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 Table of Contents  
CASE REPORT
Year : 2020  |  Volume : 6  |  Issue : 3  |  Page : 229-233

Use of lifesaving extracorporeal membrane oxygenation in a case of massive hydroxychloroquine overdose


1 Department of Medicine, Eastern Idaho Regional Medical Center, Idaho Falls, ID, USA
2 Department of Critical Care Medicine, Eastern Idaho Regional Medical Center, Idaho Falls, ID, USA

Date of Submission20-Jun-2019
Date of Acceptance05-Jun-2020
Date of Web Publication26-Sep-2020

Correspondence Address:
Dr. Asma Rashid
Department of Medicine, Eastern Idaho Regional Medical Center, 3100 Channing Way, Idaho Falls, ID 83404
USA
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/IJAM.IJAM_39_19

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  Abstract 


Hydroxychloroquine (HCQ), approved by the Food and Drug Administration in 1955, has high potential for overdose due to its increasing use related to mortality and morbidity benefit in many autoimmune diseases. Lack in the current available data regarding standardized management and practical approach needed in overdose cases necessitates a discussion on this topic. The purpose of this case presentation is to add to the current medical literature on HCQ overdose and management, to determine possible guidelines for guiding therapy in future for HCQ toxicity, and to present recommendations for more efficient and timely management that may reduce the morbidity and mortality of patients with intentional or accidental HCQ overdose.
The following core competencies are addressed in this article: Medical knowledge, Patient care, Interpersonal and communication skills, Practice-based learning and improvement

Keywords: Continuous renal replacement therapy, diazepam, extracorporeal membrane oxygenation, hydroxychloroquine, hyperkalemia, pressors, prolonged QT interval


How to cite this article:
Rashid A, Rehan MA, Sneck B, Jennifer E, Whatmore D. Use of lifesaving extracorporeal membrane oxygenation in a case of massive hydroxychloroquine overdose. Int J Acad Med 2020;6:229-33

How to cite this URL:
Rashid A, Rehan MA, Sneck B, Jennifer E, Whatmore D. Use of lifesaving extracorporeal membrane oxygenation in a case of massive hydroxychloroquine overdose. Int J Acad Med [serial online] 2020 [cited 2020 Nov 30];6:229-33. Available from: https://www.ijam-web.org/text.asp?2020/6/3/229/296143




  Introduction Top


Hydroxychloroquine (HCQ) is not only used as an antimalarial agent but is also prescribed for systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) as a disease-modifying antirheumatic drug.[1],[2] Due to its rapid systemic absorption from the gastrointestinal tract, doses as low as 4 g can be toxic in an adult and a single tablet of 200-300 mg can take life of a toddler.[3],[4] Studies have reported fatalities with ingestion of about 12 g in adults.[3] The devastating effects of hydroxycholoroquine include severe cardiac conduction defects, ventricular arrhythmias, depressed cardiac function, hypotension, respiratory depression, hypokalemia, hypoglycemia, metabolic acidosis, convulsions, central nervous system depression, and visual problems.[1],[2] The peak plasma level of the drug is usually achieved in 3–4 h.[1] The terminal half-life of the drug is approximately 50 days in blood, 32 days in plasma, and it stays in the body for about 3 months.[5],[6],[7] As the absorption half-life of the drug is approximately 3–4 h, the toxic effects of the drug start to mitigate once peak plasma concentrations is achieved in 3–4 h.[1]

There are at least 42 cases of HCQ overdose reported in the medical literature since its approval by the Food and Drug Administration in April 1955.[8] HCQ is an extremely lipophilic drug that gets readily distributed in the intracellular compartment, and so extrarenal filtration measures of drug removal are ineffective.[9],[2] Historically, HCQ overdose is managed by supportive measures of gastric lavage, activated charcoal, intubation and mechanical ventilation, sodium bicarbonate, magnesium sulfate, vasopressors, intravenous (IV) fluids, potassium, glucose, and occasionally, pacemaker placement.[2] Conventionally, diazepam use was considered a lifesaving intervention, but since the past decade, IV lipid emulsion (ILE) and extracorporeal membrane oxygenation (ECMO) have emerged as effective intervention options.

Another significant thing to consider is the paucity of data about HCQ overdose cases. The reason for this is the lack of reporting in the developed world, especially in the developing countries where it is used for malaria management and its parent compound chloroquine as perceived abortifacient in Asia, Africa, and the Pacific Islands.[10] This delineates a lack of research culture as well as the proper infrastructure needed to handle such situations judiciously.


