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Statement on Neuraxial Medication Shortage and Alternatives

Developed by: Committee on Obstetrics
Original Approval: October 18, 2023

Drug shortages have been common for over a decade, exacerbated by the COVID-19 pandemic, reaching an all-time peak in 2022.  By the end of 2022, a US Senate report indicates new drug shortages increased by almost 30%, with the average drug shortage lasting 1.5 years, with many critical drug products having been in shortage for over a decade.1  The Food and Drug Administration (FDA) lists common anesthetics among the medications most affected by shortages. 

Neuraxial medications commonly used in obstetric anesthesia have also been greatly affected, including local anesthetics (lidocaine and bupivacaine) that have had shortages for over 10 years, as well as opioids used for pain control during labor, cesarean delivery, and for post-operative pain relief.  The American Society of Anesthesiologists (ASA) has remained engaged on drug shortages for several years.2  Drug shortages create significant patient safety concerns, including possible medication errors.3  The American Society of Health System Pharmacists (ASHP) has guidelines on managing shortages that include planning ahead.4 

Anesthesiologists, particularly in obstetric anesthesia, have been forced to use alternative neuraxial medications for their patients, which may be less effective and/or less familiar to them, thus increasing the potential for medication errors.3 Below are detailed tables for relative equivalence/alternatives to the most commonly used medications in obstetric anesthesiology that are, or have been, on the drug shortage list. While these choices are supported by the scientific literature, note that many commonly administered neuraxial medications may or may not have specific FDA approval for such indications. Thus, administration of any medication is the sole decision of the individual practitioner. 

The ASA continues to work with the FDA and other organizations on anesthetic drug shortages. Other information listing current drug shortages can be found at the ASHP5 website  as well as the FDA website.6  Individuals may report drug shortages at [email protected]. 

  1. United States Senate Committee on Homeland Security & Governmental Affairs Majority Staff Report on Short Supply https://www.hsgac.senate.gov/wp-content/uploads/Drug-Shortages-HSGAC-Majority-Staff-Report-2023-03-22.pdf
  2. https://www.asahq.org/advocacy-and-asapac/advocacy-topics/drug-shortages
  3. https://www.apsf.org/article/drug-shortages-in-the-u-s-a-balanced-perspective/
  4. American Society of Health-System Pharmacists. ASHP guidelines on managing drug product shortages. Am J Health-Syst Pharm. 2018; 75:1742-50.
  5. https://www.ashp.org/drug-shortages/current-shortages/drug-shortages-list
  6. https://www.fda.gov/drugs/drug-safety-and-availability/drug-shortages

References:

  1. Chestnut DH, Bates JN, Choi WW. Continuous infusion epidural analgesia with lidocaine: efficacy and influence during the second stage of labor. Obstet Gynecol 1987; 69:323 – 27.
  2. Coffman JC, Bruner KL, Small RH. Is low concentration 2-chloroprocaine for epidural labor analgesia a better option? AA Practice 2018; 10:95.
  3. Lee SL, Moll V. Continuous epidural analgesia using an ester-linked local anesthetic agent, 2-chloroprocaine, during labor: a case report. AA Case Report 2017; 8:297 – 99.
  4. Kamath A, Raghove V, Kalstein A, Yarman J. Labor epidural in a patient who is allergic to lidocaine: A case series. Local Reg Anesth 2021; 14:21 – 23.
  5. Carvalho B, Durbin M, Drover DR et al. The ED50 and ED95 of intrathecal isobaric bupivacaine with opioids for cesarean delivery. Anesthesiology 2005; 103:606 – 12.
  6. Sng BL, Siddiqui FJ, Leong WL et al. Hyperbaric versus isobaric bupivacaine for spinal anaesthesia for caesarean section. Cochrane Database Syst Rev 2016; 9:CD005143.
  7. Reschke MM, Monks DT, Varaday SS, Ginosar Y, Palanisamy A, Singh PM. Choice of local anaesthetic for epidural caesarean section: a Bayesian network meta-analysis. Anaesthesia 2020; 75:674–682.
  8. El-Boghdadly K, Pawa A, Chin KJ. Local anesthetic systemic toxicity: current perspectives. Local Reg Anesth. 2018 Aug 8;11:35-44.
  9. Maes S, Laubach M, Poelaert J. Randomised controlled trial of spinal anaesthesia with bupivacaine or 2-chloroprocaine during caesarean section. Acta Anaesthesiol Scand 2016;  60:642 – 49.
     
