Reducing Hypotension and Bradycardia after a Subarachnoid Block in the Obstetric Population: Is...

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Reducing Hypotension and Bradycardia after a Subarachnoid Block in the Obstetric Population:

Is Zofran the Answer?

Lauren Tennis, BSN, RN, SRNA

York College of Pennsylvania

Objectives

• Review of SAB and the physiologic effects• Discuss the role of important reflexes• Review serotonin and the 5-HT3 receptor• Review pharmacology of Zofran• Appraise literature on the use of Zofran to attenuate

hypotension and bradycardia• Evaluate what the literature says on recommended dosing• Discuss areas of concern: Zofran and adverse fetal

outcomes

Subarachnoid Blocks

Subarachnoid Block

Subarachnoid BlocksClass A-α A-β A-γ A-δ B CFunction Motor Light Touch,

Pressure& Pain

Proprioception

Muscle Spindles

Temp &

Pain

Autonomic Pain & Pressure

Myelin +++ ++ ++ ++ + -Diameter(μm)

12-20 5-12 5-12 1-4 1-3 0.5-1

Conduction Speed (m/sec)

70-120 30 - 70 30 - 70 12 - 30 15 1.2

Block Progression

Last First

SNS blockade exceeds sensory dermatome by about 2 dermatomes.Motor blockade is about 2 dermatomes below the sensory blockade.

Neural• Blocks C fiberA fibers• Sympathetic > Temperature >

sensory > motor

Cardiovascular• Block cardio-accelerator fibers• Dilation of arteries and venous

capacitance vessels

Physiologic Effects of SABRespiratory• Paralysis of intercostal and

abdominal muscles• Phrenic nerve usually preserved

Gastrointestinal

• Nausea and Vomiting• Decreased hepatic blood flow

Why do we have hypotension & bradycardia after SAB?

• Sympathetic blockade• Activation of the Bezold-Jarisch Reflex• Activation of baroreceptors• Blockade of cardio-accelerator fibers T1-T4• Unopposed parasympathetic nervous system

Sympathetic Blockade•Sympathetic chain located in thoracolumbar region

•Efferent stimulus from spinal cord in blocked and unable to transmit through sympathetic ganglion

•Inability to vasoconstrict and increase HR

Bezold-Jarisch Reflex•Inhibitory reflex

•Mechanoreceptors detect low volume and decreased stretch

•Chemoreceptors sense increased levels of serotonin

•Heart attempts to compensate by hypercontracting the LV

•Afferent vagal nerve endings in LV send signal to NTS of brain

•Brain sends out parasympathetic signals via vagus nerve and slows HR and causes vasodilation

Baroreceptor Activation

Low Volume

Heart Rate Decreased

Baroreceptor Activation

Blockade of Cardio-accelerator Fibers

• Originate from T1-T4 from the stellate sympathetic ganglion

• SAB at T4 level blocks sympathetic output to heart

• Unopposed parasympathetic system causes bradycardia

Ways to Treat Hypotension and Bradycardia

• IV Fluids• Vasoactive medications• Head down position• Zofran?

Ondansetron (Zofran)

• 5-HT3 receptor antagonist• Works peripherally (GI tract) and centrally (chemoreceptor

trigger zone)• Dosing: 2-8mg• Onset: 3-5min (IV)• Half-life: 3-6 hours• Metabolized by the liver• Common routes of administration: PO, IV• FDA Category B

Serotonin

• Excitatory and inhibitory neurotransmitter• Located in…

– Enterochromaffin cells 90%peristalsis, N/V, diarrhea– Platelets 8-10%local vasoconstriction– CNS 1-2%mood, appetite, pain, sleep

• Receptors are both metabotropic and ionotropic

5-HT3 Receptor

• Ligand-gated ion channel• Structurally similar to nAch

receptor• Located in CNS, blood

vessels, GI tract, afferent vagal nerve endings

Zofran and the Bezold-Jarisch Reflex

Decreased blood volume and blood flow

Sympathectomy from SAB

Release of serotonin from platelets and enterochromaffin cells

Increased serotonin levels bind to the afferent vagal nerve endings stimulating the BJR and N/V

Parasympathetic outflow

Bradycardia, vasodilation and N/V

Zofran: 5-HT3

AntagonistNo transmission of vagal afferents and block CTZ

Less parasympathetic outflow

Reduced vasodilation, bradycardia, and N/V

Literature Review

Max Dose of Phenylephrine Use

240 mcg 209 mcg 106 mcg 125 mcg 195 mcg

Dosing Recommendations

• 1/3 of Group 04 and Group 06 experienced hypotension

• 40-60% of Group S, Group 02, and Group 08 experienced hypotension

• 4mg and 6mg of Zofran is adequate

Dosing Recommendations

• 6mg vs 12 mg vs control group (NSS)

