BACKGROUND:Chronic axial spinal pain is a major contributor to disability and healthcare expenditures, with facet joints recognized as one of the established sources of pain. OBJECTIVE:To provide evidence-based guidance in performing diagnostic and therapeutic facet joint interventions. METHODS:A multidisciplinary panel of experts from various medical and pharmaceutical disciplines, convened by the American Society of Interventional Pain Physicians (ASIPP), reviewed the available evidence, considered patient perspectives, and formulated recommendations for facet joint interventions in the management of chronic pain.The methodology included the development of key questions with evidence-based statements and recommendations. Grading of the evidence and recommendations followed a modified approach described by ASIPP, the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology, and the Agency for Healthcare Research and Quality (AHRQ) methods for grading strength of recommendations. The evidence review included existing guidelines, systematic reviews, comprehensive reviews, randomized controlled trials (RCTs), and observational studies evaluating the effectiveness and safety of facet joint interventions in chronic pain management.In the development of consensus statements and guidelines, a modified Delphi technique was utilized to minimize bias related to group interactions. Panelists without a primary conflict of interest voted on approval of specific guideline statements. Each panelist was permitted to suggest revisions to guideline wording and provide additional qualifying remarks or comments regarding implementation of the guidelines in clinical practice. To achieve consensus and inclusion in the final guidelines, each guideline statement required at least 80% agreement among eligible panel members without a primary conflict of interest. RESULTS:A total of 48 authors participated in the development of these guidelines, of whom 39 participated in the voting process. A total of 37 recommendations were developed, with 100% acceptance for all items. The Summary of Recommendations is presented separately. These recommendations addressed diagnostic, therapeutic, and special considerations related to facet joint interventions. For diagnostic and therapeutic interventions, the level of evidence ranged from II to III, with moderate to strong recommendations. For special considerations and safety assessments, the level of evidence ranged from II to V. The evidence provided recommendations regarding diagnosis, treatment, sedation, concurrent antithrombotic therapy, and precautions required in special clinical circumstances. LIMITATIONS:The limitations of these guidelines include a paucity of high-quality studies in some aspects of diagnosis and therapy. CONCLUSION:These guidelines for facet joint interventions were developed through a comprehensive review of the literature, including methodologic quality assessment and determination of the level of evidence and strength of recommendations. DISCLAIMER:These guidelines are based on the best available evidence and do not constitute inflexible treatment recommendations. Due to the changing body of evidence, this document is not intended to be a "standard of care."

Background: Peripheral nerve stimulation (PNS) has been used for over 50 years to treat chronic pain by delivering electrical pulses through small electrodes placed near targeted peripheral nerves those outside the brain and spinal cord. Early PNS systems often required invasive neurosurgical procedures. However, since 2015, the Food and Drug Administration (FDA) approved percutaneously implanted PNS leads and neurostimulators offering a much less invasive, non-opioid option for managing recalcitrant chronic pain. The following FDA-cleared PNS systems are commercially available in the United States for the management of chronic, intractable pain: center dot Freedom (R) Peripheral Nerve Stimulator (PNS) System (Curonix LLC, 2017) center dot StimRouter (R) Neuromodulation System (Bioness, now Bioventus, 2015) center dot SPRINT (R) PNS System (SPR (R) Therapeutics, Inc., 2016) center dot Nalu (TM) Neurostimulation System (Nalu Medical Inc., 2019) center dot ReActiv8 (R) Implantable Neurostimulation System (Mainstay Medical Limited, 2020) The American Society of Interventional Pain Physicians (ASIPP) has published evidence-based consensus guidelines for the application of PNS systems in managing chronic pain. Objective: The guidelines aim to provide evidence-based recommendations for the utilization of peripheral nerve stimulation (PNS) in the management of moderate to severe chronic pain. These guidelines exclude field stimulation, or sacral nerve stimulation. Methods: A multidisciplinary panel of experts in various medical and pharmaceutical fields, convened by ASIPP, reviewed the evidence, considered patient perspectives, and formulated recommendations for implantable peripheral nerve stimulation in chronic pain management. The methodology included developing key questions with evidence-based statements and recommendations. The grading of evidence and recommendations followed a modified approach described by ASIPP, the Grading of Recommendations Assessment, Development and Evaluation (GRADE) method, and the Agency for Healthcare Research and Quality (AHRQ) strength of recommendations methods. The evidence review includes existing guidelines, systematic reviews, comprehensive reviews, randomized controlled trials (RCTs), and observational studies on the effectiveness and safety of implantable peripheral nerve stimulation in managing chronic pain The quality of published studies was assessed using appropriate instruments for systematic reviews, RCTs, and observational studies.In the development of consensus statements and guidelines, we used a modified Delphi technique, which has been described to minimize bias related to group interactions. Panelists without a primary conflict of interest voted to approve specific guideline statements. Each panelist could suggest edits to the guideline statement wording and could suggest additional qualifying remarks or comments as to the implementation of the guideline in clinical practice to achieve consensus and for inclusion in the final guidelines, each guideline statement required at least 80% agreement among eligible panel members without primary conflict of interest.Results: A total of 31 authors participated in the development of these guidelines. Of these, 23 participated in the voting process. A total of 8 recommendations were developed. Overall, 100% acceptance was obtained for 8 of 8 items. Thus, with appropriate literature review, consensus-based statements were developed for implantable peripheral nerve stimulation in chronic pain management. In preparation of these guidelines, evidence synthesis included 7 systematic reviews, 8 RCTs, and 9 observational studies covering all PNS treatments. The evidence was developed using GRADE criteria or certainty of evidence, and qualitative synthesis based on the best available evidence. The evidence level and recommendations are as follows: center dot For implantable peripheral nerve stimulation systems following a trial or selective lumbar medial branch stimulation without a trial, the evidence is Level III or fair with moderate certainty. Evidence Level: Fair; Strength of Recommendation: Moderate center dot For temporary peripheral nerve stimulation for 60 days, the evidence is Level III or fair, with moderate certainty. Evidence Level: Fair; Strength of Recommendation: ModerateBased on the available evidence, it is our recommendation to expand the existing PNS related local coverage determination (LCD) to include craniofacial pain, phantom limb pain, and nociceptive pain in the lower back as present evidence shows Level III or fair with moderate certainty.Limitations: The primary limitation of these guidelines is the paucity of the available literature. Conclusion: These evidence-based guidelines support the use of implantable peripheral nerve stimulation leads and neurostimulators in patients with moderate to severe chronic pain refractory to two or more conservative treatments. These guidelines aim to optimize patient outcomes and promote health equity through the integration of PNS technology in clinical practice.

