Volume 10- No. 4 2022 Texas Christian University “The Science Behind the Art” Volume 10 - No.4 2022 Anesthesia eJournal - Online ISSN 2333-2611 Page 3 Ondansetron Prior to Spinal Anesthesia to Prevent Hypotension during Cesarean Delivery Haley Marie Jordan, BSN, RN, RRNA Affiliation: Texas Christian University Grant/Financial Support: None KEYWORDS: Cesarean Section, 5 Hydroxytryptamine-3 Receptor Antagonist, Hypotension, Spinal Anesthesia, Bezold-Jarisch Reflex Abstract Subarachnoid blocks (SABs) are gold standard for elective cesarean sections, but this anesthetic technique commonly causes hypotension leading to undesirable effects for the mother (eg, nausea, vomiting) and baby (eg, decreased placental blood flow).9 Vasoactive drugs are often administered, but this may also affect the placental blood flow.6 The purpose of this case report is to explore effects of administering ondansetron, a 5HT3 receptor antagonist, on spinal anesthesia- induced hypotension when administered prior to the SAB and synthesize recent literature to make recommendations for future practice. AEJ About the Author: Haley Jordan is currently a graduate nurse anesthesia student at Texas Christian University Harris School of Nurse Anesthesia, Class of 2022. She has obtained a Bachelor of Science in Nursing at Texas A&M University Health Science Center, 2017. She has been a cardiothoracic and transplant intensive care unit registered nurse, primarily working at Baylor University Medical Center, Dallas, TX and McAllen Heart Hospital, McAllen, TX. Haley is obtaining her DNP-A and will be working at Baylor Scott and White, Temple, TX after graduation. Texas Christian University “The Science Behind the Art” Volume 10 - No.4 2022 Anesthesia eJournal - Online ISSN 2333-2611 Page 4 PowerPoint Template ©2009 Texas Christian University, Center for Instructional Services. For Educational Use Only. Content is the property of the presenter and their resources. Introduction • Spinal anesthesia (SA) is the standard of care for elective cesarean delivery, but consistently causes maternal hypotension from spinal-induced sympathectomy1 • Maternal hypotension can have numerous undesirable effects, which can potentially lead to a cascade of issues for the mother and fetus (figure 1)1-7 • Hypotension post-SA is due to sympathectomy, causing venous pooling and arterial dilation. Many receptors are involved in the activation of the Bezold-Jarisch reflex, including 5- Hydroxytryptamine receptors 3 (5HT3), a serotonin-type of receptor1,8,9 • It has been theorized that utilizing a 5HT3 receptor antagonist prior to inducing SA may attenuate the Bezold-Jarisch reflex, decreasing the amount of hypotension1-7 • The purpose of this case study is to explore the effects of ondansetron administration prior to a subarachnoid block on spinal-induced hypotension Discussion • All studies indicated that ondansetron prior to the administration of a spinal attenuate hypotension, but the degree of hypotension prevented is difficult to determine, as some studies measure hypotension alone1,4-7 and some the amount measure vasopressor consumption2,3 • Ondansetron prevention of hypotension is not common knowledge, perhaps because many systematic reviews and meta-analyses have identified publication bias in the past, hindering its exposure. More recent studies have no indication of systematic bias 12 • Many anesthesia providers posit ondansetron may be unsafe during pregnancy, however no adverse events reported in the literature.1-7,11 No significant major congenital malformations or adverse events with the use of ondansetron during pregnancy10,11 • The most productive method of applying this information to practice would be to educate providers of the potential benefit of administering ondansetron prior to a SAB • Ondansetron is not adequate to rely on as the only medication to use to prevent hypotension, just an additional medication to aid in minimizing hypotension Case Critique • For this case, the patient was given ondansetron 2 minutes prior to the spinal anesthetic. To follow the current literature, it would have been ideal to administer the ondansetron 5 minutes prior to the SAB • The patient’s blood pressure dropped minimally and only 1.5 mL of phenylephrine (100 mcg/ml) was administered • Applying this clinically may be difficult as the timing of spinal anesthesia may be difficult to predict Ondansetron Prior to Spinal Anesthesia to Prevent Hypotension During a Cesarean Delivery Haley Jordan, BSN, RN, Texas Christian University Case Report • 34-year-old, G3P2, 39-weeks pregnant female, Ht 65 in, Wt 97 kg, BMI 35.6, ASA II, scheduled for elective repeat cesarean section Preanesthetic evaluation • PMH: preeclampsia with second pregnancy, but no other comorbidities; No issues this pregnancy • Current medications: The patient was prophylactically on low-dose aspirin with her history of preeclampsia, but she was not preeclamptic for this pregnancy. • PSH: Prior cesarean section x1 • Labs: CBC (WNL), urine drug screen, type and screen • Medications: Aspirin • Premedication: 500 mL LR • Anesthetic Plan: Subarachnoid block with nasal cannula Intraoperative course • Standard monitors and 2L O2 via nasal cannula. Sitting for SAB • Pre-procedure VS: BP: 150/80 (nervous), HR: 82 • 4 mg ondansetron administered 2 minutes before 0.75% bupivacaine (1.6mL) with 0.2 mg Duramorph + 15 mcg fentanyl for SAB. T6 sensory block confirmed, full motor block obtained • BP 3 min post-SAB: 130/65 mmhg, 6 min: 118/50 mmhg (treated with 100 mcg phenylephrine to prevent nausea). 