Randomized Placebo-Controlled Trial of 60-Day Percutaneous Peripheral Nerve Stimulation Treatment Indicates Relief of Persistent Postoperative Pain, and Improved Function After Knee Replacement.

OBJECTIVES: Total knee arthroplasty (TKA) is an effective surgery for end-stage knee osteoarthritis, but chronic postoperative pain and reduced function affect up to 20% of patients who undergo such surgery. There are limited treatment options, but percutaneous peripheral nerve stimulation (PNS) is a promising nonopioid treatment option for chronic, persistent postoperative pain. The objective of the present study was to evaluate the effect of a 60-day percutaneous PNS treatment in a multicenter, randomized, double-blind, placebo-controlled trial for treating persistent postoperative pain after TKA. MATERIALS AND METHODS: Patients with postoperative pain after knee replacement were screened for this postmarket, institutional review board-approved, prospectively registered (NCT04341948) trial. Subjects were randomized to receive either active PNS or placebo (sham) stimulation. Subjects and a designated evaluator were blinded to group assignments. Subjects in both groups underwent ultrasound-guided placement of percutaneous fine-wire coiled leads targeting the femoral and sciatic nerves on the leg with postoperative pain. Leads were indwelling for eight weeks, and the primary efficacy outcome compared the proportion of subjects in each group reporting ≥50% reduction in average pain relative to baseline during weeks five to eight. Functional outcomes (6-minute walk test; 6MWT and Western Ontario and McMaster Universities Osteoarthritis Index) and quality of life (Patient Global Impression of Change) also were evaluated at end of treatment (EOT). RESULTS: A greater proportion of subjects in the PNS groups (60%; 12/20) than in the placebo (sham) group (24%; 5/21) responded with ≥50% pain relief relative to baseline (p = 0.028) during the primary endpoint (weeks 5-8). Subjects in the PNS group also walked a significantly greater distance at EOT than did those in the placebo (sham) group (6MWT; +47% vs -9% change from baseline; p = 0.048, n = 18 vs n = 20 completed the test, respectively). Prospective follow-up to 12 months is ongoing. CONCLUSIONS: This study provides evidence that percutaneous PNS decreases persistent pain, which leads to improved functional outcomes after TKA at EOT.

Pain and Opioid use Following Total Knee Arthroplasty: Psycho-Social Factors are More Predictive Than Pharmacogenomics.

BACKGROUND: This prospective, observational study was designed to assess the phenotype variation of the genes associated with pain and opioid use following total knee arthroplasty (TKA) in comparison to psycho-social elements. METHODS: Preoperative demographic data and Patient-Reported Outcomes Measurement Information System-43 scores were obtained on 305 elective TKA patients. Patient visual analog scale pain scores and opioid use were extracted from the hospital record. Following discharge, participants completed a daily log of visual analog scale pain score, and medications used over 30 days. Pharmacogenomic testing was performed for three genes, CYP2D6, COMT, and OPRM1, which are involved in the opioid pathway and pain modulation. RESULTS: Other than increased pain seen in the COMT high activity group while in the hospital, none of the phenotype variations of the three genes were significantly associated with the participants' pain or opioid use. The Patient-Reported Outcomes Measurement Information System-43 domains of pain interference and anxiety were significantly associated with pain and opioid use using multiple logistic regression. CONCLUSIONS: Pharmacogenomic testing in this study was not predictive of pain and opioid use following TKA compared with psycho-social variables.

Remote Management of Spinal Cord Stimulation Devices for Chronic Pain: Expert Recommendations on Best Practices for Proper Utilization and Future Considerations.

