This study found that the amount and rate of ONSD change were significantly associated with neurologic outcomes. Further, there was no significant between-group difference in the post-CA ONSD. However, there was no independent association of the rate of ONSD change with neurologic outcomes after adjusting for confounding variables. Together with other established predictors, the rate of ONSD change may be useful for predicting neurologic outcomes. To our knowledge, this is the first study to investigate individual differences in ONSD changes among post-CA survivors.
Previous studies have reported an association of neurologic outcomes in critically ill patients, including post-CA survivors, with increased ICP.[3, 4, 21, 22] The optic nerve sheath covers the optic nerve and is comprised of a subarachnoid space layer filled with cerebrospinal fluid (CSF).[23] ICP is positively correlated with the CSF pressure and ONSD length.[23, 24] ONSD is a potential non-invasive ICP estimator and could be useful for assessing intracranial hypertension.[24] In patients with post-CA hypoxic cerebral injury, increased ICP is associated with neurologic outcome.[3, 21, 22]
Several studies have reported that ONSD can predict neurologic outcomes in post-CA survivors. A retrospective cohort study from Korea reported an association of longer ONSD on initial brain CT with poor neurologic outcome.[15] Chelly et al. demonstrated that ONSD could be an early prediction tool for outcomes in post-CA patients treated using TTM.[19] Other studies have used ONSD combined with other predictors, including GWR or albumin levels, to enhance the predictive value. Moreover, a recent meta-analysis reported that ONSD could be useful for predicting neurologic outcome.[14, 20, 21] Inconsistent with these findings, a registry-based multicenter study reported no correlation between ONSD on early unenhanced brain CT and neurologic outcome in post-CA survivors managed using TTM.[25] Previous studies have reported that predicting neurologic outcomes in post-CA survivors using post-CA ONSD alone is insufficient with limitations.
ONSD can allow non-invasive ICP measurement and could serve as a surrogate marker for increased ICP.[17, 18] However, in healthy adults, there are differences in the baseline ONSD according to individual characteristics, including sex, body mass index (BMI), race, or eyeball size.[26, 27] Most studies of healthy volunteers have reported that the mean ONSD ranges from about 3 mm to 5 mm; moreover, the reported mean or median ONSD values have varied across study cohorts depending on the race or measurement tools.[26–29] Ultrasonographic evaluation of healthy Asians revealed a longer ONSD in males and individuals with high BMI.[26, 27] Therefore, these individual differences could confound the interpretation of post-CA ONSD; moreover, it may be useful to consider the baseline ONSD for improving the prognostic value. Therefore, ONSD changes may be useful markers for ICP measurement changes. A prospective observational study on ONSD changes in patients with hydrocephalus reported a significant reduction in ONSD after ventriculoperitoneal shunt operation.[30] In our study, ONSD changes were more reliable than the ONSD itself for predicting neurologic outcomes in patients with post-CA.
A recent meta-analysis reported that compared with CT and MR, sonographic measurement allowed more accurate prediction of neurologic outcome in patients with post-CA.[20] However, obtaining and comparing pre-CA and post-CA ONSD using ultrasound could be limited in clinical settings. Moreover, determining the pre-CA ONSD using brain MR has limitations given its specific modality. Recent studies have indicated that the axial proton density/T2-weighted turbo spin-echo fat-suppressed sequence is required for ONSD measurements using MR. However, in most post-CA patients, the T2-TSE image is not included in the diffusion-weighted MR.[31, 32] Additionally, there is a strong association of ONSD with eyeball transverse diameter (ETD) and ONSD/ETD ratio in healthy adults.[33] There is a need for further studies on the association between ONSD/ETD ratio and neurologic outcome in post-CA patients.
This study has several limitations. First, this was a single-center study with a limited sample size that led to an insufficient statistical power; however, we calculated the sample size, which was relatively large compared with that of other studies. Second, this retrospective study included patients who underwent both pre- and post-CA brain CT, which could lead to selection bias affecting the results. Third, although we attempted to extensively collect variables, there could be hidden confounders. Fourth, there could have been minor measurement errors given the very small size of the ONSD in brain CT. However, to minimize these errors, two blinded emergency physicians performed measurements using a standardized method with consensus. Fifth, current guidelines recommend neurologic outcome assessment at 3 months after discharge. However, we measured the neurologic outcome at discharge and did not determine the long-term outcome. Sixth, this was a retrospective study and the clinical utility of the predictive value for prognosis remains unclear. There is a need for large-scale prospective studies to enhance our findings.