In-hospital cardiac arrest: incidence, prognosis and possible measures to improve survival

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1 Intensive Care Med (2007) 33: DOI /s z SPECIAL ARTICLE Claudio Sandroni Jerry Nolan Fabio Cavallaro Massimo Antonelli In-hospital cardiac arrest: incidence, prognosis and possible measures to improve survival Received: 2 February 2006 Accepted: 20 July 2006 Published online: 22 September 2006 Springer-Verlag 2006 C. Sandroni ( ) F. Cavallaro M. Antonelli Catholic University School of Medicine, Intensive Care Unit, Rome, Italy sandroni@rm.unicatt.it Tel.: Fax: J. Nolan Royal United Hospital, Intensive Care Unit, Bath, UK Abstract Design: Review. Objective: Medical literature on in-hospital cardiac arrest (IHCA) was reviewed to summarise: (a) the incidence of and survival after IHCA, (b) major prognostic factors, (c) possible interventions to improve survival. Results and conclusions: The incidence of IHCA is rarely reported in the literature. Values range between 1 and 5 events per 1,000 hospital admissions, or events/bed annually. Reported survival to hospital discharge varies from 0% to 42%, the most common range being between 15% and 20%. Pre-arrest prognostic factors: the prognostic value of age is controversial. Among comorbidities, sepsis, cancer, renal failure and homebound lifestyle are significantly associated with poor survival. However, pre-arrest morbidity scores have not yet been prospectively validated as instruments to predict failure to survive after IHCA. Intra-arrest factors: ventricular fibrillation/ventricular tachycardia (VF/VT) as the first recorded rhythm and a shorter interval between IHCA and cardiopulmonary resuscitation or defibrillation are associated with higher survival. However, VF/VT is present in only 25 35% of IHCAs. Short-term survival is also higher in patients resuscitated with chest compression rates above 80/min. Interventions likely to improve survival include: early recognition and stabilisation of patients at risk of IHCA to enable prevention, faster and better in-hospital resuscitation and early defibrillation. Mild therapeutic hypothermia is effective as post-arrest treatment of out-ofhospital cardiac arrest due to VF/VT, but its benefit after IHCA and after cardiac arrest with non-vf/vt rhythms has not been clearly demonstrated. Keywords Cardiac arrest Heart arrest Cardiopulmonary resuscitation Advanced cardiac life support Sudden cardiac death Introduction Between 370,000 and 750,000 in-hospital resuscitation attempts are made in the United States each year [1]. Intensivists are frequently involved in the management of in-hospital cardiac arrests (IHCAs), either as members of cardiac arrest teams (CATs) [2], or to provide postresuscitation care. Unfortunately, the majority of patients resuscitated successfully from IHCA die before hospital discharge, and their prognosis has changed little over the past 30 years [3, 4]. This review focuses on the main issues relating to in-hospital resuscitation and on the factors which need improvement. This review is based on the literature published during the past 25 years. The search was carried out on Medline (January 1981 January 2006). MeSH terms used were heart arrest and cardiopulmonary resuscitation plus the key words in-hospital and hospital. For the section medical emergency team the key words medical emergency team and MET were used. The computer search was supplemented by

2 238 consulting the bibliographies from the articles retrieved. Only human studies in English language were considered. Definition There are at least ten different definitions for IHCA [3]. This variability in definition has influenced the inclusion criteria and consequently the reported incidence and prognosis of IHCA. To ensure uniform reporting on inhospital cardiopulmonary resuscitation, guidelines known as the Utstein style for in-hospital resuscitation research were published in 1997 [5] and updated recently [6]. The Utstein-style definition of cardiac arrest is the cessation of cardiac mechanical activity... confirmed by the absence of a detectable pulse, unresponsiveness and apnoea (or agonal respirations). This definition distinguishes cardiac arrest from respiratory arrest, which is characterised by apnoea with palpable pulses. According to the Utstein criteria, a cardiac arrest is classified as in-hospital if it occurs in a hospitalised patient who had a pulse at the time of admission. Incidence Few studies have reported the incidence of IHCA. The incidence can be calculated either as the number of events per hospital beds per year or as the number of events per number of patient admissions. The first approach gives an estimate of the number of the expected events in a single institution, while the second method takes into account the patients turnover. The first method has been used by the National Registry of Cardiopulmonary Resuscitation (NR- CPR), which reported an incidence of events/bed annually over a total of 14,720 arrests in 287 American hospitals [4]. Other studies [7, 8, 9] have used the second method and report an incidence of 1 to 5 arrests per 1000 patient admissions. Studies comparing the incidence of IHCA in different hospital areas have yet to be undertaken. Survival Survival from cardiac arrest can be expressed in relation to time as: immediate (return of spontaneous circulation, ROSC), short-term (discharged alive from the hospital), and long-term (6 12 months). ROSC represents mainly a success of the cardiopulmonary resuscitation (CPR) manoeuvres. Unfortunately, between 25% and 67% of the successfully resuscitated patients die during the first 24 h after ROSC [9, 10, 11]. Survival to hospital discharge is the most commonly quoted outcome. documented survival rates for IHCA range from 0% to 42%, although major studies report a survival to discharge of approx. 