OBJECTIVE: Emerging spinal cord stimulation (SCS) remote monitoring and programming technologies provide a unique opportunity to address challenges of in-person visits and improve patient care, although clinical guidance on implementation is needed. The goal of this document is to establish best clinical practices for integration of remote device management into the care of patients with SCS, including remote monitoring and remote programming. MATERIALS AND METHODS: A panel of experts in SCS met in July 2022, and additional experts contributed to the development of recommendations after the meeting via survey responses and correspondence. RESULTS: Major goals of remote SCS device management were identified, including prompt identification and resolution of SCS-related issues. The panel identified metrics for remote monitoring and classified them into three categories: device-related (eg, stimulation usage); measurable physiologic or disease-related (eg, patient physical activity or pedometry); and patient-reported (eg, sleep quality and pain intensity). Recommendations were made for frequency of reviewing remote monitoring metrics, although providers should tailor follow-up to individual patient needs. Such periodic reviews of remote monitoring metrics would occur separately from automatic monitoring system notifications (if key metrics fall outside an acceptable range). The guidelines were developed in consideration of reimbursement processes, privacy concerns, and the responsibilities of the care team, industry professionals, manufacturers, patients, and caregivers. Both existing and needed clinical evidence were covered, including outcomes of interest for future studies. CONCLUSIONS: Given the expansion of SCS device capabilities, this document provides critical guidance on best practices for using remote device management, although medical necessity should drive all remote monitoring decisions, with individualized patient care. The authors also describe the potential of these emerging technologies to improve outcomes for patients with SCS, although more clinical evidence is needed.

Treatment of Refractory Low Back Pain Using Passive Recharge Burst in Patients Without Options for Corrective Surgery: Findings and Results From the DISTINCT Study, a Prospective Randomized Multicenter Controlled Trial.

OBJECTIVE: Spinal cord stimulation (SCS) is effective for relieving chronic intractable pain conditions. The Dorsal spInal cord STImulatioN vs mediCal management for the Treatment of low back pain study evaluates the effectiveness of SCS compared with conventional medical management (CMM) in the treatment of chronic low back pain in patients who had not undergone and were not candidates for lumbar spine surgery. METHODS AND MATERIALS: Patients were randomized to passive recharge burst therapy (n = 162) or CMM (n = 107). They reported severe pain and disability for more than a decade and had failed a multitude of therapies. Common diagnoses included degenerative disc disease, spondylosis, stenosis, and scoliosis-yet not to a degree amenable to surgery. The six-month primary end point compared responder rates, defined by a 50% reduction in pain. Hierarchical analyses of seven secondary end points were performed in the following order: composite responder rate (numerical rating scale [NRS] or Oswestry Disability Index [ODI]), NRS, ODI, Pain Catastrophizing Scale responder rate, Patient Global Impression of Change (PGIC) responder rate, and Patient-Reported Outcome Measure Information System-29 in pain interference and physical function. RESULTS: Intention-to-treat analysis showed a significant difference in pain responders on NRS between SCS (72.6%) and CMM (7.1%) arms (p < 0.0001). Of note, 85.2% of those who received six months of therapy responded on NRS compared with 6.2% of those with CMM (p < 0.0001). All secondary end points indicated the superiority of burst therapy over CMM. A composite measure on function or pain relief showed 91% of subjects with SCS improved, compared with 16% of subjects with CMM. A substantial improvement of 30 points was observed on ODI compared with a

Multiorganizational consensus to define guiding principles for perioperative pain management in patients with chronic pain, preoperative opioid tolerance, or substance use disorder.

Significant knowledge gaps exist in the perioperative pain management of patients with a history of chronic pain, substance use disorder, and/or opioid tolerance as highlighted in the US Health and Human Services Pain Management Best Practices Inter-Agency Task Force 2019 report. The report emphasized the challenges of caring for these populations and the need for multidisciplinary care and a comprehensive approach. Such care requires stakeholder alignment across multiple specialties and care settings. With the intention of codifying this alignment into a reliable and efficient processes, a consortium of 15 professional healthcare societies was convened in a year-long modified Delphi consensus process and summit. This process produced seven guiding principles for the perioperative care of patients with chronic pain, substance use disorder, and/or preoperative opioid tolerance. These principles provide a framework and direction for future improvement in the optimization and care of 'complex' patients as they undergo surgical procedures.

Best Practices for Dorsal Root Ganglion Stimulation for Chronic Pain: Guidelines from the American Society of Pain and Neuroscience.

