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Pharmacological treatment for pain in Guillain-Barré syndrome

  1. Jia Liu1,*,
  2. Lu-Ning Wang1,
  3. Ewan D McNicol2

Editorial Group: Cochrane Neuromuscular Disease Group

Published Online: 20 OCT 2013

Assessed as up-to-date: 27 AUG 2012

DOI: 10.1002/14651858.CD009950.pub2


How to Cite

Liu J, Wang LN, McNicol ED. Pharmacological treatment for pain in Guillain-Barré syndrome. Cochrane Database of Systematic Reviews 2013, Issue 10. Art. No.: CD009950. DOI: 10.1002/14651858.CD009950.pub2.

Author Information

  1. 1

    Chinese PLA General Hospital, Department of Geriatric Neurology, Beijing, China

  2. 2

    Tufts Medical Center, Departments of Anesthesiology and Pharmacy, Boston, Massachusetts, USA

*Jia Liu, Department of Geriatric Neurology, Chinese PLA General Hospital, Fuxing Road 28, Beijing, 100853, China. Jason_liu1984@163.com.

Publication History

  1. Publication Status: New
  2. Published Online: 20 OCT 2013

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This is not the most recent version of the article. View current version (09 APR 2015)

 
Characteristics of included studies [ordered by study ID]
Pandey 2002

MethodsDouble-blinded, placebo-controlled, cross-over study


Participants18 (13 male) participants (mean age 31.05 years), with acute phase GBS admitted to ICU for ventilatory support


InterventionsGabapentin phase (n = 18): 15 mg/kg/day in 3 divided doses. Powder dissolved in 5 ml of water and administered through feeding tube

Placebo phase (n = 18): inert powder on same schedule as gabapentin phase

Each administered for 7 days with 2-day washout between phases


OutcomesReductions in the scores of Numeric Pain Rating Scale and Ramsay Sedation Scale, rescue analgesic consumption and adverse events were investigated each day from day 0 to day 7 of treatment


NotesFentanyl 2 µg/kg was administered as a rescue analgesic on patient demand or when the pain score was > 5 on a numeric rating scale of 0 to 10

Single centre, ICU in India

No funding information or declarations of interest provided


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskInsufficient information to judge

Allocation concealment (selection bias)Unclear riskInsufficient information to judge

Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskInsufficient information to judge

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskInsufficient information to judge

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo withdrawals or deaths

Selective reporting (reporting bias)Low riskAll outcomes were reported

Other biasLow riskNone detected

Pandey 2005

MethodsDouble-blinded, placebo-controlled, parallel study


Participants36 (22 male) participants with acute phase GBS admitted to ICU for ventilatory support. The mean age was 31.0 in the gabapentin group (n = 12), 34.7 in the carbamazepine group (n = 12) and 30.9 in the placebo group (n = 12)


InterventionsParticipants were randomly assigned to 3 equal groups (n = 12) to receive gabapentin powder (300 mg 3 times a day), carbamazepine powder (100 mg 3 times a day), or matching placebo powder (3 times a day) - all dissolved in 10 ml of water and administered through feeding tube

Each group received therapy for 7 days


OutcomesReductions in the scores of Numeric Pain Rating Scale and Ramsay Sedation Scale, rescue analgesic consumption and adverse events were investigated each day from day 0 to day 7 of treatment


NotesAnalgesia was provided with intravenous fentanyl 2 µg/kg on patient demand, given over 2 min

Single centre, ICU in India

No funding information or declarations of interest provided


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskInsufficient information to judge

Allocation concealment (selection bias)Unclear riskInsufficient information to judge

Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskInsufficient information to judge

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskInsufficient information to judge

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo withdrawals or deaths

Selective reporting (reporting bias)Low riskAll outcomes were reported

Other biasLow riskNone detected

Ruts 2007

MethodsDouble-blinded, placebo-controlled, parallel study


Participants223 (129 male) participants with acute phase GBS were randomised. The median age was 51 in the IVIg/methylprednisolone group, and 50 in the IVIg/placebo group


InterventionsIVIg/methylprednisolone (500 mg for 5 days, n = 111) versus IVIg/placebo (n = 112)


OutcomesPain severity at baseline: none, mild (pain but no real complaints), moderate (complaints but no analgesics necessary) or severe (analgesics necessary)

