Real-Time Brain Monitoring by Near-Infrared Spectroscopy Predicts Neurological Outcome after Cardiac Arrest and Resuscitation in Rats: A Proof of Concept Study of a Novel Prognostic Measure after Cardiac Arrest

Clinical studies have demonstrated that dynamic changes in regional cerebral oxygen saturation (rSO2) after cardiac arrest (CA) and cardiopulmonary resuscitation (CPR) have a role in predicting neurological outcomes after the return of spontaneous circulation (ROSC). Our study evaluated whether the timing of rSO2 decline shortly after CPR reflects the severity of brain injury in a rat model of CA. Rats were subjected to different durations of asphyxia to produce variable severities of brain injury, due to CA. Time from ROSC to achieving the initial minimum rSO2 was defined as Tnadir. A Tnadir cut-off of 24 min had optimal sensitivity and specificity for predicting good neurological outcomes at 72 h after ROSC (AUC, 0.88; sensitivity, 89%; specificity, 86%; p < 0.01). Immunohistochemistry at 72 h post-CA revealed that the number of Fluoro-Jade B positive degenerating neurons in the hippocampus CA1 sector were markedly higher in animals with Tnadir > 24 min than that in animals with Tnadir ≤ 24 min. There was no difference in the gene expressions of cytokines and mitochondrial fission proteins in the brain at 2 h after ROSC between rats with Tnadir > 24 min and with Tnadir ≤ 24 min. In conclusion, Tnadir can be a novel predictor of good neurological outcomes after CA/CPR.

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Abstract 273: Noninvasive Mitochondrial Modulation: Neuroprotection in a Translational Model of Cardiac Arrest and Resuscitation

Circulation ◽

10.1161/circ.140.suppl_2.273 ◽

2019 ◽

Vol 140 (Suppl_2) ◽

Author(s):

Joseph M Wider ◽

Erin Gruley ◽

Jennifer Mathieu ◽

Emma Murphy ◽

Rachel Mount ◽

...

Keyword(s):

Cardiac Arrest ◽

Brain Injury ◽

Near Infrared ◽

Small Animal ◽

Spontaneous Circulation ◽

Infrared Light ◽

Swine Model ◽

Treatment Groups ◽

The Brain ◽

Neuroprotective Therapies

Background: Mitochondrial dysfunction contributes to cardiac arrest induced brain injury and has been a target for neuroprotective therapies. An emerging concept suggests that hyperactivation of neuronal mitochondria following resuscitation results in hyperpolarization of the mitochondrial membrane during reperfusion, which drives generation of excess reactive oxygen species. Previous studies from our group demonstrated that limiting mitochondrial hyperactivity by non-invasively modulating mitochondrial function with specific near infrared light (NIR) wavelengths can reduce brain injury in small animal models of global and focal ischemia. Hypothesis: Inhibitory wavelengths of NIR will reduce neuronal injury and improve neurocognitive outcome in a clinically relevant swine model of cardiac arrest. Methods: Twenty-eight male and female adult swine were enrolled (3 groups: Sham, CA/CPR, and CA/CPR + NIR). Cardiac arrest (8 minutes) was induced with a ventricular pacing wire and followed by manual CPR with defibrillation and epinephrine every 30 seconds until return of spontaneous circulation (ROSC), 2 of the 20 swine that underwent CA did not achieve ROSC and were not enrolled. Treatment groups were randomized prior to arrest and blinded to the CPR team. Treatment was applied at onset of ROSC by irradiating the scalp with 750 nm and 950 nm LEDs (5W) for 2 hours. Results: Sham-operated animals all survived (8/8), whereas 22% of untreated animals subjected to cardiac arrest died within 45 min of ROSC (CA/CPR, n= 7/9). All swine treated with NIR survived the duration of the study (CA/CPR + NIR, n=9/9). Four days following cardiac arrest, neurological deficit score was improved in the NIR treatment group (50 ± 21 CA/CPR vs. 0.8 ± 0.8 CA/CPR + NIR, p < 0.05). Additionally, neuronal death in the CA1/CA3 regions of the hippocampus, assessed by counting surviving neurons with stereology, was attenuated by treatment with NIR (17917 ± 5534 neurons/mm 3 CA/CPR vs. 44655 ± 5637 neurons/mm 3 CA/CPR + NIR, p < 0.05). All data is reported as mean ± SEM. Conclusions: These data provide evidence that noninvasive modulation of mitochondria, achieved by transcranial irradiation of the brain with NIR, mitigates post-cardiac arrest brain injury.

