Extracorporeal membrane oxygenation combined with prone ventilation for the treatment of high-dose metoprolol and amlodipine poisoning: A case report

Abstract

Extracorporeal life support (ECLS) represents the ultimate intervention for respiratory and circulatory failure. By maintaining hemodynamic stability, ECLS facilitates drug metabolism and organ recovery, thereby improving survival outcomes. We report a case of severe respiratory and circulatory failure resulting from the oral ingestion of 35 extended-release metoprolol tablets (25 mg each) and 100 extended-release amlodipine tablets (5 mg each). The patient responded favorably to venoarterial extracorporeal membrane oxygenation (VA-ECMO) combined with prone-position ventilation.

Medical history information

A 15-year-old female presented 14 h after ingesting 35 extended-release metoprolol tablets (25 mg each) and over 100 extended-release amlodipine tablets (5 mg each), reporting dizziness. Her mother disclosed the overdose occurred at 1:00 a.m. in a suicide attempt. At 3:00 a.m., gastric lavage revealed no residual pills, yet by nine hours post-ingestion her blood pressure remained critically low, reaching a nadir of 65/35 mmHg (1 mmHg = 0.133 kPa). The patient’s history was significant for depression and bipolar disorder.

Upon arrival at our emergency department, her temperature was 36.3 °C, heart rate 80 bpm, respiratory rate 20 breaths/min, and blood pressure 71/35 mmHg while on dopamine 10 µg/kg/min and norepinephrine 1 µg/kg/min. A 10 % calcium gluconate infusion (0.6–1.2 mL/kg·h; equivalent to 0.06–0.12 g/kg·h) was administered via central venous catheter, with serum ionized calcium levels monitored every 2 h to maintain a target range of 1.5–2.0 times the upper limit of normal. Physical examination revealed normal development and clear mentation; pupils were equal, round (≈2.5 mm), and reactive. Lung auscultation disclosed coarse breath sounds with scattered wet rales. Cardiac rhythm was regular without murmurs. Arterial blood gas analysis showed pH 7.398, PaCO₂ 30.6 mmHg, PaO₂ 101.1 mmHg, Na⁺ 134.2 mmol/L, K⁺ 3.95 mmol/L, HCO₃^– 20.7 mmol/L, Ca²⁺ 1.165 mmol/L. ECG demonstrated normal sinus rhythm (Fig. 1a). Transthoracic echocardiography revealed an ejection fraction of 62 % (Fig. 1b), and chest X-ray was unremarkable (Fig. 1c). Laboratory studies included NT-proBNP 532.4 ng/L (<125 ng/L), IL-6 6.31 pg/mL (<7 pg/mL), WBC 22.43 × 10^⁹/L (neutrophils 90 %, lymphocytes 5.2 %), RBC 3.27 × 10^¹²/L, hemoglobin 96 g/L, and platelets 236 × 10^⁹/L.

Fig. 1.

Pre–VA-ECMO ECG and imaging. a. ECG at 14 h post-overdose demonstrating normal sinus rhythm. b. Transthoracic echocardiogram at 14 h showing an ejection fraction of 62%. c. Chest X-ray at 14 h with no abnormalities. d. Bedside chest X-ray at 34 h demonstrating bilateral pulmonary edema. e. Bedside chest X-ray at 60 h showing progression of bilateral pulmonary edema.

Therapeutic measures

During the first 60 h post-overdose, vasoactive infusions of dopamine, norepinephrine, and dobutamine were titrated to manage refractory shock and hypotension (Fig. 2a). A bedside chest X-ray at 34 h demonstrated pulmonary edema (Fig. 1d), which progressed by 60 h (Fig. 1e). Despite initial treatments, including nasal catheter oxygenation, transnasal high-flow oxygen therapy, and tracheal intubation-assisted respiration combined with prone position ventilation, no significant improvement was observed (Fig. 2b). Targeted antidotal therapies for β-blocker and calcium-channel-blocker toxicity (high-dose insulin, lipid emulsion, glucagon, hemoperfusion) were instituted (Fig. 2c), alongside interventions for coagulopathy and metabolic derangements (CRRT, fresh frozen plasma, packed red blood cells).

