The first step in cardiac arrest management is clearly to achieve return of spontaneous circulation (ROSC). However, there are many important steps in the management from here that can maximise the chances of a good outcome.
There is a complex chain of events within the body following cardiac arrest relating to the initial ischaemic insult and subsequent reperfusion effects. This produces the post-cardiac arrest syndrome:
Post-cardiac arrest brain injury
Post-cardiac arrest myocardial dysfunction
Systemic ischaemic/reperfusion response
Persisting initial pathology e.g. coronary vessel disease
The extent of this is generally related to the nature and duration of the initial arrest and will impact on the degree of multi-organ dysfunction and support needed after ROSC. It is similar to sepsis in this regards and needs support in a similar way. Importantly, optimisation of this support can hopefully mitigate some of the negative aspects of this syndrome and improve outcome e.g. targeted temperature management.
Click here for the Resuscitation Council (UK) guidance
Post-cardiac arrest brain injury
The brain is particularly vulnerable to injury following cardiac arrest, hence the high incidence of neurological complications following such an event. This is through a combination of its vulnerability to ischaemia and its unique response to reperfusion. These mechanisms include: excitotoxicity, disrupted calcium homoestasis, free radical formation, pathological protease cascades, and activation of programmed cell death pathways. As noted, this pathway of injury is prolonged beyond the initial arrest period, opening up the potential for neuroprotective strategies. Following the initial period of ischaemia, during which microthrombi can form, there is generally a period of hyperaemia with the resumption of cardiac output. However, there is also suggestion of general microcirculatory failure, with areas of hypoperfusion persisting, despite what would appear to be an adequate perfusion pressure. Indeed, there seems to be a clear loss of the autoregulation that couples local blood blow with local metabolic activity, and hence the change in flow to be more dependent on cerebral perfusion pressure. These circulatory changes often lead to a period of cerebral oedema following the arrest, but this tends to have little effect on intracranial pressure.
Post-cardiac arrest myocardial dysfunction
This dysfunction of the myocardium following a cardiac arrest can contribute to mortality and morbidity following the arrest, yet appears to be a reversible phenomenon that is responsive to treatment. It is described as a ‘myocardial stunning’ in that it isn’t related to persisting ischaemia or infarction. This follows a pattern seen in more chronic myocardial failure, with a reduced ejection fraction and elevated end diastolic pressures. The detrimental effects occur rapidly following the arrest (within 30 mins) appear to peak at 8 hours, with recovery between 24 and 48 hours later. The use of dobutamine infusions seem to help reverse the systolic and diastolic dysfunction seen in this state.
Systemic ischaemic/reperfusion syndrome
The loss of perfusion to the bodies tissue causes a significant impact due to loss of oxygen delivery and removal of metabolic waste products. Even high quality CPR fails to combat these effects, which will also persist following ROSC due to the suboptimal physiological state. This oxygen debt can lead to activation of the many inflammatory pathways that are also seen in sepsis, with a release of cytokines and endotoxin. Similarly, there is activation of the coagulation cascade, with microthrombus formation in different vessels that can cause persisting microcirculatory perfusion problems. There is also often a period of relative adrenal insufficiency with the subsequent problems. This component of the post-cardiac arrest syndrome requires general supportive care, similar to the sepsis syndrome.
The prognosis of a cardiac arrest is generally grim, but even those that achieve ROSC still have a fairly poor prognosis. The survival to hospital discharge of comatose cardiac arrest survivors seems very variable, being quoted at somewhere between 30 – 50% (1,4). Many of these actually have a fairly good neurological status, but there is often some cognitive impairment. There is minimal evidence to suggest that survival rates have really changed recently with advances in critical care management. The incidence of clinical brain death following cardiac arrest is between 8 – 16% (4) Cardiovascular failure is the most common cause of early death (within 3 days). Post-cardiac arrest brain injury is the most common cause of later deaths. Withdrawal of care is also an important cause of death in this later group (around 50% of deaths (1)), as prognostication in these patients is very important given the potentially very poor neurological outcomes. Other causes of late deaths include multi-organ dysfunction and sepsis.
An initial A to E approach is recommended, as is common to the varied resuscitation strategies and protocols.
