Treatment of a patient with aconitine poisoning using veno-arterial membrane oxygenation: A case report

Abstract

BACKGROUND

Aconitine poisoning is highly prone to causing malignant arrhythmias. The elimination of aconitine from the body takes a considerable amount of time, and during this period, patients are at a significant risk of death due to malignant arrhythmias associated with aconitine poisoning.

CASE SUMMARY

A 30-year-old male patient was admitted due to accidental ingestion of aconitine-containing drugs. Upon arrival at the emergency department, the patient intermittently experienced malignant arrhythmias including ventricular tachycardia, ventricular fibrillation, ventricular premature beats, and cardiac arrest. Emergency interventions such as cardiopulmonary resuscitation and defibrillation were promptly administered. Additionally, veno-arterial extracorporeal membrane oxygenation (VA-ECMO) therapy was initiated. Successful resuscitation was achieved before ECMO placement, but upon initiation of ECMO, the patient experienced recurrent malignant arrhythmias. ECMO was utilized to maintain hemodynamics and respiration, while continuous blood purification therapy for toxin clearance, mechanical ventilation, and hypothermic brain protection therapy were concurrently administered. On the third day of VA-ECMO support, the patient’s respiratory and hemodynamic status stabilized, with only frequent ventricular premature beats observed on electrocardiographic monitoring, and echocardiography indicated recovery of cardiac contractile function. On the fourth day, a significant reduction in toxin levels was observed, along with stable hemodynamic and respiratory functions. Following a successful pump-controlled retrograde trial occlusion test, ECMO assistance was terminated. The patient gradually improved postoperatively and achieved recovery. He was discharged 11 days later.

CONCLUSION

VA-ECMO can serve as a bridging resuscitation technique for patients with reversible malignant arrhythmias.

Key Words: Poisoning; Arrhythmia; Blood purification; Veno-arterial extracorporeal membrane oxygenation; Resuscitation; Case report

Core Tip: A patient poisoned by aconitine was treated with detoxification therapy under Veno-arterial extracorporeal membrane oxygenation (VA-ECMO) support and made a full recovery. VA-ECMO can stabilize the hemodynamics of patients poisoned by drugs, providing a therapeutic opportunity for toxin elimination and the recovery of spontaneous cardiac activity and vital signs. We believe that VA-ECMO is an effective method for treating malignant arrhythmias caused by drug poisoning, which can reduce the risk of patient mortality. VA-ECMO is an effective method for treating malignant arrhythmias caused by drug poisoning.

INTRODUCTION

Cases of aconitine poisoning are not commonly encountered worldwide, and reports of it causing sudden cardiac death are rare. The treatment principles for aconitine poisoning are not well established. In traditional Chinese medicine, Aconiti Kusnezoffii Radix is commonly used for dispelling wind, relieving pain and dehumidification, but it is highly toxic. Chemical and pharmacological studies have shown that diester-alkaloids in Aconiti Kusnezoffii Radix are both important effective ingredients and toxic ingredients, mainly including aconitine, hypaconitine and mesaconitine[1]. Aconitine is a highly toxic alkaloid found in several plants of the Aconitum genus, commonly known as monkshood or wolfsbane[2]. Aconitine poisoning occurs when individuals ingest or come into contact with these plants or their derivatives[3]. Aconitine often affects myocardial cell function by acting on sodium channels, leading to arrhythmias, tachycardia, and potentially fatal ventricular fibrillation[3]. These effects can result in cardiovascular collapse and sudden death. In severe cases of aconitine poisoning, respiratory paralysis may occur due to its toxic effects on the nerves controlling the respiratory muscles, leading to respiratory failure and death. Current treatment for aconitine poisoning involves gastric lavage for toxin removal, administration of antiarrhythmic drugs, and symptomatic supportive care such as mechanical ventilation[4]. In this patient, veno-arterial extracorporeal membrane oxygenation (VA-ECMO) support was provided alongside gastric lavage, blood purification, and respiratory support, aiming to prevent recurrent malignant arrhythmias leading to death or irreversible brain damage before toxin removal could be achieved.