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Abstract 10029: Near-Infrared Spectroscopy Assessments for the Prediction of Neurological Outcome in the Rat Model of Cardiac Arrest

Circulation ◽

10.1161/circ.144.suppl_2.10029 ◽

2021 ◽

Vol 144 (Suppl_2) ◽

Author(s):

Ryosuke Takegawa ◽

Kei Hayashida ◽

Santiago Miyara ◽

Rishabh Choudhary ◽

Houman Khalili ◽

...

Keyword(s):

Infrared Spectroscopy ◽

Brain Injury ◽

Near Infrared Spectroscopy ◽

Rat Model ◽

Neurological Outcome ◽

Near Infrared ◽

Mitochondrial Fission ◽

Good Neurological Outcome ◽

Gene Expressions ◽

The Brain

Introduction: Clinical studies have demonstrated that the initial rapid decrement in regional cerebral oxygen saturation (rSO 2 ) level by near-infrared spectroscopy shortly after ROSC was associated with good neurological outcomes. Aim: To evaluate whether the timing of rSO 2 decline shortly after ROSC reflects the severity of brain injury in a well-established rat model of CA/CPR. Methods: We used a total of 85 Wister SD rats (male, 435.2±3.1 g).To produce variable severities of brain injury, CA was induced by different asphyxial times and resuscitated by finger chest compressions and mechanical ventilation. Survival time was recorded for 72 hours after ROSC. Daily neurofunctional scores (NFS) were evaluated by an investigator blinded to the experiments. Electroencephalography (EEG), immunohistochemistry, plasma IL-6, and the gene expressions of cytokines (IL-1, IL-6, TNF-α, HMGB-1) and mitochondrial fission-related proteins (Dnm1L, Fis1, Mief1) in the brain were also evaluated. Result: Animals in the 12-min CA group exhibited a longer time to EEG recovery after CA/CPR compared with the 6-min group (P<.0001), suggesting the longer CA duration induces a delayed brain electrical recovery. Time from ROSC to achieving the initial minimum rSO 2 value (defined as T nadir ) was significantly prolonged as CA time increased; 15.3 ± 2.3, 32.1 ± 22.1, and 44.0 ± 2.8 min in 6, 9, and 12min CA, respectively (ANOVA: P<.0001). T nadir cut-off of 24-min provided the optimal sensitivity and specificity for predicting good neurologic outcomes (NFS≥60%) at 72 hours after ROSC (AUC, 0.88; sensitivity, 89%; specificity, 86%; P<.01). T nadir showed a better predictive power for the good neurological outcome compared with plasma IL-6. Immunohistochemistry at 24 hours post-CA revealed that FJB-positive degenerating neurons in cortex, caudoputamen, and hippocampus were conspicuous in animals with T nadir >24-min, but not in animals with T nadir ≤24-min. Animals with T nadir >24 tended to have a higher gene expression level of IL-6 in the brain at 2 hours post-ROSC compared to those with T nadir ≤24. T nadir did not show associations with other inflammatory or mitochondrial fission markers. Conclusion: T nadir can be a novel predictor for a good neurological outcome after CA/CPR.

