ECMO: The last resort for refractory beta-blocker overdose

Harish M.M1, Alankrita Agarwal2, Chaitra S2, Mohammad Abbas3, Gururaj V Gunda3, Shridhar M Gidaganti3, Ashwini N A3, Goura Lokanand3

1Director-Institute of Critical Care Medicine, Kauvery Hospital, Marathahalli

2Senior Resident, Critical Care Medicine, Kauvery Hospital, Marathahalli

3Consultant, Critical Care Medicine, Kauvery Hospital, Marathahalli

Introduction

Extracorporeal membrane oxygenation (ECMO) can be a life-saving intervention for patients with beta-blocker toxicity that is refractory to conventional treatment, particularly when cardiogenic shock or cardiac arrest develops. ECMO provides hemodynamic support and improves tissue perfusion, allowing time for the body to metabolize and eliminate the toxic substance. While ECMO is effective in such situations, it is important to remember that it is a rescue therapy and should be considered when other conventional treatments have failed.

Case Presentation

A 28yr old female patient was taken to an outside hospital for generalised weakness and giddiness followed by fall. On arrival she was in severe hypotension and drowsy (e4v5m6), hypoglycaemic and hypoxic. She was resuscitated with fluids and dextrose infusion, started on noradrenaline and epinephrine infusion low dose, oxygen 6l/min and no significant history was provided. Further patient developed acute kidney injury and arterial blood analysis showed worsening base deficits and lactates. In view of this she was put of SLED. On day 2, her hypoxia was worsening following which she was intubated and started on mechanical ventilation. on repeated probing it was revealed that she had consumed high dose of bisoprolol 10mg on day 3. She was treated with high dose insulin, glucagon, ionotropic support and dialysis on mechanical ventilation.in view of poor condition and advanced care was transferred to our hospital on mechanical ventilation on 100%fio2 and triple inotropic support that is noradrenaline 6.5mg/hr, epinephrine 800mcg/hr and vasopressin 2.4ml/hr.

She was continued on mechanical ventilation with sedation and neuromuscular blockers. In view of refractory shock, she was treated with methylene blue 1gm iv slow. Investigations revealed deranged KFT (urea 53.5, cr 3.26 with nil urine output), LFT (SGOT 424, SGPT 106) started her on n-acetyl cysteine infusion 200mg/hr. CTVS reference was sought for iniation of ECMO. ECMO preparations were done and attenders were explained regarding the cons and pros of and was canulated for VA ECMO with venous cannulation in right femoral vein(25F) and arterial canulation (17F) in left femoral artery.

Day 1 ECMO: she was started on VA – ECMO MAQUET with pump flow 3.89 L and 3425rpm, gas flow 2.5l/min increased to 4l/min to remove co2.shw was started to heparin infusion to keep ACT 14-200 and pre and post membrane oxygenation was monitored. upper and lower limb saturation and temperature monitoring was started. Right IJV HD catheter was secured and was put on sled nil heparin for 6 hr and around 500ml removed.

ACT was done every 4th hrly and heparin infusion titrated accordingly. 2 units PRBC (Packed Red Blood Cells), 2 units FFP (Fresh Frozen Plasma) was transfused. her vitals were 114bpm,110/57mmhg on triple support 94% on 70 fio2.lower limb Doppler was done hourly and flow was present.

Day 2: continued on ECMO with same settings, her adrenaline was tapered to 1-2ml/hr and noradrenaline 2-5ml/hr, vasopressin 0.6ml/hr and PRBC s and SDPs  were transfused in view of low hb 8.7gm/dl , platelet 54000 to maintain a target of a round of hb 10gm and platelet  80-1lac.heparin infusion was adjusted according to the ACT and her fio2 requirement had step down to 40-45%.she developed hypoglycemia and was treated with dextrose boluses. her ECMO flow was reduced to 3.61-3.73l/min and 3350rpm and gas flow increased to 5l/min. another session of dialysis done and around 1200ml ultrafiltrate was removed. her vitals were 112bpm,110/59mmhg on noradrenaline 2ml/hr and epinephrine 0.5ml/hr spo2 95 on 40fio2(shock Improved). Patient developed harlequin syndrome, which was managed with aggressive diuresis to improve the lung function quickly.

Day 3: ECMO was continued with same settings and continued on low dose inotropic supports. her vitals 117bpm and bp 113/60mmg off supports and 96% on fio40%.she was managed on NAC (N-acetylcysteine), heparin, fentanyl and atracurium infusion with 4th hrly ACT (Activated Clotting Time) and 6th hrly ABG. weaning from ECMO was started.

Day 4: she was slowly weaned from ECMO and heparin infusion stopped. She was decannulated when ACT was normal and mobilised on chair.

Next day she was extubated successfully. RFT and LFT improved. She slowly started producing urine output 15–20ml/hr and off dialysis.

