JICNA^R○| Journal of the International

Child Neurology Association

A peer reviewed open access e-journal in Child Neurology

The assessment and management of pain in children with

GuillainBarré Syndrome in a sub-Saharan setting

Hayley Hutton

¹, Jo Wilmshurst

¹Department of Paediatrics and Child Health, Red Cross War Memorial Children’s Hospital,

University of Cape Town, South Africa

Corresponding author: Jo Wilmshurst; Email: Jo.Wilmshurst@uct.ac.za; Tel.: +27-21-658 5434;

fax:+27-21-689-1287; Head of Paediatric Neurology, Red Cross War Memorial Children’s Hospital,

University of Cape Town, South Africa.

https://doi.org/10.17724/jicna.2019.144

Received: 16 April 2018

Received in revised form: 22 November 2018

Accepted: 21 July 2019

Abstract

Introduction: Neuropathic pain is challenging to manage in children compounded by inappropriate assessment tools.

The lack of evidence-based pain control guidelines for children results in clinicians deferring to expert opinion and per-

sonal preference. Children with Guillain-Barré Syndrome are particularly at risk is of neuropathic pain. Objectives and

Methods: This is a retrospective study of children with Guillain-Barré Syndrome who were admitted to Red Cross War

Memorial Children’s Hospital, Cape Town, South Africa over a 10 year period. The study reviewed their pain assessment

and management practice. Results: Eighty-four children were identified with Guillain-Barré Syndrome. 76% had symp-

toms of pain and 53% had breakthrough pain reported. Standardised pain rating scales were used in 3 patients. A mean

of 2.7 analgesics were used per patient. Carbamazepine and gabapentin, were utilised in 27 and 20 patients respectively.

The use of gabapentin increased 73% per annum from 2009. There was no statistical difference between these two groups

for length of hospital stay or long-term disability. Conclusion: This study identified a significant gap in the assessment

of pain in children with Guillain-Barré Syndrome. Tools to adequately assess pain are needed, especially in immobile

and non-verbal children. Management of pain revealed a high use of adjuvant drugs. The dramatic increase in the use

of gabapentin related to clinician preference and was not supported by any evidence. Clinical outcomes for both the

carbamazepine and the gabapentin group were no different.

Kewords:Pain Assessment tools; Gabapentin; Carbamazepine; Children; Acute Inflammatory demyelinating

Polyradiculoneuropathy; Guillain-Barré syndrome.

Introduction

neuropathic pain, cancer related neuropathies, human im-

munodeficiency virus (HIV) neuropathy, and autoimmune

The prevalence of moderate to severe pain in the paediatric

conditions such as Guillain-Barré Syndrome, or acute in-

hospital setting is high [1]. Pain management and analge-

flammatory demyelinating polyradiculoneuropathy (AIDP)

sia is often suboptimal due to lack of training and knowl-

[8, 9, 10].

edge, negative attitudes towards analgesics, inappropriate

In Guillain-Barré Syndrome the sensory changes include

assessment of pain and the lack of algorithms to guide clin-

pain and paresthesia. The pain experienced is both nocicep-

ical practice [2, 3, 4, 5]. In Africa, there are additional

tive and neuropathic and is documented in up to 80-90%

challenges of access to facilities, affordability and sustained

of patients, of whom two-thirds are considered to be severe

availability of medications. As a result, paediatric pain re-

[11, 12, 13, 14]. The natural history is variable in children

lief often falls short of World Health Organization stan-

with a mean length of time to symptom free recovery of 67

dards [6, 7]. Neuropathic pain, is increasingly recognized

days. Improved pain control impacts on overall patient care

to occur in children and reported in diseases such as com-

and the illness experience [15, 16]. This is thought due to

plex regional pain syndrome, spinal injuries, postoperative

improved coping mechanisms, decreased stress and anxiety,

HUTTON H. & WILMSHURST J.,JICNA 2019, 19:144

improved capacity to deliver acute and longterm rehabilita-

tients who received gabapentin and those who received nei-

tion, all of which may reduce the length of hospital stay and

ther agent. The groups were compared for duration of doc-

overall illness duration.

umented pain, severity, length of hospital stay and outcome.