CASE PRESENTATION

Chief complaints

The patient, a 30-year-old male, presented to the emergency department six hours after ingesting Chinese herbal medicine.

History of present illness

He mistakenly ingested topical herbal medicine, subsequently experiencing dizziness, nausea, vomiting, numbness, and weakness in the limbs.

History of past illness

Besides a history of hemorrhoids, he had no other medical history.

Personal and family history

Besides a history of hemorrhoids, he had no other personal, or family history.

Physical examination

Blood pressure was 103/64 mmHg, pulse was 78 beats/min, body temperature was 37 °C, respiratory rate as 20 breaths/min, and peripheral capillary oxygen saturation was 95%. No obvious abnormalities were found on cardiac, pulmonary, or abdominal examinations.

Laboratory examinations

Aconitine poisoning was suspected upon arrival in the emergency department (aconitine in the blood was detected by gas chromatography-mass spectrometry and liquid chromatography-mass spectrometry), the herbal medicine contained aconitine; toxin levels measured four hours later were reported as follows: Aconitine 235 ng/mL, hypaconitine 144 ng/mL, mesaconitine 51 ng/mL).

Imaging examinations

Electrocardiogram, toxic substance detection reports, examination results, and other data are presented in Figures 1-3.

Figure 1 The patient's electrocardiogram and cardiac monitoring changes after entering the hospital. A: Ventricular fibrillation and ventricular tachycardia on electrocardiogram 1 (September 8, 2022 16:27-17:06); B: Ventricular fibrillation and ventricular tachycardia on electrocardiogram 1 (September 8, 2022 16:59); C: Ventricular fibrillation and ventricular tachycardia on electrocardiogram 1 (September 8, 2022 17:06); D: Ventricular fibrillation and ventricular tachycardia on electrocardiogram 2 (September 8, 2022 17:22); E: Ventricular fibrillation and ventricular tachycardia on electrocardiogram 2 (September 8, 2022 17:24); F: Ventricular fibrillation and ventricular tachycardia on electrocardiogram 2 (September 8, 2022 17:26); G: Electrocardiogram 3 after resuscitation (September 8, 2022 16:35).

Figure 2 Electrocardiogram overview on days 2-3 and 5-8. A: An overview of the ECG monitoring: From 19:00 on September 8, 2022 to 8:00 on September 9, 2022, electrocardiogram monitoring for 15 hours, 6 minutes, and 2 seconds. Total number of heartbeats: 72266 times, average heart rate: 80 beats per minute (bpm), maximum heart rate: 162 bpm, minimum heart rate: 44 bpm, tachycardia: 19 times. Ventricular premature beats: 10184 times (14%), single: 4034 times, in pairs: 137 episodes, in triplets: 412 episodes, couplets/triple beats: 2456/29 episodes, ventricular tachycardia: 7 times. Supraventricular premature beats: 4379 times (6%), single: 4293 times, in pairs: 5 episodes, in triplets: 5 episodes, couplets/triple beats: 2709/4 episodes, atrial fibrillation: 2 times, irregular rhythm: 77 times, missed beats: 7 times; B: An overview of the electrocardiogram monitoring: From 8:00 on September 9, 2022 to 8:00 on September 10, 2022, electrocardiogram monitoring for 23 hours and 59 minutes. Total number of heartbeats: 122851 times, average HR: 85 bpm, maximum heart rate: 113 bpm at 10:39, minimum heart rate: 47 bpm at 16:07. Bradycardia: 3 times. Ventricular premature beats: 124 times (1%), single: 106 times, in pairs: 9 episodes, couplets/triple beats: 35/2 episodes. Supraventricular premature beats: 162 times (1%), single: 92 times, in pairs: 2 episodes, in triplets: 3 episodes, couplets/triple beats: 42/2 episodes, irregular rhythm: 1 time.

