**9. Side effects of cooling**

82 Coronary Interventions

Fig. 5. Endovascular catheter cooling via CoolGard 3000TM and Icy femoral cathether TM, Alsius Corp., Irvine, USA. Published with the permission of P. Ostadal, M.D., PhD.,

It can be used also for controlling normothermia after the rewarming phase and guide the patients through the whole early post-resuscitation period. Cooling efficacy and safety was documented not only for cardiac arrest patients but also for patients with traumatic brain injury, stroke and acute myocardial infarction (Diringer et al., 2004; Schmutzhard et al., 2002; Lyden et al., 2005; Guluma et al., 2008; Georgiadis et al., 2001; Keller et al., 2003; De Georgia et al., 2004; Dixon et al., 2002; Kandzari et al., 2004; Stone et al., 2006). Dixon et al. randomized 42 patients with AMI to primary PCI with or without endovascular cooling (target core temperature 33 degrees C) for 3 hours after reperfusion. Reduction of infarct size ws not identifyed but the study confirmed the safety of endovascular cooling as an adjunct to primary PCI. Kandzari et al. reached similar results in a nonrandomized study of 18 patients. Intranasal cooling is a new and safe method to easily cool down the brain. It is a very simple method with minimal burdening of the staff (Castrén et al., 2010). Like RIVA, it is convenient for the rapid induction of TH and suitable for pre-hospital care and emergency

There are many other experimental thermoregulatory methods. Some of them, like cardiopulmonary bypass, femorocarotic bypass with extracorporeal cooling of blood, peritoneal cooling or total liquid ventilation cooling are too invasive and/or complicated in comparison with the current effective techniques (Reed et al., 2002; Mori et al., 2001; Hong et al., 2002; Xiao et al., 1995). The others are just in the beginning of their development and perhaps represent the future. On the gate of science-fiction stands the possibility of pharmacological induction of hibernation. Hibernation is a behavioural, physiological, and molecular adaptation exhibited by diverse mammalian species to withstand protracted periods or seasons of insufficient or unpredictable food availability (Kelly, 2007). Distribution of this process amongst different species argues that hibernation genes required for hibernation are common to all mammals (Srere et al., 1992). Such capacity to profoundly

Department of Cardiology, Na Homolce Hospital, Czech republic.

medicine departments.

TH treatment may be associated with adverse events (Table 8) (Polderman et al., 2009; Skulec et al., 2008; Nielsen et al., 2009). These are related to the cooling device or caused by hypothermia itself. While the former are rare, the latter are quite common. However, we should keep in mind the fact that some of them are physiological responses to hypothermia rather than avderse events.


Table 8. Adverse effects of therapeutic hypothermia (Nielsen et al., 2009).

Often, it is not possible to distinguish whether the event is caused by hypothermia or by post-cardiac arrest syndrome itself. This is especially the case of post-cardiac arrest shock syndrome. It may affect as much as 18 – 50% of cardiac arrest patients. Although TH induces cold diuresis, hypovolemia, bradycardia and decrease of cardiac output, post-cardiac arrest myocardial dysfunction and precipitating pathology arises independently of TH and all must be treated together. It was shown that TH does not worsen the course of the disease even in the presence of shock syndrome (Škulec et al., 2008). Pneumonia, cardiac arrhythmias, metabolite disturbances and seizures have been identified as the most common adverse events of cooling.

Recently, Nielsen et al analyzed a set of 765 patients and identified that sustained hyperglycaemia and seizures are associated with increased mortality while other adverse events are not (Nielsen et al., 2011). Randomized clinical studies showed comparable incidence of adverse events except for pneumonia and sepsis, which exhibited a trend of increased appearance in cooled patients (Hypothermia after Cardiac Arrest Study Group, 2002; Bernard et al., 2002).

