Pharmacological Approach for Neuroprotection After Cardiac Arrest-A Narrative Review of Current Therapies and Future Neuroprotective Cocktail

Rishabh C Choudhary; Muhammad Shoaib; Samantha Sohnen; Daniel M Rolston; Daniel Jafari; Santiago J Miyara; Kei Hayashida; Ernesto P Molmenti; Junhwan Kim; Lance B Becker

doi:10.3389/fmed.2021.636651

Pharmacological Approach for Neuroprotection After Cardiac Arrest-A Narrative Review of Current Therapies and Future Neuroprotective Cocktail

Front Med (Lausanne). 2021 May 18:8:636651. doi: 10.3389/fmed.2021.636651. eCollection 2021.

Authors

Rishabh C Choudhary^{1

2}, Muhammad Shoaib^{1

3}, Samantha Sohnen⁴, Daniel M Rolston^{2

3

5}, Daniel Jafari^{2

3

5}, Santiago J Miyara^{1

6}, Kei Hayashida^{1

2}, Ernesto P Molmenti⁷, Junhwan Kim^{1

2

3}, Lance B Becker^{1

2

3}

Affiliations

¹ Laboratory for Critical Care Physiology, The Feinstein Institutes for Medical Research, Northwell Health, Manhasset, NY, United States.
² Department of Emergency Medicine, Northshore University Hospital, Northwell Health, Manhasset, NY, United States.
³ Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, Hempstead, NY, United States.
⁴ Department of Anesthesiology, Dartmouth-Hitchcock Medical Center, Lebanon, NH, United States.
⁵ Department of Surgery, North Shore University Hospital, Northwell Health, Manhasset, NY, United States.
⁶ Elmezzi Graduate School of Molecular Medicine, Manhasset, NY, United States.
⁷ Department of Surgery, Northwell Health, Manhasset, NY, United States.

Abstract

Cardiac arrest (CA) results in global ischemia-reperfusion injury damaging tissues in the whole body. The landscape of therapeutic interventions in resuscitation medicine has evolved from focusing solely on achieving return of circulation to now exploring options to mitigate brain injury and preserve brain function after CA. CA pathology includes mitochondrial damage and endoplasmic reticulum stress response, increased generation of reactive oxygen species, neuroinflammation, and neuronal excitotoxic death. Current non-pharmacologic therapies, such as therapeutic hypothermia and extracorporeal cardiopulmonary resuscitation, have shown benefits in protecting against ischemic brain injury and improving neurological outcomes post-CA, yet their application is difficult to institute ubiquitously. The current preclinical pharmacopeia to address CA and the resulting brain injury utilizes drugs that often target singular pathways and have been difficult to translate from the bench to the clinic. Furthermore, the limited combination therapies that have been attempted have shown mixed effects in conferring neuroprotection and improving survival post-CA. The global scale of CA damage and its resultant brain injury necessitates the future of CA interventions to simultaneously target multiple pathways and alleviate the hemodynamic, mitochondrial, metabolic, oxidative, and inflammatory processes in the brain. This narrative review seeks to highlight the current field of post-CA neuroprotective pharmaceutical therapies, both singular and combination, and discuss the use of an extensive multi-drug cocktail therapy as a novel approach to treat CA-mediated dysregulation of multiple pathways, enhancing survival, and neuroprotection.

Keywords: cardiopulmonary arrest; cerebral ischemia; cocktail therapy; ischemia and reperfusion injury; neuroprotection; pharmacological intervention; resuscitation.

Publication types

Review