Comparison of analgesic effects of Gabapentin and Paracetamol post-operatively in patients with hand injury

Design

Single-center, double-blind, randomized controlled trial

N= 50

Objective

To compare the analgesic effects of gabapentin and paracetamol post-operatively in patients with hand injury

Study Groups

Gabapentin (n= 25)

Paracetamol (n= 25)

Inclusion Criteria

Aged 18 to 60 years with hand injury

Exclusion Criteria

Pregnant women, presenting with signs of arrhythmia, myocardial ischemia, cognitive impairment, psychiatric disorders, drug abuse, taking any anti-epileptic drug, severe and multiple injuries

Methods

Patients were randomized (1:1) to receive gabapentin 600 mg or paracetamol 1,000 mg once the nil-per-oral (NPO) period was concluded after hand surgery. Surgery was done under general anesthesia.

Duration

Study period: March to August 2019

Follow-up: after 6 hours of drug administration

Outcome Measures

Pain intensity assessed by 0-10 visual analog scale (VAS)

Baseline Characteristics

Gabapentin (n= 25)

Age, years

Female

Source of injury

Road accident

Sudden fall

Machinery

Glass/knife cut

Other

8%

4%

28%

52%

8%

0

0

8%

68%

24%

VAS score before drug intake

5.68 ± 1.108

5.15 ± 1.650

Results

Endpoint

Gabapentin (n= 25)

Paracetamol (n= 25)

VAS score six hours after drug intake

p-value vs. baseline

1.60 ± 1.55

0.197

1.80 ± 1.528

0.604

Adverse Events

Common Adverse Events: dizziness (36% vs. 16%), nausea (44% vs. 36%), vomiting (20% vs. 8%), increased sleep (28% vs. 16%), anxiety (20% vs. 28%)

Serious Adverse Events: Not disclosed

Percentage that Discontinued due to Adverse Events: N/A

Study Author Conclusions

Both gabapentin and paracetamol were found to be effective in pain management, but the latter had slightly better pain control with relatively less side-effects.

InpharmD Researcher Critique

Statistical analyses comparing the gabapentin and paracetamol group were not conducted. Therefore, it is unknown how gabapentin compares to paracetamol for postoperative analgesia following hand injury aside from the descriptive statistics provided. This study is further limited by its small sample size and single-center nature.

A double-blind, randomized controlled trial of gabapentin vs. placebo for acute pain management in critically ill patients with rib fractures

Design

Randomized, double-blind, placebo-controlled trial

N= 40

Objective

To evaluate the efficacy of gabapentin in the acute setting for analgesia in patients with rib fractures

Study Groups

Gabapentin (n= 20)

Placebo (n= 20)

Inclusion Criteria

Adult patients with ≥ 1 rib fractures requiring hospital admission, study enrollment within 24 hours of initial injury

Exclusion Criteria

Intubated, age > 65 years, inability to tolerate oral medication, renal or hepatic impairment, traumatic brain injury, pregnant, hypersensitivity to gabapentin

Methods

Patients were randomized 1:1 to gabapentin 300 mg or placebo TID for 30 days following injury. All patients were prescribed additional non-narcotic analgesia per institutional guidelines, including acetaminophen 650 mg and ibuprofen 600 mg orally every 6 hours. 

Daily average numeric pain score (NPS; range 0-10) was obtained by averaging hourly scores recorded by nursing staff over 24 hour period x 7 days or until discharge, whichever came first. 

Duration

Trial: November 2016 to November 2017

Intervention: 30 days

Outcome Measures

Primary: daily average NPS

Secondary: opioid consumption, oxygen requirement, respiratory rate, best incentive spirometry recording

Baseline Characteristics

Placebo (n= 20)

Gabapentin (n= 20)

Age, years

Male

Body mass index, kg/m²

Injury severity 

Injury severity score (ISS)

Total rib fractures

Solid organ injury

Surgery during index admission

16

5

25%

40%

12

7

10%

55%

Doses received as inpatient out of total possible

Length of stay

Hospital

Intensive care unit

8

3

8

3

Baseline characteristics were generally comparable between groups. 

Results

Data were primarily presented as graphs. No significant difference was reported in any primary or secondary endpoint between groups. No differences were noted in additional pain modalities utilized during index admission between the two groups. 

Adverse Events

No serious adverse events were determined to be related to the study drug. There were no instances of pneumonia, respiratory failure, or mortality in either group.

Study Author Conclusions

The authors did not observe any benefit to adding gabapentin to a multi-modal analgesic regimen for rib fractures, using a dose of 300 mg thrice daily for 30 days. Although these data do not support the routine use of gabapentin for this indication, there may be specific patients for whom it is effective, and there may be unappreciated benefit at both higher doses and for longer courses of therapy. 

