Ecmo in Acute Poisoning

ECMO Conference 5/17/2019

OBJECTIVES

• Indications for ECMO in acute poisoning • 3 representative cases ECMO IN ACUTE POISONING • Essential treatments • Special considerations when using ECMO in acute poisoning Clara Zamorano, MD • Conclusions Intensivist Abbott Northwestern Hospital

May 17, 2019

Indications for ECMO in Acute Poisoning Cardiogenic shock in toxicology

VV-ECMO VA-ECMO • Calcium channel blocker or beta-blocker • • ARDS: • Ingestions that cause Sodium channel blocker: TCAs, buproprion, SNRIs, anti- • Inhalant exposure causing lung injury cardiovascular collapse due to: epileptics (carbamazepine, lacosamide, lamotrigine, • Aspiration of toxic agents • Dysrrhythmias phenytoin), amiodarone, lidocaine and bupivicaine (LAST) • Drug side effect • Acute cardiomyopathy • Not shown to be beneficial in • Heavy metals: cobalt vasodilatory shock • Imidazolines (clonidine) • Ketamine (ACS) • Many more

Patient 1: Massive Calcium Channel Overdose

• 41 y/o F h/o depression found • Hypotensive, pressors titrated to Drug and confused at home with several 15mcg/kg/min dopamine, empty pill bottles 12mcg/min epinephrine, 12 Patient • Amlodipine – at least 90 tabs 5 mg mcg/min norepi, 100 mgc/min Factors in • Losartan – unknown amount phenylephrine, vasopressin 0.04 • BP on arrival of EMS 70/32 units ECMO • ED 60/p • TTE: LVEF 35% • Intubated and sent to ANW • Develops multi-organ failure • Epi, dopamine, norepi; remains in • Taken for VA ECMO cannulation refractory shock

Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy, Volume: 37, Issue: 2, Pages: 221-235, First published: 08 December 2016, DOI: (10.1002/phar.1882)

©AllinaHealthSystems 1 ECMO Conference 5/17/2019

Patient 1 CCB / ßBlocker Overdose Presentation

• Given trial bolus of intralipids • Hemodynamics improved by CCBs BetaBlockers • Unable to check labs until circuit HD 2-3, EF normal on TTE changed • Dihydropyridines- Relax vascular • Decrease myocardial contractility • HD #3: Converted to VV ECMO smooth muscle • Thrombocytopenia and high due to ARDS • Hypotension • Bradycardia and hypotension post-oxygenator pressures • HD#7: decannulated • Tachycardia • HYPOglycemia • Non-dihydropyridines-decrease • Develops progressive hypoxic • HD# 9: extubated. myocardial contractility • Altered mental status respiratory failure • HD#10: transferred to floor • Hypotension • Seizures • Bradycardia • Started on high dose insulin • QTc prolongation • HD #12: transferred to infusion • HYPERglycemic psychiatry unit. • Awake • Given methylene blue • Discharged home after 17 days • Difference in effect between 2 classes converges as dose increases

CCB / ßBlocker OD Treatment IV Lipid Emulsion

• Used as a lipid sink for lipid soluble drugs with higher LogP CCB ßB • In ECMO: • Cracking of stopcocks • Atropine 0.5-1mg q3-5 minutes up to • Clogging and malfunction of membrane oxygenator 4 mg • Increased clot formation in circuit • Calcium chloride 1g IVP, consider • ARDS/non-cardiogenic pulmonary edema (side effect even without use of ECMO) infusion • Lab interference for many hours • Dextrose for hypoglycemia • • Glucagon 5-10 mg IV, then 2-10 mg/h Could give/use prior to cannulation and plan to change circuit after 6-12 hours • Pressors (Epi/NE) if possible • High dose insulin protocol • If considering use for sequestration of lipophilic drug, ECMO circuit may be as • Intralipid effective in sequestration • 1-1.5ml/kg bolus + 0.25-0.5ml/kg/min infusion. May repeat bolus

