Massive Amlodipine Overdose Complicated by Multiorgan Failure and Cardiac Arrest: A Case Report

Abstract

Introduction:

Calcium channel blocker (CCB) overdose, particularly with dihydropyridines like amlodipine, can cause profound vasodilatory shock and multi-organ dysfunction. Such poisoning often requires aggressive critical care interventions.

Case presentation:

A 23-year-old Ethiopian man attempted suicide by ingesting ⩾300 mg of amlodipine (plus diclofenac). He developed refractory hypotension, bradyarrhythmia, acute kidney injury, and non-cardiogenic pulmonary edema. He subsequently required intubation and suffered a cardiac arrest.

Management and outcome:

He received standard supportive therapy: Intravenous (IV) crystalloid boluses, calcium gluconate, escalating vasopressors (norepinephrine/epinephrine), and high-dose insulin-glucose infusion with potassium supplementation. Despite multiorgan failure (renal failure, pulmonary edema) and arrest, he recovered gradually over 2 weeks with full neurologic return. Corticosteroids, diuretics, and broad-spectrum antibiotics were adjunctively used.

Conclusion:

This case illustrates that even a massive amlodipine overdose with multiorgan failure and arrest can be survived with early, multimodal intensive care. It showcases the need for early recognition of CCB toxicity and prompt use of therapies such as high-dose insulin and extracorporeal support if needed.

Introduction

Calcium channel blockers (CCBs), including dihydropyridines like amlodipine, are widely prescribed for hypertension and other cardiovascular conditions.^1,2 Overdose is relatively uncommon but often life-threatening. In one large poison-center series, CCB exposures comprised only ~0.3% of all calls, yet 81% of these cases required hospitalization.^2,3 Amlodipine accounts for the majority of CCB ingestions (71% of reported cases) and is implicated in ~29% of CCB-related deaths. ² Notably, US data show that CCBs cause more overdose fatalities than any other cardiovascular drug class, with one review estimating ~35% mortality in severe cases. ¹ These deaths are most often associated with intentional suicide attempts.^2,3

CCBs block L-type calcium channels, reducing calcium influx into smooth muscle and cardiac myocytes. ⁴ Dihydropyridines like amlodipine predominantly affect vascular smooth muscle, causing profound vasodilation.^2,4 In overdose, tissue selectivity is lost; large ingestions may also depress cardiac contractility and conduction. ⁵ Clinically, severe amlodipine poisoning presents with vasodilatory (distributive) shock, often with reflex tachycardia, although bradycardia may occur in extreme cases.^6,7 Patients may develop metabolic acidosis, hyperglycemia (due to inhibited insulin release), and non-cardiogenic pulmonary edema. ⁷ Cardiac conduction blocks or idioventricular rhythms can emerge in massive poisoning.^5,8 Diagnosis rests on history of ingestion and recognition of this toxidrome; there are no rapid confirmatory tests.^5,9 Hyperglycemia can be an early clue to CCB toxicity. ⁷

Initial management follows advanced life-support principles.^5,10 Gastrointestinal decontamination (activated charcoal, lavage) is indicated if presentation is early. ⁶ Hemodynamic support is critical: IV crystalloids and vasopressors (norepinephrine or epinephrine) to maintain perfusion pressure.^9,10 IV calcium salts (calcium gluconate or chloride) are routinely given to partially overcome channel blockade.^6,11 High-dose insulin–glucose euglycemic therapy (HIET) is strongly advocated, as insulin increases inotropy and glucose uptake.^10,11 Other adjuncts include IV glucagon and lipid emulsion (to bind lipophilic CCB) in refractory cases. ⁶ In the extreme refractory shock, extracorporeal membrane oxygenation (ECMO) has been lifesaving. ¹² Despite these measures, evidence is limited (mostly case reports), and recommendations rely largely on expert consensus.^5,7,11 We present a case of severe amlodipine overdose complicated by multiorgan failure, idioventricular rhythm, and cardiac arrest, which required prolonged intensive care support and HIET. This report tries to emphasize the clinical challenges of managing extreme CCB toxicity and adds valuable insight to the limited literature on successful recovery from life-threatening amlodipine poisoning.

