Therapeutic strategies in managing cardiac arrest

Updated resuscitation guidelines emphasize the need for minimally interrupted high quality chest compressions as a prerequisite for successful resuscitation outcome.
Resuscitation involves the integration of complex systems and the interdisciplinary coordination of multispecialty emergency and critical care providers.
The immediate period following return of spontaneous circulation (ROSC) is crucial and is dominated by the presence of two critical goals- identification of pathophysiological cause, and the assessment and initiation of time- dependent interventions, directed at preventing recurrent arrest, and improving immediate and long- term outcome.
There is no vasopressor or anti-arrhythmic agent whose use is associated with improved outcome at discharge. In-hospital resuscitation should focus on the provision of high quality chest compressions and the search for immediate treatable precipitants of the arrest in those patients who achieve ROSC.
A systematic checklist may aid in the systematic evaluation of patients following ROSC.

Management after resuscitation from cardiac arrest

Following return of spontaneous circulation, the quality of the treatment provided in the post-arrest period influences outcome.
Most patients resuscitated after a prolonged period of cardiac arrest will develop the post-cardiac arrest syndrome.
All survivors of out-of-hospital cardiac arrest should be considered for urgent coronary angiography unless the cause of cardiac arrest was clearly non-cardiac or continued treatment is considered futile.
Several interventions may impact on neurological out-come, the most significant of these is targeted temperature management.
In patients remaining comatose after resuscitation from cardiac arrest, prediction of the final outcome in the first few days may be unreliable. Prognostication should normally be delayed until at least 3 days after return to normothermia and should involve more than one than one mode (e.g. clinical examination combined with another investigation).

Key components of the post-cardiac arrest syndrome.

Post- cardiac arrest brain injury- this manifests as coma and seizures.
Post- cardiac-arrest myocardial dysfunction –this can be severe and usually recovers after 48 hours.
Systemic ischemia/reperfusion response –tissue reperfusion can cause programmed cell death (apoptosis) effecting all organ systems.
Persisting precipitating pathology-coronary artery disease is the commonest precipitating cause after OHCA

Severe sepsis is the result of an infectious stimulus that triggers a hyper-inflammatory response and results in multiple organ failure. This hyper immune response triggers a phase of immunoparalysis that results in the patient’s inability to resist and clear infections, causing the delayed mortality observed is some septic patients.
The inflammatory and coagulation cascades are closely linked such that a significant aspect of the disease process is attributed to the activation of the coagulation cascade by circulating inflammatory mediators.
Therapeutic approaches to sepsis have targeted the hyper-inflammatory response, inhibition of the subsequent coagulation cascade, and immunostimulation during the immunoparalysis phase.
Proven beneficial therapies for sepsis are limited to the mechanical eradication of the source of infection, antibiotics to clear the organism, the judicious use of fluids to support organ perfusion, and oxygen supplementation. Studies evaluating immunotherapeutics for the treatment of severe sepsis have failed to show efficacy in clinical trials.
Further research may demonstrate effectiveness using a strategy of targeting therapies based on an improved identification of the patient’s phase of sepsis, use of combination therapies, a better understanding and strategy aimed at specific host-organism interactions, and /or better specified therapies in relation to identified biomarkers.

Conclusion:

Studies evaluating the use of immunotherapeutics for severe sepsis are plagued with multiple confounding factors including the pre-dominant phase of sepsis (hyperimmune versus hypoimmune), differing offending organisms, differing host-organism interactions, heterogeneity in the patient populations, and underpowered study designs.
Perhaps the correct immunotherapy will need to be tailored in order to decrease the immune response in the hyperimmune phase and increase it during the hypoimmune phase. In order to do so, better markers of these phases of sepsis are needed. Further studies may also find more efficacy in using multiple therapies simultaneously to obtain best results.
Finally, there exists a close interaction between in the immune and coagulation system. Further study of this link and therapies to temper the coagulation cascade many prove to be a successful modality of therapy in order to halt the body’s progression to multiple organ failure.