Pupillometry and Somatosensory Evoked Potential in Cardiac Arrest (PASCA)

The Capacity of Neurological Pupil Index to Predict the Absence of Somatosensory Evoked Potentials in Comatose Survivors of Cardiac Arrest

Somatosensory Evoked Potentials (SSEP) and Pupillary Light Reflex (PLR) are key methods for neurologic prognostication in comatose survivors of cardiac arrest. Both methods have low false positive rates.Though they assess different functions of the brain, they should both be sensitive to severe anoxic/ischemic injury from cardiac arrest. The aim of this observational prospective study with an estimated recruitment of 50 patients is to examine the interrelation between PLR and SSEP. PLR will be assessed by Neurological Pupil index (NPi) and SSEP by the cortical N20 response to stimulation of the median nerve.

Study Overview

• Status: Recruiting
• Conditions: Cardiopulmonary Arrest With Successful Resuscitation; Cardiac Arrest; Resuscitation
• Intervention / Treatment: Diagnostic test: Somatosensory Evoked Potentials; Diagnostic test: Automated Pupillometry

Detailed Description

Background:

Anoxic/ischemic brain injury is the most common cause of death among comatose survivors of cardiac arrest (CA). The neurological prognosis of these patients is assessed using the multimodal prognostication model, which includes several methods. Somatosensory Evoked Potentials (SSEP) and Pupillary Light Reflex (PLR) are key methods for prognostication, as both have low false positive rates. Though they assess different functions of the brain, they should both be sensitive to severe anoxic/ischemic injury from cardiac arrest. The primary aim of the study is to describe the association between PLR quantified as the Neurological Pupil index (NPi) and bilateral absence of the cortical SSEP signal in patients remaining comatose after cardiac arrest. The secondary aim is to define a NPi cut-off value that renders a false positive rate (FPR) of less than 5% for a bilaterally absent SSEP response.

Methods:

An explorative, prospective, observational, cohort of 50 adult (>18 years) comatose survivors of CA admitted to the intensive care unit at Sahlgrenska University Hospital. The results from routine SSEP performed > 48 hours after CA and PLR assessed using NPi calculated by automated pupillometry are compared. Neurological outcome at hospital discharge is classified using the modified Rankin Scale (mRS), where poor neurological outcome is defined by mRS 4-6.

Statistical analysis:

In order to find a significant difference in NPi of 0.7 with a power of 95% with two-sided Fisher's non-parametric permutation test, 45 patients are needed assuming allocation 2:1 and unequal SD in the groups 0.37 and 0.67, calculated from the IQR above, and significance level 0.01. To account for uncertainty within these estimates, we aim to include 50 patients with a complete protocol.

A receiver operating characteristics curve (ROC-curve) will be used to find the NPi cut-off values resulting in a false positive rate of less than 5% for absent SSEP to predict poor neurological outcome. NPi values below the cut-off i.e., values consistent with poor outcome, will be used to calculate the predictive value for SSEP at its given prevalence. Fisher's exact test will be used to assess correlation between NPi and SSEP.

Discussion:

A clear correlation between the absence of cortical SSEP response and NPi values will permit application of the adequate method to the individual patient. This may also enable rationalisation of the multimodal assessment of the neurological prognosistication using a smaller number of methods. In clinical practice, this may render the prognostication of neurological function of comatose patients after cardiac arrest more accurate, as well as more cost- and time efficient.

• Study Type: Observational
• Enrollment (Anticipated): 50

Contacts and Locations

• Study Contact: Name: Christian CA Rylander, MD, PhD; Phone Number: +46313421096; Email: christian.rylander@vgregion.se
• Study Contact Backup: Name: Meena K Thuccani, Med. Lic; Phone Number: +46709282625; Email: meena.thuccani@vgregion.se

Study Locations

• Sweden
  • Göteborg, Sweden, 413 45
    • Recruiting
    • avd 96 CIVA Sahlgrenska University Hospital
    • Contact: Christian Rylander, MD, PhD; Phone Number: +46 31 342 10 00
    • Principal Investigator: Christian Rylander, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Adult (>18 year old) comatose survivors of cardiac arrest admitted to the central intensive care unit at Sahlgrenska University Hospital in Gothenburg, Sweden.

Description

Inclusion Criteria:

>18-year-old comatose survivors of cardiac arrest with Glasgow coma scale < 9.

Exclusion Criteria:

return of consciousness before SSEP is performed; pregnancy; intracranial bleeding; traumatic brain injury; palliative care and lack of next of kin.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Comatose survivors of cardiac arrest; Adult (>18 years) patients remaining comatose during intensive care 48 hours after cardiac arrest. All patients are submitted to both clinical routine measurements: pupillometry and somatosensory evoked potentials.	Diagnostic test: Somatosensory Evoked Potentials; SSEP performed bilaterally with stimulation of the median nerve; Other Names: Cortical N20 response; Diagnostic test: Automated Pupillometry; PLR quantified as NPi using a handheld automated pupillometer; Other Names: Neurological Pulpil index

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The association between NPi and bilateral absence of the cortical SSEP response.	ROC curve analysis	SSEP and pupillometry performed 48 hours after cardiac arrest

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
NPi cut-off value that renders a false positive rate (FPR) of less than 5% for a bilaterally absent SSEP response.	Analysed by stepwise crosstabulation of NPi values against absent cortical SSEP response.	SSEP and pupillometry performed 48 hours after cardiac arrest

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Predictive capacity for SSEP and NPi for death at 30 days and neurological outcome at hospital discharge	Analysed as sensitivity, specificity and odds ratio	Assessed from medical records within a month after cardiac arrest

Collaborators and Investigators

• Sponsor: Sahlgrenska University Hospital, Sweden
• Collaborators: Göteborg University

Publications and helpful links

General Publications

• Lilja L, Thuccani M, Joelsson S, Nilsson J, Redfors P, Lundgren P, Rylander C. The capacity of neurological pupil index to predict absence of somatosensory evoked potentials after cardiac arrest-A study protocol. Acta Anaesthesiol Scand. 2021 Jul;65(6):852-858. doi: 10.1111/aas.13822. Epub 2021 Mar 29.

Study record dates

Study Major Dates

• Study Start (Actual): February 3, 2020
• Primary Completion (Anticipated): June 30, 2022
• Study Completion (Anticipated): June 30, 2022

Study Registration Dates

• First Submitted: September 5, 2020
• First Submitted That Met QC Criteria: January 18, 2021
• First Posted (Actual): January 22, 2021

Study Record Updates

• Last Update Posted (Actual): January 26, 2021
• Last Update Submitted That Met QC Criteria: January 22, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Arrest
• Other Study ID Numbers: PASCA

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No