Ictal Hypoxemia in Localization-Related Epilepsy: Analysis of Incidence, Severity and Risk Factors

Lisa M. Bateman; Chin-Shang Li; Masud Seyal


Brain. 2008;131(12):3239-3245. 

In This Article


There were 34 (60.7%) female patients in this group of 56 patients. The mean age was 36.9 ± 14 (34.5; 16-63) years. At the time of hospital admission, patients were taking between zero and five anti-epileptic medications. Eleven patients were on monotherapy, one patient was not on anti-epileptic medication and the remaining patients were on polypharmacy.

Oxygen saturation data was available in 304 seizures of partial onset, 51 of which progressed to generalized convulsions. We first looked at the entire group of partial onset seizures with or without secondarily generalized convulsions. A total of 101 of these 304 seizures were associated with desaturations below 90%; 30 seizures occurred in sleep, 69 during wakefulness and with two seizures the patient's state could not be determined. Of these 101 seizures, 31 (30.7%) seizures were associated with desaturations below 80% and 11 (10.9%) seizures with desaturations below 70% (Fig. 1A and B). The mean oxygen saturation nadir following secondary generalization was 75.4% ± 11.4% (77%; 42-100%). Review of oxygen saturation data acquired during continuous video-EEG telemetry confirmed that no patient had oxygen desaturation below 90% unless temporally associated with a seizure.

Figure 1.

(A) Oxygen saturation nadir (percent saturation) for each seizure. Recorded saturation values below 50% were truncated at 50%. The vertical lines above the hatched bar separate data from the 56 individual patients. (B) Pronounced oxygen desaturation with a complex partial left temporal onset seizure without secondary generalization. Patient was a 19-year-old male with a BMI of 19.9. Seizure onset occurred with the patient awake and sitting in bed. He became unresponsive with lip smacking, a slight head turn to the left followed by forceful head turning to the right. He remained sitting for the duration of the seizure. The heart rate (b.p.m.) at various times is shown. Two other complex partial seizures in this patient (one left and one right temporal onset) were accompanied by oxygen desaturations below 50%. Oxygen saturation percent is shown on the ordinate.

The mean duration for all seizures was 80.6 ± 76.1 s (64.0; 3-610). There was a statistically significant correlation between the level of desaturation and seizure duration (P = 0.001). Seizure localization was statistically significantly associated with desaturation below 90% [P = 0.005, odds ratio (OR) of temporal versus extratemporal onset = 5.202; 95% CI = (1.665, 16.257)]. Seizure lateralization was statistically significantly associated with desaturation below 90% [P = 0.001, OR of right versus left = 2.098; 95% CI = (1.078, 40.85)]. Contralateral spread of seizures was statistically significantly associated with desaturation below 90% [P = 0.028, OR of contralateral spread versus no contralateral spread of seizures = 2.591; 95% CI = (1.112, 6.039)]. Patient position at seizure onset (recumbent versus semi-recumbent or sitting), state of the patient at seizure onset (awake versus asleep), age of patient and BMI were not associated with desaturation below 90%. There was a statistically significant association of gender with desaturation below 90% [P = 0.048, OR of female versus male = 0.422; 95% CI = (0.179, 0.994)]. Heart rate change (ictal peak heart rate - baseline heart rate) was not associated with desaturation below 90%. In the smaller group of seizures with more pronounced desaturations (<85%), a statistically significant association of desaturation with seizure lateralization or localization was not present, possibly because of lower power in this group. In a given patient with a seizure related desaturation of <85%, the probability that a subsequent seizure would be accompanied by a desaturation of <85% was 0.433.

For all seizures, the mean delay from seizure onset to the onset of desaturation below 90% was 66.7 ± 37.6 s (59; 6-226). The mean saturation nadir occurred 98.3 ± 63.3 s (86; 8-521) after seizure onset. The delay to desaturation from seizure onset is, in part, a reflection of circulation time and processing delay in the oximeter. For all seizures, the mean duration of desaturation (from <90% to ≥90%) was 69.2 ± 65.2 s (47; 2-327). Oxygen saturation recovery to within 2% of preictal baseline value was further delayed. The mean duration from desaturation below 90% to recovery to preictal baseline level was 104.4 ± 78.4 s (90; 8-407). These data are summarized in Table 1 .

We next looked at the subset of partial onset seizures that did not progress to generalized convulsions. Of the 304 seizures for which oxygen saturation data was available, 253 (83.2%) did not result in secondarily generalized convulsions. Desaturation nadirs below 90% occurred with 88 (34.8%) of the 253 seizures. In 28 (31.8%) of these seizures, oxygen saturations fell below 80% and in 11 (12.5%) seizures saturations fell below 70%. The mean desaturation nadir in these 88 seizures was 80.7%. Fifty-five of the 88 seizures with desaturations below 90% were complex partial seizures of temporal onset. Eleven were electrographic seizures of temporal onset without any discernable behavioural manifestations. In another 11 seizures of temporal onset there was inadequate testing to determine whether impairment of consciousness was present. The remaining seizures included three complex partial frontal onset seizures, one gelastic seizure and seven seizures with inadequate electrographic localization. Desaturations below 90% occurred with 52 of 101 (51.5%) recorded seizures of right temporal onset and in 23 of 58 seizures of left temporal onset (39.7%). In the remaining two patients, there was near simultaneous electrographic involvement of the left and right temporal scalp regions at seizure onset. In this group of seizures that did not generalize, seizure duration statistically significantly correlated with the level of desaturation (P ≤ 0.001) (Fig. 2). The level of desaturation also correlated with electrographic spread of the seizure to the contralateral hemisphere (P = 0.003). Seizure duration and electrographic spread to the contralateral hemisphere were statistically significantly correlated (P = 0.003). BMI and the state of the patient at seizure onset were associated with only the more severe desaturations. The BMI was statistically significantly associated with desaturations below 85% [P = 0.021; OR = 1.116; 95% CI = (1.017, 1.225)]. The state of the patient was statistically significantly associated with desaturations below 85% [P = 0.001; OR of awake versus asleep = 3.674; 95% CI = (1.719, 7.851)].