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Brain monitoring using near-infrared spectroscopy to predict outcome after cardiac arrest: a novel phenotype in a rat model of cardiac arrest

Journal of Intensive Care ◽

10.1186/s40560-020-00521-9 ◽

2021 ◽

Vol 9 (1) ◽

Author(s):

Ryosuke Takegawa ◽

Kei Hayashida ◽

Rishabh Choudhary ◽

Daniel M. Rolston ◽

Lance B. Becker

Keyword(s):

Cardiac Arrest ◽

Infrared Spectroscopy ◽

Brain Injury ◽

Near Infrared Spectroscopy ◽

Near Infrared ◽

Cerebral Oximetry ◽

Neurological Outcomes ◽

Non Invasive ◽

Real Time Measurement ◽

Ca Model

AbstractImproving neurological outcomes after cardiac arrest (CA) is the most important patient-oriented outcome for CA research. Near-infrared spectroscopy (NIRS) enables a non-invasive, real-time measurement of regional cerebral oxygen saturation. Here, we demonstrate a novel, non-invasive measurement using NIRS, termed modified cerebral oximetry index (mCOx), to distinguish the severity of brain injury after CA. We aimed to test the feasibility of this method to predict neurological outcome after asphyxial CA in rats. Our results suggest that mCOx is feasible shortly after resuscitation and can provide a surrogate measure for the severity of brain injury in a rat asphyxia CA model.

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Clinical Trials in Cardiac Arrest and Subarachnoid Hemorrhage: Lessons from the Past and Ideas for the Future

Stroke Research and Treatment ◽

10.1155/2013/263974 ◽

2013 ◽

Vol 2013 ◽

pp. 1-42

Author(s):

Jennifer A. Frontera

Keyword(s):

Clinical Trials ◽

Cardiac Arrest ◽

Subarachnoid Hemorrhage ◽

Brain Injury ◽

Randomized Clinical Trials ◽

Early Brain Injury ◽

Aneurysm Rupture ◽

Neurological Outcomes ◽

Injury Research ◽

The Brain

Introduction. Elevated intracranial pressure that occurs at the time of cerebral aneurysm rupture can lead to inadequate cerebral blood flow, which may mimic the brain injury cascade that occurs after cardiac arrest. Insights from clinical trials in cardiac arrest may provide direction for future early brain injury research after subarachnoid hemorrhage (SAH).Methods. A search of PubMed from 1980 to 2012 and clinicaltrials.gov was conducted to identify published and ongoing randomized clinical trials in aneurysmal SAH and cardiac arrest patients. Only English, adult, human studies with primary or secondary mortality or neurological outcomes were included.Results. A total of 142 trials (82 SAH, 60 cardiac arrest) met the review criteria (103 published, 39 ongoing). The majority of both published and ongoing SAH trials focus on delayed secondary insults after SAH (70%), while 100% of cardiac arrest trials tested interventions within the first few hours of ictus. No SAH trials addressing treatment of early brain injury were identified. Twenty-nine percent of SAH and 13% of cardiac arrest trials showed outcome benefit, though there is no overlap mechanistically.Conclusions. Clinical trials in SAH assessing acute brain injury are warranted and successful interventions identified by the cardiac arrest literature may be reasonable targets of the study.

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Abstract 9180: Importance of Preventing Decreased Levels of Lysophosphatidylcholine—DHA in Brain and Plasma for Attenuating Brain Injury After Cardiac Arrest

Circulation ◽

10.1161/circ.144.suppl_2.9180 ◽

2021 ◽

Vol 144 (Suppl_2) ◽

Author(s):

Mitsuaki Nishikimi ◽

Muhammad Shoaib ◽

Tomoaki Aoki ◽

Rishabh Choudhary ◽

Santiago J Miyara ◽

...

