Baseline Opioid Dose Research Articles

Low-dose ketamine infusion to facilitate opioid tapering in chronic non-cancer pain with opioid-use disorder: a historical cohort study

BackgroundLong-term opioid use is associated with pharmacological tolerance, a risk of misuse and hyperalgesia in patients with chronic pain (CP). Tapering is challenging in this context, particularly with comorbid opioid-use...

Low Dose Buprenorphine Induction With Full Agonist Overlap in Hospitalized Patients With Opioid Use Disorder: A Retrospective Cohort Study.

To describe the outcomes of buprenorphine/naloxone low dose induction with overlap of full opioid agonists among hospitalized patients with opioid use disorder (OUD) as an alternative to standard induction strategies. Retrospective cohort study of patients with OUD who were admitted to the hospital over a 1-year period and initiated ono buprenorphine using initial doses of 0.5 mg and gradually increased while the patient remained on full agonists. Descriptive variables included basic demographics, reason for switching to buprenorphine, baseline opioid and morphine equivalent dose. The primary outcome was a successful transition defined by the patient leaving the hospital with a buprenorphine prescription. Bivariate analysis identified factors associated with unsuccessful medication transitions. Secondary outcomes included reported withdrawal symptoms and 30 day follow up to an outpatient buprenorphine program. Sixty two patients underwent low dose with overlap induction during the study period. Fourteen patients were on methadone for OUD before hospital admission. Fifty one patients (82%) successfully left the hospital with a prescription for buprenorphine. Factors associated with lower likelihood of success included older age, transitioning due to discharge placement needs and presence of withdrawal symptoms during the transition. Overall, 66% (N = 23) of patients referred within the same health care system followed up within 30 days. Low dose inductions with overlap of full opioid agonists were largely successful in transitioning hospitalized patients from full agonist opioids to buprenorphine. However, there were several factors associated with lower likelihood of success. Future work could focus on treatment of withdrawal symptoms and system-level changes ensuring patient-centered medication decisions.

A Comprehensive, Multimodal, Interdisciplinary Approach to Chronic Non-Cancer Pain Management in a Family Medicine Clinic: A Retrospective Cohort Review.

The complexity of chronic non-cancer pain in the setting of regulatory efforts to curb opioid usage presents a novel challenge for the medical community. Much of this burden falls on primary care clinics. We retrospectively quantified the reduction of opioid usage by patients in a multimodal, interdisciplinary, primary care clinic for chronic pain. A multimodal, interdisciplinary, chronic pain clinic embedded in a large academic military family medicine clinic operated one-half day weekly to address referrals from within the clinic at large. Appointment times were longer than typical primary care appointments. The clinic was equipped with support staff, ancillary specialty providers, and non-pharmacologic complementary treatment resources. A retrospective cohort review was conducted on 78 patients referred to this clinic from March 1, 2015 (the inception date of the clinic) through December 31, 2015. Fifty-four of 78 patients met inclusion criteria. Overall mean morphine equivalent daily dosing (MEDD) dropped from 31.5 MEDD to 20.5 MEDD (p = 0.0005) 12 months post-intervention and from 31.5 MEDD to 9.5 MEDD (p < 0.0001) 36 months post-intervention. Four patients with a high mean baseline opioid dose of 185.2 MEDD dropped to 29.9 MEDD 36 months post-intervention. The mean 0-10 pain score decreased from 5.3 ± 2.2 to 4.0 ± 2.5 (p = 0.001). A multimodal, interdisciplinary, primary care-based, chronic pain clinic equipped with extended appointment times, non-pharmacologic treatment resources, and specialty access can curb opioid usage. Leadership support for protracted appointment duration, complementary treatment resources, and interdisciplinary personnel is crucial to success.