  Case Report Top
[Figure 1]
Figure 1: Timeline of events in the case

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A 15-year-old girl presented to the emergency department (ED) 40 min after an intentional overdose of 40 g HCQ. On presentation, her Glasgow Coma Scale (GCS) was 11, heart rate: 61, blood pressure: 70/55, respiratory rate: 20, and O2 saturations 77% on RA. She was immediately started on IV crystalloids via two peripheral lines. Within minutes following arrival, GCS dropped to 3, and she developed resistant hypotension requiring simultaneous norepinephrine (NE) and epinephrine infusions. The patient started vomiting and was unable to maintain her airway, so she was intubated and mechanical ventilation was started. Her metabolic panel showed K + of 2.1 and glucose of 45 mg/dl which were replaced as needed. Her QRS complex and QTc interval were prolonged to 166 and 730 ms [Figure 2], and within minutes, the patient started to experience arrhythmias ranging from Ventricular tachycardia to Ventricular Fibrillation requiring multiple shocks and two rounds of Cardiopulmonary resuscitation, sodium bicarbonate, magnesium sulfate, epinephrine, and amiodarone pushes. Due to severe refractory cardiovascular collapse, the patient was cannulated, VA-ECMO started, and she was transferred to the intensive care unit (ICU).
Figure 2: Electrocardiogram of the patient

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In the ICU, the patient required ongoing support for continued hypotension including fluids and vasopressin, in addition to NE and epinephrine. She was also started on diazepam. She received a continuous infusion of KCl, in total over 450 meq in 24 h. Her refractory hypokalemia on presentation switched to rebound hyperkalemia 24 h post admission, leading to ectopy, VT, and wide complex tachycardia for which the patient received multiple shocks, lidocaine, and amiodarone. Continuous renal replacement therapy was started and her potassium normalized over 36 h. The patient was started on milrinone and was de-cannulated from VA-ECMO at around 60 h. Milrinone was weaned at 4.5 days. The patient's hospital course was complicated by right lower extremity reperfusion injury post-ECMO and she required fasciotomy. Psychiatric consultation was also done, and the patient was successfully discharged for rehabilitation at day 14.


  Discussion Top


Fung, et al. in January 2007 reported 20 cases of hydroxychlorquine overdose.[13] Following an extensive review of medical literature, we found 42 reports of HCQ overdose [Table 1]. The maximum ingested dose was 60 g,[11] and our patient consumed 40 g which is so far the second-highest dose reported. The reviewed cases showed cardiovascular collapse as the major cause of mortality and morbidity. Studies have indicated that the degree of hypokalemia is a good index of the severity of HCQ overdose.[12] Almost all the patients reported intentionally took the medication except a 64-year-old female and a 2-year-old male. Eighty percent of the patients were females and majority had a history of psychiatric disorders and some were diagnosed with RA or SLE. By reviewing previous case reports, it is obvious that the mainstay of therapy is supportive which includes gastric decontamination, activated charcoal, intubation and mechanical ventilation, vasopressors, inotropes, dextrose, NaHCO3, magnesium sulfate, and potassium.[13],[3],[12],[9] Diazepam was once considered an unofficial antidote which had a major role in treatment until 2008–2009.[13],[12],[9] ILE, first introduced for local anesthetic related cardiovascular collapse, is gaining popularity in chloroquine and HCQ overdose cases as well.[14] Although the first two cases reported by Wong, et al. died even after ILE use, this could be related to the late arrival of patients in the ED, around 150 min and 180 min post ingestion.[15] Apart from these two cases, ILE is successful in reducing the burden of the drug in the system and increasing the survivability.[9] Mongenot, et al. in 2006, reported the first case of HCQ overdose survival in France in which ECMO was used as a definitive treatment.[16] The second case in which ECMO was used was also reported in France. Our case is the first in the US and third overall to use ECMO as a last and lifesaving resort after exhausting all other treatment options except ILE. Analysis of the available data from the 42 case reports shows that the survival rate on ECMO support is 100% (3/3 cases survived), on ILE is 71.43% (5/7 cases survived), and on diazepam is 81.82% (9/11 cases survived). Of 43 cases, there were eight fatalities, among which 75% died secondary to Cardiovascular collapse.
Table 1: Details of 42 case reports reviewed

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  Conclusions Top


Therapy for HCQ overdose includes electrolyte and glucose support as well as ILE, VA-ECMO, and possibly, diazepam. If the known drug ingested is HCQ, the patient should get activated charcoal within an hour following ingestion. Unstable patients need early intubation and mechanical ventilation, pressor support, and arrhythmia management, along with advanced management options of ILE and ECMO. Stentz, et al.in 2018 reported growth of ECMO from 1.06 to 1.77 cases per 100,000 persons per year from 2011 to 2014 in 34 participating states.[17] Based on this report, we anticipate that ECMO use will continue to increase, and it will be more readily available in small community-based hospitals. As CV collapse is the major cause of mortality in HCQ overdose cases, we recommend that patients should be transported to the nearest ECMO facility if possible. Apart from supportive therapy, ECMO, ILE, and possibly, diazepam combined will have the highest beneficial effect on the overall survivability of the patient.

