Abstract

Background: Optic nerve sheath diameter (ONSD) has been shown to be a noninvasive and quick method to calculate intracranial pressure (ICP) and subsequent neurologic outcomes, although with variable cutoffs. ICP can be indirectly assessed by noninvasive methods such as transcranial Doppler, ONSD, tympanic membrane displacement, and fundoscopy. Knowledge regarding the diagnostic accuracy of ONSD for predicting unfavorable outcomes within 72 hours (h) of moderate and severe head injury is limited. The objective of this study was to measure ONSD measurements at 24-h intervals in moderate to severe head injury patients and to find its association with clinical outcomes in the target population.

Methods: This prospective observational study was done on moderate to severe head injury patients. ONSD was measured twice at 24-h intervals over 48 h. The clinical outcome was divided into the favorable group (patients who were in conservative treatment with a stable Glasgow Coma Scale [GCS] score and discharged following treatment) and the unfavorable group (patients who had a drop in GCS motor score of one or more, or expired or underwent surgical intervention) within 72 h following traumatic brain injury. The Kruskal–Wallis test, Mann– Whitney test, and receiver operating characteristic curves were used to establish the association between ONSD and clinical outcomes.

Results: ONSD values measured at 24-h intervals >6.1 mm (P P

Conclusion: ONSD is an efficient screening tool to assess neurological outcomes in severe head injury patients. It can reliably predict the need for secondary DC at an earlier stage before secondary brain damage ensues in these patients.

Keywords: Decompressive craniectomy, Neurological outcome, Optic nerve sheath diameter, Traumatic brain injury

INTRODUCTION

Intracranial pressure (ICP) rises in various neurological and nonneurological conditions and requires rapid diagnosis and treatment due to its fulminant nature.[ 25 ] Brain trauma foundation (BTF) has enumerated specific indications for ICP monitoring following traumatic brain injury (TBI).[ 3 ] ICP can be measured by either invasive or noninvasive methods. Noninvasive methods assess the ICP indirectly without inserting a catheter into the brain parenchyma. They also exclude the adverse effects of invasive techniques.[ 18 ] In this context, a noninvasive, safe tool that may be used in the emergency department (ED) to screen patients at risk of developing raised ICP, especially in the early stages, would be beneficial.[ 21 ] Most noninvasive methods are based on transcranial Doppler (TCD) and optic nerve sheath diameter (ONSD) measurement by ultrasonography (USG).[ 7 , 8 , 10 , 24 , 29 ] Although ONSD measurement cannot replace invasive ICP monitoring, it can indirectly differentiate between normal and raised ICP. It can also be used to screen the at-risk population when invasive methods are not available or undesirable.[ 18 ] However, knowledge regarding the diagnostic accuracy (DA) of ONSD for predicting unfavorable outcomes in TBI within 72 h is limited. Hence, this study was done to measure the ONSD in moderate and severe head injury patients and to find whether ONSD can be used as a reliable indicator of clinical outcomes in these patients.

MATERIALS AND METHODS

This study was conducted as a single-center prospective observational study at a tertiary care referral center for neurological disorders in South India between March 2019 and April 2020. The study was prior reviewed and approved by the Postgraduate Research Monitoring Committee and the Institute Ethics Committee [JIP/IEC/2018/166].

Inclusion criteria

Individuals between 18 and 60 who were admitted to the hospital ED within 24 h following moderate and severe head injuries (Glasgow coma scale [GCS] score 3–12) were included in the study.

Exclusion criteria

Patients with active medical conditions such as diabetes mellitus, hypertension, ophthalmic disorders with optic nerve changes, polytrauma, hemodynamically unstable, penetrating head injury, skull base fracture with cerebrospinal fluid (CSF) leak, and ocular lesions precluding assessment of ONSD were excluded from the study.

Sampling method

Based on a pilot study by Robba et al., the area under the curve (AUC) of ICP in predicting surgical intervention was 0.75.[ 20 ] By taking this as a reference value, δ as 0.13 and 5% level of significance, the calculated sample size was 29 patients. We evaluated the feasibility of the study in 72 patients. Since the next of kin of 12 patients declined to participate in the study, 60 patients were evaluated for eligibility. After applying exclusion criteria, presence of active medical conditions (n = 18), and failure to find an ocular window (n = 14), 32 patients were further excluded from the study. Hence, 28 patients (21 males and seven females) were enrolled in this study [ Figure 1 ]. A convenient sampling technique was followed for the recruitment of patients, and the study was conducted by the Department of Neurosurgery in Emergency Medical Services (EMS). The study procedures were explained, and written informed consent was obtained from all the study participant’s next of kin before enrolling them in the study. The sociodemographic details of the participants were collected and entered into a data sheet.

