Reduction of Postoperative Opioid Use After Elective Spine and Peripheral Nerve Surgery Using an Enhanced Recovery After Surgery Program.

OBJECTIVE: Enhanced recovery after surgery (ERAS) pathways have previously been shown to be feasible and safe in elective spinal procedures. As publications on ERAS pathways have recently emerged in elective neurosurgery, long-term outcomes are limited. We report on our 18-month experience with an ERAS pathway in elective spinal surgery. METHODS: A historical cohort of 149 consecutive patients was identified as the control group, and 1,141 patients were prospectively enrolled in an ERAS protocol. The primary outcome was the need for opioid use one month postoperation. Secondary outcomes were opioid and nonopioid consumption on postoperative day (POD) 1, opioid use at three and six months postoperation, inpatient pain scores, patient satisfaction scores, postoperative Foley catheter use, mobilization/ambulation on POD0-1, length of stay, complications, and intensive care unit admissions. RESULTS: There was significant reduction in use of opioids at one, three, and six months postoperation (38.6% vs 70.5%, P < 0.001, 36.5% vs 70.9%, P < 0.001, and 23.6% vs 51.9%, P = 0.008) respectively. Both groups had similar surgical procedures and demographics. PCA use was nearly eliminated in the ERAS group (1.4% vs 61.6%, P < 0.001). ERAS patients mobilized faster on POD0 compared with control (63.5% vs 20.7%, P < 0.001). Fewer patients in the ERAS group required postoperative catheterization (40.7% vs 32.7%, P < 0.001). The ERAS group also had decreased length of stay (3.4 vs 3.9 days, P = 0.020). CONCLUSIONS: ERAS protocols for all elective spine and peripheral nerve procedures are both possible and effective. This standardized approach to patient care decreases opioid usage, eliminates the use of PCAs, mobilizes patients faster, and reduces length of stay.

Pennsylvania State Core Competencies for Education on Opioids and Addiction.

OBJECTIVE: The objective of this project was to develop core competencies for education on opioids and addiction to be used in all Pennsylvania medical schools. METHODS: The Pennsylvania Physician General created a task force that was responsible for the creation of the core competencies. A literature review was completed, and a survey of graduating medical students was conducted. The task force then developed, reviewed, and approved the core competencies. RESULTS: The competencies were grouped into nine domains: understanding core aspects of addiction; patient screening for substance use disorder; proper referral for specialty evaluation and treatment of substance use disorder; proper patient assessment when treating pain; proper use of multimodal treatment options when treating acute pain; proper use of opioids for the treatment of acute pain (after consideration of alternatives); the role of opioids in the treatment of chronic noncancer pain; patient risk assessment related to the use of opioids to treat chronic noncancer pain, including the assessment for substance use disorder or increased risk for aberrant drug-related behavior; and the process for patient education, initiation of treatment, careful patient monitoring, and discontinuation of therapy when using opioids to treat chronic noncancer pain. Specific competencies were developed for each domain. CONCLUSIONS: These competencies will be incorporated into the educational process at all Pennsylvania medical schools. It is hoped that these curriculum changes will improve student knowledge and attitudes in these areas, thus improving patient outcomes.

Cardiac Effects of Opioid Therapy.

OBJECTIVE: The use of opioids to treat chronic pain has come under increased scrutiny, as such use has been associated with significant risk of death, with limited data regarding the long-term effectiveness, especially when used to treat noncancer pain. The purpose of this manuscript is to discuss the cardiac effects associated with long-term opioid therapy. DESIGN: A literature search was performed using OVID. RESULTS: Most opioids have little direct negative effect on cardiac contractility. However, opioid administration can be associated with decreased cardiac function when administered in combination with other medications, including benzodiazepines. Opioids can lead to bradycardia and vasodilation, and as a result can rarely lead to edema, hypotension, orthostatic hypotension, and syncope when used at analgesic doses. While most opioids have no effect on cardiac conductivity, methadone, and buprenorphine can prolong QTc, especially when used in patients at increased risk for QTc prolongation. Electrocardiogram (ECG) monitoring of QTc at baseline and following dose increases is appropriate in patients receiving these medications. CONCLUSIONS: There are limited data to suggest that chronic opioid administration may be associated with an increased risk for cardiac-related adverse effects. However, this observation has not yet been confirmed. Regardless, while opioids are an important medication for the treatment of a multitude of chronic pain conditions, careful patient selection, and diligent monitoring is likely to decrease the risk of harm and improve patient outcomes.

