13RC2 Post resuscitation care improving outcome

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1 13RC2 Post resuscitation care improving outcome K. Sunde Department of Anaesthesiology and Institute for Experimental Medical Research, Oslo University Hospital Ulleval, Oslo, Norway Saturday, June 6, :00-16:45 Room: Red 2 Background It is estimated that approximately Europeans suffer an out-of- hospital cardiac arrest (OHCA) and are treated by the local Emergency Medical System (EMS) annually [1]. In a report from 37 different European communities, the average survival rate was 10.7%, varying from 5-20% [1]. The huge spread in successful outcome is mainly due to differences in the local chain of survival: early arrest recognition and call for help, early cardiopulmonary resuscitation (CPR), early defibrillation and early post resuscitation care [2]. Whereas CPR and defi brillation have benefi ted from research and focus, post-resuscitation care has, until recently, been regarded as the weak link in the chain of survival [3]. After the publication of two landmark articles showing improved survival after ventricular fibrillation (VF) OHCA treated with mild therapeutic hypothermia (32-34 ºC) for h [4, 5], hospital treatment after return of spontaneous circulation (ROSC) has received more attention. A global ischaemic injury occurs after ROSC - the post-cardiac arrest syndrome, recently described in a consensus statement from the International Liaison Committee on Resuscitation (ILCOR) [6]. This starts a cascade of deleterious infl ammatory reactions in the body that may continue for several days, and treatment directed at improving vital organ function, minimising the infl ammatory response and cell death in the reperfusion period may improve outcome following cardiac arrest [6]. The type of hospital care after ROSC affects outcome [7, 8]. One-month survival among patients admitted to ICU varied from 14-41% in a Swedish study [7], and in Norway survival to discharge varied between 34% and 56% in four different hospital regions [8]. Factors such as high temperature, high blood glucose, presence of seizures and acidosis during the first 24 h were associated with a worse outcome [8]. Moreover, in Stavanger (with the best survival rate) treatment followed a standardised treatment plan, whereas the treatment in the Oslo hospitals (with the worst survival rate) had no systematic plan, depended on the doctor on-call, with patients spread out in different ICUs [8]. In UK, 28.6 % of cardiac arrest patients survived to hospital discharge after being admitted to ICU [9]. New treatment strategy Based on the poor outcome data from Oslo, the promising results with mild therapeutic hypothermia and the recommendations from ILCOR, we reorganised our treatment plan for post-resuscitation care in 2003 and designed a practicable and easy to follow standardised treatment protocol [11]. The main aim was to treat the cause of the arrest early and at the same time to focus on the reperfusion injury to optimise vital organ (brain and heart) function through a multidisciplinary approach including several treatment goals [11]. Table 1 summarises the most important parts of our treatment plan. We focused on the implementation strategy including an intensive information campaign for all participating doctors and nurses, identifi cation of barriers and key-collaborators, availability of a local champion and increased enthusiasm and focus on the patients. Another important aspect was to specialise two ICUs to take care of the patients, instead of the previous six. Continuous feedback to involved personal and close monitoring of complications were important parts of the implementation plan

2 Table 1 Required monitoring and associated treatment goals during the early post-cardiac arrest period. Required monitoring Direct arterial catheter O 2 -saturation Continuous ECG Central venous pressure Treatment goals MAP > mmhg 95-98% bpm 8-12 mmhg Temperature Urine output 33 C for 24h ml.kg.h Arterial blood gases - po 2 - pco 2 - ph - BE Lactate Blood glucose Electrolytes - especially Na, K, Mg, Phosphate 9-12 kpa kpa (± 3) mmol.l < 2.0 mmol.l 5-8 mmol.l Normal values Haemoglobin svo 2 Echocardiography (1-2 times a day) > 9-10 g.dl >70% Haemodynamic optimisation Chest x-ray (daily) EEG if indicated (seizures) (CT/MRI) The following six issues were considered the most important in our new treatment strategy: Early treatment of the cause of the arrest Coronary artery disease is present in the majority of cardiac arrest patients and acute myocardial infarction is the single most common cause [6, 11]. Thus, early coronary angiography with subsequent percutaneous coronary intervention (PCI) should be recommended for primary resuscitated cardiac arrest patients with any evidence of myocardial infarction or severe coronary heart disease [6, 11, 12]. Other causes of arrest, both cardiac and non-cardiac (such as pulmonary embolism, sepsis, hypoxia, hypovolaemia, hypo- or hyperkalaemia, metabolic disorders, accidental hypothermia, tension pneumothorax, cardiac tamponade, toxins or cerebrovascular