With continued innovations in neuromodulation comes the need for evolving reviews of best practices. Dorsal root ganglion stimulation (DRG-S) has significantly improved the treatment of complex regional pain syndrome (CRPS), and it has broad applicability across a wide range of other conditions. Through funding and organizational leadership by the American Society for Pain and Neuroscience (ASPN), this best practices consensus document has been developed for the selection, implantation, and use of DRG stimulation for the treatment of chronic pain syndromes. This document is composed of a comprehensive narrative literature review that has been performed regarding the role of the DRG in chronic pain and the clinical evidence for DRG-S as a treatment for multiple pain etiologies. Best practice recommendations encompass safety management, implantation techniques, and mitigation of the potential complications reported in the literature. Looking to the future of neuromodulation, DRG-S holds promise as a robust intervention for otherwise intractable pain.

Primary Ewing's Sarcoma of the Penis: First Reported Case in the United Kingdom.

Penile cancer is generally rare, and Squamous cell cancer of the penis is the most common histological type. Sarcoma of the penis has a low incidence, but they tend to grow faster than other penile cancers. One of the rarest types of penile sarcomas is Extra-Skeletal Ewing's Sarcoma (EES). The management of such cases can be challenging, and treatment guidelines do not exist for these rare cases. We present a rare case of EES that has developed in the penis of a young patient in the United Kingdom.

Male urethral stricture disease: why management guidelines are challenging in low-income countries.

Urethral stricture disease (USD) is one of the commonest urological pathologies in adult men in low- or low-middle-income countries, providing a significant work burden for the small number of specialist surgeons who are able to provide appropriate treatment. The underlying causes of anterior urethral stricture relate to urethral fibrosis from sexually transmitted infection, with posterior urethral disruption secondary to pelvic trauma being an equally common cause of USD in many countries in sub-Saharan Africa. Anterior urethral strictures are often long, and multifocal, and bulbo-prostatic disruptions are usually due to relatively low-velocity pelvic trauma. The management options available in resource-poor settings are often severely limited by the individual's ability to pay for care, the availability of a specialist surgeon and, importantly, a shortage of functioning endoscopic equipment for less-invasive treatments. Consequently, reconstructive surgery is often regarded by the patient, and surgeon, as the most cost-effective and, therefore, primary means of treating a urethral stricture once urethral dilatation has failed. Regional anaesthetic techniques have limited the adoption of free-graft augmentation as an alternative to pedicled flaps of locally available skin for reconstruction, whilst an inability to provide tension-free bulbo-prostatic anastomoses has negatively impacted the outcome from the treatment of pelvic fracture disruption injuries in much of sub-Saharan Africa. However, Urolink has found that local surgeons can be taught sustainable skills required for successful complex urethroplasty when supported by longitudinal mentorship in the management of difficult clinical issues. Evidence-based practice is known to improve the standard of care in specific conditions in high-income countries, including the management of male USD. However, guidelines developed in high-income countries are not necessarily appropriate for stricture management in less well-resourced healthcare environments but could be adapted to help improve the delivery of stricture care for men in low- or low-middle income countries.

Impact of Ketamine in the Management of Painful Sickle Cell Disease Vaso-Occlusive Crisis.

The aim of the study is to determine if ketamine infusions in combination with opioid therapy for the management of sickle cell disease (SCD) presenting with vaso-occlusive crisis (VOC) resulted in a length-of-stay difference compared to when ketamine was not utilized. This single center, retrospective, observational study performed at an academic medical center evaluated 12 adult patients with SCD-VOC who received a ketamine infusion with standard opioid therapy between 2014 and 2017. Patients were excluded if the primary diagnosis was not VOC or they did not survive to discharge. Additionally, safety and oral morphine equivalents at various time points were compared. Patients were used as their own control using the previous SCD-VOC hospitalization to evaluate the relative impact of ketamine. Wilcoxon signed-rank and rank sum were used in statistical analysis. When comparing opioid doses during the ketamine infusion, a P-value <.005 was considered statistically significant to account for multiple comparisons. The median length-of stay when ketamine was employed was similar to the previous admission with only opioid therapy (12 vs 12 days, P = .317). The median opioid dose 24 hours prior to starting ketamine was greater than during the first 24 hours of ketamine use (1278 vs 1020 mg, P = .022) and 24 hours after stopping ketamine (1278 vs 1035 mg, P = .014); however, this was not statistically significant. During 5 ketamine infusions, patients experienced side effects; however, only 1 necessitated transfer to the intensive care unit. Compared to standard opioid therapy, ketamine infusions were generally well tolerated and may be effective at reducing opioid use during SCD-VOC but did not decrease hospital length-of-stay.