Background: Opioid prescribing in the United States is decreasing, however, the opioid epidemic is continuing at an uncontrollable rate. Available data show a significant number of opioid deaths, primarily associated with illicit fentanyl use. It is interesting to also note that the data show no clear correlation between opioid prescribing (either number of prescriptions or morphine milligram equivalent [MME] per capita), opioid hospitalizations, and deaths. Furthermore, the data suggest that the 2016 guidelines from the Centers for Disease Control and Prevention (CDC) have resulted in notable problems including increased hospitalizations and mental health disorders due to the lack of appropriate opioid prescribing as well as inaptly rapid tapering or weaning processes. Consequently, when examined in light of other policies and complications caused by COVID-19, a fourth wave of the opioid epidemic has been emerging.Objectives: In light of this, we herein seek to provide guidance for the prescription of opioids for the management of chronic non-cancer pain. These clinical practice guidelines are based upon a systematic review of both clinical and epidemiological evidence and have been developed by a panel of multidisciplinary experts assessing the quality of the evidence and the strength of recommendations and offer a clear explanation of logical relationships between various care options and health outcomes. Methods: The methods utilized included the development of objectives and key questions for the various facets of opioid prescribing practice. Also utilized were employment of trustworthy standards, and appropriate disclosures of conflicts of interest(s). The literature pertaining to opioid use, abuse, effectiveness, and adverse consequences was reviewed. The recommendations were developed after the appropriate review of text and questions by a panel of multidisciplinary subject matter experts, who tabulated comments, incorporated changes, and developed focal responses to questions posed.The multidisciplinary panel finalized 20 guideline recommendations for prescription of opioids for chronic non-cancer pain.Summary of the results showed over 90% agreement for the final 20 recommendations with strong consensus. The consensus guidelines included 4 sections specific to opioid therapy with 1) ten recommendations particular to initial steps of opioid therapy; 2) five recommendations for assessment of effectiveness of opioid therapy; 3) three recommendations regarding monitoring adherence and side effects; and 4) two general, final phase recommendations.Limitations: There is a continued paucity of literature of long-term opioid therapy addressing chronic non-cancer pain. Further, significant biases exist in the preparation of guidelines, which has led to highly variable rules and regulations across various states. Conclusion: These guidelines were developed based upon a comprehensive review of the literature, consensus among expert panelists, and in alignment with patient preferences, and shared decision-making so as to improve the long-term pain relief and function in patients with chronic non-cancer pain. Consequently, it was concluded - and herein recommended - that chronic opioid therapy should be provided in low doses with appropriate adherence monitoring and understanding of adverse events only to those patients with a proven medical necessity, and who exhibit stable improvement in both pain relief and activities of daily function, either independently or in conjunction with other modalities of treatments.

INTRODUCTION:Surgical site infiltration with bupivacaine hydrochloride (HCl) is a standard element of postoperative analgesia for soft tissue surgeries, but results in short-lived analgesia. A novel bupivacaine implant, XARACOLL (bupivacaine HCl), is Food and Drug Administration approved for treatment of acute postsurgical pain following adult inguinal herniorrhaphy. This study examined the efficacy and safety of the bupivacaine implant (300 mg) compared with placebo for postsurgical pain after abdominoplasty.METHODS:In this double-blind, placebo-controlled study, patients undergoing abdominoplasty were randomized to three 100 mg bupivacaine implants or three placebo collagen implants, in a 1:1 ratio, implanted intraoperatively. No other analgesics were administered into the surgical site. Patients were allowed opioids and acetaminophen for postoperative pain. Patients were followed for up to 30 days after treatment.PRIMARY OUTCOME:the analgesic effect of the bupivacaine implants through 24 hours postsurgery, measured by the sum of time-weighted pain intensity (SPI24). Prespecified key secondary outcomes included SPI48 and SPI72, percentage of opioid-free patients through 24, 48, and 72 hours, and adverse events, which were tested sequentially to control for multiplicity (ie, if the first variable failed to reach significance, no subsequent variables were declared statistically significant).RESULTS:The bupivacaine implant patients (n=181) reported statistically significant lower SPI24 (mean (SD) SPI24=102 (43), 95% CI 95 to 109) compared with placebo patients (n=184; SPI24=117 (45), 95% CI 111 to 123, p=0.002). SPI48 was 190 (88, 95% CI 177 to 204) for INL-001 and 206 (96, 95% CI 192 to 219) for placebo, and not significantly different between groups. The subsequent secondary variables were therefore declared not statistically significant. SPI72 was 265 (131, 95% CI 244 to 285) for INL-001 and 281 (146, 95% CI 261 to 301) for placebo. The opioid-free percentage of patients at 24, 48, and 72 hours was 19%, 17%, and 17% for INL-001 and 6.5% for placebo patients (at all timepoints). The only adverse event occurring in ≥5% of patients and for which proportion INL-001 >placebo was back pain (7.7% vs 7.6%).CONCLUSION:The study design was limited by not containing an active comparator. Compared with placebo, INL-001 provides postoperative analgesia that is temporally aligned with the period of maximal postsurgical pain in abdominoplasty and offers a favorable safety profile.TRIAL REGISTRATION NUMBER:NCT04785625.