S187 A Pooled Analysis of the Efficacy and Safety of Methylnaltrexone for Opioid-Induced Constipation in Patients With Severe Medical Illness: The Impact of Baseline Opioid Equivalent Dose

S187 A Pooled Analysis of the Efficacy and Safety of Methylnaltrexone for Opioid-Induced Constipation in Patients With Severe Medical Illness: The Impact of Baseline Opioid Equivalent Dose

6: Nerve Blocks With Targeted Muscle Reinnervation Reduce Acute Postoperative Opioid Use in Major Lower Extremity Amputation

Purpose:Major amputations of the lower extremity, specifically through and below the knee, are morbid procedures requiring general anesthesia typically followed by high doses of postoperative opioids. Many are performed on highly comorbid, chronic wound patients with a potential for increased opioid use following surgery. Given the current opioid epidemic, perioperative narcotic-reduction strategies are paramount. Our center instituted a protocol for major amputations that includes continuous regional anesthesia, for intraoperative and postoperative pain control, and targeted muscle reinnervation (TMR) nerve transfers to mitigate long-term pain. The aim of this study was to analyze the impact of continuous regional anesthesia and TMR on early postoperative opioid requirements after major lower extremity amputation at our limb salvage center.Methods:We retrospectively reviewed our center’s below-knee and through-knee-amputations from 2017-2019 for utilization of regional pain catheters and TMR nerve transfers. Opioid usage as morphine milligram equivalents (MMEs) was tracked for the first seven postoperative days. Baseline opioid dose was defined by the documented opioid use one day before amputation. Patients were categorized into one of four groups, based on whether regional pain catheter and/or TMR were used. Kruskal-Wallis testing was used to assess baseline opioid use between groups. Bivariate linear regression was used to assess postoperative opioid use of each group compared to the control group. Logistic regression analysis was conducted to examine association between TMR and changes in opioid use postoperatively versus baseline.Results:198 patients were reviewed. 95 patients received perioperative regional anesthesia, of which 81 underwent TMR. 103 patients did not receive regional anesthesia, of which 30 underwent TMR. Average baseline opioid use was 40.6 MME in patients treated with TMR and regional anesthesia, 60.2 MME with TMR and without regional anesthesia, 28.7 MME without TMR and with regional anesthesia, and 132.6 MME without TMR and regional anesthesia (p=0.0004). Multivariate analysis showed that undergoing TMR, without regional anesthesia, significantly decreased postoperative opioid use by 111.7 MME, compared to the control group (p=0.006). Use of regional anesthesia, with TMR, provided an additive effect, significantly decreasing postoperative opioid use by 124.3 MME, compared to control (p<0.0001). Interestingly, regional anesthesia without TMR decreased postoperative opioid use by 93.4 MME, but without significance (p=0.08). Odds of decreased opioid use postoperatively compared to baseline was 1.91 times higher with TMR than without TMR (p=0.04).Conclusion:TMR nerve transfers were found to be independently effective at reducing postoperative opioid requirements after major lower extremity amputation. Concurrent use of regional anesthesia compounded this effect. Minimizing baseline opioid use prior to amputation may decrease opioid use postoperatively. TMR nerve transfer with continuous regional anesthesia protocol can decrease reliance on postoperative pain control with opioids in lower extremity major amputation patients.

Opioid Reduction and Risk Mitigation in VA Primary Care: Outcomes from the Integrated Pain Team Initiative.

National guidelines advise decreasing opioids for chronic pain, but there is no guidance on implementation. To evaluate the effectiveness of an Integrated Pain Team (IPT) clinic in decreasing opioid dose and mitigating opioid risk. This study prospectively compared two matched cohorts receiving chronic pain care through IPT (N = 147) versus usual primary care (UPC, N = 147) over 6 months. Patients were matched on age, sex, psychiatric diagnoses, and baseline opioid dose. Veterans receiving care at a VA medical center or VA community-based clinics. Interdisciplinary IPT, consisting of a collocated medical provider, psychologist, and pharmacist embedded in VA primary care providing short-term biopsychosocial management of veterans with chronic pain and problematic opioid use. Change in opioid dose expressed as morphine equivalent daily dose (MEDD) and opioid risk mitigation evaluated at baseline, 3 months, and 6 months. Compared with veterans receiving UPC, those followed by IPT had a greater mean MEDD decrease of 42 mg versus 8 mg after 3 months and 56 mg versus 17 mg after 6 months. In adjusted analysis, compared with UPC, veterans in IPT achieved a 34-mg greater mean reduction at 3 months (p = 0.002) and 38-mg greater mean reduction at 6 months (p = 0.003). Nearly twice as many patients receiving care through IPT versus UPC reduced their daily opioid dose by ≥50%, representing more than a two-fold improvement at 3 months, which was sustained at 6 months [odds ratio = 2.03; 95% CI = 1.04-3.95, p = 0.04]. Significant improvements were also demonstrated in opioid risk mitigation by 6 months, including increased urine drug screen monitoring, naloxone kit distribution, and decreased co-prescription of opioids and benzodiazepines (all p values < 0.001). Interdisciplinary biopsychosocial models of pain care can be embedded in primary care and lead to significant improvements in opioid dose and risk mitigation.