 
Table 5

References:

  1. George RB, Carvalho B, Butwick A, Flood P. Postoperative Analgesia. In Chestnut’s Obstetric Anesthesia Principles and Practice, 6th edition. Pgs. 635-49.
  2. Herman NL, Sheu KL, Van Decar TK, et al. Determination of the analgesic dose response relationship for epidural fentanyl and sufentanil with bupivacaine 0.125% in laboring patients. J Clin Anesth 1998;10:670-77.
  3. Yau G, Gregory MA, Gin T, et al. The addition of fentanyl to epidural bupivacaine in the first stage of labour. Anaesth Intensive Care, 1990;18:532-35.
  4. Grass JA, Sakima NT, Schmidt R, et al. A randomized, double-blind, dose-response comparison of epidural fentanyl versus sufentanil analgesia after cesarean section. Anesth Analg 1997;85:365-71.
  5. Bauchat JR, Weiniger CR, Sultan P. Society for Obstetric Anesthesia and Perinatology Consensus Statement: Monitoring Recommendations for Prevention and Detection of Respiratory Depression Associated With Administration of Neuraxial Morphine for Cesarean Delivery Analgesia. Anesth Analg 2019;129(2):458-74.
  6. Fuller JG, McMorland GH, Douglas MJ, Palmer L. Epidural morphine for analgesia after cesarean section: a report of 4880 patients. Can J Anaesth 1990;37:636-40.
  7. Chestnut DH, Choi WW, Isbell TJ. Epidural hydromorphone for postcesarean analgesia. Obstet Gynecol 1986;68:65-69.
  8. Halpern SH, Arellano R, Preston R et al. Epidural morphine vs. hydromorphone in post- cesarean section patients. Can J Anaesth 1996;43:595-98.
  9. Ngan Kee WD, Lam KK, Chen PP, Gin T. Epidural meperidine after cesarean section. A dose-response study. Anesthesiology 1996;85:289-94.
  10. James P. Rathmell, MD, Timothy R. Lair, MD, and Bushra Nauman. The Role of Intrathecal Drugs in the Treatment of Acute Pain. Anesth Analg 2005;101:S30–S43.
  11. Wong CA, Scavone BM, Slavenas JP, et al. Efficacy and side effect profile of varying doses of intrathecal fentanyl added to bupivacaine for labor analgesia. Int J Obstet Anesth 2004;13:19-24.
  12. Palmer CM, Cork RC, Hays R, et al. The dose-response relation of intrathecal fentanyl for labor analgesia. Anesthesiology 1998;88:355-61. 
  13. Dahlgren G, Hulstrand C, Jakobsson J, et al. Intrathecal sufentanil, fentanyl or placebo added to bupivacaine for cesarean section. Anesth Analg 1997;85:1288-93.
  14. Wilwerth M, Majcher JL, Van der Linden P. Spinal fentanyl vs. sufentanil for post-operative analgesia after c-section: a double-blinded randomized trial. Acta Anaesthesiol Scand 2016;60:1306-13.
  15. Sultan P, Halpern SH, Pushpanathan  E, Patel S, Carvalho B. The Effect of Intrathecal Morphine Dose on Outcomes After Elective Cesarean Delivery: A Meta-Analysis. Anesth Analg 2016;123(1):154-64.
  16. Berger JS, Gonzalez A, Hopkins A, et al. Dose-response of intrathecal morphine when administered with intravenous ketorolac for post-cesarean analgesia: a two-center, prospective, randomized, blinded trial. Int J Obstet Anesth 2016;28:3-11.
  17. Wong JY, Carvalho B, Riley ET. Intrathecal morphine 100 and 200 µg for post-cesarean delivery analgesia: a trade-off between analgesic efficacy and side effects. Int J Obstet Anesth 2013:22:36-41.
  18. Wong CA, Scavone BM, Loffredi M, et al. The dose-response of intrathecal sufentanil added to bupivacaine for labor analgesia. Anesthesiology 2000;92:1553-58.
  19. Honet JE, Arkoosh VA, Norris MC, et al. Comparison among intrathecal fentanyl, meperidine and sufentanil for labor analgesia. Anesth Analg 1992;75:734-39.
  20. Yu SC, Ngan Kee WD, Kwan AS. Addition of meperidine to bupivacaine for spinal anesthesia for cesarean section. Br J Anaesth 2002;88:379-83.
  21. Sharpe EE, Molitor RJ, Arendt KW, et al. Intrathecal Morphine versus Intrathecal Hydromorphone for Analgesia after Cesarean Delivery: A Randomized Clinical Trial. Anesthesiology 2020 Jun;132(6):1382-1391.
  22. Sviggum HP, Arendt KW, Jacob AK. Intrathecal Hydromorphone and Morphine for Postcesarean Delivery Analgesia: Determination of the ED90 Using a Sequential Allocation Biased-Coin Method. Anesth Analg 2016;123(3):690-97.
  23. Marroquin B, Feng C, Balofsky A. Neuraxial opioids for post-cesarean delivery analgesia: can hydromorphone replace morphine? A retrospective study. IJOA 2017;30:16-22.
  24. O'Reilly-Shah V,  Lynde  GC. Determination of ED50 and time to effectiveness for intrathecal hydromorphone in laboring patients using Dixon's up-and-down sequential allocation method. BMC Anesthesiol 2018 Oct 5;18(1):140.