There are no clear guidelines to manage neuropathic

Inclusion criteria: Children admitted over the study pe-

pain in children, which has led to anecdotal practices

riod (January 2002 to December 2012) between 1 month

and polypharmacy [3, 4, 17, 18]. Combination therapy

and 12 years of age with a confirmed diagnosis of Guillain-

and adjuvant therapies such as tricyclic antidepressants,

Barré Syndrome, based on history and clinical examination,

antiepileptic drugs (AEDs), calcitonin and local anaesthet-

cerebrospinal fluid (CSF) findings and special investigations

ics are used in conjunction with United State Food and Drug

(neuroimaging and or nerve conduction studies) [29].

Administration (FDA) approved analgesics [19, 20, 21].

Exclusion criteria: Acute flaccid paralysis (AFP) due to

Whilst AEDs such as carbamazepine, gabapentin and pre-

an alternative cause such as acute transverse myelitis or

gabalin are used for pain control, there is a lack of class

non-polio enterovirus infections. Also, the dual use of

one studies [19, 20, 22, 23, 24]. Small study size trials sup-

gabapentin and carbamazepine for maintenance pain con-

port the efficacy and safety of these drugs as analgesics, and

trol since this precluded comparison of the outcome results

there are reports that they are at least as effective as opioids

from a single intervention and study numbers proved too

for neuropathic pain relief with the additional advantage of

small for this category.

reducing opioid requirements [25, 26, 27, 28]. This study

Data collected included patient demographics, disease

reviewed the trends in the assessment and management of

pattern and course, standard and adjuvant analgesic inter-

pain in children admitted to a tertiary centre in sub-Saharan

ventions, and the severity of illness. The medical records

Africa with Guillain-Barré Syndrome.

were reviewed for documentation of the analysis of pain as-

sessment either via a formal pain score (e.g. FLACC [30]

or COMFORT [31]) (Appendix A), as an annotation in the

Methods

medical, nursing or rehabilitation staff medical records, or

through the frequency of additional analgesic doses. Data

This was an observational retrospective study of clinical

was recorded from those children who underwent cere-

practice from 1st January 2002 to 31st December 2012,

brospinal fluid screening (CSF), nerve conduction studies

based at the Red Cross War Memorial Children’s Hospital

and magnetic resonance imaging (MRI). Immediate out-

(RCWMCH) in Cape Town, South Africa. This is a university

comes were documented with regards to duration of stay

affiliate tertiary teaching hospital. It is the largest children’s

and resolution of respiratory compromise. All data were

hospital in sub-Saharan Africa. The centre offers special-

captured using Epidata and was analyzed using Matlab

ist and sub-specialist care to the paediatric population from

Statistics program.

the Western Cape and wider afield. Children with Guillain-

Barré Syndrome are managed according to current standard

recommended guidelines. Children are clinically assessed to

Results

have pain, typically based on parental, nursing and ancillary

staff feedback, are prescribed paracetamol with tilidine as a

Between

2002-2012,

patients were admitted to

rescue dose for breakthrough pain. As part of standard hos-

RCWMCH with Guillain-Barré syndrome. The group demo-

pital policy morphine is used for moderate to severe pain.

graphics are summarized in Table 1. Sixty-five (76%) of

Current practice in our centre for pain control of patients

the children had symptoms of pain recorded in their medi-

with Guillain-Barré Syndrome is the off-label use of the

cal records, predominantly by the rehabilitation therapists.

antiepileptic drugs, namely carbamazepine and gabapentin.

However, the severity of the pain could not be quantified

Either agent is initiated following the diagnosis of Guillain-

due to suboptimal assessment of the pain and inadequate

Barré Syndrome when pain, or the perceived risk of pain,

use of objective pain rating tools. Pain rating tools were only

is present. The later relates to the child who cannot ex-

used in 3 patients. More than half of patients had break-

press that they are in pain, for example whilst they are ven-

through pain (53%) reported in their folders with the ma-

tilated, or if they have profound motor impairment. Carba-

jority of this documented in relation to physiotherapy ses-

mazepine is titrated up to a maximum of 10-15 mg/kg/day

sions. A mean of 2.7 analgesics were used per patient. Other

over 2 to 3 weeks and gabapentin up to 40mg/kg/day over 2

modalities to relieve pain were also used inconsistently and

weeks. Maintenance dose is based on the point of apparent

to a lesser extent. The characteristics of analgesic usage are

pain control. Treatment is weaned off over 2 weeks during

demonstrated in Table 2.

