Increasing mean arterial pressure or cardiac output in comatose out-of-hospital cardiac arrest patients undergoing targeted temperature management: Effects on cerebral tissue oxygenation and systemic hemodynamics

Abstract Background: The authors investigated whether patients with out-of-hospital cardiac arrest with an initial low cerebral oxygen level during cardiopulmonary resuscitation are more prone to develop hyperfibrinolysis than patients with normal cerebral oxygenation levels and which part of the fibrinolytic system is involved in this response. Methods: In 46 patients, hyperfibrinolysis was diagnosed immediately upon emergency department admission using rotational thromboelastometry and defined as a lysis more than 15%. Simultaneously, initial cerebral tissue oxygenation was measured using near-infrared spectroscopy, and oxygen desaturation was defined as a tissue oxygenation index (TOI) of 50% or less. Blood sample analysis included markers for hypoperfusion and fibrinolysis. Results: There was no difference in prehospital cardiopulmonary resuscitation duration between patients with or without hyperfibrinolysis. An initial TOI of 50% or less was associated with more clot lysis (91% [17 to 100%; n = 16]) compared with patients with a normal TOI (6% [4 to 11%]; n = 30; P < 0.001), with lower levels of plasminogen (151.6 ± 61.0 vs. 225.3 ± 47.0 μg/ml; P < 0.001) and higher levels of tissue plasminogen activator (t-PA; 18.3 ± 7.4 vs. 7.9 ± 4.7 ng/ml; P < 0.001) and plasminogen activator inhibitor-1 (19.3 ± 8.9 vs. 12.1 ± 6.1 ng/ml; P = 0.013). There were no differences in (activated) protein C levels among groups. The initial TOI was negatively correlated with t-PA (r = −0.69; P < 0001). Mortality rates were highest in patients with hyperfibrinolysis. Conclusion: Activation of the fibrinolytic system is more common in out-of-hospital cardiac arrest patients with an initial cerebral tissue oxygenation value of 50% or less during resuscitation and is linked to increased levels of t-PA rather than involvement of protein C.

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Arterial blood pressure during targeted temperature management after out-of-hospital cardiac arrest and association with brain injury and long-term cognitive function

European Heart Journal Acute Cardiovascular Care ◽

10.1177/2048872619860804 ◽

2019 ◽

Vol 9 (4_suppl) ◽

pp. S122-S130 ◽

Cited By ~ 4

Author(s):

Johannes Grand ◽

Gisela Lilja ◽

Jesper Kjaergaard ◽

John Bro-Jeppesen ◽

Hans Friberg ◽

...

Keyword(s):

Cardiac Arrest ◽

Brain Injury ◽

Cognitive Function ◽

Mean Arterial Pressure ◽

Arterial Pressure ◽

Neuron Specific Enolase ◽

Targeted Temperature Management ◽

Temperature Management ◽

Impaired Cognitive Function ◽

Hospital Cardiac Arrest

Objectives: During targeted temperature management after out-of-hospital cardiac arrest infusion of vasoactive drugs is often needed to ensure cerebral perfusion pressure. This study investigated mean arterial pressure after out-of-hospital cardiac arrest and the association with brain injury and long-term cognitive function. Methods: Post-hoc analysis of patients surviving at least 48 hours in the biobank substudy of the targeted temperature management trial with available blood pressure data. Patients were stratified in three groups according to mean arterial pressure during targeted temperature management (4–28 hours after admission; <70 mmHg, 70–80 mmHg, >80 mmHg). A biomarker of brain injury, neuron-specific enolase, was measured and impaired cognitive function was defined as a mini-mental state examination score below 27 in 6-month survivors. Results: Of the 657 patients included in the present analysis, 154 (23%) had mean arterial pressure less than 70 mmHg, 288 (44%) had mean arterial pressure between 70 and 80 mmHg and 215 (33%) had mean arterial pressure greater than 80 mmHg. There were no statistically significant differences in survival ( P=0.35) or neuron-specific enolase levels ( P=0.12) between the groups. The level of target temperature did not statistically significantly interact with mean arterial pressure regarding neuron-specific enolase ( Pinteraction_MAP*TTM=0.58). In the subgroup of survivors with impaired cognitive function ( n=132) (35%) mean arterial pressure during targeted temperature management was significantly higher ( Pgroup=0.03). Conclusions: In a large cohort of comatose out-of-hospital cardiac arrest patients, low mean arterial pressure during targeted temperature management was not associated with higher neuron-specific enolase regardless of the level of target temperature (33°C or 36°C for 24 hours). In survivors with impaired cognitive function, mean arterial pressure during targeted temperature management was significantly higher.

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Abstract 159: Epinephrine Increases Cerebral Perfusion and Oxygenation in a Pre-Clinical Model of Pediatric In-Hospital Cardiac Arrest

Circulation ◽

10.1161/circ.138.suppl_2.159 ◽

2018 ◽

Vol 138 (Suppl_2) ◽

Author(s):

Constantine D Mavroudis ◽

Tiffany S Ko ◽

Ryan W Morgan ◽

Marco M Hefti ◽

William P Landis ◽

...

