Hance Clarke

The Prevention of Chronic Postsurgical Pain Using Gabapentin and Pregabalin: A Combined Systematic Review and Meta-Analysis

BACKGROUND:Many clinical trials have demonstrated the effectiveness of gabapentin and pregabalin administration in the perioperative period as an adjunct to reduce acute postoperative pain. However, very few clinical trials have examined the use of gabapentin and pregabalin for the prevention of chronic postsurgical pain (CPSP). We (1) systematically reviewed the published literature pertaining to the prevention of CPSP (≥2 months after surgery) after perioperative administration of gabapentin and pregabalin and (2) performed a meta-analysis using studies that report sufficient data. A search of electronic databases (Medline, Embase, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, IPA, and CINAHL) for relevant English-language trials to June 2011 was conducted. METHODS:The following inclusion criteria for identified clinical trials were used for entry into the present systematic review: randomization; double-blind assessments of pain and analgesic use; report of pain using a reliable and valid measure; report of analgesic consumption; and an absence of design flaws, methodological problems or confounders that render interpretation of the results ambiguous. Trials that did not fit the definition of preventive analgesia and did not assess chronic pain at 2 or more months after surgery were excluded. RESULTS:The database search yielded 474 citations. Eleven studies met the inclusion criteria. Of the 11 trials, 8 studied gabapentin, 4 of which (i.e., 50%) found that perioperative administration of gabapentin decreased the incidence of chronic pain more than 2 months after surgery. The 3 trials that used pregabalin demonstrated a significant reduction in the incidence of CPSP, and 2 of the 3 trials also found an improvement in postsurgical patient function. Eight studies were included in a meta-analysis, 6 of the gabapentin trials demonstrated a moderate-to-large reduction in the development of CPSP (pooled odds ratio [OR] 0.52; 95% confidence interval [CI], 0.27 to 0.98; P = 0.04), and the 2 pregabalin trials found a very large reduction in the development of CPSP (pooled OR 0.09; 95% CI, 0.02 to 0.79; P = 0.007). CONCLUSIONS:The present review supports the view that perioperative administration of gabapentin and pregabalin are effective in reducing the incidence of CPSP. Better-designed and appropriately powered clinical trials are needed to confirm these early findings.

Rates and risk factors for prolonged opioid use after major surgery: population based cohort study

Objective To describe rates and risk factors for prolonged postoperative use of opioids in patients who had not previously used opioids and undergoing major elective surgery. Design Population based retrospective cohort study. Setting Acute care hospitals in Ontario, Canada, between 1 April 2003 and 31 March 2010. Participants 39 140 opioid naïve patients aged 66 years or older who had major elective surgery, including cardiac, intrathoracic, intra-abdominal, and pelvic procedures. Main outcome measure Prolonged opioid use after discharge, as defined by ongoing outpatient prescriptions for opioids for more than 90 days after surgery. Results Of the 39 140 patients in the entire cohort, 49.2% (n=19 256) were discharged from hospital with an opioid prescription, and 3.1% (n=1229) continued to receive opioids for more than 90 days after surgery. Following risk adjustment with multivariable logistic regression modelling, patient related factors associated with significantly higher risks of prolonged opioid use included younger age, lower household income, specific comorbidities (diabetes, heart failure, pulmonary disease), and use of specific drugs preoperatively (benzodiazepines, selective serotonin reuptake inhibitors, angiotensin converting enzyme inhibitors). The type of surgical procedure was also highly associated with prolonged opioid use. Compared with open radical prostatectomies, both open and minimally invasive thoracic procedures were associated with significantly higher risks (odds ratio 2.58, 95% confidence interval 2.03 to 3.28 and 1.95 1.36 to 2.78, respectively). Conversely, open and minimally invasive major gynaecological procedures were associated with significantly lower risks (0.73, 0.55 to 0.98 and 0.45, 0.33 to 0.62, respectively). Conclusions Approximately 3% of previously opioid naïve patients continued to use opioids for more than 90 days after major elective surgery. Specific patient and surgical characteristics were associated with the development of prolonged postoperative use of opioids. Our findings can help better inform understanding about the long term risks of opioid treatment for acute postoperative pain and define patient subgroups that warrant interventions to prevent progression to prolonged postoperative opioid use.

