A randomized study of the effects of single-dose gabapentin versus placebo on postoperative pain and morphine consumption after mastectomy

BACKGROUND: The anticonvulsant gabapentin has proven effective for neuropathic pain in three large placebo-controlled clinical trials. Experimental and clinical studies have demonstrated antihyperalgesic effects in models involving central neuronal sensitization. It has been suggested that central neuronal sensitization may play an important role in postoperative pain. The aim of the study was to investigate the effect of gabapentin on morphine consumption and postoperative pain in patients undergoing radical mastectomy. METHODS: In a randomized, double-blind, placebo-controlled study, 70 patients received a single dose of oral gabapentin (1,200 mg) or placebo 1 h before surgery. Patients received patient-controlled analgesia with morphine at doses of 2.5 mg with a lock-out time of 10 min for 4 h postoperatively. Pain was assessed on a visual analog scale at rest and during movement, and side effects were assessed on a four-point verbal scale 2 and 4 h postoperatively. RESULTS: Thirty-one patients in the gabapentin group and 34 patients in the placebo group completed the study. Gabapentin reduced total morphine consumption from a median of 29 (interquartile range, 21-33) to 15 (10-19) mg (P< 0.0001). Pain during movement was reduced from 41 (31-59) to 22 (10-38) mm at 2 h postoperatively (P < 0.0001) and from 31 (12-40) to 9 (3-34) mm at 4 h postoperatively (P = 0.018). No significant differences between groups were observed with regard to pain at rest or side effects. CONCLUSION: A single dose of 1,200 mg oral gabapentin resulted in a substantial reduction in postoperative morphine consumption and movement-related pain after radical mastectomy, without significant side effects. These promising results should be validated in other acute pain models involving central neuronal sensitization.     

Gabapentin in postamputation phantom limb pain: a randomized,double-blind,placebo-controlled,cross-over study

BACKGROUND AND OBJECTIVES: Severe phantom limb pain after surgical amputation affects 50% to 67% of patients and is difficult to treat. Gabapentin is effective in several syndromes of neuropathic pain. Therefore, we evaluated its analgesic efficacy in phantom limb pain. METHODS: Patients attending a multidisciplinary pain clinic with phantom limb pain were enrolled into this randomized, double-blind, placebo-controlled, cross-over study. Other anticonvulsant therapy was discontinued. Each treatment was 6 weeks separated by a 1-week washout period. Codeine/paracetamol was allowed as rescue analgesia. The daily dose of gabapentin was titrated in increments of 300 mg to 2400 mg or the maximum tolerated dose. Patients were assessed at weekly intervals. The primary outcome measure was visual analog scale (VAS) pain intensity difference (PID) compared with baseline at the end of each treatment. Secondary measures were indices of sleep interference, depression (Hospital Anxiety and Depression [HAD] scale), and activities of daily living (Bartel Index). RESULTS: Nineteen eligible patients (mean age, 56 years; range, 24 to 68 years; 16 men) were randomized, of whom 14 completed both arms of the study. Both placebo and gabapentin treatments resulted in reduced VAS scores compared with baseline. PID was significantly greater than placebo for gabapentin therapy at the end of the treatment (3.2 +/- 2.1 v 1.6 +/- 0.7, P =.03). There were no significant differences between placebo and gabapentin therapy in terms of the number of tablets of rescue medication required, sleep interference, HAD scale, or Bartel Index. The medication was well tolerated with few reports of adverse effects. CONCLUSIONS: After 6 weeks, gabapentin monotherapy was better than placebo in relieving postamputation phantom limb pain. There were no significant differences in mood, sleep interference, or activities of daily living, but a type II error cannot be excluded for these variables.     