Case Presentation

A 23-year-old Ethiopian male university student was brought to the emergency department approximately 36 hours after intentional ingestion of more than 30 tablets of Amlodipine 10 mg (estimated ⩾ 300 mg) and an unknown quantity of Diclofenac 50 mg. The ingestion was a suicide attempt in the context of a 3-month history of depressive symptoms, including hopelessness, worthlessness, anhedonia, and poor concentration. There was no prior psychiatric care, though he described significant psychosocial stressors, including the bereavement of his father and financial hardship while completing his thesis. He reported 2 to 3 episodes of vomiting soon after ingestion.

At triage, his vital signs were: blood pressure 85/36 mmHg, pulse 66 beats/min, respiratory rate 20/min, and oxygen saturation 86% on room air. An arterial blood gas (ABG) was not performed during the initial evaluation; therefore ABG values are not available. The triage early warning score (TEWS) was 4, and he was categorized as “yellow.” On examination, he was lethargic but fully oriented (Glasgow Coma Scale (GCS) 15/15). Findings included cool peripheries, bradycardia with hypotension, reduced air entry over both lower lung fields, and Grade I bilateral pitting edema. No focal neurologic deficit was identified.

Initial laboratory evaluation demonstrated marked leukocytosis (WBC 27.1 × 10³/µL, neutrophils 93%), serum creatinine 2.8 mg/dL, and urea 7 mg/dL. Electrolytes were within normal limits. An electrocardiogram revealed bradyarrhythmia with idioventricular rhythm.

The patient was immediately resuscitated with intravenous crystalloids, followed by calcium gluconate 2 g IV over 30 minutes. Vasopressor therapy was initiated with epinephrine infusion at 0.1 mcg/kg/min, titrated every 20 minutes up to 0.23 mcg/kg/min. Admission ECG (Figure 1) showed bradycardia with intermittent wide-complex ventricular escape beats, suggestive of an idioventricular/ventricular-escape rhythm. Atropine (1 mg IV, up to 3 doses) was trialed per ACLS for symptomatic bradyarrhythmia but produced minimal hemodynamic effect. Given persistent hypotension, HIET was commenced with a 50 IU IV bolus followed by continuous infusion at 1 IU/kg/h, alongside intravenous dextrose and close potassium monitoring. The patient was placed on continuous cardiac monitoring, and a glucagon trial was considered but not available.

Figure 1.

Admission 12-lead ECG showing bradycardia with intermittent wide-complex ventricular escape beats, suggestive of an idioventricular/ventricular-escape rhythm.

During the first 48 hours, his course was complicated by acute kidney injury (serum creatinine rising to 3.1 mg/dL, urine output 300 mL/24 hours) and non-cardiogenic pulmonary edema with bilateral pleural effusions (Figure 2). Renal replacement therapy (hemodialysis/CRRT) was not required; renal function improved with supportive care. Point-of-care ultrasound confirmed preserved renal size and corticomedullary differentiation, and echocardiography showed a left ventricular ejection fraction of 50% to 55%. Bilateral pleural taps drained 700 mL on the right and 400 mL on the left. Broad-spectrum antibiotics (ceftazidime, later vancomycin) were initiated for suspected sepsis.

Figure 2.

Frontal (AP upright) chest radiograph demonstrating pulmonary vascular congestion and bilateral perihilar/lower-zone interstitial–alveolar opacities. Small bilateral pleural effusions with meniscus formation (L > R) are present.

On hospital day 3, despite high-flow nasal oxygen, the patient developed worsening respiratory distress requiring endotracheal intubation. During induction, he suffered a cardiac arrest, and return of spontaneous circulation (ROSC) was achieved after 3 cycles of cardiopulmonary resuscitation and epinephrine administration. This was most likely precipitated by acute hypoxemia from severe non-cardiogenic pulmonary edema with airway compromise in the context of refractory vasodilatory shock; the precise proximate rhythm could not be definitively established from available records. He was subsequently sedated with ketamine and maintained on mechanical ventilation.