References:

  1. Eisenach JC, Grice SC, Dewan DM. Epinephrine enhances analgesia produced by epidural bupivacaine during labor. Anesth Analg. 1987;66:447-451.
  2. Geerinckx K, Vanderrick G, Van Steenberge AL, Bouche R, De Muylder E. Bupivacaine 0.125% in epidural block analgesia during childbirth: Maternal and foetal plasma concentrations. Br J Anaesth. 1974;46:937-941.
  3. Craft Jr. JB, Epstein BS, Coakley CS. Effect of lidocaine with epinephrine versus lidocaine (plain) on induced labor. Anesth Analg. 1972;51(2):243-246.
  4. Bleyaert A, Soetens M, Vaes L, Van Steenberge AL, Van der Donck A. Bupivacaine, 0.125 percent, in obstetric epidural analgesia: experience in three thousand cases. Anesthesiology. 1979;51(5):435-438.
  5. Sakura S, Sumi M, Morimoto N, Saito Y. The addition of epinephrine increases intensity of sensory block during epidural anesthesia with lidocaine. Reg Anesth Pain Med. 1999;24(6):541-546.
  6. Brose WG, Cohen SE. Epidural lidocaine for cesarean section: Effect of varying epinephrine concentration. Anesthesiology. 1988;69:936-940.
  7. Gurbet A, Turker G, Kose DO, Uckunkaya N. Intrathecal epinephrine in combined spinal-epidural analgesia for labor: dose-response relationship for epinephrine added to a local anesthetic-opioid combination. Int J Obstet Anesth. 2005;14(2):121-125.
  8. Katz D, Hamburger J, Gutman D, Wang R, Lin HM, Marotta M, et al. The effect of adding subarachnoid epinephrine to hyperbaric bupivacaine and morphine for repeat cesarean delivery: A double-blind prospective randomized control trial. Anesth Analg. 2018;127(1):171-178.
  9. Abouleish EI. Epinephrine improves the quality of spinal hyperbaric bupivacaine for cesarean section. Anesth Analg. 1987;66:395-400.
  10. Galante D. Adjuvant drugs in labor anaglesia. BJA. 2010;105. https://doi.org/10.1093/bja/el_5571
  11. Syal K, Dogra RK, Ohri A, Chauhan G, Goel A. Epidural labour analgesia using bupivacaine and clonidine. J Anaesthesiol Clin Pharmacol. 2011;27(1):87-90.
  12. Roelants F, Lavand'homme PM, Mercier-Fuzier VM. Epidural administration of neostigmine and clonidine to induce labor analgesia: Evaluation of efficacy and local anesthetic-sparing effect. Anesthesiology. 2005;102:1205-1210.
  13. Lee A, Landau R, Lavin T, Goodman S, Menon P, Smiley R. Comparative efficacy of epidural clonidine versus epidural fentanyl for treating breakthrough pain durin labor: a randomized double-blind clinical trial. IJOA. 2020;42:26-33.
  14. Bajwa SJS, Bajwa SK, Kaur J. Comparison of epidural ropivacaine and ropivacaine clonidine combination for elective cesarean sections. Saudi J Anaesth. 2010;4(2):47-54.
