Adrenaline‐induced hypotension in the context of significant quetiapine overdose

Abstract

In patients presenting with hypotension due to significant quetiapine or mixed overdose, adrenaline should be avoided and consider medications such as noradrenaline or vasopressin as an alternative. If using noradrenaline peripherally, use a lower concentration (4 mg in 50 mL 5% glucose) and use a large bore cannula in a large vein.

In patients presenting with hypotension due to significant quetiapine or mixed overdose, adrenaline should be avoided and consider medications such as noradrenaline or vasopressin as an alternative. If using noradrenaline peripherally, use a lower concentration (4 mg in 50 mL 5% glucose) and use a large bore cannula in a large vein.

1. INTRODUCTION

Mixed overdose is a common presentation to the Emergency Department with a high impact on clinical services. ¹ These patients often require intubation for airway protection, acute behavioral disturbance, or multiorgan failure. In severe cardiovascular collapse, it is not uncommon to use dilute adrenaline (traditionally 10 μg/mL) to stabilize the patient prior to rapid sequence induction of anesthesia and intubation.

As this case demonstrates, adrenaline can cause refractory hypotension when used to stabilize a patient who has taken a significant overdose of quetiapine. The dose required to cause the antagonistic alpha receptor effect is unknown. Therefore, an awareness of the effect of adrenaline in the presence of these medications is required to avoid cerebral hypoperfusion or cardiac arrest.

Peripheral noradrenaline or vasopressin infusion ² , ³ should be used in these cases, obtaining central access promptly to avoid extravasation injury.

2. CASE HISTORY

A 33‐year‐old female patient presented to the Emergency Department having collapsed at 19:10 in front of a family member. She was reported by the pre‐hospital crew to have taken a mixed overdose including quetiapine, duloxetine, pregabalin, and alcohol. The patient was on a regular prescription of 100 mg once a day of quetiapine. It was noted that 3 weeks of quetiapine was missing from her medication dosette box, which had been issued by her pharmacy less than 72 h before presentation. This gives an approximate total of 2100 mg quetiapine. Only one dose of pregabalin and duloxetine was missing from the dosette box. The amount of alcohol consumed is unknown.

She presented to the Emergency Department at approximately 20:20. She had a Glasgow Coma Score (GCS) of 3 and required airway adjuncts to maintain a patent airway. A Mapleson‐C circuit was used to assist ventilation due to poor respiratory effort. She was hypotensive with a systolic blood pressure (SBP) of 65 mmHg having already received 500 mL of 0.9% sodium chloride with the pre‐hospital crew.

The decision was made to intubate her to protect her airway and ensure adequate ventilation, and assistance was sought urgently from the intensive care team. As a temporizing measure, a 0.5 mg/mL metaraminol infusion was started initially at a rate of 5 mL/h and titrated quickly to 20 mL/h. Simultaneously, we provided further fluid resuscitation. Despite adequate fluid resuscitation (2.5 L of crystalloid), the patient remained profoundly hypotensive. Due to the risk of cardiovascular collapse post‐induction, the decision was made to use dilute adrenaline (10 μg/mL) to stabilize the patient prior to induction.

Upon administration of two 10 μg boluses, the patient became increasingly hypotensive with a systolic blood pressure of 55 mmHg. She received further aliquots totaling 50 μg which rendered the patient peri‐arrest with a SBP of 40 mmHg. At this point, no more adrenaline was administered and advice from the on‐call intensive care consultant was sought urgently.

As part of the fluid status assessment, all medications were double checked for correct dose and concentration. The patient's venous access was reviewed and concluded to be satisfactory. Point of care ultrasound (POCUS) was used to visualize the inferior vena cava to check for venous collapse. Following this assessment, it was concluded the patient was adequately fluid resuscitated, and therefore, a different vasopressor should be used.