Number of participants with pain, number of participants with decreased pain severity, and number of participants with increased pain severity after 4 weeks


NotesThe study also included a 52-week retrospective study in a subset of participants (results not included in this review)

Multicentre study (setting unclear) in the Netherlands

No funding information or declarations of interest provided


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskBlock randomisation with random block sizes of 4, 6, or 8 generated by computer

Allocation concealment (selection bias)Low riskWhen a neurologist identified a participant, they phoned a 24-h hotline and were given a number according to the randomisation list

Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskInsufficient information to judge

Blinding of outcome assessment (detection bias)
All outcomes
Low riskIn most cases, neurologists who knew the medication allocation were not involved in assessment of treatment effect

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo withdrawals or deaths

Selective reporting (reporting bias)Low riskAll outcomes were reported

Other biasLow riskNone detected

 
Characteristics of excluded studies [ordered by study ID]

StudyReason for exclusion

Brisby 2002Not an RCT

Forsberg 2004Not an RCT

Korinthenberg 2005No pain outcomes

Morgenlander 1990Not an RCT

Odaka 2005Not an RCT

Tripathi 2000Duration of treatment was less than one week (only 3 days for each phase)

 
Summary of findings for the main comparison. Gabapentin compared with placebo for pain in Guillain-Barré syndrome

Gabapentin compared with placebo for pain in Guillain-Barré syndrome

Patient or population: patients with pain in Guillain-Barré syndrome

Settings: intensive care units in India

Intervention: gabapentin

Comparison: placebo

OutcomesIllustrative comparative risks* (95% CI)Relative effect
(95% CI)
No of Participants
(studies)
Quality of the evidence
(GRADE)
Comments

Assumed riskCorresponding risk

PlaceboGabapentin

Number of patients with self reported pain relief of 50% or greater (not measured)Not reportedNot reported

Pain score

(numerical rating scale of 0 to 10: 0 = no pain, 10 = worst pain)
In Pandey 2002, mean pain scores decreased from 7.83 ± 0.78 (SD) at baseline (day 0) to 5.67 ± 0.91 on day 7.

In Pandey 2005, median pain scores decreased from 8.0 (1.0 (IQR)) at baseline (day 0) to 6.0 (1.8) on day 7.
In Pandey 2002, mean pain scores decreased from 7.22 ± 0.83 at baseline to 2.06 ± 0.63 on day 7.

In Pandey 2005, median pain scores decreased from 8.0 (1.0) at baseline (day 0) to 2.0 (0.8) on day 7.
Pandey 2002

mean difference-3.61 (-4.12 to -3.1) on day 7

Pandey 2005

not reported
54
(2 studies)
⊕⊝⊝⊝
very low1,2,3
Gabapentin superior to placebo in reducing pain scores

Sedation score

(numerical rating scale of 1 to 6: 0 = anxious, agitated, or restless, 6 = asleep, no response)
In Pandey 2002, mean sedation scores changed from 1.44 ± 0.51 (SD) at baseline (day 0) to 3.63 ± 0.51 on day 7.

In Pandey 2005, median sedation scores changed from 1.0 (1.0 (IQR)) at baseline (day 0) to 4.0 (1.0) on day 7.
In Pandey 2002, mean sedation scores changed from 1.38 ± 0.50 at baseline to 2.44 ± 0.50 on day 7.

In Pandey 2005, median sedation scores changed from 2.0 (1.0) at baseline to 2.0 (0.0) on day 7.
Pandey 2002

mean difference -1.19 (-1.52 to -0.86) on day 7

Pandey 2005

not reported
54
(2 studies)
⊕⊝⊝⊝
very low1,2,3
Gabapentin superior to placebo in reducing sedation scores

Rescue analgesic consumptionIn Pandey 2002, mean fentanyl consumption change from day 1 to day 7 was -3 µg.

At day 7, mean fentanyl consumption was 317 ± 24 µg

In Pandey 2005, mean fentanyl consumption change from day 1 to day 7 was -240 µg.
At day 7, mean fentanyl consumption was 351 ± 34 µg.
In Pandey 2002, mean fentanyl consumption change from day 1 to day 7 was -146 µg.

At day 7, mean fentanyl consumption was 66 ± 16 µg

In Pandey 2005, mean fentanyl consumption change from day 1 to day 7 was -214 µg.

