Methadone In Patients Research Articles

Comparison of low-dose ketamine to methadone for postoperative pain in opioid addicts: a randomized clinical trial.

Postoperative pain can lead to several complications. The effectiveness of different opioids in relieving pain after surgery has been widely studied. However, managing pain in patients with opioid addiction is still challenging. This study aimed to examine the impact of ketamine and methadone on postoperative pain in patients with addiction. This was a non-inferiority randomized clinical trial. All included patients were monitored for morphine use, pain scores, and vital signs every 3 h. The intervention group received 0.5 mg/kg ketamine administered intravenously every 6 h. The control group received 5 mg of methadone intramuscularly every 8 h. The patient received intravenous morphine if their visual analog scale was above 3. All side effects in each group were recorded. Two hundred and twenty patients were included in this study. There were 127 men (57.7%) with an average age of 57.1 ± 19.5 and 93 women (42.3%) with an average age of 57.1 ± 21.0. There were no significant differences in demographic characteristics between the groups. There was no significant difference in the dose or frequency of morphine administration between groups. There was no significant difference between the groups in pain scores and vital signs at different time points. Drug side effects, including delirium and gastrointestinal symptoms, did not differ significantly between the methadone and ketamine groups. Our clinical data support the hypothesis that ketamine is not inferior to methadone in patients with addiction. Future randomize clinical trials are needed to confirm these observations.

Effect of Intravenous Vitamin C on Serum Level and Urinary Excretion of Methadone in Patients with Methadone Poisoning: A Randomized Single-Blind Clinical Trial

Background: Methadone poisoning intentionally or accidentally leads to a high rate of treatment burden and cost and deaths. The evaluation of the factors affecting the severity of poisoning can reduce recovery time, costs, and potential risks. Objectives: This study aimed to investigate the effect of intravenous vitamin C (ascorbic acid) administration on serum level and urinary excretion of methadone. Patients and Methods: In this single-blind study, 54 patients who were diagnosed with methadone poisoning were divided into three groups. The two intervention groups received different doses of vitamin C, including 12 and 24 g, and the control group received normal saline. The serum methadone level and urine pH were measured at the time of arrival and 24 hours after admission. The data were analyzed using repeated measure analysis of variance (ANOVA) in STATA version 12. Results: In this study, 18 patients were placed in each group. The three groups were not significantly different in basic variables, such as age, gender, and methadone dosage. Between and within-group comparison showed a significant decrease in the serum methadone levels over time after adjusting age, gender and methadone dosage (P < 0.05). Post-hoc analyses revealed a significant difference in methadone reduction between 12 g of vitamin C and control groups (P = 0.04), and there was no significant difference between the control and 24 g of vitamin C groups (P > 0.05). However, between and within-group comparisons showed no significant difference between the three groups in terms of urine pH (P > 0.05). In addition, interaction was observed between intervention and time on serum methadone levels (P < 0.001) and urine pH (P = 0.04) variables. Conclusions: Consuming 12 g of vitamin C further reduced the serum methadone level in patients with methadone poisoning. There was no effect on methadone urinary excretion in patients.

Clinical effectiveness and safety of intraoperative methadone in patients undergoing laparoscopic hysterectomy: a randomised, blinded clinical trial

BackgroundLaparoscopic hysterectomy is often carried out as day-stay surgery. Minimising postoperative pain is therefore of utmost importance to ensure timely discharge from hospital. Methadone has several desirable pharmacological features, including a long elimination half-life. Therefore, a single intraoperative dose could provide long-lasting pain relief. MethodsPatients scheduled to undergo laparoscopic hysterectomy were randomly allocated to receive methadone (0.2 mg kg−1) or morphine (0.2 mg kg−1) intraoperatively, 60 min before tracheal extubation. Primary outcomes were opioid consumption (oral morphine equivalents in milligrams) at 6 and 24 h. Secondary outcomes included pain intensity at rest and during coughing, patient satisfaction, postoperative nausea and vomiting, and adverse events up to 72 h after completion of surgery. ResultsThe postoperative median opioid consumption was reduced in the methadone group compared with the morphine group at 6 h (35.5 [0–61] mg vs 48 [31–74.5] mg; P=0.01) and 24 h (42 [10–67] mg vs 54.5 [31–83] mg; P=0.03). On arrival at the PACU, pain at rest was significantly lower in patients receiving methadone (numeric rating scale: 3 [2–5] vs 5 [3–6]), whereas pain scores at rest and coughing were not significantly different throughout the rest of the observation period. No differences in other secondary outcomes were found. ConclusionsIn this randomised, blinded, controlled trial, opioid consumption was reduced during the first 24 postoperative hours in patients receiving methadone without causing an increase in adverse events. The difference observed might be considered as small and of limited clinical relevance. Clinical trial registrationNCT03908060; EudraCT no. 2018-004351-20.