Figure 3 Toxic substance detection report (September 8, 2022).

MULTIDISCIPLINARY EXPERT CONSULTATION

The patient received multidisciplinary treatment from the vascular surgery, cardiology, emergency medicine, and critical care departments.

FINAL DIAGNOSIS

Aconitine poisoning.

TREATMENT

Indications for VA-ECMO

VA-ECMO is a critical therapy that offers simultaneous respiratory and cardiac assistance, generally used in the fields of heart failure, myocarditis, pulmonary embolism, post-cardiac surgery, and heart transplantation[5].

Blood purification parameters

Prescription Dose 35 mL/kg/h, blood flow rate 150 mL/min, replacement fluid rate 1225 mL/h, dialysis fluid rate 1225 mL/h, sodium bicarbonate 81 mL/h, calcium gluconate 8 mL/h, target balance volume 0 mL/h, ultrafiltration rate: 81 + X (X is adjusted by the nurse based on the hourly infusion volume of fluid). Hemoperfusion is performed using the HA380.

Gastric lavage and fluid resuscitation were initiated. Approximately 1.5 h after arrival in the emergency room, the patient developed ventricular tachycardia, followed by ventricular fibrillation and loss of consciousness. Arterial pulsation disappeared, and blood pressure became unmeasurable. Immediate treatment included defibrillation, cardiopulmonary resuscitation, adrenaline, amiodarone, and endotracheal intubation for assisted ventilation. After thirty minutes of resuscitation, the patient reverted to sinus rhythm, with subsequent occurrences of ventricular ectopic beats and couplets. Ventricular fibrillation intermittently recurred, with intermittent defibrillation and cardiopulmonary resuscitation administered (during which toxin analysis results were obtained, as shown in Figure 4). Considering that the patient had refractory arrhythmia and was at risk of recurrent cardiac arrest, the use of VA-ECMO was indicated for supportive treatment. We therefore decided to administer VA-ECMO treatment. The ECMO team determined the indication for VA-ECMO support. Three hours after presentation to the emergency department, a 17F cannula was inserted via the right femoral artery, and a 21F cannula was inserted via the femoral vein. VA-ECMO was successfully established, stabilizing blood pressure and limb perfusion status. The patient was transferred to the Emergency Intensive Care Unit (EICU). Aconitine is a lipophilic drug that quickly enters tissues and organs such as the heart. Hemoperfusion can effectively clear lipophilic drugs[3]. The present patient had repeatedly experienced cardiac arrest, which suggested a cascade reaction of inflammatory factors. We thought that it was necessary to provide the patient with volume management and acid-base adjustment[4]. To avoid the repeated administration of hemoperfusion that might compromise the integrity of ECMO management and to reduce the risk of blood loss and contamination, we decided to treat the patient with continuous veno-venous hemodiafiltration (CVVHDF) plus hemoperfusion[6,7]. With a central venous pressure of 6 cmH2O, fluid resuscitation was administered, and CVVHDF with hemoperfusion was initiated. Amiodarone and lidocaine were administered to control arrhythmias, alongside mild hypothermia therapy. Three hours after admission to the EICU, the patient experienced paroxysmal ventricular tachycardia and ventricular fibrillation. Echocardiography revealed a wriggling motion of the heart during ventricular tachycardia and ventricular fibrillation episodes, with electrical cardioversion and antiarrhythmic drugs proving ineffective. At 9:00 am on the second day of hospitalization, the patient reverted to sinus rhythm, with ventricular ectopic beats and couplets detected on electrocardiogram monitoring, and ECMO speed was reduced. At 15:50 on the second day of hospitalization, the patient's blood pressure suddenly dropped to 72/42 mmHg, with a gradual decrease in heart rate to a minimum of 47 bpm and prolongation of the QT interval. Treatment included intravenous atropine (0.5 mg), and intravenous magnesium sulfate (2.5 g) in 250 mL of 0.9% sodium chloride solution, resulting in a heart rate increase to 93 bpm and a blood pressure increase to 136/66 mmHg. On the third day of hospitalization, the patient reverted to sinus rhythm, with occasional ventricular premature beats. Echocardiography showed improved cardiac contractile function compared to previously. Vasopressors were discontinued, with a velocity time integral of 15 cm/s, a Mitral Annular Plane Systolic Excursion of 18 mm, and an ejection fraction of 50%. Over the next three days, the patient experienced frequent episodes of ventricular tachycardia, ventricular fibrillation, sinus bradycardia, atrioventricular block, and prolonged QT interval, with alternating slow and rapid arrhythmias. The patient's cardiac function improved after returning to sinus rhythm. On the fourth day of hospitalization, the patient's hemodynamics and ventilation were relatively stable. ECMO blood flow rate was gradually reduced to 1.5 L/min, with stable circulation and oxygenation. The "pump-controlled retrograde trial-off" was successfully conducted, leading to the termination of VA-ECMO support. Three days after ECMO withdrawal, the patient's respiratory and circulatory functions stabilized, with no detectable toxins. The endotracheal tube was removed, and high-flow oxygen therapy was initiated. Blood purification was discontinued. Four days after ECMO withdrawal, the patient was alert, with good oxygenation and stable vital signs. Changes in circulatory parameters with extracorporeal membrane oxygenation involvement are placed in Tables 1 and 2.

