis and IVIg groups was different. But there were
Treatments N Mean ± Std. Error Mean
no statistically significant clinical differences between the
groups in age and duration of before the treatment was
Plasmapheresis 61 1.65 ± 0.147 initiated after the diagnosis of GBS. The results suggested
IVIg 29 1.07 ± 0.230
The Z value is 2.329 (p ¼ 0.000*) that the plasmapheresis was marginally, superior to the IVIg
(the Z value is 2.329, p value ¼ 0.000*) in improving the
*Significance at 0.05 level. disability grading in the entire group and also in respiratory
(mechanical ventilation) patients.
In a recent systemic review the immunotherapy of GBS
has been discussed.14 There were six publications comparing
plasma exchange and IVIg with adults constituting as
predominant population. In addition, there was one similar
study in pediatric patients of GBS.13,15–20
The previous studies are reviewed in the Table 4. A review
of these studies revealed that the IVIg had comparable
efficacy in five of the studies and PE was found to be superior
only in one study. This last study was in pediatric population.
In this study, it is possible that the children might have had an
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intense autoantibody production with a high percentage of

these antibodies already bound to nerves on development of
respiratory failure. Hence, the removal of already bound
antibodies with PE, in comparison to blocking antibody
production, IVIg is helpful.
Guillain–Barré syndrome is appeared to be mediated by a
Figure 1. Reduction in disability grade between immediate post-therapy monophasic IgM, anti-peripheral nerve myelin antibody and
and after 4 weeks in both the groups. by high titers of IgG antiganglioside antibodies. The IgM
For personal use only.

antibody can be removed by plasma exchange. The plasma

exchange reduces the antibody to 520% by 2–3 weeks,
Table 2 shows that there was a statistically significant whereas without plasma exchanges the antibody levels
improvement in the disability grade in both the modalities of decrease to 20% by 3–9 weeks.21 The advantage of the
the treatments not only when studied as an overall effect but removal of autoantibodies, by plasma exchange is that it
also in the respiratory patients who were on ventilator creates a concentration gradient between the lowered blood
support. level and the extravascular space forcing antibody movement
However, plasmapheresis was found to be associated with from the extra to the intra vascular space to be removed
more improvement in comparison to IVIg with the application during the subsequent session.22 Plasma exchange is most
of Mann–Whitney U test in both the groups (Table 3). beneficial when started within 7 days of disease onset, but is
On graphical representation of the same it was further also efficacious when started after 30 days.23 In the present
evident that the average reduction in disability grade was study, the plasma exchange was started within 7 days, but
superior in plasmapheresis group over IVIg group (Figure 1). there was approximately a median difference of 2 days
We further studied the association between the prognostic between the initiation of plasma exchange and IVIg. This
variables: age, sex, history of preceding infection, duration of difference was, however not significant as the disability
illness till the start of the treatment and distal motor grade was similar both groups at the initiation of treatment.
amplitude values and the differenced value of disability In the Plasma Exchange/Sandoglobulin Guillain–Barré
grade obtained from immediate post-therapy and after 4 Syndrome Trial Group study,17 the patients randomized
weeks of therapy. We found a significant association between later had a significantly more improvement. The explanation
the distal motor amplitude and differenced disability grade for this finding was that those randomized later were closer
with both the treatments using chi-squared test (p value to spontaneous recovery. With the same analogy the IVIg
50.01) and there was no association between the remaining group, in our study should have done better.
factors and differenced disability grade (p value40.05). We also present the strengths and the deficiencies in our
However, we observed that the duration of illness at study. The literature is sparse on the role plasmapheresis
presentation was found to be more in IVIg group from developing countries. Management with plasmapher-
(8.4483 days) in comparison to plasmapheresis group esis is comparatively cheaper than IVIg. Plasmapheresis
(6.442 days) amounting to late presentation in IVIg group costs $1300 while the IVIg is $2400. Ours is a
(2.001 days). retrospective study. A prospective study would definitely
answer whether the patients from developing nations would
respond in the similar way as was seen from the
Discussion
developed world.
The present study is a retrospective study done with an Our observations brought out the following, both the
objective to find the outcome in disability grade in GBS with plasmapheresis and IVIg treatments were effective in
 4 C.K. Kishore et al. Ren Fail, Early Online: 1–5

Table 4. Intravenous immunoglobulin versus plasma exchange in Guillain–Barré syndrome.