Analgesic effects of intravenous lidocaine and morphine on postamputation pain: a randomized double-blind, active placebo-controlled, crossover trial

BACKGROUND: Phantom and stump pains, common sequelae of limb amputations, are significant impediments to rehabilitation of amputees. The pathophysiology and optimal treatment of postamputation pain states are unclear. While stump pain may result from neuromas in the stump, phantom pain is thought to be related to cortical reorganization. The authors hypothesized that morphine and lidocaine may have differential effectiveness on stump and phantom pains. METHODS: The authors conducted a randomized double-blind, active-placebo-controlled, crossover trial to compare the analgesic effects of intravenous morphine and lidocaine on postamputation stump and phantom pains. An intravenous bolus followed by an intravenous infusion of morphine (0.05 mg/kg bolus + 0.2 mg/kg infusion over 40 min), lidocaine (1 mg/kg bolus + 4 mg/kg infusion) and the active placebo, diphenhydramine (10 mg bolus + 40 mg infusion), were performed on three consecutive days. Phantom and stump pain ratings and sedation scores were recorded at 5-min intervals using a 0-100 visual analog scale. Pain measures were initiated 30 min before drug infusion and continued until 30 min after the end of infusion. Subjects' self-reported pain relief and satisfaction were assessed at the end of each infusion. RESULTS: Thirty-one of 32 subjects enrolled completed the study. Eleven subjects had both stump and phantom pains, 11 and 9 subjects had stump and phantom pain alone, respectively. Baseline pain scores were similar in the three drug groups. Compared with placebo, morphine reduced both stump and phantom pains significantly (P < 0.01). In contrast, lidocaine decreased stump (P < 0.01), but not phantom pain. The changes in sedation scores for morphine and lidocaine were not significantly different from placebo. Compared with placebo, self-reported stump pain relief was significantly greater for lidocaine (P < 0.05) and morphine (P < 0.01), while phantom pain relief was greater only for morphine (P < 0.01). Satisfaction scores were significantly higher for lidocaine (mean +/- SD: 39.3 +/- 37.8, P < 0.01) and morphine (45.9 +/- 35.5, P < 0.01) when compared with placebo (9.6 +/- 21.0). CONCLUSIONS: Stump pain was diminished both by morphine and lidocaine, while phantom pain was diminished only by morphine, suggesting that the mechanisms and pharmacological sensitivity of stump and phantom pains are different.     

Oral ketamine therapy in the treatment of postamputation stump pain

Background: Hyperacti vity of N-methy l-D-aspartate (NMD A) receptors may be one of the factors in the maintenance of post-amputation stump pain.
Conclusion: NMDA receptor antagonists may have a potential in the treatment of neuropathic pain, including stump pain.     

Optimal dose of pre-incision/post-incision gabapentin for pain relief following lumbar laminectomy: a randomized study

Background: Gabapentin has been introduced as an effective agent for post‐operative pain control. This study aimed to test the effects of pre‐ and post‐incision administration of different doses of gabapentin on post‐operative morphine requirement and pain following lumbar laminectomy. Methods: In this randomized clinical trial, 175 patients were allocated into seven groups of 25 patients each to receive placebo or gabapentin 600, 900 or 1200 mg pre‐ or post‐incision. Total patient‐controlled intravenous morphine consumption during the first 24 post‐operative hours, and the time to the first demand for morphine were recorded. Pain score at rest (visual analogue scale) was recorded every 30 min in the first 4 h and then every 2 h until 24 h post‐operatively. Side‐effects were observed. Results: In the first 12 h, morphine consumption was less, pain scores were lower and the time to the first demand for analgesia was longer in groups receiving gabapentin 900 or 1200 mg either pre‐ or post‐incision, compared with placebo and gabapentin 600 mg (P<0.001). There was no difference between gabapentin 900 and 1200 mg. Pain score, morphine consumption and time to the first demand for analgesia in equal pre‐ or post‐incision doses of gabapentin were not significantly different. No differences in the side‐effects were observed between groups. Conclusion: Gabapentin 900 or 1200 mg, administered either pre‐ or post‐incision, was found to be effective in pain management following lumbar laminectomy. Similar doses of gabapentin provide the same post‐operative analgesia whether administered pre‐ or post‐incision.     

