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Literature Review - February 2021

Feb 1, 2021, 00:10 AM by Jerry Jones, MD; Anthony Machi, MD; and Sudheer Potru, DO

Editor’s note: “Literature Review” is a feature designed to provide you with brief summaries of recent articles of interest, particularly from sources that our readers might not normally consume. 

Opioids After Surgery in the United States Versus the Rest of the World: The International Patterns of Opioid Prescribing (iPOP) Multicenter Study

Kaafarani HMA, Han K, El Moheb M, et al. Annals of Surgery. 2020;272(6):879-86. 

Selection and summary by Jerry Jones, MD

Background:  An unprecedented opioid epidemic in the United States followed an increase in opioid prescribing practices over the last two decades. Increased opioid prescriptions paralleled increases in substance use disorder and opioid-related deaths, partly driven by the diversion of unused opioid pills. The United States accounts for less than 5% of the world’s population but consumes more than 80% of its opioids, and postoperative opioid prescribing patterns in the U.S. vary widely, even within institutions and among similar patient populations.      

A multicenter prospective cohort study from 14 hospitals in 8 countries compared postoperative opioid prescribing patterns over six months for three surgeries: appendectomy, cholecystectomy, and inguinal hernia repair. A total of 4,690 adult patients (14% from the United States) were included. Patient demographics, intraoperative and postoperative adverse events (AE), length of stay, preoperative opioid use, discharge pain scale use, discharge pain severity rating, discharge opioid and non-opioid prescription details, and opioid refills within 3 months postoperatively were compared between the U.S. and other countries. Sub-analyses were conducted to exclude patients from China (0% opioid prescribing postoperatively), patients with adverse events, patients with a prior history of opioid use, and patients requiring emergency surgery.

Results: Four percent of patients had a preoperative history of opioid use (19% U.S. vs 1% non-U.S., P < 0.001). The mean total hospital length of stay for all patients was 4.2 days (2.7 U.S. vs 4.4 non-U.S.; P < 0.001). Adverse events occurred in 4% of all patients (intraoperative: 7% U.S. vs 4% non-U.S.; P < 0.001; postoperative: 9% U.S. vs 3% non-U.S.; P < 0.001). Only 43% of patients were asked about their pain level upon discharge (45% U.S. vs 43% non-U.S.; P < 0.001). Mean discharge pain level was 1.8 (3.9 U.S. vs 1.5 non-U.S.; P< 0.001).

Compared to only 5% of non-U.S. patients, 91% of U.S. patients were prescribed opioids (P < 0.001).

The median and range of number of opioid pills prescribed were 20 (0–135 pills) in U.S. patients versus 0 (0–50 pills) for non-U.S. patients (P < 0.001). The median and range of oral morphine milligram equivalents prescribed were 150 (0–1680) mg in U.S. patients versus 0 (0–600) mg in non-U.S. patients (P < 0.001). Four percent of patients receiving an initial opioid prescription upon discharge received opioid prescription refills (5% U.S. vs 1% non-U.S.; P < 0.001). The four sub-analyses showed similar results.

Key points:  The U.S. prescribes much larger amounts of opioids postoperatively and has a significantly larger variation in pattern of opioid prescribing compared to the rest of the world. Few U.S. patients receive opioid refills, but the percent is still higher than in non-U.S. patients. Multiple patient-related, physician-related, and system-related reasons can explain the excess opioid prescribing observed in the U.S. compared to other countries.  


Risk Factors for Complications and Return to the Emergency Department after Interscalene Block Using Liposomal Bupivacaine for Shoulder Surgery

Malige A, Yeazell S, Ng-Pellegrino A, Carolan G. J Shoulder Elbow Surg. 2020 Nov;29(11):2332-8.  


Selection and summary by Anthony Machi, MD

Background: Shoulder surgery is often associated with moderate to severe pain that can be difficult to adequately control. Interscalene brachial plexus blockade is well established as an effective method of analgesia for shoulder surgery as a single injection or continuous perineural block. In April 2018 the Food and Drug Administration approved liposomal bupivacaine for interscalene brachial plexus nerve block. There is little data on the incidence of adverse events when liposomal bupivacaine is used for interscalene brachial plexus nerve block.

