European Journal of Cardiovascular Medicine

The Bezold-Jarisch reflex (BJR) is a cardioinhibitory response characterised by peripheral vasodilation, hypotension, and bradycardia. It originates from cardiac sensory receptors, primarily located in the inferoposterior wall of the left ventricle, which transmit signals via unmyelinated vagal afferent fibres. Stimulation of these receptors by mechanical stretch, chemical mediators such as serotonin, or certain drugs activates parasympathetic output and suppresses sympathetic activity. In hypovolemic states, underfilling of the ventricles may activate mechanoreceptors, while serotonin-mediated chemoreceptor stimulation further contributes to the reflex. These combined effects, particularly in individuals with high baseline vagal tone, can lead to severe bradycardia or even asystole. The incidence of cardiac arrest due to BJR is estimated at 2–3 per 10,000 anaesthetic procedures.¹ We report a case of a 30-year- old ASA I female patient who developed asystole during combined spinal-epidural anesthesia for exploratory laparotomy.

A 30-year-old female with a right ovarian mucinous cystadenoma was posted for exploratory laparotomy. The patient was preoperatively classified as ASA I, with no significant comorbidities, and was planned for combined spinal-epidural anaesthesia in sitting position.

Following the siting of the epidural catheter at L1-2, a test dose of 3 ml of 2% lignocaine with adrenaline, there were no signs of intra-arterial or intrathecal deposition of the drug. However, immediately after the spinal needle was inserted, the patient became unresponsive, and her heart rate fell to less than 35 bpm, eventually progressing to asystole on the electrocardiogram (ECG). Immediately the patient was made supine, and resuscitation measures were initiated, including chest compressions, 1 mg of adrenaline intravenously, and bag-mask ventilation. The patient regained consciousness within 30 seconds, with a blood pressure of 160/90 mmHg and sinus rhythm; an injection of ondansetron 8 mg was also given in view of the differential diagnosis of Bezold-Jarisch reflex.

Despite initial stabilisation, few minutes after ROSC, the patient had to be monitored in the Intensive Care Unit (ICU) due to persistent hypotension (SBP < 90 mmHg) and bradycardia (HR 40-45bpm), requiring norepinephrine intravenous infusion and glycopyrrolate given intravenously twice to correct acute unstable bradycardia to which she responded with correction of rate and symptoms.

The hypotension was persistent, and the patient did not tolerate tapering of the norepinephrine infusion. Simultaneously, a 2D echocardiography was performed in the ICU, which revealed a good ejection fraction of 64% and no regional wall motion abnormality. ABG was normal with all parameters well within normal range. Further investigations exhibited elevated troponin I and NT-pro BNP levels (Table 1), though there was no evidence of myocardial infarction on ECG or echocardiography. The chest radiograph (Fig 1) was normal. There were no changes in laboratory or echocardiographic values to suggest any major pathology for hypotension, and an empirical dose of steroid hydrocortisone 100 mg was given intravenously after 24 hours of hypotension. This resulted in an immediate response of de-escalation of noradrenaline infusion and discontinuation over the next six hours. The patient was discharged after 72 hrs from the ICU.

The BJR can be triggered during spinal or epidural anaesthesia due to the sympathetic blockade caused by these techniques. The blockade reduces venous return and systemic vascular resistance, causing the ventricles to become underfilled, which stimulates cardiac mechanoreceptors. This, in turn, triggers an exaggerated parasympathetic response, resulting in bradycardia, hypotension and, in severe cases, asystole. Pre-induction volume loading is important in maintaining adequate preload and decreases the risk of severe bradycardia and cardiac arrest. ²

Several risk factors for BJR have been identified in the literature, which include young healthy adults with strong vagal tone, individuals with low baseline heart rate, hypovolemia, and sitting position.

