The QTc effect of low-dose methadone for chronic pain: a prospective pilot study.

OBJECTIVE: Methadone is associated with QT prolongation and serious cardiac complications, but this has been primarily demonstrated in opioid dependent patients receiving moderate to high doses. This study investigates the effect of low-dose methadone on the QTc interval in a chronic pain population. DESIGN AND SUBJECTS: We conducted a prospective cohort study in a chronic pain clinic including 82 patients receiving methadone and 102 patients receiving non-methadone opioid therapy. METHODS: We analyzed automated QTc calculations from 12-lead electrocardiograms at baseline and during the subsequent 6 months. The primary outcome of interest was the incidence of QTc greater than 470 milliseconds or an increase from baseline of greater than 60 milliseconds. RESULTS: The methadone group did not manifest an overall higher frequency of QTc > 470 milliseconds (6% for the methadone group vs 5% for controls, P = 0.722) or an increase in the QTc of > 60 milliseconds (4% for the methadone group vs 4% for controls, P = 0.94). In the first month after initiating methadone, patients demonstrated an increase in QTc compared to controls (5% for the methadone group vs 0% for the controls, P = 0.073) but the difference disappeared in the third and sixth months. CONCLUSION: Data from our chronic pain clinic support a potential association of QTc prolongation during the initiation of methadone, but this effect is small and short lived. We believe larger scale studies to further characterize the safety profile of low-dose methadone are warranted.

The association of gender and body mass index with postoperative pain scores when undergoing ankle fracture surgery.

BACKGROUND: Intraoperative administration of opiates for postoperative analgesia requires a dosing strategy without clear indicators of pain in an anesthetized patient. Preoperative patient characteristics such as body mass index (BMI), gender, age, and other patient characteristics may provide important information regarding opiate requirements. This study intends to determine if there is an association between gender or BMI and the immediate postoperative pain scores after undergoing an open reduction and internal fixation (ORIF) of an ankle fracture with general anesthesia and morphine only analgesia. MATERIALS AND METHODS: Using a retrospective cohort design, the perioperative records were reviewed at a university healthcare hospital. One hundred and thirty-seven cases met all inclusion and no exclusion criteria. Postanesthesia care unit (PACU) records were reviewed for pain scores at first report and 30 min later as well as PACU opiate requirements. T-test, chi-square, and Mann-Whitney tests compared univariate data and multivariate analysis was performed by linear regression. RESULTS: There were no statistically significant PACU pain score group differences based on gender or BMI. Post hoc analysis revealed that in the setting of similar pain scores, obese patients received a similar weight based intraoperative morphine dose when using adjusted body weight (ABW) compared to nonobese subjects. A further finding revealed a negative correlation between age and pain score (P = 0.001). CONCLUSION: This study did not find an association between obesity or gender and postoperative pain when receiving morphine only preemptive analgesia. This study does support the use of ABW as a means to calculate morphine dosing for obese patients and that age is associated with lower immediate pain scores.

Drug-Free Noninvasive Thermal Nerve Block: Validation of Sham Devices.

Headache is a leading cause of disability and suffering. One major challenge in developing device treatments is demonstrating their efficacy given devices' often-high placebo rate. This paper reviews the importance of validating sham devices as part of finalizing the design for larger-scale prospective randomized controlled trials in patients with chronic headache as well as the results of a prospective, single-blind trial to validate two potential sham noninvasive thermal nerve block devices. Study participants were trained to self-administer thermal nerve block treatment using sham devices in an office visit. Two different sham systems with different temperature profiles were assessed. Devices were offered for patients to use daily at-home for one week to assess the durability of sham placebo effects before participants were given active treatment in a second office visit followed by another optional week of self-administered active treatment at-home use. Sham treatments reduced pain scores by an average of 31% from 6.0 ± 2.3 to 4.3 ± 3.3, including two participants who fell asleep during the in-office treatment and woke up with no pain, but whose pain recurred after returning home during at-home use of the sham system. In-office active treatments reduced pain scores by 52% from 6.7 ± 2.1 to 3.3 ± 2.9 with sustained pain relief during optional at-home use. Successful blinding for the study was confirmed with an ideal Bang's Blinding Index of 0 and an ideal James' Blinding Index of 1. Both the sham and active treatments were viewed by participants as highly credible, and credibility increased from the beginning to end of sham treatments on average.

Diagnosis, Treatment, and Management of Painful Scar: A Narrative Review.

Painful scars can develop after surgery or trauma, with symptoms ranging from a minor itch to intractable allodynia. The problem of the painful scar may involve both intraneural and extraneural structures, requiring a systematic approach to diagnosis and treatment of this neuropathic pain condition that can impact quality of life and function profoundly. In this review, we outline the algorithm for the diagnosis, management, medical and surgical treatment of painful scars.