Fig. 2.

Hemodynamic, respiratory, and toxicologic interventions before VA-ECMO. a. Trends in arterial blood pressure and vasopressor dosages prior to ECMO initiation. b. Trends in PaO₂ and FiO₂ alongside respiratory support measures before ECMO. c. Timeline of targeted poisoning therapies and adjunctive treatments for complications.

At 60 h, her condition deteriorated with persistent hypoxemia (PaO₂ 48.1 mmHg, SO₂ 88.4 %), hypotension (75/51 mmHg), and NT-proBNP elevated to 9756 pg/mL. Arterial blood gas: pH 7.463; PaCO₂ 35 mmHg; Horowitz index 75.8 mmHg. To prevent end-organ hypoxic injury, venoarterial ECMO was initiated via right femoral cannulation (20Fr venous cannula to 36 cm; 16 Fr arterial cannula to 12 cm) to support circulation and gas exchange (Fig. 3a). During this period, the patient's Activated clotting time (ACT)and coagulation function were dynamically monitored. A chest X-ray at the 62nd hour of poisoning showed that the degree of pulmonary edema was more severe than at the 60th hour (Fig. 3b). We conducted chest X-ray examinations on the 3rd (Fig. 3c), 4th (Fig. 3e), and 5th (Fig. 3f) days during the period of VA-ECMO-assisted treatment. Concurrently, we provided nocturnal prone position ventilation therapy (Fig. 3d).

Fig. 3.

VA-ECMO support and serial chest X-ray progression. a. VA-ECMO cannulation at 62 h post-overdose. b. Bedside chest X-ray 2 h after ECMO initiation. c. Bedside chest X-ray on ECMO Day 3. d. Prone-position ventilation during ECMO support. e. Bedside chest X-ray on ECMO Day 4. f. Bedside chest X-ray on ECMO Day 5.

Following VA-ECMO, oxygen saturation (Fig. 4a) and arterial blood pressure (Fig. 4b) improved markedly. CRRT and hemoperfusion continued to optimize toxin clearance and hemodynamics (Fig. 4c). By Day 5 of ECMO support, pulmonary edema had resolved (Fig. 3f), cardiac function stabilized (EF 55 %), and ECMO flow was weaned. The patient was extubated 12 h post-ECMO decannulation, transferred to the general ward three days later, and discharged on hospital Day 14 without complications.

Fig. 4.

Hemodynamic, respiratory, and toxicologic parameters before, during, and after VA-ECMO support. a. Trends in arterial blood pressure and vasopressor dosages pre-, intra-, and post-ECMO. b. Trends in PaO₂, FiO₂, and respiratory support measures around ECMO initiation and withdrawal. c. Timeline of targeted poisoning therapies and adjunctive treatments for complications before, during, and after ECMO.

Discussion

Beta-blockers reduce blood pressure and heart rate, treating hypertension, tachycardia, angina pectoris, and heart failure in adults.¹ Their rapid onset and potency confer high toxicity risk in overdose. Metoprolol is lipophilic (t_1/2 3–4 h),² with ∼50 % oral bioavailability,³ and can induce central neurotoxicity such as delirium.⁴

Calcium channel blockers (CCBs), mortality ranges 0.3–25 % if untreated.⁵ Higher blood concentrations worsen prognosis.⁶ Most CCBs absorb within 1–2 h, whereas extended-release formulations like amlodipine peak in 6–12 h.⁷ Overdose may delay peaks to 24 h. Clearance relates to half-life; amlodipine’s half-life is 30–50 h. Symptoms delay reflects metabolic saturation and long half-life.⁸ Clinical poisoning manifests as severe hypotension, bradycardia,⁹ pulmonary edema, confusion, agitation, impaired consciousness, and seizures,¹⁰ possibly from inadequate CNS perfusion. Mild cases need decontamination, fluids, and electrolyte correction. Moderate to severe poisoning requires vasopressors, calcium gluconate, lipid emulsion, sodium bicarbonate, and other therapies.