Pain, apprehension and reduced venous return may lead to vasovagal syncope, which can be additive to BJR in some circumstances such as regional anaesthesia, haemorrhage, or the compression of the inferior vena cava in pregnant women.³ These factors could have played arole in this situation as the spinal drug had not been injected. Interestingly, she had three uneventful previous anaesthetics, and spinal was given in the sitting posture.

5-Hydroxytryptamine receptors 3 (5HT3), a serotonin-type of receptor present on vagal afferent nerve endings in the heart, are involved in the Bezold-Jarisch reflex. Ondansetron has been previously given successfully prior to SA to counteract the BJR, as serotonin has been associated with the pathogenesis of inhibition of the sympathetic system via both the peripheral 5HT3 receptors and the central 5HT1 and 5HT2 receptors.^4,5,6

Arthroscopic shoulder surgery with interscalene block has also been associated with a high number of BJR (20 patients in a group of 116 patients) where the authors have postulated that the underlying mechanism could be due to the sitting position and high circulating epinephrine levels.⁷

Cardiac arrest under spinal anaesthesia has reduced over the last 50 years from 6.5 in 10,000 to 2-3 per 10,000, due to improvement in monitoring systems as well as reduction of sedation practices in anaesthesia.^1,8 Cardiac arrest under spinal anaesthesia is complex and multifactorial, and intrinsic cardiac inhibitory reflexes can play a role when other causes have been excluded. Lacey et al. have discussed the potential interaction of BJR, reverse Bainbridge reflex and the pacemaker stretch reflex leading to bradycardia, hypotension and asystole.⁹

This patient was unusual, as she received the test dose of lignocaine with adrenaline in the epidural space, and the spinal needle was just introduced into the space, which points to a BJR aggravated by the sitting position and strong resting vagal tone, leading to asystole. However, there is no conclusive evidence that it is BJR, which is a diagnosis after elimination of other causes. The cause for the persistent hypotension in the post-resuscitation phase could be due to a relative adrenal insufficiency leading to vasoplegia.¹⁰

A retrospective analysis conducted in Taiwan showed improved survival to hospital discharge, as well as improved one-year survival, when steroids were administered during post-cardiac arrest care.¹¹

An RCT conducted in three hospitals in Greece demonstrated improved survival outcomes and favourable neurological status when hydrocortisone was included in post-ROSC care.¹²

In our case, ultrasonography was performed to assess IVC collapsibility, which excluded hypovolemia. An ABG analysis was conducted to rule out metabolic disturbances, and neurological causes were excluded due to the very short duration of bradycardia and asystole (<1 minute), making compromised perfusion of neurological structures unlikely. There was no history of sepsis or evidence of any infectious foci.

After excluding all possible causes of post-ROSC hypotension, adrenal insufficiency was considered as a potential cause. A trial of steroids was administered, which elicited a surprisingly positive response. The underlying mechanism is probably by correcting adrenal insufficiency, enhancing the vascular response to catecholamines, reducing systemic inflammation induced by ischaemia-reperfusion injury, and stabilising vascular tone. The patient tolerated the gradual tapering of inotropic support, and we were able to successfully wean off inotropes. Therefore, in post-resuscitation hypotension, their judicious use can be lifesaving, particularly when traditional therapies like fluids and vasopressors fail. The administration of hydrocortisone post-ROSC was associated with higher early post-ROSC systolic arterial pressure and mean arterial pressure (MAP), suggesting a stabilising effect on haemodynamics.¹³

The abrupt onset of bradycardia, hypotension, and asystole following spinal needle insertion suggests a vasovagal-mediated BJR event, possibly exacerbated by sitting posture and pre- existing strong vagal tone. Prophylactic use of 5-HT3 antagonists and maintaining adequate preload may have prevented reflex-mediated cardiovascular collapse during regional anaesthesia. This case highlights the importance of recognising BJR as a cause of perioperative cardiac instability, the role of serotonin receptors in its pathophysiology, and the need for early steroid intervention in cases of persistent hypotension post-cardiac arrest.