the rehabilitation period or at the time of discharge, when

The use of analgesics paracetamol, morphine and tili-

pain is no longer a complaint. As such the baseline acute

dine remained constant throughout the study period. From

pain care for these children is standard (paracetamol, tili-

2002 until 2008 all patients with documented pain were

dine and morphine) and the variable adjuvant drug decided

prescribed carbamazepine but from 2009 gabapentin was

upon by the attending clinician is either carbamazepine or

the preferred agent, and almost completely replaced car-

gabapentin. This allowed us to analyse the sample in three

bamazepine. From 2009, the overall trend of gabapentin

distinct groups: patients who received carbamazepine, pa-

usage was dramatic with an average increase of 73% per

HUTTON H. & WILMSHURST J.,JICNA 2019, 19:144

Table 1 Demographics of patients admitted to RCWMCH with GBS from 2002-2012

Characteristic

Result Total

Carbamazepine

Gabapentin

Neither Carbamazepine nor Gabapentin P value

n = 84

n = 27

n = 20

n = 37

Age (median)

52 ± 42 months range: [8-144]

60 ± 42 months range: [8-144]

48 ± 35 months range: [13-138]

52 ± 35 months range: [11-144]

0.41

Male:Female (percentage ratio)

50:50

45:55

55:45

51:49

Length of hospital stay (median days)

14 ± 43 range = [2-121]

45 ± 33 range = [5-119]

48 ± 36 range = [8-121]

10 ± 15 range = [2-90]

0.85

Proportion needing ICU

41%

59%

64%

17%

0.62

Length of ICU stay (median days)

21,5 ± 33 range = [1-83]

31 ± 24 range = [1-83]

26 ± 24 range = [1-83]

15 ± 30 range = [2-75]

0.18

Proportion needing ventilator support

31%

52%

50%

0.87

Proportion needing a tracheostomy

28%

52%

45%

0.62

Table 2 Characteristics of pain assessment and analgesic usage

Pain characteristic

Total Study Results

Carbamazepine

Gabapentin

Neither Carbamazepine nor Gabapentin P value^∗

Number of patients

n=84

n=27

n=20

n=37

Number of patients with documented pain

76% (n= 65)

86% (n= 24)

100% (n= 21)

54% (n= 20)

0.67

Pain rating tools used

FLACC scale (2), Visual Analogue (1)

3% (n= 1) Visual Analogue

14% (n= 2) FLACC scale (2)

0% (n= 0)

Mean number analgesics used

2.3 ± 1.8 range = [0-9]

3.2 ± 0.8 range = [2-5]

1.2 ± 2.1 range = [0-9]

0.76

Duration pain documented (median days)

4 ± 8 range = [0-59]

13.4 ± 12 range = [2-56]

12.7 ± 13.4 range = [2-59]

4.2 ± 4.2 range = [1-20]

0.9

Number of patients experiencing breakthrough pain

55% (n= 47)

79% (n= 22)

77% (n=16)

24% (n= 9)

Agent used to treat breakthrough pain

Tilidine

84%

87%

88%

71%

Paracetamol

14%

Morphine

Ketamine

Not documented

15%

Allied therapy used

Physiotherapy

95%

100%

89%

Occupational therapy

85%

97%

100%

68%

Speech Therapy

52%

79%

86%

14%

Play

27%

Music

18%

Aromatherapy

Primary caregiver at bedside

93% (n= 80)

93% (n= 26)

86% (n= 18)

95% (n= 35)

^∗P - Value: Comparison between Carbamazepine and Gabapentin treatment groups only.

annum (Figure 1). Of 49 children, 20 received gabapentin,

on 79 of the 84 patients with abnormally raised protein in

27 carbamazepine and 2 subsequently received both agents

53%. Nerve conductions studies were performed in 38 pa-

separately.

tients and were supportive of the diagnosis in the majority

(95%). Twenty-five patients underwent spine MRI, 10 were

normal and the remaining 15 had enhancement of the nerve

roots. Neuroimaging was performed when there was diag-

nostic concern, such as for the children on artificial ventila-

tion who were paralysed and could not be formally neuro-

logically assessed.

