Seizure-related respiratory factors in SUDEP
[Part 2: Questions; Bateman LM & Seyal M]
Respiratory compromise is commonly described by witnesses of SUDEP and near-SUDEP events (Tomson et al., 2008). Increased (tachypnea) or decreased (bradypnea) breathing rates, cessation of breathing (apnea), gasping, sighing, coughing, airway obstruction and fluid accumulation in the lungs (neurogenic pulmonary edema) have all been described with seizures. The MORTEMUS study, which examined cardiorespiratory arrests (CRAs) occurring in epilepsy monitoring units (EMUs), found that in all fatal CRAs, apnea preceded cardiac arrest (Ryvlin et al., 2013). Respiratory mechanisms are therefore likely to play an important role in SUDEP in some individuals.
We previously studied respiratory function in over 300 seizures occurring in 56 patients with pharmacoresistant localization-related epilepsy undergoing epilepsy surgery evaluations in the EMU. In one-third of these seizures, blood oxygen saturation dropped below 90% (hypoxemia). In some cases, this was particularly severe (<70%). Hypoxemia occurred whether or not the seizure progressed to a generalized convulsion (Bateman et al., 2008). Similar results have been noted in other studies involving both adults and children with epilepsy (Moseley et al., 2011; Singh et al., 2013). Ictal hypoxemia has been associated with male gender, younger age in children, symptomatic generalized epilepsy, temporal lobe epilepsy, side of seizure origin (right in adults; left in children), seizure duration, seizure spread to the opposite hemisphere, taking multiple antiepileptic drugs and having a normal MRI (Bateman et al., 2008; Moseley et al., 2011; Singh et al., 2013).
Apnea and bradypnea commonly accompany ictal hypoxemia (Bateman et al., 2008; Seyal & Bateman, 2009; Seyal et al., 2010; Singh et al., 2013). There is a rise in carbon dioxide levels in expired air (hypercapnia), sometimes profound (>70 mm Hg) (Bateman et al., 2008; Seyal et al., 2010). Hypercapnia may outlast a seizure by several minutes, even though both the depth and rate of breathing are enhanced after a seizure ends (Seyal et al., 2010). This suggests that some seizures may result in persistent dysfunction of respiratory control or gas exchange within the lungs.
Ictal respiratory dysfunction could also increase SUDEP risk through secondary mechanisms, including effects on the heart and brain. Ictal hypoxemia has been associated with slowing (bradycardia) or pauses (sinus arrest) in the heart rhythm (Nashef et al., 1996; Singh et al., 2013), as well as with an increased heart rate (tachycardia) (Moseley et al., 2011), itself linked to SUDEP risk (Nei et al., 2004). Changes in how the heart muscle recovers between beats (repolarization), including abnormal lengthening and shortening of QT intervals on the EKG, are more likely to occur in seizures with hypoxemia (Seyal et al., 2011). These changes could increase the risk of a fatal cardiac arrhythmia. Post-ictal generalized EEG suppression (PGES), a possible marker of SUDEP risk (Lhatoo et al., 2010), is associated with the severity and duration of ictal hypoxemia (Seyal et al., 2012). Lack of movement after a seizure, which could worsen respiratory compromise, is also associated with PGES and ictal hypoxemia (Purves et al., 1992; Semmelroch et al., 2012).
Community and EMU-based studies suggest that early intervention after a seizure could rescue a patient from a potentially fatal event (Langan et al., 2005; Ryvlin et al., 2013). However, large scale studies of specific interventions in epilepsy patients are lacking. Nursing actions in the EMU, including turning a patient to the side, suctioning the mouth and giving oxygen, were found to reduce ictal hypoxemia, PGES and seizure duration in one study (Seyal et al., 2013). In a mouse model of seizure-induced respiratory arrest, giving oxygen within a short time window surrounding a seizure, but not before a seizure occurred or after it had ended, protected against death (Venit et al., 2004). A role for using oxygen to protect against SUDEP in epilepsy patients has not been established. Selective serotonin reuptake inhibitors (SSRIs), commonly used to treat depression, also improved seizure-associated respiratory dysfunction in mice (Tupal & Faingold, 2006). In one small retrospective study, patients taking SSRIs in the EMU were less likely to have severe ictal hypoxemia compared with patients not taking SSRIs. This benefit was not seen, however, with seizures that progressed to generalized convulsions, the seizure type most associated with SUDEP (Bateman et al., 2010). Recently, a machine simulation study suggested that special lattice pillows could partially improve respiratory compromise if a patient were to be face down and immobile after a seizure, but only for a limited time (Catcheside et al., 2014). These pillows have not been studied directly in patients with epilepsy.
Seizure-associated respiratory dysfunction likely plays an important role in SUDEP in some patients. Further large-scale studies are needed to better define the mechanisms of ictal respiratory dysfunction and to develop meaningful clinical interventions to reduce the risk of SUDEP.
Lisa M Bateman, Department of Neurology, Columbia University, USA
Masud Seyal, Department of Neurology, University of California, USA
How to cite:
Bateman LM & Seyal M. Seizure-related respiratory factors in SUDEP. In: Hanna J, Panelli R, Jeffs T, Chapman D, editors. Continuing the global conversation [online]. SUDEP Action, SUDEP Aware & Epilepsy Australia; 2014 [retrieved day/month/year]. Available from: www.sudepglobalconversation.com.