A search for therapeutic targets in cardiac arrest and cardiogenic shock

Abstract

This thesis explores potential therapeutic targets for cardiac arrest and cardiogenic shock both of which have high mortality following ICU admission.

The effect of blood pressure on mortality following out-of-hospital cardiac arrest: a retrospective cohort study of the United Kingdom Intensive Care National Audit and Research Centre database. Although the association between hypotension and poor outcomes following OHCA has been documented, the association between exposure to high blood pressure and outcome has been poorly studied. I report the association between exposure to both hypotension and hypertension and mortality following cardiac arrest.

The association between time of in hospital cardiac arrest and mortality; a retrospective analysis of two UK databases. Diurnal variation has been reported in the incidence and outcome following cardiac arrest. Blunting or manipulation of the circadian rhythm may provide potential therapeutic options. This study reports loss of diurnal variation in survival following IHCA in those admitted to ICU. This suggests patient factors and processes of care, not circadian rhythm, explain the previously observed diurnal variation.

Drug therapy versus placebo or usual care for comatose survivors of cardiac arrest; a systematic review with meta-analysis. In this review, reduced mortality was reported with penehyclidine hydrochloride, Shenfu, and steroids when co-administered with vasopressin.

Vasoactive drugs in cardiogenic shock: A systematic review and meta-analysis of randomized controlled trials. In comparison to usual care, there was no evidence of an effect with catecholamines, phosphodiesterase-3-inhibitors, levosimendan, nitric oxide synthase inhibitors or adrecizumab.

Phenotypes in cardiac arrest: a latent class analysis of the Targeted Temperature Management Trial. In a large trial of patients who remain comatose following OHCA, we identified brain injury and a cardiovascular subphenotypes. However, no heterogeneity of treatment effect to the trialled therapies of 33°C or 36°C was observed.

Thesis is embargoed until 31 December 2030.

Date of Award	Dec 2025
Original language	English
Awarding Institution	Queen's University Belfast
Sponsors	Belfast Health and Social Care Trust
Supervisor	Danny McAuley (Supervisor) & Bronagh Blackwood (Supervisor)