Via Research Recognition Day 2024 VCOM-Carolinas

Clinical Case-Based Reports

Calcium Channel Blocker Overdose Causing Acute Respiratory Distress Syndrome and Acute Kidney Injury in Fifteen-Year-Old Female Larsen H. Welsh, OMS-IV 1 , Jeremy T. Bose, OMS-IV 1 , Hanna S. Sahhar, MD, FAAP, FACOP 1,2 1 Edward Via College of Osteopathic Medicine, Spartanburg, SC; 2 Spartanburg Regional Healthcare System, Spartanburg, SC

Hospital Course

Discussion & Conclusion

Abstract

Hospital #1 - Patient remained profoundly hypotensive after receiving 2L of fluids and one gram of calcium gluconate; 0.3 mcg/kg/min norepinephrine drip was urgently started and later increased to 1.6 mcg/kg/min - Over the next 24 hours, the patient developed significant dyspnea; CXR revealed bilateral pleural effusions most suggestive of pulmonary edema with the possibility of aspiration in the setting of persistent emesis - Echocardiogram confirmed normal structure and function, EF of 70% - Patient became oliguric and her creatinine increased from 2.0 mg/dL on admission to 3.33 mg/dL overnight; due to the possible need for renal dialysis, she was transferred to a higher-level facility Hospital #2 - Upon arrival, the patient was in significant respiratory distress with desaturations in the mid-to-upper 80s and she was experiencing mentation difficulties; she required emergent sedation and endotracheal intubation and was placed on continuous mandatory ventilation (CMV) - Patient was started on a 4 mcg/kg/min dopamine drip in addition to the norepinephrine drip; calcium chloride, intralipid, glucagon, and insulin drips were also started - Due to her high risk for acute decompensation, the patient was transferred to a different facility in possible need of extracorporeal membrane oxygenation (ECMO) Hospital #3 - Patient arrived with an improved blood pressure of 110/38 and heart rate of 111; she was prone and oxygenating in the low 90s - CXR revealed persistent bilateral lung opacities consistent with acute respiratory distress syndrome (ARDS) (Figure 1) - Due to continued hypoxic hypercarbic respiratory failure, the patient was transitioned from CMV to high flow oscillatory ventilation (HFOV) - HFOV uses low tidal volumes, a high respiratory rate, and constant mean airway pressures to provide sufficient ventilation and oxygenation while also eliminating the full-scale respiratory cycle, which can be traumatic for injured lungs - Dopamine drip was discontinued and norepinephrine drip was titrated down to 0.8 mcg/kg/min; patient required aggressive diuresis with furosemide, chlorothiazide, bumetanide, and acetazolamide; electrolytes were replaced as needed and she was weaned off all diuretics as her creatinine down-trended; insulin, calcium chloride, and intralipid drips were gradually discontinued as her clinical status improved - After two days on HFOV, the patient was transitioned back to CMV and was successfully extubated two days later, remaining on room air for the remainder of her admission without further hypoxemic events; CXR showed improved aeration of lungs with decreased edema (Figure 2) - Renal ultrasound revealed normal kidneys and the patient’s creatinine decreased to 0.7 mg/dL - Patient was deemed medically stable for discharge ten days after her initial presentation and was admitted to an inpatient psychiatric unit

