Opioid Misuse and a Broken Heart: Pulmonary Edema and Takotsubo Cardiomyopathy Post Naloxone Use

Abstract

INTRODUCTION: Noncardiogenic pulmonary edema from naloxone is a rare adverse effect; but even more uncommon is the development of Takotsubo Cardiomyopathy (TCM).CASE PRESENTATION: A 75-year-old woman with a history of breast cancer s/p bilateral mastectomy & post-herpetic neuralgia on chronic opioids, presented with clostridium colitis. On day 3 of admission, she was noted to have decreased responsiveness, pinpoint pupils & an empty bottle of Hydrocodone/acetaminophen was found at bedside. She was given IV naloxone 0.4mg. Two hours after naloxone admission, RR 32, HR 115 bpm, BP 133/86mmHg, SpO2 97% on RA. Physical exam revealed normal pupils, hyperdynamic apex with no murmurs, basilar crackles throughout, BNP 1,170 pg/ml (normal 0-100PG/ ML). EKG sinus tachycardia, CXR showed pulmonary edema and ABG 7.49/<16.1/65.8/CNC. She was initiated on BIPAP but subsequently intubated due to continued respiratory distress. She remained intubated for 2 days where she received IV Lasix with improvement of pulmonary congestion. ECHO showed LVEF 20-25 % with mid-ventricle extending to apex is akinetic in a circumferential pattern, sparing the base which was hyperdynamic, consistent with TCM. Cardiac catherization showed 30% occlusion of mid-LAD & 20% occlusion of mid LCX with severely elevated LVEDP 34mmhg with wall motion abnormality consistent with TCM. She was discharged on daily metoprolol 25mg, losartan 25 mg, ASA 81 mg & lasix 20mg.DISCUSSION: Though undoubtedly an important tool in addressing the magnitude of opioid overdose cases both in & outside of hospitals, naloxone is not without its own concerns; many of which are related to the heart. It has been demonstrated in animal & human models that naloxone induces catecholamine release which has direct positive inotropic effects on the heart (2). It reverses the usual inhibitory effects that endogenous opioids have in regulating catecholamine release in peripheral sympathetic nerves & adrenal medullae(2). This mechanism results in hypertension including at the level of the pulmonary vasculature leading to pulmonary vasoconstriction & increased capillary permeability, (1) decreased gaseous exchange and subsequent translocation of fluid into the alveoli. This results in the pulmonary edema as well as the resultant hypoxia with eventual acute hypoxic respiratory failure.Similarly, it is plausible that this same mechanism of acute surge in plasma catecholamine levels leads to direct toxicity on cardiomyocytes. Acute catecholamine surge is purported to result in stunning of the myocardium leading to characteristic changes noted in TCM. The findings of TCM are transient and are the main distinguishing feature of this condition from other cardiomyopathies.