Introduction: Postoperative mobilization requires effective management of pain with movement. Vocacapsaicin (formerly CA-008) is a water-soluble prodrug of capsaicin, a well-characterized TRPV1 receptor agonist. Intraoperative injection of vocacapsaicin reduced pain and opioid consumption for 2 weeks after total knee arthroplasty and bunionectomy. This randomized, double-blind, placebo-controlled pilot study evaluated safety and efficacy of vocacapsaicin after open laparotomy for ventral hernia repair (VHR). Methods: After internal review board approval and written informed consent, patients underwent elective, open VHR with mesh (Rives-Stoppa) under general anesthesia with standard-of-care perioperative analgesia including bilateral bupivacaine rectus blocks and peri-incisional bupivacaine infiltration. (ClinicalTrials.gov:NCT04774328). Before closing, placebo or vocacapsaicin 24 mg in 80 mL saline was infiltrated into the surgical site. Endpoints included serial numerical rating scales (NRS) for pain with activity (coughing, ambulation) and opioid consumption over 96 hours. Multiple local and systemic safety endpoints, including wound healing, were measured repeatedly through postoperative day 28. Results: Twenty-four patients were enrolled. Through the first 96 hours, vocacapsaicin reduced pain on coughing 46% (p = 0.02, ANOVA), pain on ambulation 35% (p = 0.08), pain at rest 21% (p = nonsignificant [NS]) and cumulative opioid consumption 26% (p = NS). A trend towards improved analgesia persisted through 8 days. There was no difference between vocacapsaicin and placebo in the safety analysis through day 28. Conclusion: This pilot study suggests that a single intraoperative dose of vocacapsaicin provides clinically meaningful pain reduction for 96 hours after open laparotomy when added to a standard-of-care analgesic regimen. There were no safety concerns. The results are consistent with previous results in orthopaedic surgery.

BACKGROUND:Ultrasonography is increasingly being used in every field of medicine, especially regional anesthesia. To successfully perform the procedure, a knowledge of anatomy and ultrasonoanatomy as well as technical 3D hand-eye coordination skills are required. Medical practitioners who use ultrasound devices to perform regional blocks have to correlate the position of the ultrasound probe on the patient, needle position, and ultrasound picture. To achieve that, the practitioner has to intermittently look between the patient and the ultrasonography screen. This requires extra head rotations, increasing the time and complexity of the procedure. Newer technologies are available that can alleviate the need for these extra head movements, such as head-mounted displays (HMDs), which are connected to the ultrasonography machine and project the ultrasonography picture onto the HMD goggles so that the provider can see the monitor without unnecessary head rotations.OBJECTIVE:Our theory was that the use of the HMD goggles would decrease the overall procedure duration as well as provider head rotations.STUDY DESIGN:This was a randomized clinical study.SETTING:The research was conducted at an academic medical center at the University of Texas Medical Branch, Galveston, TX.METHODS:We secured Institutional Review Board (IRB) approval to perform the study. We chose an HMD, which can be mounted on the head like regular goggles. By connecting the HMD with the ultrasonography machine, the ultrasound picture can be projected directly in front of the physician's eyes. Twenty-four patients were randomized to receive a regional anesthetic performed by anesthesiology residents using a conventional ultrasound-guided approach or using the HMD in addition. We measured the number of attempts, head rotations, and time needed to obtain a satisfactory nerve stimulation in addition to outcomes and adverse effects. Our data were interpreted by our statistician with P < .05 indicating statistical significance.RESULTS:Regional anesthetics performed with the HMD were significantly faster (59.08 vs 175.08 seconds) with significantly fewer head movements (0.83 vs 4.75) and attempts (1 vs 1.42). There were no significant differences in patient demographics, type of regional anesthetic, level of resident training, or outcomes. No complications were noted.LIMITATIONS:A limitation of our research is that neither observers nor providers were blinded to the way blocks were performed. This would have been practically impossible because participants had to wear an HMD.CONCLUSIONS:The HMD could provide advantages in regional anesthesia by decreasing the time and attempts and improving ergonomics. These findings can be easily translated into other ultrasound- or optic/camera-guided procedures outside of regional anesthesia, such as vascular access or laparoscopic surgery.IRB: UTMB IRB #12-143.

