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 Table of Contents  
ORIGINAL ARTICLE
Year : 2020  |  Volume : 5  |  Issue : 2  |  Page : 173-177

A retrospective study on patients of Guillain-Barre syndrome treated with therapeutic plasma exchange at a tertiary care hospital in Western Maharashtra


1 Department of Immunohematology and Blood Transfusion, Armed Forces Medical College, Pune, Maharashtra, India
2 Department of Transfusion Medicine, Bharati Vidyapeeth University, Pune, Maharashtra, India
3 Armed Forces Transfusion Centre, New Delhi, India
4 Department of Community Medicine, Armed Forces Medical College, Pune, Maharashtra, India

Date of Submission24-Aug-2020
Date of Decision24-Sep-2020
Date of Acceptance14-Oct-2020
Date of Web Publication13-Nov-2020

Correspondence Address:
Himanshu Kumar Singh
Department of Immunohematology and Blood Transfusion, Armed Forces Medical College, Pune, Maharashtra
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/GJTM.GJTM_90_20

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  Abstract 


Background and Objectives: The procedure of removal of pathologic substances present in the plasma of the patients and its substitution with a suitable replacement fluid is known as therapeutic plasma exchange (TPE). It has been seen that this procedure has an ameliorating effect on the clinical condition of the patient of Guillain-Barré syndrome (GBS). This study aims to assess the clinical improvement in GBS patients treated with TPE at a tertiary care center.
Methods: A retrospective chart review was conducted in a series of 57 GBS patients treated with TPE using an intermittent flow cell separator system. GBS disability and Medical Research Council (MRC) muscle strength scoring systems were used as final endpoints. Statistical analysis was done through the R software version 3.2.0. A value of P < 0.05 was considered to be statistically significant.
Results: After 05 alternate day cycles, TPE treatment led to a significant improvement in both MRC muscle strength scores and GBS disability scores. Before TPE, the MRC muscle strength score was 1.38 ± 1.19 (range: 0–4) and this increased to 3.15 ± 1.57 (range: 0–5) after TPE, (P = 0.002). Similarly, before TPE, the mean GBS disability score was 4.00 ± 0.81 (range: 2–5) and this decreased to 2.69 ± 1.31 (range: 1–5) after TPE, (P = 0.003).
Conclusion: The result of this study showed TPE to be an effective mode of treatment for GBS. The safety profile was found to be acceptable and going by the findings of this study, TPE must be considered as an early line of management.

Keywords: Guillain-Barré syndrome disability scale, Guillain-Barré syndrome, medical research council muscle strength score, therapeutic plasma exchange


How to cite this article:
Biswas AK, Singh HK, Philip J, Pawar AA, Joshi RK. A retrospective study on patients of Guillain-Barre syndrome treated with therapeutic plasma exchange at a tertiary care hospital in Western Maharashtra. Glob J Transfus Med 2020;5:173-7

How to cite this URL:
Biswas AK, Singh HK, Philip J, Pawar AA, Joshi RK. A retrospective study on patients of Guillain-Barre syndrome treated with therapeutic plasma exchange at a tertiary care hospital in Western Maharashtra. Glob J Transfus Med [serial online] 2020 [cited 2020 Nov 27];5:173-7. Available from: https://www.gjtmonline.com/text.asp?2020/5/2/173/300644




  Introduction Top


Guillain-Barré syndrome (GBS) is a severe acute polyneuropathy with a variable degree of weakness. The severe, generalized manifestation of GBS with respiratory failure may affect 20%–30% of the cases.[1] The disease is mostly preceded by an infection and generally runs a monophasic course. It may manifest as areflexia, sensory loss and limb weakness which may lead to neuromuscular paralysis that can involve respiratory functions and may affect the facial and bulbar functions too. Symptoms reach their maximum severity within 2–4 weeks. The annual global incidence of GBS is reported to be around 1.3–2.2/100,000.[2] It was seen that with an increase in age, the frequency of GBS increases (0.8/100,000 in 0–34 year olds and further increases to 4.67/100,000 in 71–90 year olds) with a slight predominance toward the male gender.[3] Both intravenous immunoglobulin (IVIg) and plasma exchange (PE) are effective in GBS. Rather surprisingly, steroids alone are ineffective.[4],[5]

