scholarly journals Association of deranged cerebrovascular reactivity with brain injury following cardiac arrest: a post-hoc analysis of the COMACARE trial

Critical Care ◽  
2021 ◽  
Vol 25 (1) ◽  
Author(s):  
Johanna Laurikkala ◽  
Anders Aneman ◽  
Alexander Peng ◽  
Matti Reinikainen ◽  
Paul Pham ◽  
...  

Abstract Background Impaired cerebrovascular reactivity (CVR) is one feature of post cardiac arrest encephalopathy. We studied the incidence and features of CVR by near infrared spectroscopy (NIRS) and associations with outcome and biomarkers of brain injury. Methods A post-hoc analysis of 120 comatose OHCA patients continuously monitored with NIRS and randomised to low- or high-normal oxygen, carbon dioxide and mean arterial blood pressure (MAP) targets for 48 h. The tissue oximetry index (TOx) generated by the moving correlation coefficient between cerebral tissue oxygenation measured by NIRS and MAP was used as a dynamic index of CVR with TOx > 0 indicating impaired reactivity and TOx > 0.3 used to delineate the lower and upper MAP bounds for disrupted CVR. TOx was analysed in the 0–12, 12–24, 24–48 h time-periods and integrated over 0–48 h. The primary outcome was the association between TOx and six-month functional outcome dichotomised by the cerebral performance category (CPC1-2 good vs. 3–5 poor). Secondary outcomes included associations with MAP bounds for CVR and biomarkers of brain injury. Results In 108 patients with sufficient data to calculate TOx, 76 patients (70%) had impaired CVR and among these, chronic hypertension was more common (58% vs. 31%, p = 0.002). Integrated TOx for 0–48 h was higher in patients with poor outcome than in patients with good outcome (0.89 95% CI [− 1.17 to 2.94] vs. − 2.71 95% CI [− 4.16 to − 1.26], p = 0.05). Patients with poor outcomes had a decreased upper MAP bound of CVR over time (p = 0.001), including the high-normal oxygen (p = 0.002), carbon dioxide (p = 0.012) and MAP (p = 0.001) groups. The MAP range of maintained CVR was narrower in all time intervals and intervention groups (p < 0.05). NfL concentrations were higher in patients with impaired CVR compared to those with intact CVR (43 IQR [15–650] vs 20 IQR [13–199] pg/ml, p = 0.042). Conclusion Impaired CVR over 48 h was more common in patients with chronic hypertension and associated with poor outcome. Decreased upper MAP bound and a narrower MAP range for maintained CVR were associated with poor outcome and more severe brain injury assessed with NfL. Trial registration ClinicalTrials.gov, NCT02698917.

Circulation ◽  
2018 ◽  
Vol 138 (Suppl_2) ◽  
Author(s):  
Johannes Grand ◽  
Christian Hassager ◽  
Matilde Winther-Jensen ◽  
Sebastian Wiberg ◽  
Jakob H Thomsen ◽  
...  

Introduction: Hemodynamic instability is common after resuscitated out-of-hospital cardiac arrest (OHCA). However, data on hemodynamic treatment-goals are sparse. This study investigates mean arterial pressure (MAP) in patients surviving 48 hours after OHCA in relation to organ injury and survival as a post hoc analysis of a large multicenter trial cohort. Hypothesis: We hypothesized that low MAP during TTM was associated with more organ injury. Methods: Post-hoc analysis of the prospective randomized TTM-trial including 851 comatose OHCA patients surviving more than 48 hours with available blood pressure data. Neuron-specific enolase (NSE) (brain injury) was the primary endpoint and estimated glomerular filtration rate (eGFR) (renal function) was the secondary endpoint. Measurements and Main Results: Patients were stratified by mean MAP during TTM in the following groups; <70 mmHg (22%), 70-80 mmHg (43%), and >80 mmHg (35%). NSE at 24, 48 and 72 hours was inversely related to mean MAP: 28 ng/ml [95% confidence interval (CI) 24-33], 26 [23-29], 21 [19-24] ng/mL; p group =0.002 for low, intermediate and high MAP groups. After adjusting for potential confounders, this association remained significant (p group_adjusted =0.006). A similar result was seen for eGFR (p group_adjusted =0.003). Mean MAP was not associated with mortality after 180 days, however higher mean MAP was independently associated with lower odds of renal replacement therapy (odds ratio adjusted = 0.75 [95% CI, 0.63-0.88] per 5 mmHg increase; p < 0.001]) (figure 1). Conclusions: Lower mean MAP during TTM was independently associated with increased biomarkers of brain injury and initiation of renal replacement therapy in a large cohort of comatose OHCA patients. Increasing blood pressure above the guideline-recommended threshold of 65 mmHg during TTM could potentially mitigate organ injury and be renal-protective. This hypothesis should be investigated in prospective trials.