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.

Can assessing chronic pain outcomes data improve outcomes?

OBJECTIVE: This manuscript reviews how patient-reported outcomes data can be used to guide efforts to improve patient outcomes. DESIGN: Review Manuscript. SETTING: The clinical management of chronic, non-cancer pain. SUBJECTS: Adult patients receiving treatment for chronic, non-cancer pain. RESULTS: While there have been great advances in the science of pain and various therapeutic medications and interventions, patient outcomes are variable. This manuscript reviews how outcomes data can be used to guide efforts to improve patient outcomes. CONCLUSIONS: Patient outcomes can be improved with standardization of the process of patient care, as well as through other quality improvement efforts. The cornerstone to any effort to improve patient outcomes starts with the integration of valid outcomes data collection into ongoing patient care. Outcome measurement tools should provide information on several key domains, yet the process of data collection should not pose a significant burden on either the patient or health care team. Efforts to improve patient outcomes are ongoing, and should be a high priority for every health care team.

The efficacy and safety of fentanyl buccal tablet compared with immediate-release oxycodone for the management of breakthrough pain in opioid-tolerant patients with chronic pain.

BACKGROUND: Current clinical guidelines have identified the need for studies comparing the effect of different short-acting or rapid-onset opioids for the treatment of breakthrough pain (BTP). In this study we evaluated the efficacy and safety of treatment with fentanyl buccal tablet (FBT) in comparison with immediate-release oxycodone in alleviating BTP in opioid-tolerant patients with chronic pain. METHODS: In this cross-over design study, opioid-tolerant patients were randomized to open-label titration with FBT (200, 400, 600, 800 µg) followed by oxycodone (15, 30, 45, 60 mg) or vice versa for the management of BTP. After titration to a successful dose of both study drugs, patients were rerandomized to double-blind treatment for 10 BTP episodes with 1 of the already identified successful doses of study drug followed by cross-over to double-blind treatment for 10 BTP episodes with the other study drug. The primary efficacy measure was the difference in pain intensity (based on an 11-point numerical scale) 15 minutes after administration of study drug (PID(15)). Other efficacy measures included PID at other time points postdose (5 through 60 minutes), the sum of pain intensity differences (SPID) at 30 and 60 minutes postdose, pain relief (5 through 60 minutes), proportion of BTP episodes for which patients experienced meaningful reduction in pain intensity, and patient preference for BTP medication. Adverse events were also recorded. RESULTS: Of the 323 patients enrolled, 203 achieved a successful dose of both study drugs, 191 completed the titration phase, and 180 completed the double-blind phase. PID(15) was significantly greater after FBT versus oxycodone (mean [SD], 0.82 [1.12] vs. 0.60 [0.88]; 95% confidence interval [CI] = 0.18, 0.29; P < 0.0001). Secondary efficacy measures favored FBT and showed differences versus oxycodone from 5 minutes postdose for PID and 10 minutes postdose for pain relief. SPID(30) and SPID(60) were greater with FBT than with oxycodone (P < 0.0001 for both measures). A ≥33% improvement in pain intensity occurred in a larger proportion of FBT-treated episodes versus oxycodone beginning 15 through 45 minutes postdose (P < 0.05). FBT was preferred by 52% of patients, oxycodone by 33%. Adverse events with both study drugs were generally typical of opioids, and the majority occurred during titration. Two serious adverse events (pneumonia) were reported in 1 patient; both occurrences were considered unrelated to study drug. CONCLUSION: FBT resulted in more rapid onset of analgesia and was generally well tolerated in comparison with oxycodone for the treatment of BTP in opioid-tolerant patients.

Targeted Program in an Academic Rheumatology Practice to Improve Compliance With Opioid Prescribing Guidelines for the Treatment of Chronic Pain.