The underlying etiology of GBS is autoimmune, and the infiltration of the peripheral nerve by leukocytes and antibodies directed against the nerve constituents is characteristic of this disease. In most cases, the trigger for this is infection with some pathogens. The most commonly implicated ones are Campylobacter jejuni, Mycoplasma pneumonia and Haemophilus influenzae.[5] This acts as a trigger for the production of anti-ganglioside antibodies. Cytomegalovirus and Epstein-Barr virus have also been implicated in the production of these antiganglioside antibodies. It is believed that previous infections with such pathogens can lead to a host humoral-immune response that cross-reacts with neural and myelin antigens due to molecular mimicry. The pathophysiology of this disease can be explained by the presence of antibodies directed against peripheral myelin.[6]

Therapeutic PE (TPE) is an extracorporeal technique involving the removal of plasma, together with the pathologic substances present in it, out of the patient and substituting it with a suitable replacement fluid using an apheresis device. This procedure is very commonly used for treating autoimmune or immune-mediated disorders.[7] TPE exerts its beneficial effects by removing both autoantibodies and alloantibodies from the circulation of the patient.[8] In addition, it also removes monoclonal proteins, toxins and immune complexes that might be present in the patient's circulation.[9] A definite beneficial effect has been seen on the course of this illness after treatment with TPE as well as IVIG. The reduction in autoantibody load after TPE is due to the removal of cytokines and antibodies (mainly IgG), which leads to the alteration of the Th1-Th2 ratio.[9] This, in turn, leads to a decrease in the severity of the symptoms. Many studies have shown that recovery in GBS is accelerated in patients undergoing TPE. Studies done in the past have demonstrated TPE to be an efficient modality for treating TPE. Successful treatment has been achieved with a total of 3–5, one plasma volume exchanges, delivered over 1–2 weeks period.[10]

Most GBS patients recover spontaneously over time and have no or limited neurological deficits. Some patients, however, have severe weakness and develop respiratory distress and require intensive care unit (ICU) care. Severe and lasting disability is very commonly seen in this subset of patients due to neuropathy and frequently leads to difficulty in walking, and the patient can even need ventilator support.[11]

The efficacy of TPE has been found to be similar to that of IVIG for the treatment of GBS. However, there have been reports of increased risk of thrombotic events in case of IVIG treatment.[12] TPE, followed by treatment with IVIG, does not appear to lead to an improvement in the outcomes.[2] However, due to the limited choices available in patients who have severe disease, both the above treatment modalities have been applied in such cases at some centers.

In view of the above, this study was undertaken to assess the efficacy of TPE on the clinical improvement status of patients of GBS at our tertiary care center.


  Materials and Methods Top


Study design and patients

The study population comprised 57 patients. The data were retrospectively analyzed from this series of patients with GBS for 5 years (Jan 2014 and Dec 2018), who were treated with TPE at our center. A retrospective chart review was conducted by reviewing TPE data manually from the records present in the department. The patient's demographic data (age, sex), complications encountered during the procedures and the outcome of the treatment were analyzed using the departmental records. The age and gender of the patients showed a well-distributed cohort with no skewing [Figure 1]. Fifteen of these patients (26.4%) had the acute motor axonal neuropathy subtype, whereas 42 patients had the acute inflammatory demyelinating polyradiculoneuropathy subtype (73.6%).
Figure 1: The age and sex distribution of 57 patients who underwent therapeutic plasma exchange for Guillain–Barré Syndrome. Age range is represented on X axis and sex wise and total no of patients on Y axis

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Therapeutic plasma exchange procedure

TPE was performed using an intermittent flow cell separator, i.e., the “Haemonetics MCS + LN 9000.” The procedures were performed on every alternate day using a central venous catheter. During each procedure, around 1–1.5 plasma volume was exchanged with replacement fluids such as fresh frozen plasma (FFP) and normal saline in an approximate ratio of 4–5:1. Mean blood volume processed for males was 6124 ml, whereas for females, it was 5724 ml. Similarly, the mean replacement volume was 2695 ml for males and 2421 ml for females. The average time taken for each procedure was 183 min and the average number of cycles required to complete each procedure was 22.

The ACD (Acid Citrate Dextrose):Blood ratio was kept at 1:10. However, it was reduced to 1:12 only if the patient experienced symptoms of hypocalcemia which were not alleviated even by reducing the blood draw rate. Calcium supplementation in the form of 1 g oral calcium was administered to the patients 1 h before the initiation of each procedure. However, parenteral calcium was administered in case the patient still developed symptoms of hypocalcemia despite giving oral calcium.

