1.3 1) 1.2 −in 1.1 1−m· 1 gk· g 0.9 cm ( 0.8 lon i 0.7 am r 0.6 tea M 0.5 800 700 600 500 400 300 200 100 0 r h r e p s t i n U 4 92 88 g 84 H80 m Pm76 AM72 68 64 60 95 90 85 80 75 )70 gH65 m60 (m55 50 45 40 35 30 Metaraminol boluses until infusion setup 38 40 42 44 46 48 50 52 54 56 58 60 62 64 66 Time (hrs since ED admission) Metaraminol mcg·kg−1·min−1 MAP mmHg Metaraminol bolus Figure 3: MAP after starting metaraminol infusion (hours 38– 66). Note left y-axis MAP in mmHg, right y-axis metaraminol in mcg·kg−1·min−1. Arrows show metaraminol boluses. 5 15 25 35 45 55 65 75 85 95 Time (hrs since ED admission) MAP mmHg Insulin units per hr Figure 4: The eﬀect of hyperinsulinaemia-euglycaemia on MAP. The patient was started on a metaraminol infusion 46- 47 hrs after admission to ED following a discussion with the team about her initial response to the drug. There was an immediate striking response, the MAP increasing from below 70 mmHg to more than 80 mmHg for the ﬁrst time since admission (aside from the boluses given at 5 hours), but even more striking was the change in urine output which increased dramatically (Figure 5). The eﬀect of metaraminol permitted the other ionotropes to be weaned over the next few hours (Figure 2). Her urine output improved but she developed hyperkalaemia (6.3 mmol·l−1)—a likely side eﬀect of hyperinsulinaemia-euglycaemia therapy cessation. She made a slow recovery and was discharged to Medical High Dependency 6 days after admission. She was discharged from hospital, after psychiatric input, shortly afterwards. 3. Discussion This is the ﬁrst case report of severe calcium channel blocker and angiotensin II receptor blocker overdose that was 1.4 1.3 1.2 )1.1 1− 1 in0.9 m·0.8 1−0.7 g0.6 g·0.5 k c0.4 (m0.3 0.2 0.1 0 Case Reports in Medicine 800 700 600 200 100 0 500 1) − 400 rh· L 300 (m 5 15 25 35 45 55 65 75 85 95 Time (hrs since ED admission) Metaraminol mcg·kg−1·min−1 UO mls·hr−1 Figure 5: The eﬀect of metaraminol on urine output. successfully treated with a metaraminol infusion where other treatment options failed or had not been tried. The only other case report in the literature did not use metaraminol by infusion, as the drug was not available to them. Direct personal communication with the lead author conﬁrmed this [11]. The paper by Wood et al. which successfully used metaraminol did not use hyperinsulinaemia-euglycaemia at all and the overdose, although mixed, had a much lower (120 mg) dose of an angiotensin converting enzyme inhibitor compared with the 16.6 g of the angiotensin II receptor blocker that the patient in our case had ingested [4]. Hyperinsulinaemia-euglycaemia appears to work by allowing the switch of cellular metabolism from fatty acids to carbohydrates that is required in stress conditions, especially in the myocardium and vascular smooth muscle, resulting in an improvement in cardiac contractility and restored peripheral resistances [2]. Most of the current evidence around hyperinsulinaemia- euglycaemia (from the various case reports quoted) seems to suggest that starting it early is crucial to its success. We started it within 14 hours. There is not a consistent time frame in the literature that constitutes early administration. However, as described in a couple of other case reports, we found that it had little eﬀect [12, 15]; however, there was perhaps a transient increase at the start when we were infusing 800 units per hour; however, multiple infusions were initiated between 11 and 16 hours so it is diﬃcult to attribute this to the hyperinsulinaemia-euglycaemia and the ionotropes were greatly uptitrated during this period (Figure 4). In our case, we did however ﬁnd that keeping up with the blood sugar was problematic and dangerous. Large amounts of glucose were required with intensive nursing care to prevent hypoglycaemia. We found that the glucose suddenly dropped over the space of 3 minutes between checks after a long period of not changing consistent with the reported 40 minutes or so for the hyperinsulinaemia-euglycaemia to start working. Previous case reports and reviews have mentioned the low side eﬀects of hyperinsulinaemia-euglycaemia mak- ing it an attractive option [2].