Discussion

Pain measurement in children is difficult [15, 31]. Pain as-

sessment tools are not standardized and as this study il-

lustrates, this forms a major barrier to real understand-

ing of the degree of pain suffered by children and the ef-

ficacy of the interventions used to control the complica-

tions. Appendix A summaries the pain tools which could

be considered in these children. The few validated tools are

mostly used in acute settings and resource equipped settings

[15, 32]. These tools may be less reliable in an African set-

Figure 1 Number of times each analgesic initiated per annum for

ting due to ethnic variation and differences in beliefs. There

children with Guillain-Barre Syndrome.

are no observational tools developed for measuring neuro-

pathic or chronic pain in children [9, 32, 33]. Self-reporting

For the whole group there was no statistical difference

is considered the most reliable method, especially in the set-

in any of the clinical interventions between the two AED

ting of chronic pain [32, 34, 33]. But children, especially

groups. The children treated with carbamazepine received

manijky of those in this cohort, would be too young to self-

a mean dose of 4.3mg/kg/day (range 1.5-10) for 31 days

report, and those old enough may not be able to self-report

(range 5-75) and those who received gabapentin received

for the initial period due to being sedated and/or ventilated

9.38mg/kg/day (range 3-15) for 47 days (range 7-123

[28]. The autonomic dysfunction which occurs in patients

days). Thirty-seven children did not receive regular pro-

with Guillain-Barré syndrome would be a significant con-

phylaxis with either AED, these children tended to have a

founding factor when considering pain rating tools that rely

shorter, less severe course (p=0.0001). CSF was performed

on physiological measures [28]. Inadequate measurement

HUTTON H. & WILMSHURST J.,JICNA 2019, 19:144

and assessment of pain during the study period limits defini-

ropathic pain conditions such as complex regional pain syn-

tive or useful comment on the degree of pain experienced by

drome, post-operative neuralgia, burns, neuropathies re-

these children.

lated to cancer and HIV, and autoimmune syndromes such

Neuropathic pain is a difficult entity for a clinician to

as GuillainBarré Syndrome [39]. Despite the lack of class

manage. More than half the patients in this study were

I evidence, the usage of gabapentin on and off-label has

prescribed either gabapentin or carbamazepine as adjuvant

increased. The increasing trends of gabapentin usage in

analgesics. From the modalities recorded there was no dif-

this study occurred due to clinicians’ personal preference.

ference in the apparent efficacy or safety for either agent.

The widely accepted anecdotal support of gabapentin needs

Whilst there is slightly more data to support gabapentin,

more data to support a stronger recommendation for use.

overall the evidence is limited for both, especially in chil-

dren [22, 24]. There are two class I studies assessing

the efficacy of gabapentin in adults with GuillainBarré syn-

Conclusion

drome. The first reviewed 18 adults in a randomized, dou-

This study draws to light two important issues. Firstly, the

bleblinded, placebo-controlled crossover study [25]. In ad-

need for improvement and education in the use of standard-

dition to a numerical pain score, the amount of adjuvant

ized, objective and reproducible tools to rate pain on a regu-

analgesia with fentanyl was used as a measure of pain con-

lar basis in patients with GuillainBarré Syndrome. Secondly,

trol. The study period was for 7 days and a significant re-

with the increase of the use of gabapentin to control pain

duction in pain and adjuvant therapy was evident during the

associated with Guillain-Barré Syndrome in children in our

gabapentin periods. The second study reviewed 36 adults

setting, the safety and efficacy needs to be established in

with GuillainBarré Syndrome in a randomized, prospective,

comparison to other AEDs such as carbamazepine and pre-

double-blinded, placebocontrolled study for patients in an

gabalin. This information will be vital in generating guide-

intensive care setting who were ventilated [26]. Patients

lines and protocols for pain management in various painful

were allocated to receive gabapentin, carbamazepine or

conditions and will in turn improve the way that we manage

placebo. The group concluded that both AEDs were more ef-

children experiencing pain with Guillain-Barré Syndrome.

