Case Reports in Medicine It was unclear why glucagon appeared to have a transient eﬀect in our case. It did, however, cause severe vomiting. Vomiting is a well-documented side eﬀect of glucagon, particularly in high doses as given in this case. Intralipid was also tried. Due to amlodipine being highly lipophilic, it would seem plausible that intralipid would work to bind it. Young et al. reported a case of verapamil overdose that resulted in cardiac arrest that was successfully treated with intralipid [18]. We could not ﬁnd any other case reports of signiﬁcant calcium channel blocker/angiotensin II receptor blocker overdose where intralipid was used but TOXBASE advises that “If life threatening arrhythmias (e.g., ventricular tachycardia, ﬁbrillation, heart block, and asys- tole) are unresponsive to the above consider the use of a lipid emulsion (e.g., 1 mL/kg of 20% intralipid as an intravenous bolus followed by 3 mL/kg/hour to an initial maximum of 500 mL lipid in an adult).” This did not appear to have any clinical eﬀect. It is unclear if it would have been more eﬀective if it had been given earlier in the clinical course. There is weak evidence for the use of intralipid in verapamil overdose [16]. However, overall the evidence for the use of intralipid in overdose is limited to case reports and animal studies and although promising results have been reported the current guidance for its use is limited to individual agents. For example, the Association of Anaesthetists of Great Britain and Northern Ireland (AAGBI) recommend its use for local anaesthetic toxicity, perhaps the group of drugs where the greatest body of anecdotal evidence exists. 4. Why Did Metaraminol Work When All Else Failed? It is unclear why a synthetic, predominantly alpha-agonist (metaraminol) should have such a profound eﬀect when other agents with alpha-1 eﬀects, most notably nora- drenaline did not seem to. Whether it is the mechanism of action, a direct alpha agonist and an indirect alpha and beta agonist (via noradrenaline and adrenaline), or whether it has a property that has not yet been elucidated is speculative. The end product of metaraminol and other predominantly alpha-1 agents is calcium, but this is due to inositol triphosphate (which can act extracellularly), due to an increase in phospholipase C rather than from increased cAMP that results from adrenaline or noradrenaline. This additional pathway may go some way to explain why metaraminol worked. It has been recognised that pure alpha agonists such as phenylephrine and methoxamine have a role in the management of anaphylaxis where adrenaline has failed to have an eﬀect. Most notably in a case of anaphylaxis during open cardiac surgery where the ionotropic and chronotropic eﬀects were visible to the authors but the lack of SVR and underﬁlling meant that phenylephrine was crucial to the successful management of the patient [19]. Another reason why metaraminol may have worked where other agents did not is the possibility of dynamic left ventricular outﬂow obstruction. The diagnosis in critical care is important as reducing catecholamines and adding vasopressing agents may actually improve the situation [20]. 5 The metaraminol infusion was started later in the course of this case, and it could be proposed that the eﬀect of the calcium channel blocker and angiotensin II receptor blockers were wearing oﬀ by this time. Once-daily administration of losartan is possible because the drug’s eﬀects are extended by the EXP-3174 metabolite (which has a half-life of 6–9 hours), which is 40 times more potent than losartan and has been found to produce consistent reductions in blood pressure over a 24-hour period. [21] However, the half-life of amlodipine is 35–50 hours although the eﬀects can persist for signiﬁcantly longer [1]. A striking change was seen when metaraminol was given at the very start of the case (Table 1) and then again when it was bloused and started as an infusion (Figures 2 and 3). The patient was weaned from all other ionotropes within 2 hours (Figure 2). Conventional methods have often failed to improve haemodynamics in severe overdoses of this kind and Lheureux mentions in his excellent review that people have resorted to extreme measures such as intra-aortic balloon counterpulsation and extracorporeal circulatory support [2]. We propose a less extreme measure (the use of metaraminol by infusion) that is readily available and relatively cheap and that may avoid the need for more invasive cardiovascular or renal support. 5. Conclusions Care must be taken when hyperinsulinaemia-euglycaemia is used to avoid hypoglycaemia. A trial of metaraminol early in severe cases of calcium channel blocker and angiotensin II receptor antagonist toxicity may be of beneﬁt, especially when conventional ionotropic treatment measures are fail- ing. Conﬂict of Interests Acknowledgment The authors declared that there is no conﬂict of interests. This paper was published with the written consent of the patient. References [1] D. R. Abernethy, “Pharmacokinetics and pharmacodynamics of Amlodipine,” Cardiology, vol. 80, supplement 1, pp. 31–36, 1992. [2] P. E. R. Lheureux, S. Zahir, M. Gris, A. S. Derrey, and A. Penaloza, “Bench-to-bedside review: hyperinsulinaemia/ euglycaemia therapy in the management of overdose of calcium-channel blockers,” Critical Care, vol. 10, no. 3, article 212, 2006. [3] C. Sandroni, F. Cavallaro, C. Addario, G. Ferro, F. Gallizzi, and M. Antonelli, “Successful treatment with enoximone for severe poisoning with atenolol and verapamil: a case report,” Acta Anaesthesiologica Scandinavica, vol. 48, no. 6, pp. 790– 792, 2004. [4] D. M. Wood, K. D. Wright, A. L. Jones, and P. I. Dargan, “Metaraminol (Aramine in the management of a signiﬁcant