Tag Archives: pain management

Anesthesiology, Pain Medicine, Regional Anesthesiology

Resetting the Bar for Acute Perioperative Pain Management

Despite previously published guidelines and practice recommendations, there remains unwarranted variation in the quality of pain management provided to patients having surgery. Unwarranted variations in healthcare are inconsistencies in clinical practice that have no basis in science or patient preference.

In 2019, the U.S. Health and Human Services (HHS) Pain Management Best Practices Inter-Agency Task Force published its report, which called on medical societies to work together to develop evidence-based guidelines to improve the quality of pain care delivery. The Task Force, which was Chaired by Stanford anesthesiology and pain medicine specialist Dr. Vanila Singh when she was Chief Medical Officer of HSS, recommended individualized, multimodal, and multidisciplinary approaches to pain management to help decrease an over-reliance on opioids, increase access to care, and promote widespread education on pain and substance use disorders.

Following the release of this Task Force report, leaders of the American Society of Anesthesiologists (ASA) decided to take action and launched a 2-year project. As Chair of the ASA Committee on Regional Anesthesia and Pain Medicine, I participated as a member of the steering committee and served as Co-Chair of the Pain Summit. ASA invited 13 other medical societies to join a new consortium dedicated to improving pain management (in alphabetical order):

  • American Academy of Orthopaedic Surgeons
  • American Academy of Otolaryngology-Head and Neck Surgery
  • American Association of Neurological Surgeons
  • American Association of Oral and Maxillofacial Surgeons
  • American College of Obstetricians and Gynecologists
  • American College of Surgeons
  • American Hospital Association
  • American Medical Association
  • American Society of Breast Surgeons
  • American Society of Plastic Surgeons
  • American Society of Regional Anesthesia and Pain Medicine
  • American Urological Association
  • Society of Thoracic Surgeons

For its first initiative, the consortium agreed to focus on the pain care of the routine, non-complex (i.e., opioid-naïve) adult surgical patient. Over the course of several months, using Delphi methodology and culminating in the first live virtual Pain Summit involving all participating societies, this multiorganizational consensus process resulted in the establishment of 7 guiding principles for acute perioperative pain management.

Now published in Regional Anesthesia & Pain Medicine, these principles are intended to help healthcare systems and individual clinicians provide better care for patients having surgery. These principles include the need for preoperative evaluation of medical and psychological conditions and potential substance use disorders, a focus on multimodal analgesia including nonpharmacologic interventions, use of validated pain assessment tools to guide and adjust treatment, and the importance of individualized care and education, among others.

The final seven principles are:

  1. Clinicians should conduct a preoperative evaluation including assessment of medical and psychological conditions, concomitant medications, history of chronic pain, substance use disorder, and previous postoperative treatment regimens and responses, to guide the perioperative pain management plan.
  2. Clinicians should use a validated pain assessment tool to track responses to postoperative pain treatments and adjust treatment plans accordingly.
  3. Clinicians should offer multimodal analgesia, or the use of a variety of analgesic medications and techniques combined with nonpharmacological interventions, for the treatment of postoperative pain in adults.
  4. Clinicians should provide patient and family-centered, individually tailored education to the patient (and/or responsible caregiver), including information on treatment options for managing postoperative pain, and document the plan and goals for postoperative pain management.
  5. Clinicians should provide education to all patients (adult) and primary caregivers on the pain treatment plan, including proper storage and disposal of opioids and tapering of analgesics after hospital discharge.
  6. Clinicians should adjust the pain management plan based on adequacy of pain relief and presence of adverse events.
  7. Clinicians should have access to consultation with a pain specialist for patients who have inadequately controlled postoperative pain or are at high risk of inadequately controlled postoperative pain at their facilities (e.g., long-term opioid therapy, history of substance use disorder).

The formation of this consortium is a critical first step to widespread quality improvement in perioperative pain management for surgical patients across the country. The fact that 14 professional healthcare organizations could agree on these 7 principles means that the bar for acute perioperative pain management has been reset.