Airway & Breathing
Hypoxia is both a potential cause of cardiac arrest and a contributor to post arrest tissue injury. Hence is should be a priority to ensure adequate oxygenation. In patients who are obtunded post-arrest, this will often mandate definitive airway control i.e. intubation and ventilation. However, patients who have had a very short arrest may have a rapid recovery of conscious level and need only facemask/nasal oxygen. There is some weak evidence that hyperoxia is also associated with a worse neurological outcome following cardiac arrest. There is also evidence that this is the case for increased myocardial injury too. This is suggested to be particularly the case for early hyperoxia (first hour after arrest). Control of CO2 levels (and therefore control of ventilation) is also important. There is suggestion that hypocapnia can lead to reflex cerebral vasoconstriction, and therefore impaired perfusion and worse outcomes. Mild hypercapnia may actually be beneficial for the converse reason but this is not yet clearly demonstrated, and hence a target of normocapnia is recommended. It is important to remember the importance of general good ventilation management e.g. lung-protective volumes. Short term sedation +/- paralysis is likely needed for this. It is suggested that short term paralysis (<48 hours) will not increase the risk of ICU related weakness. Care must be taken to not mask seizure activity though. Therefore:
Achieve definitive airway control if patient remains comatose post-arrest
Target supplementary oxygen therapy to SpO2 of 94-98%.
Provide lung protective ventilation – tidal volume of 6-8ml/kg ideal body weight and PEEP of 4-8 cm H20.
Provide sedation +/- paralysis to tolerate this, ensuring appropriate monitoring for this.
Insert on NG tube to decompress the stomach and optimise ventilation.
Routinely perform a CXR to assess for post resuscitation complications and ETT placement
There is often post-arrest myocardial and vascular dysfunction that can manifest as hypotension and reduced cardiac output, as well as arrhythmias. There is often need for fluid resuscitation initially, and this is generally well tolerated. Persisting dysfunction may require introduction of vasopressors or inotropes. Early and serial echocardiography can help guide management in this regard. Use of an intra-aortic balloon pump may also be considered, though the evidence for its benefit remains inconclusive. The targets for this therapy remain unclear but a composite of targets seems reasonable – ensuring adequate urine production (1ml/kg/hour), lactate clearance, a blood pressure target guided by the patients normal BP, heart rate, mixed venous oxygen saturations. Bradycardia has been suggested to be associated with a good outcome so when present (e.g. associated with hypothermia) shouldn’t be treated unless compromising cardiac output. Hypokalaemia predisposes to dysrhythmias and so K+ levels should be targeted to 4.0 – 4.5 mmol/L.
The role of coronary reperfusion therapy seems to be slightly controversial. The prevalence of an acute coronary lesion is quoted as 59-71% in cases of OOHCA without an obvious non-cardiac cause. This is higher than 80% in patients with ST elevation or left bundle branch block on their post arrest ECG. The evidence isn’t strong but it suggests that these patients should go for early primary percutaneous coronary intervention (PCI) and that their neurological state at this time shouldn’t be an influencing factor. Indeed, observational studies have reported the best outcomes with a combination of targeted temperature management and early PCI. This is less clear for those without ST elevation. These patients may still have a primary cardiac cause of their arrest, but this is less easy to approach with the traditional approach to NSTEMI.
Perform ECG to assess for cardiac cause of arrest and help decisions on PCI
Perform early echocardiography to help assess extent of myocardial dysfunction
Cary out adequate fluid resuscitation
Establish invasive blood pressure monitoring.
Commence appropriate vasopressors/inotropes to achieve adequate organ perfusion depending on nature of any circulatory compromise - based on a composite of target values (urine output, lactate values, normal BP values)
Strongly consider early PCI in patients with ST elevation or LBBB, and consider it for patients without these features but a strong suspicion of a primary cardiac cause of their arrest.
Alternative causes of the arrest should be investigated if a primary cardiac cause isn’t suspected e.g. CTPA
This is a vital component of the management to optimise the chances of a good neurological outcome.
Cerebral Perfusion There is a high potential for loss of cerebral autoregulation following the cardiac arrest insult, meaning that cerebral perfusion will be more dependent on mean arterial blood pressure (MAP). As such it is generally recommended to maintain a MAP close to the patient’s normal blood pressure.