catastrophes), must be diagnosed early and receive specifi c treatment, were possible. Early mild therapeutic hypothermia Mild hypothermia has been shown to improve survival after VF OHCA [4, 5], mostly due to a reduction in the different pathways leading to global cerebral injury [6]. Hypothermia is the only therapy used in the post-cardiac arrest setting that has been shown to improve survival. The identifi cation of which patients that may benefit, the ideal cooling technique (used alone or in combination), the target temperature, the optimal maintenance technique and rewarming times have yet to be established. We chose to use a combination of different cooling techniques - fast and simple induction with ice cold intravenous fluids and ice packs (placed in the groins, armpits, around the head and neck), and maintenance was continued with either endovascular (Alsius CoolGard 3000/Icy Catheter Heat Exchange System, Alsius Corp, Irvine, USA) or external cooling methods (Arctic Sun Temperature Management System, Medivance, Lousiville, USA) [11]. According to our treatment plan all cardiac arrest patients with ROSC, independent of the initial - 2 -

3 rhythm or cause of the arrest (except traumatic arrest), were to be treated with mild therapeutic hypothermia when active treatment was planned. The decision to use active treatment follows normal ethical considerations. Early stabilisation of haemodynamics It is important to stabilise and normalise haemodynamics early [6]. We do not know the optimal blood pressure after ROSC, but both the damaged brain and heart must both be adequately perfused without placing undue strain on the myocardium. The post cardiac arrest phase may be characterised as a sepsis like syndrome [13] associated with myocardial dysfunction [14]. A positive fluid balance, vasopressors, inotropic drugs and an intra-aortic balloon pump (IABP) may be required depending on the clinical situation, remaining myocardial function and cause of the arrest [6, 11]. Haemodynamic instability is common, with hypotension, low cardiac index and arrhythmias typical [14]. Early echocardiography is easy to perform and an important tool for assessment of myocardial function and is recommended to guide therapy, especially in the fi rst few critical days. Early control of oxygenation and ventilation It is important to emphasise that patients with short arrest times who show adequate signs of awakening within the first 5-10 min after ROSC should be kept awake. Comatose patients should receive controlled ventilation as early as possible and be sedated, aiming for normal oxygenation and ventilation [6]. Adequate sedation will reduce oxygen consumption which is then further reduced with hypothermia. Hypoxia, hyperoxia and hyperventilation may all worsen the reperfusion injury and global cerebral damage [6]. When inducing hypothermia frequent blood gas analyses are necessary to adjust tidal volumes, as cooling will decrease metabolism and required ventilation. Early blood sugar and electrolyte management Observational studies have shown increased mortality among cardiac arrest patients with raised blood glucose [8, 15]. Aggressive insulin treatment in patients with critical illness has reduced long-time mortality [16]. Thus, hyperglycaemia should be avoided and treated with insulin [6]. We don t know the optimal target, but a strict protocol does not seem necessary and may lead to hypoglycaemic episodes [17]. A target level of 5-8 mmol.l seems appropriate [6, 11, 17]. There is no randomised trial evaluating the value of changing electrolyte levels in post-resuscitation care; however, hyperkalaemia is an adverse prognostic factor among these patients [15]. Hypothermia causes a tubular dysfunction with increased diuresis, and may lead to hypophosphataemia, hypomagnesaemia, hypocalcaemia or hypokalaemia. Both hypophosphataemia and hypomagnesaemia frequently occur in critically ill patients, and replacement of these ions, combined with hypothermia, may have a role in reducing the neurological injury [6]. In general, it seems to make sense to target normal values for all electrolytes. Early seizure management Seizures were present in < 10% of patients in the Hypothermia after Cardiac Arrest study [4], and in 3-23% of patients during the first 24 h in the study by Langhelle et al (8). Seizures and, in particular, early status epilepticus are associated with poor outcome [6, 8]. There are no studies that directly address the use of prophylactic anticonvulsant drugs after cardiac arrest in adults. Continuous EEG is not part of our treatment protocol, but we emphasise that EEG should be performed when indicated and that adequate treatment with clonazepam, phenytoin or, in the presence of persistent status epilepticus, thiopental should be administered as early as possible [11]. The results of using the new strategy We recorded outcome at fi nal hospital discharge and one year later using the Cerebral Performance Category (CPC): 1 - conscious, no neurological disability; 2 - conscious, moderate neurological disability, able to work; 3 - conscious, severe neurological disability, dependent; 4 - coma or vegetative state and 5 - dead. With the new treatment strategy survival was signifi cantly improved among patients admitted to our hospital after OHCA [11]. In the historical control period ( ), 31% of the patients with cardiac - 3 -

