Cerebral monitoring in a pig model of cardiac arrest with 48 h of intensive care

Lauge Vammen; Cecilie Munch Johannsen; Andreas Magnussen; Amalie Povlsen; Søren Riis Petersen; Arezo Azizi; Michael Pedersen; Anders Rosendal Korshøj; Steffen Ringgaard; Bo Løfgren; Lars W Andersen; Asger Granfeldt

doi:10.1186/s40635-022-00475-2

Cerebral monitoring in a pig model of cardiac arrest with 48 h of intensive care

Intensive Care Med Exp. 2022 Oct 26;10(1):45. doi: 10.1186/s40635-022-00475-2.

Authors

Lauge Vammen^{1

2}, Cecilie Munch Johannsen^{1

2}, Andreas Magnussen², Amalie Povlsen^{2

3}, Søren Riis Petersen², Arezo Azizi², Michael Pedersen⁴, Anders Rosendal Korshøj^{2

5}, Steffen Ringgaard⁶, Bo Løfgren^{2

7

8}, Lars W Andersen^{1

2

9}, Asger Granfeldt^{10

11}

Affiliations

¹ Department of Anesthesiology and Intensive Care, Aarhus University Hospital, Palle Juul Jensens Blvd. 99 G304, 8200, Aarhus N, Denmark.
² Department of Clinical Medicine, Aarhus University, Aarhus N, Denmark.
³ Department of Cardiothoracic Anesthesia, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark.
⁴ Comparative Medicine Laboratory, Aarhus University, Aarhus N, Denmark.
⁵ Department of Neurosurgery, Aarhus University Hospital, Aarhus N, Denmark.
⁶ MR Research Centre, Aarhus University, Aarhus N, Denmark.
⁷ Research Center for Emergency Medicine, Aarhus University Hospital, Aarhus N, Denmark.
⁸ Department of Medicine, Randers Regional Hospital, Randers, Denmark.
⁹ Prehospital Emergency Medical Services, Central Denmark Region, Aarhus N, Denmark.
¹⁰ Department of Anesthesiology and Intensive Care, Aarhus University Hospital, Palle Juul Jensens Blvd. 99 G304, 8200, Aarhus N, Denmark. granfeldt@gmail.com.
¹¹ Department of Clinical Medicine, Aarhus University, Aarhus N, Denmark. granfeldt@gmail.com.

Abstract

Background: Neurological injury is the primary cause of death after out-of-hospital cardiac arrest. There is a lack of studies investigating cerebral injury beyond the immediate post-resuscitation phase in a controlled cardiac arrest experimental setting.

Methods: The aim of this study was to investigate temporal changes in measures of cerebral injury and metabolism in a cardiac arrest pig model with clinically relevant post-cardiac arrest intensive care. A cardiac arrest group (n = 11) underwent 7 min of no-flow and was compared with a sham group (n = 6). Pigs underwent intensive care with 24 h of hypothermia at 33 °C. Blood markers of cerebral injury, cerebral microdialysis, and intracranial pressure (ICP) were measured. After 48 h, pigs underwent a cerebral MRI scan. Data are presented as median [25th; 75th percentiles].

Results: Return of spontaneous circulation was achieved in 7/11 pigs. Time to ROSC was 4.4 min [4.2; 10.9]. Both NSE and NfL increased over time (p < 0.001), and were higher in the cardiac arrest group at 48 h (NSE 4.2 µg/L [2.4; 6.1] vs 0.9 [0.7; 0.9], p < 0.001; NfL 63 ng/L [35; 232] vs 29 [21; 34], p = 0.02). There was no difference in ICP at 48 h (17 mmHg [14; 24] vs 18 [13; 20], p = 0.44). The cerebral lactate/pyruvate ratio had secondary surges in 3/7 cardiac arrest pigs after successful resuscitation. Apparent diffusion coefficient was lower in the cardiac arrest group in white matter cortex (689 × 10^-6 mm²/s [524; 765] vs 800 [799; 815], p = 0.04) and hippocampus (854 [834; 910] vs 1049 [964; 1180], p = 0.03). N-Acetylaspartate was lower on MR spectroscopy in the cardiac arrest group (- 17.2 log [- 17.4; - 17.0] vs - 16.9 [- 16.9; - 16.9], p = 0.03).

Conclusions: We have developed a clinically relevant cardiac arrest pig model that displays cerebral injury as marked by NSE and NfL elevations, signs of cerebral oedema, and reduced neuron viability. Overall, the burden of elevated ICP was low in the cardiac arrest group. A subset of pigs undergoing cardiac arrest had persisting metabolic disturbances after successful resuscitation.

Keywords: Acute myocardial infarction; Heart arrest; Post-cardiac arrest intensive care; Targeted temperature management.