Newsletter

The Crisis of Drug Shortages in Regional Anesthesia and Analgesia

Jul 20, 2018

Edward R. Mariano, MD, MAS
drug shortage

The crisis of prescription opioid overuse and abuse has affected countries around the world, and anesthesiologists are well positioned to make positive changes.[1] Even minor outpatient surgical procedures and their associated anesthesia and analgesia techniques can lead to long-term opioid use.[2],[3] Patients who present for surgery with an active opioid prescription are very likely to still be on opioids after a year.[4]


“The new crisis of drug shortages threatens to reverse the many advancements in perioperative pain control.”


Anesthesiologists have been working to establish regional anesthesiology and acute pain medicine programs with careful coordination of inpatient and outpatient pain management to improve patient outcomes. Regional anesthesia, especially with continuous peripheral nerve block (CPNB) techniques, has been shown repeatedly to reduce patients' need for opioid analgesia.[5]

Today, the new crisis of drug shortages threatens to reverse our many advancements in perioperative pain control. Local anesthetics or numbing medications represent a class of drugs that is our strongest weapon against opioids. These drugs (eg, bupivacaine, lidocaine, ropivacaine) are currently in shortage.[6] Regional anesthesia with targeted injections of local anesthetic eliminates sensation at the site of surgery and can obviate the need for injectable opioids (eg, fentanyl, hydromorphone, morphine), which also happen to be in short supply.[6]

The following are potential ramifications of the current drug shortages affecting anesthesia and pain management on patient care.

Decreased Quality of Perioperative Pain Management

Peripheral nerve blocks (also referred to as “regional anesthesia techniques”) offer patients many potential advantages in the immediate postoperative period, including decreased pain, nausea and vomiting, and time spent in the recovery room.[7],[8] Long-acting local anesthetics (eg, bupivacaine, levobupivacaine, and ropivacaine) generally provide analgesia of similar duration for 24 hours or less.[9–12] The clinical effects of nerve blocks typically last long enough for patients to meet discharge eligibility from recovery and prevent unnecessary hospitalization for pain control.[13] A continuous peripheral nerve block (CPNB, also known as “perineural catheters”) permits delivery of local anesthetic solutions to the site of a peripheral nerve on an ongoing basis.[14] 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 infusion temporarily when patients feel too numb.[15],[16]

In a meta-analysis comparing CPNB to single-injection peripheral nerve blocks in humans, CPNB resulted in lower patient-reported worst pain scores and pain scores at rest on postoperative day (POD) 0, 1, and 2.[17] Patients who receive CPNB also experience less nausea, consume less opioids, sleep better, and are more satisfied with pain management.[17] By using local anesthetic medication to interrupt nerve transmission along peripheral nerves, patients continue to experience decreased sensation as long as the infusion is running.

A shortage of local anesthetic medications makes it impossible for anesthesiologists to provide this potent form of opioid-sparing pain control for all surgical patients. This also means that local anesthetics cannot be administered by surgeons as wound infiltration to help patients with incisional pain, and epidural analgesia for laboring women may not be universally available.

Increased Incidence of Postoperative Complications

Based on a study by Memtsoudis and colleagues,[18] overall 30-day mortality for total knee arthroplasty patients is lower for patients who receive regional anesthesia, either neuraxial and combined neuraxial–general anesthesia, compared to general anesthesia alone. In most categories, the rates of occurrence of in-hospital complications (eg, all-cause infections, pulmonary, cardiovascular, acute renal failure) were also lower for the neuraxial and combined neuraxial–general anesthesia groups combined with the general anesthesia-only group, and transfusion requirements were lowest for neuraxial anesthesia patients compared to all other groups.[18] That said, the inability to offer regional anesthesia (ie, spinal or epidural) to all patients because of lack of local anesthetics represents a threat to patient safety.

Increased Risk for Persistent Postsurgical Pain

Chronic pain may develop after many common operations, including breast surgery, hernia repair, thoracic surgery, and amputation, and is associated with severe acute pain in the postoperative period.[18] Researchers conducting a Cochrane systematic review and metaanalysis reviewed published studies on the subject, and the results favored epidural analgesia for prevention of persistent postsurgical pain (PPSP) after thoracotomy and favored paravertebral block for prevention of PPSP after breast cancer surgery at 6 months.[20] Only regional blockade with local anesthetics can block patients' sensation during and after surgery. Without local anesthetics for nerve blocks, spinals, and epidurals, patients will experience greater-than-expected acute pain, require additional opioid treatment, and are potentially at higher risk for developing chronic pain.