OBJECTIVE: The Centers for Disease Control and Prevention (CDC) and many state governments have issued guidelines for opioid prescribing for the treatment of chronic noncancer-associated pain. We sought to decrease practice variation and increase compliance with these guidelines in a tertiary academic rheumatology practice by developing an interdisciplinary opioid working group and using electronic health record (EHR)-integrated data feedback. METHODS: Division leadership and providers established shared goals at interdisciplinary meetings involving rheumatology, pain medicine, nursing, and pharmacy. Interventions included educational sessions on opioid prescribing guidelines and the sharing of individual de-identified prescribing patterns. An opioid dashboard page within the EHR allowed every provider to see individualized and division-wide data that tracked process measures based on CDC and state-specific guidelines. Baseline data from June to August 2017 were compared with monthly data through December 2018. RESULTS: At baseline, 40% of patients had an active opioid agreement (a Pennsylvania guideline and a New Jersey law), 25% had a urine drug screen result within 12 months of their most recent opioid prescription, and 24% had a concurrent benzodiazepine prescription. After 16 months, these percentages improved to 88%, 66%, and 16%, respectively. The average number of opioid tablets prescribed per month decreased from 59,733 to 48,966 (-18%; P = 0.02). CONCLUSION: Shared goals developed through interdisciplinary input and readily accessible data feedback can markedly increase provider compliance with national and state-specific guidelines for opioid prescribing for the treatment of chronic noncancer-associated pain in rheumatology.

Research design considerations for chronic pain prevention clinical trials: IMMPACT recommendations.

Although certain risk factors can identify individuals who are most likely to develop chronic pain, few interventions to prevent chronic pain have been identified. To facilitate the identification of preventive interventions, an IMMPACT meeting was convened to discuss research design considerations for clinical trials investigating the prevention of chronic pain. We present general design considerations for prevention trials in populations that are at relatively high risk for developing chronic pain. Specific design considerations included subject identification, timing and duration of treatment, outcomes, timing of assessment, and adjusting for risk factors in the analyses. We provide a detailed examination of 4 models of chronic pain prevention (ie, chronic postsurgical pain, postherpetic neuralgia, chronic low back pain, and painful chemotherapy-induced peripheral neuropathy). The issues discussed can, in many instances, be extrapolated to other chronic pain conditions. These examples were selected because they are representative models of primary and secondary prevention, reflect persistent pain resulting from multiple insults (ie, surgery, viral infection, injury, and toxic or noxious element exposure), and are chronically painful conditions that are treated with a range of interventions. Improvements in the design of chronic pain prevention trials could improve assay sensitivity and thus accelerate the identification of efficacious interventions. Such interventions would have the potential to reduce the prevalence of chronic pain in the population. Additionally, standardization of outcomes in prevention clinical trials will facilitate meta-analyses and systematic reviews and improve detection of preventive strategies emerging from clinical trials.

An organized, comprehensive, and security-enabled strategic response to the Haiti earthquake: a description of pre-deployment readiness preparation and preliminary experience from an academic anesthesiology department with no preexisting international disaster response program.

BACKGROUND: On Tuesday, January 12, 2010 at 16:53 local time, a magnitude 7.0 M(w) earthquake struck Haiti. The global humanitarian attempt to respond was swift, but poor infrastructure and emergency preparedness limited many efforts. Rapid, successful deployment of emergency medical care teams was accomplished by organizations with experience in mass disaster casualty response. Well-intentioned, but unprepared, medical teams also responded. In this report, we describe the preparation and planning process used at an academic university department of anesthesiology with no preexisting international disaster response program, after a call from an American-based nongovernmental organization operating in Haiti requested medical support. The focus of this article is the pre-deployment readiness process, and is not a post-deployment report describing the medical care provided in Haiti. METHODS: A real-time qualitative assessment and systematic review of the Hospital of the University of Pennsylvania's communications and actions relevant to the Haiti earthquake were performed. Team meetings, conference calls, and electronic mail communication pertaining to planning, decision support, equipment procurement, and actions and steps up to the day of deployment were reviewed and abstracted. Timing of key events was compiled and a response timeline for this process was developed. Interviews with returning anesthesiology members were conducted. RESULTS: Four days after the Haiti earthquake, Partners in Health, a nonprofit, nongovernmental organization based in Boston, Massachusetts, with >20 years of experience providing medical care in Haiti contacted the University of Pennsylvania Health System to request medical team support. The departments of anesthesiology, surgery, orthopedics, and nursing responded to this request with a volunteer selection process, vaccination program, and systematic development of equipment lists. World Health Organization and Centers for Disease Control guidelines, the American Society of Anesthesiology Committee on Trauma and Emergency Preparedness, published articles, and in-country contacts were used to guide the preparatory process. CONCLUSION: An organized strategic response to medical needs after an international natural disaster emergency can be accomplished safely and effectively within 6 to 12 days by an academic anesthesiology department, with medical system support, in a center with no previously established response system. The value and timeliness of this response will be determined with further study. Institutions with limited experience in putting an emergency medical team into the field may be able to quickly do so when such efforts are executed in a systematic manner in coordination with a health care organization that already has support infrastructure at the site of the disaster.