The work product of this consortium can now form the basis of all future guidelines and influence the products of legislation and regulation that affect pain management for surgical patients. There is still so much work to do, however, and this consortium is already looking at how to tailor these principles to more complex surgical populations, better assess barriers to change implementation, and provide each organization’s members with the tools they need to improve acute perioperative pain management where they are.

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Anesthesiology, Healthcare, Pain Medicine

7 Guiding Principles for Acute Perioperative Pain Management

I had the privilege of co-chairing the 2021 Pain Summit hosted by American Society of Anesthesiologists (ASA). In the months preceding the summit, ASA physician volunteers and staff as well as representatives from 14 other surgical specialty and healthcare organizations worked towards achieving consensus on a common set of principles to guide physicians and other clinicians who manage acute perioperative pain.

These 7 proposed principles are:

  1. Conduct a preoperative evaluation including assessment of medical and psychological conditions, concomitant medications, history of chronic pain, substance abuse disorder, and previous postoperative treatment regimens and responses, to guide the perioperative pain management plan.
  2. Use a validated pain assessment tool to track responses to postoperative pain treatments and adjust treatment plans accordingly.
  3. Offer multimodal analgesia, or the use of a variety of analgesic medications and techniques combined with nonpharmacological interventions, for the treatment of postoperative pain in adults.
  4. Provide patient and family-centered, individually tailored education to the patient (and/or responsible caregiver), including information on treatment options for managing postoperative pain, and document the plan and goals for postoperative pain management.
  5. Provide education to all patients (adult) and primary caregivers on the pain treatment plan, including proper storage and disposal of opioids and tapering of analgesics after hospital discharge.
  6. Adjust the pain management plan based on adequacy of pain relief and presence of adverse events.
  7. Have access to consultation with a pain specialist for patients who have inadequately controlled postoperative pain or at high risk of inadequately controlled postoperative pain at their facilities (e.g., long-term opioid therapy, history of substance use disorder).

This is the first project from this new collaborative, which focused on the adult surgical patient, and there are already plans for future projects. The participating organizations are:

  • American Academy of Orthopaedic Surgeons
  • American Academy of Otolaryngology-Head and Neck Surgery
  • American Association of Neurological Surgeons
  • American Association of Oral and Maxillofacial Surgeons
  • American College of Obstetricians and Gynecologists
  • American College of Surgeons
  • American Hospital Association
  • American Medical Association
  • American Society of Breast Surgeons
  • American Society of Plastic Surgeons
  • American Society of Regional Anesthesia and Pain Medicine
  • American Urological Association
  • Society of Thoracic Surgeons

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Anesthesiology, COVID-19, Healthcare, Pain Medicine, Patient Safety, Regional Anesthesiology

We Still Have an Opioid Epidemic

COVID-19 has changed every aspect of our personal and professional lives.

In the midst of this pandemic, we still have an opioid epidemic. It is not one thing unfortunately, and the Centers for Disease Control and Prevention (CDC) describe three distinct waves of opioid-related overdose deaths.

Centers for Disease Control and Prevention

Given the complexity of the opioid epidemic, we have to keep working within our spheres of influence. For those of us in anesthesiology, that means focusing on surgical patients: improving their outcomes and providing effective perioperative pain management along with opioid stewardship.

Dr. Chad Brummett and his colleagues at Michigan OPEN have been leading the way in procedure-specific opioid prescribing recommendations. Their process, which takes into account data from the Collaborative Quality Initiative (CQI), published studies, and expert input, specifically focuses on the perioperative care of patients who are not taking any opioids prior to surgery.

Continue reading We Still Have an Opioid Epidemic →

Through multimodal analgesia, we prevent and treat pain in a variety of ways without depending solely on opioids.

At our institution, we offer patients regional anesthesia and have been able to decrease the amount of opioid pills that patients are given when they leave the hospital by basing the prescription on how much they use the prior day. Patients participate in this process, and we give them clear instructions on how to safety taper their opioids at home.