Figure 1:

Flow chart of included patients and outcome. ONSD: Optic nerve sheath diameter

Measurement of ONSD

Patients who were planned for conservative management on admission based on the clinical examination, computerized tomography (CT) brain findings, and BTF guidelines were taken for ONSD measurements over a period of 48 h. Three readings were taken from each eye by a single investigator (resident neurosurgeon) twice with an interval of 24 h. The mean ONSD value was calculated from the average of six readings each time. The first mean ONSD reading was taken in EMS or trauma intensive care unit (ICU) within 24 h of TBI (ONSD1), and the second was taken after 24 h (ONSD2) from the first reading in the trauma ICU. If the interval between the first CT brain and ONSD1 measurement happened to be more than 6 h, a repeat CT was taken before the ONSD measurement to ensure the patient management (conservative as per initial assessment) remained unaffected. A total of 336 ONSD measurements were taken from 28 moderate to severe head injury patients (3 in each eye 24 h apart). The average ONSD measurement in each eye was utilized in statistical analysis to minimize the effects of the laterality of any lesion. Fifty-six average ONSD measurements were obtained in the study.

Since most TBI patients tend to deteriorate in the first 72 h of TBI, all the participants were observed until 24 h following the second ONSD measurement (ONSD2).[ 1 ] The treating team was blinded to the ONSD values so as to avoid unnecessary surgery by the treating team based on the unproven investigation (ONSD).

The ONSD was measured using a 7.5-MHz linear ultrasound probe (CHISON digital color Doppler system Ebit60) with the lowest possible acoustic power that could measure the ONSD [ Figure 2 ]. Tegaderm (transparent dressing – usually used for central line dressings) was applied over the closed eyelids before the procedure. The probe was placed on the closed eyelids of patients (on both eyes) in the supine position. It was oriented perpendicularly in the vertical plane and around 30° in the horizontal plane. We were able to determine ONSD in the visual axis by placing the probe over the closed eyelids after applying the ultrasound gel. The probe was moved slightly until the optic nerve appeared as a linear hypoechoic object with defined margins behind the globe. After freezing the screen image, we manually determined the ONSD 3 mm behind the globe.[ 14 ]

Figure 2:

(a and b) Ultrasonographic measurement of optic nerve sheath diameter.

Clinical outcome

The clinical outcome of importance was defined as a drop in GCS by a motor score of one or more, or surgical intervention, or death within 24 h following ONSD2 measurements. The clinical outcomes were compared with ONSD values and divided into the favorable group (patients who were in conservative treatment with a stable GCS score and discharged following treatment) and unfavorable group (patients who had a drop in GCS motor score of one or more, or expired or underwent surgical intervention) within 72 h following TBI.[ 1 ] Those who required surgery were subjected to decompressive craniectomy (DC) as per BTF guidelines.[ 3 ] In the deceased individuals, extracranial causes of death were ruled out.

Statistical method

The data were entered in the MS EXCEL spreadsheet, and analysis was done using the Statistical Package for the Social Sciences version 21.0, IBM, USA. Continuous variables were reported as mean ± standard deviation and median, whereas categorical variables were presented as numbers and percentages. The receiver operating characteristic (ROC) curve was used to find out the AUC of ONSD for predicting surgery. Kruskal–Wallis test was applied to find the association between ONSD with the outcome. Mann–Whitney test was applied to establish the relation between ONSD and clinical outcome. The ROC curve of ONSD was plotted to predict an unfavorable outcome. P < 0.05 was considered statistically significant. The sensitivity, specificity, and DA of ONSD were assessed.

RESULTS

Twenty-eight patients (21 males and seven females) with moderate and severe head injuries were enrolled in this study. The median (interquartile range) age, GCS score, ONSD1, and ONSD2 of the study participants were 31 (21–50), 9 (7–11), 6.3 mm (6.075–6.4), and 6 mm (5.5–6.325), respectively [ Table 1 ]. Fifteen study participants had moderate TBI, among which seven underwent surgery, and eight were managed conservatively and discharged. The remaining 13 patients had severe TBI, of which five underwent surgery, four were conservatively managed and discharged, and four died [ Table 2 ].