Keyword(s):

Cardiac Arrest ◽

Tissue Oxygenation ◽

Cerebral Oxygenation ◽

Neurological Injury ◽

Tissue Oxygen Saturation ◽

Swine Model ◽

Cerebral Tissue ◽

Clinical Model ◽

Cerebral Tissue Oxygenation ◽

Hospital Cardiac Arrest

Introduction: Despite controversies, epinephrine remains a mainstay of CPR. Recent animal studies have suggested that epinephrine may decrease cerebral blood flow (CBF) and cerebral oxygenation, possibly potentiating neurological injury during CPR. We investigated the cerebrovascular effects of intravenous epinephrine in a swine model of pediatric in-hospital cardiac arrest. Hypothesis: Epinephrine will increase CBF and cerebral oxygenation during CPR. Methods: One-month old piglets (n=20, 8-10kg) underwent asphyxia for 7 minutes, VF, and CPR according to AHA guidelines for 10-20 minutes. Epinephrine boluses (20 mcg/kg) were administered at minutes 2, 6, 10, and 14 of CPR. Invasive (laser Doppler) and noninvasive (diffuse optical) continuous measurements of CBF and oxygenation were recorded. Wilcoxon Rank-Sum test was used to compare measurements 15 seconds prior to epinephrine doses to sequential measurements at 1-minute intervals following epinephrine; data are described as median [IQR]. Results: Compared to pre-epinephrine values, CBF was most significantly increased one minute after the first dose of epinephrine (noninvasive: +37.7% [6.1, 79]; invasive: +24% [-0.3, 118], p<0.004 for both) and returned to baseline by 3 minutes post-epinephrine. Cerebral tissue oxygenation was also most significantly increased one-minute after the first dose of epinephrine (noninvasive: +25.2% [9.0, 45]; invasive: +160% [30.3, 428], p<0.001 for both) and remained elevated 4 minutes post-epinephrine. Effects were also significant one minute following the second dose on CBF (noninvasive: +11.5% [4.5, 29]; invasive: +9.5% [0.6, 19, p<0.03 for both) and on cerebral tissue oxygenation (noninvasive: +12.3% [1.6, 19]; invasive: +17.8% [-2.3,34, p<0.037 for both). There was no significant effect on any parameter following the third and fourth doses. Conclusions: In a swine model of pediatric in-hospital cardiac arrest, bolus-dosed epinephrine increases CBF and cerebral tissue oxygen saturation. These effects are only significant following the first two doses. Our findings are underscore the importance of further research to elucidate the transient pharmacodynamics of epinephrine to optimize both survival and neurological outcomes.

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Haemodynamics and vasopressor support during prolonged targeted temperature management for 48 hours after out-of-hospital cardiac arrest: a post hoc substudy of a randomised clinical trial

European Heart Journal Acute Cardiovascular Care ◽

10.1177/2048872620934305 ◽

2020 ◽

pp. 204887262093430

Author(s):

Johannes Grand ◽

Christian Hassager ◽

Markus B Skrifvars ◽

Marjaana Tiainen ◽

Anders M Grejs ◽

...

Keyword(s):

Clinical Trial ◽

Heart Rate ◽

Cardiac Arrest ◽

Mean Arterial Pressure ◽

Arterial Pressure ◽

Randomised Clinical Trial ◽

Hazard Ratio ◽

Targeted Temperature Management ◽

Temperature Management ◽

Hospital Cardiac Arrest

Background Comatose patients admitted after out-of-hospital cardiac arrest frequently experience haemodynamic instability and anoxic brain injury. Targeted temperature management is used for neuroprotection; however, targeted temperature management also affects patients’ haemodynamic status. This study assessed the haemodynamic status of out-of-hospital cardiac arrest survivors during prolonged (48 hours) targeted temperature management at 33°C. Methods Analysis of haemodynamic and vasopressor data from 311 patients included in a randomised, clinical trial conducted in 10 European hospitals (the TTH48 trial). Patients were randomly allocated to targeted temperature management at 33°C for 24 (TTM24) or 48 (TTM48) hours. Vasopressor and haemodynamic data were reported hourly for 72 hours after admission. Vasopressor load was calculated as norepinephrine (µg/kg/min) plus dopamine(µg/kg/min/100) plus epinephrine (µg/kg/min). Results After 24 hours, mean arterial pressure (mean±SD) was 74±9 versus 75±9 mmHg ( P=0.19), heart rate was 57±16 and 55±14 beats/min ( P=0.18), vasopressor load was 0.06 (0.03–0.15) versus 0.08 (0.03–0.15) µg/kg/min ( P=0.22) for the TTM24 and TTM48 groups, respectively. From 24 to 48 hours, there was no difference in mean arterial pressure ( Pgroup=0.32) or lactate ( Pgroup=0.20), while heart rate was significantly lower (average difference 5 (95% confidence interval 2–8) beats/min, Pgroup<0.0001) and vasopressor load was significantly higher in the TTM48 group ( Pgroup=0.005). In a univariate Cox regression model, high vasopressor load was associated with mortality in univariate analysis (hazard ratio 1.59 (1.05–2.42) P=0.03), but not in multivariate analysis (hazard ratio 0.77 (0.46–1.29) P=0.33). Conclusions In this study, prolonged targeted temperature management at 33°C for 48 hours was associated with higher vasopressor requirement but no sign of any detrimental haemodynamic effects.

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