As a representative of the American Society of Anesthesiologists (ASA), I have been able to collaborate with surgical societies such as the American Society of Breast Surgeons and the American Academy of Orthopaedic Surgeons to develop pain management recommendations and toolkits that emphasize multimodal analgesia, use of regional anesthesia techniques for targeted non-opioid pain management when it is available, and opioid safety in the hospital and at home.

ASA-AAOS Pain Alleviation Toolkit

I also represent ASA as a member of the National Academy of Medicine (NAM) Action Collaborative Countering the U.S. Opioid Epidemic. The first discussion paper from the NAM pain management workgroup was released on Aug 10: Best Practices, Research Gaps, and Future Priorities to Support Tapering Patients on Long-Term Opioid Therapy for Chronic Non-Cancer Pain in Outpatient Settings. This paper highlights best practices in opioid tapering and identifies evidence gaps to drive future research.

Despite the massive amount of resources, human effort, and time dedicated to the fight against COVID-19, we have still managed to make progress in decreasing opioid-related risk in the perioperative period. However, there is still a lot of work left to do, and our patients are depending on us.

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Anesthesiology, Healthcare, Leadership, News, Pain Medicine, Patient Safety, Regional Anesthesiology

My Trip to Washington: Speaking Out Against Drug Shortages

UPDATE: The MEDS Act was incorporated into the Coronavirus Aid, Relief, and Economic Security (CARES) Act and passed into law on March 27, 2020. I commented on the COVID-19 pandemic’s exacerbation of ongoing drug shortages in this interview with CBS news.

On November 5, 2019, I had the opportunity to participate in a Congressional briefing related to drug shortages at the Capitol in Washington, DC. Senator Susan Collins (R-ME) opened the session and co-sponsored the Mitigating Emergency Drug Shortages (MEDS) Act with Senator Tina Smith (D-MN). I was one of only two physicians on the panel and tried to represent the voice of clinicians involved in perioperative care and the patients we care for (video). Below are the notes from my presentation.

As a physician specializing in anesthesiology, this ongoing crisis of drug shortages in the United States is frankly terrifying.

Continue reading My Trip to Washington: Speaking Out Against Drug Shortages →

Anesthesiology is a unique specialty within medicine. Our patients are the most vulnerable in the hospital. Patients under general anesthesia cannot advocate for themselves and trust us with their lives.

We do not know what the next drug shortage will be or how long it will last. This week it is prefilled syringes of lidocaine, a life-saving emergency medication we give in case of a dangerous heart rhythm. Two weeks ago it was phenylephrine, a routine medication we use to increase blood pressure when it goes down after inducing anesthesia.

Last year, we had complete shortages of common injectable opioids and local anesthetics used for numbing injections. This directly affected surgical patients in terms of anesthesia and pain management. For 3 months in 2018, we did not have the local anesthetic indicated for spinal anesthesia. We know this is the safest anesthetic for patients having certain surgeries. During this shortage, we used an alternative anesthetic in order to continue providing spinal anesthesia, but our patients experienced more side effects. The reasons for this shortage were complex and involved a limited number of manufacturers and quality issues.

Thankfully, the shortage of spinal local anesthetic ended. We do not know when or if the rest of our current drug shortages will end. All we know for sure is that there will be another one.

The predictably unpredictable cycle of drug shortages puts physicians in an impossible position. Medicine is a calling, and we physicians have sworn an oath to support the well-being of our community and humanity in general.

Not having access to the right drugs at the right time for every patient and being forced to use less acceptable alternatives, if any exist at all, represents a form of moral injury. Moral injury “is being unable to provide high-quality care and healing in the context of health care” and is now recognized as a contributor to the epidemic of physician burnout.

Listen to my interview with Paul Costello on SoundCloud.