fective than placebo and that gabapentin was more effective

than carbamazepine for decreasing pain and the need for

adjuvant analgesia. Cohort sizes and duration of interven-

Aknowledgments

tion were limiting factors for both these studies. The system-

Ethical approval was obtained by the University of

atic review by Pena et al concluded that there was no robust

Cape Town’s Human Research Ethics Committee

(Ref

evidence to recommend a single treatment option to man-

no:231/2013).

age pain in people with Guillain-Barré Syndrome [23]. The

group supported the need for further clinical studies with

larger numbers, longer duration of monitoring and more ef-

Appendix A. Comparison of pain tools

fective measures to document intensity of pain objectively

used in children

[23]. A Cochrane review also could not conclude that there

was sufficient evidence to support use of a specific pharma-

https://jicna.org/index.php/journal/article/view/

cological intervention, the follow-up meta-analysis 2 years

jicna-2019-144/149

later conclude the same [24, 35]. The authors concluded

that whilst reductions in pain severity were evident with

Competing interests

both gabapentin and carbamazepine compared to placebo,

the evidence for this remained limited and of low quality,

The authors have declared that they have no competing in-

further highlighting the need for larger, well designed ran-

terests.

domised controlled trials.

Carbamazepine is associated with adverse effects related

Authors’ contributions

to its toxic metabolite and drug-drug interactions [36]. In

All the authors contributed to data collection and also crit-

the sub-Saharan setting due to the high prevalence of HIV,

ically reviewed the manuscript. The final version of the

carbamazepine is ideally avoided in combination with an-

manuscript was approved by all the authors.

tiretroviral therapy to avoid AED toxicity and HIV treat-

ment failure [37]. In this setting, Gabapentin has a more

This is an Open Access article distributed under the terms of

favourable pharmacokinetic profile as it has an equivalent

the Creative Commons Attribution License which permits un-

bioavailability to carbamazepine, is excreted unchanged via

restricted use, distribution, and reproduction in any medium,

the kidneys, does not induce cytochrome p450, has fewer

provided the original work is properly credited. The Cre-

drug interactions and an overall better side effect profile

ative Commons Public Domain Dedication waiver applies to

[38].

the data made available in this article,unless otherwise stated.

Gabapentin is approved by the FDA for use in post-

herpetic neuralgia and focal epilepsy, off-label usage in both

adult and paediatric practice has extended to various neu-

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Appendix A - Comparison of Pain Tools used in Children

TOOL

USES

PROS

CONS

COMMENTS

FLACC [30]

>11yr; Acute; Post op;

Validated in children;

Acute pain

Use in measuring; neu-

Minor non-invasive

Class I evidence; Ob-

ropathic/chronic pain;

procedures

servational

Simple;

use has not been estab-

Low cost;

lished; Paralysis.

COMFORT [40]

Newborn-17yrs; Venti-

Class II

evidence;

Acute pain

Ventilated/sedated pa-

lated patients

Validated in venti-

tients.

lated patients; Can

be used in critical

care/PICU

setting;

Good inter-rater vari-

ability; Observational;

Simple; Low cost.

VAS Numerical

Verbal child; Acute or

Self-report regarded as

Requires awake and

Ventilated/sedated

FACES [41]

chronic pain

best tool in chronic

orientated patient

patients; Challenging

pain

in young or paralysed

children.

LANSS [42]

Adult

Neuropathic

Specific

Questionnaire format;

Challenging in young

pain

Complex.

or paralysed children

CHEOPS [43]

1-7yrs;

Acute and

Proposed

1month-

Better in acute setting

Paralysis

chronic pain; Post op;

17yrs; Observational;

fractures; sickle cell

Valid.

disease;

immunisa-

tions.

APPT [44]

8-17 yrs.

Proposed

2-68

yrs.;

Adolescents;

Acute

Challenging in young

Valid; Reliable; Sen-

pain.

or paralysed children;

sitive; May be able

Translation of lists; Se-

to differentiate be-

dation/ventilation.

tween

neuropathic

and nociceptive pain

NCCPC-R [45]

3-18

yrs.; With neu-

Incorporates

phys-

Neurocognitive

im-

Autonomic instability

rological impairment;

iological

variables;

pairment

may occur as part of

Children who are un-

Simple; Cost effective.

GBS; Paralysis.

able to speak