Closing the gaps in opioid use disorder research, policy and practice: conference proceedings.

Drug overdose deaths involving opioids have surged in recent years and the economic cost of the opioid epidemic is estimated to be over $500 billion annually. In the midst of calls for declaring a national emergency, health policy decision makers are considering the best ways to allocate resources to curb the epidemic. On June 9, 2017, 116 invited health researchers, clinicians, policymakers, health system leaders, and other stakeholders met at the University of Pennsylvania to discuss approaches to address the gaps in evidence-based substance use disorder policy and practice, with an emphasis on the opioid epidemic. The conference was sponsored by the Center for Health Economics of Treatment Interventions for Substance Use Disorder, HCV, and HIV (CHERISH), a NIDA-funded National Center of Excellence, and hosted by the Leonard Davis Institute of Health Economics of the University of Pennsylvania. The conference aims were to: (1) foster new relationships between researchers and policymakers through a collaborative work process and (2) generate evidence-based policy recommendations to address the opioid epidemic. The conference concluded with an interactive work session during which attendees self-identified as researchers or policymakers and were divided equally among 13 tables. These groups met to develop and present policy recommendations based on an opioid use disorder case study. Thirteen policy recommendations emerged across four themes: (1) quality of treatment, (2) continuity of care, (3) opioid prescribing and pain management, and (4) consumer engagement. This conference serves as a proposed model to develop equitable, working relationships among researchers, clinicians, and policymakers.

The Initiation of Chronic Opioids: A Survey of Chronic Pain Patients.

This study reports the results of a researcher-administered survey with 115 patients receiving chronic opioid therapy (>90 days) to obtain information regarding how chronic opioid therapy was started. Chronic opioids were started after surgery (27.0%, 95% confidence interval [CI], 18.5-35.5) or for the treatment of acute injury-related pain (27.0%, 95% CI, 18.5-35.5). Many who initiated opioid therapy after surgery reported postoperative complications (61.3%, 95% CI, 50.8-71.8) and many with injury-related pain reported follow-up corrective surgery (58.1%, 95% CI, 47.5-68.7), which led to the continuation of opioids. A large percentage of patients had concurrent depression (43.5%, 95% CI, 34.0-53.0) and anxiety (23.5%, 95% CI, 15.3-31.7). Many participants had a medical history of aberrant drug-related behavior (32.5%, 95% CI, 23.5-41.5) and self-reported history of addiction (21.7%, 95% CI, 13.7-29.7). Almost one-quarter reported taking opioids for a different indication than that for which opioids were started (95% CI, 26.6-45.0). Patients receiving long-term opioid therapy often transitioned to chronic use after starting opioids for the short-term treatment of postoperative or injury-related pain. It is not evident if a clear decision to continue opioids on a chronic basis was made. This survey provides insight as to how chronic opioid therapy is started, and may suggest opportunities for improved patient selection for opioid therapy. PERSPECTIVE: This article explores the reasons why patients using chronic opioid therapy (>90 days) initiated opioid medications. The results of this study may help clinicians better select patients for chronic opioid therapy.

The Pain Medical Home: A Patient-Centered Medical Home Model of Care for Patients with Chronic Pain.