Review article: Preventive analgesia: quo vadimus?

The classic definition of preemptive analgesia requires 2 groups of patients to receive identical treatment before or after incision or surgery. The only difference between the 2 groups is the timing of administration of the drug relative to incision. The constraint to include a postincision or postsurgical treatment group is methodologically appealing, because in the presence of a positive result, it provides a window of time within which the observed effect occurred, and thus points to possible mechanisms underlying the effect: the classic view assumes that the intraoperative nociceptive barrage contributes to a greater extent to postoperative pain than does the postoperative nociceptive barrage. However, this view is too restrictive and narrow, in part because we know that sensitization is induced by factors other than the peripheral nociceptive barrage associated with incision and subsequent noxious intraoperative events. A broader approach to the prevention of postoperative pain has evolved that aims to minimize the deleterious immediate and long-term effects of noxious perioperative afferent input. The focus of preventive analgesia is not on the relative timing of analgesic or anesthetic interventions, but on attenuating the impact of the peripheral nociceptive barrage associated with noxious preoperative, intraoperative, and/or postoperative stimuli. These stimuli induce peripheral and central sensitization, which increase postoperative pain intensity and analgesic requirements. Preventing sensitization will reduce pain and analgesic requirements. Preventive analgesia is demonstrated when postoperative pain and/or analgesic use are reduced beyond the duration of action of the target drug, which we have defined as 5.5 half-lives of the target drug. This requirement ensures that the observed effects are not direct analgesic effects. In this article, we briefly review the history of preemptive analgesia and relate it to the broader concept of preventive analgesia. We highlight clinical trial designs and examples from the literature that distinguish preventive analgesia from preemptive analgesia and conclude with suggestions for future research.

Adding Gabapentin to a multimodal regimen does not reduce acute pain, opioid consumption or chronic pain after total hip arthroplasty

Background: Gabapentin (GPN) is effective in reducing post‐operative pain and opioid consumption, but its effects with regional anesthesia for total hip arthroplasty (THA) are not known. We designed this study to determine whether (1) gabapentin administration reduces pain and opioid use after THA using a multimodal analgesic regimen including spinal anesthesia; (2) pre‐operative administration of gabapentin is more effective than post‐operative administration.

Perioperative gabapentin reduces 24 h opioid consumption and improves in-hospital rehabilitation but not post-discharge outcomes after total knee arthroplasty with peripheral nerve block

BACKGROUND This study was designed to determine whether a 4 day perioperative regimen of gabapentin added to celecoxib improves in-hospital rehabilitation and physical function on postoperative day 4 and 6 weeks and 3 months after total knee arthroplasty (TKA). METHODS After Research Ethics Board approval and informed consent, 212 patients were enrolled in a randomized, double-blinded, placebo-controlled study. Two hours before surgery, patients received celecoxib 400 mg p.o. and were randomly assigned to receive either gabapentin 600 mg or placebo p.o. Two hours later, patients received femoral, sciatic nerve blocks, and spinal anaesthesia. After operation, patients received gabapentin 200 mg or placebo three times per day (TID) for 4 days. All patients also received celecoxib 200 mg q12 h for 72 h and i.v. patient-controlled analgesia for 24 h. Pain and function were assessed at baseline, during hospitalization, on postoperative day 4 (POD4), and 6 weeks and 3 months after surgery. RESULTS The gabapentin group used less morphine in the first 24 h after surgery [G=38.3 (29.5 mg), P=48.2 (29.4 mg)] (P<0.0125) and had increased knee range of motion compared with the placebo group in-hospital (P<0.05). There were no differences between groups in favour of the gabapentin group for pain or physical function on POD 4 [95% confidence interval (CI): pain: -1.4, 0.5; function: -6.3, 2.0], 6 weeks (95% CI: pain: 0.1, 1.9; function: -0.2, 6.5) or 3 months (95% CI: pain: -0.2, 1.7; function: -2.2, 4.3) after TKA. CONCLUSIONS In the context of celecoxib, spinal anaesthesia, femoral and sciatic nerve blocks, a dose of gabapentin 600 mg before operation followed by 4 days of gabapentin 200 mg TID decreased postoperative analgesic requirements and improved knee range of motion after TKA. Gabapentin provided no improvement in pain or physical function on POD4 and 6 weeks or 3 months after surgery.