The analgesic effects of perioperative gabapentin on postoperative pain: a meta-analysis

BACKGROUND AND OBJECTIVES: Gabapentin is an anticonvulsant that has been shown to be effective in the treatment of neuropathic and inflammatory pain in animal and human studies. The analgesic effect of its perioperative use has not been fully elucidated. METHODS: This systematic review (meta-analysis) included 12 randomized controlled trials of 896 patients undergoing a variety of surgical procedures that investigated the impact of perioperative administration of gabapentin on postoperative outcome. RESULTS: The pooled visual analog scores for pain at 4 hours and 24 hours were significantly less in those patients who received gabapentin (weighted mean difference [WMD] = -1.57; 95% confidence interval [CI], -2.14 to -0.99 and WMD = -0.74; CI, -1.03 to -0.45, respectively). A concomitant decrease in opioid usage by those patients who received gabapentin was also noted (odds ratio [OR] = -17.84; CI, -23.50 to -12.18). Gabapentin administration was associated with sedation and anxiolysis (OR = 3.28; CI, 1.21-8.87) but not associated with a difference in lightheadedness, dizziness, nausea, or vomiting. CONCLUSIONS: Based on this systematic review, perioperative oral gabapentin is a useful adjunct for the management of postoperative pain that provides analgesia through a different mechanism than opioids and other analgesic agents and would make a reasonable addition to a multimodal analgesic treatment plan.     

Evaluation of the optimal preemptive dose of gabapentin for postoperative pain relief after lumbar diskectomy: a randomized, double-blind, placebo-controlled study

We evaluated the optimal preemptive dose of gabapentin for postoperative pain relief after single-level lumbar diskectomy and its effect on fentanyl consumption during the initial 24 hours in a randomized, double-blinded, placebo-controlled study in 100 patients with American Society of Anesthesiologists physical status I and II. Patients were divided into five groups to receive placebo or gabapentin 300, 600, 900, or 1200 mg 2 hours before surgery. After surgery, patients were transferred to the postanesthesia care unit (PACU). A blinded anesthesiologist recorded the pain scores at time points of 6, 12, 18, and 24 hours in the PACU on a Visual Analog Scale (VAS; 0-10 cm) at rest. Patients received patient-controlled analgesia (fentanyl 1.0 mug/kg on each demand with lockout interval of 10 minutes); total fentanyl consumption during initial 24 hours was recorded. Data were entered into the statistical software package SPSS 9.0 for analysis (one-way analysis of variance and Student-Newman-Keuls test). Patients who received gabapentin 300 mg had significantly lower VAS score at all time points. They consumed less fentanyl (patients who received placebo processed 1217.5 +/- 182.0 versus 987.5 +/- 129.6 mug; P < 0.05). Patients who received gabapentin 600, 900, and 1200 mg had lower VAS scores at all time points than patients who received gabapentin 300 mg (P < 0.05). Increasing the dose of gabapentin from 600 to 1200 mg did not decrease the VAS score, nor did the increasing dose of gabapentin significantly decrease fentanyl consumption (702.5, 635, and 626.5 microg). Thus, gabapentin 600 mg is the optimal dose for postoperative pain relief following lumbar diskectomy.     

A prospective study on the role of gabapentin in post-burn pruritus

Gabapentin, used in the treatment of neuropathic pain, is suggested as an alternative treatment to antihistamines for post-burn itching. There is insufficient awareness about the etiopathogenesis and available treatment options for post-burn pruritus. To study the effect of gabapentin on post-burn itching, patients with post-burn pruritus not relieved with cetirizine tablet were offered gabapentin and assessed for response by the numerically graded self-report questionnaire ‘Itch Severity Scale’ for 6?months. Treatment success was determined by reduction in the itch scores, which were statistically analysed. Twenty-three patients with post-burns pruritic hypertrophic scars were studied. All patients had history of delayed burn healing (over 3?weeks). Twenty patients completed follow-up. All 20 reported a reduction in itching with gabapentin. Mean reduction in itch severity was 4.99 (statistically significant) within the first month of starting the therapy, with sustained effect seen for the duration of treatment. No serious side effects were reported. Eighty-seven per cent of patients showed good relief from itching within 1?month of starting treatment. Overall quality of life improved considerably. Gabapentin is suggested as a protocol for second-line option in post-burn pruritus. The ‘Itch Severity Scale’ is a reliable tool for pruritus measurement, including subjective parameters.     