Background and Objective Oral tramadol, an atypical opioid approved in the United States (US) since 1995 and a Schedule IV controlled substance, has less abuse liability compared to Schedule II conventional opioids. Intravenous (IV) tramadol is not available in the US, but has the potential to fill a gap between non-opioid medications and conventional opioids for treatment of acute pain. This study evaluates IV tramadol in the management of postoperative pain compared to placebo and standard-of-care active control. Methods A phase 3, multicenter, double-blind, three-arm, randomized, placebo- and active-controlled, multiple-dose, parallel-group study was conducted to evaluate the efficacy and safety of 50 mg IV tramadol versus placebo and 4 mg IV morphine over 48 h in patients with postoperative pain following abdominoplasty surgery. Results IV tramadol was statistically superior ( p < 0.05) to placebo and comparable to IV morphine for the primary and all key secondary efficacy outcomes and demonstrated numerically lower rates for the incidence of most common treatment-emergent adverse events (TEAEs) compared to morphine. No unexpected findings were observed for TEAEs, laboratory tests, vital signs, or electrocardiograms (ECGs). Over 90% of patients completed the study. Conclusion The study demonstrated that IV tramadol 50 mg is highly effective in the management of postoperative pain following abdominoplasty. The consistency of effects between tramadol and morphine (as compared to placebo) for primary and key secondary endpoints validates the efficacy of tramadol observed. The study also provided direct evidence of improved tolerability of IV tramadol over a standard-of-care conventional Schedule II opioid. IV tramadol may become a useful option in patients where exposure to conventional opioids is not desired.

Objectives: We sought to evaluate the efficacy, efficiency, and physiologic consequences of automated, endpoint-directed resuscitation systems and compare them to formula-based bolus resuscitation. Design: Experimental human hemorrhage and resuscitation. Setting: Clinical research laboratory. Subjects: Healthy volunteers. Interventions: Subjects (n = 7) were subjected to hemorrhage and underwent a randomized fluid resuscitation scheme on separate visits 1) formula-based bolus resuscitation; 2) semiautonomous (decision assist) fluid administration; and 3) fully autonomous (closed loop) resuscitation. Hemodynamic variables, volume shifts, fluid balance, and cardiac function were monitored during hemorrhage and resuscitation. Treatment modalities were compared based on resuscitation efficacy and efficiency. Measurements and Main Results: All approaches achieved target blood pressure by 60 minutes. Following hemorrhage, the total amount of infused fluid (bolus resuscitation: 30 mL/kg, decision assist: 5.6 ± 3 mL/kg, closed loop: 4.2 ± 2 mL/kg; p < 0.001), plasma volume, extravascular volume (bolus resuscitation: 17 ± 4 mL/kg, decision assist: 3 ± 1 mL/kg, closed loop: –0.3 ± 0.3 mL/kg; p < 0.001), body weight, and urinary output remained stable under decision assist and closed loop and were significantly increased under bolus resuscitation. Mean arterial pressure initially decreased further under bolus resuscitation (–10 mm Hg; p < 0.001) and was lower under bolus resuscitation than closed loop at 20 minutes (bolus resuscitation: 57 ± 2 mm Hg, closed loop: 69 ± 4 mm Hg; p = 0.036). Colloid osmotic pressure (bolus resuscitation: 19.3 ± 2 mm Hg, decision assist, closed loop: 24 ± 0.4 mm Hg; p < 0.05) and hemoglobin concentration were significantly decreased after bolus fluid administration. Conclusions: We define efficacy of decision-assist and closed-loop resuscitation in human hemorrhage. In comparison with formula-based bolus resuscitation, both semiautonomous and autonomous approaches were more efficient in goal-directed resuscitation of hemorrhage. They provide favorable conditions for the avoidance of over-resuscitation and its adverse clinical sequelae. Decision-assist and closed-loop resuscitation algorithms are promising technological solutions for constrained environments and areas of limited resources.

Objectives The goal of this study was to assess the success of the morphine microdose method in a community pain clinic setting by monitoring follow-up frequency, dose escalation, and monotherapy/polytherapy ratio. The morphine microdose method involves a pretrial reduction or elimination of systemic opioids followed by a period of abstinence. Intrathecal (IT) morphine is then started at doses of less than 0.2 mg per day. Systemic opioid abstinence is then continued after pump implant and IT morphine monotherapy. Design Retrospective review of medical records. Setting Private and academic pain clinic practices. Subjects Chronic noncancer pain patients. Methods We reviewed the charts of 60 patients who had completed a microdose regimen and had an IT pump implanted between June 11, 2008, and October 11, 2014. During IT therapy, dose change over time, pain scores, side effects, max dose, and duration were recorded. Results The majority of patients (35/60, 58%) were successfully managed solely on morphine microdose monotherapy. These patients did not require additional oral therapy. There was a significant reduction in mean pain scores, from 7.4 ± 0.32 before microdose therapy to 4.8 ± 0.3 after microdose therapy. Conclusions Microdose therapy achieved analgesia, improved safety, and avoided systemic side effects. The safety of IT therapy was increased by using a lower concentration (2 mg/mL) and lower daily doses (<3 mg/d) of morphine. Furthermore, microdose therapy was feasible, safe, and cost-effective in the outpatient setting.