Table 1:

Clinical characteristics of subjects.

Table 2:

Distributions and management of patients based on severity of TBI.

Among the 28 study subjects, 12 patients (43%) had no deterioration in GCS score during conservative management and were subsequently discharged. Twelve patients (43%) underwent DC, and 4 (14%) expired [ Tables 1 and 2 ].

ONSD and clinical outcomes

Significantly different ONSD1 values were observed between the discharged (6.05 mm), dead (6.25 mm), and operated (6.4 mm) groups (P = 0.022). Similarly, significantly different ONSD2 values were observed between the discharged (5.6 mm), dead (6.35 mm), and operated (6.3 mm) groups (P = 0.006) [ Table 3 ].

Table 3:

The relationship between ONSD, and clinical (favorable and unfavorable) outcomes.

DA of ONSD1 and 2

ONSD1 had a strong discriminating power (AUC 0.747; 95% confidence interval (CI): 0.548–0.891), and an ONSD1 value >6.1 mm was found in 93.75% (sensitivity) of patients with unfavorable outcomes. If the ONSD1 valve was >6.1 mm, there was a 75% positive predictive value (PPV) of predicting an unfavorable outcome. An ONSD1 value was ≤6.1 mm indicated a favorable outcome. The DA of ONSD1 (mm) in predicting unfavorable outcomes was 78.57% [ Table 4 and Figure 3 ].

Figure 3:

(a and b) Receiver operating characteristics curve of optic nerve sheath diameter (ONSD) 1 and 2 for predicting unfavorable outcome.

Table 4:

Prognostic values of measures.

Similarly, ONSD2 also had a strong discriminating power (AUC 0.844; 95% CI: 0.657–0.952), and ONSD2 value >6.2 mm was found in 62.5% (sensitivity) of patients with unfavorable outcomes. If the ONSD2 valve was >6.2 mm, there was a 90.9% PPV of predicting an unfavorable outcome. An ONSD2 value was ≤6.2 mm indicated a favorable outcome. The DA of ONSD2 (mm) in predicting unfavorable outcomes was 75% [ Table 4 and Figure 3 ].

It was observed that four patients, despite high ONSD values, survived, while three patients with low ONSD values deteriorated and underwent surgery [ Table 5 ].

Table 5:

Patients survived with high ONSD values and deteriorated in spite of low ONSD values.

DISCUSSION

The primary aim of this study was to measure the ONSD among 28 patients with moderate to severe head injury and to determine the relationship between ONSD and clinical outcomes in these patients. Significantly different ONSD1 and ONSD2 values were observed between the discharged, dead, and operated groups. The DA of ONSD1 and ONSD2 in predicting unfavorable outcomes was 78.57% and 75%.

The novelty of this study is that it has demonstrated the reliability of ONSD to predict neurological outcomes and the need for secondary DC in the early stages of TBI, where clinical signs and computerized tomography (CT) brain findings are of ambiguous nature. To the best of our knowledge, this is the first study where ONSD values were taken in both eyes at regular intervals in all the study participants, twice within 72 h of TBI, during which most of the patients tend to deteriorate due to intracranial hypertension and loss of autoregulation.[ 11 ]

The need for noninvasive methods in TBI patients

Invasive ICP monitoring is presently considered the standard of care in moderate and severe head injury patients despite its lack of level I evidence. Physicians often have to make decisions on a case-by-case basis in the management, particularly in borderline scenarios.[ 4 - 6 ] As a result, it is preferable to have a reliable noninvasive method to anticipate the development of intracranial hypertension and secondary brain injury in the early stages.