Keyword(s):

Cardiac Arrest ◽

Brain Injury ◽

Brain Damage ◽

Cell Cultures ◽

Brain Function ◽

Causative Role ◽

Metabolic Alterations ◽

Neurological Outcomes ◽

The Brain

Introduction: Lysophosphatidylcholine (LPC) was found to be decreased in plasma in the early phase of resuscitation after cardiac arrest (CA), including a species containing docosahexaenoic acid (LPC-DHA). Supplementing this deficiency of plasma LPC-DHA post-CA significantly attenuated brain dysfunction implicating a causative role of plasma decreased LPC-DHA for brain injury. Previous studies showed the importance of LPC-DHA as a carrier of DHA to maintain proper brain function. However, the role of LPC-DHA for brain function has not been fully understood. Objective: This study is aimed at determining the importance of maintaining proper brain LPC-DHA level via plasma supplementation to prevent brain damage after CA using human patients, animal model, and in-vitro cell studies. Methods and Results: We first evaluated associations between the plasma LPC-DHA levels and neurological outcomes using 45 post-CA patients. We then measured LPC-DHA levels and histological, biochemical, metabolic alterations in the plasma and brain after 10 min CA rat model and examined how these alterations were attenuated by supplementing LPC-DHA. Finally, we further investigated the beneficial effect of LPC-DHA using cell cultures. We found that the decreased plasma LPC-DHA was strongly associated with neurological outcomes and disappearance of difference between gray and white matter in the brain after CA in human patients. In rats, the decreased plasma LPC-DHA was associated with decreased level of brain LPC-DHA after CA, and supplementing plasma LPC-DHA normalized the brain levels of LPC-DHA and alleviated neuronal cell death, activation of astrocyte, and expression of various inflammatory and mitochondrial dysfunction genes. We also found normalized overall metabolic alterations from the untargeted metabolomics analysis. Furthermore, LPC treatment showed a similar protective effect for neurons and astrocytes in mixed primary brain cell cultures. Conclusion: The attenuation of biochemical and physiologic alterations, and the normalization of decreased brain LPC-DHA post-CA with LPC-DHA supplementation demonstrate plasma LPC-DHA is important for the maintenance of proper brain LPC-DHA levels, which is essential for preventing brain damage post-CA.

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Use of hemoglobin-based oxygen-carrying solution–201 to improve resuscitation parameters and prevent secondary brain injury in a swine model of traumatic brain injury and hemorrhage

Journal of Neurosurgery ◽

10.3171/jns/2008/108/3/0575 ◽

2008 ◽

Vol 108 (3) ◽

pp. 575-587 ◽

Cited By ~ 34

Author(s):

Guy Rosenthal ◽

Diane Morabito ◽

Mitchell Cohen ◽

Annina Roeytenberg ◽

Nikita Derugin ◽

...

Keyword(s):