Strategies Aimed at Preventing Chronic Post-surgical Pain: Comprehensive Perioperative Pain Management after Total Joint Replacement Surgery.

PURPOSE Chronic post-surgical pain (CPSP) is a frequent outcome of musculoskeletal surgery. Physiotherapists often treat patients with pain before and after musculoskeletal surgery. The purposes of this paper are (1) to raise awareness of the nature, mechanisms, and significance of CPSP; and (2) to highlight the necessity for an inter-professional team to understand and address its complexity. Using total joint replacement surgeries as a model, we provide a review of pain mechanisms and pain management strategies. SUMMARY OF KEY POINTS By understanding the mechanisms by which pain alters the bodys normal physiological responses to surgery, clinicians selectively target pain in post-surgical patients through the use of multi-modal management strategies. Clinicians should not assume that patients receiving multiple medications have a problem with pain. Rather, the modern-day approach is to manage pain using preventive strategies, with the aims of reducing the intensity of acute postoperative pain and minimizing the development of CPSP. CONCLUSIONS The roles of biological, surgical, psychosocial, and patient-related risk factors in the transition to pain chronicity require further investigation if we are to better understand their relationships with pain. Measuring pain intensity and analgesic use is not sufficient. Proper evaluation and management of risk factors for CPSP require inter-professional teams to characterize a patients experience of postoperative pain and to examine pain arising during functional activities.

Transversus abdominis plane (TAP) catheters inserted under direct vision in the donor site following free DIEP and MS-TRAM breast reconstruction: A prospective cohort study of 45 patients

INTRODUCTION The transversus abdominis plane (TAP) block is a peripheral nerve block of T6-L1 intercostal nerves of the abdominal wall. The purpose of this study was to evaluate the usefulness of intermittent TAP blockade for the first two postoperative days following free muscle sparing-transverse rectus abdominis muscle (MS-TRAM) or deep inferior epigastric perforator (DIEP) flap reconstruction of the breast. Therapeutic--Level II evidence. MATERIAL AND METHODS This prospective cohort consisted of 45 consecutive patients who underwent DIEP or MS-TRAM free-flap breast reconstruction. Intra-operatively, a multi-orifice epidural catheter was inserted under direct vision into the TAP. Ten millilitres of 0.25% bupivacaine was injected into each TAP catheter every 12 h until removal on day 3. The control group consisted of 80 consecutive patients who underwent free MS-TRAM or DIEP free-flap breast reconstructions by the same two surgeons without TAP block. Postoperatively, both groups had patient-controlled analgesia (PCA) and the primary outcome was intravenous (IV) PCA opioid consumption in the first 48 h. RESULTS There were no complications associated with using TAP catheters. The 48-h PCA-delivered opioid requirement was significantly less (p<0.001) in the TAP block group (17.10±17.23 mg IV morphine equivalent) compared to the control group (48.44±39.53 mg). CONCLUSION Intermittent delivery of bupivacaine through the TAP block significantly reduced postoperative parenteral opioid requirements following free MS-TRAM or DIEP flap reconstruction of the breast. This is the first report of the TAP block being inserted under direct vision to provide postoperative analgesia at the abdominal flap donor site following microsurgical breast reconstruction.