Predictors of duloxetine response in patients with neuropathic cancer pain: a secondary analysis of a randomized controlled trial-JORTC-PAL08 (DIRECT) study.

Duloxetine has some effect against cancer neuropathic pain (CNP); however, predictors of duloxetine response are unclear. This study sought to identify predictors of duloxetine response in patients with CNP. Patients (N = 70) with CNP unresponsive to or intolerant of opioid-pregabalin combination therapy, with a brief pain inventory-short form (BPI-SF) Item 5 score (average pain) ≥ 4, and with a total hospital anxiety and depression scale score < 20, were randomized to a duloxetine or a placebo group. Multiple linear regression analysis was conducted to identify predictors of duloxetine response as a secondary analysis with the change in the average pain score on day 10 from day 0 as the dependent variable, and the following five covariates; baseline (day 0) average pain score, baseline opioid dose, continuation/discontinuation of pregabalin, and items 20 and 21 score of the short-form McGill pain questionnaire 2 (SF-MPQ-2) as independent variables. Of the four domains (continuous pain, intermittent pain, neuropathic pain, and affective descriptors) score of SF-MPQ-2 on day 0, significant differences were observed in the neuropathic pain domain (p = 0.040) in change on the average pain between day 10 and day 0 in the duloxetine group. Multiple linear regression analysis revealed that patients with a high score for SF-MPQ-2 Item 21 (tingling pain) on day 0 had a significantly greater change in average pain between day 10 and day 0 (p = 0.046). Patients with a high score for SF-MPQ-2 Item 21 might benefit more from duloxetine.

Integrated Behavioral Treatment for Veterans With Co-Morbid Chronic Pain and Hazardous Opioid Use: A Randomized Controlled Pilot Trial

Opioid prescription in the treatment of chronic pain is frequent and carries a risk of increased morbidity and mortality in a clinically significant number of patients, particularly those who are using opioids in a hazardous manner. Few treatment options are available that target both pain-related interference and hazardous opioid use among patients with chronic pain. In military Veterans, this issue is of particular importance as numerous reports indicate continued high rates of opioid prescription for chronic pain, as well as significant opioid-related problems. The overall aim of the present study was to determine the feasibility of an integrated psychosocial treatment in Veterans with chronic pain, who also have evidence of hazardous opioid use. To examine this aim, a random design was used to assess the feasibility and initial efficacy of integrating 2 empirically supported interventions: Acceptance and Commitment Therapy for chronic pain and Mindfulness Based Relapse Prevention for opioid misuse. Half of participants were randomized to the integrated treatment group and all participants received usual care through a Veteran's Administration co-occurring disorders medical clinic to treat chronic pain and opioid misuse. In total, 37 participants were randomized and included in intent-to-treat analyses and 32 individuals were included in per protocol analyses with 6-month follow-up serving as the primary study endpoint. Feasibility indicators included recruitment, retention, and treatment completion rates. Recruitment fell short of targeted enrollment, although retention and completion were excellent. Primary outcome measures were opioid misuse, pain interference, and pain behavior. Simultaneous multiple regression analyses controlled for pain duration, baseline opioid dose, and baseline value for outcome measures. Results of both the intent-to-treat and per protocol indicated a significant effect in favor of the integrated intervention for opioid misuse, pain interference, and pain behavior. Results support the feasibility of providing an integrated treatment for both opioid risk and pain interference. PerspectiveOpioid misuse occurs in some opioid-prescribed individuals with chronic pain. Few treatment options exist that target both pain interference and opioid misuse. This study examined feasibility and initial efficacy of an integrated behavioral treatment for Veterans. Feasibility was supported, except recruitment. Efficacy was supported compared to usual care.

Stereotactic radiosurgery for trigeminal pain secondary to recurrent malignant skull base tumors.

