Short summary

Monitoring of intracranial pressure (ICP) remains invasive with external ventricular drain being the golden standard. Although several different methods such as optic nerve sheath diameter have shown some promise, no non-invasive ICP monitoring modalities have been implemented. Correlation between intraocular hemodynamics, intraocular pressure (IOP) and ICP is well-known, but not fully understood. Current study is a follow-up study regarding arteriole-venule ratio and estimation of ICP.

Rationale

Purpose

The purpose of this study is to evaluate if non-invasive fundoscopy of the eye's vessels (arterioles and venules) can estimate absolute or change in intracranial pressure in either competent or incompetent patients admitted to the neurosurgical intensive care unit.

We aim to enroll patients who are in risk of having a high intracranial pressure (ICP). These patients are monitored using ICP monitors (e.g. Camino-system or temporary ventricle shunt). However, these patients are often sedated to decrease risk of brain injury, which makes them incompetent.

We aim to compare Arteriole/venule ratio (AV-ratio) of the eye to ICP. Furthermore, we wish to include intraocular pressure (IOP) in our analysis, since this can affect the AV-ratio (Lashutka et al. 2004.(1) The relationship of intraocular pressure to intracranial pressure).

Hypothesis: Primary:

We hypothesize we can detect changes in ICP using AV-ratio and even estimate absolute ICP based on AV-ratio. Secondary: We hypothesize AV-ratio is dependent of IOP.

Rational:

At the moment there are no gold standard non-invasive ICP measurement methods available. Department of Neurosurgery at OUH has already performed a study with a similar method on competent patients with suspected normal pressure hydrocephalus with promising results (Appendix 1 figure 1), 2) and 3)) [yet unpublished data].

Previous literature states crucial ICP is above 20 mmHg. As shown in Figure 1) we can detect a difference between patients having 15-19 mmHg and >19 mmHg. This means potential harmful ICP (above 20 mmHg) can be detected with our method with a sensitivity of 90,6% and a specificity of 37,0%, AUC=0.74, P=0,0002, likelihood ratio 1,4. This correlate well with an initial assessment (screening) but warrants further tests e.g. CT-cerebrum in the critical ill patient.

We wish to test our hypothesis in incompetent patients, because

1) patients are unable to tell the physician how they feel, and a non-invasive measurement is warranted,

2) the incompetent patients in neurocritical ICU tend to have a lot higher ICP than awake patients.

Background

Intracranial pressure (ICP) is defined as the pressure inside the skull, which is affected by the volume of the brain, blood and cerebrospinal fluid (CSF).

Monro proposed in 1783 that

1) the brain is encased in a rigid structure;

2) the brain is incompressible;

3) the volume of the blood in the cranial cavity is then constant; and

4) a constant drainage of venous blood is necessary to make room for the arterial supply (2). Normal ICP is usually considered 5-15 mmHg in a healthy adult, in children 3-7 mmHg and 1,5-6 mmHg in infants (3, 4).

Threshold value for intracranial hypertension varies not only throughout the literature but also in clinical practice. In general, ICP above twenty is considered elevated (5, 6). ICP higher than twenty to twenty-five mmHg often require treatment (7), and continuous ICP values greater than forty mmHg indicate severe, life-threatening intracranial hypertension. Elevated ICP could potentially lead to secondary irreversible brain injury and death harmful (8). ICP monitoring is paramount in diseases like intracranial hemorrhages, traumatic brain injury, subarachnoid hemorrhages, malignant infarction, cerebral edema and infections of the central nervous system to avoid secondary brain injuries via better management and thereby improve outcomes (9).

There are multiple modalities to acquire knowledge of ICP: 1) clinical examination, 2) CT or MRI scans or 3) direct ICP monitoring - both invasive and non-invasive (10). Best result is achieved using all three. Neuromonitoring still heavily relies on invasive methods such as intraparenchymal strain gauge or fiber optic monitor (parenchymal) and an intraventricular monitor using ventriculostomy (EVD), which are placed through a burr hole (11). EVD is considered gold standard, however methods such as the Camino also provides with similar results in daily practice (12-14). Invasive procedures carry the risk of bleeding and infection. The risk of bleeding is 2-10% for EVD (15) and 2,5% for parenchymal monitors (16).

The consequences of an intracranial hemorrhage can be severe and lead to irreversible brain injury, ultimately death. Parenchymal neuromonitoring devices carry almost no risk of infection (0-0,1%) in comparison to EVD (5-20%) (17). Furthermore, EVD is prone to device failure due to drift of probe in the tissue and breakage of equipment (16, 18, 19). Most promising non-invasive methods studied are transcranial Doppler ultrasound pulsality index and optic nerve sheeth diameter. However, they are not validated for daily clinical use and are prone to inter-observational variation (20).

In the US and Europe the incidence of traumatic brain injury (TBI) is 500/100.000 and more than 200/100.000 patients are admitted due to TBI related incidence in Europe (21, 22). These numbers reveal a need for a quick screening tool, which is easy to use and non-invasive. We aim further study non-invasive fundoscopy to estimate intracranial pressure by assessing the arteriole and venule of the eye. We will show in an upcoming publication that there is a correlation between rise in ICP and fall in A/V-ratio with the venule's diameter increasing. The beforementioned pilot study is done on competent patients mostly with normal ICP.

Now we aim to study incompetent patients with higher ICP to assess if our method is feasible in the intensive care unit with higher ICP.

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Description of the cohort

This study is an observational, prospective cohort study approved by The Regional Committees on Health Research Ethics for Southern Denmark and will be from September 2020

Incompetent or competent patients with an invasive intracranial pressure probe/external ventricular drain will be enrolled from the Neurosurgical Intensive Care Unit at Odense University Hospital, OUH

Data and biological material

Data will be collected from patients and patient journal

Publications associated with the project

Andersen, M.S., Pedersen, C.B. & Poulsen, F.R. A new novel method for assessing intracranial pressure using non-invasive fundus images: a pilot study. Sci Rep 10, 13062 (2020). https://doi.org/10.1038/s41598-020-70084-0