In the intensive care unit (ICU), the patient required continued vasopressor support, HDI, corticosteroids, and loop diuretics. Low-dose hydrocortisone (stress-dose steroid) was administered as adjunctive therapy for vasopressor-refractory shock (hydrocortisone 50 mg IV q6h), per local critical-care protocol. Intravenous lipid emulsion and ECMO were considered as rescue options but were not available at our center, and transfer was not feasible given the patient’s instability; therefore these interventions were not used. Serial laboratory monitoring demonstrated gradual improvement: creatinine fell to 0.5 mg/dL, WBC normalized to 6.7 × 10³/µL by day 10, and electrolytes were stabilized with supplementation. He was successfully extubated on day 7 of mechanical ventilation. His course was further complicated by left leg cellulitis, managed with antibiotics and supportive care.

By hospital day 15 (11th day in ICU, fourth day post-extubation), he was alert, oriented, hemodynamically stable (BP 130/70 mmHg, heart rate (HR) 86/min, SpO₂ 96% on room air), and producing adequate urine (3 L/24 hours). He was transferred to the medical ward and later discharged after a total of 14 days of hospitalization (11 ICU, 3 ward). At discharge, he had complete neurologic recovery and was referred to psychiatry, where he was diagnosed with major depressive disorder and commenced interpersonal therapy. The patient expressed gratitude for survival and reported guilt and regret about his suicide attempt.

Discussion

CCB overdose is relatively rare but of high concern. National data indicate that CCB exposures are rising; they are now the third fastest growing toxin reported to U.S. poison centers, after opioids and sympathomimetics. ¹⁰ Danish registry data (2009–2014) found 339 CCB exposures in 6 years, with 80% requiring hospital admission. Amlodipine was involved in the majority (71%) of these cases. ² Consistent with other reports, nearly all fatalities occurred in adults ingesting a significant amount of CCBs (chiefly suicide), and the overall mortality was low (~2%). ² However, published case series (often severe poisonings) report mortality ~15% to 18%, reflecting selection bias toward sicker patients.^8,10 In summary, intentional CCB ingestions are uncommon but, when massive, are associated with high morbidity and a significant risk of death.^1,9

CCB toxicity can be diagnostically elusive. Patients present in refractory shock that may mimic septic or cardiogenic shock.^5,8 Clues include the context (known ingestion or suicide attempt) and certain laboratory findings.^8,9 Hyperglycemia is common, as calcium blockade inhibits pancreatic insulin release.^7,13 Mild acidosis and elevated lactate may develop due to poor perfusion. ¹⁴ An electrocardiogram (ECG) may show bradyarrhythmias or conduction delays, but is not specific. ⁹ Notably, standard decontamination or initial vasopressor support often fails to correct the shock if the overdose is large.^6,11 In our patient, the marked hypotension with cool extremities and an idioventricular rhythm, unresponsive to fluids and atropine, should prompt consideration of CCB overdose in the differential, especially given the ingestion history. BRASH syndrome was considered but felt less likely given the patient’s normokalemia and the predominant vasodilatory shock consistent with massive CCB toxicity. ¹⁵

Treatment is primarily supportive and multimodal. IV fluids and vasopressors are first-line to maintain perfusion pressure.^6,10 In practice, norepinephrine (or epinephrine) is often preferred ¹⁶ ; our patient received high-dose epinephrine with eventual taper. IV calcium administration is routine: supra-therapeutic calcium (1-3 g calcium chloride or 2-6 g calcium gluconate) can transiently improve blood pressure.^5,17 HIET is regarded as a key intervention. Insulin (eg, 1 IU/kg/h after a bolus) enhances myocardial carbohydrate utilization and contractility.^7,13 Patients not treated with insulin had worse outcomes in some series. ¹³ In our patient, HIET likely contributed to his eventual improvement after fluids/pressors alone had failed.