From left to right: Daniel Teich (Fairview Pharmacy Services), Dr. Peter Adamson (Children’s Hospital of Philadelphia), Senator Susan Collins, me, and Brian Marden (MaineHealth Pharmacy)

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Anesthesiology, Medical Education, Pain Medicine, Regional Anesthesiology

Extending Nerve Block Pain Relief after Surgery: Review of the Evidence

nerve firingNerve blocks (also referred to as “regional anesthesia”) offer patients many potential advantages in the immediate postoperative period such as decreased pain, nausea and vomiting, and time spent in the recovery room (1,2). However, these beneficial effects are time-limited and do not last beyond the duration of the block (2). While the clinical effects of nerve blocks typically last long enough for patients to meet discharge eligibility from recovery and avoid hospitalization for pain control (3), these results can be easily negated if patients’ pain or opioid-related side effects warrant a return trip to the hospital and readmission following block resolution (4). Thus, extending block duration to provide longer-term, site-specific analgesia for patients on an ambulatory basis has been a high research priority. What options are currently available?

Continuous Peripheral Nerve Blocks

Continuous peripheral nerve block (CPNB) techniques (also known as perineural catheters) permit delivery of local anesthetic solutions to the site of a peripheral nerve on an ongoing basis (5). Portable infusion devices can deliver a solution of plain local anesthetic for days after surgery, often with the ability to titrate the dose up and down or even stop the infusion temporarily when patients feel too numb (6,7). In a meta-analysis comparing CPNB to single-injection peripheral nerve blocks, CPNB results in lower patient-reported worst pain scores and pain scores at rest on postoperative day (POD) 0, 1, and 2 (8). Patients who receive CPNB also experience less nausea, consume less opioids, sleep better, and are more satisfied with pain management (8). We also know how CPNB works: local anesthetic medication interrupts nerve transmission, so patients experience decreased sensation.

Managing CPNB patients (especially at home) can sometimes be challenging, and not all patients are good candidates for outpatient perineural infusion (7). Patients must have a reliable means of follow-up and should have a caretaker at home for at least the first night after surgery (7). A health care provider must be available at all times to manage common issues associated with CPNB and call patients once daily to assess for analgesic efficacy and side effects (9). Patients, especially those undergoing lower extremity surgery, and their caretakers should receive clear instructions regarding the care of their infusion device and catheter as well as their anesthetized extremities (10,11) including fall precautions (12,13).

Although the optimal duration for CPNB is unknown, 2 to 7 days has been reported for orthopedic inpatients (14) with durations as long as 34 days under special circumstances (15). At the completion of the local anesthetic infusion, perineural catheters must be removed. To date, CPNB is the only technique that offers patients the longest potential duration of block paired with the ability to titrate to the desired level of block.

Despite more than a decade of published data supporting CPNB for extending the duration of postoperative pain control, adoption of these techniques is not universal. Many of the issues are arguably system-based, and the lack of a “block” room (16) or time pressure (17) may be responsible. However, lack of training in these techniques may also be a factor (18) or negative experiences with failed placement attempts using traditional techniques (19).

Adjuvants to Local Anesthetic Solutions for Single-Injection Peripheral Nerve Blocks

For nerve blocks intended to last 1-2 days, there are a few options.  Long-acting local anesthetics (e.g., bupivacaine, levobupivacaine, and ropivacaine) generally provide analgesia of similar duration for 24 hours or less (20-23). Several different drugs have been investigated for their potential to extend single-injection peripheral nerve block duration when added to local anesthetic solutions. Epinephrine when added to local anesthetic solutions provides vasoconstriction to decrease uptake but has little or no clinical effect on the duration of longer-acting local anesthetics (24). Opioids in general do not provide additional benefits in terms of duration (25) except for buprenorphine (26) although how it works is unclear. To date, there are insufficient data to support the addition of tramadol or neostigmine to local anesthetic solutions (25). Of the available adjuvants, clonidine has been demonstrated in clinical studies and systematic reviews to extend the duration of analgesia for intermediate-acting local anesthetics (e.g., mepivacaine) with few side effects in doses up to 150 mcg but probably do not extend long-acting local anesthetics (25,27). There has been increasing interest in dexamethasone as an adjuvant to local anesthetic solutions based on clinical reports of extended duration when added to intermediate-acting local anesthetics (28,29). The mechanism is not well understood and may be less pronounced with long-acting local anesthetics; one study reported block durations of only 22 hours with dexamethasone added to either ropivacaine or bupivacaine (30). Giving dexamethasone intravenously may actually produce the same effect (31). Caution is warranted when experimenting with adjuvant mixtures that have not been specifically approved for nerve blocks (i.e., “off-label” use) as many of the usual FDA safeguards have not been performed, and these drugs may contribute to neurotoxicity or other side effects not yet known.