BACKGROUNDOpioid use, abuse, and adverse consequences, including death, have escalated at an alarming rate since the 1990s. In an attempt to control opioid abuse, numerous regulations and guidelines for responsible opioid prescribing have been developed by various organizations. However, the US opioid epidemic is continuing and drug dose deaths tripled during 1999 to 2015. Recent data show a continuing increase in deaths due to natural and semisynthetic opioids, a decline in methadone deaths, and an explosive increase in the rates of deaths involving other opioids, specifically heroin and illicit synthetic fentanyl. Contrary to scientific evidence of efficacy and negative recommendations, a significant proportion of physicians and patients (92%) believe that opioids reduce pain and a smaller proportion (57%) report better quality of life. In preparation of the current guidelines, we have focused on the means to reduce the abuse and diversion of opioids without jeopardizing access for those patients suffering from non-cancer pain who have an appropriate medical indication for opioid use.OBJECTIVESTo provide guidance for the prescription of opioids for the management of chronic non-cancer pain, to develop a consistent philosophy among the many diverse groups with an interest in opioid use as to how appropriately prescribe opioids, to improve the treatment of chronic non-cancer pain and to reduce the likelihood of drug abuse and diversion. These guidelines are intended to provide a systematic and standardized approach to this complex and difficult arena of practice, while recognizing that every clinical situation is unique.METHODSThe methodology utilized included the development of objectives and key questions. The methodology also utilized trustworthy standards, appropriate disclosures of conflicts of interest, as well as a panel of experts from various specialties and groups. The literature pertaining to opioid use, abuse, effectiveness, and adverse consequences was reviewed, with a best evidence synthesis of the available literature, and utilized grading for recommendation as described by the Agency for Healthcare Research and Quality (AHRQ).Summary of Recommendations:i. Initial Steps of Opioid Therapy 1. Comprehensive assessment and documentation. (Evidence: Level I; Strength of Recommendation: Strong) 2. Screening for opioid abuse to identify opioid abusers. (Evidence: Level II-III; Strength of Recommendation: Moderate) 3. Utilization of prescription drug monitoring programs (PDMPs). (Evidence: Level I-II; Strength of Recommendation: Moderate to strong) 4. Utilization of urine drug testing (UDT). (Evidence: Level II; Strength of Recommendation: Moderate) 5. Establish appropriate physical diagnosis and psychological diagnosis if available. (Evidence: Level I; Strength of Recommendation: Strong) 6. Consider appropriate imaging, physical diagnosis, and psychological status to collaborate with subjective complaints. (Evidence: Level III; Strength of Recommendation: Moderate) 7. Establish medical necessity based on average moderate to severe (≥ 4 on a scale of 0 - 10) pain and/or disability. (Evidence: Level II; Strength of Recommendation: Moderate) 8. Stratify patients based on risk. (Evidence: Level I-II; Strength of Recommendation: Moderate) 9. Establish treatment goals of opioid therapy with regard to pain relief and improvement in function. (Evidence: Level I-II; Strength of Recommendation: Moderate) 10. Obtain a robust opioid agreement, which is followed by all parties. (Evidence: Level III; Strength of Recommendation: Moderate)ii. Assessment of Effectiveness of Long-Term Opioid Therapy 11. Initiate opioid therapy with low dose, short-acting drugs, with appropriate monitoring. (Evidence: Level II; Strength of Recommendation: Moderate) 12. Consider up to 40 morphine milligram equivalent (MME) as low dose, 41 to 90 MME as a moderate dose, and greater than 91 MME as high dose. (Evidence: Level II; Strength of Recommendation: Moderate) 13. Avoid long-acting opioids for the initiation of opioid therapy. (Evidence: Level I; Strength of Recommendation: Strong) 14. Recommend methadone only for use after failure of other opioid therapy and only by clinicians with specific training in its risks and uses, within FDA recommended doses. (Evidence: Level I; Strength of Recommendation: Strong) 15. Understand and educate the patients of the effectiveness and adverse consequences. (Evidence: Level I; Strength of Recommendation: Strong) 16. Similar effectiveness for long-acting and short-acting opioids with increased adverse consequences of long-acting opioids. (Evidence: Level I-II; Strength of recommendation: Moderate to strong) 17. Periodically assess pain relief and/or functional status improvement of ≥ 30% without adverse consequences. (Evidence: Level II; Strength of recommendation: Moderate) 18. Recommend long-acting or high dose opioids only in specific circumstances with severe intractable pain. (Evidence: Level I; Strength of Recommendation: Strong)iii. Monitoring for Adherence and Side Effects 19. Monitor for adherence, abuse, and noncompliance by UDT and PDMPs. (Evidence: Level I-II; Strength of Recommendation: Moderate to strong) 20. Monitor patients on methadone with an electrocardiogram periodically. (Evidence: Level I; Strength of Recommendation: Strong). 21. Monitor for side effects including constipation and manage them appropriately, including discontinuation of opioids when indicated. (Evidence: Level I; Strength of Recommendation: Strong)iv. Final Phase 22. May continue with monitoring with continued medical necessity, with appropriate outcomes. (Evidence: Level I-II; Strength of Recommendation: Moderate) 23. Discontinue opioid therapy for lack of response, adverse consequences, and abuse with rehabilitation. (Evidence: Level III; Strength of Recommendation: Moderate) CONCLUSIONS: These guidelines were developed based on comprehensive review of the literature, consensus among the panelists, in consonance with patient preferences, shared decision-making, and practice patterns with limited evidence, based on randomized controlled trials (RCTs) to improve pain and function in chronic non-cancer pain on a long-term basis. Consequently, chronic opioid therapy should be provided only to patients with proven medical necessity and stability with improvement in pain and function, independently or in conjunction with other modalities of treatments in low doses with appropriate adherence monitoring and understanding of adverse events.Key words: Chronic pain, persistent pain, non-cancer pain, controlled substances, substance abuse, prescription drug abuse, dependency, opioids, prescription monitoring, drug testing, adherence monitoring, diversionDisclaimer: The guidelines are based on the best available evidence and do not constitute inflexible treatment recommendations. Due to the changing body of evidence, this document is not intended to be a "standard of care."