Continuous Blood Purification (CBP) employs diffusion, convection, and adsorption eliminate metabolites, toxins, drugs, and pathogenic biomolecules.¹¹ This technology offers efficient solute clearance with hemodynamic stability. Continuous Veno-Venous Hemodiafiltration (CVVHDF) removes toxins¹², while plasma exchange or hemoperfusion improves clinical outcomes.¹³ Furthermore, hemoperfusion intervention toxin clearance rates diltiazem and metoprolol.¹⁴ In the present case, clinicians implemented a treatment strategy combining CRRT with hemoperfusion for a mixed overdose of high-dose metoprolol extended-release tablets and amlodipine extended-release tablets. This approach not only facilitated effective toxin elimination but also ensured precise volume management.

If the clinical manifestations of toxic overdose cannot be adequately reversed with conventional therapeutic measures, the initiation of extracorporeal life support (ECLS) techniques should be considered.15, 16 ECLS is the last defense for respiratory and circulatory failure from intoxication.¹⁵ temporary and reversible, ECLS improves survival by maintaining perfusion and facilitating toxin elimination.¹⁷ Intra-aortic balloon counterpulsation (IABP) has been used for refractory bradycardia and hypotension.¹⁸ ECMO supports both respiration and circulation in severe failure.¹⁹ ECMO offers continuous dual support versus IABP.²⁰ ECLS rescues 88 % of cardiogenic shock patients but only 42.9 % of poisoning-induced cardiac arrest survivors.²¹ In-depth studies have found ECLS to be most effective as a form of mechanical circulatory support for cardiotoxic heart failure and less effective for sedative-hypnotic drug overdose.¹⁵

In this case, the patient developed non-cardiogenic pulmonary edema and intractable hypotensive shock after ingesting metoprolol and amlodipine. Reports of acute non-cardiogenic pulmonary edema due to these overdoses are limited, and the mechanism is unclear. Precapillary dilatation increases pulmonary capillary hydrostatic pressure,⁵ and massive fluid resuscitation during shock exacerbates edema.²²

Conclusion

In this case of refractory shock and acute respiratory distress syndrome from metoprolol and amlodipine toxicity, VA-ECMO combined with prone-position ventilation bridged the patient through the critical phase, allowing sufficient time for drug clearance after conventional measures had failed. The patient recovered uneventfully and was discharged in stable condition on Day 14.

Author contributions

All authors made a significant contribution to the work reported, gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Data availability

All relevant patient data are contained within the patient case files.

CRediT authorship contribution statement

Zhiwen Zhao: Writing – review & editing, Writing – original draft, Supervision, Software, Formal analysis, Data curation, Conceptualization. Bo Wang: Data curation. Daiqiang Liu: Methodology. Wengtao Tao: Supervision. Haowen Tang: Data curation. Ziyu Wu: Validation, Resources. Xiaolin Zhang: Writing – review & editing, Writing – original draft. Zhicheng Fang: Resources, Data curation.

Ethics approval and consent to participate

This study was exempted from requiring patient informed consent, as approval Letter of medical Ethics Committee of Shiyan Taihe Hospital (Reference Number: 2024KS01).

The study adhered to the Declaration of Helsinki and relevant ethical guidelines. The patient in this case is a 15-year-old minor. According to the legal age requirements in China, individuals under the age of 18 are considered minors and must obtain consent from their immediate family members (father and/or mother) in order to sign the informed consent form. In this instance, the patient's family members (father and/or mother) provided consent for the publication of the case report. Additionally, the patient herself also gave her consent for the publication of this article. Both the patient and her parents signed written informed consent for publication.

Funding

Thanks to Shiyan Leading Scientific Research Project (24Y044) for the support of the Fund.

Declaration of competing interest

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Appendix A. Supplementary material

The following are the Supplementary data to this article: