Clinical trial NCT02637258: Can Optic Nerve Sheath Diameter Measurement Predict Negative Neurological Outcome ?
Official title: Can Bedside Ultrasonographic Measurements of Optic Nerve Sheath Diameter Following the Return of Spontaneous Circulation Predict Negative Neurological Outcome in Out of Hospital Cardiac Arrest Patients?
Study type: OBSERVATIONAL
Overall status: UNKNOWN
Conditions: Out of Hospital Cardiac Arrest
Neurologic Symptoms
Keywords: optic nerve sheath diameter
neurological outcome
OHCA
Lead sponsor: Emergency Medicine Association of Turkey
Sponsor class: OTHER
First posted: 2015-12-22
Enrollment: 203
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: The non-traumatic, non-intracranial event related OHCA patients in whom the ROSC is achieved will render the sampling group

Brief summary: This study is designed as a multicenter, prospective, cohort clinical study. The out of hospital cardiac arrest (OHCA) patients presenting to the adult emergency departments of the participating hospitals will render the study population. The non-traumatic, non-intracranial event related OHCA patients in whom the return of spontaneous circulation (ROSC) is achieved will render the sampling group.

The primary aim of this study is to evaluate the relationship of bedside ultrasound (USG) measurements of Optic Nerve Sheath Diameter (ONSD) following the ROSC after Cardiopulmonary resuscitation (CPR) for OHCA patients, with early (3rd day) neurological evaluation and 30 days survival rate, proposing that increased ONSD may be related to negative neurological outcomes. Considering a relationship is found, the secondary goals of the study are established as, identifying a cut-off value for ONSD related to negative neurological outcome and the optimal time to measure ONSD.

The sampling size with a power of 95% is calculated to be 203 patients. The patients whose available next of kin has given consent will be admitted to the study.

Detailed description: Introduction:

Current medical literature reveals that the life expectancy after cardiopulmonary resuscitation (CPR) for out of hospital cardiac arrest (OHCA) is 6.7-9.6%.1,2 The hypoxic process, also referred to as post-resuscitation encephalopathy (PRE), is a major factor affecting the neurological outcome following return of spontaneous circulation (ROSC).3 Many studies, aiming the early prediction of the neurological outcome via vital signs, scoring systems, various biochemical markers and imaging techniques exist in literature.1-8 Optic nerve is a part of central nervous system and its posterior part is covered with dura mater. Studies have found that, elevations in intracranial pressure (ICP) resulted in elevated subarachnoid fluid pressure, leading to increased optic nerve sheath diameter (ONSD).9 Bedside USG measurements of ONSD are reported to be utilizable for evaluation of ICP.9,10

Aim of the study:

The primary aim of this study is to evaluate the relationship of bedside USG measurements of ONSD following the ROSC after CPR for OHCA patients, with early (3rd day) neurological evaluation and 30 days survival rate, proposing that increased ONSD may be related to negative neurological outcomes. Considering a relationship is found, the secondary goals of the study are established as, identifying a cut-off value for ONSD related to negative neurological outcome and the optimal time to measure ONSD.

Material and Methods:

This study is designed as a multicenter, prospective, cohort clinical study. The Utstein Templates for Resuscitation Registries are used for OHCA records.11 The associate researchers are demanded to have an experience of at least 5 years in USG use and be certified by the Emergency Medicine Association of Turkey (EMAT) for participating and/or being a faculty in the Emergency USG courses on ONSD evaluation, by the EMAT USG study group (EMATUS), which organizes planned USG courses for Emergency Physicians. A one-day education to standardize the researchers of the study, with theoretical and implementation sections are planned to be held by the authors of the study, regarding the methodology of the study and standardization of the USG techniques for ONSD measurements. In the implementation section, the researchers will perform ONSD measurements with ocular USG on healthy volunteers and the reliability among performers will be measured with Interclass Correlation test.

This study will be performed in the adult emergency departments of the participating hospitals, after the ethics committee approval. The OHCA patients presenting to the adult emergency departments of the participating hospitals will render the study population. The non-traumatic, non-intracranial event related OHCA patients in whom the ROSC is achieved will render the sampling group. The sampling size with a power of 95% is calculated to be 203 patients. The patients whose available next of kin has given consent will be admitted to the study.

All patients will receive standardized advanced cardiac life support (ACLS) measures in line with the most recent American Heart Association (AHA) guidelines by emergency department teams, uncommitted to the study. Following the ROSC, a time period of 20 minutes is determined in order to appropriate tissue perfusion to be stated, with a systolic blood pressure ≥90 mmHg or mean arterial pressure ≥65 mmHg and peripheral capillary saturation ≥94%.14 ONSD measurements will be performed in patients who had uninterrupted ROSC for 20 minutes with bedside USG and the time between the achievement of ROSC and the measurement will be recorded. The routine care plan of the patients will not be manipulated. In case the clinician decides that a cranial computed tomography (CT) is indicated according to routine practices and current guidelines, a copy of the CT images will be taken to investigate the presence of an intracranial mass leading to increased ICP.

The neurologic evaluation of the patients in the study group will be performed in three steps. Primary neurological evaluation will be performed following the achievement of appropriate tissue perfusion after ROSC, prior to any sedative or paralyzing drug application. This step is about identifying and recording the alertness, presence of activity, and the level of motor response, brain stem reflexes and myoclonic status epilepticus. The second neurological evaluation will take place after the 72nd hour following the ROSC. The alertness, presence of spontaneous motor activity, and the level of motor response, brain stem reflexes and myoclonic status epilepticus will also be identified and recorded in the second step, as well. The third evaluation will be the evaluation of neurological final outcome at 30th day or hospital discharge, utilizing the Modified Rankin Scale (MRS).

Statistical Package for the Social Sciences 22.0 for Windows will be used for statistical analysis. Descriptive statistical values will be presented as quantity and percentiles for categorical variables and as mean and standard deviation for numerical variables. Comparisons of numerical variables between two independent groups will be performed by Student-t Test if normal distribution is obtained and by Mann-Whitney U test if it is not obtained. The differences between the mean values of categorical variables of two independent groups will be tested with Chi-Square analysis. The relationships between the numerical variables will be reviewed with Pearson Correlation analysis under parametric test conditions, and Spearman Correlation Analysis under non-parametric test conditions. The appropriateness of four separately measures ONSD values will be evaluated with concordance correlation coefficient measurement. The cut-off value will be determined with Receiver Operating Characteristics Curve Analysis. The statistical alpha significance level will be accepted as p\<0.05.

Eligibility criteria: Inclusion Criteria:

1-Out-hospital cardiac arrest

Exclusion Criteria:

1. In-hospital cardiac arrest
2. Unstable patients requiring rapid intervention (i.e. emergent surgery, percutaneous coronary intervention)
3. Age \<18
4. Concomitant trauma
5. Pregnancy
6. Any event known to increase ONSD without raised ICP (optic neuritis, arachnoid cysts of optic nerve, optic nerve trauma, anterior orbital mass, cavernous sinus mass)
7. Any event known to increase ONSD with raised ICP \[previously diagnosed intracranial space occupying lesion or tumor, pseudotumor cerebri, conditions causing decreased Cerebrospinal fluid (CSF) reabsorption (venous sinus thrombosis, inflammation, meningitis, subarachnoid hemorrhage)
8. Conditions causing increased production CSF (tumors), ventricular obstructions, cerebral edema, craniosynostosis
9. Anatomical eye malformations preventing the USG examination
10. Previously diagnosed malignity, glaucoma, multiple sclerosis, previously diagnosed terminal stage liver and renal disease,
11. Cardiac arrest secondary to trauma and refusing to give consent to participate

Primary outcomes:
measure: Modified Rankin Scale (MRS).
timeFrame: 30 day after ROSC
Secondary outcomes:
measure: Neurological Examination
timeFrame: 72 hours after ROSC
Other outcomes:
Locations:
city: Adana
country: Turkey
facility: Başkent University
city: Ankara
country: Turkey
facility: Ankara Education and Research Hospital
city: Ankara
country: Turkey
facility: Hacettepe University
city: Antalya
country: Turkey
facility: Akdeniz University Hospital
city: Antalya
country: Turkey
facility: Antalya Education and Research Hospital
city: Denizli
country: Turkey
facility: Denizli State Hospital
city: Erzurum
country: Turkey
facility: Erzurum Education and Research Hospital
city: Eskisehir
country: Turkey
facility: Eskisehir Osmangazi University
city: Eskişehir
country: Turkey
facility: Yunus Emre State Hospital
city: Istanbul
country: Turkey
facility: Istanbul Education and Research Hospital
city: Istanbul
country: Turkey
facility: Istanbul Haseki Education and Research Hospital
city: Istanbul
country: Turkey
facility: Istanbul Sıslı Hamidiye Etfal Education and Research Hospital
city: Istanbul
country: Turkey
facility: Koç University Hospital
city: Izmır
country: Turkey
facility: Dokuz Eylul University
city: Izmır
country: Turkey
facility: Ege University
city: Izmır
country: Turkey
facility: Izmır Tepecik Education and Research Hospital
city: İzmir
country: Turkey
facility: Izmır University
city: Kocaeli
country: Turkey
facility: Kocaeli Derince Education and Research Hospital
city: Nevşehir
country: Turkey
facility: Nevşehir State Hospital
Study officials:
affiliation: Depertment Of Emergency Medicine, Akdeniz University, Antalya
name: Aslıhan Yürüktümen Ünal, Ass. Prof.
role: STUDY_CHAIR
affiliation: Depertment Of Emergency Medicine, Akdeniz University, Antalya
name: Erkan Göksu, Ass. Prof.
role: STUDY_CHAIR
affiliation: Depertment Of Emergency Medicine, Antalya Education and Research Hospital, Antalya
name: Faruk Güngör, MD
role: STUDY_CHAIR
affiliation: Depertment Of Emergency Medicine, Başkent University, Adana
name: Betül Günalp, Ass. Prof
role: STUDY_CHAIR
affiliation: Depertment Of Emergency Medicine, Denizli State Hospital, Denizli
name: Alten Oskay, MD
role: STUDY_CHAIR
affiliation: Depertment Of Emergency Medicine, Denizli State Hospital, Denizli
name: Mert Özen, MD
role: STUDY_CHAIR
affiliation: Depertment Of Emergency Medicine, Dokuz Eylul University, İzmir
name: Başak Bayram, Assist. Prof
role: STUDY_CHAIR
affiliation: Depertment Of Emergency Medicine, Ege University, İzmir
name: Funda Karbek Akarca, Assist. Prof
role: STUDY_CHAIR
affiliation: Depertment Of Emergency Medicine, Ege University, İzmir
name: İlhan Uz, MD
role: STUDY_CHAIR
affiliation: Depertment Of Emergency Medicine, Eskisehir Osmangazi University, Eskisehir
name: Nurdan Ergün Acar, Ass. Prof
role: STUDY_CHAIR
affiliation: Depertment Of Emergency Medicine, Eskisehir Osmangazi University, Eskisehir
name: Mustafa E. Çanakçı, Resident
role: STUDY_CHAIR
affiliation: Depertment Of Emergency Medicine, Hacettepe University, Ankara
name: Bülent Erbil, Ass. Prof.
role: STUDY_CHAIR
affiliation: Depertment Of Emergency Medicine, Hacettepe University, Ankara
name: Mehmet A. Karaca, Ass. Prof.
role: STUDY_CHAIR
affiliation: Depertment Of Emergency Medicine, Istanbul Education and Research Hospital, Istanbul
name: Özgür Dikme, MD
role: STUDY_CHAIR
affiliation: Depertment Of Emergency Medicine, Istanbul Haseki Education and Research Hospital, Istanbul
name: Adnan Yamanoglu, MD
role: STUDY_CHAIR
affiliation: Depertment Of Emergency Medicine, Istanbul Sıslı Hamidiye Etfal Education and Research Hospital, Istanbul
name: Özgür Cevrim, MD
role: STUDY_CHAIR
affiliation: Depertment Of Emergency Medicine, Izmır University, İzmir
name: Cem Ertan, Ass. Prof.
role: STUDY_CHAIR
affiliation: Depertment Of Emergency Medicine, Izmır University, İzmir
name: Tanzer Korkmaz, Assist. Prof
role: STUDY_CHAIR
affiliation: Depertment Of Emergency Medicine, Izmır Tepecik Education and Research Hospital, Izmir
name: Murat Yeşilaras, MD
role: STUDY_CHAIR
affiliation: Depertment Of Emergency Medicine, Izmır Tepecik Education and Research Hospital, Izmir
name: Turgay Y. Kılıç, MD
role: STUDY_CHAIR
affiliation: Depertment Of Emergency Medicine, Nevşehir State Hospital, Nevşehir
name: Mehmet A. Aslaner, MD
role: STUDY_CHAIR
affiliation: Depertment Of Emergency Medicine, Koc University, İstanbul
name: Salih Ekinci, MD
role: STUDY_CHAIR
affiliation: Depertment Of Emergency Medicine, Kocaeli Derince Education and Research Hospital, Kocaeli
name: Onur Karakayalı, MD
role: STUDY_CHAIR
affiliation: Depertment Of Emergency Medicine, Erzurum Education and Research Hospital, Erzurum
name: Ali Batur, MD
role: STUDY_CHAIR
affiliation: Depertment Of Emergency Medicine, Ankara Education and Research Hospital, Ankara
name: Volkan Arslan, MD
role: STUDY_CHAIR
affiliation: Depertment Of Emergency Medicine, Yunus Emre State Hospital, Eskişehir
name: Davut Kaplan, MD
role: STUDY_CHAIR
References:
citation: Sasson C, Rogers MA, Dahl J, Kellermann AL. Predictors of survival from out-of-hospital cardiac arrest: a systematic review and meta-analysis. Circ Cardiovasc Qual Outcomes. 2010 Jan;3(1):63-81. doi: 10.1161/CIRCOUTCOMES.109.889576. Epub 2009 Nov 10.
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citation: Daubin C, Quentin C, Allouche S, Etard O, Gaillard C, Seguin A, Valette X, Parienti JJ, Prevost F, Ramakers M, Terzi N, Charbonneau P, du Cheyron D. Serum neuron-specific enolase as predictor of outcome in comatose cardiac-arrest survivors: a prospective cohort study. BMC Cardiovasc Disord. 2011 Aug 8;11:48. doi: 10.1186/1471-2261-11-48.
citation: Hwan Kim Y, Ho Lee J, Kun Hong C, Won Cho K, Hoon Yeo J, Ju Kang M, Weon Kim Y, Yul Lee K, Joo Kim J, Youn Hwang S. Feasibility of optic nerve sheath diameter measured on initial brain computed tomography as an early neurologic outcome predictor after cardiac arrest. Acad Emerg Med. 2014 Oct;21(10):1121-8. doi: 10.1111/acem.12477.
citation: Hassen GW, Bruck I, Donahue J, Mason B, Sweeney B, Saab W, Weedon J, Patel N, Perry K, Matari H, Jaiswal R, Kalantari H. Accuracy of optic nerve sheath diameter measurement by emergency physicians using bedside ultrasound. J Emerg Med. 2015 Apr;48(4):450-7. doi: 10.1016/j.jemermed.2014.09.060. Epub 2014 Dec 9.
citation: Dubourg J, Javouhey E, Geeraerts T, Messerer M, Kassai B. Ultrasonography of optic nerve sheath diameter for detection of raised intracranial pressure: a systematic review and meta-analysis. Intensive Care Med. 2011 Jul;37(7):1059-68. doi: 10.1007/s00134-011-2224-2. Epub 2011 Apr 20.