InpharmD Researcher Critique

Patients were administered 300 mg of gabapentin three times daily, which is substantially lower than the maximum dose of 1,200 mg three times daily. However, patients were not titrated, as the trial limited follow-up to one month after surgery. Based on the results of this study, surgeons at this institution suspended use of gabapentin for this indication pending further research. 

Arthroscopic Bankart Surgery: Does Gabapentin Reduce Postoperative Pain and Opioid Consumption

Design

Triple-blind randomized clinical trial 

N=76

Objective

To examine the effects of a preemptive single dose of gabapentin on pain management and opioid consumption in patients undergoing arthroscopic Bankart surgery

Study Groups

Gabapentin (n=38)

Placebo (n=38)

Inclusion Criteria

Age between 18–75, types I or II in American Society of Anesthesiology (ASA) physical status, operation duration time less than one hour, no concomitant lesions, diagnosed during arthroscopy

Exclusion Criteria

The presence of any accompanied cartilage lesions; any known allergy to gabapentin; having previous history of epilepsy, hepatic, renal, or psychological disorders; alcohol and/or drug abuse; daily consumption of analgesics, corticosteroids, or anticonvulsants

Methods

The eligible patients were randomized to receive either gabapentin 600 mg or matching placebo. The capsules were administered randomly two hours prior to the operation.

Duration

Enrollment: May 2011 to May 2013

Follow-up: 6h and 24h follow-up visits

Outcome Measures

Primary: Pain intensity assessed based on Visual Analogue Scale (VAS)

Secondary: Opioid consumption and side effects, dizziness, sedation, nausea, and vomiting at 6 h and 24 h follow-up visits. 

Baseline Characteristics

Gabapentin (n=38)

Placebo (n=38)

Age, years

Male

Operation time, minutes

Weight, kg

Results

Gabapentin (n=38)

Placebo (n=38)

p-value

Pain score (95% CI)

First postoperative visit (6 h)

Second post-operation visit (24 h)

4.9 (4.6-5.3)

4.7 (4.3-5.2)

5.4 (5.0-5.7)

5.3 (4.9-5.6)

>0.05

>0.05

Dizziness

First postoperative visit (6 h)

Second post-operation visit (24 h)

16%

14%

24%

9%

>0.05

>0.05

Sedation

First postoperative visit (6 h)

Second post-operation visit (24 h)

14%

8%

12%

6%

>0.05

>0.05

Nausea/vomiting

First postoperative visit (6 h)

Second post-operation visit (24 h)

3%

3%

32%

6%

0.001

>0.05

Adverse Events

N/A

Study Author Conclusions

The preemptive single dose of gabapentin 600 mg administered prior to arthroscopic Bankart surgery does not decrease post-operation pain but reduces opioid consumption. Gabapentin restrained postoperative nausea and vomiting for a short while (less than 6 h).

InpharmD Researcher Critique

The dosage of Gabapentin should be further evaluated as it has been argued that gabapentin 600 mg is more effective than gabapentin 300 mg and is as effective as higher doses (900 mg and 1200 mg).

Gabapentin is Ineffective as an Analgesic Adjunct in the Immediate Postburn Period

Design

Prospective, randomized, placebo-controlled, double-blind study

Objective

To determine whether gabapentin would have an impact on patient-reported pain levels and evaluate the presence of neuropathic pain (NP) in acute burn injury

Study Groups

Gabapentin (n= 27)

Placebo (n= 26)

Inclusion Criteria

Patients older than 18 years, with at least a 5% burn injury and an expected length of stay of 48 hours 

Exclusion Criteria

Pregnant, lactating, or had renal insufficiency

Methods

Patients were randomized 1:1 to receive either gabapentin or placebo. Patients received a loading dose of study drug on day 1 and began dosing per the dose-escalation schedule the day after. Patients were followed up for pain control, opioid consumption, and study drug tolerance while in the hospital. At discharge, patients were given a 3-day taper per the dose de-escalation schedule. Pain was assessed with 11 point Numeric Rating Scale (NRS). Rest pain, average pain and worst pain were assessed during the preceeding 24 hours.

Outcome Measures

Primary outcome: Morphine consumption & NRS pain scores

Baseline Characteristics

Placebo (n=26)

Gabapentin (n= 27)

Age, years

Body Surface Area Burned, %

Male

Etiology (flame)

Inhalation injury

Length of stay, days

Surgery

Autograft, cm²

Include relevant baseline characteristics that will provide a general (big picture) view of the patients in the study.