Therapeutic Hypothermia in Cardiac Arrest Survivors 85

unnecessary hyperoxia should be avoided. This can be achieved by adjusting the FiO2 to produce an arterial oxygen saturation of 94 – 96% (Nolan et al., 2008). Secondly, in braininjured patients, cerebral vasoconstriction caused by hyperventilation may induce cerebral ischaemia (Coles et al., 2007). Hyperventilation also decrease cardiac output via increased intrathoracic pressure (Aufderheide & Lurie, 2004). On the other hand, hypoventilation may cause hypoxia and hypercapnia could increase intracranial pressure and cause acidosis. Therefore, ventilation should be adjusted to achieve normocapnia and should be monitored

Seizures and/or myoclonus occur in 10–40% of succesfully resuscitated comatose cardiac arrest patients. It increases oxygen demand dramaticaly and may aggravate neurological injury (Ingvar, 1986). It should be treated after the first event and followed by maintainance therapy. Drugs of choice are benzodiazepines, phenytoin, sodium valproate, propofol, or a

Treatment of other conditions like adrenal dysfunction, organ dysfunctions and infection

It has been recommended that the target therapeutic temperature should be reached as soon as possible (Safar, 2002). In successfully resuscitated out-of-hospital cardiac arrest (OHCA) patients, pre-hospital initiation of cooling appears to be the method of choice. However, initiation of cooling in the field is not a simple shift of in-hospital procedure to pre-hospital area. A pre-hospital emergency team frequently operates in demanding conditions and is engaged in the process of cardiopulmonary resuscitation, early post-cardiac arrest stabilisation and decision on transport direction. Therefore, pre-hospital cooling calls for a very simple, efficient and safe cooling method and its usage should not cause a transport delay. A background of regional hospitals practicing TH is essential to ensure cooling continuity.

A few studies demonstrating the efficacy and safety of this strategy, predominantly for the RIVA method, have been published (Kim et al., 2007; Kämäräinen et al., 2008). When performed properly, it can decrease BT by >1.4 °C during transport. Moreover, a dose of 10 – 20 ml/kg of cold normal saline can contribute to hemodynamic stabilization. In addition, this way of cooling exhibits an excelent safety profile with minimal risk of volume overload. Considering its simplicity and low costs, the RIVA method is the first choice for pre-hospital

A major barrier for a wide recommendation of pre-hospital cooling in successfully resuscitated OHCA patients is the absence of clear evidence of the outcome benefit. Apparently, improved survival is not related to pre-hospital hypothermia itself but to the close coupling of PTH with its in-hospital continuation (Škulec et al., 2010; Castrén et al.,

Considering the pros and cons, at present, in the setting of proper collaboration of the emergency medical service and the target in-hospital facility, it is justifiable to implement prehospital cooling even in the absence of unambiguous evidence to support this practice. Other possibilities suitable for pre-hospital cooling include surface cooling via

by regular measurement of arterial blood gas values (Nolan et al., 2008).

barbiturate (Nolan et al., 2008). Preventive treatment has not been studied yet.

therapy do not differ from common practice in critically ill patients.

2010). In any case, a large randomized trial is required.

manufactured cooling pads and intanasal local brain cooling.

**11. Pre-hospital cooling** 

cooling (Figure 6).

Device related adverse events depend on the cooling method. Surface cooling may be complicated by frostbite, the RIVA method may lead to volume overload and pulmonary oedema, endovascular catheter cooling may be complicated by deep venous thrombosis (Škulec et al., 2009). The occurance of these can be minimalized by proper and careful practicing of TH.

### **10. Complex post-cardiac arrest intensive care**

An intensivist should be aware of the fact that TH is not a self-salvable technique after cardiac arrest. Care must be contextualized to the complex neuroprotective and cardioprotective post-cardiac arrest support. The main components are:


It has been shown by Sunde et al that a transition from the conventional passive approach to the standardised active treatment protocol including all mentioned items can improve prognosis of the patients (Sunde et al., 2007). Further studies have confirmed this observation (Škulec et al., 2008; Tømte et al., 2011; Werling et al., 2007). Thus, it is of major importance to consider every cardiac arrest patient as to be like any other critically ill patient requiring complex, active and protocolized therapy, beyond the scope of isolated TH procedure.

The most sophisticated component of such approach is the ensurance of availability of immediate coronary angiography and PCI. At present, the discussion is held whether all OHCA patients should be transfered to cardiac arrest centers with PCI facility or not. To answer this question needs further studies. Nevertheless, all patients with supposed cardiac origin of cardiac arrest are candidates of such approach and those with ST elevation acute myocardial infarction undoubtly.

There is an association between post-cardiac arrest hyperglycaemia and poor neurological outcome. However, tight glucose control (4.5 – 6.0 mmol/l) should not be practiced after cardiac arrest because of the increased risk of hypoglycaemia. Blood glucose should be maintained at ≤10mmol/l (Padkin, 2009; Deakin et al., 2010).