Increased Health Care Costs

Approximately 31% of costs related to inpatient perioperative care is attributable to the ward admission.[21] As perioperative physicians, anesthesiologists have an opportunity to influence the cost of surgical care by decreasing hospital length of stay through effective pain management and by developing coordinated, multidisciplinary clinical pathways.[22],[23] Regional anesthesia and analgesia can improve outcomes through integration into clinical pathways that involve a multipronged approach to streamlining surgical care.[24],[25] Inadequate pain control can delay rehabilitation, prolong hospital admissions, increase the rate of readmissions,[26] and increase the costs of hospitalization for surgical patients.

Addressing the Problem Of Drug Shortages

ASRA convened a late-breaking session on April 21, 2018, at the World Congress of Regional Anesthesia and Pain Medicine in New York City to address the continuing problem of analgesic drug shortages. Dr Jim Grant, president of the American Society of Anesthesiologists (ASA), returned to New York to participate in the live session. Other special guests included Paul Pomerantz, chief executive officer of ASA, and Dr Ruth Landau, first vice president of the Society for Obstetric Anesthesia and Perinatology (SOAP) and author of the SOAP Advisory in Response to Shortages of Local Anesthetics in North America.[27]

The meeting room was full of attendees representing academic and private practices from the United States, Canada, and Europe. Dr Grant opened with an update of ASA efforts to advocate for a long-term solution to drug shortages, specifically mentioning the lifting of production quotas through the Drug Enforcement Agency and decreasing delays at the Food and Drug Administration (FDA) in processing generic drug application approvals and imports of pharmaceuticals produced outside North America. He emphasized that this is ASA's number one priority. The present shortages have multiple contributing factors, but big ones included Pfizer's acquisition of Hospira[28] with subsequent closing of a major Hospira facility because of quality issues and the slow recovery of manufacturing facilities based in Puerto Rico. Dr Grant also pointed out important collaborators in this fight: the American Hospital Association, American Society of Health-System Pharmacists, American Association of Clinical Oncology, and Institute for Safe Medication Practices. In my research, I discovered a letter sent to the FDA specifically about local anesthetic shortages from multiple societies representing dentists, dermatologists, and head and neck surgeons.

ASA recently surveyed members[29] to gather stories about drug shortages affecting clinical care, receiving approximately 2,500 responses with 98% reporting personal experiences with drug shortages, and has now launched a new online registry that ASA members can use to report new and ongoing drug shortages affecting their practices.

Dr Landau shared Columbia University Medical Center's experience of managing shortages of hyperbaric 0.75% bupivacaine and other local anesthetic solutions since February 2018. She and the central hospital pharmacy stockpiled remaining 0.75% hyperbaric bupivacaine for emergency cesarean deliveries, and these cases have taken priority over all other surgical cases for access to hyperbaric bupivacaine. For other nonurgent cesarean deliveries, Dr. Landau and her team are using other preservative-free local anesthetic solutions as alternatives. Conservation strategies have included dividing large, single-use vials in the pharmacy under sterile conditions into multiple syringes good for 24 hours, which are delivered to labor and delivery and exchanged with new syringes daily. While implementing these local practice guidelines, Dr Landau spearheaded the SOAP Advisory with the SOAP Board of Directors, which is the first Societal statement to be released nationally, with careful consideration for potential liability and ongoing review and revision based on member feedback.[27]

The attendees, both residents and practicing anesthesiologists, were actively involved in the discussion with questions for Drs Grant and Landau, sharing their own experiences with managing ongoing drug shortages, which have been remarkably similar around the world. Examples of alternative dosing strategies and techniques, using other available medications, and improving communication between anesthesiology and pharmacy were presented. Dr Grant referred to this session as the “first real think tank” on this topic that he has participated in.