In following days, she developed weakness and decreased sensation in lower limbs more in left limb, venous and arterial doppler was done which showed small thrombus in femoral vein but no hamper in blood flow, MRI brain done which was normal and Nerve conduction study, finally diagnosed as critical ill polyneuromyopathy. Her urine output increased over the days to 30–40ml/hr and off oxygen support. She was shifted toward successfully. She was discharged successfully and back to her normal routine life.

Discussion

Overdose of beta-blockers can lead to a range of symptoms, including bradycardia, hypotension, and even cardiogenic shock. These symptoms result from the drug’s effect on the heart, interfering with its ability to pump blood effectively [1] Bradycardia with hypotension may be the first hint towards diagnosing beta-blocker overdose. The symptoms resulting from beta-blocker overdose in most cases appear early and are typically seen within one to two hours, while the maximum risk of toxicity in scenarios with sotalol overdose are up to twenty hours [2]

Treatment options include airway securement with cuffed endotracheal tube due to intrinsic lipophilicity causing CNS depression, bradycardia with atropine where one case report showed improvement in heart rate and blood pressure on multiple intravenous boluses of atropine [2,3] gastrointestinal decontamination with gastric lavage who present shortly after massive ingestion of betablockers  [2]

High-dose insulin euglycaemic therapy showed a mortality benefit in 10 case series whereas 2 case reports showed hemodynamic improvement corresponding to insulin bolus then continuous infusion ,maintenance dosing ranging from 1-10u/kg/hr observed side effects include hypokalemia and hypoglycemia.[3] Glucagon was associated with minor improvements in haemodynamics through an increase in heart rate in two cases series.[3] dose  required to reverse severe beta-blockade are 50 micrograms/kg iv loading dose, followed by a continuous infusion of 1-15 mg/h, titrated to patient response.[4] Methylthioninium chloride (methylene blue) is  associated  with improvement in haemodynamics in four case reports but in the setting of co-ingestion with amlodipine. Due to the refractory nature of the shock, the patient was given a trial of IV methylene blue at 1 mg/kg/dose over 10 min.

ECMO provides a mechanical circulatory support system that maintains adequate oxygenation and blood flow, allowing the body to overcome the toxic effects of the beta-blocker and recover [5] ECMO should be considered when patients are unresponsive to conventional treatments, such as glucagon, calcium supplements, high-dose insulin, vasopressors, and lipid emulsion [6] Venoarterial ECMO (VA ECMO) is often used to support both the lungs and the heart, while venovenous ECMO (V-V ECMO) primarily supports the lungs.[6]ECMO can improve survival rates, reduce the risk of cardiac arrest, and allow the patient’s body to recover from the toxic effects of the overdose.

Veno-arterial extracorporeal membrane oxygenation was associated with improved survival in patients with severe cardiogenic shock or cardiac arrest in an observational study and four cases series [3]. In a study by Masson et. al, patient on ECMO survived cardiac arrest 3/3 patients versus 0/7 patients without ECMO. In patients suffering from severe shock, 9 /11 patients survived compared to 23/41 patients who did not have ECMO [7]

VA-ECMO, while life-saving, can lead to several complications, including bleeding, infection, vascular issues, and neurological problems. Bleeding is a major concern due to anticoagulation required for the ECMO circuit, and can be severe, even fatal. Infections, particularly bacteremia and sepsis, are also common and can worsen outcomes, especially with longer ECMO runs [8]

Harlequin syndrome is a rare dysautonomic condition where one side of the face flushes and sweats while the other side remains pale and dry. It’s caused by a unilateral dysfunction in the sympathetic nervous system, which controls involuntary functions like sweating and blood flow. This condition is often triggered by heat, exercise, or emotional stress.[9]

In cases of Harlequin syndrome, we usually transition patients to V-AV ECMO for management. When this patient presented to us, she was experiencing severe hypoxaemia, with her lungs severely congested with fluids, and also had pneumonia. However, in this case, we anticipated Harlequin syndrome, we opted for a more aggressive approach with fluid removal, which led to a remarkable improvement in lung function, helping us avoid the need for hybrid ECMO. We took a calculated risk by ventilating with 100% oxygen, accepting slightly higher PEEP, peak airway pressures, and lower PO2 levels, while continuing aggressive fluid removal. V-AV ECMO option was kept on standby. As a result, the patient’s oxygenation improved rapidly, allowing us to avoid the hybrid ECMO conversion.

Fig (1): During Cannulation for ECMO

Fig (2): Days Before Discharge

Conclusion

ECMO can be a life-saving option for severe beta-blocker toxicity, especially when conventional treatments fail to stabilize the patient. Early initiation of ECMO, before significant organ damage or cardiac arrest, is crucial and may lead to better outcomes. While ECMO provides hemodynamic and respiratory support, allowing the body to metabolize the toxic substance, it’s essential to consider potential risks and benefits in each individual case.

Reference

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