Incidence and mechanisms of cardiorespiratory arrests in epilepsy monitoring units (MORTEMUS): a retrospective study

Ryvlin P, Nashef L, Lhatoo SD, Bateman LM, Bird J, Bleasel A, Boon P, Crespel A, Dworetzky BA, Høgenhaven H, Lerche H, Maillard L, Malter MP, Marchal C, Murthy JM, Nitsche M, Pataraia E, Rabben T, Rheims S, Sadzot B, Schulze-Bonhage A, Seyal M, So EL, Spitz M, Szucs A, Tan M, Tao JX, Tomson T. (2013) Incidence and mechanisms of cardiorespiratory arrests in epilepsy monitoring units (MORTEMUS): a retrospective study. Lancet Neurol 12(10): 966-77

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Abstract: BACKGROUND: Sudden unexpected death in epilepsy (SUDEP) is the leading cause of death in people with chronic refractory epilepsy. Very rarely, SUDEP occurs in epilepsy monitoring units, providing highly informative data for its still elusive pathophysiology. The MORTEMUS study expanded these data through comprehensive evaluation of cardiorespiratory arrests encountered in epilepsy monitoring units worldwide. METHODS: Between Jan 1, 2008, and Dec 29, 2009, we did a systematic retrospective survey of epilepsy monitoring units located in Europe, Israel, Australia, and New Zealand, to retrieve data for all cardiorespiratory arrests recorded in these units and estimate their incidence. Epilepsy monitoring units from other regions were invited to report similar cases to further explore the mechanisms. An expert panel reviewed data, including video electroencephalogram (VEEG) and electrocardiogram material at the time of cardiorespiratory arrests whenever available. FINDINGS: 147 (92%) of 160 units responded to the survey. 29 cardiorespiratory arrests, including 16 SUDEP (14 at night), nine near SUDEP, and four deaths from other causes, were reported. Cardiorespiratory data, available for ten cases of SUDEP, showed a consistent and previously unrecognised pattern whereby rapid breathing (18-50 breaths per min) developed after secondary generalised tonic-clonic seizure, followed within 3 min by transient or terminal cardiorespiratory dysfunction. Where transient, this dysfunction later recurred with terminal apnoea occurring within 11 min of the end of the seizure, followed by cardiac arrest. SUDEP incidence in adult epilepsy monitoring units was 5·1 (95% CI 2·6-9·2) per 1000 patient-years, with a risk of 1·2 (0·6-2·1) per 10,000 VEEG monitorings, probably aggravated by suboptimum supervision and possibly by antiepileptic drug withdrawal. INTERPRETATION: SUDEP in epilepsy monitoring units primarily follows an early postictal, centrally mediated, severe alteration of respiratory and cardiac function induced by generalised tonic-clonic seizure, leading to immediate death or a short period of partly restored cardiorespiratory function followed by terminal apnoea then cardiac arrest. Improved supervision is warranted in epilepsy monitoring units, in particular during night time.

Context

• Comprehensive, retrospective study of possible mechanisms for SUDEP, evaluating cardiorespiratory arrests in epilepsy monitoring units from around the world. Twenty-nine cardiorespiratory arrests were reported, which were there classified as either SUDEP (definite or probable), near SUDEP (fatal or non-fatal), or non-SUDEP. Incidence of death, cardiorespiratory arrest, near SUDEP, and SUDEP was calculated on the basis of an estimation of total patient-years spent in the epilepsy monitoring units. 56% of the cases of SUDEP and near SUDEP had reported Generalized tonic-clonic seizures (GTCSs) within the preceding 3 months, in concurrence with many studies (Timmings, Nashef et al., Opeskin et al., Lhatoo et al., Walczak et al., Langan et al., and Surges et al.). Among the 16 SUDEP cases in which position could be assessed, 14 were prone. SUDEP was successfully continuously monitored in 10 and four consistent features were noticed: rapid breathing during the immediate postictal phase, postictal generalized EEG suppression, early cardiorespiratory dysfunction, and terminal apnea always preceded terminal asystole. Findings of apnea in these SUDEP cases can help support the reports of oxygen desaturation from Blum et al., Hewertson J, Poets CF et al., and Hewertson J, Boyd SG et al..