4 aetiology (approximately 80% of all arrests) survived to hospital discharge, of whom 26% were classifi ed as successful survivors, defined as CPC 1 or 2 (50% of the survivors with CPC 1). In the intervention period ( ) the number of patients surviving to hospital discharge increased to 56% (p=0.001), and all survivors were in CPC 1 or 2 (91% of the survivors with CPC 1) [11]. Whereas three patients from the control period died during the fi rst year, all patients from the intervention period were still alive one year after discharge. According to our new treatment protocol several new interventions were introduced in the intervention period; 49% received reperfusion treatment with PCI, 66% mild therapeutic hypothermia, 80% inotropic agents, 15% IABP, 44% insulin treatment, 18% anti-epileptic medication and a signifi cantly higher fl uid balance [11]. All patients were treated in one of the two predefi ned ICUs. It is impossible to determine which single intervention, if any, was the major component leading to the improved outcome. In a multivariate analysis the only independent prognostic factor was being in the intervention period. Although the patients were younger in the intervention period, young age (defi ned as age < 70 yr) did not reach statistical signifi cance in the multivariate analysis. Important prognostic factors such as initial VF, witnessed arrest, bystander CPR, response time, time to ROSC were similar in both periods [11]. It is unlikely that the control period was associated with an unrealistically poor outcome, as the 31% survival compares well with Swedish [7] and UK data [9]. Moreover, recent reports from other institutions with a similar approach have reported similar effects on survival compared with historical data [18, 19]. The number of complications, time receiving mechanical ventilation and total length of stay in ICU were the same during the control and intervention periods [11]. Although it may be expected that treatment with hypothermia may be complicated and lead to more side-effects, we, and others [4, 18, 19] have demonstrated that it is feasible, safe and not associated with an increased number of complications. Our data did demonstrate that the number of pneumonias was high (around 50%) in both groups, irrespective of hypothermia treatment [11]. Future aspects The increased focus, team-work and enthusiasm related to introduction of a new treatment strategy would, in itself, contribute to improved survival, but one would expect that this positive effect would be reduced over time. This has, however, not happened inside our institution, as we see the same survival data today as we had previously (data not published). It seems that our post-resuscitation care strategy is well established, and that the improved survival rate has reached an acceptable level comparable with other institution with a similar approach [18, 19]. To improve the treatment after cardiac arrest with the aim of increasing the number of neurologically intact survivors, all links in the chain of survival have to be optimised [2]. It is, therefore, promising that post-resuscitation care, the previous weak link [3], has recently gained a lot more attention and focus [6]. Post-resuscitation care starts already immediately after ROSC out in the fi eld, and has to be continued all the way through the Emergency Department, to the angiographic laboratory, the ICU and ward, and, eventually, inside different hospitals. In a recent Finnish study, survival was signifi cantly associated (odds ratio of 2.5) with use of a post-rosc protocol before the patient reached the hospital [20]. Thus, post-resuscitation care affects several different providers of different professional levels and requires a multidisciplinary approach with a clearly defi ned logistic plan according to local infrastructure. We have been able to improve the outcome within our institution, but these results may not be generalisable to other institutions. Moreover, the scientific interpretation of our results is diffi cult due to the comprehensive nature of the changes and a number of different interventions. Although we seem to know more about treatment options and survival potential following arrest there are several unanswered questions that need to be solved through future studies. The most important ones are: Should all primary successful resuscitated comatose patients be treated with mild therapeutic hypothermia? What about non-vf arrests or arrests of non-cardiac origin? Should patients be cooled for 24 h, or should patients with more severe reperfusion injury (asphyctial arrests, initial asystole or pulseless electric activity) be treated longer, for example for 48 h or even 72 h? What about pre-hospital cooling? The earlier the better? What is the optimal haemodynamic strategy after ROSC? How early should haemodynamics be optimised? What should the target mean arterial pressure be? What is optimal haemodynamic monitoring? Should all patients be brought to the angiographic laboratory for early coronary angiography with the possibility for early PCI? When and how should we prognosticate these patients? Too early prognostication may result in treatment withdrawal too early in patients with potential for successful survival. What are the optimal prognostication tools after cardiac arrest (EEG, - 4 -