Sedation This is generally required to tolerate the impact of therapeutic hypothermia or other interventions and so should be considered on this basis. Sedation will also provide the theoretical benefit of a reduced cerebral metabolic rate. Shorter acting sedatives have the benefit of allowing earlier neurological assessment and prognostication.
Seizures These are relatively common in patients following cardiac arrest, occurring in about one third of patients. Myoclonus is the most common manifestation (about 20-25%) The activity may not always be clinically detectable, though the benefits of actively searching for them remains unclear. Seizure activity increases cerebral metabolic demands and so have the potential to exacerbate the brain injury. As such it is recommended that they are treated – valproate, leviteracetam, phenytoin, propofol and barbituates are all potential drugs of choice. Routine prophylaxis isn’t recommended though.
Glucose Control There is evidence that hyperglycaemia is associated with worse outcomes for patients following cardiac arrest. However, hypoglycaemia is similarly harmful, with comatose patients being at particularly at risk, and this is often an inadvertent effect of strict glucose control. As such, glucose should a less restrictive control of glucose is advocated to balance these risk, aiming to keep the glucose below 10 mmol/L and avoid hypoglycaemia.
Temperature Management There is fairly good evidence that pyrexia in the 48 hours following cardiac arrest is associated with a worse outcome. There is suggestion that hypothermia is neurologically protective. The theory behind this is that hypothermia reduces cellular apoptosis, metabolic rate and responsiveness to damaging excitotoxin exposure, as well as reducing the production of damaging injury products such as free radicals. Being cool before a cardiac arrest is pretty well established as protective, but this is usually only found in animal studies or ice water drowning and so of less clinical relevance. Some initial trials provided fairly strong support for this, though the latest large trial suggests minimal benefit from 33oC compared to 36oC. There has been variable discussion about the meaning of this, but current advice focuses more on the clear benefits of avoiding hyperthermia. As such, recommendations have advocated a temperature of 32 to 36oC after cardiac arrest. The duration of this is similarly unclear, but at least 24 hours is recommended, with avoidance of pyrexia (Temp >37.5oC) for 72 hours. 36oC is generally the temperature that is targeted due to the greater ease with management (less vasopressor requirement, shorter rewarming period, reduced risk of rebound hyperthermia) The method of initiating and maintaining cooling is very variable, including simple methods such as ice packs and cooled fluid, though to external and internal cooling systems with feedback to temperature measurement. The process of rewarming can cause complications (e.g. electrolyte shifts) and so a rate of 0.25 – 0.5oC is recommended.
There are several effects of hypothermia which need managing and monitoring:
Shivering – a normal physiological response which may need controlling to help achieve cooling. Sedation, neuromuscular blockade and magnesium can prove effective at managing it.
Bradycardia – can be beneficial (like beta blockers) and shouldn’t be treated unless affecting cardiac output.
Hyperglycaemia – due to decreased insulin sensitivity and reduced secretion. May require intervention as noted above.
Reduced immune system activity – increased number of infections, including pneumonia. Needs close monitoring and early antibiotic treatment.
Coagulopathy – Impairs clotting function but the impact of this seems to be minimal.
Amylase rise – of unclear significance.
Reduced drug clearance – this can be by up to 30%.
In summary for neurological protection:
Provide targeted temperature management (with a target of 32 – 36oC) as soon as possible for at least 24 hours.
Avoid pyrexia for the first 72 hours.
Implement management to keep blood glucose levels below 10 mmol/L but avoid hypoglycaemia
Maintain an adequate cerebral perfusion pressure based on the patient’s baseline BP.
Diagnose and treat seizures.
Provide appropriate sedation to tolerate interventions, preferably short acting.
This is an important step given the high incidence of significant neurological injury that results from cardiac arrest. This is quite detailed and is covered here. In general, it requires a delay until 72 hours after ROSC and then assessment for features that are reliably associated with a poor outcome.
This will be commonly required to optimise the outcome for these patients as there is a high incidence of cognitive and psychological sequelae, as well as the physical impact of the illness.
The high incidence of poor neurological outcomes in these patients means that there are frequent scenarios where consideration of organ donation may be appropriate. There is great potential for conflict of interest with the treating clinicians but there is often support available from specialist organ donation teams e.g Specialist nurse in organ donation (SNOD).