One-year survey of methadone-induced cardiac complications.

Methadone is one of the most useful opioids that can be used to achieve many therapeutic goals, and also it may be abused as an illicit drug. Methadone can cause different gastrointestinal, neurological, and cardiac complications. This study was performed to obtain a better understanding of the cardiac side effects of methadone in patients with methadone poisoning. This cross-sectional study was performed on 210 samples in Sina Hospital of Hamadan in a one-year period from March 2019 to March 2020. After assessing patients who had methadone poisoning and completing their demographic information and evaluation of changes in patients' EKGs, the data was collected and analyzed by SPSS 16 software. Out of 210 participants, 178 (84.8%) were males and the rest were females. The average age of the studied patients was 39.56 years old. The study found that 6.1% of methadone-poisoned patients were illiterate. It was found in this study that the most common cardiac complications of methadone intoxication were sinus tachycardia (20%), QT interval prolongation (6.64%), and sinus bradycardia (4.3%), respectively; nevertheless, 66.2% of patients did not have any EKG abnormalities. According to the findings, it is necessary to have continuous cardiac monitoring for patients with methadone intoxication and by transferring such findings to medical centers, steps can be taken to use methadone more intelligently.

No rise in methadone OD deaths with new take‐home rules

In another step toward increasing take‐home methadone for patients in opioid treatment programs (OTPs), the National Institute on Drug Abuse (NIDA) has found that the percentage of methadone‐involved overdose deaths relative to all drug overdose deaths declined from January 2019 to August 2021. The study showing this data was published last week in JAMA Psychiatry and was a collaborative effort of NIDA and the Centers for Disease Control and Prevention (CDC).

Expert Panel Consensus on Management of Advanced Cancer-related Pain in Individuals with Opioid Use Disorder

Develop consensus on the appropriateness of cancer pain management strategies in individuals with co-occurring advanced cancer and OUD. Three-round modified-Delphi process with two cases: patient with advanced cancer, pain and OUD treated with buprenorphine/naloxone or methadone. Participants rated management strategies in Round 1, discussed results in Round 2, and provided final responses in Round 3 in an online modified-Delphi panel. Participants included experts in palliative care, addiction, or both, recruited by email from palliative care and addiction-focused professional groups, lists from prior studies, and snowball sampling. Of 120 experts, the majority of whom held MD or DO degrees (115, 96%), 70% participated in all rounds. For a patient with OUD on buprenorphine/naloxone, it was deemed appropriate to continue buprenorphine/naloxone with three-times-per-day dosing. Continuing buprenorphine/naloxone and adding a full-agonist opioid was deemed appropriate for patients with a prognosis of weeks-months, and of uncertain appropriateness for a prognosis of months-years. For a patient with OUD on methadone dispensed at a methadone clinic, it was deemed appropriate to take over prescribing and dose 2-3x/day. Continuing methadone daily while adding another full-agonist opioid was deemed appropriate for patients with a prognosis of weeks-months and of uncertain appropriateness for a prognosis of months-years. This qualitative study, urgently needed, consensus-based guidance for clinicians, and highlighted critical research and policy gaps needed to facilitate implementation. Findings underscore the importance of additional research to investigate optimal dosing of buprenorphine/naloxone and methadone in patients with advanced cancer pain and OUD, and factors influencing the preferred choice. Grant support from the Cambia Health Foundation.

