Background

Catecholamine is commonly used to support circulation, and each catecholamine agent has different effects on different receptors. Catecholamine action on α-adrenergic receptors promotes peripheral vasoconstriction, on β1-adrenergic receptors it increases chronotropic and inotropic effects, and on β2-adrenergic receptors it increases vasodilation (Fig. 1) [1]. In distributive shocks such as septic shock, we generally use catecholamine agents, including noradrenaline and dopamine, to promote vasoconstriction because they mainly affect the α-adrenergic receptor [1]. However, in a special situation, these catecholamine agents may cause unexpected hypotension. Here we describe a case of unexpected hypotension in response to the use of catecholamine agents.

Fig. 1
figure 1

Alpha-adrenergic and β-adrenergic effects of vasoactive catecholamines. Alpha-adrenergic receptors promote peripheral vasoconstriction, β1-adrenergic receptors increase chronotropic and inotropic effects, and β2-adrenergic receptors increase vasodilation. If α-adrenergic receptor antagonists are simultaneously administered with catecholamine agents, α-adrenergic effects are masked, and β-adrenergic effects are predominantly enhanced. Consequently, vasodilation occurs and blood pressure decreases. HR heart rate

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Case presentation

A 29-year-old Japanese man with schizophrenia was transferred to our emergency department. On arrival, he presented with shock and coma. His blood pressure (BP) was 57/29 mmHg, heart rate (HR) was 135 beats per minute (bpm), respiratory rate was 40/minute, and his body temperature was 35.6 °C. His Glasgow Coma Scale score was (E1V1M1) 3. We immediately performed intubation because of his shock and coma. Fluid resuscitation of 3000 ml crystalloid temporarily increased his BP to 73/28 mmHg, but his shock still persisted. Before a central venous line was inserted, we tentatively initiated dopamine infusion at 5 μg/kg per minute, which was increased to 10 μg/kg per minute; however, his hypotension gradually worsened to 66/37 mmHg (Fig. 2). Sixty minutes after arrival, we inserted the central venous line and initiated noradrenaline infusion at 0.1 μg/kg per minute, which was subsequently increased to 0.3 μg/kg per minute. Moreover, 90 minutes after arrival, we initiated dobutamine at 5 μg/kg per minute. However, his BP unexpectedly decreased to 59/40 mmHg. Head computed tomography, enhanced chest-abdominal computed tomography, point of care sonography, and laboratory data (Table 1) did not reveal the cause of coma and hypotension. His systemic vascular resistance index (SVRI) was very low (432 dynes/second/cm/m2; normal range, 1970 to 2400 dynes/second/cm/m2; Vigileo FloTrac™, Edwards, USA). Thus, we suspected unknown distributive shock refractory to a large amount of catecholamine infusion. Therefore, in addition to catecholamine infusion, we initiated vasopressin at 3 U/hour 150 minutes after arrival. Subsequently, his BP markedly improved to 135/45 mmHg. Three hours after arrival, we transferred him to our intensive care unit. We performed continuous hemodiafiltration because of the presence of metabolic acidosis (Table 2). We gradually decreased the amount of catecholamine infused. Approximately 12 hours after arrival, his SVRI improved to 2271 dynes/second/cm/m2 and his hemodynamic state became stable: BP, 140/80 mmHg; HR, 95 bpm. Subsequently, we completely terminated catecholamine infusion. Moreover, we terminated continuous hemodiafiltration because his metabolic acidosis was improved: pH, 7.386; partial pressure of oxygen in arterial blood (PaO2), 73.8 mmHg; partial pressure of carbon dioxide in arterial blood (PaCO2), 39.3 mmHg; bicarbonate (HCO3 -), − 1.2 mmol/l; lactate (Lac), 1.5 mmol/l; and fraction of inspired oxygen (FiO2), 0.3. On day 2, we terminated vasopressin infusion. After extubation, his condition was stable: BP, 123/75 mmHg; HR, 100 bpm; and Glasgow Coma Scale score (E4V5M6), 15. He was transferred to our general ward. He admitted to ingesting approximately 150 mg risperidone to attempt suicide. The risperidone concentration in his blood sample on admission was very high (398 ng/ml at admission, recommended therapeutic range, 20 to 60 ng/ml [2]), which decreased to 3.60 ng/ml on day 2. Consequently, we diagnosed risperidone overdose. Subsequently, his condition was stable without any event, and he was transferred to a psychiatric ward for psychiatric care on day 5.

Fig. 2
figure 2

Clinical course after admission. Blood pressure gradually decreased in response to an increase in catecholamine administration. After initiating vasopressin, hypotension markedly improved. BP blood pressure, CHDF continuous hemodiafiltration, DBP diastolic blood pressure, DOA dopamine, DOB dobutamine, HR heart rate, NAD noradrenaline, SBP systemic blood pressure, VAS vasopressin

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Table 1 Laboratory data on admission
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Table 2 Arterial blood gas analysis in intensive care unit
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Discussion

We experienced unexpected hypotension in response to catecholamine infusion, and we believe that this unexpected hypotension was caused by a pharmacological phenomenon: the catecholamine effect under the α-adrenergic blockade effect of risperidone. In animal experiments, if adrenaline is simultaneously administered with α-adrenergic receptor blockers such as phentolamine, the α-adrenergic effects are masked and the β2-adrenergic effects are predominantly enhanced (Fig. 1) [3]. Consequently, vasodilation occurs and the BP decreases. This unique phenomenon is called “adrenaline reversal” [3]. Adrenaline reversal has also been reported in clinical situations; paradoxical hypotension due to adrenaline infusion has been reported in a case of massive quetiapine overdose because quetiapine has an α-adrenergic blockade effect [4]. This report suggested that adrenaline reversal occurs even in cases of massive antipsychotic overdose. This report recommended selecting noradrenaline for hypotension under an α-adrenergic blockade effect, such as an overdose of quetiapine; however, we disagree with this. This is because other animal experiments proved that noradrenaline could also cause the same phenomenon as “noradrenaline reversal” [5], although noradrenaline has stronger α-adrenergic effects than β-adrenergic effects. Therefore, we suggest that we should avoid noradrenaline in such a situation.

Dopamine and dobutamine also have both α-adrenergic and β-adrenergic effects [6]; we think that there is a possibility that dopamine and dobutamine also may cause catecholamine reversal. Thus, catecholamine agents other than adrenaline can potentially provoke “catecholamine reversal” in patients who have used α-adrenergic antagonists. In our case, because risperidone has an α-adrenergic blockade effect, a large amount of catecholamine infused under the effect of an α-adrenergic blockade might have caused hypotension in the same mechanism.

On the other hand, vasopressin is a type of vasoactive agent that increases peripheral vasoconstriction via V1 receptors [3] and is commonly used to maintain vasoconstriction, particularly in distributive shock [1]. In our patient, severe hypotension immediately improved after administering vasopressin. This could be attributed to the fact that the mechanism action of vasopressin is different from that of catecholamines. Thus, vasopressin may be useful to support circulation in patients who have used α-adrenergic antagonists.

This is the first clinical case to describe unexpected hypotension as “catecholamine reversal.” Most antipsychotic agents have α-adrenergic blockade; thus, this educational case highlights that we should determine which vasoactive agent should be selected for the patient who uses these medicines.

Conclusions

We described the first clinical case of “catecholamine reversal” and highlighted that if unexpected hypotension occurs in response to catecholamine infusion, we should suspect that the patient has used α-adrenergic antagonists. In such a situation, we should consider administration of vasopressin instead.