At day 7, mean fentanyl consumption was 126 ± 26 µg.
Pandey 2002

mean difference -251 mcg (-265 to -238 mcg) on day 7

Pandey 2005

-225 mcg (-249 to -200 mcg) on day 7
54
(2 studies)
⊕⊝⊝⊝
very low1,2,3
Gabapentin superior to placebo in reducing fentanyl consumption

Nausea111 per 100056 per 1000
(6 to 560)
RR 0.50 (0.05 to 5.04)18
(1 study)
⊕⊝⊝⊝
very low1,2,4
From Pandey 2002, no significant
difference

Constipation167 per 100023 per 1000
(2 to 423)
RR 0.14 (0.01 to 2.54)18
(1 study)
⊕⊝⊝⊝
very low1,2,4
From Pandey 2002, no significant
difference

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% CI) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: confidence interval; IQR: interquartile range; RR: risk ratio; SD: standard deviation

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

 1 Insufficient information for random sequence generation and allocation concealment was provided.
2 Insufficient information to assess adequacy of methods to ensure blinding.
3 Only 54 participants.
4 Only 18 participants.
 
Summary of findings 2. Carbamazepine compared with placebo for pain in Guillain-Barré syndrome

Carbamezapine compared with placebo for pain in Guillain-Barré syndrome

Patient or population: patients with pain in Guillain-Barré syndrome

Settings: intensive care units in India

Intervention: carbamazepine

Comparison: placebo

OutcomesIllustrative comparative risks* (95% CI)Relative effect
(95% CI)
No of Participants
(studies)
Quality of the evidence
(GRADE)
Comments

Assumed riskCorresponding risk

ControlCarbamazepine

Number of patients with self reported pain relief of 50% or greater (not measured)Not reportedNot reported

Pain score

(numerical rating scale of 0 to 10: 0 = no pain, 10 = worst pain)
In Pandey 2005, median pain scores decreased from 8.0 (1.0 (IQR) at baseline (day 0) to 6.0 (1.8) on day 7.

Median daily scores from day 1 to 7 were 4.0, 4.0, 4.0, 6.0, 6.0, 6.0, and 6.0, respectively).
In Pandey 2005, median pain scores decreased from 8.0 (1.0) at baseline to 3.0 (1.0) on day 7.

Daily scores from day 1 to 7 (3.0, 3.0, 3.0, 4.0, 4.0, 3.5, and 3.0, respectively) were significantly lower than placebo from day 4 onwards (P < 0.05).
Not reported24
(1 study)
⊕⊝⊝⊝
very low1,2,3

Sedation score

(numerical rating scale of 1 to 6: 0 = anxious, agitated, or restless, 6 = asleep, no response)
In Pandey 2005, median sedation scores changed from 1.0 (1.0 IQR) at baseline (day 0) to 4.0 (1.0) on day 7.

Median daily scores from day 1 to 7 were 4.0, 4.0, 4.0, 4.0, 4.0, 4.0, and 4.0, respectively.
In Pandey 2005, median sedation scores changed from 2.0 (1.0) at baseline to 3.0 (1.0) on day 7.

Daily scores from day 1 to 7 (3.0, 3.0, 3.0, 3.5, 3.0, 3.0, and 3.0, respectively) were significantly lower than placebo on all days.
Not reported24
(1 study)
⊕⊝⊝⊝
very low1,2,3

Rescue analgesic consumption In Pandey 2005, mean fentanyl consumption change from day 1 to day 7 was -240 µg.

At day 7, mean fentanyl consumption was 351 ± 34 µg.
In Pandey 2005, mean fentanyl consumption change from day 1 to day 7 was - 173 µg.

At day 7, mean fentanyl consumption was 174 ± 30 µg.
Mean difference -176 µg (-202 to -150 µg) on day 724
(1 study)
⊕⊝⊝⊝
very low1,2,3
Relative effect was calculated at the endpoint. Carbamazepine is superior to placebo in reducing fentanyl consumption

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% CI) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: confidence interval; IQR: interquartile range; SD: standard deviation

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

 1 Insufficient information for random sequence generation and allocation concealment was provided.
2 Insufficient information to assess adequacy of methods to ensure blinding.
3 Only 24 participants.
 