Clarification

In the Feb. 14 issue, the article on the proposed Centers for Disease Control and Prevention guidelines for opioid prescribing for pain (“CDC proposes new guideline for opioid pain prescribing,” ADAW, Feb. 14; https://onlinelibrary.wiley.com/doi/10.1002/adaw.33347) should have stated that buprenorphine and methadone for patients who develop opioid use disorder while being treated for pain are recommended.

Buprenorphine/naloxone versus methadone opioid rotation in patients with prescription opioid use disorder and chronic pain: study protocol for a randomized controlled trial

BackgroundOpioids are effective in pain-management, but long-term opioid users can develop prescription opioid use disorder (OUD). One treatment strategy in patients with OUD is rotating from a short-acting opioid to a long-acting opioid (buprenorphine/naloxone (BuNa) or methadone). Both BuNa and methadone have been shown to be effective strategies in patients with OUD reducing opioid misuse, however data on head-to-head comparison in patients with chronic non-malignant pain and prescription OUD are limited.MethodsThis two-armed open-label, randomized controlled trial aims to compare effectiveness between BuNa and methadone in patients with chronic non-malignant with prescription OUD (n = 100). Participants receive inpatient rotation to either BuNa or methadone with a flexible dosing regimen. The primary outcome is opioid misuse 2 months after rotation. Secondary outcomes include treatment compliance, side effects, analgesia, opioid craving, quality of life, mood symptoms, cognitive and physical functioning over 2- and 6 months follow-up. Linear mixed model analysis will be used to evaluate change in outcome parameters over time between the treatment arms.DiscussionThis is one of the first studies comparing buprenorphine/naloxone and methadone for treating prescription OUD in a broad patient group with chronic non-malignant pain. Results may guide future treatment for patients with chronic pain and prescription OUD.Trial registrationhttps://www.trialregister.nl/, NL9781

264 Racial Inequities in Emergency Department Administration of Buprenorphine and Methadone Among Patients With Opioid Use Disorder

The COVID-19 pandemic has exacerbated longstanding inequities in opioid use disorder (OUD) that reflect multiple facets of structural racism. In Massachusetts, opioid overdose deaths in 2020 rose by nearly 70% in Black men compared to just 5% overall. Emergency department (ED) visits in people with OUD may represent key touchpoints for overdose prevention. Although racial inequities in buprenorphine and methadone maintenance initiation, dosing, and retention have been well documented, less is known about the administration of medications for opioid use disorder (MOUD, buprenorphine and methadone), in the ED. ED leadership initiated an internal review to explore racial equity in multiple clinical quality metrics, including frequency of MOUD administration in patients with OUD. Retrospective data were analyzed for quality improvement (QI) purposes. Patients presenting to the ED with OUD July 29, 2020-March 12, 2021 were identified via ICD-10 codes. Patient demographics and MOUD administration were explored using descriptive statistics; c2 tests compared the frequency of MOUD administration by race. An intensive QI intervention to improve MOUD utilization will be delivered to all ED prescribers in June 2021. The intervention includes content on racial inequities in OUD treatment and factors that drive them, including provider bias, reasons for mistrust of the medical system among patients of color, and structural barriers to OUD treatment and retention. Through educational sessions for providers, transparency of data of current MOUD trends in the ED, and structured on-shift reminders by ED pharmacists, we plan to improve provider-patient communication and MOUD utilization in the ED. The QI initiative will be followed by a three-month monitoring period (July-September 2021) to evaluate for changes in MOUD administration. A total of 998 unique patients with OUD were seen for 1452 ED visits. Documented race was 56.7% White, 21.5% Black, 13.5% Hispanic, 1.7% Other, and 6.6% unknown. MOUD were administered during 945/1452 visits (65.1%). The likelihood of administration varied significantly by race: 80.3% of White patients received MOUD compared to 35.9% of Black patients, and 59.9% of Hispanic patients (p<0.001, Table 1). Significant differences in treatment were also observed when comparing white and Black patients (p<0.001) and white and Hispanic patients (p<0.001) directly. Renewed attention to ensuring racial equity in clinical practice prompted an exploration of ED data at our institution, including equitable administration of buprenorphine and methadone in patients with OUD. This QI analysis identified a racial inequity, prompting the development of a QI initiative to improve overall utilization of MOUD, with a specific focus on mitigating observed racial inequities. Data analysis from the post-QI intervention period will be completed prior to presentation at ACEP.

