Optic Nerve Sheath Diameter for Prediction of Sepsis Associated Encephalopathy

Study Overview
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Brief Summary
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Sepsis-associated brain dysfunction (SABD)with increased intracranial pressure is a complex pathology that can lead to unfavourable outcome. Although direct measurement of intracranial pressure using an intra-ventricular catheter remains the gold standard, it is burdened with potential serious complications due to its invasiveness. Ultrasonic measurement of optic nerve sheath diameter (ONSD) is a non-invasive method for ICP monitoring. Screening for SABD is crucial for early diagnosis and management, measurement of ONSD can detect elevated intracranial pressure in septic patients. Intracranial hypertension in septic patients might be a sign of SABD. Using ONSD for SABD screening requires further research. So, we hypothesized that ONSD could be used as an objective screening tool to predict and early diagnose SABD in adult septic patients.

Detailed Description
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Sepsis is the most common complication in adult critically ill patients, and it has been become the leading cause of morbidity and mortality worldwide. The essential component of sepsis is the presence of an acute organ dysfunction. The brain is highly vulnerable to the inflammatory storm associated with infection and it may be the first organ to show signs of life-threatening organ dysfunction caused by infection. This brain dysfunction is known as sepsis-associated encephalopathy (SAE). Sepsis-associated brain dysfunction is considered the commonest type of encephalopathy seen in intensive care unit (ICU). it is defined as a life- threatening acute diffuse brain dysfunction due to infection outside the central nervous system (CNS) and is mostly caused by the inflammatory storm. It varies from delirium or confusion, seizure or focal neurological sign, and diffuse or multifocal neurological deficits, to stupor or coma with no other diagnoses describing the patient neurological status. SAE may occur in up to 70% of septic patients and it significantly increases mortality. It is a complex syndrome with unclear pathophysiology. The possible causes could include neuro-inflammation, excitotoxicity, impaired cerebral autoregulation, and cerebral ischemia. These Pathophysiological changes may lead to increase in the intracranial pressure (ICP) which may in turn decrease cerebral perfusion and lead to brain edema, brain damage and compromised the outcome of these patients. Therefore, early detection of increased ICP is of paramount importance for timely intervention and improved prognosis. However, direct invasive ICP monitoring is not routinely recommended in non-traumatic coma patients as well as septic patients either due to absence of intracranial infection or coagulopathy; so, a reliable non-invasive ICP monitoring method is highly recommended. Bedside ultrasonographic assessment of the optic nerve sheath diameter (ONSD) offers a satisfactory non-invasive ICP monitoring test and is documented as a sensitive and specific predictor of cerebral edema and is strongly correlated with both invasive ICP measurements and radiographic cerebral edema as diagnosed by CT scan or MRI. Considering that SAE is a diagnosis of exclusion as well as screening method for SAE is necessary for early diagnosis and timely management. We hypothesized that ONSD could have a role as an objective screening tool to predict and early diagnose ICP changes in septic patients.

Official Title
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The Role of Ultrasonographic Assessment of Optic Nerve Sheath Diameter in Prediction of Sepsis Associated Encephalopathy

Conditions
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Sepsis

Intervention / Treatment
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* Diagnostic Test: Ultrasound measurement of Optic nerve sheath diameter


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient acceptance. Age 21- 70 years old. Patients diagnosed with sepsis For diagnosis of sepsis and septic shock, the third international definition and appropriate diagnostic criteria was used. Sepsis was defined as life-threatening organ dysfunction caused by a dysregulated host response to an infection, and it is suspected in an acutely deteriorating patient in whom there is clinical evidence or strong suspicion of infection. Septic shock was defined as the need for vasopressors or vasoactive medication to maintain a mean arterial blood pressure of 65 mmHg or higher after adequate fluid resuscitation, with the presence of a high lactate (>2 mmol/l). Exclusion Criteria: Patient refusal. Ocular wound History of prior ocular trauma or surgery Conjunctival edema or orbital edema Vitreous hemorrhage Central nervous system (CNS) infection Cerebrovascular accident Brain trauma Any previous neurosurgical procedure

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 70 Years

Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Adult critically ill septic patients<br> | Diagnostic Test: Ultrasound measurement of Optic nerve sheath diameter<br>* Ocular ultrasonography will be performed by single skilled examiner with patients placed in supine position with closed eyes. A layer of ultrasound gel will be applied over the closed upper eyelid and the liner high frequency probe 7 - 12 MHz of SonoSite M-Turbo ultrasound machine is placed on temporal area of eyelid with the hand holding it resting on forehead of patient. ONSD is measured 3mm behind the globe in the transverse plane perpendicular to the optic nerve. For each eye one measurement will be made and the reported ONSD corresponds to the mean of the two values obtained for each patient. An average ONSD greater than 5 mm is considered abnormal and elevated intracranial pressure should be suspected. all enrolled subjects will be eligible for ONSD measurements, SOFA score calculation, as well as GCS assessment on daily basis for up to 10 consecutive days, until ICU discharge or death.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| correlation between ONSD measurements and the occurrence of SAE | ultrasonographic measurement of optic nerve sheath diameter (ONSD) will be performed and recorded on daily basis for up to 10 consecutive days, until ICU discharge or death then we will compare the ONSD measurements of non-SAE patients to those of SAE patients. | 10 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| the correlation between ONSD measurements and the ICU mortality of critically ill patients with sepsis | ultrasonographic measurement of optic nerve sheath diameter (ONSD) will be performed and recorded on daily basis for up to 10 consecutive days, until ICU discharge or death then we will compare the ONSD measurements of ICU survivors to those of dead patients during the ICU stay. | 30 days |