The role of ONSD in TBI patients monitoring

Techniques such as TCD, ONSD, tympanic membrane (TM) displacement, fundoscopy, and CT/magnetic resonance imaging (MRI) may be helpful in assessing the ICP by noninvasive methods. Among these, ONSD can be used as a potential screening tool for TBI patients because it is quick, efficient, and can differentiate between normal and raised ICP at the bedside. TCD has a high percentage of unsuccessful measurements. Fundoscopy and MRI have a limited role in TBI.[ 8 , 18 , 21 ]

The advantages of ONSD measurement by USG over CT or MRI

ONSD was measured by USG in previous studies such as Robba et al., Strumwasser et al., Geeraerts et al., Thotakura et al., Rajajee et al., Wang et al., and Soldatos et al.[ 8 , 10 , 19 - 21 , 23 , 24 , 26 - 28 ] Kim et al., Legrand et al., and Bekerman et al. managed to get the ONSD values by CT.[ 2 , 15 , 17 ] Geeraerts et al., and Kimberly and Noble, got ONSD values with MRI measurements.[ 11 , 16 ] USG was used in this study to measure ONSD because it is safe, quick, accurate, and can be done at the bedside in TBI patients.

Association between ONSD and clinical outcomes

ONSD1 value >6.1 mm was found in 93.75% of patients with unfavorable outcomes. It was also observed that if the ONSD2 valve was >6.2 mm, then there was a 90.9% probability of predicting unfavorable outcomes. The study could predict that if the ONSD value was <6.1 mm in the study participants, the chance of a favorable outcome was up to 87.5% [ Table 4 ]. A significant association was noted between ONSD and clinical outcomes, thus proving ONSD as a predictor of clinical outcomes, morbidity, and mortality after TBI, as mentioned in previous studies.[ 2 , 9 , 10 , 11 , 15 - 17 , 19 - 23 , 26 - 28 ]

Variation in cutoff values of ONSD

The optic nerve sheath is anatomically continuous with the dura mater of the brain, and it has a trabeculated subarachnoid space through which CSF flows. The fibrillary arrangement of arachnoid trabeculations allows the optic nerve sheath to dilate when ICP rises in TBI. The trabeculations in the anterior segment of the optic nerve sheath are sparse with respect to the posterior segment making it more distensible than the posterior segment.[ 12 , 13 ] Studies have confirmed that 3 mm behind the globe is the preferred position to measure ONSD. In line with Helmke and Hansen., the ONSD was measured at 3 mm behind the globe in the study participants.[ 14 ]

Studies by Geeraerts et al., and Kimberly and Noble, have shown that the cutoff value of ONSD to predict the raised ICP was between 4.5 and 6.3 mm. Variations in ONSD have been attributed to multiple reasons, including the technique used, variations in the machine and probe, the experience of the observer, and the study population from various ethnicities.[ 11 , 16 ]

DA of ONSD in predicting unfavorable outcomes

Studies by Robba et al., Rajajee et al., and Wang et al. have proved the high sensitivity and specificity value of ONSD in their analysis, but only a few studies have discussed its DA.[ 19 , 21 , 27 ] This study has shown the DA of ONSD1 and ONSD2 (mm) to predict unfavorable outcomes at 78.57% and 75% [ Table 4 ].

ONSD as a screening tool

Thus, the study has clearly demonstrated that ONSD could be used as a potential screening tool to infer ICP indirectly (noninvasive ICP) in moderate and severe head injury patients, the reasons being its measurement by USG, which is less time-consuming, accurate, efficient, low-cost, noninvasive, and can differentiate normal and raised ICP. While USG is readily available in many peripheral centers, the facility to measure the invasive ICP is not available or contraindicated due to various clinical conditions. This study has also proved that ONSD can predict favorable and unfavorable clinical outcomes and the need for DC in the early stages of TBI by a noninvasive method.

The limitations of the techniques, like intra/interobserver variability and nonavailability of the optimal orbital window due to ocular disorders, preclude its use as a definite substitute for invasive methods.

Limitations

The major limitations of this study are its small sample size, and short follow-up period (up to 72 h following head injury). Considering the age group of the study participants, the study results cannot be generalized to the entire population. Hence, studies with a larger sample size involving individuals of different age groups are required to substantiate the results of the study.

CONCLUSION

The ONSD is a potential screening tool for predicting favorable and unfavorable clinical outcomes in moderate and severe head injury patients. It will also provide valuable information about the need for early DC, which will avoid potential loss of time and help the patient to gain a favorable neurological outcome.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

Disclaimer

The views and opinions expressed in this article are those of the authors and do not necessarily reflect the official policy or position of the Journal or its management. The information contained in this article should not be considered to be medical advice; patients should consult their own physicians for advice as to their specific medical needs.

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