Effects of gabapentin on postoperative morphine consumption and pain after abdominal hysterectomy: a randomized, double-blind trial

BACKGROUND: Preliminary clinical studies have suggested that gabapentin may produce analgesia and reduce the need for opioids in postoperative patients. The aim of the present study was to investigate the opioid-sparing and analgesic effects of gabapentin administered during the first 24 h after abdominal hysterectomy. METHODS: In a randomized, double-blind study, 80 patients received oral gabapentin 1200 mg or placebo 1 h before surgery, followed by oral gabapentin 600 mg or placebo 8, 16 and 24 h after the initial dose. Patients received patient-controlled analgesia with morphine at doses of 2.5 mg with a lock-out time of 10 min for 24 h postoperatively. Pain was assessed on a visual analogue scale (VAS) at rest and during mobilization, nausea, somnolence and dizziness on a four-point verbal scale, and vomiting as present/not present at 2, 4, 22 and 24 h postoperatively. RESULTS: Thirty-nine patients in the gabapentin group, and 32 patients in the placebo group completed the study. Gabapentin reduced total morphine consumption from median 63 (interquartile range 53-88) mg to 43 (28-60) mg (P < 0.001). We observed a significant inverse association between plasma levels of gabapentin at 2 h postoperatively, and morphine usage from 0 to 2 h, and from 0 to 4 h postoperatively (R2 = 0.30, P = 0.003 and R2 = 0.24 P = 0.008, respectively). No significant differences in pain at rest or during mobilization, or in side-effects, were observed between groups. CONCLUSION: Gabapentin in a total dose of 3000 mg, administered before and during the first 24 h after abdominal hysterectomy, reduced morphine consumption with 32%, without significant effects on pain scores. No significant differences in side-effects were observed between study-groups.     

Effect of preemptive gabapentin on postoperative pain relief and morphine consumption following lumbar laminectomy and discectomy: a randomized, double-blinded, placebo-controlled study

Synergism between gabapentin and morphine in treating incisional pain has been demonstrated in animal experiments and clinical studies. The efficacy of gabapentin for treatment of perioperative pain remains controversial. This study was designed to detect the influence of gabapentin premedication on morphine consumption in the immediate postoperative period in patients undergoing lumbar laminectomy and discectomy. Either gabapentin 800 mg (in two equally divided doses) or placebo was given preoperatively to 60 adult patients undergoing elective lumbar laminectomy or discectomy in a double-blinded, placebo-controlled, randomized study. Standard general anesthesia was given to all the patients. Morphine was administered via patient-controlled analgesia pump in the immediate postoperative period for first 8 hours. Pain at rest and on movement was assessed using a Verbal Rating Scale (VRS) every 2 hours for the first 8 postoperative hours. There were no differences in demographics or surgical duration between the two groups. The amount of fentanyl administered in the intraoperative period was similar between the two groups. In the postoperative period, the VRS score for pain at 0, 2, 4, 6, and 8 hours was not significantly different between the two groups. Highest median VRS score was recorded at 0 hours postoperatively in both groups (VRS: rest = 6, movement = 8 in placebo group; rest = 6, movement = 8 in gabapentin group). Total morphine consumption and side effects were similar in the two groups. Gabapentin does not decrease the morphine requirement or morphine side effects in the immediate postoperative period following lumbar laminectomy and discectomy.     