20% [4, 10, 12, 13, 14, 15]. Differences in cohort disease severity, definition of cardiac arrest, and use of do-not-attempt-resuscitation (DNAR) orders may explain much of this wide variability [3]. Survival after discharge has a relatively shallow decline [14]. One year after the arrest, reported survival of the originally discharged patients ranges between 53% and 86% [7, 10, 11, 16]. In a study by Di Bari et al. [17] 53% of discharged patients (17% of original patient population) were still alive 5 years after cardiac arrest. Factors that affect survival According to the in-hospital Utstein style, factors that may be associated with survival are divided into two groups: patient variables and event variables. Patient variables Age Only few studies document an association between age and survival after cardiac arrest [7, 9, 11, 17, 18, 19], but others show a significantly lower survival in older patients [10, 13, 20, 21]. These conflicting results may be due partially to differences in methodology and inclusion criteria: some studies include only adults [9, 13, 19, 20, 21] but others also children [7, 10, 11]. Different cut-off values have been used to divide younger from older adults: 65 years [10], 70 years [13, 17, 20], or more than two cut-off values [18]. Moreover, the effect of age on survival may be confounded by selection bias: patients aged 70 years or over are less likely to receive CPR than younger persons [18, 22]. Very old patients have a low survival rate to hospital discharge. Two studies [18, 23] found a significantly lower survival in patients aged over 80 years than in younger ones; no patient older than 90 years survived. A recent large study [15] based on the NRCPR database reported significantly higher survival rates to hospital discharge following cardiac arrest in children than in adults (27% vs. 18%; relative risk of death in children vs. adults, 0.89; 95% confidence interval ). Gender, race and ethnicity The majority of studies on IHCA do not document any effect of gender on survival. However, at least one study [24] reported that after adjustment for age, cause, site of arrest and cardiac rhythm, female gender was an independent predictor for survival to discharge. A strong association between race and outcomes from cardiovascular disease has been reported [25]. Survival after both out-ofhospital [26] and in-hospital [27] cardiac arrest is lower

3 239 in black patients. Ethnicity could obviously include other variables which can influence outcome, such as socioeconomic status, health style, and utilisation of health care resources. Morbidity Some clinical diagnoses such as sepsis [19, 28], renal failure [20], metastatic cancer [28, 29], house-bound life style [19], and stroke [20] are associated with worse prognosis after IHCA. These diagnoses are used as morbidity variables in pre-arrest predictive models such as the Pre-Arrest Morbidity score [30] (score range 0 25) and Prognosis After Resuscitation score [28] (score range 2 31). These models have been developed to predict failure to survive after cardiac arrest in an attempt to avoid futile resuscitation; however, these scores have never been validated prospectively for this purpose because it would require a very large patient population. When used retrospectively, pre-arrest morbidity scores show high specificity but low sensitivity, i.e. only a minority of the patients destined to die after cardiac arrest can be identified. In a study of 274 consecutive cardiac arrests [30] a Pre-Arrest Morbidity score higher than 4 and a Prognosis After Resuscitation score higher than 5 identified patients with 100% mortality. However, their sensitivity for the prediction of failure to survive was only 9.2% and 23.7%, respectively. Combining pre-arrest morbidity scores may increase their sensitivity by up to 42% [31]. Clinical severity scores designed specifically for ICU patients, such as the Acute Physiology and Chronic Health Evaluation (APACHE) II and III, have also been evaluated as pre-arrest predictors of survival after IHCA, but results have been unsatisfactory. An APACHE II score of 15 or higher calculated on admission [32] has proven unreliable to predict mortality: 6.1% of patients predicted to die actually survived to discharge, and 80.3% of patients predicted to survive actually died. Since patient s conditions on admission may not reflect those immediately before the occurrence of cardiac arrest, other authors have calculated the APACHE II score using parameters in the 24 h preceding the arrest. In one study [33] this score was correlated with survival to discharge, but no threshold which predicted 100% mortality could be individuated. The APACHE III [34] score calculated retrospectively on admission was significantly different between survivors and non-survivors at hospital discharge, but the area under the receiver operating characteristic curve for the APACHE III score was only 0.587, with 95% confidence interval including 0.5, indicating a predictive value no better than chance. In conclusion, pre-arrest morbidity scores show some degree of correlation with patient survival to discharge, but outcome of cardiac arrest cannot be completely explained by the pre-arrest