A single-center, retrospective, observational cohort study was performed over an 8-month period in patients who received an interscalene single-injection block with liposomal bupivacaine for shoulder surgery. 352 patients were included. An ultrasound-guided posterior approach was utilized for blockade with a mixture of liposomal bupivacaine and plain bupivacaine in an amount that was not reported. Demographics, comorbidities, American Society of Anesthesiologists (ASA) score, the 5-Factor Frailty Index score, and the Charlson Comorbidity Index were recorded or calculated. Symptoms that the patient reported for which they did not return to the emergency department were recorded as minor complications, while those that caused return to the emergency department were recorded as major complications. Univariate analyses and multivariate logistic regression analyses were performed.

Results: Postoperative complications occurred in 58/352 patients (16.5%) of which 37 were minor (10.5%) and 21 were major (6.0%). 41 patients complained of dyspnea (11.6%). Elevated ASA score was the only significant predictor of minor and major complications, while congestive heart failure and pulmonary history trended toward significance, and age was significant for major complications with univariate analysis only. 12 patients (3.4%) were readmitted to the hospital.

Key point: Interscalene brachial plexus block with liposomal bupivacaine for shoulder surgery is associated with a higher rate of complications than previously reported in the literature, primarily due to dyspnea that can cause patients to return to the emergency department and be admitted. Elevated ASA score, age, and cardiopulmonary comorbidities appear to be the strongest predictors for dyspnea.

Opioids in Total Joint Arthroplasty: The Clinical Practice Guidelines of the American Association of Hip and Knee Surgeons, American Society of Regional Anesthesia and Pain Medicine, American Academy of Orthopaedic Surgeons, Hip Society, and Knee Society


Hannon CP, Fillingham YA, Nam D, et al. J Arthroplasty. 2020 Oct;35(1):2709-14. 

Selection and summary by Anthony Machi, MD

A multidisciplinary committee representing orthopedic, anesthesiology, and pain management clinicians wrote a combined clinical practice guideline addressing opioid utilization in primary total joint arthroplasty (TJA). Their goal is to improve the treatment of orthopedic surgical patients and reduce practice variations. The committee conducted a systematic review and meta-analyses to support their recommendations, which are published in the same issue.

The following are some of their findings and recommendations. Preoperative opioid use is associated with inferior outcomes including increased opioid consumption after surgery, increased risk for chronic opioid use, and increased risk of complications after TJA. Reduction in opioid use prior to TJA may lead to improved outcomes after TJA. Pre-emptive administration of opioids presurgery and intraoperative administration of opioids may improve analgesia postsurgery at the expense of an increased risk of opioid related adverse events, including respiratory depression and sedation. Postsurgery scheduled opioid administration is discouraged due to an increased risk of respiratory depression and sedation. Patients should be prescribed the fewest number of opioid pills possible without adversely impacting pain control and clinical outcomes. This may lead to reduced opioid consumption and fewer unused pills after TJA.

The committee also requested future research in key areas including the impact of the reduction of chronic opioid use prior to TJA and determining the role of perioperative opioid administration in the era of modern multimodal anesthesia and analgesia protocols for TJA.

Key point: The perioperative treatment of orthopedic patients undergoing primary total joint arthroplasty may be improved by judicious application of opioid utilization practice guidelines.



Ingestion of a THC-Rich Cannabis Oil in People with Fibromyalgia:  A Randomized, Double-Blind, Placebo-Controlled Clinical Trial

Chaves C, Bittencourt PCT, Pelegrini A. Pain Med. 2020;21:2212-8. 

Selection and summary by Sudheer Potru, DO

Introduction: Fibromyalgia (FM) is an extremely challenging clinical condition to treat.  Cannabis therapy may be beneficial for the pain, sleep, mood, and fatigue problems associated with fibromyalgia.