2020 ◽  
Vol 132 (6) ◽  
pp. 1952-1960 ◽  
Author(s):  
Seung-Bo Lee ◽  
Hakseung Kim ◽  
Young-Tak Kim ◽  
Frederick A. Zeiler ◽  
Peter Smielewski ◽  
...  

OBJECTIVEMonitoring intracranial and arterial blood pressure (ICP and ABP, respectively) provides crucial information regarding the neurological status of patients with traumatic brain injury (TBI). However, these signals are often heavily affected by artifacts, which may significantly reduce the reliability of the clinical determinations derived from the signals. The goal of this work was to eliminate signal artifacts from continuous ICP and ABP monitoring via deep learning techniques and to assess the changes in the prognostic capacities of clinical parameters after artifact elimination.METHODSThe first 24 hours of monitoring ICP and ABP in a total of 309 patients with TBI was retrospectively analyzed. An artifact elimination model for ICP and ABP was constructed via a stacked convolutional autoencoder (SCAE) and convolutional neural network (CNN) with 10-fold cross-validation tests. The prevalence and prognostic capacity of ICP- and ABP-related clinical events were compared before and after artifact elimination.RESULTSThe proposed SCAE-CNN model exhibited reliable accuracy in eliminating ABP and ICP artifacts (net prediction rates of 97% and 94%, respectively). The prevalence of ICP- and ABP-related clinical events (i.e., systemic hypotension, intracranial hypertension, cerebral hypoperfusion, and poor cerebrovascular reactivity) all decreased significantly after artifact removal.CONCLUSIONSThe SCAE-CNN model can be reliably used to eliminate artifacts, which significantly improves the reliability and efficacy of ICP- and ABP-derived clinical parameters for prognostic determinations after TBI.


2020 ◽  
Vol 8 (S1) ◽  
Author(s):  
Chiara Robba ◽  
Dorota Siwicka-Gieroba ◽  
Andras Sikter ◽  
Denise Battaglini ◽  
Wojciech Dąbrowski ◽  
...  

AbstractPost cardiac arrest syndrome is associated with high morbidity and mortality, which is related not only to a poor neurological outcome but also to respiratory and cardiovascular dysfunctions. The control of gas exchange, and in particular oxygenation and carbon dioxide levels, is fundamental in mechanically ventilated patients after resuscitation, as arterial blood gases derangement might have important effects on the cerebral blood flow and systemic physiology.In particular, the pathophysiological role of carbon dioxide (CO2) levels is strongly underestimated, as its alterations quickly affect also the changes of intracellular pH, and consequently influence metabolic energy and oxygen demand. Hypo/hypercapnia, as well as mechanical ventilation during and after resuscitation, can affect CO2 levels and trigger a dangerous pathophysiological vicious circle related to the relationship between pH, cellular demand, and catecholamine levels. The developing hypocapnia can nullify the beneficial effects of the hypothermia. The aim of this review was to describe the pathophysiology and clinical consequences of arterial blood gases and pH after cardiac arrest.According to our findings, the optimal ventilator strategies in post cardiac arrest patients are not fully understood, and oxygen and carbon dioxide targets should take in consideration a complex pattern of pathophysiological factors. Further studies are warranted to define the optimal settings of mechanical ventilation in patients after cardiac arrest.


2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Ferran Rueda ◽  
Germán Cediel ◽  
Cosme García-García ◽  
Júlia Aranyó ◽  
Marta González-Lopera ◽  
...  

