Elsevier

Medical Hypotheses

Volume 73, Issue 1, July 2009, Pages 97-99
Medical Hypotheses

Statins for post resuscitation syndrome

https://doi.org/10.1016/j.mehy.2009.01.021Get rights and content

Summary

After sudden cardiac arrest, successful resuscitation and return of spontaneous circulation, a multi-faceted ischaemia/reperfusion related disorder develops. This condition now known as post resuscitation syndrome is characterised by marked increases in the inflammatory response and changes in coagulation profile and vascular reactivity. Additionally, the production of reactive oxygen species and activation of cytotoxic cascades of metabolism add to these injury mechanisms resulting in multiorgan perfusion deficits and dysfunction. Especially in the cerebrum these injuries may be the cause of significant morbidity and mortality.

Recent evidence has shown that statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) exert numerous beneficial effects in cardiovascular diseases irrespective of the lipid status. Remarkably, these pleiotropic effects seem to extended beyond cardiovascular diseases such as immunomodulative and antioxidative properties.

We hypothesised that administration of statins early in the post resuscitation phase would prove beneficial in the resuscitated patient via several pleiotropic effects. These include inhibition of excessive coagulation and inflammatory response, suppression of oxygen radical production and improved vascular reactivity. The discussed effects are mediated via multiple pathways activated in the cardiac arrest victim, to which statins have been shown to have a beneficial modulating effect in experimental settings and non-cardiac arrest patients.

To test this hypothesis in clinical practice, a randomized, controlled trial with sufficient power and standardised post resuscitation treatment would be necessary. The generally good tolerance of statin therapy with minimal adverse effects would support this experiment, although a parenteral form of the drug to ensure adequate dosage might be a prerequisite.

Introduction

Following successful cardiopulmonary resuscitation (CPR) after cardiac arrest a multi-faceted disorder currently known as the post resuscitation syndrome develops [1]. There is evidence that this syndrome carries similarities to the systemic inflammatory changes of sepsis with the presence of circulating endotoxins and leukocyte dysregulation, increase in plasma cytokines, and adrenal dysfunction [2], [3], [4]. The disorder includes systemic reperfusion deficits due to endothelial swelling, vasospasm, increased blood viscosity, disseminated intravascular coagulopathy (DIC) and leukocyte interactions with the endothelium [5], [6], [7], [8]. These changes are more pronounced in the cerebrum as the autoregulation of cerebral blood flow is lost for an imbalance of vasoactive substances such as nitrous oxide, adenosine, endothelin and cyclic guanosine monophosphate causing vasoconstriction [8], [9], [10].

In addition, reoxygenation after return of spontaneous circulation accelerates the production of reactive oxygen species that alongside continued glutamate mediated excitatory neurotoxicity and renewed calcium shifts further activate cytotoxic enzymes such as endonucleases, proteases, phospholipases and xanthine oxidase [11], [12]. This reperfusion cascade leads to disseminated cell death and apoptosis following fragmentation of the DNA and mitochondrial lesions, thereby exacerbating the primary intra-arrest injury [8]. The importance of these injury mechanisms especially in the cerebrum is reflected by the fact that two thirds of the patients who eventually die after successful resuscitation from prehospital cardiac arrest and ICU admission die due to neurological injury [13].

Optimal treatment of the resuscitated patient includes early coronary reperfusion and haemodynamic optimization if necessitated, control of ventilation, blood glucose control, temperature control and the treatment of seizures [1]. In this hypothesis, we propose an additional pharmacological approach to the post resuscitation syndrome with statins and their pleiotropic effects for suppression of the exacerbated inflammatory/coagulation disorder.

Section snippets

Hypothesis

In addition to the lipid profile adjusting function of the 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors or statins, they also exert effects independent of lipid metabolism via inhibition of isoprenoid synthesis [14], [15]. These pleiotropic effects are numerous and some may have a beneficial role in the post resuscitation phase. We have postulated a hypothesis that administrating statins immediately after cardiac arrest and resuscitation, or more preferably, already during the

Discussion

We propose four intertwined injury cascades of post resuscitation syndrome with potential for treatment with HMG CoA reductase inhibitors more commonly known as statins. Although the present data to support our hypothesis are mainly derived from clinical and experimental studies on cardiovascular diseases and focal ischaemia, there is evidence that similar injury cascades potentially responsive to statins are present in human cardiac arrest victims also [2], [3], [11], [12]. This hypothesis

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