BACKGROUND:There is experimental evidence that dexmedetomidine has neuroprotective effects. So, it could be expected that its intrathecal or epidural administration presents no harm. However, whether dexmedetomidine is neurotoxic to the spinal cord remains to be fully elucidated.OBJECTIVE:To evaluate the effect of preservative-free dexmedetomidine administered as a subarachnoid single injection on the spinal cord and meninges of rabbits.STUDY DESIGN:Research article.SETTING:Experimental research laboratory.METHODS:Twenty young adult female rabbits, each weighing between 3200 and 4900 g, and having a spine length between 36 and 40 cm, were divided by lot into 2 groups (G): 0.9% saline in G1 and preservative-free dexmedetomidine in G2 (dose of 10 µg). After intravenous anesthesia with ketamine and xylazine, the subarachnoid space was punctured at S1-S2 under ultrasound guidance, and a random 5 µl.cm-1 of spinal length (0.2 mL) of solution (saline or dexmedetomidine) was injected. The animals remained in captivity for 21 days under medical observation and were sacrificed by decapitation. The lumbosacral spinal cord portion was removed for immunohistochemistry to assess the glial fibrillary acidic protein (GFAP), and histology was assessed using hematoxylin and eosin (HE) stain.RESULTS:None of the animals had impaired motor function or decreased nociception during the period of clinical observation. None of the animals from the control group showed signs of injuries to meninges. In the dexmedetomidine group, however, 9 animals presented with signs of meningeal injury. The main histological changes observed were areas with meningeal thickening and lymphoplasmocitary infiltration in the pia-mater and arachnoid. Further histological examination also revealed adherence areas among the pia and arachnoid. There was no signal of injury in neural tissue in any animal of both groups.LIMITATIONS:Evaluation of the possible analgesic effects of the intrathecal dexmedetomidine was not performed.CONCLUSION:On the basis of the present results, dexmedetomidine administered in the subarachnoid space in a single dose of 10 µg is capable of producing histological changes over the meninges of rabbits.

ABSTRACT Obtaining intravenous (i.v.) access for fluid administration is a critical step in treating hemorrhage. However, expertise, supplies, and personnel to accomplish this task can be delayed or even absent in austere environments. An alternative approach that can “buy time” and improve circulation when i.v. fluids are absent is needed. Preclinical studies show that intrathoracic pressure regulation (ITPR) can increase perfusion in hypovolemia in the absence of i.v. fluid. We compared ITPR with placebo in humans undergoing a 15% hemorrhage under general anesthesia. Paired healthy volunteers (n = 7, aged 21 – 35 years) received either ITPR or placebo on different study days. Institutional review board informed consent was obtained. Subjects were anesthetized using propofol, intubated, and mechanically ventilated and hemorrhaged (10 mL/kg). Twenty minutes after hemorrhage, ITPR (−12 cm H2O vacuum) or placebo (device but no vacuum) was administered for another 60 min. Intravenous fluid was administered when systolic blood pressure was less than 85 mmHg. Hemodynamics, cardiac function by echocardiography, and volumetric data were compared. Data were expressed in &Dgr;mean ± SEM before and after ITPR/placebo intervention. There were no differences in mean arterial pressure (ITPR, 2.1 ± 3 mmHg; placebo, −0.7 ± 3 mmHg) or fluid infused (ITPR, 17.4 ± 4 mL/kg; placebo, 18.6 ± 5 mL/kg). Urinary output and plasma volume also were not significantly different. Intrathoracic pressure regulation augmented stroke volume (ITPR, 22 ± 5 mL, placebo, 6 ± 4 mL; P < 0.05), ejection fraction (ITPR, 4% ± 1%; placebo, 0% ± 1%), and diastolic function (&Dgr;E/e′) (ITPR, −0.8 ± 0.4 vs. placebo, +0.81 ± 0.6; P < 0.05). Intrathoracic pressure regulation did not improve mean arterial pressure in healthy volunteers aged 21 to 35 years. However, ITPR augmented stroke volume, which could be caused by improved ventricular function.

BACKGROUND AND OBJECTIVES:Although there is no documented evidence that tattoo pigments can cause neurological complications, the implications of performing neuraxial anesthesia through tattooed skin are unknown. In this study, we aimed to assess whether spinal puncture performed through tattooed skin of rabbits determines changes over the spinal cord and meninges. In addition, we sought to evaluate the presence of ink fragments entrapped in spinal needles.METHODS:Thirty-six young male adult rabbits, each weighing between 3400 and 3900 g and having a spine length between 38.5 and 39 cm, were divided by lot into 3 groups as follows: GI, spinal puncture through tattooed skin; GII, spinal puncture through tattooed skin and saline injection; and GIII, spinal puncture through skin free of tattoo and saline injection. After intravenous anesthesia with ketamine and xylazine, the subarachnoid space was punctured at S1-S2 under ultrasound guidance with a 22-gauge 2½ Quincke needle. Animals in GII and GIII received 5 μL/cm of spinal length (0.2 mL) of saline intrathecally. In GI, the needle tip was placed into the yellow ligament, and no solution was injected into the intrathecal space; after tattooed skin puncture, 1 mL of saline was injected through the needle over a histological slide to prepare a smear that was dyed by the Giemsa method to enable tissue identification if present. All animals remained in captivity for 21 days under medical observation and were killed by decapitation. The lumbosacral spinal cord portion was removed for histological analysis using hematoxylin-eosin stain.RESULTS:None of the animals had impaired motor function or decreased nociception during the period of clinical observation. None of the animals from the control group (GIII) showed signs of injuries to meninges. In GII, however, 4 animals presented with signs of meningeal injury. The main histological changes observed were focal areas of perivascular lymphoplasmacyte infiltration in the pia mater and arachnoid. There was no signal of injury in neural tissue in any animal of both groups. Tissue coring containing ink pigments was noted in all GI smears from the spinal needles used to puncture the tattooed skin.CONCLUSIONS:On the basis of the present results, intrathecal injection of saline through a needle inserted through tattooed skin is capable of producing histological changes over the meninges of rabbits. Ink fragments were entrapped inside the spinal needles, despite the presence of a stylet.