Results

Variable

Intention-to-Treat Analysis

Per-protocol Analysis

Treatment Effect

p-value

Treatment Effect

Daily Opioid 

   Use (yes or no)

   Dose (mg)

3.62

-0.73

<0.01

0.80

3.81

2.29

NRS

   Rest

   Hydrotherapy

   Intolerable pain rating

0.43

0.81

0.96 

0.40

0.22

0.80 

0.26

0.63

0.84 

NPS

   NPS total score

   NPS-NP

-0.86

1.10 

0.84

0.81 

0.22

1.21 

HADS-anxiety

   Score

   >8

-0.98

0.36

0.26

0.11

-0.83

0.41

Univariate analysis of the effect of treatment on outcome variables

Adverse Events

Not disclosed

Study Author Conclusions

Our study showed that Gp failed to show an opioid-sparing effect in acutely burned patients. We postulate that this is likely because of both a lesser role of NP in acute burn injuries and the ineffectiveness of Gp in the inhibition of sensitization in burn injuries.

InpharmD Researcher Critique

Gabapentin is useful for treating neuropathic pain which plays a role in a burn injuries but not enough to have a noticeable effect. It is hard to determine wheter or not gabapentin would be safe as an add-on to opioids because there was no safety data collected. In the future, it would be beneficial to see what adverse effects patients may have experienced to make a well-rounded clinical decision.

The Analgesic Effects of Preemptive Gabapentin in Patients Undergoing Surgery for Brachial Plexus Injury—A Preliminary Study

Design

Randomized, double-blinded, placebo-controlled

N= 20

Objective

To evaluate gabapentin as a preemptive analgesic for intraoperative period and during the acute postoperative period at rest and during movement

Study Groups

Placebo (n= 10)

Gabapentin (n= 10)

Inclusion Criteria

Aged 18 to 50, American Society of Anesthesiologists (ASA) physical status I and II, scheduled for elective brachial plexus exploration

Exclusion Criteria

Epilepsy, chronic pain disorders, drug allergy, psychiatric disorders, substance abuse, impaired liver, or renal functions, pregnancy

Patients were randomized 1:1 to oral gabapentin 800 mg or placebo capsules 2 hours before surgery. All patients were premedicated with intramuscular glycopyrrolate 0.2 mg 1 hour before surgery. Surgery was done under general anesthesia.

Visual analog scale (VAS; range 0 to 100) was assessed at rest and during movement in the intensive care unit hourly for 24 hours. For data analysis, mean VAS values were obtained at time intervals of 0 to 6 hours, 6 to 12 hours, 12 to 18 hours, and 18 to 24 hours. Patients with VAS scores of > 50 may receive additional pain treatment with ketorolac injection. 

Duration

Follow-up: 24 hours postoperative period

Outcome Measures

Pain score at rest and during movement assessed by VAS  

Baseline Characteristics

Placebo (n= 10)

Gabapentin (n= 10)

p-value

Age, years

Female

Total intraoperative propofol, mg

Total doses of rescue analgesic in 24 h postoperative

Results

Endpoint

Placebo (n= 10)

Gabapentin (n= 10)

VAS score at rest#

0 h

6 h

12 h

18 h

24 h

46 ± 14.3

47.5 ± 14.4

49 ± 17.3

49 ± 14.5

54 ± 13.5

31.5 ± 11.6

37.5 ± 11.1

38 ± 10.3

34.5 ± 4.4* 

38.5 ± 10.0**

VAS score on movement$

0 h

6 h

12 h

18 h

24 h

67 ± 15.7

65 ± 19.6

66 ± 17.8

63 ± 12.5

66.5 ± 16.3

52 ± 14.8

52.5 ± 10.9

54 ± 11.0

50.5 ± 10.1

54.5 ± 10.1

9

3; p= 0.02

#p= 0.01 between the 2 groups; $p= 0.04 between 2 groups; *p= 0.007 after post hoc correction; **p= 0.009 after post hoc correction

Adverse Events

Study Author Conclusions

The preliminary study with 800 mg single oral dose of gabapentin as a preemptive analgesic in patients undergoing surgery for brachial plexus injury is found to be an effective adjunct to intraoperative and postoperative pain. Pain is reduced not only at rest but also during movement. The dose of gabapentin used did not produce any side effects and was well tolerated by the patients. Further trials may be needed to evaluate the appropriate dose of gabapentin as a preemptive analgesic.

InpharmD Researcher Critique

In this preliminary study, the VAS scores of the gabapentin group were significantly lower compared to the placebo group. Additionally, most of the placebo patients required rescue analgesics compared to gabapentin. With no side effects requiring intervention with the studied dose, additional trials are needed for an appropriate dose of gabapentin. The study is also limited by its small sample size and the preliminary report in nature. 

The Use Of Gabapentin For Post-operative and Post-traumatic Pain In Thoracic Surgery Patients

Design

Prospective observational trial

N= 60

Objective

To evaluate the safety and efficacy of gabapentin in the treatment of persistent pain following thoracic surgery or trauma

Study Groups

Followed-up patients (n= 45)

Inclusion Criteria

Any major general thoracic surgical procedure or required initial in-patient treatment for blunt thoracic trauma, presented to the clinic four weeks or more after the initial operation or trauma with persistent chest wall pain or paresthesia which was refractory to conventional analgesics

Exclusion Criteria

Initial pathology which invaded or involved the chest wall, surgery involving extensive parietal pleural trauma, post-operative complications which may affect the pain experience, history of analgesic dependence or abuse, history of epilepsy or any neurological condition for which the drug treatment may be affected by gabapentin, any known contraindications for gabapentin use, any previous allergy or adverse effect from gabapentin,

Methods

Each patient was commenced on regular oral gabapentin at 300 mg daily at bedtime. The dose of gabapentin was titrated up to 300 mg twice daily on Day 4, and 300 mg three times daily on Day 7 if the pain relief was inadequate and no adverse effect from the gabapentin was noted. All other analgesics were stopped, but paracetamol/dextropropoxyphene 650/65 mg preparation was taken for breakthrough pain. 

Duration

Enrollment: January 1, 2003 - April 30, 2004 

Intervention: median 21 months (range 12-28 months) 

Outcome Measures

Pain and paresthesia (assessed by 10-point analog scale), adverse effects

Baseline Characteristics

Followed-up patients (n= 45)

Age, years

Female, n

Duration of chest wall pain, months (range)

Chest wall paresthesia distinct from sharp wound pain

Duration of gabapentin, weeks (range)

Operation/trauma for patients with pain, n

Video-assisted thoracic surgery (VATS)

Thoracotomy

Median sternotomy

Blunt chest trauma

22

8

3

12

Initial pain severity, n

Mild (1-3)

Moderate (4-6)

Severe (7-10)

9

12

24

Final titrated dose of gabapentin for patients with pain, n

300 mg at bedtime

300 mg twice daily

300 mg three times daily

21

10

14

Operation/trauma for patients with paresthesia, n

VATS

Thoracotomy

Sternotomy

Blunt trauma

15

8

2

7

Initial paresthesia severity, n

Mild (1-3)

Moderate (4-6)

Severe (7-10)

5

9

18

Final titrated dose of gabapentin for patients with paresthesia, n

300 mg at bedtime

300 mg twice daily

300 mg three times daily

14

6

12

Results

Pain improved

Followed-up patients (n= 45)

p-value

Operation/trauma

VATS

Thoracotomy

Sternotomy

Blunt trauma

14/22 (63.6%)

7/8 (87.5%)

3/3 (100%)

9/12 (75%)

Initial pain severity

Mild

Moderate

Severe

3/9 (33.3%)

9/12 (75%)

21/24 (87.5%)

Final titrated dose of gabapentin

300 mg at bedtime

300 mg twice daily

300 mg three times daily

16/21 (76.2%)

7/10 (70%)

10/14 (71.4%)

Paresthesia improved

Followed-up patients (n= 45)

Operation/trauma

VATS

Thoracotomy

Sternotomy

Blunt trauma

9/15 (60%)

7/8 (87.5%)

1/2 (50%)

6/7 (85.7%)

Initial pain severity

Mild

Moderate

Severe

3/5 (60%)

5/9 (55.6%)

16/18 (88.9%)

Final titrated dose of gabapentin

300 mg at bedtime

300 mg twice daily

300 mg three times daily

9/14 (64.3%)

6/6 (100%)

9/12 (75%)

Adverse Events

Common Adverse Events: somnolence (24.4%), dizziness (6.7%)

Serious Adverse Events: None

Percentage that Discontinued due to Adverse Events: No patients died or had any major adverse events as a result of gabapentin use. Three patients (6.7%) discontinued use of gabapentin due to intolerance of side effects (dizziness in two patients and diarrhea in one patient).

Study Author Conclusions

Gabapentin appears safe and well tolerated when used for persistent post-operative and post-traumatic pain in thoracic surgery patients, although minor side effects do occur. Gabapentin may relieve refractory chest wall pain in some of these patients, particularly those with more severe pain. Further studies are warranted to define the role of gabapentin in cardiothoracic surgical practice.

InpharmD Researcher Critique

Despite the safety results, drawing overly strong conclusions or recommendations regarding the analgesic properties of gabapentin in thoracic surgery patients at this stage is discouraged given the limitations of the current study, and a further trial investigating the analgesic efficacy of the drug in treating post-thoracotomy pain is warranted.