Scrotal Masson's tumour masquerading as dysplastic polyorchidism - a case report.

This case describes a rare genitourinary presentation of a Masson's tumour, preoperatively assumed to be a dysplastic third testis.

An Anatomy-Informed, Novel Technique for S1 Dorsal Root Ganglion Stimulation Lead Placement.

OBJECTIVE: A heightened and organized understanding of sacral anatomy could potentially lead to a more effective and safe method of dorsal root ganglion stimulation (DRG-S) lead placement. The aim of this technical note is to describe a standardized access method for S1 DRG-S lead placement. DESIGN: Technical note. METHODS: The described approach utilizes alignment of the lumbosacral prominence and is measurement-based, allowing for standardized sacral access, even when visualization is suboptimal. The medial-to-lateral needle trajectory is designed to limit interaction with the sensitive neural structures and allows for a more parallel orientation of the lead to the DRG and nerve root. CONCLUSIONS: The described technique potentially improves the safety of S1 DRG-S lead placement. The parallel lead orientation to the DRG may also increase efficacy while lowering energy requirements.

A multisociety organizational consensus process to define guiding principles for acute perioperative pain management.

The US Health and Human Services Pain Management Best Practices Inter-Agency Task Force initiated a public-private partnership which led to the publication of its report in 2019. The report emphasized the need for individualized, multimodal, and multidisciplinary approaches to pain management that decrease the over-reliance on opioids, increase access to care, and promote widespread education on pain and substance use disorders. The Task Force specifically called on specialty organizations to work together to develop evidence-based guidelines. In response to this report's recommendations, a consortium of 14 professional healthcare societies committed to a 2-year project to advance pain management for the surgical patient and improve opioid safety. The modified Delphi process included two rounds of electronic voting and culminated in a live virtual event in February 2021, during which seven common guiding principles were established for acute perioperative pain management. These principles should help to inform local action and future development of clinical practice recommendations.

A paramedian approach for dorsal root ganglion stimulation placement developed to limit lead migration and fracture.

INTRODUCTION: Dorsal root ganglion stimulation (DRG-S), has demonstrated superiority in the treatment of complex regional pain syndrome and causalgia. Lead migration and fracture impact DRG-S therapeutic stability. Lead anchoring reduces DRG-S lead migration without increasing lead fracture. Lead fracture may be related to lead entrapment in the superficial fascial plane. A novel medialized approach for lead placement and anchoring is presented to address these issues. METHODS: We suggest an alternative technique for implanting percutaneous DRG-S leads at the T10-L5 levels. RESULTS: A novel medialized ipsilateral technique for lead placement and anchoring for single, bilateral, and adjacent segment placement is presented. The Tuohy needle puncture site is medial to the pedicle and adjacent to the spinous process, two vertebral levels caudad to the target foramen. Trajectory is maintained in the sagittal plane, to access the caudad interlaminar space near the midline. This technique allows for ipsilateral or contralateral lead placement. After epidural access, the introducer sheath is rotated toward the targeted foramen and advanced. The guidewire followed by the lead is passed, and once lead position is confirmed, tension "S" loops are created, followed by anchoring to the deep fascia. CONCLUSION: We describe a new paramedian technique for DRG-S lead placement. We propose it will decrease DRG-S complication rates through anchoring to reduce migration and by avoiding the fascial planes thought to be responsible for fracture. Long-term outcomes applying our proposed techniques are required for determining the true impact, however, early anecdotal results suggest that these new techniques are favorable.