The objective of this study was to assess outcomes after Gamma Knife radiosurgery (GKRS) re-irradiation for palliation of patients with trigeminal pain secondary to recurrent malignant skull base tumors. From 2009 to 2016, 26 patients who had previously undergone radiation treatment to the head and neck received GKRS for palliation of trigeminal neuropathic pain secondary to recurrence of malignant skull base tumors. Twenty-two patients received single-fraction GKRS to a median dose of 17 Gy (range 15-20 Gy) prescribed to the 50% isodose line (range 43%-55%). Four patients received fractionated Gamma Knife Extend therapy to a median dose of 24 Gy in 3 fractions (range 21-27 Gy) prescribed to the 50% isodose line (range 45%-50%). Those with at least a 3-month follow-up were assessed for symptom palliation. Self-reported pain was evaluated by the numeric rating scale (NRS) and MD Anderson Symptom Inventory-Head and Neck (MDASI-HN) pain score. Frequency of as-needed (PRN) analgesic use and opioid requirement were also assessed. Baseline opioid dose was reported as a fentanyl-equivalent dose (FED) and PRN for breakthrough pain use as oral morphine-equivalent dose (OMED). The chi-square and Student t-tests were used to determine differences before and after GKRS. Seven patients (29%) were excluded due to local disease progression. Two experienced progression at the first follow-up, and 5 had local recurrence from disease outside the GKRS volume. Nineteen patients were assessed for symptom palliation with a median follow-up duration of 10.4 months (range 3.0-34.4 months). At 3 months after GKRS, the NRS scores (n = 19) decreased from 4.65 ± 3.45 to 1.47 ± 2.11 (p < 0.001); MDASI-HN pain scores (n = 13) decreased from 5.02 ± 1.68 to 2.02 ± 1.54 (p < 0.01); scheduled FED (n = 19) decreased from 62.4 ± 102.1 to 27.9 ± 45.5 mcg/hr (p < 0.01); PRN OMED (n = 19) decreased from 43.9 ± 77.5 to 10.9 ± 20.8 mg/day (p = 0.02); and frequency of any PRN analgesic use (n = 19) decreased from 0.49 ± 0.55 to 1.33 ± 0.90 per day (p = 0.08). At 6 months after GKRS, 9 (56%) of 16 patients reported being pain free (NRS score 0), with 6 (67%) of the 9 being both pain free and not requiring analgesic medications. One patient treated early in our experience developed a temporary increase in trigeminal pain 3-4 days after GKRS requiring hospitalization. All subsequently treated patients were given a single dose of intravenous steroids immediately after GKRS followed by a 2-3-week oral steroid taper. No further cases of increased or new pain after treatment were observed after this intervention. GKRS for palliation of trigeminal pain secondary to recurrent malignant skull base tumors demonstrated a significant decrease in patient-reported pain and opioid requirement. Additional patients and a longer follow-up duration are needed to assess durability of symptom relief and local control.

Opioid dose reduction and pain control with medical cannabis.

189 Background: The use of medical cannabis (MC) for palliation of symptoms is on the rise in cancer and rheumatological patients. Whether there is a potential for opioid dose reduction (ODR) and or quality of life improvements (QOL) is unclear. Methods: A retrospective cohort was evaluated to understand the pattern of care and QOL outcomes with MC use across rural multidisciplinary practices in New Mexico. MC use (&gt; 1 mo.), EMR interrogation, urine toxicology screening were used to identify patients. QOL questionnaire included a graded pain scale. Morphine equivalent (ME) dose was used to estimate changes in opioid dose. ODR was defined as any reduction of baseline opioid dose. A chi-square was performed to evaluate associations. Results: A total of 133 patients were identified between Jan 2017- May 2017. (M/F) 65/68; median age of 53 (range 20 - 84). Nineteen percent (25/133) had a cancer diagnosis. Pain score improved in 80 % of patients with cancer and in 75% (64/89) of non-cancer patients (x2 0.24 p = 0.62). ODR was achieved in 41% (54/133) of all patients on MC. Of these, 63% (34/54) had a 25% ODR and 37% (20/54) had 26% or more ODR (x2 12.8 p = 0.002). In cancer patients, a 25% ODR was achieved in 73% (x2 0.51 p = 0.771). All patients (15/15) using MC and high dose opioid (morphine equivalent ≥ 50 mg/day) had some ODR. Co-adjuvant NSAIDs with MC improved pain score in 67% of all cases vs 33% among non-NSAID cohort (x2 10.7 p = 0.001). ODR was achieved in 32% of patients with active depression vs 68% of patients without (x2 0.044 p = 0.83). Conclusions: In this rural cohort, MC use led to ODR in 41% of all patients. Depression was a negative predictor of ODR. NSAID use facilitated ODR. It will be important to assess MC toxicity before considering this intervention. This study did not include toxicity data due to the retrospective nature of this study and its inherent limitations. Prospective data are needed to confirm these findings.