variables. Therefore none of these scores can be recommended as a prognostic tool to support clinical judgement in the individual patient. Event variables The major event variables influencing outcome are the first monitored rhythm, the event intervals and duration, and the event location. First monitored rhythm As occurs in out-of-hospital cardiac arrest (OHCA), the outcome from IHCA is consistently better when the first monitored rhythm is ventricular fibrillation/pulseless ventricular tachycardia (VF/VT) rather than non-vf/vt, i.e. asystole or pulseless electrical activity (PEA). Survival rates range from 18% to 64% for VF/VT and from 1.2% to 14% for non-vf/vt [4, 7, 11, 12, 15, 16, 21, 35, 36, 37]. There are two major reasons for the better outcome reported in VF/VT rhythms. First, VF/VT rhythms can be treated promptly and successfully with defibrillation. Second, since VF/VT rhythms deteriorate to asystole if not treated promptly, the presence of a VF/VT implies a recent onset of cardiac arrest. Unfortunately, in the majority of studies VF/VT is the first monitored rhythm in only 20 35% of IHCAs [2, 4, 9, 11, 12, 13, 16, 38], although higher percentages have been reported [36, 39]. This contrasts with OHCA, where the majority of cases which occur with a monitor in place are precipitated by VF/VT [40]. The lower prevalence of VF/VT rhythms in IHCA than in OHCA may be explained partially by differences in pathophysiology: IHCA is frequently precipitated by hypoxia or hypotension [4, 41], which are more likely to cause PEA or asystole than VF/VT. Conversely, VF/VT rhythms are more common when ischaemia is the precipitating cause of cardiac arrest, as often occurs in OHCA. In selected in-hospital cohorts comprising a high percentage of patients with cardiac ischaemia, the prevalence of VF/VT is high and exceeds 50% [42]. In children, in whom coronary artery disease is rare and cardiac arrest usually results from hypoxia due to respiratory insufficiency or shock, the prevalence of VF/VT rhythms is even lower than in adults, but non-vf/vt rhythms have a relatively better prognosis [15]. Event intervals The importance of early CPR and defibrillation for survival from OHCA has been well recognised [43] and constitutes the rationale for the chain of survival concept. Evidence suggests that the same concept can be applied to IHCA. Herlitz et al. [44] showed that survival to discharge after IHCA was significantly higher when CPR was started within the 1st min after collapse (33% vs. 14%, p = 0.008).

4 240 In VF/VT IHCA Peberdy et al. [4] reported survival rates of 38% vs. 21% when the first shock was given within or after 3 min (p < 0.001) respectively. Similar results have been reported by other authors [11, 45]. In many hospitals defibrillation and advanced life support (ALS) skills and equipment are available only in critical care areas, while general ward staff can perform only CPR. With this type of organisation, defibrillation and ALS are delayed until the arrival of the cardiac arrest team, which may be more than 6 min in larger hospitals [2]. To reduce the collapse-todefibrillation interval, early in-hospital defibrillation programmes have been studied (see below). about one-half that during the day; the incidence of unwitnessed arrest was significantly higher at night. Another study [46] found that survival rate was lower during the late afternoon and night, although the incidence of unwitnessed arrests did not vary with time. Elsewhere [13] no relationship between time and survival was reported. The lower survival rates observed during night could be due to a less efficient response of the hospital emergency system. Another possible explanation is that futile resuscitation attempts are more likely to be made after hours when senior physicians and patient s relatives, who might otherwise have agreed a DNAR order, are absent. Event duration Patients with a shorter duration of cardiac arrest have better outcomes [15, 21]. This is because shorter arrests are usually due to rapidly treatable causes, but also because longer resuscitation times are associated with generalised tissue hypoperfusion and hypoxic damage. Hospital location Patients admitted to ICU are on average more seriously ill than patients in a general ward and can therefore be expected to show higher mortality rates after cardiac arrest. Conversely, with some exceptions [38], the majority of studies [9, 10, 46, 47] report better outcomes for IHCA occurring in critical care areas than for those occurring in wards. Possible explanations for the apparent paradox associated with the ICU environment include: (a) monitored and witnessed status of virtually all cardiac arrests, (b) immediate availability of ALS, (c) younger age, and (d) better selection of patients to be resuscitated-effective use of a DNAR policy. Moreover, in some studies [47] critical care areas include the coronary care unit, where cardiac arrests are often secondary to readily reversible dysrhythmias associated with acute myocardial infarction, and have a relatively good prognosis. Reported survival rates for IHCA in the emergency room (ER) vary widely. In some studies [9, 10] the ER is the hospital area with the highest survival rate, while other studies [11, 46, 48] report opposite results. However, in at least one of the latter studies [48] the ER population included patients who had a cardiac arrest in the community, and who had arrived in hospital with CPR in progress. These patients have a poor prognosis and, according to the Utstein