Clinical Practice Guideline: Opioid Prescribing for Analgesia After Common Otolaryngology Operations.

OBJECTIVE: Opioid use disorder (OUD), which includes the morbidity of dependence and mortality of overdose, has reached epidemic proportions in the United States. Overprescription of opioids can lead to chronic use and misuse, and unused narcotics after surgery can lead to their diversion. Research supports that most patients do not take all the prescribed opioids after surgery and that surgeons are the second largest prescribers of opioids in the United States. The introduction of opioids in those with OUD often begins with prescription opioids. Reducing the number of extra opioids available after surgery through smaller prescriptions, safe storage, and disposal should reduce the risk of opioid use disorder in otolaryngology patients and their families. PURPOSE: The purpose of this specialty-specific guideline is to identify quality improvement opportunities in postoperative pain management of common otolaryngologic surgical procedures. These opportunities are communicated through clear actionable statements with explanation of the support in the literature, evaluation of the quality of the evidence, and recommendations on implementation. Employing these action statements should reduce the variation in care across the specialty and improve postoperative pain control while reducing risk of OUD. The target patients for the guideline are any patients treated for anticipated or reported pain within the first 30 days after undergoing common otolaryngologic procedures. The target audience of the guideline is otolaryngologists who perform surgery and clinicians who manage pain after surgical procedures. Outcomes to be considered include whether the patient has stopped using opioids, has disposed of unused opioids, and was satisfied with the pain management plan.The guideline addresses assessment of the patient for OUD risk factors, counseling on pain expectations, and identifying factors that can affect pain duration and/or severity. It also discusses the use of multimodal analgesia as first-line treatment and the responsible use of opioids. Last, safe disposal of unused opioids is discussed.This guideline is intended to focus on evidence-based quality improvement opportunities judged most important by the guideline development group. It is not a comprehensive guide on pain management in otolaryngologic procedures. The statements in this guideline are not intended to limit or restrict care provided by clinicians based on their experiences and assessments of individual patients. ACTION STATEMENTS: The guideline development group made strong recommendations for the following key action statements: (3A) prior to surgery, clinicians should identify risk factors for opioid use disorder when analgesia using opioids is anticipated; (6) clinicians should advocate for nonopioid medications as first-line management of pain after otolaryngologic surgery; (9) clinicians should recommend that patients (or their caregivers) store prescribed opioids securely and dispose of unused opioids through take-back programs or another accepted method.The guideline development group made recommendations for the following key action statements: (1) prior to surgery, clinicians should advise patients and others involved in the postoperative care about the expected duration and severity of pain; (2) prior to surgery, clinicians should gather information specific to the patient that modifies severity and/or duration of pain; (3B) in patients at risk for OUD, clinicians should evaluate the need to modify the analgesia plan; (4) clinicians should promote shared decision making by informing patients of the benefits and risks of postoperative pain treatments that include nonopioid analgesics, opioid analgesics, and nonpharmacologic interventions; (5) clinicians should develop a multimodal treatment plan for managing postoperative pain; (7) when treating postoperative pain with opioids, clinicians should limit therapy to the lowest effective dose and the shortest duration; (8A) clinicians should instruct patients and caregivers how to communicate if pain is not controlled or if medication side effects occur; (8B) clinicians should educate patients to stop opioids when pain is controlled with nonopioids and stop all analgesics when pain has resolved; (10) clinicians should inquire, within 30 days of surgery, whether the patient has stopped using opioids, has disposed of unused opioids, and was satisfied with the pain management plan.

Clinical Practice Guideline: Opioid Prescribing for Analgesia After Common Otolaryngology Operations Executive Summary.