South Gloucestershire Opioid Pain Review Pilot study: a mixed methods evaluation

BackgroundPrimary care can be an appropriate setting to address opioid analgesic dependence among patients with chronic non-cancer pain. This study evaluated the South Gloucestershire Opioid Pain Review Pilot which aims to help patients understand their relationship with opioids and to develop alternative, non-drug-based, pain management strategies. MethodsPatients from two general practices in South Gloucestershire, UK, were invited to take part in the pilot (September 2016-October 2018). They were given an individually tailored intervention, based on the shared care model, and social prescribing including pain management, and referred to external services. Experiences of the pilot were explored with semi-structured interviews. Routine quantitative data were collected on demographics; opioid use and dose; wellbeing and quality of life; and pain intensity, pain relief, and interference with life. A mixed-methods approach supported a comprehensive evaluation of the pilot. Interviews were analysed thematically. Quantitative and qualitative data were integrated using “following a thread” and triangulation. The study was given ethics approval by West Midlands – Coventry and Warwickshire Research Ethics Committee, and participants gave written or verbal informed consent. FindingsOf 59 invited patients, 34 (58%) enrolled into the service and contributed quantitative data. 18 of the 34 service-users and seven service providers were interviewed. On average, service-users showed improvement in all outcomes except pain relief from medication. Baseline opioid dose (median 90, IQR 60-240)]reduced at follow-up (median 90 mg, IQR 60–240 vs 72 mg, 30–160, Wilcoxon signed-rank test p=0·00013). Service-users received the pilot positively, valuing their relationship with the project worker, time to discuss pain management, and individually tailored support. Individual needs and readiness to change shaped responses to the intervention. Perceived benefits related to understanding of pain, wellbeing, and quality of life; pain management strategies; and medication changes. InterpretationThis novel pilot has shown promise. We recommend that future initiatives within primary care are individually tailored. Project worker and service-user relationships are important. A randomised controlled trial is needed to test the impact of this care-pathway. FundingThis research was funded by the National Institute for Health Research (NIHR) Collaboration for Leadership in Applied Health Research and Care (CLAHRC) West. The pain review pilot was funded by the Public Health and Wellbeing Division at South Gloucestershire Council.

Use of parecoxib by continuous subcutaneous infusion for cancer pain in a hospice population

ObjectivesTo characterise the use of the parenteral non-steroidal anti-inflammatory drug parecoxib when given by continuous subcutaneous infusion (CSCI) in a hospice population. Clinical experience suggests parecoxib CSCI may be of...

Population pharmacokinetics of naloxegol in a population of 1247 healthy subjects and patients.

Naloxegol, a polyethylene glycol conjugated derivative of the opioid antagonist naloxone, is in clinical development for treatment of opioid-induced constipation (OIC). The aim of the study was to develop a population pharmacokinetic model describing the concentration vs. time profile of orally administered naloxegol, and determine the impact of pre-specified demographic and clinical factors and concomitant medication on population estimates of apparent clearance (CL/F) and apparent central compartment volume of distribution (Vc /F). Analysis included 12,844 naloxegol plasma concentrations obtained from 1247 healthy subjects, patients with non-OIC and patients with OIC in 14 phase 1, 2b and 3 clinical studies. Pharmacokinetic analysis used the non-linear mixed effects modelling program. Goodness of fit plots and posterior predictive checks were conducted to confirm concordance with observed data. The final model was a two compartment disposition model with dual absorptions, comprising one first order absorption (ka1 4.56 h(-1) ) and one more complex absorption with a transit compartment (ktr 2.78 h(-1) ). Mean (SE) parameter estimates for CL/F and Vc /F, the parameters assessed for covariate effects, were 115 (3.41) l h(-1) and 160 (27.4) l, respectively. Inter-individual variability was 48% and 51%, respectively. Phase of study, gender, race, concomitant strong or moderate CYP3A4 inhibitors, strong CYP3A4 inducers, P-glycoprotein inhibitors or inducers, naloxegol formulation, baseline creatinine clearance and baseline opioid dose had a significant effect on at least one pharmacokinetic parameter. Simulations indicated concomitant strong CYP3A4 inhibitors or inducers had relevant effects on naloxegol exposure. Administration of strong CYP3A4 inhibitors or inducers had a clinically relevant influence on naloxegol pharmacokinetics.

