Scopolamine & Delayed Emergence from Anesthesia: A Case Report

1. Scopolamine & Delayed Emergence from Anesthesia: A Case Report Sally Wenger, SRNA York College of Pennsylvania/ WellSpan Health

2. Case Studies are descriptive studies that are prepared for illustrating novel, unusual, or atypical features identified in patients in anesthesia practice and they potentially generate new research questions.In compliance with the Health Insurance Portability and Accountability Act (HIPPA) all patient data has been de-identified and every attempt has been made to ensure patient privacy and data security.

3. Objectives • Discuss case and anesthetic course • Discuss implications of Central Anticholinergic Syndrome • Discuss scopolamine and implications for nurse anesthetists • Review physostigmine pharmacology and uses in anesthesia

4. Patient Demographics • 63 y/o male • ASA 3 • Allergies: penicillin, adhesive, codeine • 102 kg, BMI 30.7 kg/m2 • Thoracic and lumbar decompression with fusion and instrumentation T12 – pelvis

5. Pre-operative Assessment • PMH: HTN, asthma, degenerative disc disease, GERD, PONV • Home medications Amiodarone Albuterol Gabapentin Amlodipine Singulair Oxycodone Metoprolol Escitalopram Ambien • PSH: lumbar fusion (October ’18), shoulder replacement, ERCP, cholecystectomy

6. Pre-operative Assessment • ECG: normal sinus rhythm • CXR: within normal limits, no acute processes • Labwork within normal limits • Starting H&H 11.8/ 36.2

7. Surgical Course • 0708 : patient in room • 0715: induction • 0810: incision • 1536: procedure stop

8. Surgical Course

9. Surgical Course • 0708 : patient in room • 0715: induction • 0810: incision • 1536: procedure stop • 1740: out of OR • 1800: CT scan • 1830: handoff to PACU 1515: sedation off

10. Central Anticholinergic Syndrome • What is it: A manifestation of central and peripheral competitive antagonism of acetylcholine at the muscarinic receptor • M1 receptors: CNS • M2 receptors: heart, CNS • M3 receptors: glandular organs • M4 receptors: heart, CNS • M5 receptors: CNS Dawson & Buckley, 2016; Nagelhout & Plaus, 2014; Renner , Oertel, & Kirch, 2005

11. Dawson & Buckley, 2016

12. Scopolamine • Non-selective, competitive antagonist of peripheral and central muscarinic receptors • Tertiary amine • Administration via transdermal route • Priming dose 140 mcg with 1.5 mg drug reservoir • Contraindicated in pregnant women, patients with glaucoma, plaster allergy Gan & Habib, 2016; Knuf, Spaulding, & Stevens, 2019; Renner et al., 2005

13. Dawson & Buckley, 2016

14. Differential Diagnoses • Respiratory: hypoxia, hypercarbia • Neuropsychiatric: cerebral hypoxia, intracerebral hemorrhage, acute psychosis • Metabolic: glucose, electrolytes • Illicit drug use • Acute withdrawal from alcohol and opiates Schneck & Rupreht, 1989

15. CAS Treatment • Current recommended treatment is a centrally acting acetylcholinesterase inhibitor • Selective M1 receptor agonist? Pharmacological Blog, 2013 Dawson & Buckley, 2016

16. Physostigmine • Derived from calabar bean – native of tropical Africa • Cited to be used in trial by ordeal – early 1800s First clinical use in 1863 First systemic use in 1864 Main alkaloid physostigmine isolated in 1864 Nickalls & Nickalls, 1988; Rygnestad, 1992

17. Pharmacology • Volume of distribution: 1.35 L/kg • Distribution half-life: 2.3 min • Elimination half-life: 22 min • Clearance: 4.3 L/min • Duration of action: 30-60 min • Metabolized by cholinesterase-mediated hydrolysis Dawson & Buckley, 2016; Hartvig, Wiklund, & Lindström, 1986

18. Dawson & Buckley, 2016

19. Dosing Dawson & Buckley, 2016; Quang et al. 2015

20. Afterthoughts

21. Scopolamine and PONV • Effective in reducing rates of PONV during initial 24 hours • Monotherapy vs. combo-therapy • Zofran + scopolamine • Decadron + scopolamine • Most frequently reported side effects include dry mouth and vision disturbances Apfel et al., 2010; Gan et al., 2009; Lee et al., 2010; Pergolizzi et al., 2015 Zhang et al., 2016

22. Handoff of Care • Critical points • MDA to CRNA • CRNA to SRNA • MDA to MDA • What was missed • Chart review at handoff and at end of case Agarwala, Firth, Albrecht, Warren, & Musch, 2015

23. Good things • Write up in bi-weekly anesthesia newsletter • Pharmacy and physostigmine • Patient was clear headed and cognitively intact in post-op period, no stroke-like symptoms