Exposure-Based Methadone and Lorazepam Weaning Protocol Reduces Wean Length in Children.

Determine if a standardized methadone and lorazepam weaning protocol that is based on dose and duration of exposure can reduce the length of opioid and benzodiazepine weaning and shorten hospital stay. Retrospective cohort study performed in a 24-bed medical/surgical PICU. A total of 177 patients on opioid and/or benzodiazepine infusions for >3 days were included; 75 patients pre protocol (June 2012- June 2013) were compared with 102 patients post implementation of a standardized weaning protocol of methadone and lorazepam (March 2014-March 2015). The recommended wean was based on duration of infusions of >3 days up to 5 days (no wean), 5 to 13 days (short wean), and ≥14 days (long wean). Median number of days on methadone for patients on opioid infusions for 5 to 13 days was reduced from 8.5 to 5.7 days (p = 0.001; n = 45 [pre], n = 68 [post]) and for patients on opioid infusions for ≥14 days, from 29.7 to 11.5 days (p = 0.003; n = 9 [pre], n = 9 [post]) after protocol implementation. The median number of days on lorazepam for patients on benzodiazepine infusions for 5 to 13 days was reduced from 8.1 to 5.2 days (p = 0.020; n = 43 [pre], n = 55 [post]) and for patients on benzodiazepine infusions for ≥14 days, from 27.4 to 9.3 days (p = 0.011; n = 9 [pre], n = 8 [post]). There was no difference in methadone or lorazepam wean length for patients on 3 to 5 days of infusions. There was no difference in adverse events or hospital length of stay. A methadone and lorazepam weaning protocol based on patient's exposure to opioids and benzodiazepines (dose and duration) reduces weaning length.

The use of methadone in adult patients with cancer pain at a governmental cancer center in India

Background:Management of cancer-related pain relies on the access to opioids. When regular opioids as morphine are not tolerated or are insufficient, adjuvant opioids as methadone are an affordable and effective analgesic.Aim:The aim of the project was to describe the pattern of use and clinical experiences of methadone in patients with cancer-related pain at a low-resource hospital in Hyderabad, one of few Indian cancer centers with permission to prescribe methadone.Methods:Medical records of all patients who had been prescribed methadone, September 9, 2017 and November 19, 2019 were studied retrospectively. Data on analgesic treatment and opioid side effects were analyzed.Results:A total of 93 adult cancer patients were included in the study. A majority of patients (79%) were prescribed opioid analgesic, mainly morphine, before methadone introduction. The initial daily dose of methadone ranged between 5 and 22.5 years and in the vast majority of the patients 5 mg, divided in two daily administrations. A good analgesic effect, with decreased pain, was reported in 60% of the patients. No severe side effects were reported.Conclusions:In this study, methadone as a primary opioid was used with a good analgesic effect for cancer pain in a low-resource setting. Indication for methadone was mainly uncontrolled pain with a regular opioid treatment. No severe adverse effects were reported. Further research and prospective studies are needed on methadone treatment in low-resource settings to establish the robust guidelines to support prescribing physicians.

Impact of Pharmacological Treatments for Opioid Use Disorder on Mortality

The use of pharmacological treatments for opioid use disorders, including methadone, buprenorphine and naltrexone has been associated with a reduction in mortality compared with illicit opioid use. However, these treatments can also contribute significantly to the risk of death. The opioid agonists methadone and buprenorphine achieve clinical efficacy in patients with an opioid use disorder through suppressing craving and diminishing the effectiveness of illicit opioid doses, while the antagonist naltrexone blocks the action of opioids. Pharmacological differences between opioid pharmacotherapies then create different temporal patterns of protection and mortality risk, different risks of relapse to illicit opioid use, and variations in direct and indirect toxicity, which are revealed in clinical and epidemiological studies. Induction onto methadone and the cessation of oral naltrexone treatment are associated with an elevated risk of opioid poisoning, which is not apparent in patients treated with buprenorphine or sustained-release naltrexone. Beyond drug-related mortality, these pharmacotherapies can impact a participant's risk of death. Buprenorphine may also have some advantages over methadone in patients with depressive disorders or cardiovascular abnormalities. Naltrexone, which is also commonly prescribed to manage problem alcohol use, may reduce deaths in chronic co-alcohol users. Understanding these pharmacologically driven patterns then guides the judicious choice of drug and dosing schedule and the proactive risk management that is crucial to minimising the risk of death in treatment.