References 1. Sahney S. A review of calcium channel antagonists in the treatment of pediatric hypertension. Paediatr Drugs . 2006;8(6):357-373. doi:10.2165/00148581-200608060 00004 2. Bartlett JW, Walker PL. Management of Calcium Channel Blocker Toxicity in the Pediatric Patient. J Pediatr Pharmacol Ther . 2019;24(5):378-389. doi:10.5863/1551 6776-24.5.378 3. Agarwal MA, Flatt D, Khouzam RN. The potential detrimental effects of calcium channel blockers’ overdose and current available management. Annals of Translational Medicine . 2018;6(1):16-16. doi:10.21037/atm.2018.01.03 4. Chakraborty RK, Hamilton RJ. Calcium Channel Blocker Toxicity. [Updated 2023 Jan 30]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK537147/ 5. Lodhi FAK, Shogren SL, Vedre JG, Haque N, Reriani M, Ali R. Calcium Channel Blocker Toxicity Causing Acute Respiratory Distress Syndrome: A Commonly Used Drug Triggering a Life-Threatening Condition. WMJ . 2020;119(1):66-68. 6. Kenny J. Treating overdose with calcium channel blockers. BMJ . 1994;308:992-993. 7. Upreti V, Ratheesh VR, Dhull P, Handa A. Shock due to amlodipine overdose. Indian J Crit Care Med . 2013;17(6):375-377. doi:10.4103/0972-5229.123452 8. Siddiqi TA, Hill J, Huckleberry Y, Parthasarathy S. Non-cardiogenic pulmonary edema and life-threatening shock due to calcium channel blocker overdose: A case report and clinical review. Respiratory Care . 2013;59(2). doi:10.4187/respcare.02244 9. Han S, Mallampalli RK. The acute respiratory distress syndrome: from mechanism to translation [published correction appears in J Immunol. 2015 Jun 1;194(11):5569]. J Immunol . 2015;194(3):855-860. doi:10.4049/jimmunol.1402513 10. Bulsara KG, Cassagnol M. Amlodipine. [Updated 2023 Jan 22]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK519508/ 11. Meyers M, Rodrigues N, Ari A. High-frequency oscillatory ventilation: A narrative review. Can J Respir Ther. 2019;55:40-46. Published 2019 May 2. doi: 10.29390/cjrt 2019-004 Treatment of Calcium Channel Blocker Toxicity: - I nitial management is directed at stabilizing the airway and achieving sufficient circulation - IV crystalloid fluids and vasopressors are commonly used to attain compatible blood pressures and adequate tissue perfusion - IV calcium gluconate or calcium chloride are used in many settings to promote movement of calcium back into cells via L-type calcium channels - High-dose insulin has been shown to decrease mortality and improve hemodynamics, as CCBs decrease insulin secretion, increase resistance to insulin, and interfere with glucose metabolism, resulting in lactic acidemia and metabolic acidosis - Hemodialysis and other filtration methods are ineffective due to amlodipine’s lipophilicity and significant protein binding capacity injury. Complicating management even further is the lack of treatment modalities available for CCB toxicity. Prompt recognition and judicious management of CCB overdoses can considerably attenuate associated morbidity and mortality. Acute respiratory distress syndrome is a form of hypoxemic respiratory failure, defined as acute hypoxemia with the presence of bilateral pulmonary infiltrates which cannot be attributed to heart failure or fluid overload. It is postulated that immunologic processes involving neutrophils and macrophages mediate inflammatory tissue damage to bronchial and vascular epithelium, leading to an accumulation of protein-rich fluid in alveoli. This innate immune response subsequently impairs gas exchange, resulting in hypoxemia. Additionally, the immune cells generate reactive oxygen species, proteases, cytokines, and other inflammatory mediators. These mediators can have a significant impact on Type II epithelial cells, the cells that synthesize surfactant in the lungs, which reduces alveolar surface tension. In the setting of CCB toxicity, the pathophysiology of ARDS is not completely understood; however, two possible mechanisms have been proposed. The first of which proposes that calcium channel blockers inhibit surfactant secretion from type II epithelial cells, resulting in alveolar collapse. The second suggests that precapillary vasodilation caused by CCBs results in massive transudation of fluid from pulmonary capillaries into alveoli. ARDS is a relatively rare, yet feared complication of CCB overdose, likely due to the drug’s rapid uptake in the body, quick peak plasma concentrations of 6-12 hours, long half-life of 30-50 hours, and highly lipophilic properties. Amlodipine is a dihydropyridine calcium channel blocker that exerts its vasodilatory effects by blocking L-type calcium channels in vascular smooth muscle cells. The primary concern with CCB overdoses is the severe hypotension and reflex tachycardia that occurs as a result of massive vasodilation. Intentional, inadvertent, or exploratory overdose of calcium channel blockers can lead to serious, life-threatening complications in the pediatric population, including vasodilatory shock, acute respiratory distress syndrome and acute kidney

Calcium channel blockers (CCBs) are among the most commonly prescribed cardiovascular medications in the adult population. Similarly, in the pediatric population, CCBs such as nifedipine and amlodipine are frequently prescribed in the management of pediatric hypertension. Despite the prevalence of CCB usage, the available literature on the management of calcium channel blocker toxicity in the pediatric population remains scarce. In the absence of formal guidelines, the management of CCB overdoses comes from case reports. This case identifies a fifteen-year-old Hispanic female who developed acute respiratory distress syndrome (ARDS) and acute kidney injury (AKI) after an overdose of amlodipine. Our patient presented with profound, refractory hypotension, requiring substantial inotropic support. She subsequently developed significant dyspnea, desaturating into the 80s with radiological evidence of ARDS and required endotracheal intubation. After aggressive diuresis and electrolyte replacement, along with inotropic agents to maintain adequate blood pressure, our patient began to make significant clinical progress. With continued improvement and resolution of her AKI and ARDS, she was successfully weaned off ventilatory support and all infusions. Our patient was deemed medically appropriate for discharge ten days after initial presentation and was admitted to an inpatient psychiatric unit. Calcium channel blocker toxicity can pose considerable risks, as was seen with our patient. Prompt recognition and judicious management of CCB overdoses can mitigate associated morbidity and mortality, resulting in favorable outcomes for patients. History of Present Illness A fifteen-year-old Hispanic female with no significant medical history presented to the Emergency Department (ED) after ingesting 20 tablets of 10 mg amlodipine one day prior and 14 tablets of 5 mg tizanidine two days prior to admission. The morning after the patient ingested a total of 200 mg of amlodipine, she began to experience mild chest pain, nausea, multiple episodes of vomiting and dizziness, which prompted her visit to the ED. Physical Exam Vitals: BP 91/38, HR 120, T 36.6 o C, RR 20, SpO 2 97% Constitutional: Well developed, well nourished. Awake & alert. No acute distress HEENT: Atraumatic, Normocephalic. PERRL, EOMI. Mucous membranes moist and intact Cardiovascular: Hypotensive, tachycardic. Regular rhythm. No murmurs, rubs, or gallops. Distal pulses 2+ and symmetric Pulmonary: No evidence of respiratory distress. Clear to auscultation bilaterally Abdominal: Soft and non-distended. No tenderness, guarding, or rigidity Neurological: Alert, awake, and oriented to person, place, time, and situation. Normal speech Psychiatric: Good eye contact. Normal interaction, affect, behavior Case Presentation

Labs

Acetaminophen: <10.0 Salicylate: <3.0 Urine Drug Screen: Neg Urine Pregnancy: Neg Urinalysis: Neg

Publications & Acknowledgements

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This case report was published in the Cureus Journal of Medical Science, DOI: 10.7759/cureus.43806

Figure 1. CXR Day 3

Figure 2. CXR Day 5

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