Novel Extended-Duration Local Anesthetics

There has been interest in liposomal formulations of extended-release bupivacaine for regional anesthesia for over two decades (32,33). A recent formulation consisting of bupivacaine encapsulated in multivesicular liposomes to produce slow release is FDA-approved for local infiltration (34) but not yet for nerve blocks although this is expected soon. A nerve block with liposomal bupivacaine can be expected to last 1-3 days. Initial nerve block studies in animals suggest a lower maximum serum concentration with the liposomal formulation compared to plain bupivacaine (35)–unless co-administered with lidocaine which facilitates release of liposomal bupivacaine (36)–and epidural administration in human volunteers more than doubles duration of sensory block (37). Once it receives FDA approval, I expect many comparative studies versus CPNB for postoperative analgesia. There are still concerns regarding local anesthetic systemic toxicity with liposomal bupivacaine as well as prolonged motor block and unpleasant numbness given the drug’s long-lasting effects. In addition, there is no option for “giving more” to augment a block in the event of inadequate pain relief.

In summary, there are currently few options to extend the duration of regional analgesia at home beyond the one day expected from most single-injection nerve blocks. CPNB with plain local anesthetic perineural infusion is the most established way to provide days of postoperative pain control and allows titration, but training in insertion techniques and a system to manage ambulatory CPNB patients are necessary. Adjuvants or liposomal formulations of local anesthetics may offer potential options for limited extension of block duration, but further studies regarding efficacy and safety for regional anesthesia as well as comparative-effectiveness versus CPNB are necessary. For major surgery like total knee replacement, block duration of several days may be optimal (38).

