Since the release of the 2005 Resuscitation Council (UK) guidelines (Nolan J et al, 2006) there has been an emphasis on the active management of the physiological derangement that follows Return of Spontaneous Circulation (ROSC). This has occurred because despite increasing number of patients achieving ROSC, the number of patients leaving hospital neurologically intact has not increased by a similar magnitude (Nolan et al, 2007; 2008) As a result, clinicians are now focusing their attention on what is perceived to be the weak link in the ‘chain of survival’.
In 1966, Friedrich Wilhelm Ahnefeld coined the phrase ‘rescue chain concept’, which was the original German name for the ‘chain of survival’ (Baskett and Baskett, 2007). Since then, clinician have been striving to reduce the number of deaths from sudden cardiac arrest and with the clinical advancements that have been made in the intervening years, it would be logical to conclude that hospital discharge rates would have increased dramatically. However, survival rates to hospital discharge after OHCA are still only 7–10 % (Nolan et al, 2007, 2008). A review conducted in 2008 by The International Liaison Committee On Resuscitation (ILCOR), found considerable variation in patient management outcomes in the post cardiac arrest phase. They also identified that where protocols existed to standardize post resuscitation care across the multidisciplinary team, the institutions involved demonstrated improved outcomes (Nolan et al, 2008). More recently, the Department of Health has introduced a series of clinical performance indicators for ambulance trusts, including ROSC on arrival at hospital and survival to discharge following OHCA (Ambulance Statistics Team, 2011). This makes a review of treatment guidelines for the last link in the chain of survival, post resuscitation care, necessary.
Post resuscitation care
Following ROSC the patient undergoes a number of pathophysiological processes not dissimilar to those suffered during severe sepsis (Adrie et al, 2004). This has been termed Post Cardiac Arrest Syndrome (PCAS) and can include loss of vasomotor control, thermal regulation and cardiogenic dysfunction. ILCOR have listed 4 key components of PCAS:
It is important to note that this insult does not occur in all patients or to the same degree. The earlier ROSC is obtained after cardiac arrest, the less likely PCAS is to occur, as whole body ischaemia has not had time to develop. However, in the presence of co-morbidities, the time to ischaemic injury may be significantly shorter.
There are four time phases related to the management PCAS following ROSC:
As pre-hospital clinicians, we are most concerned with the immediate and early phases of PCAS and management is focused towards preventing recurrence of cardiac arrest, limiting ongoing injury and providing organ support.
Eigel et al (2010) and Peberdy et al (2010) have identified six treatment recommendations that direct therapy of PCAS:
Normal oxygenation
In recent years, concerns have been raised that uncontrolled oxygen therapy may cause an increase in mortality and morbidity due to oxidative damage to proteins, lipids and Deoxyribonucleic acid (DNA). In 2008, the British Thoracic Society recommended that in the post cardiac arrest phase, patients should receive titrated oxygen therapy with a target saturation of 94-98 % (O’Driscoll et al, 2008). Subsequently, Kilgannon et al (2010) demonstrated that post-resuscitation hyperoxia increased mortality when compared to normoxia. It is thought that mitochondrial superoxide production is partly responsible for this, as superoxides are one of a number of chemically reactive molecules containing oxygen. Collectively, these molecules are known as reactive oxygen species (ROS) or oxygen free radicals, and are a by-product of normal aerobic metabolism.
Under normal haemostatic conditions, cells are able to defend themselves against damage from ROS thanks to enzymes such as peroxiredoxins, catalases and superoxide dismutases. These enzymes do not provide complete protection for the cells and over time, ROS accumulate damaging the cell DNA and ribonucleic acid (RNA) irreparably, as part of the normal ageing process. However, in a cardiac arrest where whole body aerobic metabolism is interrupted for a prolonged period, the protective enzymes become inactive, increasing levels of ROS and leading to oxidative stress. Severe oxidative stress causes necrosis due to adenosine tri-phosphate (ATP) depletion, which prevents apoptosis and results in complete cell disintegration. Reducing the levels of ROS can be facilitated by maintaining the oxygen saturations of post-ROSC patients within the range of 94-98 %.