Physical Functioning and Opioid use in Patients with Neuropathic Pain.

To evaluate the association between opioid dosage and ongoing therapy with physical function and disability in patients with neuropathic pain (NeP). Secondary analysis of a prospective cohort. Multicenter clinical NeP registry. Seven hundred eighty-nine patients treated for various NeP diagnoses. The following measures were included: dependent variables. 12-month self-reported physical function (pain disability index [PDI] and medical outcomes study short form-12 physical function [PCSS-12]); independent variables: baseline opioid dose (none, ≤200 mg and >200 mg of morphine equivalent), ongoing opioid use; potential confounding variables: age, sex, baseline pain intensity, and psychological distress (profile of mood states). Analysis of covariance models was created to examine the relationship between opioid therapy and both physical functioning outcomes with adjustment for confounding. Complete data was available for 535 patients (68%). Compared with the lower and high dose opioid groups, NeP patients not taking opioids had statistically lower disability and higher physical functioning scores, after adjusting for disease severity. Compared with patients prescribed opioid therapy on an ongoing basis, NeP patients who were not prescribed had statistically lower disability and higher physical functioning scores, after adjusting for disease severity. Improvements in disability and physical functioning scores from baseline and 12-months in all groups were modest and may not be clinically significant. Physical functioning and disability did not improve in patients with NeP who were prescribed opioids compared with those who are not prescribed, even after adjusting for disease severity.

Sublingual buprenorphine/naloxone for chronic pain in at-risk patients: Development and pilot test of a clinical protocol

Objective: Sublingual buprenorphine/naloxone (Bup/Nx) is approved for addiction treatment and may be useful for pain management, particularly in opioid-treated patients with pain with nonadherence behaviors. The transition of opioid-treated patients with pain to buprenorphine carries the risk of precipitated withdrawal and increased pain. This study convened pain and addiction specialists to develop and pilot a clinical protocol for safe transitioning to Bup/Nx. Design: The protocol was revised three times based on outside expert review and pilot study observations. The pilot was conducted with a prospective cohort of 12 patients with moderate to severe chronic pain, who were receiving long-term opioid therapy with any full µ-agonist drug, and had exhibited one or more aberrant drugrelated behaviors. Patients were followed up for 3-6 months with the expectation that they would experience few adverse events (AEs) and report lower pain severity. Results: The three patients on the highest baseline opioid dose (equivalent to 303-450 mg of oral morphine) and the three on the lowest doses (=20 mg) had early AEs when switched to Bup/Nx and did not complete the trial. Of the remaining six, one withdrew due to AEs; one responded well, then withdrew; and four completed a 3-month trial. A mixed-effects model controlling for dropouts found that average and worst pain significantly decreased after the switch to Bup/Nx (both p &lt; 0.01). Conclusion: Based on this experience, the protocol recommends Bup/Nx for pain only when baseline opioid doses are within bounds that reduce AEs at transition and incorporates dose flexibility to further reduce risks. This protocol warrants further testing. Keywords: buprenorphine, chronic pain, treatment guidelines, opioid therapy, withdrawal DOI:10.5055/jom.2012.0137

Sublingual buprenorphine/naloxone for chronic pain in at-risk patients: Development and pilot test of a clinical protocol