Table 1: Investigations of the patient post resuscitation

(ng/L: nanogram / litre; pg/ml: picogram / millilitre; mcg/dL: microgram / decilitre.

Fig 1: Post-resuscitation Chest X-ray

1. Kopp, S. L., Horlocker, T. T., Warner, M. E., et al. "Cardiac Arrest during Neuraxial Anesthesia: Frequency and Predisposing Factors Associated with Survival." Anesthesia and Analgesia, vol. 100, 2005, pp. 855–865.
2. Louro da Cruz, J., Gomes, C., Oliveira, C., and Fragoso, P. "Bezold-Jarish Reflex and Cardiac Arrest under Spinal Anaesthesia: 8AP6-6." European Journal of Anaesthesiology, vol. 30, 2013, p. 133.
3. Kinsella, S. M., and Tuckey, J. P. "Perioperative Bradycardia and Asystole: Relationship to Vasovagal Syncope and the Bezold-Jarisch Reflex." British Journal of Anaesthesia, vol. 86, no. 6, 2001, pp. 859–868. https://doi.org/10.1093/bja/86.6.859
4. Martinek, R. M. "Witnessed Asystole during Spinal Anesthesia Treated with Atropine and Ondansetron: A Case Report." Canadian Journal of Anaesthesia, vol. 51, no. 3, 2004, pp. 226–230. https://doi.org/10.1007/BF03019100
5. Grubb, B. P., and Karas, B. J. "The Potential Role of Serotonin in the Pathogenesis of Neurocardiogenic Syncope and Related Autonomic Disturbances." Journal of Interventional Cardiac Electrophysiology, vol. 2, 1998, pp. 325–332.
6. Bhiwal, Anil Kumar, et al. "Intravenous Ondansetron to Prevent Hypotension during Cesarean Section under Spinal Anaesthesia." Journal of Obstetric Anaesthesia and Critical Care, vol. 11, no. 1, Jan.–June 2021, pp. 15–19. https://doi.org/10.4103/joacc.JOACC_61_20
7. D'Alessio, J. G., Weller, R. S., and Rosenblum, M. "Activation of the Bezold-Jarisch Reflex in the Sitting Position for Shoulder Arthroscopy Using Interscalene Block." Anesthesia and Analgesia, vol. 80, no. 6, 1995, pp. 1158–1162. https://doi.org/10.1097/00000539-199506000-00016
8. Auroy, Y., Narchi, P., Messiah, A., et al. "Serious Complications Related to Regional Anesthesia." Anesthesiology, vol. 87, 1997, pp. 479–486.
9. Lacey, J. R., Dubowitz, J. A., and Riedel, B. "Asystole Following Spinal Anaesthesia: The Hazards of Intrinsic Cardiac Reflexes." Anaesthesia Reports, vol. 10, no. 2, 2022, e12198. https://doi.org/10.1002/anr3.12198
10. Pene, F., Hyvernat, H., Mallet, V., et al. "Prognostic Value of Relative Adrenal Insufficiency after Out-of-Hospital Cardiac Arrest." Intensive Care Medicine, vol. 31, no. 5, 2005, pp. 627–633.
11. Tsai, M. S., Chuang, P. Y., Huang, C. H., et al. "Postarrest Steroid Use May Improve Outcomes of Cardiac Arrest Survivors." Critical Care Medicine, vol. 47, no. 2, 2019, pp. 167–175.
12. Mentzelopoulos, S. D., Malachias, S., Chamos, C., et al. "Vasopressin, Steroids, and Epinephrine and Neurologically Favorable Survival after In-Hospital Cardiac Arrest: A Randomized Clinical Trial." JAMA, vol. 310, no. 3, 2013, pp. 270–279.
13. Mentzelopoulos, S. D., and Chalkias, A. "A Critical Reappraisal of Vasopressin and Steroids in In-Hospital Cardiac Arrest." Critical Care, vol. 28, 2024, article 191. https://doi.org/10.1186/s13054-024-04962-8