Normal ventilation
During resuscitation, it is common for patients to be hyperventilated due to inappropriately high ventilation rates and volumes provided by rescuers (Aufderheide and Lurie, 2004; O’Neill and Deakin, 2007). It also well recognized that as a result of hyperventilation, post-ROSC patients have lowered partial pressures of carbon dioxide (pCO2), causing vasospasm of the cerebral blood vessels, reducing blood flow and contributing to hypoxic brain injury. In addition, excessive intrathoracic pressure reduces venous return and cardiac output. Bag-valve-mask (BVM) ventilation prior to definitive airway management results in significant quantities of air entering the stomach and the subsequent gastric insufflation can impede diaphragmatic movement, further compromising ventilation. It has also been noted that excessive lung inflations and/or high airway pressures increase the risk of barotrauma and may lead to the release of inflammatory mediators from the lung parenchyma (ARDSN (Acute Respiratory Distress Syndrome Network), 2000; Nolan et al, 2008; Peberdy et al, 2010).
To avoid these complications, post-ROSC patients should generally be ventilated at a tidal volume of approximately 7-8 mls per kilogram, an airway pressure below 35 mmH2O and at a rate of 10 breaths/min (ARDSN, 2000; Nolan et al, 2008; Peberdy et al, 2010). Decompression of the stomach with an oro-gastric tube may reduce the degree of diaphragmatic splinting caused by a hyper-inflated stomach, although this is often more problematic in the paediatric population (Maconochie et al, 2011).
The use of capnography is crucial in guiding ventilatory requirements during OHCA and during the post-ROSC phase. Capnography can give an indication that ROSC has occurred due to sudden increases in end-tidal CO2 (EtCO2) levels (Booth and Bloch, 2011; Nolan et al, 2011), even before a palpable output. Initial levels of EtCO2 are often high (>50 mmHg, 6.7 kpa) due to the sudden washout of carbon dioxide from the peripheral circulation that accumulates as a result of poor circulation. A number of studies have indicated that there is a weak correlation between EtCO2 and the partial pressure of arterial carbon dioxide (PaCO2) (Corbo et al, 2005; Delerme et al, 2010). However, it is sufficiently accurate to guide practitioners in controlling the ventilatory requirements of their patient. A target EtCO2 of 35-40 mmHg (4.6-5.3kpa) correlates with a reduction in PaCO2 that will facilitate an appropriate blood pH. Waveform capnography and SpO2 monitoring together, can aid the practitioner in delivering ventilations and supplemental oxygen at levels that will reduce the impact of the pathophysiological processes. Ventilation of post-ROSC patients aim to produce chest wall movement that is not excessive. This can be achieved by estimating the patient’s weight so that the ventilator produces volumes appropriate to the patient size and physiological needs.
Haemodynamic optimization
The first line of management for hypotensive patients post-ROSC is to improve right ventricular filling (Nolan et al, 2008) by taking advantage of the Frank-Starling mechanism. In the absence of significant pulmonary oedema, this is best achieved by the administration of 1.5-2.0 litres of cold sodium chloride 0.9 %, which, in addition to assisting in the reversal of hypotension also reduces core temperature.
Poor haemodynamics post-ROSC is not purely a result of inadequate myocardial function. Systemic ischemia and reperfusion are also partly responsible, creating a clinical picture similar to severe sepsis (Jacobshagen et al, 2010). As with sepsis, there is often haemodynamic instability requiring considerable volume expansion (Adrie et al, 2004). The goal of any fluid replacement should be a central venous pressure (CVP) of 8-12 mmHg. Due to the difficulty of measuring CVP in the pre-hospital environment, an alternative target is a mean arterial pressure (MAP), which is displayed on most non-invasive blood pressure monitors. A target MAP of 65-100 mmHg (Nolan et al, 2008) can be achieved with fluid challenges or small aliquots of inotropes such as adrenaline 1:100,000, for those practitioners experienced in doing so.
Inotropes should be used with care, as agents such as adrenaline are both inotropic and chronotropic in their actions, leading to increased myocardial oxygen demand which can cause further damage to the myocardium and increase infarct size. Therefore, it is important to understand the α and (β affects of adrenaline when given intravenously to a haemodynamically unstable patient. For this reason, this method of haemodynamic support should only be used by practitioners with experience of using such agents in patients with spontaneous circulation.
Another key intervention in post-ROSC patient care is the management of peri-arrest arrhythmias due to an irritated myocardium. Termination of tachy-arrhythmias, either by DC cardioversion in unconscious unstable patients, or by the use of pharmacological interventions in stable patients (amiodarone, for example) should be undertaken. Brady-arrhythmias will also need to be controlled with atropine or external pacing by appropriately trained practitioners.
Moderate glycaemic control
As a result of intravenous (IV) administration of adrenaline during cardiac arrest, vascular levels of glucose can be significantly elevated (Heringlake et al, 2007) due to the effects of adrenaline on cc-adrenergic receptors. This results in inhibition of insulin secretion by the pancreas, glycogenolysis in the liver and muscles, and also glycolysis in the muscles.
