Gabapentin

Gabapentin

PEP Topic 
Acute Pain
Description 

Gabapentin, which belongs to the class of medications called anticonvulsants, treats seizures by decreasing excitement in the brain. Gabapentin has been studied for its effect in patients with cancer who have neuropathic pain or symptoms of peripheral neuropathy. The drug changes the way the body senses pain. It has also been studied for its effect on anxiety, chemotherapy-induced nausea and vomiting, and hot flashes.

Likely to Be Effective

Research Evidence Summaries

Bala, I., Bharti, N., Chaubey, V.K., & Mandal, A.K. (2012). Efficacy of gabapentin for prevention of postoperative catheter-related bladder discomfort in patients undergoing transurethral resection of bladder tumor. Urology, 79, 853–857.

doi:10.1016/j.urology.2011.11.050
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Study Purpose:

To evaluate the effect of 600 mg and 1200 mg oral gabapentin pretreatment for the prevention of postoperative catheter-related bladder discomfort (CRBD) in patients undergoing catheterization after transurethral resection of bladder tumor (TURBT)

Intervention Characteristics/Basic Study Process:

Patients were randomized to three groups. Group I received four placebo capsules. Group II received two capsules of 300 mg gabapentin and two identical placebo capsules. Group III received four capsules of 300 mg gabapentin. All patients received the study drug orally, with sips of water, one hour prior to administration of anesthesia. Lumbar subarachnoid block was administered with 2.5 ml 0.5% hyperbaric bupivacaine. An anesthesiologist unaware of group assignment observed patients in the Postanesthesia Care Unit (PACU) at 1, 2, 4, 6, 12, and 24 hours.

Sample Characteristics:

  • The sample was composed of 100 patients.
  • Mean patient age was 52.2 years.
  • Of all patients, 79% were male and 21% were female.
  • All patients had been diagnosed with a bladder tumor.

Setting:

  • Single site
  • Inpatient
  • United States

 

Phase of Care and Clinical Applications:

Active antitumor treatment

Study Design:

Randomized controlled double-blind trial

Measurement Instruments/Methods:

  • Four-point scale, to record severity of bladder discomfort
  • Observations of postoperative nausea, vomiting, and any adverse effect (e.g., sedation, dizziness, ataxia, tinnitus, diplopia, vertigo) related to the study drug

Results:

  • At 1, 2, and 24 hours after surgery, patients in group II, who received 600 mg gabapentin, had significantly lower incidence of CRBD (p < 0.0001) than did patients in the control group (group I).
  • At all time points, the incidence of CRBD was significantly lower (p < 0.0001) in patients receiving 1200 mg gabapentin (group III) than in the control group (group I).
  • At 4, 6, 12, and 24 hours, the incidence of CRBD was significantly lower (p < 0.0001) in patients receiving 1200 mg gabapentin (group III) than in group II.
  • Compared to the severity of CRBD in group I, the severity of CRBD was significantly lower (p < 0.0001) in groups II and III.

Conclusions:

Pretreatment with gabapentin reduces bladder discomfort in patients with an indwelling postoperative catheter. Gabapentin 1200 mg is more effective than gabapentin 600 mg in decreasing the incidence and severity of CRBD.

Limitations:

  • The study had risk of bias due to sample characteristics. The sample was primarily male, though the male-to-female ratio was similar in all three groups.
  • Findings are not generalizable.

Nursing Implications:

To decrease the postoperative discomfort of patients undergoing catheterization after transurethral resection of bladder tumor, nurses may want to advocate for the preoperative use of 1200 mg gabapentin.

Bharti, N., Bala, I., Narayan, V., & Singh, G. (2013). Effect of gabapentin pretreatment on propofol consumption, hemodynamic variables, and postoperative pain relief in breast cancer surgery. Acta Anaesthesiologica Taiwanica, 51, 10–13.

doi: 10.1016/j.aat.2013.03.009
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Study Purpose:

To evaluate the effects of preoperative gabapentin on anesthesia requirements and postoperative pain

Intervention Characteristics/Basic Study Process:

Patients were randomized to receive either 600 mg gabapentin or placebo two hours prior to surgery for breast cancer. Patients were followed for 24 hours after surgery. Postoperative analgesia was provided with intramuscular diclofenac sodium 1.5 mg every eight hours and IV morphine 3 mg on demand or when the pain score was 4 or higher.