OBJECTIVE: Opioid use disorder (OUD), which includes the morbidity of dependence and mortality of overdose, has reached epidemic proportions in the United States. Overprescription of opioids can lead to chronic use and misuse, and unused narcotics after surgery can lead to their diversion. Research supports that most patients do not take all the prescribed opioids after surgery and that surgeons are the second largest prescribers of opioids in the United States. The introduction of opioids in those with OUD often begins with prescription opioids. Reducing the number of extra opioids available after surgery through smaller prescriptions, safe storage, and disposal should reduce the risk of opioid use disorder in otolaryngology patients and their families. PURPOSE: The purpose of this specialty-specific guideline is to identify quality improvement opportunities in postoperative pain management of common otolaryngologic surgical procedures. These opportunities are communicated through clear actionable statements with explanation of the support in the literature, evaluation of the quality of the evidence, and recommendations on implementation. Employing these action statements should reduce the variation in care across the specialty and improve postoperative pain control while reducing risk of OUD. The target patients for the guideline are any patients treated for anticipated or reported pain within the first 30 days after undergoing common otolaryngologic procedures. The target audience of the guideline is otolaryngologists who perform surgery and clinicians who manage pain after surgical procedures. Outcomes to be considered include whether the patient has stopped using opioids, has disposed of unused opioids, and was satisfied with the pain management plan.The guideline addresses assessment of the patient for OUD risk factors, counseling on pain expectations, and identifying factors that can affect pain duration and/or severity. It also discusses the use of multimodal analgesia as first-line treatment and the responsible use of opioids. Last, safe disposal of unused opioids is discussed.This guideline is intended to focus on evidence-based quality improvement opportunities judged most important by the guideline development group. It is not a comprehensive guide on pain management in otolaryngologic procedures. The statements in this guideline are not intended to limit or restrict care provided by clinicians based on their experiences and assessments of individual patients. ACTION STATEMENTS: The guideline development group made strong recommendations for the following key action statements: (3A) prior to surgery, clinicians should identify risk factors for opioid use disorder when analgesia using opioids is anticipated; (6) clinicians should advocate for nonopioid medications as first-line management of pain after otolaryngologic surgery; (9) clinicians should recommend that patients (or their caregivers) store prescribed opioids securely and dispose of unused opioids through take-back programs or another accepted method.The guideline development group made recommendations for the following key action statements: (1) prior to surgery, clinicians should advise patients and others involved in the postoperative care about the expected duration and severity of pain; (2) prior to surgery, clinicians should gather information specific to the patient that modifies severity and/or duration of pain; (3B) in patients at risk for OUD, clinicians should evaluate the need to modify the analgesia plan; (4) clinicians should promote shared decision making by informing patients of the benefits and risks of postoperative pain treatments that include nonopioid analgesics, opioid analgesics, and nonpharmacologic interventions; (5) clinicians should develop a multimodal treatment plan for managing postoperative pain; (7) when treating postoperative pain with opioids, clinicians should limit therapy to the lowest effective dose and the shortest duration; (8A) clinicians should instruct patients and caregivers how to communicate if pain is not controlled or if medication side effects occur; (8B) clinicians should educate patients to stop opioids when pain is controlled with nonopioids and stop all analgesics when pain has resolved; (10) clinicians should inquire, within 30 days of surgery, whether the patient has stopped using opioids, has disposed of unused opioids, and was satisfied with the pain management plan.

AAAPT Diagnostic Criteria for Acute Low Back Pain with and Without Lower Extremity Pain.

OBJECTIVE: Low back pain is one of the most common reasons for which people visit their doctor. Between 12% and 15% of the US population seek care for spine pain each year, with associated costs exceeding $200 billion. Up to 80% of adults will experience acute low back pain at some point in their lives. This staggering prevalence supports the need for increased research to support tailored clinical care of low back pain. This work proposes a multidimensional conceptual taxonomy. METHODS: A multidisciplinary task force of the ACTTION-APS-AAPM Pain Taxonomy (AAAPT) with clinical and research expertise performed a focused review and analysis, applying the AAAPT five-dimensional framework to acute low back pain. RESULTS: Application of the AAAPT framework yielded the following: 1) Core Criteria: location, timing, and severity of acute low back pain were defined; 2) Common Features: character and expected trajectories were established in relevant subgroups, and common pain assessment tools were identified; 3) Modulating Factors: biological, psychological, and social factors that modulate interindividual variability were delineated; 4) Impact/Functional Consequences: domains of impact were outlined and defined; 5) Neurobiological Mechanisms: putative mechanisms were specified including nerve injury, inflammation, peripheral and central sensitization, and affective and social processing of acute low back pain. CONCLUSIONS: The goal of applying the AAAPT taxonomy to acute low back pain is to improve its assessment through a defined evidence and consensus-driven structure. The criteria proposed will enable more rigorous meta-analyses and promote more generalizable studies of interindividual variation in acute low back pain and its potential underlying mechanisms.