High Dose Insulin Patient 2: Sodium Channel Blocker Overdose

• Increases uptake of • Degraded an eliminated by liver • 17y/o F found unresponsive ~5pm • 11AM: refractory seizures carbohydrates by myocardium and kidney • empty pill bottles holding up to 150 • HypotensionPEA arrest, pills of 150 mg Wellbutrin SR cardiogenic shock with EF 10% • Glucose preferred fuel substrate • No data regarding insulin during stress adsorption by circuit, however • EMS called to roadside, • Given intralipid and IV lidocaine to continued to seize and vomit no avail • Strong inotropic effect in patients on ECMO, relative • Accelerates oxidation of insulin resistance is common • Intubated and brought to ED at • Cannulated and initiated on VA Mercy Hospital ECMO with Impella, sent to ANW myocardial lactate • Some centers prime circuit with • EKG • Arterial vasodilation in insulin • Wide QRS and long QTc microcirculation • ANW does not do this currently • Started on sodium bicarb infusion • Propofol

©AllinaHealthSystems 2 ECMO Conference 5/17/2019

Patient 2 Sodium Channel Blockers Presentation Treatment • Harlequin syndrome noted due • HD#4:Transitioned to VV • TCAs, SSRIs, SNRIs, MAOIs • Treat seizures to severe pulmonary edema/ ECMO • Block sodium channels in • Benzos / barbiturates concomitant hypoxic respiratory • HD#6: Decannulated and myocardium conduction and • Propofol if EF and BP tolerate failure contractility derangement • Sodium bicarbonate infusion extubated • Profound CM, tachycardia, HTN • Bolus 1-3 amps • Reconfigured to VAV ECMO • HD#7: Transferred to floor • Obtundation • Infusion with pH goal >7.55 • N/V • 3% saline • Completed therapeutic • Clonus/hyperreflexia, seizures • Rehabbed and was followed by • Consider lidocaine (avoid in LAST) • QTc prolongation and widening of QRS hypothermia protocol psych while awaiting psych bed • Replace magnesium and potassium • TTE HD#3 with EF 60-65% • Discharged to psych on HD#14 • Local anesthetics • Intralipids • Anti-epileptics • GI symptoms, hyponatremia, tremor, drowsiness

Bicarb Infusion Patient 3: Cobalt Poisoning

• Potential benefits: • 64 F h/o CAD, mild ischemic CM, • Now with progressive AKI, • High sodium load cardiogenic shock, elevated LFTs, • Metabolic alkalosis with decreased tissue penetration and enhanced excretion in urine DJD hip s/p L hip arthroplasty encephalopathy, elevated lactate • Ionize the drug into inactive form (‘09),hypothyroidism, obesity, • Side effects: admitted to hospital following total • Transferred to ICU on HD #3: • Electrolyte abnormalities- hypo calcemia and kalemia • EF 20%, PAWP 45mmHg • Volume overload hip revision. • Creatinine 3.14 with bicarb 15 • Respiratory failure • Worsening of CHF for 2 years, also • LFT: ALT 716/AST1293 • Usually target pH 7.5 -7.55 with paresthesias, hypothyroidism, • Sodium loading and pH increase drive therapeutic effects to varying degrees • HD#4: ALT 700/AST 3511 depending on specific overdose drug previous pericardial effusions • Lactate: 9.9 • Animal and lab models • Patient had metal on metal hip • Cobalt level found to be 222.8ng/mL • ECMO circuit highly efficient for blowing of CO2 explanted on HD#1 prior to surgery (normal <1ng/mL) • Can adjust sweep to keep pH slightly alkalotic • CRRT started HD#4 • Watch for evolution of pulmonary edema/signs of volume overload

Patient 3 Cobalt Toxicity

• Started on dobutamine, nitrates. • After initial improvement, • Started on N-acetylcysteine, developed refractory cardiogenic • Metal on metal prosthetic joints • Interferes with calcium’s shock thiamine 500 mg TID • Insidious onset of multi-organ inotropic effects • Intubated due to progressive • EDTA obtained, started on HD#4, failure including dilated • Interrupts aerobic cellular encephalopathy HD#10 completed 5 day course cardiomyopathy, pericardial respiration • LFTs rapidly normalized • Started on VA ECMO HD#12 effusion, renal failure, liver • Citric acid cycle • Acidosis improved • Extubated HD#20 disease • CRRT initiated for renal failure • HeartMate 3 with central RVAD • Treatment: • • Gradually able to wean off Often co-exists with • Removal of exposure as able inotropes, RVAD hypothyroidism or thiamine • Chelation • Discharged to home HD #49 deficiency

