ECMO for Salvage Therapy in Severe Salicylate Toxicity

Salicylate toxicity is a potentially life-threatening condition that can lead to severe metabolic derangements, multi-organ dysfunction, and cardiac arrest.^1-2 While supportive care and enhanced elimination strategies such as hemodialysis are cornerstone treatments, refractory cases may require advanced life support. This case report describes the initiation of veno-arterial extracorporeal membrane oxygenation (VA-ECMO) as salvage therapy in an otherwise healthy young male.^3-5 

Introduction 

Salicylate toxicity, commonly due to aspirin overdose, presents a complex clinical picture ranging from mild symptoms to profound metabolic acidosis, central nervous system depression, and cardiovascular collapse.¹ The hallmark metabolic disturbance is a mixed acid-base disorder, typically a primary respiratory alkalosis followed by a high anion gap metabolic acidosis. Severe toxicity can lead to non-cardiogenic pulmonary edema, cerebral edema, acute kidney injury, and liver failure. Management primarily involves gastric decontamination when appropriate, urinary alkalinization, and hemodialysis for severe cases. However, when these measures prove insufficient and life-threatening complications like cardiac arrest ensue, advanced supportive measures such as ECMO may be considered as a last resort.^3-5 

Case Presentation 

A young male, with a recent history of polytrauma from an auto-pedestrian accident, presented to the emergency center with nausea, vomiting, chills, and diaphoresis. He had been discharged home 6-7 days prior after undergoing multiple orthopedic surgeries for lower extremity fractures, including ex-fix removal, open reduction and internal fixation (ORIF) of several foot and ankle fractures, and intramedullary nailing (IMN) of the right tibia. He denied headache, chest pain, abdominal pain, diarrhea, constipation, dysuria, or dyschezia. 

Upon initial physical examination, the patient appeared acutely distressed and ill. Vitals showed tachycardia and tachypnea with increased work of breathing. His cardiovascular and pulmonary exams were otherwise unremarkable. Abdominal examination was benign. Bilateral lower extremity surgical sites were clean and well-kept without signs of infection. Neurologically, he was alert and oriented. 

Initial medical decision-making focused on sepsis of unknown etiology with concerns for surgical site infection, pneumonia, bacteremia, or urinary tract infection. A comprehensive workup was initiated, including complete blood count (CBC), basic metabolic panel (BMP), troponin, magnesium, phosphorus, coagulation studies, venous blood gas (VBG), lactic acid, urinalysis (UA), chest X-ray, plain films of bilateral lower extremities, and electrocardiogram (ECG). Broad-spectrum antibiotics and fluid resuscitation were administered. Orthopedic consultation deemed a surgical site infection unlikely. 

Initial laboratory results revealed no leukocytosis but a left shift. Hemoglobin had improved since discharge. Other initial labs are seen in table 1-1. 

Table 1-1: Initial Labs 

Due to persistent tachycardia and a subsequent reassessment noting the patient was diaphoretic and slightly confused, a CT pulmonary angiogram (CTPA) was ordered to evaluate for pulmonary embolism. Over the course of his hospital stay, the patient's clinical status continued to deteriorate with increasing tachypnea, tachycardia, and altered mental status. Given the persistent anion gap acidosis without significantly elevated lactate, the differential diagnosis was broadened to include diabetic ketoacidosis (DKA) and ingestions. Upon further discussion with the patient’s family, an empty aspirin bottle was discovered as a part of his belongings, raising strong suspicion for salicylate ingestion. Toxicology labs, including a salicylate level, were urgently added, and nephrology was consulted for dialysis.  

The CTPA was negative for pulmonary embolism. A salicylate level of 89 mg/dL confirmed the suspected ingestion. The patient immediately received two ampules of sodium bicarbonate and was started on a continuous bicarbonate drip. Nephrology was re-engaged and emergent hemodialysis was planned with vascular access pursued. 