A randomized double-blind controlled trial studied 17 Brazilian female fibromyalgia patients of poor socioeconomic status living in an area of endemic violence and the effects of THC-rich oil on FM symptoms. FM criteria were confirmed using the American College of Rheumatology criteria (2010).  Inclusion criteria included age over 18 years and presence of moderate to severe symptoms of FM, resulting in functional limitations.  Exclusion criteria included pregnancy, psychiatric conditions, cognitive impairment, and cannabinoid sensitivity.

The cannabis group was given a cannabis oil extract (proportion 48/1 THC/CBD) provided by the Brazilian Association of Medical Cannabis Patients, while the control group was given an identical bottle containing olive oil.  The initial dose in both groups was one drop of oil (1.2 mg of THC and 0.02 mg of CBD in the cannabis group) and escalated by a drop at each visit.  Participants in both groups were seen every 10 days for eight weeks and filled out the Fibromyalgia Impact Questionnaire (FIQ), which evaluates physical function, work status, overall well-being, and physical/mental symptoms of FM. The use of antidepressants, opioids, and benzodiazepines was comparable between the two groups. 

Results:  Of the 18 eligible participants, 17 finished the study (8 in cannabis group, 9 in placebo group).  At baseline, there were no significant differences between groups on FIQ mean scores; at eight weeks, however, the cannabis group demonstrated a statistically significantly lower total FIQ score.  After the intervention, statistical differences were found in the “feel good,” “do work,” and “pain items” in the cannabis group compared to the placebo group.  Post-intervention FIQ scores were lower in the cannabis group compared to pre-intervention scores, while they were maintained in the placebo group.

Key point: THC-rich oil may be useful for symptomatic treatment of fibromyalgia patients and may improve quality of life in this challenging patient population.



BURST(able):  A Retrospective, Multicenter Study Examining the Impact of Spinal Cord Stimulation with Burst on Pain and Opioid Consumption in the Setting of Salvage Treatment and “Upgrade”

Hunter CW, Carlson J, Yang A, et al. Pain Physician. 2020;23:E643-E658.

Selection and summary by Sudheer Potru, DO

Introduction: Although recent technical improvements in spinal cord stimulation (SCS) have substantially improved outcomes, loss of efficacy (LOE) past the one-year mark continues to be a significant issue (>30% per some studies) and a very common cause of SCS explant.  DeRidder burst stimulation (D-Burst) has been found to be superior to low-frequency or “tonic” SCS in SCS-naïve patients; more recently, there are some case series demonstrating that stimulation utilizing the D-Burst waveform can be used as salvage therapy for situations in which tonic SCS does not have sustained effect. 

A multicenter, retrospective, physician-directed study from seven independent pain practices nationwide evaluated 307 patients who were either experiencing treatment failure (i.e. less than 50% relief, unwanted stimulation or insufficient coverage) with their SCS (salvage subgroup) or those with greater than 50% relief with SCS but looking for increased pain relief (upgrade subgroup).  All 307 of these patients underwent conversion to burst stimulation either via surgical revision or software upgrade.  This corresponded to 127 patients who underwent conversion to D-Burst via surgical revision (93 salvage, 34 upgrade) and 180 via non-surgical revision (123 salvage, 57 upgrade).  Evaluation was made of numeric pain scores, amount of pain relief, and percentage of opioid dose reduction.  There were 13 reported diagnoses noted with “mixed” pain from different body regions as most common and failed back surgery syndrome and radiculopathy as second and third, respectively. Of the 127 patients who underwent surgical revision, 22 were switched from devices capable of high-frequency (10 kHz) and 21 had their entire system replaced. 

Results:  There were statistically significant reductions in both numeric rating scale scores and daily opioid use across all cohorts and subgroups.  The surgical revision group demonstrated a significant reduction in pain that was sustained for over 10 months.  Interestingly, there were no statistically significant differences between those who had both leads and implantable pulse generator (IPG) changed versus those who changed only IPG and used adaptors to preserve the previously-placed leads. 

Key points:  Implementing D-Burst stimulation may be an effective method to reduce loss of efficacy with SCS.  In addition, this indicates that failure of one type of SCS may not preclude the possibility of pain relief with other SCS modalities.










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