9 min after: 125/59 mmhg. The lowest BP reading was 100/45 mmhg, which was 35 min after the SAB. • Total medication administration: 150 mcg phenylephrine, 800 mL LR • EBL: 800 mL Postoperative course • VS: HR: BP: 122/67, HR: 75 References 1. Heesen M, Klimek M, Hoeks SE, Rossaint R. Prevention of spinal anesthesia-induced hypotension during cesarean delivery by 5-hydroxytryptamine-3 receptor antagonists: a systematic review and meta-analysis and meta-regression. Anesth Analg. 2016;123(4):977-988. doi:10.1213/ANE.0000000000001511 2. Qian J, Liu L, Zheng X, Xiao F. Does an earlier or late intravenous injection of ondansetron affect the dose of phenylephrine needed to prevent spinal-anesthesia induced hypotension in cesarean sections? Drug Design, Development and Therapy. 2020;14, 2789–2795. doi: 10.2147/DDDT.S257880 3. Tatikonda CM, Rajappa GC, Rath P, Abbas M, Madhapura M, Gopal NV. Intravenous ondansetron on spinal anesthesia-induced hypotension and bradycardia: a randomized controlled double- blinded study. Anesthesia, Essays and Researches. 2019;13(2), 340–346. doi: 10.4103/aer.AER_22_19 4. Abbas N, Shah S, Naqvi S. Role of prophylactic ondansetron for prevention of spinal anesthesia induced hypotension in lower segment cesarean section. PAFMJ. 2016;66(6), 790-94. 5. Owczuk R, Wenski W, Twardowski P, Dylczyk-Sommer A, et al. Ondansetron attenuates the decrease in blood pressure due to spinal anesthesia in the elderly: a double blind, placebo- controlled study. Minerva Anestesiologica. 2015;81(6), 598–607 6. Owczuk R, Wenski W, Polak-Krzeminska A, et al. Ondansetron given intravenously attenuates arterial blood pressure drop due to spinal anesthesia: a double-blind, placebo-controlled study. Reg Anesth Pain Med. 2008;33(4):332-339. doi:10.1016/j.rapm.2008.01.0 7. Gao L, Zheng G, Han J, Wang Y, Zheng J. Effects of prophylactic ondansetron on spinal anesthesia- induced hypotension: a meta-analysis. International Journal of Obstetric Anesthesia. 2015;24(4), 335–343. https://doi.org/10.1016/j.ijoa.2015.08.012 8. Warltier DC, Campagna JA, Carter C. Clinical relevance of the Bezold–Jarisch reflex. Anesthesiology. 2003;98(5):1250-1260 9. Raju S, Kapoor A. Illustrated Medical Pharmacology. 1st ed. Jaypee Digital; 2013; 1(16). DOI: 10.5005/jp/books/12078_29 10. Bérard A, Sheehy O, Gorgui J, Jin-Ping Z, Cristiano Soares DM, Bernatsky S. New evidence for concern over the risk of birth defects from medications for nausea and vomiting of pregnancy. J Clin Epidemiol. 2019;116:39-48 11. Suarez EA. Use of Ondansetron for nausea and vomiting during pregnancy and adverse pregnancy outcomes. The University of North Carolina at Chapel Hill; 2019 12. Tubog T, Kane T, Pugh M. Effects of ondansetron on attenuating spinal anesthesia–induced hypotension and bradycardia in obstetric and non-obstetric Subjects: a systematic review and meta- analysis. AANA Journal. 2017;85 (2). Conclusions & Practice Recommendations • Consider 4 mg ondansetron administration prior to spinal insertion to improve BP and decrease vasopressor use during elective cesarean section • Ondansetron administration as a sole intervention may not be ideal, so use as an adjunct in a multimodal approach to decreasing overall maternal hypotension • Protocol implementation may be excessive evidence utilization. However, dissemination of information and education regarding ondansetron prior to SAB may lead to increased use by anesthesia providers and leading to further research.Background of the Bezold-Jarisch Reflex with Spinal Anesthesia • After local anesthetic is injected into the subarachnoid space, a sympathetic blockade occurs 2-6 dermatomes above the sensory blockade8 • The sympathectomy causes arterial dilation and venous pooling, causing decrease blood return to the heart. Baroreceptors initially sense the decrease in blood pressure, decreasing their rate of fire to the vasomotor center of the medulla. A sympathetic response occurs1,2,3,8,9 • The contraction of a poorly filled ventricle activates mechanoreceptors and chemoreceptors • The 5HT-3 receptors are among the chemoreceptors involved in transmission of signals to the vasomotor center. This receptor is not the typical g-protein coupled serotonin receptor. This receptor is a ligand-gated ion channel that produces effects much more rapidly1,8 • When activated, the 5HT3 receptor signals the vasomotor center to activate the Bezold-Jarisch reflex via unmyelinated C-fibers8,9 • The Bezold-Jarisch reflex is cardioinhibitory and causes an increase in parasympathetic activity, which leads to bradycardia, increased venous pooling, and hypotension (figure 2)1,2,8,9 • Studies have been conducted to evaluate the effects of ondansetron, a 5HT3 antagonist, on reducing the amount of hypotension seen with a spinal anesthetic1-7 Figure 2. Depiction of Bezold-Jarisch Reflex9 Figure 1. Potential Cascade of Events during Maternal Hypotension1-7