Although a study in 2001 suggested that tight glycaemic control of critically ill surgical patients reduced mortality (Van De Berghe et al, 2001), their findings have not been supported through subsequent research and with the publication of NICE-SUGAR trial (Finfer et al, 2009), the concept of tight glycaemic control lost credibility. However, large and rapid swings in glucose levels are undesirable as it is a fundamental requirement of metabolism, therefore, blood glucose levels should be ascertained as soon as is practical during cardiac arrest, since hypoglycaemia is a reversible metabolic disorder which may have contributed to the cardiac arrest initially. Post-ROSC, blood glucose should be reassessed, particularly if hypoglycaemia was present during the arrest as even supplemental glucose may have been metabolised. Where blood glucose levels are high during the arrest or in the post-ROSC phase, it is important to handover this information, since the treatment of the hyperglycaemia is an important step in neuro-protection of the patient.
Therapeutic hypothermia
Therapeutic hypothermia (TH) has been advocated by the resuscitation guidelines since 2003 (Nolan et al, 2003) after two studies demonstrated that improved neurological outcomes could be achieved by cooling patients to a core body temperature of 32 °-34 °C (Bernard et al, 2002; Holzer et al, 2002). However, there are even earlier studies conducted (Benson et al, 1959) that demonstrated a benefit of this technique. The implementation of this treatment in the prehospital environment is still in its infancy, although practitioners are already accustomed to the problems that hypothermia can cause in trauma patients, and there are similar issues in post-ROSC patients too (Table 1).
Despite these problems, TH offers substantial benefits and it appears that the earlier cooling is initiated the better the outcome, supporting the use of cooling in the pre-hospital setting (Nolan et al, 2011).
Two key considerations regarding TH are the mechanism by which the patient is cooled and the method of monitoring patient temperature during transport. There are multiple ways in which cooling can be achieved, from the expensive and highly technical, to simple and cheap methods which require no additional clinical skills (Glencorse and Glencorse, 2011). The easiest way to start cooling a patient is to strip them completely and allow them to cool through convection, and this can be supplemented by using air conditioning in the saloon area of the vehicle. In addition, cold water soaked sheets over the patient and/or the use of wrapped ice packs in the groin, axilla and back of neck will also improve temperature reduction via evaporation. A more invasive method to cool the patient is to use cold intravenous fluids. Whichever method is used, care should be taken not to cool the face or head directly as this can cause inaccurate temperature readings from tympanic thermometers, which are the easiest way to confirm patient temperature. However, they can give false readings if the ear has liquid in the canal or is blocked by cerumen (Alzaga et al, 2006). Even if there is no facility to implement TH, pyrexia should be prevented, as this has serious neurological sequelae, which increase for every degree above 37 °C (Nolan et al, 2008)
Nolan et al (2008) advised that where a patient shows no improvement in their level of consciousness 5–10 minutes post-ROSC, then they should be sedated and paralysed. These procedures will help reduce core body temperature since the patient will not be able to shiver, which would increase oxygen and metabolic demands. Sedation and paralysis will also facilitate endotracheal (ET) intubation, further protecting the airway and enabling greater control of the patient’s ventilations, and furthermore will also reduce the likelihood of arrhythmias caused by activation of the gag reflex as an ET tube is placed. Sedation and paralysis is not without risk however, and it is essential that waveform capnography is in place before these procedures are undertaken by appropriately qualified and experienced practitioners. Pre-hospital providers who do not have this skill set should consider the need to call upon those who do. TH may reduce the incidence of post-ROSC seizures, however, should seizures occur, they should still be managed as directed by JRCALC (2006) clinical guidelines.
Coronary reperfusion
Following ROSC, it is important to identify the presence of an acute coronary syndrome (ACS) and obtain a 12 lead ECG. Where ACS is identified or suspected, the patient should be transported to a facility capable of providing percutaneous coronary intervention (PCI) (O’Connor et al, 2010). Emerging evidence suggests that bypassing smaller centres for larger centres of excellence is not detrimental to the patient unless journey times and/or distance are excessive, in which case thrombolysis might still be appropriate (Nolan et al, 2011).
Conclusion
High quality, post-ROSC care includes:
Only by starting to provide the last and substantial link in the chain of survival are we likely to see improved outcomes in post-ROSC patients. Evidence suggests that the implementation of a care bundle throughout the patients’ pathway can significantly reduce mortality (Walters et al, 2011). Pre-hospital personnel can have a significant impact on the post-ROSC patient and achieve the ultimate aim in the chain of survival, discharge from hospital neurologically intact.