Effects of gabapentin on experimental somatic pain and temporal summation

BACKGROUND AND OBJECTIVES: Gabapentin is used for treatment of neuropathic pain, but its effect on different somatic pain modalities and integrative mechanisms are not completely understood. The aim of this double-blind, placebo-controlled experimental pain study, conducted on 20 healthy volunteers, was to examine the effect of a single dose of 1200 mg gabapentin on multi-modal experimental cutaneous and muscle pain models. METHODS: The following pain models were applied: (1) pain thresholds to single and repeated cutaneous and intramuscular electrical stimulation (temporal summation to 5 stimuli delivered at 2 Hz); (2) stimulus-response function relating pain intensity scores (visual analog scale, VAS) to increasing current intensities for electrical skin and muscle stimuli (single and repeated, determined at baseline); and (3) the pain intensity (VAS) and pain areas after intramuscular injection of hypertonic saline. Pain assessments were performed prior to, and at 4, 6, and 8 hours after medication. RESULTS: When responses were averaged across the post-dose times, gabapentin: (1) significantly increased the temporal summation pain threshold in skin compared with placebo (P = .03); (2) significantly reduced the area under the pain intensity curve to hypertonic saline injections in the muscle (P = .02); and (3) significantly reduced the area of pain evoked by hypertonic saline (P = .03). CONCLUSIONS: Gabapentin reduces temporal summation of skin stimuli at pain threshold intensities; this may have potential as a biomarker for drugs with efficacy on neurogenic pain. The data also suggest that tonic muscle pain is responsive to gabapentin treatment and suggest further clinical studies.     

A clinical randomized study on the effects of invasive monitoring on burn shock resuscitation

BACKGROUND: Ever since Charles Baxter's recommendations the standard regime for burn shock resuscitation remains crystalloid infusion at a rate of 4 ml/kg/% burn in the first 24h following the thermal injury. A growing number of studies on invasive monitoring in burn shock, however, have raised a debate regarding the adequacy of this regime. The purpose of this prospective, randomised study was to compare goal-directed therapy guided by invasive monitoring with standard care (Baxter formula) in patients with burn shock. PATIENTS AND METHODS: Fifty consecutive patients with burns involving more than 20% body surface area were randomly assigned to one of two treatment groups. The control group was resuscitated according to the Baxter formula (4 ml/kg BW/% BSA burn), the thermodilution (TDD) group was treated according to a volumetric preload endpoint (intrathoracic blood volume) obtained by invasive haemodynamic monitoring. RESULTS: The baseline characteristics of the two treatment groups were similar. Fluid administration in the initial 24h after burn was significantly higher in the TDD treatment group than in the control group (P = 0.0001). The results of haemodynamic monitoring showed no significant difference in preload or cardiac output parameters. Signs of significant intravasal hypovolemia as indicated by subnormal values of intrathoracic and total blood volumes were present in both treatment groups. Mortality and morbidity were independent on randomisation. CONCLUSION: Burn shock resuscitation due to the Baxter formula leads to significant hypovolemia during the first 48 h following burn. Haemodynamic monitoring results in more aggressive therapeutic strategies and is associated with a significant increase in fluid administration. Increased crystalloid infusion does not improve preload or cardiac output parameters. This may be due to the fact that a pure crystalloid resuscitation is incapable of restoring cardiac preload during the period of burn shock.     

Rodent model of chronic central pain after spinal cord contusion injury and effects of gabapentin

Spinal cord injury (SCI) often results in abnormal pain syndromes in patients. We present a recently developed SCI mammalian model of chronic central pain in which the spinal cord is contused at T8 using the NYU impactor device (10-g rod, 2.0-mm diameter, 12.5-mm drop height), an injury which is characterized behaviorally as moderate. Recovery of locomotor function was assessed with an open field test and scored using the open field test scale (BBB scale). Somatosensory tests of paw withdrawal responses accompanied by supraspinal responses to both mechanical punctate (von Frey hairs) and nonpunctate (4 mm diameter blunt probe) as well as thermal (radiant heat) peripheral stimuli were performed. Comparisons at the level of the individual animal between precontusion and postcontusion responses indicated significant increases in reactions to low threshold punctate mechanical stimuli, non-punctate stimuli and thermal stimuli (p < 0.05). To demonstrate the validity of this model as a central pain model, gabapentin, an agent used clinically for central pain, was given i.p. at 10 or 30 mg/kg. Gabapentin treatment significantly and reversibly changed the responses, consistent with the attenuation of the abnormal sensory behavior, and the attenuated responses lasted for the duration of the drug effect (up to 6 h). These results support the use of the spinal contusion model in the study of chronic central pain after SCI.