Data collection

Five alternate day TPE procedures were carried out for each patient. The disability and muscle strength were used as the markers of the severity of the disease for deciding the number of cycles required for each patient. The Medical research council (MRC) muscle strength score [Table 1] and GBS disability score [Table 2] were noted as study endpoints.[11] The GBS disability score ranges from 0 (normal) to 6 (dead). When the disability scores were ≥3 at 6 months, poor outcomes have been seen whereas with disability scores ≤2 at 6 months, and the outcomes have been fairly good. MRC muscle strength score is calculated by adding the scores of six muscles from the upper and lower limbs on both sides. Scores may range from 0 (quadriplegic) to 5 (normal). Preprocedure neurological clinical status was compared to neurological status immediately postprocedure and after 10 days. Adverse events were also assessed during and after the treatment.
Table 1: MRC muscle strength scoring system

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Table 2: GBS disability score

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Statistical analysis

Data analysis was performed using the R software (official part of the Free Software Foundation's GNU project) ver 3.2.0. Data were summarized by calculating range, mean, and standard deviation. Pre- and post-Muscle Strength Scores and GBS Disability Scores were compared by using the Wilcoxon signed-rank test. A P < 0.05 was considered to be statistically significant.

Ethics

Approval of the Institutional Ethics Committee was obtained for this study.


  Results Top


The study comprised 57 patients of GBS. After five alternate day cycles of TPE, there was a significant improvement in both MRC muscle strength score and GBS disability score, when compared with the preprocedure scores. Before TPE, the mean MRC muscle strength score was 1.38 ± 1.19 (range: 0–4) which increased to 3.15 ± 1.57 (range: 0–5) after TPE, (P = 0.002) [Figure 2]. Similarly, before TPE, the mean GBS disability score was 4.00 ± 0.81 (range: 2–5) which decreased to 2.69 ± 1.31 (range: 1–5) after TPE, (P = 0.003) [Figure 3].
Figure 2: Increase in median medical research council muscle strength score after 05 alternate day cycles of therapeutic plasma exchange on the box and whisker graph. Pre- and post-procedure status are represented on X axis and median medical research council muscle strength score on Y axis. From the box and whisker graph we can see that as the median medical research council muscle strength score is increasing after 05 alternate day cycles of therapeutic plasma exchange

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Figure 3: Decrease in median Guillain-Barré syndrome disability score after 05 alternate day cycles of therapeutic plasma exchange on the box and whisker graph. Pre and post procedure status are represented on X axis and median Guillain-Barré syndrome disability score on Y axis. From the box and whisker graph we can see that as the median Guillain-Barré syndrome disability score is decreasing after 05 alternate day cycles of therapeutic plasma exchange

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Adverse events were observed in 13 of the 277 procedures (4.7%) [Figure 4]. Hypocalcemia and allergic reactions were the most common ones. Parenteral calcium supplements, decreasing the ACD: blood ratio and slowing down the rate of PE were used to manage the episodes of hypocalcemia effectively and none of these procedures had to be discontinued. Allergic reactions to replacement fluids were managed by giving anti-histamines. Only in two cases, difficulty with venous access was recorded (0.7%). Technical difficulties related to cell separators were not encountered.
Figure 4: The adverse events encountered during therapeutic plasma exchange in a series of 57 patients with Guillain-Barré Syndrome in the form of a pie – chart

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  Discussion Top


Significant improvements were seen in both GBS disability score and MRC muscle strength score in the retrospective analysis of the data of 5 years from our center. TPE was seen to be well tolerated in patients with minimal adverse events. Mild hypocalcemia was the most frequent adverse event observed.[13] This adverse event is quite common during TPE and can be attributed to citrate, which is a calcium chelator and is used as an anti-coagulant. However, hypocalcemia occurred only in 07 out of 277 procedures (2.5%) and was managed easily by the administration of intravenous calcium.

An increased risk of infections may be associated with the use of FFP as a replacement fluid.[11] However, in our series of patients, follow-up did not reveal any TPE associated infections. Previous studies have shown no difference in the efficacy between FFP and albumin as replacement fluids.[14] These studies have also shown that the GBS disability score, together with the MRC muscle strength scores can be used for the assessment of the outcomes at 6 months.