Chronic pain affects an estimated 100 million people a year in the United States and costs society anywhere from $560 to $635 billion annually. The patient-centered medical home and the patient-centered medical home-neighbor models of care have been advocated to improve patient outcomes. These models of care advocate improved coordination of care within the primary care and specialty care setting. The authors present the patient-centered medical home model of care and suggest how this model of care might be used to improve patient outcomes for patients with chronic pain.

Research design considerations for chronic pain prevention clinical trials: IMMPACT recommendations.

Although certain risk factors can identify individuals who are most likely to develop chronic pain, few interventions to prevent chronic pain have been identified. To facilitate the identification of preventive interventions, an IMMPACT meeting was convened to discuss research design considerations for clinical trials investigating the prevention of chronic pain. We present general design considerations for prevention trials in populations that are at relatively high risk for developing chronic pain. Specific design considerations included subject identification, timing and duration of treatment, outcomes, timing of assessment, and adjusting for risk factors in the analyses. We provide a detailed examination of 4 models of chronic pain prevention (ie, chronic postsurgical pain, postherpetic neuralgia, chronic low back pain, and painful chemotherapy-induced peripheral neuropathy). The issues discussed can, in many instances, be extrapolated to other chronic pain conditions. These examples were selected because they are representative models of primary and secondary prevention, reflect persistent pain resulting from multiple insults (ie, surgery, viral infection, injury, and toxic or noxious element exposure), and are chronically painful conditions that are treated with a range of interventions. Improvements in the design of chronic pain prevention trials could improve assay sensitivity and thus accelerate the identification of efficacious interventions. Such interventions would have the potential to reduce the prevalence of chronic pain in the population. Additionally, standardization of outcomes in prevention clinical trials will facilitate meta-analyses and systematic reviews and improve detection of preventive strategies emerging from clinical trials.

The pharmacokinetics of transdermal fentanyl delivered with and without controlled heat.

Preliminary reports have demonstrated that the application of local heat to the transdermal fentanyl patch significantly increased systemic delivery of fentanyl. The objective of this study was to further evaluate the pharmacokinetic effect of local heat administration on fentanyl drug delivery through the transdermal fentanyl patch delivery system in volunteers. In addition, the study was intended to document the effect of heat on steady-state transdermal fentanyl delivery. This was an open, 3-period, crossover study that evaluated the pharmacokinetics and safety of 25 microg/h transdermal fentanyl administered with and without local heat. During Sessions A and B, subjects received transdermal fentanyl for a 30-hour period. During Session A, heat was applied for 1 hour at the 24-hour time point during the 30-hour period. During Session B, heat was applied for the first 4 hours and then again for 1 hour at the 24-hour time point during the 30-hour period. The order of Sessions A and B was randomized, and a minimum of 2 weeks separated the sessions. Five of the 10 subjects returned to participate in Session C. During Session C, subjects received transdermal fentanyl 25 microg/h for 18 hours. Heat was applied during the first 4 hours of administration and then again for 15-minute periods at the 12- and 16-hour time points. Arterial blood samples for determination of serum fentanyl concentration were collected. Maximum concentration (C(max)), time to maximum concentration (t(max)), and area under the curve (AUC) were determined for each treatment period. Sedation, vital signs, oxygen saturation, and adverse events were recorded. During a period of 36 hours, there were no significant differences in C(max), AUC, or T(max) between transdermal fentanyl delivery with no heat and heat. However, significant differences were seen during the first 4 hours, with C(max) and AUC values almost 3 times higher for the heated administrations than for the administrations without heat. With heat, the mean C(max) was 0.63 ng/mL compared with a C(max) of 0.24 ng/mL without heat (P =.007). With early heat, the mean AUC was 1.22 ng/mL. h compared with 0.42 ng/mL. h without heat (P =.003). There was no statistically significant difference between the median times to achieve peak values (T(max)) during the first 4 hours. The addition of heat at 24 hours resulted in rapid increases in serum fentanyl concentrations for both groups and higher serum fentanyl concentrations for the administration that did not receive heat previously. Applying heat for 15 minutes at the 12-hour and 16-hour time points produced a rapid but short duration increase in serum fentanyl concentrations. The results suggest controlled heat might be used to significantly shorten the time needed to reach clinically important fentanyl concentrations. Controlled heat might be useful to produce rapid increases in serum concentrations for the rapid treatment of breakthrough pain.