Shortly thereafter, the patient developed ventricular tachycardia that progressed to pulselessness. Cardiopulmonary resuscitation (CPR) was initiated, and additional sodium bicarbonate was administered. The patient was intubated and left femoral central venous access was obtained. CPR was transitioned to a mechanical compression device, and the extracorporeal membrane oxygenation (ECMO) team was activated. The patient was successfully placed on veno-arterial (VA)-ECMO. The total downtime from pulselessness to full ECMO flow was 1 hour and 4 minutes, during which there were no purposeful movements or brainstem reflexes.  

Post-ECMO initiation, a CT scan of the brain was normal. However, a CT chest/abdomen/pelvis showed no contrast movement in the heart, a large intracardiac thrombus, bowel ischemia, splenic and renal infarcts, diffuse liver necrosis, and severe stenosis/thrombus in the celiac, superior mesenteric, and inferior mesenteric arteries. 

Despite ECMO, the patient remained profoundly ill. An arterial line showed mean arterial pressures (MAPs) of 35-40 mmHg, and point-of-care ultrasound (POCUS) revealed cardiac standstill. He was on maximal doses of norepinephrine, vasopressin, and epinephrine infusions, along with epinephrine boluses, to achieve MAP goals at 50 mmHg. He continued to receive a 1:1 bicarbonate drip, multiple ampules of bicarbonate, and calcium for a pH below 6.8 and a lactate of 28 mmol/L. His ECMO circuit experienced repeated chattering and flow drops, attributed to severe vasoplegic shock, necessitating over 6 liters of crystalloids/colloids. He received an additional 10,000 units of intravenous heparin due to concern for ECMO clotting. He was emergently taken to the cardiac catheterization lab for an antegrade cannula placement for distal limb perfusion. Right heart catheterization showed elevated right atrial and pulmonary artery pressures with inability to wedge and calculate cardiac output due to persistent asystole. He received 4 units of packed red blood cells due to concern for hemorrhagic shock secondary to disseminated intravascular coagulation (DIC) and shock liver. 

Serial BMPs showed progressive organ dysfunction: creatinine trended from 1.21 to 0.70 to 2.39 mg/dL. Potassium levels escalated from 3.9 to 4.4 to greater than 10 mEq/L. Magnesium levels increased from 2.47 to 5.34 to 6.72 mg/dL. Calcium levels decreased from 8.5 to 7.0 to 6.3 mg/dL. Liver function tests showed a dramatic rise in transaminases, with ALT/AST trending from 31/30 to 18/22 to 3262/4136 U/L.  

The patient was transferred to the Heart Failure and Intensive Care Unit (HFICU). He remained without pulsatility, in persistent asystole, and lacked brainstem reflexes. He exhibited bleeding from every puncture site and body orifice and was in rigor mortis. VA-ECMO flows persistently dropped to 1-2 L/min. The patient was pronounced dead. The final blood gas prior to cardiac arrest showed a profound acidemia: pH less than 6.8, PCO2 72 mmHg, PO2 427 mmHg, non-calculable HCO3 and base excess. 

Discussion 

This case highlights the catastrophic consequences of severe salicylate toxicity and the challenging nature of managing profound multi-organ failure. The patient's initial presentation with non-specific symptoms of nausea, vomiting, chills, and diaphoresis, combined with a recent surgical history, led to an initial workup for sepsis, DKA, and pulmonary embolism. However, the rapidly escalating anion gap metabolic acidosis without significant correlation in lactate elevation, coupled with the discovery of aspirin use, quickly pointed towards salicylate overdose. 

