ST Elevation, Long QT, and Ventricular Arrhythmias Related to Propofol Infusion Syndrome without Biological Abnormalities in a Child after Head Injury ^†

DOI: 10.19102/icrm.2014.050105

CORINE VUILLAUME, MD, THOMAS GEERAERTS, MD, ANNE ROLLIN, MD, OLIVIER FOURCADE, MD and PHILLIPPE MAURY, MD

University of Hospital Rangueil, Department of Cardiology, Toulouse, France

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ABSTRACT. We describe the case of a child presenting with head injury and severe cardiac arrhythmias associated with transient ST elevation and long QT occurring during propofol infusion but without the significant biological abnormality usually associated with the propofol infusion syndrome.

KEYWORDS. Brugada, long QT, propofol, propofol, infusion syndrome.

^†The patient's written signed consent was obtained before publication.

The authors report no conflicts of interest for the published content.
Manuscript received October 18, 2013, final version accepted December 16, 2013.

Address correspondence to: Phillippe Maury, MD, Federation of Cardiology, University Hospital Rangueil, 31059 Toulouse, Cedex 09, France.
E-mail: mauryjphil@hotmail.com

Case report

An 11-year-old girl without any remarkable previous medical history was admitted to neurology intensive care unit after a severe traumatic head injury caused by a road crash. The initial brain computed tomography (CT) scan revealed an occipital skull fracture without parenchymal abnormalities. Because of elevated intracranial pressure (ICP), she underwent urgent neurosurgery and heavy sedation with midazolam and sufentanil. As the ICP remained high, propofol was added at a rate of 1.5 mg/kg/h. The maximal rate of propofol infusion was reached 24 h later (2.5 mg/kg/h). ICP then decreased. Norepinephrine infusion was introduced to maintain cerebral perfusion pressure, while prokinetic drugs (erythromycin and metoclopramide) were introduced 72 h later for promoting gastric emptying and improving enteral nutrition.

Ninety-two hours after the beginning of propofol infusion, a wide QRS tachycardia evocative of monomorphic ventricular tachycardia (VT) suddenly occurred during electrocardiogram (ECG) monitoring (Figure 1). An infusion of lidocaine (1 mg/kg over 5 min) followed by infusion of amiodarone (150 mg intravenous then 3.75 mg/kg daily) and magnesium sulfate (50 mg/kg daily) were administered. A minor hypokalemia (3.2 mmol/l) was noticed and rapidly corrected, and macrolides and prokinetic agents were stopped because of the potential action of these drugs on QT duration. No fever was notified. A transthoracic echocardiography was performed and revealed no abnormalities.

Seven hours later, monomorphic VT recurred, alternating with episodes of sinus bradycardia and then asystole, which resolved after external chest compression. The amiodarone infusion rate was decreased. At this time, it was noticed that the patient's urine was dark brown in color. Propofol infusion syndrome (PRIS) was suspected, thus propofol infusion was immediately stopped, i.e. 100 h after infusion onset. At this time, the 12-lead ECG showed alternately of sinus rhythm and undetermined rhythm with widened QRS complexes, together with coved-type ST elevation in the lateral, inferior, and right precordial leads and long QT intervals (Figure 2a). Echocardiography was repeated and was again strictly normal. Amiodarone was finally stopped 48 h after initiation.

Biological testing failed to reveal any significant abnormality, since there was no metabolic acidosis, hyperkaliemia, renal failure, or elevated levels of triglycerides, but only moderate rhabdomyolysis possibly related to corporeal injury (troponin Ic peak 2.2 ng/ml for normal values <0.05). Plasma levels of calcium and magnesium were in the normal range.

Lumbar cerebrospinal fluid drainage was then performed to control ICP. Sedation was stopped and a correct wakening was observed, allowing weaning from mechanical ventilation 3 days after the first cardiac signs. Repeated 12-lead ECGs after propofol weaning demonstrated disappearance of arrhythmias and normalization of the QRS complexes and of ST elevation, replaced by slowly regressive diffuse inverted negative or biphasic T waves with long QT intervals (Figure 2b). The patient fully recovered without any cardiovascular or neurologic sequellae. ECG performed 2 months later was found to be unremarkable, as were the ambulatory ECG recording and treadmill. Because the patient was resident in another country, ajmaline challenge was not performed.

Discussion

We describe here an original case of severe cardiac arrhythmias associated with transient ST elevation and long QT, which were suspected to be related to propofol infusion but without the significant biological abnormality usually associated with the PRIS.