Other therapies have adjunctive roles. Glucagon stimulates cyclic AMP and contractility and is often recommended, though evidence is anecdotal.^9,10 Intravenous lipid emulsion (Intralipid) can sequester lipophilic CCB and has been used in refractory cases.^6,10 Recommended 20% ILE dosing is an initial bolus of 1.5 mL/kg IV (over 1-3 minutes) followed by an infusion of 0.25 mL/kg/min; boluses may be repeated and many protocols limit the cumulative dose to ≈10–12 mL/kg in the first 30–60 minutes. ¹⁸ Mechanical ventilation and diuretics are used if pulmonary edema develops (as in our patient); respiratory failure from CCB-induced non-cardiogenic edema has been reported and often requires intubation.^6,11 Renal replacement therapy does not remove amlodipine (highly protein-bound), but continuous renal replacement therapy (CRRT) may be needed for refractory acidosis or fluid management.^5,8,9 In patients with persistent life-threatening shock or arrest despite maximal medical therapy, extracorporeal membrane oxygenation (ECMO) is a rescue option.^9,12 Case reports (including a recent series) demonstrate survival using VA-ECMO, even after prolonged hypotension. ¹² Early ECMO initiation was “pivotal” in stabilizing perfusion in a recent patient with massive amlodipine ingestion and may be considered when resources permit.^5,12

Severe CCB poisoning often demands prolonged ICU care but can result in full recovery.^2,5 Literature reviews indicate that many patients require mechanical ventilation and some develop acute kidney injury.^2,7 In one case series (n = 66), 63% of patients were intubated and 47% had renal failure; overall mortality was ~16%. ⁷ When death occurs, it is usually due to intractable shock or cardiac arrest.^2,5,8 Our patient exemplified the critical phase: he developed distributive shock complicated by acute respiratory distress syndrome (ARDS) and acute kidney injury (AKI), culminating in in-hospital cardiac arrest. Survival through that phase is uncommon without aggressive support.^5,12 However, if patients can be supported during the acute phase, long-term outcomes tend to be good. Published cases report complete neurologic recovery after prolonged ICU courses and even after cardiac arrest when advanced life support is provided.^11,12,17 The patient also co-ingested diclofenac, which may have contributed to the early acute kidney injury. NSAIDs can worsen renal perfusion via prostaglandin inhibition and renal vasoconstriction, particularly in the setting of hypotension.^19,20

Our case attests to these points: despite multiorgan failure and an arrest, the patient survived with intensive care. This favorable outcome aligns with the concept that aggressive, multimodal therapy (fluids, pressors, calcium, HIET, ventilatory support, etc.) can reverse even severe CCB toxicity.^6,9,10 It also emphasizes diagnostic vigilance: the combination of hypotension, pulmonary edema, and AKI following an overdose should prompt early use of therapies like HIET and consideration of ECMO.^5,7 A sustained insulin infusion and vasopressors ultimately stabilized our patient’s hemodynamics, illustrating the value of these interventions.

This case report has several important limitations. It describes a single patient and therefore the observations have limited generalizability. Only one admission ECG tracing was archived and no arterial blood gas was obtained, and full echocardiographic DICOM images were not available for submission; these omissions limit physiologic detail. Some management decisions (including non-use of ILE/ECMO) were influenced by local resource availability, which may restrict applicability in other settings. Finally, longer-term neurologic and functional follow-up beyond hospital discharge was limited; despite these constraints, the report provides useful pragmatic information on managing severe amlodipine toxicity in a resource-limited center.

Conclusion

Severe amlodipine overdose can precipitate refractory shock, pulmonary edema, and multi-organ failure; early recognition and aggressive support are critical. Clinicians should suspect CCB poisoning in unexplained distributive shock, especially with a relevant history or hyperglycemia. Management entails HIET, IV calcium, and vasopressors as first-line treatments, with lipid emulsion and ECMO as rescue options in refractory cases. This case highlights the potential for full recovery even after cardiac arrest when comprehensive critical care is applied. Key learning points include the need for prompt GI decontamination (when feasible), vigilant monitoring for pulmonary and renal complications, and early escalation to advanced therapies to improve survival in life-threatening CCB toxicity.