  15. Mendez R, Eisenach JC, Kashtan K. Epidural clonidine analgesia after cesarean secion. Anesthesiology. 1990;73:848-852.
  16. Gautier PE, De Kock M, Luc F, Steenberge AV, Hody JL. Intrathecal clonidine combined with sufentanil for labor analgesia. Anesthesiology. 1998;88:651-656.
  17. Allen TK, Mishriky BM, Klinger RY, Habib AS. The impact of neuraxial clonidine on postoperative analgesia and perioperative adverse effects in women having elective Caesarean section -- a systematic review and meta-analysis. BJA. 2018;120(2):228-240.
  18. Singh R, Gupta D, Jain A. The effect of addition of intrathecal clonidine to hyperbaric bupivacaine on postoperative pain after lower segment caesarean section: A randomized control trial. Saudi J Anaesth. 2013;7(3):283-290.
  19. Kothari N, Bogra J, Chaudhary AK. Evaluation of analgesic effects of intrathecal clonidine along with bupivacaine in cesarean section. Saudi J Anaesth. 2011;5(1):31-35.
  20. Wangping Z, Ming R. Optimal dose of epidural dexmedetomidine added to ropivacaine for epidural labor analgesia: a pilot study. Evidence-Based Complimentary and Alternative Medicine. 2017; 2017:7924148. doi: 10.1155/2017/7924148.
  21. Shaikh SI, Revur LR, Mallappa M. Comparison of epidural clonidine and dexmedetomidine for perioperative analgesia in combined spinal epidural anesthesia with intrathecal levobupivacaine: a randomized controlled double-blind study. Anesth Essays Res. 2017; 11(2): 503-507. 
  22. Hanoura SE, Hassanin R, Singh R. Intraoperative conditions and quality of postoperative analgesia after adding dexmedetomidine to epidural bupivacaine and fentanyl in elective cesarean section using combined spinal-epidural anesthesia. Anesth Essays Res. 2013; 7(2): 168-172.
  23. Yousef AA, Salem HA, Moustafa MZ. Effect of mini-dose epidural dexmedetomidine in elective cesarean section using combined spinal-epidural anesthesia: a randomized double-blinded controlled study. J Anesth. 2015; 29: 708-714.
  24. Jain N, Mathur PR, Soni P, Patodi V, Sethi SK, Mathur V. A comparative clinical study of intrathecal bupivacaine 2.5mg with dexmedetomidine 5µg versus intrathecal bupivacaine 2.5mg with fentanyl 25µg on the duration of labor analgesia using combined spinal epidural technique. J Obstet Anaesth Crit Care. 2019; 9: 24-29. 
  25. Sun Y, Xu Y, Wang GN. Comparative evaluation of intrathecal bupivacaine alone, bupivacaine-fentanyl, and bupivacaine-dexmedetomidine in Cesarean section. Drug Res. 2015; 65: 468-472.
  26. Qi X, Chen D, Li G, Huang X, Li Y, Wang X, Li Y. Comparison of intrathecal dexmedetomidine with morphine as adjuvants in cesarean sections. Biol Pharm Bull. 2016; 39: 1455-1460.
     

Date of last update: October 19, 2023