PRIS is an often underdiagnosed life-threatening adverse event described in around 30% of critically ill children and adults sedated with propofol.¹ The pathophysiology of PRIS is not fully explained but probably involves mitochondrial dysfunction related to direct propofol toxicity, leading to severe metabolic acidosis, hyperlipidemia, rhabdomyolysis, and heart and renal failure.¹ Severe head injury patients and, more generally, patients with acute central nervous system diseases are likely to develop PRIS.² A young age is a predisposing factor for PRIS, possibly because carbohydrate stores are depleted faster in children,² potentially leading to increased fat metabolism.¹ The duration (> 48 h) and the amount of propofol infusion (>4 mg/kg/h) are associated with increasing risk of PRIS.²

Severe and sometimes lethal cardiac arrhythmias may complicate the evolution of PRIS, which have been shown to be preceded by a “Brugada-like” ST elevation on ECG.^3–6 PRIS-related conduction disturbances,^7,8 increased QT duration,³ idioventricular rhythm,³ supraventricular tachycardia^3,8 and inverted negative T waves⁹ have also been described during PRIS, and may be misleading.

Some patients may present transient forms of the Brugada ECG pattern in the absence of the currently known genetic background, for example when submitted to some toxics or drugs including propofol.⁶ These are acquired extrinsic forms of Brugada syndrome, as ST elevation does not usually recur once the drug is removed—as in our case—even after pharmacological challenge, while genetic analysis failed to reveal mutations in the SCN5A gene in most cases.⁶ These acquired forms may carry some arrhythmic risk as long as ST elevation is present.⁶

Increased levels of endogenous steroids and catecholamines released into the myocardium and propofol-induced myocytolysis have been proposed for explaining the cardiac complications of PRIS.¹ On the other hand, propofol is known to impair mitochondrial metabolism and energy production, to increase the vagal tone while decreasing the sympathetic tone, and to inhibit the cardiac sodium channel current I_Na, the transient potassium outward current I_to, and the L-type calcium current I_CaL, all conditions facilitating ST elevation according to the transmural voltage gradient theory.³

However, neither ST elevation nor long QT has been described following propofol infusion in an experimental model of canine right ventricular wedge.³ Therefore, the development of ST-segment elevation or QT interval increase and related arrhythmias is probably not the direct result of propofol toxicity alone. Some other conditions (acidosis, fever, electrolyte, or still unknown metabolic abnormalities) or other medications could also play a role.^1,3 In our case, norepinephrine, hypokalemia, prokinetic and other drugs lengthening QT interval such as erythromycin or amiodarone could have led to some of the ECG changes and precipitated cardiac arrhythmias. Furthermore, there are some potential pharmacokinetic interactions between propofol and erythomycin. However, it is difficult to relate the slowly regressive long QT to the concomittant administred drugs due to their short half-lives. Even if propofol also displays a short half-life, repolarization abnormalities took several days to normalize in some of the previously reported cases of PRIS.¹⁰ Moreover ST elevation has never been reported with the concommitant drugs. Finally, although no baseline ECG was available before propofol infusion, ECG changes and related arrhythmias are unlikely to be secondary causes of elevated ICP only in the absence of associated brain lesions, which usually do not lead to significant ECG changes alone.

The usual biological abnormalities observed during PRIS are associated metabolic acidosis, hypertriglyceridemia, renal failure, hyperkaliemia, rhabdomyolysis, and myoglobinuria.¹ These biologic disorders have been considered as early markers of PRIS.² In our case, the lack of significant alteration in the usual metabolic and biological parameters initially rendered the diagnosis of PRIS doubtful. However, cases of genuine PRIS without metabolic acidosis have been published,⁴ and thus biological signs are unlikely to be mandatory for PRIS. Therefore, the possibility of coexisting severe clinical/ECG features and biological “normality” must be considered without ruling out this important diagnosis.

In cases of propofol infusion, ST-segment elevation should be immediately considered as an early precursor sign for potentially lethal arrhythmia.³ The occurrence of ST elevation preceding sudden death due to malignant ventricular arrhythmias has been reported,^6,7 even though uncomplicated cases have been also observed.¹⁰ The risk of PRIS seems to warrant closed monitoring when using propofol infusion, especially for children. The occurrence of an electrical storm associated with Brugada-like ST elevation should lead to immediate infusion of isoprenaline and/or use of quinidine, while long QT-related arrhythmias may need correction of the QT interval by magnesium and/or accelerating the heart rate.

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