Reference Type of study Age and treatment regimes Results Conclusion

13 Randomized Adults 53% of IVIg group improved 41 IVIg is at least as effective as
IVIg: 0.4 g/kg daily for 5 days; disability grade versus 34% in plasma exchange and may be
n ¼ 74 the PE group, difference 19% superior
PE: 200–250 mL of plasma/kg in (95% CI 3–24%; p ¼ 0.024)
five sessions in 7–14 days; for
days; n ¼ 73
16 Randomized Adults 61% PE treated group and 69% of The efficacy of IVIg is comparable
IVIg: 0.5 g/kg daily for 4 days the IVIg-treated group with that of PE
versus PE 40–50 mL/kg daily improved by one disability
for 5 days grade at 1 month
Total n: 50
17 Randomized IVIg 0.4 g/kg daily for 5 days; Mean change in disability grade During first 2 weeks after onset,
n ¼ 130 versus PE 250 mL/kg after 4 weeks 0.9 (SD 1.3) in plasma exchange and IVIg had
over 8–13 days; n ¼ 121 PE group and 0.8 (SD 1.3) in equivalent efficacy
IVIg group, difference 0.10
(95% CI 0.22–0.42)
18 Randomized IVIg n ¼ 20 At least a one grade improvement Study was stopped due to poor
PE n ¼ 21 in the functional score by day recruitment in IVIg group
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28: achieved by 16/20 patients

after IVIg and 15/21 patients
with plasma exchange (differ-
ence not significant)
19 Randomized Adults There was no significant difference IVIg therapy was considered to be
IVIg group n ¼ 23 between the two groups as useful as PE therapy for early
PE group n ¼ 24 (p ¼ 0.853) treatment of GBS
The immunoadsorption technique
was used mainly in the PE
group
For personal use only.

20 Retrospective IVIg n ¼ 31, LVP n ¼ 45, SVP Mean duration of MV (p ¼ 0.61), The outcome of patients treated
n ¼ 30 total hospital stay (p ¼ 0.44) with these three immunomodu-
and Hughes scale at discharge latory treatment modalities did
(p ¼ 0.31) did not differ among not vary
the three groups
15 Randomized Pediatric population; IVIg: 0.4 g/ PE group: shorter period of MV PE is superior to IVIg regarding
kg/day for 5 days; n ¼ 20 (median 11 days, IQR 11.0– the duration of MV but not
PE: one volume PE daily for 13.0) compared to IVIG group PICU stay or the short-term
5 days; n ¼ 21 (median 13 days, IQR 11.3– neurological outcome
14.5) with p ¼ 0.037.
PE group: a tendency for a shorter
PICU stay (p ¼ 0.094).
20/21 (95.2%) and 18/20 (90%)
children in the PE and IVIg
groups, respectively. could walk
unaided within 4 weeks
(p ¼ 0.606)

Notes: IVIg, intravenous immunoglobulin; PE, plasma exchange; LVP, large volume plasmapheresis; SVP, small volume plasmapheresis; MV,
mechanical ventilation; PICU, pediatric intensive care unit.

reducing the disability grade amongst all time points, i.e., at 3. The Guillain–Barré study group. Plasmapheresis and Acute
Guillain–Barré syndrome. Neurology. 1985;35:1096–1104.
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Controlled trial prednisolone in acute polyneuropathy. Lancet.
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6. Guillain–Barré syndrome steroidal trial group. Double blind study
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