Distinguishing problematic from nonproblematic postsurgical pain: a pain trajectory analysis after total knee arthroplasty.

Abstract The goal of this study was to follow a cohort of patients undergoing total knee arthroplasty over time to: (1) identify and describe the various pain trajectories beginning preoperatively and for up to 12 months after surgery, (2) identify baseline predictors of trajectory group membership, and (3) identify trajectory groups associated with poor psychosocial outcomes 12 months after surgery. One hundred seventy-three participants (female = 85 [49%]; mean age [years] = 62.9, SD = 6.8) completed pain and psychological questionnaires and functional performance tests preoperatively and 4 days, 6 weeks, and 3 and 12 months after total knee arthroplasty. Using growth mixture modeling, results showed that a 4-group model, with a quadratic slope and baseline pain data predicting trajectory group membership, best fit the data (Akaike information criterion = 2772.27). The first 3 pain trajectories represent various rates of recovery ending with relatively low levels of pain 12 months after surgery. Group 4, the constant high pain group, comprises patients who have a neutral or positive pain slope and do not show improvement in their pain experience over the first year after surgery. This model suggests that preoperative pain levels are predictive of pain trajectory group membership and moderate preoperative pain, as opposed to low or high pain, is a risk factor for a neutral or positive pain trajectory postoperatively. Consistent with previous studies, these results show that postoperative pain is not a homogeneous condition and point to the importance of examining intraindividual pain fluctuations as they relate to pain interventions and prevention strategies.

Epidural analgesia provides better pain management after live liver donation: A retrospective study

Despite the increase in surgical volumes of live liver donation, there has been very little documentation of the postoperative pain experience. The primary aim of this study was to examine the difference in acute postoperative pain intensity and adverse effects between patients who received intravenous patient‐controlled analgesia (IV PCA) or patient‐controlled epidural analgesia (PCEA) for pain control after live liver donation surgery. A retrospective chart review was performed of 226 consecutive patients who underwent right living donor hepatic surgery at the Toronto General Hospital, Toronto, Canada. Patients who received as their primary postoperative analgesic modality IV PCA (n = 158) were compared to patients who received PCEA (n = 68). Demographic profiles for the 2 groups were similar with respect to age, sex, and body mass index at the time of surgery. For the first 3 postoperative days, pain intensity was significantly lower in patients who received epidural analgesia (P < 0.01). Clinically significant moderate pain (defined as a Numeric Rating Scale pain score >4) was reported more frequently in the IV PCA group (P < 0.05) along with increased sedation (P < 0.05). Pruritus was reported more frequently in the PCEA group of patients compared to the IV PCA group (P < 0.05). Significant between‐group differences were not found for the incidence of postoperative vomiting, the time at which patients began fluid intake, the time to initial ambulation, or the length of hospital stay. In conclusion, epidural analgesia provides better postoperative pain relief, less sedation, but more pruritus than IV PCA after live liver donation. Liver Transpl, 2011.

Chronic postsurgical pain and persistent opioid use following surgery: the need for a transitional pain service

AIM To identify the 3-month incidence of chronic postsurgical pain and long-term opioid use in patients at the Toronto General Hospital. METHODS 200 consecutive patients presenting for elective major surgery completed standardized questionnaires by telephone at 3 months after surgery. RESULTS 51 patients reported a preoperative chronic pain condition, with 12 taking opioids preoperatively. 3 months after surgery 35% of patients reported having surgical site pain and 13.5% continued to use opioids for postsurgical pain relief. Postoperative opioid use was associated with interference with walking and work, and lower mood. CONCLUSION Chronic postsurgical pain and ongoing opioid use are concerns that warrant the implementation of a Transitional Pain Service to modify the pain trajectories and enable effective opioid weaning following major surgery.