Efficacy of Naloxone in reducing hypoxemia and duration of immobility following focal to bilateral tonic-clonic seizures

  1. Sylvain Rheims
  2. Fatima Chorfa
  3. Véronique Michel
  4. Edouard Hirsch
  5. Louis Maillard
  6. Luc Valton
  7. Fabrice Bartolomei
  8. Philippe Derambure
  9. Vincent Navarro
  10. Julien Biberon
  11. Arielle Crespel
  12. Anca Nica
  13. Martine Lemesle Martin
  14. Laure Mazzola
  15. Jerome Petit
  16. Vincent Rossero
  17. Sébastien Boulogne
  18. Mathilde Leclercq
  19. Laurent Bezin
  20. Catherine Mercier
  21. Pascal Roy
  22. Philippe Ryvlin
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Abstract

Purpose

Evaluating the efficacy of an opioid antagonist, naloxone (NLX), to reduce the severity of post-ictal hypoxemia and immobility after focal to bilateral tonic-clonic seizures (FBTCS).

Methods

ENALEPSY is a double-blind placebo (PCB)-controlled trial conducted in patients with focal epilepsy undergoing long-term video-EEG monitoring (LTM). Patient with a FBTCS during LTM were randomized 1:1 to receive intravenous NLX or PCB within the 2 minutes following the end of FBTCS. After database lock, a discrepancy between the allocated arm and the received treatment was detected, resulting in a 4:1 NLX:PCB ratio. To further explore the efficacy of NLX, we used historical control (HC) data collected in patients included in the REPO 2 MSE study whose characteristics matched those of patients randomized in ENALEPSY. Efficacy of NLX was then assessed versus PCB and versus HC. The primary endpoint was the delay between the end of the seizure and recovery of SpO 2 ≥ 90%. Secondary efficacy outcomes included desaturation nadir and duration of the postictal immobility.

Results

33 patients contributed to the NLX group, 7 to the PCB group and 43 to the HC group. The proportion of FBTCS type 1 or 3 was 84% in NLX, 100% in PCB and 84% in HC. NLX did not improve the delay of recovery of SpO 2 ≥ 90% or the desaturation nadir. In contrast, duration of the postictal immobility differed across groups. The time to mobility recovery within the first 5 minutes post-ictal was very similar in PCB (200.3±215.8 seconds) and HC (194.4±192.0 second) groups, and significantly shorter in the NLX group (128.9±151.1 seconds) when compared to HC (Hazard Ratio, 1.84; 95% CI, 1.11 to 3.05; p=0.021).

Conclusion

NLX did not prevent postictal respiratory dysfunction but might reduce the duration of postictal immobility. Confirmation of this effect and its impact on SUDEP risk will require additional studies

KEY BULLET POINTS

  • –

    ENALEPSY trial evaluated the efficacy of intravenous naloxone to reduce the severity of post-ictal complications after focal to bilateral tonic-clonic seizures.

  • –

    Naloxone did not improve the delay of recovery of SpO 2 ≥ 90% or the desaturation nadir

  • –

    The time to mobility recovery was significantly shorter in the NLX group when compared to historical control

  • –

    Impact of these results on SUDEP prevention will require additional studies

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    1. Version published to 10.1101/2024.12.16.24319102v1 on medRxiv