Figure 2.

Plot of seizure duration versus level of desaturation. Oxygen saturation = 94.704 - 0.083 × seizure duration.

To determine a possible effect of anti-epileptic drug load on the degree of oxygen desaturation, the two-sided Wilcoxon signed-rank test was used to determine whether there was a statistically significant difference between oxygen saturation nadirs for the first and last partial seizure in each patient. Fifty-one patients had more than one seizure with saturation data. The mean saturation nadir associated with the first partial seizure was 89.1 ± 9.9% (92%; 50-100%) and for the last seizure the mean nadir was 90.8 ± 9.0% (94%, 57-100%). In seizures that progressed to generalized convulsions, the desaturation nadir prior to the onset of secondary generalization was used. There was no statistically significant difference in desaturation nadirs between the first and last seizures (P-value = 0.366).

Nineteen of 56 patients had no desaturations below 90% with any of 85 seizures. In this group of 19 patients, 41 of the 85 seizures were of extra-temporal onset. The mean BMI in patients having no desaturations with any seizure was 26.8 ± 5.2 (25.4; 20.4-37.1). In patients with desaturations accompanying any seizure, the mean BMI was 26.2 ± 6.4 (25.4; 15.7-42.2). The BMI was not statistically significantly associated with whether or not the patients had desaturations with any seizure [P = 0.691, OR = 0.981, 95% CI = 0.892-1.079)].

Nasal airflow and abdominal excursion data were available in 100 seizures. In the remaining seizures, these data were obscured by artefact and not interpretable or were unavailable. In 44 (44%) of these 100 seizures, there was evidence of central apnoea during the seizure (Fig. 3). Six (6%) seizures were accompanied by hypopnoeas (airflow amplitude reduced by at least 30% relative to pre-ictal baseline). There were two (2%) obstructive apnoeas (absent airflow with continuing abdominal excursions) and seven (7%) mixed apnoeas (central and obstructive components during the apnoea). There were no apnoeas or hypopnoeas detected with 41 (41%) of 100 seizures.

Figure 3.

Complex partial seizure with secondary generalization recorded in a 31-year-old woman; 60 s per frame. Frame 1 shows right temporal onset seizure with central apnoea. Secondary generalization occurs in Frame 2 and oxygen desaturation is seen. Seizure ends in Frame 3 with resumption of breathing and continued but improving oxygen desaturation.

In seven patients (19 seizures), we recorded simultaneous ictal ETCO2 and oxygen saturation data. The mean preictal ETCO2 for the group, averaged over 1 min from 1 to 2 min prior to seizure onset, was 32.8 ± 8.2 mm Hg (30.3; 16.2-47.2). One patient had been hyperventilating vigorously prior to seizure onset with mean preictal ETCO2 of 16.2 and 22.6 mm Hg, respectively for two seizures. The mean increase in ETCO2 from the preictal baseline to ictal peak ETCO2 was 18.6 ± 17.7 mm Hg (13.2; 2.8-77.8). In seven of the 19 seizures, ETCO2 values were above 50 mm Hg (Fig. 4A). The mean oxygen saturation nadir during these seizures was 77% ± 8.8% (79%; 50-86%). The most pronounced increases in ETCO2 occurred in patients with secondarily generalized seizures. However, increases in ETCO2 occurred with every partial onset seizure that had a simultaneous drop in oxygen saturation to 85% or less. In some patients, the increase in ETCO2 beyond preictal values persisted >30 min following termination of the seizure (Fig. 4B).

Figure 4.

(A) Partial onset seizure with secondary generalization. There is an increase in ETCO2 above 65 mm Hg accompanying a drop in oxygen saturation. Respiratory rate increases during the period of hypercarbia. The longer arrow indicates seizure onset; the shorter arrow indicates seizure end. (B) Left temporal onset complex partial seizure. There is an abrupt increase in ETCO2 with concomitant drop in oxygen saturation. ETCO2 elevation persists above preictal levels for >30 min after the end of the seizure.

Ictal tachycardia occurred with most seizures. The mean preictal heart rate (averaged over 10 s, 1 min prior to seizure onset) was 81 ± 17 beats per minute (b.p.m.) (72; 42-144). The mean ictal heart rate increase was 38 ± 28 b.p.m. (36; -24 to +126) with a range of -24 to +126 b.p.m. The duration of ictal tachycardia (defined as the time interval during which the heart rate was >100 b.p.m.) was a mean of 129 ± 324 s (70; 10-3670) with a range of 10-3670 s (25 and 75 percentile values of 40 and 120.5 s, respectively). Premature atrial beats, premature ventricular beats and sinus pauses occurred with some seizures in 10 patients. One patient developed a bradyarrhythmia and asystole following a secondarily generalized seizure of left temporal onset. Oxygen saturation dropped below 50% following that seizure.


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