References

  1. Liu SS, Strodtbeck WM, Richman JM, Wu CL: A comparison of regional versus general anesthesia for ambulatory anesthesia: a meta-analysis of randomized controlled trials. Anesth Analg 2005; 101: 1634-42
  2. McCartney CJ, Brull R, Chan VW, Katz J, Abbas S, Graham B, Nova H, Rawson R, Anastakis DJ, von Schroeder H: Early but no long-term benefit of regional compared with general anesthesia for ambulatory hand surgery. Anesthesiology 2004; 101: 461-7
  3. Williams BA, Kentor ML, Vogt MT, Williams JP, Chelly JE, Valalik S, Harner CD, Fu FH: Femoral-sciatic nerve blocks for complex outpatient knee surgery are associated with less postoperative pain before same-day discharge: a review of 1,200 consecutive cases from the period 1996-1999. Anesthesiology 2003; 98: 1206-13
  4. Williams BA, Kentor ML, Vogt MT, Vogt WB, Coley KC, Williams JP, Roberts MS, Chelly JE, Harner CD, Fu FH: Economics of nerve block pain management after anterior cruciate ligament reconstruction: potential hospital cost savings via associated postanesthesia care unit bypass and same-day discharge. Anesthesiology 2004; 100: 697-706
  5. Ilfeld BM: Continuous peripheral nerve blocks: a review of the published evidence. Anesth Analg 2011; 113: 904-25
  6. Ilfeld BM: Continuous peripheral nerve blocks in the hospital and at home. Anesthesiol Clin 2011; 29: 193-211
  7. Ilfeld BM, Enneking FK: Continuous peripheral nerve blocks at home: a review. Anesth Analg 2005; 100: 1822-33
  8. Bingham AE, Fu R, Horn JL, Abrahams MS: Continuous peripheral nerve block compared with single-injection peripheral nerve block: a systematic review and meta-analysis of randomized controlled trials. Reg Anesth Pain Med 2012; 37: 583-94
  9. Ilfeld BM, Esener DE, Morey TE, Enneking FK: Ambulatory perineural infusion: the patients’ perspective. Reg Anesth Pain Med 2003; 28: 418-23
  10. Charous MT, Madison SJ, Suresh PJ, Sandhu NS, Loland VJ, Mariano ER, Donohue MC, Dutton PH, Ferguson EJ, Ilfeld BM: Continuous femoral nerve blocks: varying local anesthetic delivery method (bolus versus basal) to minimize quadriceps motor block while maintaining sensory block. Anesthesiology 2011; 115: 774-81
  11. Ilfeld BM, Moeller LK, Mariano ER, Loland VJ, Stevens-Lapsley JE, Fleisher AS, Girard PJ, Donohue MC, Ferguson EJ, Ball ST: Continuous peripheral nerve blocks: is local anesthetic dose the only factor, or do concentration and volume influence infusion effects as well? Anesthesiology 2010; 112: 347-54
  12. Feibel RJ, Dervin GF, Kim PR, Beaule PE: Major complications associated with femoral nerve catheters for knee arthroplasty: a word of caution. J Arthroplasty 2009; 24: 132-7
  13. Ilfeld BM, Duke KB, Donohue MC: The association between lower extremity continuous peripheral nerve blocks and patient falls after knee and hip arthroplasty. Anesth Analg 2010; 111: 1552-4
  14. Capdevila X, Pirat P, Bringuier S, Gaertner E, Singelyn F, Bernard N, Choquet O, Bouaziz H, Bonnet F: Continuous peripheral nerve blocks in hospital wards after orthopedic surgery: a multicenter prospective analysis of the quality of postoperative analgesia and complications in 1,416 patients. Anesthesiology 2005; 103: 1035-45
  15. Stojadinovic A, Auton A, Peoples GE, McKnight GM, Shields C, Croll SM, Bleckner LL, Winkley J, Maniscalco-Theberge ME, Buckenmaier CC, 3rd: Responding to challenges in modern combat casualty care: innovative use of advanced regional anesthesia. Pain Med 2006; 7: 330-8
  16. Mariano ER, Chu LF, Peinado CR, Mazzei WJ: Anesthesia-controlled time and turnover time for ambulatory upper extremity surgery performed with regional versus general anesthesia. J Clin Anesth 2009; 21: 253-7
  17. Oldman M, McCartney CJ, Leung A, Rawson R, Perlas A, Gadsden J, Chan VW: A survey of orthopedic surgeons’ attitudes and knowledge regarding regional anesthesia. Anesth Analg 2004; 98: 1486-90, table of contents
  18. Hadzic A, Vloka JD, Kuroda MM, Koorn R, Birnbach DJ: The practice of peripheral nerve blocks in the United States: a national survey [p2e comments]. Reg Anesth Pain Med 1998; 23: 241-6