The results reported here were found to be in line with previous studies on the efficacy of TPE as a treatment modality for GBS. The time required to regain walking ability has been shown to significantly reduce after TPE (30 vs. 44 days) and a decrease in the percentage of patients having walking disability was seen 4 weeks after initiation of TPE in a meta-analysis of seven trials.[13]

Compared to controls, TPE has also been seen to reduce the need for ventilator support. Patients who were treated with TPE, were found to have less motor sequelae and had a higher likelihood of regaining original muscle strength after 1 year.

The treatment protocol that was followed in this study is in line with the various standard guidelines, which state that treatment with TPE or IVIG helps in accelerating the recovery in GBS, provided that the treatment is initiated within 2–4 weeks of the onset of the disease. American Society for Apheresis has recommended GBS as Grade 1A (Category I) indication for TPE, i.e., a strong recommendation with high-quality evidence.[9],[15] Although corticosteroids have often been used in the treatment of GBS, some guidelines state that the disease outcome is not improved by these drugs and therefore, these are not recommended.[5],[16] These guidelines also emphasize that, in order to be effective and also for the prevention of long-term sequelae, TPE should be started within 2–4 weeks of the onset of GBS. The use of TPE for GBS has been designated as having class one evidence by The American Academy of Neurology Guidelines (2011).

It has been hypothesized that TPE helps in the treatment of GBS primarily by removing auto-antibodies and certain other protein factors. In addition to this, the replacement of plasma components (when FFP is used as the replacement fluid) might also be one of the mechanisms involved.[17] Lymphocyte proliferation and sensitization may, however, be an unintentional and unwanted effect of this treatment.[18]

The only effective treatment modalities that are available for the treatment of GBS at present are TPE and IVIG.[8] Various studies have shown that 20% of patients with GBS remain unable to walk and 5% have fatal outcomes despite being treated with TPE and IVIG. The results of this study show that effective treatment of GBS can be provided by TPE with varied replacement fluid formulations using the “Haemonetics MCS + LN 9000” cell separator platform and it has an acceptable safety profile. This constitutes an essential component of disease management. It also appears that TPE and IVIG have equal efficacy in the treatment of GBS.[4] There were no statistically significant differences observed in the GBS Disability scores during the overall treatment course in both treatment groups. However, the out-of-pocket cost for the immunoglobulin (IVIG) group was more than double than for TPE group without any obvious benefits in health outcome that could have justified this increased cost.[19],[20]

It has been seen in the previous studies that four sessions of TPE would be beneficial for the group with moderate-to-severe disease.[13] Five to seven TPE procedures were performed on alternate days in our study depending on the severity of the disease, which was assessed by using the GBS disability and MRC muscle strength score.

Previous studies have shown that IVIG dose of 0.4 g/kg is most effective when administered daily for 5 days.[21] Yet another study has shown that six IVIG sessions are more beneficial than four sessions in patients having severe disease. Not many studies have been done in which both TPE and IVIG have been used and that too, in the same patient. Furthermore, the application of both modes of treatments would be costly. However, this may be the best treatment strategy for patients having severe disease.

It is unclear as to which treatment option would be the best for GBS patients who continue to deteriorate despite the initiation of therapy with IVIG or TPE alone.[7] The administration of IVIG after TPE seems more logical because if IVIG is given first, then the subsequent apheresis will lead to a loss of some of the immunoglobulins that were administered earlier to the patient.[10] The patients having severe disease course are generally conspicuous from the beginning while a few of these patients go on deteriorating despite initiating treatment with TPE. IVIG can be given right after the TPE for these subsets of patients. Occasionally, some patients keep on deteriorating slowly over a period of days to weeks. IVIG could be administered in such patients. Therefore, the interval between TPE and IVIG will be different for different patients and has to be individualized.


  Conclusion Top


Although this study has limitations of being a single-center retrospective study with comparatively few number of patients, the results of this study are in concordance with those previously published. We found TPE to be an ideal option for the treatment of patients of GBS with negligible complications. It is more cost-effective than IVIG and hence, would be a more feasible treatment option in a setting with limited resources as the procedure can be conveniently delivered with a portable cell separator equipment in an ICU/acute ward setting.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
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