Key Take-Aways

Here are some take-home points raised by attendees that anesthesiologists facing analgesic drug shortages should consider:

  • Always have up-to-date information from your pharmacy department regarding inventory of local anesthetics and other medications affecting anesthesia care and perioperative pain management. One suggested best practice is to have a daily update (eg, conference call, e-mail, dashboard) on current drug shortages to facilitate communication between anesthesiology and pharmacy and among networked facilities within the same health system.
  • Avoid excessive medication waste. Identify opportunities for pharmacy to split commercially available large vials into multiple, single-dose syringes. Many single-use vials contain excessive amounts of medication. When done under proper sterile conditions, a pharmacy can divide those vials into syringes to decrease medication waste during a drug shortage crisis as well as save a significant amount of money.
  • Consider the ethics of practicing anesthesiology and surgery during this era of drug shortages. By their nature, anesthesiologists readily adapt to change, but a line has to be drawn somewhere. ASA has a statement on the ethical considerations with drug shortages that includes two key points:[30]
    • “Anesthesiologists, as well as surgeons and other proceduralists, should consider postponing an elective procedure when the risks of proceeding might outweigh the risks of using medications that are alternative to those in short supply or unavailable.”
    • “If the anesthesiologist judges the risk of increased morbidity or mortality by using alternative medications to be negligible, then there is no need to discuss this issue when obtaining informed consent. However, if the anesthesiologist judges the added risk to be significant, then the discussion of alternative plans should be part of the informed consent process.”
  • Keep working towards a longer-term solution to drug shortages through improvements in the supply chain. Some health systems have established partnerships with existing pharmaceutical manufacturers in an attempt to provide more stability in drug availability in the future. Recently a few major health systems have announced the creation of a new nonprofit generic drug company.[31]
  • Raise awareness in the community about the potential impact of analgesic drug shortages on quality and safety. If the general public is sufficiently concerned, legislators and regulators may be more likely to take action.

ASA is currently working on multiple levels in the United States government on behalf of patients and the anesthesiologists who care for them.[32] ASRA leaders will be working closely with ASA during this ongoing crisis to provide guidance to members on how to manage ongoing and ever-changing drug shortages and continue to provide the safest, high-quality care to patients.

