A randomized, placebo-controlled trial of long-acting dexamethasone viscous gel delivered by transforaminal injection for lumbosacral radicular pain.

TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03372161.

Comprehensive, Evidence-Based, Consensus Guidelines for Prescription of Opioids for Chronic Non-Cancer Pain from the American Society of Interventional Pain Physicians (ASIPP).

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.

Comprehensive, evidence-based, consensus guidelines for prescription of opioids for chronic non-cancer pain from the American Society of Interventional Pain Physicians (ASIPP)

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. 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. 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

A randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of a bupivacaine hydrochloride implant in patients undergoing abdominoplasty.

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.

Ultrasound-Guided Regional Anesthesia Using a Head-Mounted Video Display: A Randomized Clinical Study.

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.

Intravenous Tramadol is Effective in the Management of Postoperative Pain Following Abdominoplasty: A Three-Arm Randomized Placebo- and Active-Controlled Trial.

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.

Efficacy, Safety, and Feasibility of the Morphine Microdose Method in Community-Based Clinics.

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.

Closed-Loop- and Decision-Assist-Guided Fluid Therapy of Human Hemorrhage.

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.

Responsible, Safe, and Effective Prescription of Opioids for Chronic Non-Cancer Pain: American Society of Interventional Pain Physicians (ASIPP) Guidelines.

BACKGROUND: Opioid 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. OBJECTIVES: To 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. METHODS: The 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."

Clinical and Histological Effects of the Intrathecal Administration of a Single Dose of Dexmedetomidine in Rabbits.

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.

Systematic Review of the Diagnostic Accuracy and Therapeutic Effectiveness of Sacroiliac Joint Interventions.

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.

Evaluation of the Head-Mounted Display for Ultrasound-Guided Peripheral Nerve Blocks in Simulated Regional Anesthesia.

BACKGROUND AND OBJECTIVES: Anesthesiologists performing peripheral nerve blocks under ultrasound guidance look frequently back and forth between the patient and the ultrasound screen during the procedure. These head movements add time and complexity to the procedure. The head-mounted display (HMD) device is a commercially available head-mounted video display that is connected to the ultrasound machine and projects the ultrasound image onto the HMD glasses, enabling the anesthesiologist to monitor the screen without ever needing to look away from the patient. We hypothesized that the use of the HMD device would decrease the total procedure time as well as operator head and ultrasound probe movements during a simulated nerve block. METHODS: The Blue Phantom was used to simulate a nerve block target. After IRB approval, verbal consent was obtained. Twenty participants, at different levels of training/experience, were asked to perform a simulated nerve block under ultrasound guidance with and without the HMD. The number of ultrasound probe and head movements and the time required to place the needle with and without the HMD were recorded. Results were analyzed using a paired t-test and significance was accepted with P < 0.05. RESULTS: Participants were significantly faster (7.1 vs 10.9 seconds) performing the simulated block with the HMD than without. Additionally, the HMD significantly decreased the number of operator head and ultrasound probe movements. CONCLUSIONS: Use of a HMD improved efficiency and human factors during simulated nerve blocks. This suggests that a clinical study to see if this observation translates into a clinical setting is warranted.

Intrathoracic Pressure Regulation Augments Stroke Volume and Ventricular Function in Human Hemorrhage.

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 Δmean ± 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 (ΔE/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.

Serum cystatin C is a sensitive early marker for changes in the glomerular filtration rate in patients undergoing laparoscopic surgery.

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 = T2T3; 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.

Serum cystatin C is a sensitive early marker for changes in the glomerular filtration rate in patients undergoing laparoscopic surgery

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 ...

A systematic review of randomized trials on the effectiveness of opioids for cancer pain.

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.

Urine drug testing in chronic pain.

Therapeutic use, overuse, abuse, and diversion of controlled substances in managing chronic non-cancer pain continue to be an issue for physicians and patients. The challenge is to eliminate or significantly curtail abuse of controlled prescription drugs while still assuring the proper treatment of those patients. Some physicians are apprehensive regarding the use of chronic opioid therapy in chronic non-cancer pain due to a perceived lack of proven evidence, the misuse of opioids, tolerance, dependence, and hyperalgesia. However, others have criticized the underuse of opioids, resulting in the undertreatment of pain. It has been the convention that federal, state, and local governments; professional associations; as well as pharmaceutical companies, physicians, accrediting bodies, medical licensure boards, and the public all share responsibility for preventing abuse of controlled prescription drugs. To overcome the critical challenge of eliminating or significantly curtailing abuse of controlled prescription drugs and at the same time assuring the appropriate treatment for those patients who can be helped by these medications, it is crucial to practice adherence or compliance monitoring of opioid therapy. Compliance monitoring has been shown to be crucial in delivering proper opioid therapy and preserving this therapy for the future. Urine drug testing (UDT) is considered one of the mainstays of adherence monitoring in conjunction with prescription monitoring programs and other screening tools, however, UDT is associated with multiple limitations secondary to potential pitfalls related to drug metabolism, reliability of the tests, and the knowledge of the pain physician. UDT is a widely available and familiar method for monitoring opioid use in chronic pain patients. UDT can provide tools for tracking patient compliance and expose possible drug misuse and abuse. UDT is one of the major tools of adherence monitoring in the assessment of the patient's predisposition to, and patterns of, drug misuse/abuse--a vital first step towards establishing and maintaining the safe and effective use of opioid analgesics in the treatment of chronic pain. This comprehensive review provides the role of UDT in monitoring chronic opioid therapy along with reliability and accuracy, appropriate use, overuse, misuse, and abuse.