Traumatic Brain Injury ◽

Brain Injury ◽

Mr Imaging ◽

Swine Model ◽

Secondary Brain Injury ◽

Large Animal ◽

Fluoro Jade B ◽

Significant Difference ◽

Impact Injury ◽

The Brain

Object Traumatic brain injury (TBI) often occurs as part of a multisystem trauma that may lead to hemorrhagic shock. Effective resuscitation and restoration of oxygen delivery to the brain is important in patients with TBI because hypotension and hypoxia are associated with poor outcome in head injury. We studied the effects of hemoglobin-based oxygen-carrying (HBOC)–201 solution compared with lactated Ringer (LR) solution in a large animal model of brain injury and hemorrhage, in a blinded prospective randomized study. Methods Swine underwent brain impact injury and hemorrhage to a mean arterial pressure (MAP) of 40 mm Hg. Twenty swine were randomized to undergo resuscitation with HBOC-201 (6 ml/kg) or LR solution (12 ml/kg) and were observed for an average of 6.5 ± 0.5 hours following resuscitation. At the end of the observation period, magnetic resonance (MR) imaging was performed. Histological studies of swine brains were performed using Fluoro-Jade B, a marker of early neuronal degeneration. Results Swine resuscitated with HBOC-201 had higher MAP, higher cerebral perfusion pressure (CPP), improved base deficit, and higher brain tissue oxygen tension (PbtO2) than animals resuscitated with LR solution. No significant difference in total injury volume on T2-weighted MR imaging was observed between animals resuscitated with HBOC-201 solution (1155 ± 374 mm3) or LR solution (1246 ± 279 mm3; p = 0.55). On the side of impact injury, no significant difference in the mean number of Fluoro-Jade B–positive cells/hpf was seen between HBOC-201 solution (61.5 ± 14.7) and LR solution (48.9 ± 17.7; p = 0.13). Surprisingly, on the side opposite impact injury, a significant increase in Fluoro-Jade B–positive cells/hpf was seen in animals resuscitated with LR solution (42.8 ± 28.3) compared with those resuscitated with HBOC-201 solution (5.6 ± 8.1; p < 0.05), implying greater neuronal injury in LR-treated swine. Conclusions The improved MAP, CPP, and PbtO2 observed with HBOC-201 solution in comparison with LR solution indicates that HBOC-201 solution may be a preferable agent for small-volume resuscitation in brain-injured patients with hemorrhage. The use of HBOC-201 solution appears to decrease cellular degeneration in the brain area not directly impacted by the primary injury. Hemoglobin-based oxygen-carrying–201 solution may act by improving cerebral blood flow or increasing the oxygen-carrying capacity of blood, mitigating a second insult to the injured brain.

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Post–Cardiac Arrest Syndrome

AACN Advanced Critical Care ◽

10.4037/aacnacc2020535 ◽

2020 ◽

Vol 31 (4) ◽

pp. 383-393

Author(s):

Linda Dalessio

Keyword(s):

Cardiac Arrest ◽

Myocardial Dysfunction ◽

The United States ◽

Spontaneous Circulation ◽

Clinical State ◽

Precipitating Factors ◽

Patient Health ◽

Global Brain ◽

The Brain ◽

Post Cardiac Arrest Syndrome

More than 356 000 out-of-hospital cardiac arrests occur in the United States annually. Complications involving post–cardiac arrest syndrome occur because of ischemic-reperfusion injury to the brain, lungs, heart, and kidneys. Post–cardiac arrest syndrome is a clinical state that involves global brain injury, myocardial dysfunction, macrocirculatory dysfunction, increased vulnerability to infection, and persistent precipitating pathology (ie, the cause of the arrest). The severity of outcomes varies and depends on precipitating factors, patient health before cardiac arrest, duration of time to return of spontaneous circulation, and underlying comorbidities. In this article, the pathophysiology and treatment of post–cardiac arrest syndrome are reviewed and potential novel therapies are described.

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Survival analysis in out-of-hospital cardiac arrest patients with shockable rhythm directly transport to Heart Centers

10.22514/sv.2021.084 ◽

2021 ◽

Keyword(s):

Cardiac Arrest ◽

Survival Analysis ◽

Cerebral Performance Category ◽

Spontaneous Circulation ◽

Transport Time ◽

Neurological Outcomes ◽

Neurologic Outcomes ◽

Shockable Rhythm ◽

Short Time ◽

Hospital Cardiac Arrest

Background: This study aimed to evaluate whether out-of-hospital cardiac arrest (OHCA) patients with initial shockable rhythm without prehospital return of spontaneous circulation (ROSC) who are directly transported to Heart Centers in appropriate time will have better post-cardiac arrest four months survival and neurological outcomes at discharge. Methods: This retrospective study assessed the data of 1,588 OHCA patients with shockable rhythm and without prehospital ROSC collected from the registry database of Taoyuan City between January 2014 and June 2018. The relationships of transport time to Heart Centers with survival at discharge and with neurological outcomes were investigated for survival analysis. Results: Among the 1,588 OHCA patients with initial shockable rhythm and without prehospital ROSC, 1,222 (77.0%) and 366 (23.0%) were transported to Heart Centers and non-Heart Centers, respectively. However, the transport to Heart Centers was associated with an increased survival at discharge (adjusted odds ratio [aOR] 2.00, 95% confidence interval [CI], 1.42–2.81) and good neurological outcomes (cerebral performance category [CPC] 1 and 2) (aOR 3.14, 95% CI, 1.88–5.23), regardless of the transport time. The overall mortality reduction for Heart Centers was 39% (hazard ratio [HR] = 0.61; 95% CI 0.47–0.78), compared to that for non-Heart Centers. At 120 days of follow-up, the results showed a higher survival rate for patients who were transported to Heart Centers within a short time. The percentages of good CPC showed a better distribution for non-Heart Centers versus those for Heart Centers. Conclusions: Adult OHCA patients with initial shockable rhythm and without prehospital ROSC who were transported to Heart Centers directly had better post-cardiac arrest survival and good neurologic outcomes, regardless of the transport time.