Chelating Agents Summary

• Little to no published data on real • Examples: • ECMO is useful in refractory cardiogenic shock due to acute overdose of patients • EDTA-ethylenediaminetetraacetic acid many drugs • Most highly protein-bound (calciumdisodium) • DMSA-Meso-2,3-dimercaptosuccinic Acid • ECMO circuit and drug interactions impact therapy in important ways • Bind cationic metals and enhance • DMPS-sodium 2,3 Dimercaptopropane-I- • If proceeding toward ECMO in the acutely poisoned patient, consider: renal excretion sulphonate • Side effects: • Calcium trisodium • Avoiding intralipids • Renal failure diethylenetriaminepentaacetate • Titrating Sweep Flow to pH >7.4 if overdose requiring bicarb drip • CaNa DTPA • Hypocalcemia 3 • That insulin infusion may require higher than published rates of infusion • Hypotension • Deferrioxamine • Chelator use in setting of renal failure will likely require renal replacement therapy and that • Coagulopathy • N-acetylcysteine dose used may need to be higher • Zinc depletion • Chemistry suggests could be highly • Bone marrow suppression sequestered by circuit • Always involve Poison Center in overdose cases • If renal failure dialyze patient as • 1-800-222-1222 many are dialyzable

Special Thanks TO CONTACT ME

•Matt Lillyblad • Email: • [email protected] •Kate Katzung • [email protected] • Mail: Clara Zamorano, ANW Intensivists 800 W 28th St, Minneapolis, MN 55407

REFERENCES

• Bibro C, Lasich C, et al. Critically ill patients with H1N1 influenza A undergoing extracorporeal membrane oxygenation. Crit Care Nurse Oct 2011;31(5): e8-e24 • Bou-Abboud E, Nattel S. Relative role of alkalosis and sodium ions in reversal of class I antiarrhythmic drug-induced sodium channel blockade by sodium bicarbonate. Circulation. 1996 Oct; 94(8): 1954-1961 • Ciapetti M, Mancinelli P, et al. Reduction of non-enzymatic antioxidants in plasma during ECMO-treatment in ARDS by influenza A H1N1. J Crit Care 2018 Feb;43:220-224 • Flora JS, Pachuri V, et al. Chelation in Metal Intoxication. Int J Environ Res Public Health. 2010 Jul; 7(7): 2745-2788 • Goel, S, Hoskote S. Cobalt-Induced Cardiomyopathy requiring venoarterial ECMO. Critical Care Medicine 2016 Dec;44(12): supplement 1, 481 • Ha MA, Sieg AC. Evaluation of altered drug pharmacokinetics in critically ill adults receiving extracorporeal Membrane oxygenation. Pharmacotherapy 2017 Feb;37(2): 221-235. • Lee HM, Archer JR, et al. What are the adverse effects associated with the combined use of intravenous lipid emulsion and extracorporeal membrane oxygenation in the poisoned patient? Clin Toxicol (Phila) 2015 Mar;53(3): 145-50. • Martin C, Gonzalez H, et al. Acute respiratory distress syndrome following verapamil overdose treated with intravenous lipid emulsion: a rare life-threatening complication. Ann Fr Anesth Reanim 2014 Jun;33(6):e101-2 • Mirrakhimov AE, Ayach T, et al. The role of sodium bicarbonate in the management of some toxic ingestions. Int J Nephrol. 2017; 2017: 7831358 • Monico A, Martinez-Senra E, et al. Drawbacks of Dialysis Procedures for Removal of EDTA. PLoS ONE 2017 Jan; 12(1): e0169843 • Packer, M. Cobalt Cardiomyopathy. Circulation: Heart Failure 2016 Dec; 9(12). • Park TK, Yang JH, et al. Extracorporeal membrane oxygenation for refractory septic shock in adults. Crit Care Med 2013 Jul;41(7): 1616-26 • Wildschut ED, van Saet A, et al. The impact of extracorporal life support and hypothermia on drug disposition in critically ill infants and children. Pediatr Clin North Am 2012 Oct;59(5): 1183-1204.