The effects of methylene blue during and after cardiac arrest in a porcine model; a randomized, blinded, placebo-controlled study

Cecilie Munch Johannsen; Casper Nørholt; Cecilie Baltsen; Mark A Eggertsen; Andreas Magnussen; Lasse Vormfenne; Signe Østergaard Mortensen; Esben Søvsø Szocska Hansen; Lauge Vammen; Lars W Andersen; Asger Granfeldt

doi:10.1016/j.ajem.2023.08.041

The effects of methylene blue during and after cardiac arrest in a porcine model; a randomized, blinded, placebo-controlled study

Am J Emerg Med. 2023 Nov:73:145-153. doi: 10.1016/j.ajem.2023.08.041. Epub 2023 Aug 25.

Affiliations

¹ Department of Anesthesiology and Intensive Care, Aarhus University Hospital, Denmark; Department of Clinical Medicine, Aarhus University, Denmark.
² Department of Clinical Medicine, Aarhus University, Denmark.
³ Department of Clinical Medicine, Aarhus University, Denmark; MR Research Centre, Aarhus University, Denmark.
⁴ Department of Anesthesiology and Intensive Care, Aarhus University Hospital, Denmark; Department of Clinical Medicine, Aarhus University, Denmark; Prehospital Emergency Medical Services, Central Denmark Region, Aarhus, Denmark.
⁵ Department of Anesthesiology and Intensive Care, Aarhus University Hospital, Denmark; Department of Clinical Medicine, Aarhus University, Denmark. Electronic address: granfeldt@gmail.com.

PMID: 37659143
DOI: 10.1016/j.ajem.2023.08.041

Abstract

Purpose: To evaluate the effect of methylene blue administered as a bolus on return of spontaneous circulation (ROSC), lactate levels, vasopressor requirements, and markers of neurological injury in a clinically relevant pig model of cardiac arrest.

Materials and methods: 40 anesthetized pigs were subjected to acute myocardial infarction and 7 min of untreated cardiac arrest. Animals were randomized into three groups: one group received saline only (controls), one group received 2 mg/kg methylene blue and saline (MB + saline), and one group received two doses of 2 mg/kg methylene blue (MB + MB). The first intervention was given after the 3rd rhythm analysis, while the second dose was administered one hour after achieving ROSC. Animals underwent intensive care and observation for six hours, followed by cerebral magnetic resonance imaging (MRI). The primary outcome for this study was development in lactate levels after cardiac arrest. Categorical data were compared using Fisher's exact test and pointwise data were analyzed using one-way analysis of variance (ANOVA) or equivalent non-parametric test. Continuous data collected over time were analyzed using a linear mixed effects model. A value of p < .05 was considered statistically significant.

Results: Lactate levels increased in all groups after cardiac arrest and resuscitation, however lactate levels in the MB + MB group decreased significantly faster compared with the control group (p = .007) and the MB + saline group (p = .02). The proportion of animals achieving initial ROSC was similar across groups: 11/13 (85%) in the control group, 10/13 (77%) in the MB + saline group, and 12/14 (86%) in the MB + MB group (p = .81). Time to ROSC did not differ between groups (p = .67). There was no significant difference in accumulated norepinephrine dose between groups (p = .15). Cerebral glycerol levels were significantly lower in the MB + MB group after resuscitation compared with control group (p = .03). However, MRI data revealed no difference in apparent diffusion coefficient, cerebral blood flow, or dynamic contrast enhanced MR perfusion between groups.

Conclusion: Treatment with a bolus of methylene blue during cardiac arrest and after resuscitation did not significantly improve hemodynamic function. A bolus of methylene blue did not yield the neuroprotective effects that have previously been described in animals receiving methylene blue as an infusion.

Keywords: Animal experiment; Heart arrest; Hemodynamic outcomes; Methylene blue; Myocardial infarction; Neurological outcomes.