References

  1. Alam A, Juurlink DN. The prescription opioid epidemic: an overview for anesthesiologists. Can J Anaesth. 2016;63:61–68.
  2. Sun EC, Darnall BD, Baker LC, Mackey S. Incidence of and risk factors for chronic opioid use among opioid-naive patients in the postoperative period. JAMA Intern Med. 2016;176:1286–1293.
  3. Rozet I, Nishio I, Robbertze R, Rotter D, Chansky H, Hernandez AV. Prolonged opioid use after knee arthroscopy in military veterans. Anesth Analg. 2014;119:454–459.
  4. Mudumbai SC, Oliva EM, Lewis ET, et al. Time-to-cessation of postoperative opioids: a population-level analysis of the Veterans Affairs Health Care System. Pain Med. 2016;17:1732–1743.
  5. Richman JM, Liu SS, Courpas G, et al. Does continuous peripheral nerve block provide superior pain control to opioids? A meta-analysis. Anesth Analg. 2006;102:248–257.
  6. Food and Drug Administration. Current and resolved drug shortages and discontinuations reported to FDA. Available at: https://www.accessdata.fda.gov/ scripts/drugshortages/default.cfm. Accessed June 10, 2018.
  7. 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;101:1634–1642.
  8. McCartney CJ, Brull R, Chan VW, et al. Early but no long-term benefit of regional compared with general anesthesia for ambulatory hand surgery. Anesthesiology. 2004;101:461–467.
  9. Casati A, Borghi B, Fanelli G, et al. A double-blinded, randomized comparison of either 0.5% levobupivacaine or 0.5% ropivacaine for sciatic nerve block. Anesth Analg. 2002;94:987–990.
  10. Hickey R, Hoffman J, Ramamurthy S. A comparison of ropivacaine 0.5% and bupivacaine 0.5% for brachial plexus block. Anesthesiology. 1991;74:639–642.
  11. Klein SM, Greengrass RA, Steele SM, et al. A comparison of 0.5% bupivacaine, 0.5% ropivacaine, and 0.75% ropivacaine for interscalene brachial plexus block. Anesth Analg. 1998;87:1316–1319.
  12. Fanelli G, Casati A, Beccaria P, et al. A double-blind comparison of ropivacaine, bupivacaine, and mepivacaine during sciatic and femoral nerve blockade. Anesth Analg. 1998;87:597–600.
  13. Williams BA, Kentor ML, Vogt MT, et al. 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;98:1206–1213.
  14. Ilfeld BM. Continuous peripheral nerve blocks: a review of the published evidence. Anesth Analg. 2011;113:904–925.
  15. Ilfeld BM. Continuous peripheral nerve blocks in the hospital and at home. Anesthesiol Clin. 2011;29:193–211.
  16. Ilfeld BM, Enneking FK. Continuous peripheral nerve blocks at home: a review. Anesth Analg. 2005;100:1822–1833.
  17. 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;37:583–594.
  18. Memtsoudis SG, Sun X, Chiu YL, et al. Perioperative comparative effectiveness of anesthetic technique in orthopedic patients. Anesthesiology. 2013;118:1046– 1058.
  19. Kehlet H, Jensen TS, Woolf CJ. Persistent postsurgical pain: risk factors and prevention. Lancet. 2006;367:1618–1625.
  20. Andreae MH, Andreae DA. Regional anaesthesia to prevent chronic pain after surgery: a Cochrane systematic review and meta-analysis. Br J Anaesth. 2013;111:711–720.
  21. Macario A, Vitez TS, Dunn B, McDonald T. Where are the costs in perioperative care? Analysis of hospital costs and charges for inpatient surgical care. Anesthesiology. 1995;83:1138–1144.
  22. Ilfeld BM, Mariano ER, Williams BA, Woodard JN, Macario A. Hospitalization costs of total knee arthroplasty with a continuous femoral nerve block provided only in the hospital versus on an ambulatory basis: a retrospective, case-control, costminimization analysis. Reg Anesth Pain Med. 2007;32:46–54.
  23. Jakobsen DH, Sonne E, Andreasen J, Kehlet H. Convalescence after colonic surgery with fast-track vs conventional care. Colorectal Dis. 2006;8:683–687.
  24. Macario A, Horne M, Goodman S, et al. The effect of a perioperative clinical pathway for knee replacement surgery on hospital costs. Anesth Analg. 1998;86:978–984.
  25. Hebl JR, Kopp SL, Ali MH, et al. A comprehensive anesthesia protocol that emphasizes peripheral nerve blockade for total knee and total hip arthroplasty. J Bone Joint Surg Am. 2005;87(suppl 2):63–70.
  26. Hernandez-Boussard T, Graham LA, Desai K, et al. The fifth vital sign: postoperative pain predicts 30-day readmissions and subsequent emergency department visits. Ann Surg. 2017;266:516–524.
  27. Society for Obstetric Anesthesia and Perinatology. Society for Obstetric Anesthesia and Perinatology (SOAP) advisory in response to shortages of local anesthetics in North America. Available at: https://soap.org/2018-bupivacaineshortage- statement.pdf. Accessed June 10, 2018.
  28. Temporary changes to aggregate production quotas for IV opioid products to address shortages. Available at: https://www.aha.org/system/files/2018- 02/180227-joint-letter-to-dea-re-apq-for-iv-opioids.pdf. Published February 27, 2018. Accessed June 10, 2018.
  29. American Society of Anesthesiologists. Anesthesia drug shortages negatively affecting patient care, American Society of Anesthesiologists (ASA) survey finds. Available at: http://asahq.org/about-asa/newsroom/news-releases/2018/04/ anesthesia-drug-shortages-negatively-affecting-patient-care. Published April 25, 2018. Accessed June 10, 2018.
  30. American Society of Anesthesiologists. Statement on the ethical considerations with drug shortages. Available at: http://www.asahq.org/∼/media/Sites/ ASAHQ/Files/Public/Resources/standards-guidelines/statement-on-the-ethicalconsiderations- with-drug-shortages.pdf. Published October 16, 2013. Accessed June 10, 2018.
  31. Dietsche E. Four health systems and VA plan to create nonprofit drug company. Available at: https://medcitynews.com/2018/02/four-health-systems-va-plancreate- nonprofit-drug-company. Published February 28, 2018. Accessed June 10, 2018.
  32. American Society of Anesthesiologists. Drug shortages. Available at: https:// www.asahq.org/advocacy/federal-activities/regulatory-activity/drug-shortages. Accessed June 10, 2018.
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