Figure 4 The patient's electrocardiogram and cardiac monitoring changes after entering the hospital. A: Trend in creatine kinase-MB change. After admission to the hospital, the patient showed an increasing trend in creatine kinase-MB levels, indicating myocardial injury. As the patient's cardiac rhythm stabilized, the levels of cardiac enzymes gradually decreased; B: Trend in cTnI change. After being admitted to the hospital, the patient's elevated cTnI levels indicated myocardial injury. As the patient's cardiac rhythm stabilized, the cTnI levels decreased; C: Trend in Central venous oxygen saturation (ScVO2) change. The patient's ScVO2 was low in the early stages, and as the cardiac function gradually stabilized, the ScVO2 levels gradually increased; D: Trend in venoarterial carbon dioxide partial pressure difference change. The patient's glycated albumin levels gradually decreased as cardiac rhythm and function recovered; E: Trend in white blood cell (WBC) count change. The patient's WBC count gradually decreased with the change in the stress state; F: Trend in creatinine (Cr) change. The patient's Cr levels gradually decreased with early support from continuous renal replacement therapy (CRRT) and extracorporeal membrane oxygenation. After the gradual withdrawal of life support and blood purification equipment, the Cr levels rebounded. At the time of discharge, the patient's Cr levels were stable at an increased level; G: Trend in alanine aminotransferase change. The patient's transaminase levels gradually decreased after the stabilization of cardiac function, and on the 14^th day, the transaminase levels increased without treatment but returned to normal on their own; H: Trend in fibrin (ogen) degradation products (FDP) change. The patient's FDP levels showed a significant increase on the 9^th. Subsequently, with the adjustment of anticoagulation strategies, extracorporeal membrane oxygenation support, and the gradual stabilization of cardiac function, the patient's FDP levels gradually decreased to normal levels; I: Trend in serum potassium (K) change. The patient’s K levels have remained stable; J: Trend in serum sodium (Na) change. The patient’s Na levels have remained stable; K: Trend in potential of hydrogen (pH) change. The patient exhibited an excessively high pH on the 8^th due to the administration of sodium bicarbonate to correct acidosis during cardiopulmonary resuscitation. On the morning of the 9^th, a drop in pH was observed following a cardiac arrest. After adjusting the CRRT alkali supplementation strategy, the pH has been consistently maintained above 7.35, and the patient did not experience prolonged acidosis; L: Trend in lactic acid (Lac) change. The patient's Lac levels were relatively stable after extracorporeal membrane oxygenation treatment. However, there were fluctuations in lactate levels during the sympathetic storm events that occurred repeatedly from the 8^th to the 10^th. As the patient's cardiac function and rhythm gradually stabilized after the 10^th, the patient's lactate levels gradually decreased. cTnl: cTnI change; ScVO2: Central venous oxygen saturation; GAP: Glycated Albumin; WBC: White blood cell; Cr: Creatinine; ALT: Alanine aminotransferase; FDP: Fibrin (ogen) Degradation Products; K: Serum potassium; Na: Serum sodium; Lac: Lactic acid; pH: Potential of Hydrogen.