Salicylate toxicity causes a complex metabolic derangement. Salicylates uncouple oxidative phosphorylation, leading to increased oxygen consumption and heat production (fever/diaphoresis), and inhibit key enzymes in the Krebs cycle. They also directly stimulate the respiratory center, causing hyperventilation and respiratory alkalosis. As toxicity progresses and salicylate levels rise, metabolic acidosis becomes predominant due to the accumulation of organic acids (lactic acid, ketoacids, and salicylic acid itself). This patient's progressive, profound acidosis (pH < 6.8) is a critical indicator of severe toxicity and impending cardiovascular collapse.¹ 

The rapid deterioration to ventricular tachycardia and asystole underscores the direct cardiotoxic effects of severe acidosis and electrolyte derangements. The hyperkalemia (K > 10 mEq/L) and hypocalcemia observed are direct consequences of the metabolic acidosis and may have contributed to the cardiac arrest. The dramatic rise in LFTs and creatinine, along with imaging findings of bowel ischemia, splenic and renal infarcts, and diffuse liver necrosis, indicates widespread cellular dysfunction and multi-organ failure.^1-3 

While emergent hemodialysis is the definitive treatment for severe salicylate toxicity, particularly with levels > 80-100 mg/dL or in the presence of organ failure, the patient's rapid decompensation and cardiac arrest necessitated immediate and aggressive resuscitation. The decision to initiate VA-ECMO as salvage therapy in the setting of prolonged cardiac arrest and profound acidemia was a critical intervention. VA-ECMO provides both respiratory and circulatory support, allowing for oxygenation, CO2 removal, and maintenance of perfusion in the face of cardiac arrest and circulatory shock. It also provides time for definitive therapies like hemodialysis to be initiated and to potentially reverse the underlying toxic effects.^2,4-5 

However, despite ECMO initiation, the patient's outcome was fatal. Several factors likely contributed to this devastating outcome. The prolonged downtime of 1 hour and 4 minutes before achieving full ECMO flow, combined with persistent asystole and lack of brainstem reflexes, suggests irreversible cellular injury. The presence of a large intracardiac thrombus, widespread thrombotic events (bowel ischemia, splenic and renal infarcts, celiac/SMA/IMA stenosis/thrombus), diffuse liver necrosis, and ongoing severe vasoplegic shock despite maximal vasopressor support indicate widespread, irreversible systemic damage consistent with a catastrophic toxic insult and subsequent shock. The difficulty in maintaining ECMO flows due to severe vasoplegia and potential clotting, even with additional heparin, further highlights the overwhelming nature of his shock state and likely disseminated intravascular coagulation (DIC). 

Conclusion 

This case report illustrates a rare but critical application of VA-ECMO as salvage therapy in a patient with profound salicylate toxicity complicated by cardiac arrest and multi-organ failure. While ECMO provided a bridge for circulatory and respiratory support, the severity of the toxic insult, the prolonged downtime, and the extensive multi-organ damage ultimately led to a fatal outcome.  

This case underscores the importance of a high index of suspicion for toxic ingestions in patients presenting with unexplained metabolic acidosis and rapid clinical deterioration. Be mindful of the need for immediate, aggressive, and multi-faceted interventions in severe cases. Despite the best efforts with advanced life support, the overwhelming nature of the toxicity can sometimes be insurmountable. 

References 

1. Palmer BF, Clegg DJ. Salicylate Toxicity. N Eng J Med. 2020;382(26):2544-2555. 
2. American College of Medical Toxicology. Guidance Document: Management Priorities in Salicylate Toxicity. J Med Toxicol. 2015;11(1):149-52. 
3. Lavonas EJ, Akpunonu PD, Arens AM, et al. American Heart Association Focused Update on the Management of Patients with Cardiac Arrest or Life-Threatening Toxicity Due to Poisoning: An Update to the American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation. 2023;148(16):e149-e184. 
4. Pozzi M, Buzzi R, Hayek A, et al. Veno-Arterial Extracorporeal Membrane Oxygenation for Drug Intoxications: A Single Center, 14-Year Experience. J Card Surg. 2022;37(6):1512-1519. 
5. Weiner L, Mazzeffi MA, Hines EQ, et al. Clinical Utility of Venoarterial-Extracorporeal Membrane Oxygenation (VA-ECMO) in Patients with Drug-Induced Cardiogenic Shock: A Retrospective Study of the Extracorporeal Life Support Organizations' ECMO Case Registry. Clin Toxicol (Philadelphia, Pa.). 2020;58(7):705-710.