Sample Characteristics:

  • N = 40
  • MEAN AGE = 46.6 years
  • FEMALES: 100%
  • KEY DISEASE CHARACTERISTICS: Breast cancer

Setting:

  • SITE: Single site 
  • SETTING TYPE: Inpatient 
  • LOCATION: Taiwan

Phase of Care and Clinical Applications:

  • PHASE OF CARE: Active antitumor treatment

Study Design:

  • Double-blind, placebo-controlled RCT

Measurement Instruments/Methods:

  • Physiologic measures and medication dosages from medical records
  • 11-point numeric pain rating scale

Results:

Propofol requirements for induction (p = .02) and maintenance of anesthesia (p = .009) was significantly lower in the gabapentin group. Patients in the gabapentin group had significantly lower pain scores up to two hours postoperatively (p < .001). More patients in the control group required rescue analgesics (p = .03). There were no significant differences between groups in duration of surgery or intraoperative analgesics.

Conclusions:

Preoperative gabapentin may reduce anesthesia dose requirements and short-term postoperative pain.

Limitations:

  • Small sample (less than 100)
  • Baseline sample/group differences of import
  • The control group had higher American Society of Anesthesiologists scores at baseline, and although not statistically significant, this could have influenced findings. 
  • Patients were only followed for 24 hours.
  • Authors report lower anxiety with gabapentin preoperatively but do not describe the method or timing of this measure.

Nursing Implications:

Preoperative gabapentin may reduce anesthesia dose needs and postoperative pain.

Grover, V.K., Mathew, P.J., Yaddanapudi, S., & Sehgal, S. (2009). A single dose of preoperative gabapentin for pain reduction and requirement of morphine after total mastectomy and axillary dissection: Randomized placebo-controlled double-blind trial. Journal of Postgraduate Medicine, 55(4), 257–260.

doi:10.4103/0022-3859.58928
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Study Purpose:

To investigate the effect of a single low dose (600 mg) of preoperative oral gabapentin on morphine consumption after total mastectomy and axillary dissection; to determine if the specified administration of gabapentin is safe 

Intervention Characteristics/Basic Study Process:

Before total mastectomy and axillary dissection, patients received 600 mg gabapentin or placebo. Pain, sedation, nausea, vomiting, and side effects were monitored every 30 minutes for 2 hours and then every 2 hours until 12 hours after surgery.

Sample Characteristics:

  • The sample was composed of 46 patients.
  • The age range of patients was 18–75 years. In the placebo group, mean patient age was 44.9 years. In the gabapentin group, mean patient age was 46.6 years. 
  • All patients were female. All patients were undergoing total mastectomy with axillary dissection ASA I or II.

 

Setting:

  • Single setting
  • Inpatient
  • Postanesthesia care unit

 

Study Design:

Randomized double-blind placebo-controlled trial

Measurement Instruments/Methods:

  • 100-point pain rating scale
  • Observer’s assessment of alertness or sedation
  • Reports of nausea and number of episodes of vomiting

Results:

  • Postoperative morphine consumption was 48% lower in the gabapentin group than in the placebo group (P < 0.001). 
  • Compared to patients who received gabapentin, patients who received placebo had significantly higher postoperative pain scores and shorter times to rescue dose (P < 0.001).
  • Authors noted no difference between groups in regard to sedation, incidence of nausea, and other side effects.

Conclusions:

Pre-emptive administration of a single oral dose of gabapentin, 600 mg, led to a decrease in the use of postoperative analgesic.

Limitations:

  • The study had a small sample size, with fewer than 100 patients.
  • The study involved only one dose of gabapentin at a single time.
  • The study followed patients for only 12 hours after surgery.

Nursing Implications:

The use of preoperative gabapentin was associated with improved pain control and quality of life, without excessive side effects.

Misra, S., Parthasarathi, G., & Vilanilam, G.C. (2013). The effect of gabapentin premedication on postoperative nausea, vomiting, and pain in patients on preoperative dexamethasone undergoing craniotomy for intracranial tumors. Journal of Neurosurgical Anesthesiology, 25, 386–391.

doi: 10.1097/ANA.0b013e31829327eb
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Study Purpose:

To determine if prophylactically administered 600 mg oral gabapentin reduces postoperative nausea or emesis and decreases postcraniotomy pain

Intervention Characteristics/Basic Study Process:

Patients to undergo elective craniotomy were randomized to receive either placebo (a vitamin b-complex capsule) or 600 mg oral gabapentin two hours before induction of anesthesia. All received standard antiepileptic prophylaxis with 100 mg phenytoin every eight hours and 4 mg IV dexamethasone every eight hours for 48 hours prior to surgery. Patients were given 1 gm IV paracetamol every six hours for postoperative pain. Rescue analgesia was provided with 1 mcg/kg IV fentanyl for a pain score of 3. Rescue antiemetic was provided with 4 mg IV ondansetron if the patient had any emetic episode or 10 minutes or longer of nausea. All received the same anesthesia. Symptoms were assessed hourly for the first six hours postoperatively and then every two hours for the next 18 hours.

Sample Characteristics:

  • N = 73  
  • MEAN AGE = 44 years
  • MALES: 68.5%, FEMALES: 31.5%
  • KEY DISEASE CHARACTERISTICS: All were undergoing craniotomy
  • OTHER KEY SAMPLE CHARACTERISTICS: Duration of anesthesia averaged slightly more than 400 minutes and was not different between study groups.

Setting:

  • SITE: Single site   
  • SETTING TYPE: Inpatient   
  • LOCATION: India

Phase of Care and Clinical Applications:

  • PHASE OF CARE: Active antitumor treatment

Study Design:

  • Placebo-controlled RCT

Measurement Instruments/Methods:

  • Pain verbal rating scale of 0 (no pain) to 3 (moderate to severe, requiring rescue)

Results:

Incidence of nausea was 35.1% in the placebo group compared to 11.1% in the gabapentin group (p = .02). No significant difference was seen between groups in incidence of emesis, but there was a trend to lower incidence of emesis with gabapentin. No difference was seen between groups in postoperative pain scores, the number of patients who required rescue analgesia, or postoperative fentanyl consumption.

Conclusions:

Prophylactic oral gabapentin prior to surgery reduced postoperative nausea and vomiting in patients undergoing craniotomy. Perioperative gabapentin had no effect on postoperative pain.

Limitations:

  • Small sample (less than 100)
  • Risk of bias (no blinding)
  • Measurement validity/reliability questionable
  • The method of pain measurement is questionable, as a 3-point scale.

Nursing Implications:

Preoperative gabapentin may reduce postoperative symptoms of nausea and vomiting in patients undergoing craniotomy who are receiving dexamethasone perioperatively. The optimum dosage of gabapentin has not been determined.

Ture, H., Sayin, M., Karlikaya, G., Bingol, C.A., Aykac, B., & Ture, U. (2009). The analgesic effect of gabapentin as a prophylactic anticonvulsant drug on postcraniotomy pain: A prospective randomized study. Anesthesia and Analgesia, 109(5),1625–1631.

doi:10.1213/ane.0b013e3181b0f18b
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Study Purpose:

To evaluate the effectiveness of gabapentin in treating acute postoperative pain in patients who have undergone craniotomy

Intervention Characteristics/Basic Study Process:

For anticonvulsant prophylaxis, patients were randomized to one of two groups. One group received 1200 mg oral gabapentin daily (400 mg three times/day). The other received 300 mg oral gabapentin daily (100 mg three times/day). Patients took medications for seven days before surgery, as part of the surgical regimen, and postoperatively. All patients received postoperative morphine via patient controlled analgesia (PCA); the dose was titrated up to 0.1 mg/kg IV according to the pain rating on a visual analog scale (VAS). Postoperative follow-up included noting the VAS and Ramsay sedation scores, morphine consumption, and seizure activity or other adverse effects at 0, 15, and 30 minutes and at 1, 2, 4, 6, 12, 24, and 48 hours.

Sample Characteristics:

  • The sample was composed of 75 patients.
  • Mean patient age was 47 years.
  • Of all patients, 52% were female and 48% were male.
  • All patients had meningioma, glioma, or brain metastases and were undergoing elective supratentorial craniotomy for tumor resection. All patients had tumors with a diameter no larger than 30 mm and a rating of greater than or equal to 15 on the Glasgow coma scale.
  • Excluded from the sample were patients taking tricyclic antidepressants, selective serotonin reuptake inhibitors, monoamine oxidase inhibitors, or neuroleptic or antiepileptic drugs.

Setting:

  • Single site
  • Inpatient
  • Turkey

Study Design:

Randomized parallel-group trial

Measurement Instruments/Methods:

  • Visual analog scale, to measure pain
  • Ramsay sedation scale
  • Glasgow coma scale

Results:

  • During the first postoperative hour and at all time points, postoperative VAS scores were significantly higher (p < 0.0001) for those on phenytoin than for those on gabapentin.
  • Compared to patients on gabapentin, patients on phenytoin consumed significantly more morphine (p = 0.01), totally and cumulatively.
  • During the first two hours after surgery, patients on gabapentin had significantly higher sedation scores (p < 0.05) than did patients on phenytoin.
  • Two patients were removed from the study prior to surgery because of apparent side effects of gabapentin. Side effects included severe fatigue and severe dizziness.
  • Patients on gabapentin required less perioperative anesthesia than did patients on phenytoin.
  • Individuals on gabapentin had a longer time to tracheal extubation (16.6 minutes, SD = 22 minutes) compared to those on phenytoin (4.5 minutes, SD = 2 minutes) (p < 0.001).

Conclusions:

Use of gabapentin as a prophylactic anticonvulsant was associated with lower postoperative opioid consumption and lower pain severity. Gabapentin was associated with higher sedation in the immediate postoperative period and a longer time to extubation.

Limitations:

  • The study had a small sample size, with fewer than 100 patients.
  • The study had a risk of bias due to no blinding.
  • The specified use of gabapentin was in a very specific patient population. Findings may not be applicable to other groups of patients.

Nursing Implications:

Gabapentin had significant analgesic effects in patients who had undergone craniotomy, but pain relief was associated with increased sedation and longer time to extubation. In patients undergoing neurosurgery, determining causes of increased sedation or delayed extubation can be difficult and critical. Sedation and delayed extubation can contribute to difficulties in clinical care. Future research should investigate the timing and dosage of gabapentin, with the goal of taking advantage of the drug's positive effects while minimizing negative side effects.

Guideline/Expert Opinion

National Comprehensive Cancer Network. (2011). NCCN Clinical Practice Guidelines in Oncology: Adult cancer pain [v. 2.2011]. Retrieved from http://www.nccn.org/professionals/physician_gls/pdf/pain.pdf

http://www.nccn.org/professionals/physician_gls/pdf/pain.pdf
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Type of Resource/Evidence-Based Process:

These guidelines do not provide any information about search strategy or any specific evaluation of evidence. Notes state that most direct evidence is of low quality, but recommendations do result from unanimous consensus.

Guidelines & Recommendations:

The guidelines provide detailed recommendations regarding:

  • Screening and assessment
  • Management of pain in opioid-naive as well as opioid-tolerant patients
  • Ongoing care of adult patients with cancer and related pain management
  • Comprehensive pain assessment and use of pain ratings
  • Interventions for specific types of pain syndromes
  • Opioid prescribing, titration, and ongoing management
  • Management of adverse effects related to opioids
  • Psychosocial support and patient and family education
  • Nonpharmacologic interventions.

Limitations:

In general, opioids are first-line interventions. The NCCN guidelines suggest that antidepressants and anticonvulsants can be first-line treatments for adjuvant pain, although the recommendation for using them as such is still based on anecdotal experience or guidelines relating to patients who do not have cancer.

Nursing Implications:

The NCCN guidelines provide comprehensive algorithms for pain management, from screening to ongoing maintenance. The guidelines recommend considering a variety of nonpharmacologic interventions. Psychosocial support, including coping-skills training, is recommended, as is comprehensive patient and family education. The guidelines provide useful information and an overview of the full range of pain management. The work points to the ongoing need to consider multiple adjuvant and supportive interventions to achieve pain relief that works for the individual patient.


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