Early haemodynamic goal-directed therapy has been shown to improve prognosis of patients with severe sepsis and septic shock (Rivers et al., 2001). There is limited evidence that this approach can be also benefitial to cardiac arrest survivors (Gaieski et al., 2009). Reasonable goals are listed in table 4.

Several reasons make control of normoventilation an important part of post-cardiac arrest care. Firstly, while during cardiopulmonary resuscitation we should maintain FIO2 of 1.0, it is not the setting for post-cardiac arrest care. There is a body of preclinical evidence that hyperoxia may worsen neuronal ischemia-reperfusion injury by augmenting oxidative stress (Balan et al., 2006). On this basis, it is recommended to eliminate hypoxia but

Device related adverse events depend on the cooling method. Surface cooling may be complicated by frostbite, the RIVA method may lead to volume overload and pulmonary oedema, endovascular catheter cooling may be complicated by deep venous thrombosis (Škulec et al., 2009). The occurance of these can be minimalized by proper and careful

An intensivist should be aware of the fact that TH is not a self-salvable technique after cardiac arrest. Care must be contextualized to the complex neuroprotective and

It has been shown by Sunde et al that a transition from the conventional passive approach to the standardised active treatment protocol including all mentioned items can improve prognosis of the patients (Sunde et al., 2007). Further studies have confirmed this observation (Škulec et al., 2008; Tømte et al., 2011; Werling et al., 2007). Thus, it is of major importance to consider every cardiac arrest patient as to be like any other critically ill patient requiring complex, active and protocolized therapy, beyond the scope of isolated TH

The most sophisticated component of such approach is the ensurance of availability of immediate coronary angiography and PCI. At present, the discussion is held whether all OHCA patients should be transfered to cardiac arrest centers with PCI facility or not. To answer this question needs further studies. Nevertheless, all patients with supposed cardiac origin of cardiac arrest are candidates of such approach and those with ST elevation acute

There is an association between post-cardiac arrest hyperglycaemia and poor neurological outcome. However, tight glucose control (4.5 – 6.0 mmol/l) should not be practiced after cardiac arrest because of the increased risk of hypoglycaemia. Blood glucose should be

Early haemodynamic goal-directed therapy has been shown to improve prognosis of patients with severe sepsis and septic shock (Rivers et al., 2001). There is limited evidence that this approach can be also benefitial to cardiac arrest survivors (Gaieski et al., 2009).

Several reasons make control of normoventilation an important part of post-cardiac arrest care. Firstly, while during cardiopulmonary resuscitation we should maintain FIO2 of 1.0, it is not the setting for post-cardiac arrest care. There is a body of preclinical evidence that hyperoxia may worsen neuronal ischemia-reperfusion injury by augmenting oxidative stress (Balan et al., 2006). On this basis, it is recommended to eliminate hypoxia but

practicing of TH.

• therapeutic hypothermia,

• control of blood glucose,

• control of seizures.

procedure.

• control of normoventilation,

myocardial infarction undoubtly.

Reasonable goals are listed in table 4.

**10. Complex post-cardiac arrest intensive care** 

• urgent coronary angiography and PCI if indicated,

maintained at ≤10mmol/l (Padkin, 2009; Deakin et al., 2010).

• early haemodynamic goal-directed therapy,

cardioprotective post-cardiac arrest support. The main components are:

unnecessary hyperoxia should be avoided. This can be achieved by adjusting the FiO2 to produce an arterial oxygen saturation of 94 – 96% (Nolan et al., 2008). Secondly, in braininjured patients, cerebral vasoconstriction caused by hyperventilation may induce cerebral ischaemia (Coles et al., 2007). Hyperventilation also decrease cardiac output via increased intrathoracic pressure (Aufderheide & Lurie, 2004). On the other hand, hypoventilation may cause hypoxia and hypercapnia could increase intracranial pressure and cause acidosis. Therefore, ventilation should be adjusted to achieve normocapnia and should be monitored by regular measurement of arterial blood gas values (Nolan et al., 2008).

Seizures and/or myoclonus occur in 10–40% of succesfully resuscitated comatose cardiac arrest patients. It increases oxygen demand dramaticaly and may aggravate neurological injury (Ingvar, 1986). It should be treated after the first event and followed by maintainance therapy. Drugs of choice are benzodiazepines, phenytoin, sodium valproate, propofol, or a barbiturate (Nolan et al., 2008). Preventive treatment has not been studied yet.

Treatment of other conditions like adrenal dysfunction, organ dysfunctions and infection therapy do not differ from common practice in critically ill patients.