Monitoring opioid adherence in chronic pain patients: assessment of risk of substance misuse.

BACKGROUND: Use of opioids for chronic non-cancer pain (CNCP) has increased in recent years because this pain had been undertreated. There was also a simultaneous increase in misuse and abuse of opioids. Deaths due to such abuse and misuse also have risen as seen in the many reports published every day in local papers as well as in the medical literature. So, it is imperative that patients who are prescribed these medications be monitored for adherence so misuse and abuse can be curtailed and opioids are available to those who genuinely need them for chronic pain control. There are various screening tools available to monitor such adherence, and there is an abundance of literature about it in addiction and psychiatric medicine. There is, though, a paucity of such literature as applied to pain medicine. OBJECTIVES: Our objectives for this review were twofold. We wanted to identify which screening tools are available to monitor opioid adherence and we wanted to see if there were prospective comparative studies of these tools to identify a single best tool that can be applied to all chronic non-cancer pain patients managed with opioids. STUDY DESIGN: We did a review of the current literature about monitoring of opioid adherence. We also looked at their use, validity, and comparative studies. METHODS: We performed a literature search using PubMed, EMBASE, and the Cochrane library. The search was conducted using the terms opioids, non-cancer pain, monitoring, and adherence. The databases from 1996 to November 2010 were reviewed. The search included prospective and retrospective studies, review articles, and FDA records. Bibliographies and cross references were reviewed when deemed appropriate. CONCLUSION: We found 52 publications, of which 22 met the criteria to be included in this manuscript. We found only one study that was prospective, and compared the various screening tools that are available to monitor opioid adherence. In the majority of the studies the number treated was small. There was not a single screening tool that can be applied universally to all patients who are on opioid therapy for chronic non-cancer pain.

Clinical and histological effects of the intrathecal administration of methylprednisolone in dogs.

BACKGROUND: Methylprednisolone is one of the most commonly used steroids for management of chronic back pain via epidural injection. Its inadvertent injection into the intrathecal space is associated with complications such as adhesive arachnoiditis. OBJECTIVE: The present study aimed to assess the clinical and histological changes associated with the injection of methylprednisolone into the intrathecal space of dogs. STUDY DESIGN: A randomized, double blind, controlled animal trial. METHODS: After approval by the animal research ethics committee, 14 dogs were studied in a randomized double blind controlled trial. They were assigned to one of 2 groups: Group I received 1 mL of 0.9% normal saline; Group II received 1 mL (1.15mg/kg) of methylprednisolone into the intrathecal space. Animals were clinically evaluated for 21 days, and then sacrificed. The lumbar and sacral portions of their spinal cords were removed for histological examination. RESULTS: In Group I, there were no clinical or histological changes. All animals in Group II showed no clinical changes but all exhibited histological changes in the spinal cord. The main histological changes consisted of meningeal thickening and lymphocytic infiltrates in the blood vessels. In 3 animals, adhesion of pia, arachnoid, and dura matter was noted and the nerve roots were surrounded by fibrosis. In one animal, necrosis of the spinal cord was evident. LIMITATIONS: The limitations of the present study include: small sample of animals (n=14), relative short clinical follow-up (21 days), and use of a commercially available drug solution, which is not preservative free. CONCLUSION: The present study demonstrated that the intrathecal administration of commercially available methylprednisolone was responsible for causing histological changes in the spinal cord and meninges of the animals studied.

Intrathecal catheter-syringe adaptor for short-term intrathecal analgesia with an externalized pump: a case report.

BACKGROUND: In most patients, cancer pain is effectively treated with conservative medical management consisting of oral and/or transdermal analgesics. Cancer patients tend to fail conservative medical management near the end of their life expectancy, thus requiring alternative routes of analgesia such as intravenous, epidural, or intrathecal. The intrathecal route provides the most effective analgesia due to the close proximity of the opioid receptors in the spinal cord. Though there are many techniques that exist for intrathecal drug delivery, complications can limit effectiveness such as infection, bleeding, cerebrospinal fluid (CSF) leaks, post-dural puncture headaches (PDPH), pump and/or catheter malfunctions, or limitations of technical expertise. Therefore, an important goal in palliative cancer pain therapy is to use equipment that is going to have the fewest number of complications and will be the most familiar to the health care providers. We describe the combination of the Medtronic Indura 1P catheter, which has the least catheter-related complications and can be used with any external drug infusion pump. These are regular infusion pumps that the health care workers are familiar with so they can provide excellent and efficient service to the patient. METHODS: In an operating room, the intrathecal catheter was placed using sterile technique under fluoroscopic guidance. The epidural space was identified with loss of resistance technique. Then the introducer needle (supplied in the Indura 1P catheter kit) was advanced until free-flowing CSF was obtained. The spinal catheter was advanced into the intrathecal space through the introducer needle to lumbar 2-3 level. The catheter was tunneled subcutaneously 10 cm lateral to the catheter exit site. A syringe filling device was inserted into the catheter opening and was secured with silk suture. A luer lock syringe was attached to the syringe filling device and CSF was aspirated. The syringe filling device was capped and later attached to an external drug infusion pump. RESULTS: We report the successful use of the Medtronic Indura 1P, one piece intrathecal catheter, connected to the external drug pump for a 3 week period in a patient with metastatic cervical cancer for palliative pain control. LIMITATIONS: Case report only. CONCLUSION: This technique is simple to perform by pain specialists. The catheter modification allows the use of the Medtronic intrathecal catheter with standard external drug infusion pumps. This facilitates the patient's care in the hospice setting.