The decision was made to use peripheral noradrenaline infusion at a concentration of 4 mg in 50 mL of 5% glucose to facilitate induction of anesthesia and to achieve cardiovascular stability. A new 14‐gauge cannula was inserted to facilitate this. The patient's blood pressure recovered adequately. She was then intubated without an adverse event and transferred to the intensive care unit (ICU). Shortly after admission to intensive care, a central venous catheter was inserted and the noradrenaline infusion switched to central access.

2.1. Outcome and follow‐up

The patient was admitted to the ICU for 48 h. She was treated for a presumed aspiration pneumonitis, and vasopressors were successfully weaned. She was discharged to the ward from ICU without complication and followed up by the mental health team.

2.2. Patient perspective

Due to the nature of the presentation, the patient was not aware of the complications surrounding her presentation.

3. DISCUSSION

Catecholamine‐induced hypotension following overdose has been observed with the use of psychotropic medications including quetiapine and risperidone. ³ These medications cause α‐antagonism. Catecholamine agents such as adrenaline also have β₂‐agonism which increases vasodilation. ⁴ Due to the high affinity of medications such as quetiapine to α‐adrenergic receptors, ⁵ this results in an effective pharmacological blockade of α‐adrenergic receptors resulting in a profound vasodilatory effect and subsequent hypotension (Figure 1). A case report in 2009 by Grace and Newell ² described a similar phenomenon and termed it “Adrenaline reversal.”

FIGURE 1.

Alpha receptor blockade resulting in unopposed beta receptor agonism.

The case report by Okada et al. ³ recommended the use of vasopressin as rescue due to the overlapping effects of the α and β‐adrenergic receptors in most common inotropes and vasopressors. However, in this particular case, the use of noradrenaline resulted in a prompt and satisfactory increase in blood pressure to facilitate intubation. It should be noted that metaraminol was also used as a bolus medication and an infusion in this case but resulted only in bradycardia. Metaraminol mainly acts at α₁‐ adrenoceptors with some β‐adrenoceptor effects. Metaraminol also causes intra‐cytoplasmic adrenaline release, thereby increasing the “adrenaline reversal” effect.

The urgent nature of the need for vasopressors meant that noradrenaline was administered via a peripheral line. This is not common practice in UK resuscitation rooms, but it can be achieved safely with specific criteria adhered to ⁶ including dose and rate of infusion, appropriate vein choice and prompt cessation if any signs of extravasation occur. If there is no contraindication to central access, this should be obtained at the earliest opportunity and vasopressor administration continued centrally.

TOXBASE ⁷ is a reliable source of information for emergency physicians and nurses when faced with poisoning cases in the emergency department. It contains a reference to hypotension in the presence of adrenaline under the quetiapine toxicity entry. Understandably in an emergency, this is unlikely to be accessed in a timely fashion; therefore, increased awareness among emergency and critical care physicians and practitioners of this effect is necessary.

AUTHOR CONTRIBUTIONS

Enyioma Anomelechi: Conceptualization; data curation; formal analysis; investigation; methodology; validation; writing – original draft; writing – review and editing. Robert Hirst: Conceptualization; methodology; project administration; resources; supervision; writing – review and editing.

FUNDING INFORMATION

The authors did not receive funding for this article.

CONFLICT OF INTEREST STATEMENT

The authors declare they hold no conflicts of interest.

ETHICS STATEMENT

All procedures performed were in accordance with the ethical standards. The examination was made in accordance with the approved principles.

CONSENT

Written informed consent was obtained from the patient to publish this report in accordance with the journal's patient consent policy.

PERMISSION TO REPRODUCE MATERIAL FROM OTHER SOURCES

Any material reproduced from other sources made available under Creative Commons licensing.

Anomelechi E, Hirst R. Adrenaline‐induced hypotension in the context of significant quetiapine overdose. Clin Case Rep. 2023;11:e7117. doi: 10.1002/ccr3.7117

DATA AVAILABILITY STATEMENT

None.