A post-market, randomized, controlled, prospective study evaluating intrathecal pain medication versus conventional medical management in the non-cancer, refractory, chronic pain population (PROSPER).

INTRODUCTION: Intrathecal therapy has been limited by non-randomized prospective studies, particularly for those suffering from non-cancer. Further, no prospective, randomized studies investigating the efficacy, safety, and utilization of intrathecal polyanalgesic consensus guidelines exist. METHODS: After IRB approval, patients were enrolled in a 1:1 fashion for intrathecal drug delivery (IDD) or conventional management (CMM), employing standard of care, excluding intrathecal drug delivery, based on the principal investigator's discretion. They were followed 3, 6, 9, and 12 months. Assessments included PROMIS 29, NPRS, and PriceMonkey. RESULTS: Seventy-nine patients were screened, 54 patients were enrolled: 26 to IDD and 28 to CMM. At 3 months, there was no measurable difference in pain improvement in either subgroups within the CMM for chronic pain-related syndromes (CPRS) or failed back and related spine disorders (FBRS). For the IDD, early and maintained benefit from the baseline was statistically achieved. Cost analysis of pump to CMM breakeven was 4.5 months. There were no adverse events related to compounded intrathecal medications. CONCLUSION: This is the first randomized prospective, multicenter study investigating the safety, cost, and efficacy of off-label medications for intrathecal therapy, as compared to conventional management, and suggests early detection of improvement, cost savings, safety of intrathecal compounded medication use, and safety and efficacy of employing the PACC guidance.

Chronic Pain in Neurosurgery.

This review includes a summary of contemporary theories of pain processing and advocates a multimodal analgesia approach for providing perioperative care. A summary of various medication classes and anesthetic techniques is provided that highlights evidence emerging from neurosurgical literature. This summary covers opioid management, acetaminophen, nonsteroidal antiinflammatories, ketamine, lidocaine, dexmedetomidine, corticosteroids, gabapentin, and regional anesthesia for neurosurgery. At present, there is not enough investigation into these areas to describe best practices for treating or preventing chronic pain in neurosurgery; but providers can identify a wider range of options available to personalize perioperative care strategies.

Is there a dose response of dexamethasone as adjuvant for supraclavicular brachial plexus nerve block? A prospective randomized double-blinded clinical study.

STUDY OBJECTIVE: The study objective is to examine the analgesic effect of 3 doses of dexamethasone in combination with low concentration local anesthetics to determine the lowest effective dose of dexamethasone for use as an adjuvant in supraclavicular brachial plexus nerve block. DESIGN: The design is a prospective randomized double-blinded clinical study. SETTING: The setting is an academic medical center. PATIENTS: The patients are 89 adult patients scheduled for shoulder arthroscopy. INTERVENTIONS: All patients were randomly assigned into 1 of 4 treatment groups: (i) bupivacaine, 0.25% 30 mL; (ii) bupivacaine, 0.25% 30 mL with 1-mg preservative-free dexamethasone; (iii) bupivacaine, 0.25% 30 mL with 2-mg preservative-free dexamethasone; and (iv) bupivacaine, 0.25% 30 mL with 4-mg preservative-free dexamethasone. All patients received ultrasound-guided supraclavicular brachial plexus nerve blocks and general anesthesia. MEASUREMENTS: The measurements are the duration of analgesia and motor block. MAIN RESULTS: The median analgesia duration of supraclavicular brachial plexus nerve block with 0.25% bupivacaine was 12.1 hours; and 1-, 2-, or 4-mg dexamethasone significantly prolonged the analgesia duration to 22.3, 23.3, and 21.2 hours, respectively (P = .0105). Dexamethasone also significantly extended the duration of motor nerve block in a similar trend (P = .0247). CONCLUSION: Low-dose dexamethasone (1-2 mg) prolongs analgesia duration and motor blockade to the similar extent as 4-mg dexamethasone when added to 0.25% bupivacaine for supraclavicular brachial plexus nerve block.

Genetic contributions to white matter architecture revealed by diffusion tensor imaging in Williams syndrome.

Little is known about genetic regulation of the development of white matter. This knowledge is critical in understanding the pathophysiology of neurodevelopmental syndromes associated with altered cognition as well as in elucidating the genetics of normal human cognition. The hemideletion of approximately 25 genes on chromosome 7q11.23 that causes Williams syndrome (WS) includes genes that regulate cytoskeletal dynamics in neurons, especially LIMK1 and CYLN2, and therefore offers the opportunity to investigate the role of these genes in the formation of white matter tracts. We used diffusion tensor imaging to demonstrate alteration in white matter fiber directionality, deviation in posterior fiber tract course, and reduced lateralization of fiber coherence in WS. These abnormalities are consistent with an alteration of the late stages of neuronal migration, define alterations of white matter structures underlying dissociable behavioral phenotypes in WS, and provide human in vivo information about genetic control of white matter tract formation.