• Control MAPs < Zofran group MAPs

• Control required Ephredrine for hypotension and Atropine for bradycardia

• No significant difference between 6mg and 12mg Zofran

Zofran and Neonatal Outcomes•Category B

•Clinical trials had no effect on birth malformations

•APGAR scores 7-10

•PO Zofran safe: no difference in spontaneous abortions, stillbirths, premature births, malformations, or low birth weight

Summary

• Hypotension and bradycardia are common physiologic changes after a SAB

• Zofran reduces hypotension by blocking the BJR and decreasing parasympathetic outflow

• No significant change in bradycardia• 4-8mg is adequate• No evidence of adverse outcomes in neonates

ReferencesAviado, D. M., & Guevara Aviado, D. (2001). The Bezold-Jarisch reflex. A historical perspective of cardiopulmonary reflexes. Annals Of

The New York Academy Of Sciences, 94048-58.

Einarson, A., Maltepe, C., Navioz, Y., Kennedy, D., Tan, M. P., & Koren, G. (2004). The safety of ondansetron for nausea and vomiting of pregnancy: a prospective comparative study. BJOG: An International Journal Of Obstetrics And Gynaecology, 111(9), 940-943

Kinsella, S. M., & Tuckey, J. P. (n.d). Perioperative bradycardia and asystole: Relationship to vasovagal syncope and the Bezold-Jarisch reflex. British Journal Of Anaesthesia, 86(6), 859-868.

Marashi, S. M., Soltani-Omid, S., Soltani Mohammadi, S., Aghajani, Y., & Movafegh, A. (2014). Comparing Two Different Doses of Intravenous Ondansetron With Placebo on Attenuation of Spinal-induced Hypotension and Shivering. Anesthesiology And Pain Medicine, 4(2), e12055. doi:10.5812/aapm.12055

Maricq, A. V., Peterson, A. S., Brake, A. J., Myers, R. M., & Julius, D. (1991). Primary structure and functional expression of the 5HT3 receptor, a serotonin-gated ion channel. Science (New York, N.Y.), 254(5030), 432-437.

Mark, A. L. (1983). The Bezold-Jarisch reflex revisited: clinical implications of inhibitory reflexes originating in the heart. Journal Of The American College Of Cardiology, 1(1), 90-102.

Miller, R.D. (2010). Miller’s Anesthesia (7th edition). Philadelphia, PA.

Nagelhout, J. & Zaglaniczny, K. (2014). Nurse Anesthesia (5th edition). WB Saunders.

ReferencesOwczuk, R., Wenski, W., Polak-Krzeminska, A., Twardowski, P., Arszułowicz, R., Dylczyk-Sommer, A., & ... Wujtewicz, M. (2008). Ondansetron given

intravenously attenuates arterial blood pressure drop due to spinal anesthesia: a double-blind, placebo-controlled study. Regional Anesthesia And Pain Medicine, 33(4), 332-339. doi:10.1016/j.rapm.2008.01.010

Pasternak, B., Svanström, H., & Hviid, A. (2013). Ondansetron in pregnancy and risk of adverse fetal outcomes. New England Journal of Medicine, 368(9), 814-823.

Priestley, P. C. (1981). Serotonin and anesthesia. AANA Journal, 49(5), 511-515.

Reeves, D. C., & Lummis, S. R. (n.d). The molecular basis of the structure and function of the 5-HT3 receptor: A model ligand-gated ion channel (Review). Molecular Membrane Biology, 19(1), 11-26.

Sahoo, T., SenDasgupta, C., Goswami, A., & Hazra, A. (2012). Reduction in spinal-induced hypotension with ondansetron in parturients undergoing caesarean section: a double-blind randomised, placebo-controlled study. International Journal Of Obstetric Anesthesia, 21(1), 24-28. doi:10.1016/j.ijoa.2011.08.002

Sevoz, C., Nosjean, A., Callera, J., Machado, B., Hamon, M., & Laguzzi, R. (1996). Stimulation of 5-HT-3 receptors in the NTS inhibits the cardiac Bezold-Jarisch reflex response. American Journal Of Physiology, 271(1 PART 2), H80-H87.

Wang, M., Zhuo, L., Wang, Q., Shen, M., Yu, Y., Yu, J., & Wang, Z. (2014). Efficacy of prophylactic intravenous ondansetron on the prevention of hypotension during cesarean delivery: a dose-dependent study. International Journal Of Clinical And Experimental Medicine, 7(12), 5210-5216.

Wang, Q., Zhuo, L., Shen, M., Yu, Y., Yu, J., & Wang, M. (n.d). Ondansetron Preloading with Crystalloid Infusion Reduces Maternal Hypotension during Cesarean Delivery. American Journal Of Perinatology, 31(10), 913-921.