Clinical Effectiveness and Safety of Intraoperative Methadone in Patients Undergoing Laparoscopic Hysterectomy

Clinical Effectiveness and Safety of Intraoperative Methadone in Patients Undergoing Laparoscopic Hysterectomy

Low dose intramuscular methadone for acute mild to moderate opioid withdrawal syndrome

Study objectiveTo assess the efficacy of 10mg intramuscular (IM) methadone in patients with opioid withdrawal syndrome (OWS). MethodsThis was a prospective observational, convenience sample of patients presenting to the ED with mild to moderate OWS. Evaluations included the Clinical Opiate Withdrawal Scale (COWS), Withdrawal Symptoms Scale (WSS), Altered Mental Status Scale (AMSS) and a physician assessment of the patient's WSS (MDWSS). After enrollment, 10mg of IM methadone was administered and patients were reassessed at 30min post-methadone administration. The primary outcome was the change in COWS at baseline and after methadone administration. Secondary outcomes were the differences between AMSS, and WSS post-methadone. ResultsFifty-seven patients had COWS scores recorded at baseline and 30min. Fifty-six had mild to moderate OWS. The COWS improved a mean of 7.6 after methadone administration (P<0.001). The improvement was greater among patients presenting with moderate versus mild withdrawal (mean decrease=−9.1 vs. −5.5, P<0.001). Patients were more likely to self-score themselves as having withdrawal compared to MDs (93.6% vs. 76.6% respectively, P=0.027). Of the 62 patients with baseline and follow-up WSS by self-assessments, 69% improved post-methadone administration. In addition, the AMSS score remained the same or improved among 86% of cases with measurements at baseline and follow-up. ConclusionA single IM dose of 10mg methadone in the ED reduces the severity of acute mild to moderate OWS by 30min. Larger prospective, randomized controlled, and blinded studies would be needed to confirm these results.

Comparison of the solid phase and liquid-liquid extraction methods for methadone determination in human serum and whole blood samples using gas chromatography/mass spectrometry

The aim of this study was to determine the optimal biological sample and the optimal extraction technique for monitoring methadone concentrations in biological samples. We analysed methadone in serum and whole blood samples using gas chromatography/mass spectrometry (GC/MS). Before analysis, we compared five solid-phase extraction (SPE) and two liquid-liquid extraction (LLE) methods and determined that SPE with Supelco LC-18 in serum yielded the best extraction efficiency. The limit of detection was 10 ng mL-1 and the limit of quantification 25 ng mL-1. Correlation coefficient was over 0.999 for the methadone calibration curve in linear range from 50 to 2000 ng mL-1. Intra and inter-day accuracy and precision of the method was satisfactory. The method was successfully applied for determining serum methadone in patients on maintenance therapy.

Can Saliva and Plasma Methadone Concentrations Be Used for Enantioselective Pharmacokinetic and Pharmacodynamic Studies in Patients With Advanced Cancer?