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Hyperspectral Near Infrared Assessment Of The Brain In Cardiac Arrest

10.32920/ryerson.14648598 ◽

2021 ◽

Author(s):

Thu Nga Nguyen

Keyword(s):

Cardiac Arrest ◽

Oxygen Saturation ◽

Near Infrared ◽

Cerebral Oxygenation ◽

Cerebral Hypoperfusion ◽

Invasive Technique ◽

Breath Holding ◽

Transcatheter Aortic Valve ◽

Neurological Injuries ◽

The Brain

Two-thirds of out-of-hospital cardiac arrest patients, who survive to hospital admission, die in the hospital from neurological injuries related to cerebral hypoperfusion. Hyperspectral near infrared spectroscopy (hNIRS) is a non-invasive technique that measures the major chromophores in the brain, such as oxygenated hemoglobin, deoxygenated hemoglobin and cytochrome C oxidase (CCO), an intracellular marker of oxygen consumption. We have demonstrated that hNIRS can detect changes in cerebral oxygenation and metabolism in patients undergoing transcatheter aortic valve insertion (TAVI) – a procedure that temporarily induces sudden hypotension and hypoperfusion that mimics cardiac arrest. Using multi-distance hNIRS, we found that while measured regional oxygen saturation (rSO2) changes resulted mainly from the extra-cerebral tissues, CCO changes during cardiac arrests occurred mainly in the brains of patients. We also applied the hNIRS algorithm based on the “2-layer model” to the data to measure cerebral oxygen saturation and CCO in patients during the procedure. We found that changes in all the parameters scale with the thickness of the extra-cerebral layer. Finally, the results of the comparison of breath holding measurement by using multispectral NIRS algorithm with the selected wavelength combinations from a previous study on animal suggests that changes in CCO could be measured, however wavelengths need to be further optimized for the adult patients.

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How can neurological outcomes be predicted in comatose pediatric patients after out-of-hospital cardiac arrest?

Clinical and Experimental Pediatrics ◽

10.3345/kjp.2019.00941 ◽

2020 ◽

Vol 63 (5) ◽

pp. 164-170 ◽

Cited By ~ 1

Author(s):

Hyo Jeong Kim

Keyword(s):

Cardiac Arrest ◽

Brain Injury ◽

Neurological Examination ◽

Pediatric Patients ◽

Blood Biomarkers ◽

Neurological Outcomes ◽

Multiple Factors ◽

Response Recovery ◽

Hospital Cardiac Arrest ◽

Unmeasured Confounders

The prognosis of patients who are comatose after resuscitation remains uncertain. The accurate prediction of neurological outcome is important for management decisions and counseling. A neurological examination is an important factor for prognostication, but widely used sedatives alter the neurological examination and delay the response recovery. Additional studies including electroencephalography, somatosensory-evoked potentials, brain imaging, and blood biomarkers are useful for evaluating the extent of brain injury. This review aimed to assess the usefulness of and provide practical prognostic strategy for pediatric postresuscitation patients. The principles of prognostication are that the assessment should be delayed until at least 72 hours after cardiac arrest and the assessment should be multimodal. Furthermore, multiple factors including unmeasured confounders in individual patients should be considered when applying the prognostication strategy.

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