BACKGROUND The sacroiliac joint is well known as a cause of low back and lower extremity pain. Prevalence estimates are 10% to 25% in patients with persistent axial low back pain without disc herniation, discogenic pain, or radiculitis based on multiple diagnostic studies and systematic reviews. However, at present there are no definitive management options for treating sacroiliac joint pain. OBJECTIVE To evaluate the diagnostic accuracy and therapeutic effectiveness of sacroiliac joint interventions. STUDY DESIGN A systematic review of the diagnostic accuracy and therapeutic effectiveness of sacroiliac joint interventions. METHODS The available literature on diagnostic and therapeutic sacroiliac joint interventions was reviewed. The quality assessment criteria utilized were the Quality Appraisal of Reliability Studies (QAREL) checklist for diagnostic accuracy studies, Cochrane review criteria to assess sources of risk of bias, and Interventional Pain Management Techniques-Quality Appraisal of Reliability and Risk of Bias Assessment (IPM-QRB) criteria for randomized therapeutic trials and Interventional Pain Management Techniques-Quality Appraisal of Reliability and Risk of Bias Assessment for Nonrandomized Studies (IPM-QRBNR) for observational therapeutic assessments. The level of evidence was based on a best evidence synthesis with modified grading of qualitative evidence from Level I to Level V. Data sources included relevant literature published from 1966 through March 2015 that were identified through searches of PubMed and EMBASE, manual searches of the bibliographies of known primary and review articles, and all other sources. OUTCOME MEASURES For the diagnostic accuracy assessment, and for the therapeutic modalities, the primary outcome measure of pain relief and improvement in functional status were utilized. RESULTS A total of 11 diagnostic accuracy studies and 14 therapeutic studies were included. The evidence for diagnostic accuracy is Level II for dual diagnostic blocks with at least 70% pain relief as the criterion standard and Level III evidence for single diagnostic blocks with at least 75% pain relief as the criterion standard. The evidence for cooled radiofrequency neurotomy in managing sacroiliac joint pain is Level II to III. The evidence for conventional radiofrequency neurotomy, intraarticular steroid injections, and periarticular injections with steroids or botulinum toxin is limited: Level III or IV. LIMITATIONS The limitations of this systematic review include inconsistencies in diagnostic accuracy studies with a paucity of high quality, replicative, and consistent literature. The limitations for therapeutic interventions include variations in technique, variable diagnostic standards for inclusion criteria, and variable results. CONCLUSION The evidence for the accuracy of diagnostic and therapeutic effectiveness of sacroiliac joint interventions varied from Level II to Level IV.

OBJECTIVE: Pneumoperitoneum during laparoscopy results in transient oliguria and decreased glomerular filtration and renal blood flow. The presence of oliguria and elevated serum creatinine is suggestive of acute renal injury. Serum cystatin C has been described as a new marker for the detection of this type of injury. In this study, our aim was to compare the glomerular filtration rate estimated using cystatin C levels with the rate estimated using serum creatinine in patients with normal renal function who were undergoing laparoscopic surgery.METHODS: In total, 41 patients undergoing laparoscopic cholecystectomy or hiatoplasty were recruited for the study. Blood samples were collected at three time intervals: first, before intubation (T1); second, 30 minutes after the establishment of pneumoperitoneum (T2); and third, 30 minutes after deflation of the pneumoperitoneum (T3). These blood samples were then analyzed for serum cystatin C, creatinine, and vasopressin. The Larsson formula was used to calculate the glomerular filtration rate based on the serum cystatin C levels, and the Cockcroft-Gault formula was used to calculate the glomerular filtration rate according to the serum creatinine levels.RESULTS: Serum cystatin C levels increased during the study (T1 = T2, T3; p < 0.05), whereas serum creatinine levels decreased (T1 = T2. T3; p < 0.05). The calculated eGlomerular filtration rate-Larsson decreased, whereas the eGlomerular filtration rate-Cockcroft-Gault increased. There was no correlation between cystatin C and serum creatinine. Additionally, Pearson's analysis showed a better correlation between serum cystatin C and the eGlomerular filtration rate than between serum creatinine and the eGlomerular filtration rate.CONCLUSION: This study demonstrates that serum cystatin C is a more sensitive indicator of changes in the glomerular filtration rate than serum creatinine is in patients with normal renal function who are undergoing laparoscopic procedures.