5 somatosensory evoked potentials, neuron-specifi c enolase, clinical examination)? Is 72 h post-arrest too early, or should it be undertaken even later for example at 72 h following the onset of normothermia (72 h without sedation and still comatose)? Conclusions Post-cardiac arrest disease and care is complex. The patients are critically ill and require intensive care treatment depending on the cause of the arrest, severity of the post-cardiac arrest syndrome and degree of myocardial dysfunction. Each hospital should have a well defined standardised plan for intervention and treatment according to local conditions, infrastructure and logistics. Such a plan enables doctors and nurses to focus on when and how to treat, and to monitor patients in different circumstances. In our institution this new post-arrest treatment strategy has improved survival signifi cantly and should encourage other institutions to do the same. Key Learning Points Post resuscitation care should follow a standardised treatment protocol Mild therapeutic hypothermia (32-34 ºC) should be used for 24 h, irrespective of initial rhythm, if active treatment is desired Early coronary angiography with subsequent PCI, if indicated, is recommended Focus on early optimisation of haemodynamics, oxygenation, ventilation and metabolism A well defi ned implementation strategy, depending on the local infrastructure, is of utmost importance References 1. Atwood C, Eisenberg MS, Herlitz J, Rea TD. Incidence of EMS-treated out-of-hospital cardiac arrest in Europe. Resuscitation 2005; 67: Cummins RO, Ornato JP, Thies WH, Pepe PE. Improving survival from sudden cardiac arrest: the chain of survival concept. A statement for health professionals from the Advanced Cardiac Life Support Subcommittee and the Emergency Cardiac Care Committee, American Heart Association. Circulation. 1991; 83: Peberdy MA, Ornato JP. Post-resuscitation care: is it the missing link in the Chain of Survival? Resuscitation 2005; 64: The Hypothermi a After Cardiac Arrest (HACA) study group: Mild therapeutic hypothermia to improve the neurologic outcome after cardiac arrest. New England Journal of Medicine 2002; 346: Bernard SA, Gray TW, Buist MD, et al. Treatment of comatose survivors of out-of-hospital cardiac arrest with induced hypothermia. New England Journal of Medicine 2002; 346: Nolan JP, Neumar RW, Adrie C, et al. Post-cardiac arrest syndrome. Epidemiology, pathophysiology, treatment, and prognostication. A consensus statement from the International Liaison Committee on Resuscitation Resuscitation 2008; 79: Herlitz J, Engdahl J, Svensson L, et al. Major differences in 1-month survival between hospitals in Sweden among initial survivors of out-of-hospital cardiac arrest. Resuscitation 2006; 70: Langhelle A, Tyvold SS, Lexow K, et al. In-hospital factors associated with improved outcome after out-of-hospital cardiac arrest. A comparison between four regions in Norway. Resuscitation 2003; 56: Nolan JP, Laver SR, Welch CA, et al. Outcome following admission to UK intensive care units after cardiac arrest: a secondary analysis of the ICNARC Case Mix Programme Database. Anaesthesia 2007; 62: Nolan JP, Morley PT, ALS Task Force. Therapeutic hypothermia after cardiac arrest. An advisory statement by the Advanced Life Support Task Force of the International Liaison Committee on Resuscitation. Resuscitation 2003; 57: Sunde K, Pytte M, Jacobsen D, et al. Implementation of a standardised treatment protocol for post resuscitation care after out-of-hospital cardiac arrest. Resuscitation 2007; 73: Spaulding CM, Joly LM, Rosenberg A, et al. Immediate coronary angiography in survivors of out-of-hospital cardiac arrest. New England Journal of Medicine 1997; 336: Adrie C, Adib-Conquy M, Laurent I, et al. Successful cardiopulmonary resuscitation after cardiac arrest as a sepsis-like syndrome. Circulation 2002; 106: Laurent I, Monchi M, Chiche JD, et al. Reversible myocardial dysfunction in survivors of out-of-hospital cardiac arrest. Journal of American College of Cardiologists 2002; 40: Skrifvars MB, Pettilä V, Rosenberg PH, Castrén M. A multiple logistic regression analysis of in-hospital factors related to survival at six months in patients resuscitated from out-of-hospital ventricular fi brillation. Resuscitation 2003; 59: Van Den Berghe G, Wouters P, Weekers F, et al. Intensive insulin therapy in critically ill patients. New England Journal of Medicine 2001; 345: Oksanen T, Skrifvars MB, Varpula T, et al. Strict versus moderate glucose control after resuscitation from ventricular fi brillation. Intensive Care Medicine 2007; 33:

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