24. References • Agarwala, A. V., Firth, P. G., Albrecht, M. A., Warren, L., & Musch, G. (2015). An electronic checklist improves transfer and retention of critical information at intraoperative handoff of care. Anesthesia & Analgesia, 120(1), 96-104. doi: 10.1213/ANE.0000000000000506 • Apfel, C. C., Zhang, K., George, E., Shi, S., Jalota, L., Hornuss, C., ... & Kranke, P. (2010). Transdermal scopolamine for the prevention of postoperative nausea and vomiting: a systematic review and meta-analysis. Clinical therapeutics, 32(12), 1987-2002. • Dawson, A. H., & Buckley, N. A. (2016). Pharmacological management of anticholinergic delirium‐theory, evidence and practice. British journal of clinical pharmacology, 81(3), 516-524. • Gan, T. J., & Habib, A. S. (2016). Postoperative nausea and vomiting. Cambridge, New York: Cambridge University Press. • Gan, T. J., Sinha, A. C., Kovac, A. L., Jones, R. K., Cohen, S. A., Battikha, J. P., ... & Pergolizzi, J. V. (2009). A randomized, double-blind, multicenter trial comparing transdermal scopolamine plus ondansetron to ondansetron alone for the prevention of postoperative nausea and vomiting in the outpatient setting. Anesthesia & Analgesia, 108(5), 1498-1504. • Hartvig, P., Wiklund, L., & Lindström, B. (1986). Pharmacokinetics of physostigmine after intravenous, intramuscular and subcutaneous administration in surgical patients. Actaanaesthesiologicascandinavica, 30(2), 177-182. • Knuf, K. M., Spaulding, F. M., & Stevens, G. J. (2019). Scopolamine Toxicity in an Elderly Patient. Military Medicine. doi:10.1093/milmed/usz086 • Lee, H. K., Lee, J. H., Chon, S. S., Ahn, E. K., Kim, J. H., & Jang, Y. H. (2010). The effect of transdermal scopolamine plus intravenous dexamethasone for the prevention of postoperative nausea and vomiting in patients with epidural PCA after major orthopedic surgery. Korean journal of anesthesiology, 58(1), 50. • Moore, P. W., Rasimas, J. J., & Donovan, J. W. (2015). Physostigmine is the antidote for anticholinergic syndrome. J Med Toxicol, 11(1), 159-60. • Nagelhout, J. L., & Plaus, K. L. (2014). Nurse anesthesia. St. Louis, Missouri: Elsevier. • Nickalls, R. W. D., & Nickalls, E. A. (1988). The first use of physostigmine in the treatment of atropine poisoning: A translation of Kleinwachter's paper entitled ‘Observations on the effect of Calabar bean extract as an antidote to atropine poisoning’. Anaesthesia, 43(9), 776-777. • Pergolizzi, J. V., Raffa, R. B., Zamponga, G., Annabi, H. M., Pallaria, T. J., & Taylor, R. (2015). Revisiting transdermal scopolamine for postoperative nausea and vomiting. Research and Reports in Transdermal Drug Delivery, 4, 35-44. • Pharmacological Blog. (2013). Cholinergic agonists. Retrieved from http://n-pharmacology.blogspot.com/2013/06/chapter-4-cholinergic-agonists-overview.html • Renner, U. D., Oertel, R., & Kirch, W. (2005). Pharmacokinetics and pharmacodynamics in clinical use of scopolamine. Therapeutic drug monitoring, 27(5), 655-665. • Rygnestad, T. (1992). Development of physostigmine from a poisonous plant to an antidote. One of the most important drugs in the development of modern medicine? Tidsskrift for den Norske Igeforening, 112(10), 1300-1303. • Schneck, H. J., & Rupreht, J. (1989). Central anticholinergic syndrome (CAS) in anesthesia and intensive care. ActaAnaesthesiologicaBelgica, 40(3), 219-228. • Walker, A., Delle Donne, A., Douglas, E., Spicer, K., & Pluim, T. (2014). Novel use of dexmedetomidine for the treatment of anticholinergic toxidrome. Journal of Medical Toxicology, 10(4), 406-410. • Quang, C. Y., Blair, S. G., Watson, R., Brevard, S. B., Simmons, J. D., & Tan, M. C. (2017). Postoperative Central Anticholinergic Syndrome: Is it Really that Rare?. The American surgeon, 83(3), E104. • Zhang, L. L., Liu, H. Q., Yu, X. H., Zhang, Y., Tian, J. S., Song, X. R., ... & Liu, A. J. (2016). The combination of scopolamine and psychostimulants for the prevention of severe motion sickness. CNS neuroscience & therapeutics, 22(8), 715-722.