Background: In all recommended guidelines put forth for the treatment of cancer pain, opioids continue to be an important part of a physician's armamentarium. Though opioids are used regularly for cancer pain, there is a paucity of literature proving efficacy for long-term use. Cancer is no longer considered a "terminal disease"; 50% to 65% of patients survive for at least 2 years, and there are about 12 million cancer survivors in the United States. There is a concern about side effects, tolerance, abuse and addiction with long-term opioid use and a need to evaluate the effectiveness of opioids for cancer pain.Objective: The objective of this systematic review was to look at the effectiveness of opioids for cancer pain.Study Design: A systematic review of randomized trials of opioids for cancer pain.Methods: A comprehensive review of the current literature for randomized controlled trials (RCTs) of opioids for cancer pain was done. The literature search was done using PubMed, EMBASE, Cochrane library, clinical trials, national clearing house, Web of Science, previous narrative systematic reviews, and cross references. The studies were assessed using the modified Cochrane and Jadad criteria. Analysis of evidence was done utilizing the modified quality of evidence developed by United States Preventive Services Task Force (USPSTF).Outcome Measures: Pain relief was the primary outcome measure. Secondary outcome measures are quality of life (QoL) and side effects including tolerance and addiction.Results: The level of evidence for pain relief based on the USPSTF criteria was fair for transdermal fentanyl and poor for morphine, tramadol, oxycodone, methadone, and codeine.Limitations: Randomized trials in a cancer setting are difficult to perform and justify. There is a paucity of long-term trials and this review included a follow-up period of only 4 weeks.Conclusion: This systematic review of RCTs of opioids for cancer pain showed fair evidence for the efficacy of transdermal fentanyl and poor evidence for morphine, tramadol, oxycodone, methadone, and codeine.

Results:Part 2 of the guidelines on responsible opioid prescribing provides the following recommendations for initiating and maintaining chronic opioid therapy of 90 days or longer.1. A) Comprehensive assessment and documentation is recommended before initiating opioid therapy, including documentation of comprehensive history, general medical condition, psychosocial history, psychiatric status, and substance use history. (Evidence: good)B) Despite limited evidence for reliability and accuracy, screening for opioid use is recommended, as it will identify opioid abusers and reduce opioid abuse. (Evidence: limited)C) Prescription monitoring programs must be implemented, as they provide data on patterns of prescription usage, reduce prescription drug abuse or doctor shopping. (Evidence: good to fair)D) Urine drug testing (UDT) must be implemented from initiation along with subsequent adherence monitoring to decrease prescription drug abuse or illicit drug use when patients are in chronic pain management therapy. (Evidence: good)2. A) Establish appropriate physical diagnosis and psychological diagnosis if available prior to initiating opioid therapy. (Evidence: good)B) Caution must be exercised in ordering various imaging and other evaluations, interpretation and communication with the patient; to avoid increased fear, activity restriction, requests for increased opioids, and maladaptive behaviors. (Evidence: good)C) Stratify patients into one of the 3 risk categories - low, medium, or high risk.D) A pain management consultation, may assist non-pain physicians, if high-dose opioid therapy is utilized. (Evidence: fair)3. Essential to establish medical necessity prior to initiation or maintenance of opioid therapy. (Evidence: good)4. Establish treatment goals of opioid therapy with regard to pain relief and improvement in function. (Evidence: good)5. A) Long-acting opioids in high doses are recommended only in specific circumstances with severe intractable pain that is not amenable to short-acting or moderate doses of long-acting opioids, as there is no significant difference between long-acting and short-acting opioids for their effectiveness or adverse effects. (Evidence: fair)B) The relative and absolute contraindications to opioid use in chronic non-cancer pain must be evaluated including respiratory instability, acute psychiatric instability, uncontrolled suicide risk, active or history of alcohol or substance abuse, confirmed allergy to opioid agents, coadministration of drugs capable of inducing life-limiting drug interaction, concomitant use of benzodiazepines, active diversion of controlled substances, and concomitant use of heavy doses of central nervous system depressants. (Evidence: fair to limited)6. A robust agreement which is followed by all parties is essential in initiating and maintaining opioid therapy as such agreements reduce overuse, misuse, abuse, and diversion. (Evidence: fair)7. A) Once medical necessity is established, opioid therapy may be initiated with low doses and short-acting drugs with appropriate monitoring to provide effective relief and avoid side effects. (Evidence: fair for short-term effectiveness, limited for long-term effectiveness)B) Up to 40 mg of morphine equivalent is considered as low dose, 41 to 90 mg of morphine equivalent as a moderate dose, and greater than 91 mg of morphine equivalence as high dose. (Evidence: fair)C) In reference to long-acting opioids, titration must be carried out with caution and overdose and misuse must be avoided. (Evidence: good)8. A) Methadone is recommended for use in late stages after failure of other opioid therapy and only by clinicians with specific training in the risks and uses. (Evidence: limited)B) Monitoring recommendation for methadone prescription is that an electrocardiogram should be obtained prior to initiation, at 30 days and yearly thereafter. (Evidence: fair)9. In order to reduce prescription drug abuse and doctor shopping, adherence monitoring by UDT and PMDPs provide evidence that is essential to the identification of those patients who are non-compliant or abusing prescription drugs or illicit drugs. (Evidence: fair)10. Constipation must be closely monitored and a bowel regimen be initiated as soon as deemed necessary. (Evidence: good)11. Chronic opioid therapy may be continued, with continuous adherence monitoring, in well-selected populations, in conjunction with or after failure of other modalities of treatments with improvement in physical and functional status and minimal adverse effects. (Evidence: fair)Disclaimer: The guidelines are based on the best available evidence and do not constitute inflexible treatment recommendations. Due to the changing body of evidence, this document is not intended to be a "standard of care."