Systemic administration of local anesthetic agents to relieve neuropathic pain

Vidya Challapalli; Ivo W Tremont-Lukats; Ewan D McNicol; Joseph Lau; Daniel B Carr

doi:10.1002/14651858.CD003345.pub2

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Figure 1

Funnel plot of comparison 01, outcome 01. The trials by Baranowski, Fassoulaki and Stracke are on or outside the 95% confidence intervals.

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Analysis 1.1

Comparison 1: Efficacy of lidocaine or mexiletine vs. placebo control, Outcome 1: Post intervention/placebo mean VAS (0‐100) pain scores (Random effects model)

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Analysis 1.2

Comparison 1: Efficacy of lidocaine or mexiletine vs. placebo control, Outcome 2: Significant pain relief by response rates

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Analysis 2.1

Comparison 2: Subgroup analyses for comparison 01, Outcome 1: By sample size

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Analysis 2.2

Comparison 2: Subgroup analyses for comparison 01, Outcome 2: By time of outcome measurement

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Analysis 2.3

Comparison 2: Subgroup analyses for comparison 01, Outcome 3: By time of outcome measurement (minus Stracke trial)

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Analysis 2.4

Comparison 2: Subgroup analyses for comparison 01, Outcome 4: By time of outcome measurement (minus 3 trials with wide data spread)

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Analysis 2.5

Comparison 2: Subgroup analyses for comparison 01, Outcome 5: By trial design

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Analysis 2.6

Comparison 2: Subgroup analyses for comparison 01, Outcome 6: By methodological quality

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Analysis 2.7

Comparison 2: Subgroup analyses for comparison 01, Outcome 7: By etiologic category

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Analysis 3.1

Comparison 3: Efficacy of intravenous lidocaine or its oral analogs vs. other analgesics, Outcome 1: Mean pain scores post intervention/control

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Analysis 4.1

Comparison 4: Adverse effects: Lidocaine or oral analogs vs. placebo, Outcome 1: Patients with adverse effects

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Analysis 5.1

Comparison 5: Adverse effects: Lidocaine or oral analogs vs. other analgesics, Outcome 1: Patients with adverse effects

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Comparison 1. Efficacy of lidocaine or mexiletine vs. placebo control

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
1.1 Post intervention/placebo mean VAS (0‐100) pain scores (Random effects model) Show forest plot	20	750	Mean Difference (IV, Random, 95% CI)	‐11.18 [‐14.97, ‐7.40]

1.1.1 Lidocaine IV trials	11	373	Mean Difference (IV, Random, 95% CI)	‐11.26 [‐17.30, ‐5.22]
1.1.2 Mexiletine trials	9	377	Mean Difference (IV, Random, 95% CI)	‐11.11 [‐16.25, ‐5.97]
1.2 Significant pain relief by response rates Show forest plot	14	589	Odds Ratio (M‐H, Random, 95% CI)	3.39 [2.08, 5.55]

1.2.1 Lidocaine	9	229	Odds Ratio (M‐H, Random, 95% CI)	5.06 [2.36, 10.84]
1.2.2 Mexiletine	5	360	Odds Ratio (M‐H, Random, 95% CI)	2.52 [1.47, 4.31]

Comparison 1. Efficacy of lidocaine or mexiletine vs. placebo control

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Comparison 2. Subgroup analyses for comparison 01

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
2.1 By sample size Show forest plot	20		Mean Difference (IV, Random, 95% CI)	Subtotals only

2.1.1 Fewer than 25 patients	17	535	Mean Difference (IV, Random, 95% CI)	‐12.44 [‐16.92, ‐7.97]
2.1.2 More than 25 patients	3	213	Mean Difference (IV, Random, 95% CI)	‐6.72 [‐16.21, 2.76]
2.2 By time of outcome measurement Show forest plot	20	749	Mean Difference (IV, Random, 95% CI)	‐10.91 [‐14.91, ‐6.91]

2.2.1 Minutes (less than 24 h)	10	343	Mean Difference (IV, Random, 95% CI)	‐11.58 [‐18.34, ‐4.82]
2.2.2 More than 24 h	10	406	Mean Difference (IV, Random, 95% CI)	‐10.50 [‐15.71, ‐5.30]
2.3 By time of outcome measurement (minus Stracke trial) Show forest plot	19	656	Mean Difference (IV, Random, 95% CI)	‐12.21 [‐15.85, ‐8.57]