  19. Salinas FV: Location, location, location: Continuous peripheral nerve blocks and stimulating catheters. Reg Anesth Pain Med 2003; 28: 79-82
  20. Casati A, Borghi B, Fanelli G, Cerchierini E, Santorsola R, Sassoli V, Grispigni C, Torri G: A double-blinded, randomized comparison of either 0.5% levobupivacaine or 0.5% ropivacaine for sciatic nerve block. Anesth Analg 2002; 94: 987-90
  21. Hickey R, Hoffman J, Ramamurthy S: A comparison of ropivacaine 0.5% and bupivacaine 0.5% for brachial plexus block. Anesthesiology 1991; 74: 639-42
  22. Klein SM, Greengrass RA, Steele SM, D’Ercole FJ, Speer KP, Gleason DH, DeLong ER, Warner DS: A comparison of 0.5% bupivacaine, 0.5% ropivacaine, and 0.75% ropivacaine for interscalene brachial plexus block. Anesth Analg 1998; 87: 1316-9
  23. Fanelli G, Casati A, Beccaria P, Aldegheri G, Berti M, Tarantino F, Torri G: A double-blind comparison of ropivacaine, bupivacaine, and mepivacaine during sciatic and femoral nerve blockade. Anesth Analg 1998; 87: 597-600
  24. Weber A, Fournier R, Van Gessel E, Riand N, Gamulin Z: Epinephrine does not prolong the analgesia of 20 mL ropivacaine 0.5% or 0.2% in a femoral three-in-one block. Anesth Analg 2001; 93: 1327-31
  25. Murphy DB, McCartney CJ, Chan VW: Novel analgesic adjuncts for brachial plexus block: a systematic review. Anesth Analg 2000; 90: 1122-8
  26. Candido KD, Franco CD, Khan MA, Winnie AP, Raja DS: Buprenorphine added to the local anesthetic for brachial plexus block to provide postoperative analgesia in outpatients. Reg Anesth Pain Med 2001; 26: 352-6
  27. McCartney CJ, Duggan E, Apatu E: Should we add clonidine to local anesthetic for peripheral nerve blockade? A qualitative systematic review of the literature. Reg Anesth Pain Med 2007; 32: 330-8
  28. Movafegh A, Razazian M, Hajimaohamadi F, Meysamie A: Dexamethasone added to lidocaine prolongs axillary brachial plexus blockade. Anesth Analg 2006; 102: 263-7
  29. Parrington SJ, O’Donnell D, Chan VW, Brown-Shreves D, Subramanyam R, Qu M, Brull R: Dexamethasone added to mepivacaine prolongs the duration of analgesia after supraclavicular brachial plexus blockade. Reg Anesth Pain Med 2010; 35: 422-6
  30. Cummings KC, 3rd, Napierkowski DE, Parra-Sanchez I, Kurz A, Dalton JE, Brems JJ, Sessler DI: Effect of dexamethasone on the duration of interscalene nerve blocks with ropivacaine or bupivacaine. Br J Anaesth 2011; 107: 446-53
  31. Desmet M, Braems H, Reynvoet M, et al: I.V. and perineural dexamethasone are equivalent in increasing the analgesic duration of a single-shot interscalene block with ropivacaine for shoulder surgery: a prospective, randomized, placebo-controlled study. Br J Anaesth 2013; 111: 445-52
  32. Boogaerts J, Lafont N, Donnay M, Luo H, Legros FJ: Motor blockade and absence of local nerve toxicity induced by liposomal bupivacaine injected into the brachial plexus of rabbits. Acta Anaesthesiol Belg 1995; 46: 19-24
  33. Boogaerts JG, Lafont ND, Declercq AG, Luo HC, Gravet ET, Bianchi JA, Legros FJ: Epidural administration of liposome-associated bupivacaine for the management of postsurgical pain: a first study. J Clin Anesth 1994; 6: 315-20
  34. Chahar P, Cummings KC, 3rd: Liposomal bupivacaine: a review of a new bupivacaine formulation. J Pain Res 2012; 5: 257-64
  35. Richard BM, Newton P, Ott LR, Haan D, Brubaker AN, Cole PI, Ross PE, Rebelatto MC, Nelson KG: The Safety of EXPAREL (R) (Bupivacaine Liposome Injectable Suspension) Administered by Peripheral Nerve Block in Rabbits and Dogs. J Drug Deliv 2012; 2012: 962101
  36. Richard BM, Rickert DE, Doolittle D, Mize A, Liu J, Lawson CF: Pharmacokinetic Compatibility Study of Lidocaine with EXPAREL in Yucatan Miniature Pigs. ISRN Pharm 2011; 2011: 582351
  37. Viscusi ER, Candiotti KA, Onel E, Morren M, Ludbrook GL: The pharmacokinetics and pharmacodynamics of liposome bupivacaine administered via a single epidural injection to healthy volunteers. Reg Anesth Pain Med 2012; 37: 616-22
  38. Lavand’homme PM, Grosu I, France MN, Thienpont E: Pain trajectories identify patients at risk of persistent pain after knee arthroplasty: an observational study. Clin Orthop Relat Res 2014; 472: 1409-15.

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