Table 1 Changes in circulatory parameters with extracorporeal membrane oxygenation involvement.

	19:00 September 8, 2022	20:00 September 8, 2022	20:30 September 8, 2022	21:00 September 8, 2022	22:00 September 8, 2022	22:31 September 8, 2022	22:41 September 8, 2022	23:00 September 8, 2022
ECMO rotational speed (r/min)	2000	2000	2000	2000	2000	2000	2000	2800
Flow rate (L/min)	1.02	1.03	-	1.50	1.92	1.01	-	2.72
Heart rate (bpm)	138	142	138	142	106	132	73	84
Cardiac rhythm	Sinus rhythm	Ventricular tachycardia	Ventricular tachycardia	Ventricular tachycardia	Sinus rhythm	Ventricular tachycardia	Sinus rhythm	-
Invasive arterial blood pressure (mmHg)	142/90	132/82	-	146/89	106/92	-	-	100/81
Cardiac ultrasound	-	-	-	-	-	Electromechanical dissociation	-	No apparent effective contractions

ECMO: Extracorporeal membrane oxygenation.

Table 2 Changes in circulatory parameters with extracorporeal membrane oxygenation involvement.

	9:00 September 9, 2022	10:00 September 9, 2022	12:00 September 9, 2022	13:00 September 9, 2022	16:00 September 9, 2022	17:00 September 9, 2022	16:00 September 10, 2022	7:00 September 11, 2022	8:00 September 11, 2022
ECMO rotational speed (r/min)	3000	3000	3000	3000	3000	1800	1700	1500	1200
Flow rate (L/min)	2.47	2.37	2.54	2.21	2.50	1.42	1.62	1.59	1.10
	47	151	105	97	50	87	64	104	65
Heart rate (bpm)	Sinus bradycardia	Atrial fibrillation	Sinus tachycardia	Sinus rhythm	Ventricular bradycardia	Sinus rhythm	Ventricular tachycardia	Sinus rhythm	-
	80/47	82/58	139/91	142/81	83/55	111/61	127/67	144/68	99/55
Cardiac rhythm	Weak cardiac contractions	No apparent effective contractions	No apparent effective contractions	Mild recovery of cardiac contractions	No apparent effective contractions	Cardiac contractility recovery	Cardiac contractility recovery	Cardiac contractility recovery	Cardiac contractility recovery

ECMO: Extracorporeal membrane oxygenation.

OUTCOME AND FOLLOW-UP

He was transferred to a general ward and received symptomatic treatment, including rehabilitation and nutritional support. The patient was discharged seven days later. Additionally, creatine kinase-MB, lactic acid, Venous-Arterial Carbon Dioxide Partial Pressure Difference, and Central Venous Oxygen Saturation SCVO2 indicators were monitored for four days, with data shown in Figure 4.