2.3.1 Minutes (< 24 h)	10	343	Mean Difference (IV, Random, 95% CI)	‐11.58 [‐18.34, ‐4.82]
2.3.2 > 24 h	9	313	Mean Difference (IV, Random, 95% CI)	‐12.85 [‐16.71, ‐8.99]
2.4 By time of outcome measurement (minus 3 trials with wide data spread) Show forest plot	17	563	Mean Difference (IV, Random, 95% CI)	‐13.99 [‐17.25, ‐10.72]

2.4.1 Minutes (< 24 h)	9	295	Mean Difference (IV, Random, 95% CI)	‐13.83 [‐19.67, ‐7.99]
2.4.2 > 24 h	8	268	Mean Difference (IV, Random, 95% CI)	‐14.06 [‐18.00, ‐10.12]
2.5 By trial design Show forest plot	20		Mean Difference (IV, Random, 95% CI)	Subtotals only

2.5.1 Crossover	15	506	Mean Difference (IV, Random, 95% CI)	‐12.25 [‐16.70, ‐7.81]
2.5.2 Parallel	5	243	Mean Difference (IV, Random, 95% CI)	‐9.34 [‐17.88, ‐0.81]
2.6 By methodological quality Show forest plot	20	748	Mean Difference (IV, Random, 95% CI)	‐10.94 [‐14.89, ‐6.98]

2.6.1 Score: 2‐3 points	9	375	Mean Difference (IV, Random, 95% CI)	‐9.31 [‐15.78, ‐2.85]
2.6.2 Score: 4 points	7	211	Mean Difference (IV, Random, 95% CI)	‐12.56 [‐19.47, ‐5.64]
2.6.3 Score: 5 points	4	162	Mean Difference (IV, Random, 95% CI)	‐12.10 [‐20.00, ‐4.20]
2.7 By etiologic category Show forest plot	19		Mean Difference (IV, Random, 95% CI)	Subtotals only

2.7.1 Peripheral (metabolic)	5	246	Mean Difference (IV, Random, 95% CI)	‐11.06 [‐18.97, ‐3.15]
2.7.2 Peripheral (infectious)	3	118	Mean Difference (IV, Random, 95% CI)	‐4.45 [‐16.81, 7.91]
2.7.3 Peripheral (trauma)	4	166	Mean Difference (IV, Random, 95% CI)	‐8.57 [‐17.23, 0.08]
2.7.4 Peripheral (cancer)	1	20	Mean Difference (IV, Random, 95% CI)	2.80 [‐21.71, 27.31]
2.7.5 Peripheral (mixed)	3	79	Mean Difference (IV, Random, 95% CI)	‐16.80 [‐28.03, ‐5.58]
2.7.6 Central	3	98	Mean Difference (IV, Random, 95% CI)	‐12.91 [‐22.14, ‐3.67]

Comparison 2. Subgroup analyses for comparison 01

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Comparison 3. Efficacy of intravenous lidocaine or its oral analogs vs. other analgesics

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
3.1 Mean pain scores post intervention/control Show forest plot	5	206	Mean Difference (IV, Random, 95% CI)	‐0.60 [‐6.96, 5.75]

Comparison 3. Efficacy of intravenous lidocaine or its oral analogs vs. other analgesics

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Comparison 4. Adverse effects: Lidocaine or oral analogs vs. placebo

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
4.1 Patients with adverse effects Show forest plot	19	813	Odds Ratio (M‐H, Random, 95% CI)	4.60 [3.04, 6.97]

Comparison 4. Adverse effects: Lidocaine or oral analogs vs. placebo

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Comparison 5. Adverse effects: Lidocaine or oral analogs vs. other analgesics

Outcome or subgroup title	No. of studies	No. of participants	Statistical method	Effect size
5.1 Patients with adverse effects Show forest plot	5	205	Odds Ratio (M‐H, Random, 95% CI)	0.78 [0.15, 3.96]

Comparison 5. Adverse effects: Lidocaine or oral analogs vs. other analgesics

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