Sublingual buprenorphine/naloxone (Bup/Nx) is approved for addiction treatment and may be useful for pain management, particularly in opioid-treated patients with pain with nonadherence behaviors. The transition of opioid-treated patients with pain to buprenorphine carries the risk of precipitated withdrawal and increased pain. This study convened pain and addiction specialists to develop and pilot a clinical protocol for safe transitioning to Bup/Nx. The protocol was revised three times based on outside expert review and pilot study observations. The pilot was conducted with a prospective cohort of 12 patients with moderate to severe chronic pain, who were receiving long-term opioid therapy with any full m-agonist drug, and had exhibited one or more aberrant drug-related behaviors. Patients were followed up for 3-6 months with the expectation that they would experience few adverse events (AEs) and report lower pain severity. The three patients on the highest baseline opioid dose (equivalent to 303-450 mg of oral morphine) and the three on the lowest doses (≤20 mg) had early AEs when switched to Bup/Nx and did not complete the trial. Of the remaining six, one withdrew due to AEs; one responded well, then withdrew; and four completed a 3-month trial. A mixed-effects model controlling for dropouts found that average and worst pain significantly decreased after the switch to Bup/Nx (both p < 0.01). Based on this experience, the protocol recommends Bup/Nx for pain only when baseline opioid doses are within bounds that reduce AEs at transition and incorporates dose flexibility to further reduce risks. This protocol warrants further testing.

Parenteral Ketamine as an Analgesic Adjuvant for Severe Pain: Development and Retrospective Audit of a Protocol for a Palliative Care Unit

Ketamine is an effective analgesic agent for treating a variety of neuropathic and cancer pain syndromes. Recent studies indicate that ketamine may have a particular role in the management of patients with neuropathic and/or pain syndromes that are poorly responsive to opioids. To develop, implement, and subsequently assess a protocol designed to maximize the analgesic effect of ketamine while minimizing its side effects. A retrospective chart audit of 16 patients who had used the ketamine protocol over a 12-month period. Criteria for assessing the effectiveness of ketamine were defined. Ketamine was an effective, well-tolerated analgesic adjuvant for 11 of 16 patients with previously uncontrolled pain. Pain scores were reduced by at least 4 of 10 in 15 of the 16 patients. Median opioid dose reduction on starting ketamine was 25%. The audit confirmed the safety and effectiveness of ketamine as an analgesic adjuvant for patients with severe pain. Baseline opioid dose reduction and prophylactic use of haloperidol or benzodiazepine were effective in minimizing psychotomimetic side effects.

Perioperative management of acute pain in the opioid-dependent patient.

human rights. 2– 4 Noticeable shifts in attitude have occurred in recent years regarding the use of opioids for the treatment of benign and malignancy-related pain. Primary care physicians and pain specialists prescribe opioids to a greater number of patients and in doses appropriate to needs. 3–7 A variety of opioid analgesics and delivery systems have been introduced that have increased patient satisfaction, physician acceptance, and overall use. Concomitant with improvements in pain relief and quality of life, an increasing number of patients are affected by issues related to opioid tolerance and physical dependence. There have been only a small number of published reviews that address the treatment of acute pain in patients with substance abuse disorders, 3–5 and fewer have focused specifically on perioperative pain management in opioid-dependent patients. 6,7 This review outlines factors responsible for opioid tolerance, physical dependence, and addiction and provides perioperative analgesic dosing guidelines for this specialized subset of patients. Many patients who present for surgery and anesthesia may be opioid dependent or at least moderately tolerant to the therapeutic effects of opioid analgesics. 5–7 Causal factors underlying dependency include substance use disorder and, more commonly, legitimate use of opioid analgesics for treatment of chronic benign pain or malignancy-associated pain. Perioperative management of opioid-dependent patients poses a special challenge to primary caregivers, anesthesiologists, and pain specialists alike. This problem emanates from the often-conflicting needs to balance the rights of the patient on one hand and concerns of safety, diversion, and abuse on the

Opioid dose titration for severe cancer pain: a systematic evidence-based review.

Dosing strategies to achieve rapid analgesia in patients with severe or crescendo cancer pain are important. A systematic review of research trials for treatment of severe or crescendo cancer pain was conducted; nine studies were identified. Eight trials were prospective; two were randomized between different dosing strategies. Dosing frequency predicted onset to analgesia regardless of baseline opioid dose. None of the trials were associated with evidence of respiratory depression. The studies all suffered significant methodological problems limiting broad conclusions. Until better data exist, opioid dose titration for severe/crescendo pain will be guided by expert opinion and experience.