Abstract Background Growth differentiation factor 15 (GDF-15) is an inflammatory cytokine released in response to tissue injury. It has prognostic value in cardiovascular diseases and other acute and chronic conditions. Here, we explored the value of GDF-15 as an early predictor of neurologic outcome after an out-of-hospital cardiac arrest (OHCA). Methods Prospective registry study of patients in coma after an OHCA, admitted in the intensive cardiac care unit from a single university center. Serum levels of GDF-15 were measured on admission. Neurologic status was evaluated according to the cerebral performance category (CPC) scale. The relationship between GDF-15 levels and poor neurologic outcome at 6 months was analyzed. Results Among 62 patients included, 32 (51.6%) presented poor outcome (CPC 3–5). Patients with CPC 3–5 exhibited significantly higher GDF-15 levels (median, 17.1 [IQR, 11.1–20.4] ng/mL) compared to those with CPC 1–2 (7.6 [IQR, 4.1–13.1] ng/mL; p = 0.004). Multivariable logistic regression analyses showed that age (OR, 1.09; 95% CI 1.01–1.17; p = 0.020), home setting arrest (OR, 8.07; 95% CI 1.61–40.42; p = 0.011), no bystander cardiopulmonary resuscitation (OR, 7.91; 95% CI 1.84–34.01; p = 0.005), and GDF-15 levels (OR, 3.74; 95% CI 1.32–10.60; p = 0.013) were independent predictors of poor outcome. The addition of GDF-15 in a dichotomous manner (≥ 10.8 vs. < 10.8 ng/mL) to the resulting clinical model improved discrimination; it increased the area under the curve from 0.867 to 0.917, and the associated continuous net reclassification improvement was 0.90 (95% CI 0.48–1.44), which allowed reclassification of 37.1% of patients. Conclusions After an OHCA, increased GDF-15 levels were an independent, early predictor of poor neurologic outcome. Furthermore, when added to the most common clinical factors, GDF-15 improved discrimination and allowed patient reclassification.


2020 ◽  
Vol 37 (12) ◽  
pp. 847.1-847
Author(s):  
James Price ◽  
Daniel Sandbach ◽  
Ari Ercole ◽  
Alastair Wilson ◽  
Ed Barnard

Aims/Objectives/BackgroundIn the United Kingdom (UK), 20% of patients with severe traumatic brain injury (TBI) receive pre-hospital emergency anaesthesia (PHEA). Current guidance recommends an end-tidal carbon dioxide (ETCO2) of 4.0–4.5kPa to achieve a low-normal arterial partial pressure of CO2 (PaCO2), and reduce secondary brain injury. This recommendation assumes a 0.5kPa ETCO2-PaCO2 gradient. However, the gradient in the acute phase of TBI is unknown. Our primary aim was to report the ETCO2-PaCO2 gradient of TBI patients at hospital arrival.Methods/DesignA retrospective cohort study of adult patients with serious TBI, who received a PHEA by a pre-hospital critical care team in the East of England between 1st April 2015 to 31st December 2017. Linear regression was performed to test for correlation and reported as R-squared (R2). A Bland-Altman plot was used to test for paired ETCO2 and PaCO2 agreement and reported with 95% confidence intervals (95%CI). ETCO2-PaCO2 gradient data were compared with a two-tailed, unpaired, t-test.Results/Conclusions107 patients were eligible for inclusion. Sixty-seven patients did not receive a PaCO2 sample within 30 minutes of hospital arrival and were therefore excluded. Forty patients had complete data and were included in the final analysis; per protocol.The mean ETCO2-PaCO2 gradient was 1.7 (±1.0) kPa, with only moderate correlation of ETCO2 and PaCO2 at hospital arrival (R2=0.23, p=0.002). The Bland-Altman bias was 1.7 (95%CI 1.4–2.0) kPa with upper and lower limits of agreement of 3.6 (95%CI 3.0–4.1) kPa and -0.2 (95%CI -0.8–0.3) kPa respectively. There was no significant gradient correlation in patients with a co-existing serious thoracic injury (R2=0.13, p=0.10), and this cohort had a larger ETCO2-PaCO2 gradient, 2.0 (±1.1) kPa, p=0.01. Patients who underwent pre-hospital arterial blood sampling had an arrival PaCO2 of 4.7 (±0.2) kPa.Lower ETCO2 targets than previously recommended may be safe and appropriate. The use of pre-hospital PaCO2 measurement is advocated.


Circulation ◽  
2021 ◽  
Vol 144 (Suppl_2) ◽  
Author(s):  
Ericka L Fink ◽  
Patrick M Kochanek ◽  
Ashok Panigrahy ◽  
Sue R Beers ◽  
Rachel P Berger ◽  
...  