Declaration of patient consent

The authors certify that they have obtained appropriate patient consent forms. The patient has given their consent for the publication of their images and other clinical information to be reported in the journal. The patient understands that their name and initials will not be published, and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

Ethical conduct of research

The authors declare that this scientific work complies with reporting quality, formatting, and reproducibility guidelines set forth by the EQUATOR Network. The authors also attest that this clinical investigation did not require Institutional Review Board/Ethics Committee Review. For this work, formal consent of the patient was obtained.



 
  References Top

1.
Concordia Pharmaceuticals Inc. Plaquenil Hydroxychloroquine Sulfate Tablets, USP. FDA; 2017. Available from: https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/009768s037s045s047lbl.pdf. [Last accessed on 2020 Feb 17].  Back to cited text no. 1
    
2.
Wong AL, Cheung IT, Graham CA. Hydroxychloroquine overdose: Case report and recommendations for management. Europ J Emerg Med 2008;15:16-8.  Back to cited text no. 2
    
3.
Kruisselbrink RJ, Ahmed S. Acute hydroxychloroquine overdose: Case report, literature review, and management recommendations. Am J Respir Crit Care Med 2010;181:A6080.  Back to cited text no. 3
    
4.
Rickner S. Case studies in toxicology: Somehow… It's always lupus a 14-year-old girl presented with normal mental status following an intentional overdose. Within 30 minutes of arrival, she developed profound hypotension, electrocardiogram abnormalities, and hypokalemia. Emerg Med 2016;48:493-5.  Back to cited text no. 4
    
5.
Drug Bank; 2019. Available from: https://www.drugbank.ca/drugs/DB01611. [Last retrieved on 2019 Mar 12].  Back to cited text no. 5
    
6.
Long N. Chloroquine and Hydroxychloroquine. Life in the Fast Lane. 09 February, 2019. Available from: https://lifeinthefastlane.com/tox-library/toxicant/anti-malarial/chloroquine-and-hydroxychloroquine/ [Last accessed on 2020 Feb 17].  Back to cited text no. 6
    
7.
Ochsendorf FR, Runne U. Chloroquine and hydroxychloroquine: Side effect profile of important therapeutic drugs. Hautarzt 1991;42:140-6.  Back to cited text no. 7
    
8.
Friedman C. FDA approves Sanodi Aventis's Plaquenil; 2019. Available from: https://worldhistoryproject.org/1955/4/18/fda-approves-sanodi-aventiss-plaquenil [Last accessed on 2020 Feb 17].  Back to cited text no. 8
    
9.
Ten Broeke R, Mestrom E, Woo L, Kreeftenberg H. Early treatment with intravenous lipid emulsion in a potentially lethal hydroxychloroquine intoxication. Neth J Med 2016;74:210-4.  Back to cited text no. 9
    
10.
Gunja N, Roberts D, McCoubrie D, Lamberth P, Jan A, Simes DC, et al. Survival after massive hydroxychloroquine overdose. Anaesthesia Intensive Care 2009;37:130-3.  Back to cited text no. 10
    
11.
Ndukwu I, Ghahramani M. Hydroxychloroquine overdose presenting as acquired QT interval prolongation and torsade de pointes. Journal of the American College of Cardiology 2017;11,2340.  Back to cited text no. 11
    
12.
Shippey EA, Wagler VD, Collamer AN. Hydroxychloroquine: An old drug with new relevance. Cleve Clin J Med 2018;85:459-67.  Back to cited text no. 12
    
13.
Fung HT, Lam KK, Wong OF, Lau B, Kam CW. A case of fatal hydroxychloroquine overdose. Hong Kong J Emerg Med 2007;14:53-7.  Back to cited text no. 13
    
14.
Stentz MJ, Kelley ME, Jabaley CS, O'Reilly-Shah V, Groff RF, Moll V, et al. Trends in extracorporeal membrane oxygenation growth in the United States, 2011-2014. ASAIO J 2019;65:712-7.  Back to cited text no. 14
    
15.
Wong OF, Chan YC, Lam SK, Fung HT, Ho JK. Clinical experience in the use of intravenous lipid emulsion in hydroychloroquine and chloroquine overdose with refractory shock. Hong Kong J Emerg Med 2011;18:243-8.  Back to cited text no. 15
    
16.
Mongenot F, Gonthier YT, Derderian F, Durand M, Blin D. Treatment of hydroxychloroquine poisoning with extracorporeal circulation. Ann Francaises D'anesthesie et de Reanimation 2007;26:164-7.  Back to cited text no. 16
    
17.
Marquardt K, Albertson TE. Treatment of hydroxychloroquine overdose. Am J Emerg Med 2001;19:420-4.  Back to cited text no. 17
    


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