Summary of findings 3. Methylprednisolone compared with placebo for pain in Guillain-Barré syndrome

Intravenous immunoglobulin (IVIg) and methylprednisolone compared with IVIg and placebo for pain in Guillain-Barré syndrome

Patient or population: patients with Guillain-Barré syndrome, with varying severities of pain

Settings: hospitals in the Netherlands

Intervention: IVIg and methylprednisolone

Comparison: IVIg and placebo

OutcomesIllustrative comparative risks* (95% CI)Relative effect
(95% CI)
No of Participants
(studies)
Quality of the evidence
(GRADE)
Comments

Assumed riskCorresponding risk

IVIg/placeboIVIg/methylprednisolone

Number of patients with self reported pain relief of 50% or greater (not measured)Not reportedNot reported

Number of participants with pain after 4 weeks518 per 1000459 per 1000
(352 to 601)
RR 0.89 (0.68 to 1.16)223

(1 study)
⊕⊕⊝⊝
Low1
No significant
difference

Number of participants with decreased pain after 4 weeks304 per 1000288 per 1000
(191 to 431)
RR 0.95 (0.63 to 1.42)223

(1 study)
⊕⊕⊝⊝
Low1
No significant
difference

Number of participants with increased pain after 4 weeks232 per 1000197 per 1000
(121 to 327)
RR 0.85 (0.52 to 1.41)223

(1 study)
⊕⊕⊝⊝
Low1
No significant
difference

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% CI) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: confidence interval; IQR: interquartile range; IVIg: intravenous immunoglobulin; RR: risk ratio; SD: standard deviation

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

 1 Insufficient information to assess adequacy of methods to ensure blinding.
 
Summary of findings 4. Gabapentin compared with carbamazepine for pain in Guillain-Barré syndrome

Gabapentin compared with carbamazepine for pain in Guillain-Barré syndrome

Patient or population: intensive care unit in India

Settings: intensive care unit in India

Intervention: gabapentin

Comparison: carbamazepine

OutcomesIllustrative comparative risks* (95% CI)Relative effect
(95% CI)
No of Participants
(studies)
Quality of the evidence
(GRADE)
Comments

Assumed riskCorresponding risk

CarbamazepineGabapentin

Number of patients with self reported pain relief of 50% or greater (not measured)Not reportedNot reported

Pain score

(numerical rating scale of 0 to 10: 0 = no pain, 10 = worst pain)
In Pandey 2005, median pain scores from day 1 to day 7 were 6.0, 6.0, 5.0, 4.0, 4.0, 3.5, and 3.0, respectively.In Pandey 2005, median pain scores from day 1 to day 7 (3.5, 2.5, 2.0, 2.0, 2.0, 2.0, and 2.0) were significantly lower versus carbamazepine on each day (P < 0.05).

Baseline pain scores were similar between groups.
Not reported24⊕⊝⊝⊝
very low1,2,3
Gabapentin may be superior to carbamazepine in reducing pain scores

Sedation score

(numerical rating scale of 1 to 6: 0 = anxious, agitated, or restless, 6 = asleep, no response)
In Pandey 2005, median sedation scores from day 1 to day 7 were 2.0, 3.0, 3.0, 3.0, 3.5, 3.0, 3.0, and 3.0, respectively.In Pandey 2005, median sedation scores from day 1 to day 7 (2.0, 2.0, 2.0, 2.0, 2.0, 2.0, and 2.0, respectively) were significantly lower versus carbamazepine on each day (P < 0.05).

Baseline sedation scores were similar between groups.
Not reported24⊕⊝⊝⊝
very low1,2,3
Gabapentin may be superior to carbamazepine in reducing sedation scores

Rescue analgesic consumptionIn Pandey 2005, mean fentanyl consumption change from day 1 to day 7 was -173 µg.

At endpoint (day 7), mean fentanyl consumption was 174±30 µg.
In Pandey 2005, mean fentanyl consumption change from day 1 to 7 was - 214 µg.

At day 7, mean fentanyl consumption was 126 ± 26 µg.
Mean difference -48 µg (-71 to -126 µg) on day 724⊕⊝⊝⊝
very low1,2,3
Relative effect was calculated at the endpoint. Gabapentin is superior to carbamazepine in reducing sedation scores

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% CI) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: Confidence interval

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

 1 Insufficient information for random sequence generation and allocation concealment was provided.
2 Insufficient information to assess adequacy of methods to ensure blinding.
3 Only 24 participants.