PurposeMethadone is a potent analgesic used to treat refractory cancer pain. It is administered as a racemic mixture, with the l-enantiomer being primarily a μ-receptor agonist, whereas the d-enantiomer is an N-methyl-d-aspartate antagonist and inhibits serotonin and norepinephrine reuptake. Dose requirements vary greatly among patients to achieve optimal pain control and to avoid the risk of adverse effects. The relationship between plasma and saliva methadone enantiomer concentrations was investigated to determine if saliva could be a substitute for plasma in pharmacodynamic and pharmacokinetic studies for clinical monitoring and dose optimization of methadone in patients with advanced cancer. MethodsPatients with advanced cancer who were prescribed varying doses of oral methadone for pain management were recruited to obtain paired plasma and saliva samples. Pain scores were recorded at the time of sampling. The total and unbound plasma and saliva concentrations of the l- and d-enantiomers of methadone were quantified by using an HPLC-MS/MS method. The relationship between plasma (total and unbound) and saliva concentrations were compared. The saliva-to-plasma concentration ratio was compared versus the dose administered and the time after dosing for both enantiomers. The association of methadone concentrations with reported pain scores was compared by using a Mann-Whitney U test for significance. FindingsFifty patients receiving a mean dose of 11mg/d of methadone provided 151 paired plasma and saliva samples. The median age of the population was 61 years with an interquartile range of 53-71 years with total body weight ranging from 59-88 kg. Median (interquartile) total plasma concentrations for l- and d-methadone were 50.78 ng/mL (30.6–113.0 ng/mL) and 62.0 ng/mL (28.7–116.0 ng/mL), respectively. Median (interquartile range) saliva concentrations for l- and d-methadone were 81.5 ng/mL (28.0–203.2 ng/mL) and 44.2 (16.2–149.7 ng/mL). No relationship could be established between plasma and saliva concentrations for l- and d-methadone (r2 = 0.35 and 0.25). The saliva-to-plasma concentration analyzed with the methadone dose showed higher saliva concentrations at lower doses. Dose-normalized saliva concentrations followed a similar pattern over time compared with plasma concentrations. No correlation was found between l-methadone plasma, d-methadone plasma, l-methadone saliva, d-methadone saliva concentrations, and pain score. ImplicationsSaliva concentration was not a better predictor of pain control than plasma concentration for dose optimization and monitoring studies of methadone in patients with cancer. Although the saliva-to-plasma ratio of the concentration of methadone enantiomers was stable across the dosing range, due to the variability in individual saliva-to-plasma ratios, saliva sampling may not be a valid substitute in pharmacokinetic studies of methadone in cancer.

Use of Methadone as First Line Strong Opioid for Moderate-Severe Pain

The present study evaluates the use of methadone in patients with advanced cancer and moderately-severe pain under palliative care at home over a period of 5 years, from 1996 to 2000. We calculated the index for methadone dosage increase (as a percentage and value in milligrams). Of the 1,079 patients cared for, 247 (22.89%) received methadone treatment: 126 from the very beginning, average dose of 15 mg / day (5- 50), and in 121 patients treatment with methadone was initiated at a later moment during the period they were cared for (5- 40). The median period of time of methadone administration was 27 days (1-416), the median dose of methadone at the moment of treatment discontinuation being 20 mg (5-60). The main reason for methadone treatment discontinuation was impossibility of oral administration (49.8% in terminal stages, 7.3% presenting nausea, vomiting), and 62.3% showed no side effects. Dosage increase index was 0.33 mg, 2.33% respectively. Methadone has been used mainly as a potent first line opioid, and has been shown to be effective and safe.

Clinical Effectiveness and Safety of Intraoperative Methadone in Patients Undergoing Posterior Spinal Fusion Surgery: A Randomized, Double-blinded, Controlled Trial.

Patients undergoing spinal fusion surgery often experience severe pain during the first three postoperative days. The aim of this parallel-group randomized trial was to assess the effect of the long-duration opioid methadone on postoperative analgesic requirements, pain scores, and patient satisfaction after complex spine surgery. One hundred twenty patients were randomized to receive either methadone 0.2 mg/kg at the start of surgery or hydromorphone 2 mg at surgical closure. Anesthetic care was standardized, and clinicians were blinded to group assignment. The primary outcome was intravenous hydromorphone consumption on postoperative day 1. Pain scores and satisfaction with pain management were measured at postanesthesia care unit admission, 1 and 2 h postadmission, and on the mornings and afternoons of postoperative days 1 to 3. One hundred fifteen patients were included in the analysis. Median hydromorphone use was reduced in the methadone group not only on postoperative day 1 (4.56 vs. 9.90 mg) but also on postoperative days 2 (0.60 vs. 3.15 mg) and 3 (0 vs. 0.4 mg; all P< 0.001). Pain scores at rest, with movement, and with coughing were less in the methadone group at 21 of 27 assessments (all P = 0.001 to < 0.0001). Overall satisfaction with pain management was higher in the methadone group than in the hydromorphone group until the morning of postoperative day 3 (all P = 0.001 to < 0.0001). Intraoperative methadone administration reduced postoperative opioid requirements, decreased pain scores, and improved patient satisfaction with pain management.

