Early Recognition of Electrocardiographic Lambda-Wave ST Elevation during Propofol Infusion Prevents Ventricular Tachyarrhythmia and Cardiac Arrest

INTRODUCTION

Propofol is a common anesthetic agent with minimal side effects at conventional doses. But prolonged use might cause rare but lethal complications presented in a variety of symptoms like metabolic acidosis, rhabdomyolysis, acute kidney/liver injury and lambda-wave ST elevation (STE) on electrocardiography (ECG). Together these symptoms constitute the propofol infusion syndrome (PRIS) with a mortality rate > 80%.¹ The occurrence of lambda-wave STE during propofol infusion is an early sign preceding ventricular tachyarrhythmia (VT) and cardiac arrest.² Here we reported a female who had developed non-sustained VT and a lambda-wave STE in leads V_2-6 on ECG after a 9-day long propofol infusion to control her status epilepticus. Early recognition of ECG aberrancy and discontinuation of propofol later reversed the ECG abnormalities and eliminated the VT and cardiac arrest before the full development of PRIS.

CASE

A 70 year-old female with type 2 diabetes and chronic kidney disease was admitted to our hospital due to ventricular fibrillation and cardiac arrest. Coronary angiography revealed critical stenoses at proximal portions of left anterior descending and left circumflex arteries. Drug-eluting stents deployed at these lesions were uneventful. After target temperature management (TTM), her consciousness and vital signs became stable.

Eight days after the coronary intervention, sputum impaction with suffocation occurred suddenly while she was in the general ward. Cardio-pulmonary resuscitation was immediately performed. She was later transferred to the intensive care unit for TTM once more. Because of progressive elevated levels of serum creatinine (from 2.77 at baseline to 4.15 mg/dl) and oliguria, hemodialysis was applied every 2 to 3 days. At the end of TTM, she remained comatous and status epilepticus recurred frequently. Electroencephalogram revealed generalized periodic spikes and poly-spike discharges, indicating severe cerebral dysfunction. Anti-epileptic agents with levetiracetam (1 g/day), valproate (1.6 g/day), and propofol infusion (1.62-3.24 mg/kg/hr) were administrated to suppress muscle twitches at her face and limbs. Norepinephrine (1.07-5.33 ug/min) was also infused continuously to maintain her blood pressure. Nine days after the propofol infusion, recurrent non-sustained VT was observed with spontaneous termination (Figure 1A). ECG revealed a lambda-wave STE in leads V₂-V₆ with an extremely prolonged QTc interval of 694 ms (Figure 1B). Arterial blood gas data showed a pH of 7.417 and bicarbonate of 18.4 mmol/L. Serum biochemical data were all within normal limits: lactate 6.2 mg/dL, creatine kinase 37 U/L, and potassium 3.6 mEq/L. Because ECG changes as observed were presumably adverse effects of propofol, we immediately replaced propofol with midazolam to control the epilepsy. Sodium bicarbonate and calcium gluconate were used together to prevent acidosis and hyperkalemia. With these treatments, non-sustained VT episodes were reduced and finally disappeared. Serial ECG recordings showed progressive diminishment of the lambda-wave STE one and two days after these managements (Figure 1C, D). No epilepsy nor VT had occurred thereafter.

Figure 1.

(A) One of the non-sustained ventricular tachycardia episodes on the 9^th day of propofol infusion. (B) electrocardiography (ECG) on the 9^th day of propofol infusion showing lambda-wave ST elevation at V_2-6 with prolonged QTc interval. (C) ECG taken one day after discontinuing propofol. (D) ECG taken 2 days after discontinuing propofol.

DISCUSSION

Propofol is a sedative-hypnotic agent with anticonvulsant and anxiolytic properties.³ Its advantages of a rapid onset and a short-term action have favored its common use in intensive care units. However, propofol use might cause a rare but lethal complication of PRIS. Risk factors associated the occurrence of PRIS included prolonged duration and high dose of propofol use, carbohydrate depletion, severe illness, and concomitant administration of catecholamine and steroid.⁴ In a review of 37 reported adult cases with PRIS, only 7 of them survived, indicating its high mortality risk.³ Vernooy et al. also reported that 6 of the 7 PRIS patients who developed lambda-wave STE died within hours of the irrecoverable electrical storm.² The treatment of overt PRIS includes immediate discontinuation of propofol and supportive management. In the case of our patient, prolonged infusion (9 days) of propofol concomitant with norepinephrine, compounded with critical illnesses might contribute to the appearance of lambda-wave STE in leads V_2-6 and VT, prior to the full development of PRIS. Our finding indicated that the appearance of lambda-like STE during propofol infusion is likely a warning sign for subsequent VT and cardiac arrest preceding the overt PRIS. This speculation is consistent with our patient’s conditions because: (1) our patient’s biochemical data during STE and VT were normal; and (2) discontinuation of propofol reversed the ECG abnormality and eliminated the VT.

A "lambda-wave" STE in leads V₁-V₃ on ECG, or the "shark fin sign" was reported not only from patients receiving propofol infusion, but also from patients with left main coronary artery disease, STE myocardial infarction, and stress (takotsubo) cardiomyopathy.^5,6 Such ECG pattern is predictive of adverse cardiovascular events in PRIS, ischemic and stress cardiomyopathy, and should likely be considered as a marker of upcoming lethal events. For our patient, the occurrence of lambda-wave on ECG with a lengthened QT interval was attributed to prolonged propofol infusion. Mechanisms for lambda-wave STE during propofol infusion remain unclear. Some possible mechanisms are propofol might inhibit the cardiac sodium channel current, transient outward potassium current, and L-type calcium current, which together increased the trans-mural voltage gradient and the formation of lambda-wave on ECG.² However, one cannot exclude the possibility that the lambda-wave STE is originated from the occlusion of the drug-eluting stents, which had been deployed 17 days earlier. Since the lambda-wave on ECG was normalized after discontinuing propofol infusion alone, with levels of cardiac enzymes unchanged, it is less likely that the lambda-wave STE was caused by acute stent thrombosis.

In conclusion, propofol infusion could cause lambda-wave STE on ECG, which should be considered cautiously as an early warning sign for upcoming devastating VA and cardiac arrest. Such ECG manifestation might be the first aberration hours before deaths of those patients receiving propofol infusion. Early recognition of ECG abnormality, discontinuing propofol, and supportive care might all help preventing the deadly VA associated with PRIS.

LEARNING POINTS

Propofol is a sedative-hypnotics drug with anticonvulsant and anxiolytic properties. Its prolonged use causes rare but lethal complications presenting as metabolic acidosis, rhabdomyolysis, acute kidney/liver injury and lambda-wave STE on ECG. These symptoms together constitute the PRIS with a high mortality rate. The lambda-wave STE during propofol infusion is an early sign preceding VT and cardiac arrest. Early recognition of this aberrant ECG pattern followed by discontinued propofol infusion reversed the ECG abnormality and eliminated the VT and cardiac arrest before deterioration to an overt PRIS.

CONFLICT OF INTEREST

All authors declare no conflicts of interest.