Blood-based brain injury biomarkers show promise to prognosticate outcome for children resuscitated from cardiac arrest. The objective of this multicenter, observational study was to validate promising biomarkers to accurately prognosticate outcome at 1 year. Early brain injury biomarkers will be associated with outcome at one year for children with cardiac arrest. Fourteen centers in the US enrolled children aged < 18 years with in- or out-of-hospital cardiac arrest and pediatric intensive care unit admission if pre-cardiac arrest Pediatric Cerebral Performance Category score was 1-3. Glial fibrillary acidic protein (GFAP), ubiquitin carboxyl-terminal esterase L1 (UCHL1), neurofilament light (NfL), and Tau protein concentrations were measured in samples drawn post-arrest day 1 using Quanterix Simoa 4-Plex assay. The primary outcome was unfavorable outcome at one year (Vineland Adaptive Behavioral Scale < 70). Of 164 children enrolled, 120 children had evaluable data (n=50 with unfavorable outcome). Children were median (interquartile range) 1 (0-8.5) years of age, 41% female, and 60% had asphyxia etiology. Of children with unfavorable outcome, 93% had unwitnessed arrests and 43 died. While all 4 day 1 biomarkers were increased in children with unfavorable vs. favorable outcome at 1-year post-arrest, NfL had the best univariate area under the receiver operator curve to predict 1 year outcome at 0.731. In a multivariate logistic regression, NfL concentration trended toward significance on day 1 and was associated with unfavorable outcome at 1-year on days 2 and 3 (day 1: Odds Ratio [95% Confidence Interval] 1.004 [1.000-1.008], p=.062; day 2: 1.005 [1.002-1.008], p=.003, and day 3: 1.002 [1.001-1.004], p=.003, respectively). UCHL1 was associated with outcome on days 2: 1.005 [1.002-1.009], p=.003 and 3: 1.001 [1.000-1.002], p=.019) and Tau trended toward association with outcome on days 2: 1.003 [1.000-1.005], p=.08) and 3: 1.001 [1.000-1.002], p=.077. Brain injury biomarkers predict unfavorable outcome post-pediatric cardiac arrest. Accuracy of biomarkers alone and together with other prognostication tools should be evaluated to predict long term child centered outcomes post-cardiac arrest.


Circulation ◽  
2021 ◽  
Vol 144 (Suppl_2) ◽  
Author(s):  
Daniel Rob ◽  
Jana Smalcova ◽  
Tomas Kovarnik ◽  
David Zemanek ◽  
Ales Kral ◽  
...  

Background: An increasing number of cardiac centres are using immediate percutaneous coronary intervention (PCI) and extracorporeal cardiopulmonary resuscitation (ECPR) in patients with refractory out of hospital cardiac arrest (r-OHCA). Published evidence regarding PCI in OHCA has been mainly reporting to patients with early return of spontaneous circulation and the influence of PCI and ECPR on survival in the population of patients with r-OHCA and acute coronary syndrome (ACS) remains unclear. Methods: In this post hoc analysis of the randomized r-OHCA trial, all patients with ACS as a cause of r-OHCA were included. The effect of successful PCI and ECPR on 180-days survival was examined using Kaplan-Meier estimates and multivariable Cox regression. Results: In total, 256 patients were evaluated in Prague OHCA study and 127 (49.6 %) had ACS as the cause of r-OHCA constituting current study population. The mean age was 58 years (46.3-64) and duration of resuscitation was 52.5 minutes (36.5-68). ECPR was used in 51 (40.2 %) of patients. Immediate PCI was performed in 86 (67.7%) patients and TIMI flow 2 or 3 was achieved in 75 (87.2%) patients. The overall 180-days survival of patients with successful PCI was 40 % compared to 7.7 % with no or failed immediate PCI (log-rank p < 0.001). After adjustment for confounders, successful PCI was associated with a lower risk of death (HR 0.47, CI 0.24-0.93, p = 0.031). Likewise, ECPR was associated with a lower risk of death (HR 0.11, CI 0.05-0.24, p< 0.001). Conclusion: In this post hoc analysis of the randomized r-OHCA trial, successful immediate PCI as well as ECPR were associated with improved 180-days survival in patients with r-OHCA due to ACS.


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