Methadone Inpatient and Discharge Prescribing Patterns for Pain at an Academic Health System.

Methadone is effective for the treatment of chronic pain, but its unique pharmacology requires additional considerations with dosing and monitoring. The study objective was to evaluate methadone prescribing for pain and subsequent monitoring. This retrospective chart review at a single center reviewed patients who received methadone over a two-year period. Of the 100 patients, most were noncancer cases (60%) with unspecified pain (50%). The majority of methadone treatments were initiated by medicine service (37%), followed by burn service (27%), and trauma (10%). Forty-two percent of the patients were being followed by the palliative care team, primarily for the medicine patients (80%). Patients on the burn service had significantly higher oral morphine equivalent (χ2 = 10.6, p = 0.01) and longest length of stay (χ2 = 37.9, p = 0.0001). Patients on medicine service were significantly more likely to have an outpatient discharge plan for methadone starts in the hospital (odds ratio = 3.7, confidence interval: 1.4, 9.7). Only 45% of patients had an electrocardiogram (EKG) checked seven days before methadone start and 37% of those have a measured corrected QT (QTc) of greater than 450 milliseconds. Electrolytes (potassium and magnesium) were not consistently checked and, of those that were evaluated, 15-20% were abnormal. There was an average of 2.6 severe or major drug interactions per patient related to methadone, with the most common being related to concomitant sedatives and other medications that prolonged the QTc. Prescribing guidelines for methadone would provide a consistent approach for all practitioners involved in using methadone safely and effectively for chronic pain.

A randomized controlled trial (RCT) of 2 dose ratios for conversion from parenteral to oral methadone in patients with cancer pain.

206 Background: Methadone (M) is frequently used for severe cancer pain using the parenteral and oral route. The most commonly used dose ratio (DR) parenteral: oral is 1:2. However, methadone is highly bioavailable and a lower ratio might result in similar analgesia with less toxicity. The main objective of this RCT is to compare success and side effects with 2 ratios of parenteral to oral M: 1:2 vs 1:1.2 in hospitalized patients with cancer pain. Methods: Inpatients with cancer pain well controlled with parenteral M requiring rotation to the oral route. Double blind RCT. Outcomes included pain intensity (BPI), opioid toxicity (CTCAE), and M dose. Success was defined as good pain control with no toxicity at 72hs. Results: 39/44 randomized patients were evaluable (89%): 21 in DR 1:2 and 18 in DR 1:1.2. 71% male, median age 65. No significant difference between DR1:2 and DR1:1.2 in frequency of neuropathic pain (64 Vs 68%), Papscore A/B (100 Vs 91%), CAGE + (23 Vs 18%). Median M dose pre/post was 24.5mg±13.5 y 49 mg±27.3 for DR 1:2, Vs 23.3mg±9.4 (p: NS) y 28mg±11.3 (p &lt; 0.01) for DR 1:1.2. The DR1:2 group developed more cumulative toxicity at dasy 1, 2 and 3 (p &lt; 0.015, p &lt; 0.006 y p &lt; 0.001 respectively). Pain intensity pre/ post was: 1.58±1.3 and 0.87±1.0, ns for DR 1:2, Vs 1.13±0.7 (p:NS) and 1.07±0.9 (p:NS) for DR 1:1.2. Success was observed in 12 pts in DR1:2 Vs 18 in DR 1:1.2, p &lt; 0.001. Side effects related to M were observed in 33/46 pts in DR 1:2 (mainly neurotoxicity symptoms) Vs 1/6 in DR 1:1.2. Conclusions: DR 1:1.2 when changing from parenteral to oral M resulted in lower toxicity and no difference in analgesia. More conservative dose adjustment during M route change should be considered. Granted by Spanish Ministry of Health EC10-133. EUDRACT Number: 2010-024092-39. Clinical trial information: 2010-024092-39.