Antibody RING-Mediated Destruction of Endogenous Proteins.

To understand gene function, the encoding DNA or mRNA transcript can be manipulated and the consequences observed. However, these approaches do not have a direct effect on the protein product of the gene, which is either permanently abrogated or depleted at a rate defined by the half-life of the protein. We therefore developed a single-component system that could induce the rapid degradation of the specific endogenous protein itself. A construct combining the RING domain of ubiquitin E3 ligase RNF4 with a protein-specific camelid nanobody mediates target destruction by the ubiquitin proteasome system, a process we describe as antibody RING-mediated destruction (ARMeD). The technique is highly specific because we observed no off-target protein destruction. Furthermore, bacterially produced nanobody-RING fusion proteins electroporated into cells induce degradation of target within minutes. With increasing availability of protein-specific nanobodies, this method will allow rapid and specific degradation of a wide range of endogenous proteins.

Postoperative Pain and Analgesic Requirements in the First Year after Intraoperative Methadone for Complex Spine and Cardiac Surgery.

BACKGROUND: Methadone is a long-acting opioid that has been reported to reduce postoperative pain scores and analgesic requirements and may attenuate development of chronic postsurgical pain. The aim of this secondary analysis of two previous trials was to follow up with patients who had received a single intraoperative dose of either methadone or traditional opioids for complex spine or cardiac surgical procedures. METHODS: Preplanned analyses of long-term outcomes were conducted for spinal surgery patients randomized to receive 0.2 mg/kg methadone at the start of surgery or 2 mg hydromorphone at surgical closure, and for cardiac surgery patients randomized to receive 0.3 mg/kg methadone or 12 µg/kg fentanyl intraoperatively. A pain questionnaire assessing the weekly frequency (the primary outcome) and intensity of pain was mailed to subjects 1, 3, 6, and 12 months after surgery. Ordinal data were compared with the Mann-Whitney U test, and nominal data were compared using the chi-square test or Fisher exact probability test. The criterion for rejection of the null hypothesis was P < 0.01. RESULTS: Three months after surgery, patients randomized to receive methadone for spine procedures reported the weekly frequency of chronic pain was less (median score 0 on a 0 to 4 scale [less than once a week] vs. 3 [daily] in the hydromorphone group, P = 0.004). Patients randomized to receive methadone for cardiac surgery reported the frequency of postsurgical pain was less at 1 month (median score 0) than it was in patients randomized to receive fentanyl (median score 2 [twice per week], P = 0.004). CONCLUSIONS: Analgesic benefits of a single dose of intraoperative methadone were observed during the first 3 months after spinal surgery (but not at 6 and 12 months), and during the first month after cardiac surgery, when the intensity and frequency of pain were the greatest.

Pharmacogenomic considerations for medications in the perioperative setting.

Several high-profile examples of adverse outcomes from medications used in the perioperative setting are well known (e.g., malignant hyperthermia, prolonged apnea, respiratory depression, inadequate analgesia), leading to an increased understanding of genetic susceptibilities underlying these risks. Pharmacogenomic information is increasingly being utilized in certain areas of medicine. Despite this, routine preoperative genetic screening to inform medication risk is not yet standard practice. In this review, we assess the current readiness of pharmacogenomic information for clinical consideration for several common perioperative medications, including description of key pharmacogenes, pharmacokinetic implications and potential clinical outcomes. The goal is to highlight medications for which emerging or considerable pharmacogenomic information exists and identify areas for future potential research.