a b s t r a c t

Poisoning caused by calcium-channels blockers (CCB) can cause refractory vasoplegic shock, resulting in multi- ple-organ failure and death despite maximal therapy including high doses of vasopressors. We report one CCB- induced refractory shock complicated with lactate acidosis despite very high doses of epinephrine and norepi- nephrine. The hemodynamic status of the patient dramatically improved after Intermittent boluses of terlipressin, which corrected the acidosis.

(C) 2017

Discussion

A 46-year-old woman was admitted into the intensive care unit of the emergency department 4 h after ingesting 8.4 g of extended- release diltiazem. At admission, her blood pressure was low (91/48 mm Hg), clinical examination was normal, and an electrocar- diogram showed a junctional rhythm with a frequency of 70 b.p.m. Ini- tial echocardiography showed normal systolic left-ventricular function, confirming vasoplegic shock. Treatment consisting in insulin glucose and calcium was initiated, and norepinephrine was administered to maintain an acceptable mean blood pressure. Her Hemodynamic state rapidly deteriorated and 10 h after admission the patient received 83 gamma.min^-1 norepinephrine and 66 gamma.min^-1 epinephrine. Acute oliguric renal failure started (Diuresis b 0.5 mL/h/kg in the last 3 h). New echocardiography was performed and did not show any arguments for a cardiogenic shock, excluding extracorporeal life sup- port indication. Laboratory testing showed increasing lactate acidosis (9.9 mmol/L). Intermittent boluses of 0.1 mg of terlipressin (Total small dose of 0.3 mg) permitted a rapid improvement in hemodynamic status with decreased levels of both norepinephrine and epinephrine, and lactates (Fig. 1).

Normal diuresis concomitantly and quickly recovered. Epinephrine and norepinephrine were stopped, respectively, at 11 and 46 h after ad- mission. The patient was discharged on day 6.

* Corresponding author at: Service de Reanimation Medicale, Hopital Pellegrin-Tripode, Place Amelie Raba Leon, 33076 Bordeaux Cedex, France.

E-mail address: [email protected] (A. Boyer).

Diltiazem poisoning can result in vasoplegic shock and disturbances in intracardiac conduction, which can lead to death. Despite its severity, few data exist on the best management of calcium-channels blockers (CCB) poisoning. These treatments include aggressive volume resuscita- tion, euglycemic insulin, calcium, glucagon, atropine, vasopressors, Intravenous lipid emulsion, or Extracorporeal life support in cases of cardiogenic shock. Among these different options, vasopressors are crucial in maintaining hemodynamic status, especially in cases of vasoplegic shock. In their case series, Levine et al. [1] reported on the use of vasopressors in 69% of patients who had verapamil or diltiazem toxicity, using maximal doses of 100 and 150 gamma.min^-1 epineph- rine and norepinephrine, respectively. This case illustrate that, despite optimization of treatment that includes high doses of vasopressors, it is sometimes difficult to sustain hemodynamic parameters after diltia- zem poisoning. Terlipressin is a synthetic analog of vasopressin. Once intravenously administered, it is converted into lysine vasopressin, resulting in a vasopressor effect that lasts for ~ 6 h. Vasopressin and terlipressin are relevant treatments for refractory vasoplegic shock: they induce catecholamine-independent vasoconstriction via V1 recep- tors. However, terlipressin has a 6-h half-life making its intermittent ad- ministration potentially more convenient than vasopressin. A case of continuous vasopressin administration for diltiazem poisoning was also reported with similar findings than our case except for the use of vasopressin instead of terlipressin [2]. This is, to our knowledge, the sec- ond case report on terlipressin administration for diltiazem poisoning [3]. In the reported patient, no adverse effects were noted with intermit- tent administration of terlipressin.

http://dx.doi.org/10.1016/j.ajem.2017.01.062

0735-6757/(C) 2017

Fig. 1. Persistent shock despite combined vasopressors use until the addition of terlipressin at 12 h. The hemodynamic status of the patient dramatically improved after intermittent boluses of terlipressin, which corrected the lactate acidosis.

Conclusion

Terlipressin should be considered as a Rescue therapy in catechol- amine refractory shock induced by CCB poisoning.

Conflict of interest

The authors declare there is no conflict of interest.

Funding

This research received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

References

1. Levine M, Curry SC, Padilla-Jones A, et al. Critical care management of verapamil and diltiazem overdose with a focus on vasopressors: a 25-year experience at a single center. Ann Emerg Med 2013;62:252-8.
2. Kanagarajan K, Marraffa JM, Bouchard NC, et al. The use of vasopressin in the setting of recalcitrant hypotension due to Calcium-channel blocker overdose. Clini Toxicol 2007;45:56-9.
3. Leone M, Charvet A, Delmas A, et al. Terlipressin: a new therapeutic for calcium-chan- nel blockers overdose. J Crit Care 2005;20:114-5.