DISCUSSION

Aconitine poisoning is relatively rare clinically. The symptoms of aconite poisoning include paresthesia, nausea, and sweating, followed by abdominal pain, diarrhea, vomiting, and then skeletal muscle paralysis, which typically occurs approximately 20 minutes to 2 h after the oral administration of aconitine[8]. Arrhythmia and neurological symptoms are common clinical manifestations of aconitine poisoning[8,9], but they are not specific and there are very few relevant studies. The mortality rate of aconitine poisoning is very high[10]. The identification and diagnosis of this disease are not difficult, but the impact of aconitine on cardiac rhythm makes treatment more difficult. Aconitine exerts its toxic effects mainly by interfering with Na⁺, Ca²⁺, and K⁺ channels in the nervous system[11,12]. It binds to voltage-gated sodium channels present on nerve cell membranes, especially in the heart and muscle systems[13]. Aconitine binds to sodium channels in an open or inactive state, prolonging their activation time, resulting in sustained depolarization of the cell membrane and sustained discharge of action potentials. Prolonged activation of sodium channels results in the excessive release of excitatory neurotransmitters (such as acetylcholine, norepinephrine, and dopamine), which can affect cardiac muscle cells and cause arrhythmias (irregular heartbeats), tachycardia (excessive rapid heartbeats) and potentially fatal ventricular fibrillation, and these effects may lead to cardiovascular failure and sudden death[14]. Activation of sodium channels can also overstimulate nerve cells, produce toxic effects on the nerves that control respiratory muscles, cause respiratory paralysis, and can also cause symptoms such as muscle twitching, tremors, and epileptic seizures in skeletal muscles[15]. Ingestion of aconitine-containing plants or preparations can also cause gastrointestinal symptoms such as nausea, vomiting, abdominal pain, and diarrhea[16]. Respiratory paralysis and skeletal muscle symptoms caused by aconitine poisoning can be controlled by treatments such as mechanical ventilation, analgesia, sedation, and muscle relaxation to provide time for drug metabolism. However, arrhythmias do not give patients much time to wait for the metabolism of toxic substances and often lead to the death of patients due to various malignant arrhythmias. The patient in this case had symptoms such as numbness, nausea and vomiting, abdominal pain, and diarrhea before admission. After entering the emergency department, he was diagnosed with aconitine poisoning based on his medical history. Toxin analysis was performed and symptomatic treatment such as gastric lavage and rehydration was performed. The patient soon developed a malignant arrhythmia event. There is no specific antidote for aconitine poisoning. Intravenous infusion is routinely given to maintain hydration and electrolyte balance. Drugs such as lidocaine, phenytoin, β-blockers or antiarrhythmic drugs are used under electrocardiographic monitoring to manage abnormal heart rhythms and treatments such as seizure control[17,18]. Extracorporeal cardiopulmonary resuscitation patterns are independently associated with mortality, so it is important to initiate Extracorporeal Cardiopulmonary Resuscitation before physiologic deterioration or cardiac arrest occurs. For patients with severe respiratory and circulatory failure, VA-ECMO can effectively improve tissue perfusion and provide patients with a time window for surgery or other treatments for the original disease[19]. It provides patients with the opportunity to undergo surgery or cardiac recovery. Currently, ECMO is widely used in the rescue treatment of cardiac arrest patients. Early use of ECMO may have a good therapeutic effect in stabilizing circulation and maintaining organ function in patients with reversible malignant arrhythmias. The next step is to continue to confirm the efficacy of ECMO in patients with aconitine poisoning through extensive multicenter prospective trials. Blood purification technology is used to shorten the retention time of poisons and reduce the impact of poisons on sodium channels. However, the elimination of aconitine takes time, and it is extremely important to maintain organ perfusion during this period. Current drugs such as lidocaine or phenytoin can be used to stabilize the cardiac membrane and reduce the risk of arrhythmia, but the effect is unclear. Patients with aconitine poisoning have coexisting fast and slow arrhythmias, and beta blockers are required. Use is on an individual basis under close supervision. With the popularity of ECMO technology, ECMO emergency teams can provide immediate support in life-threatening emergencies to improve circulation status in the shortest possible time.

CONCLUSION

Our experience proves that VA-ECMO is a feasible treatment option for reversible malignant arrhythmias caused by drug poisoning. Extracorporeal life support is an effective method for drug poisoning and is worth exploring.

ACKNOWLEDGEMENTS

We would like to acknowledge the hard and dedicated work of all the staff who implemented the intervention and evaluation of the study.