guidelines, should not be considered as IHCAs. Time of day as a predictor of survival One study [44] showed that the survival rate for in-hospital patients who had a cardiac arrest during the night was Functional outcome The Cerebral Performance Category (CPC) score [49] is the most commonly used instrument to assess functional outcome after cardiac arrest; its categories are: 1. Conscious and alert with good cerebral performance; able to work and lead a normal life; may have minor neurological deficits 2. Conscious with moderate cerebral disability; independent for activities of daily life; sufficient cerebral function for part-time work in sheltered environment; may have seizures or permanent memory or mental changes 3. Conscious with severe disability; dependent on others for activities of daily life because of impaired brain function 4. Not conscious (comatose or persistent vegetative state) 5. Brain dead or death from other causes The majority of papers [4, 14, 39] report a relatively good functional outcome in survivors from IHCA. At discharge the NRCPR database [4] reports 85.1% of patients having CPC 1 or 2 (patient conscious and alert with minimal or moderate disability) in comparison with 91.4% on admission. In a study of 827 patients [14] after a median of 15 months after discharge, 75% of survivors were independent in daily life and 83% were cognitively intact. Poor functional outcome was significantly associated with age over 70 years but was not correlated with duration of CPR or severity of coma after the arrest. In contrast with these positive results other investigators [50] report that 44% of survivors after IHCA had poorer CPC function 2 months after CPR compared with their function before the event. How to improve the outcome? Pre-arrest factors: recognising the critically ill patient and prevention of cardiac arrest Since only a minority of cardiac arrest patients survive, the prevention of this event is crucial. In hospital, cardiac

5 241 arrest is often neither a sudden nor an unpredictable event. Evidence of deterioration during the 8 h before the arrest has been reported in up to 84% of cases, the most common findings being respiratory problems, deterioration of mental status and haemodynamic instability [41, 51, 52]. In a study by Hodgetts et al. [8], the case summaries of 118 IHCAs were reviewed by an expert panel, which concluded that 61.9% of arrests were potentially avoidable. Clinical signs of deterioration were not acted on in 48% of cases. The odds of potentially avoidable cardiac arrests were 5.1 times higher in patients in general wards than in critical care areas. Medical emergency teams In some hospitals the CAT has been replaced by a Medical Emergency Team (MET) that responds not only to patients in cardiac arrest but also to those with acute physiological deterioration. The MET usually comprises medical and nursing staff from intensive care and general medicine and responds to specific calling criteria (e.g. changes in blood pressure, respiratory rate or consciousness, a critical reduction in blood oxygen saturation). The introduction of a MET is usually preceded by an educational period, during which the medical and nursing staff are trained to detect the warning signs and initiate treatment. Early involvement of the MET may reduce cardiac arrests, deaths and unanticipated intensive care unit admissions. In a trial conducted before and after the introduction of an intensive-care based MET Bellomo et al. [53] observed a significant reduction in the incidence of IHCA (relative risk reduction 65%), death following cardiac arrest (56%) and overall in-hospital mortality (88%). In a similar study Buist et al. [54] demonstrated a significant reduction in the incidence of unexpected cardiac arrest (from 3.77 to 2.05 per 1,000 hospital admissions) and mortality (from 77% to 55%). Despite their positive results these studies on METs have some important limitations: they were not double-blinded or placebo-controlled, and the observed reduction in mortality can be explained not just by the effect of MET s interventions but also by the effect of educating ward staff [55] and by an increase in the number of DNARs [56]. Some of these shortcomings have been addressed by a multicentre randomised cluster control study [57] which randomised Australian hospitals to continue functioning as usual or to introduce a MET system. Unfortunately, in this study the MET system greatly increased emergency team calling but did not substantially affect the incidence of cardiac arrest, unplanned ICU admissions or unexpected death. In conclusion, METs show some potential in reducing the incidence and mortality of unexpected cardiac arrest in hospitals, but their independent effect remains to be clearly demonstrated. Identification of DNAR status The percentage of in-hospital resuscitation attempts over total cardiac arrests varies from 5% to 31% [7, 9, 18, 19, 39]. This means that the majority of in-hospital patients who undergo cardiac arrest are not resuscitated because for them the cardiac arrest is simply the final event of the dying process. Early evaluation of patients during the course of their illness may prevent deterioration leading tocardiacarrestandcouldalsohelptoidentifythose patients for whom resuscitation would not be appropriate. Clearly both the reported incidence and outcome of IHCA may depend on how criteria for resuscitation are applied [58]. Adherence to the DNAR policy is important to avoid futile resuscitation in patients with no chance of survival. Intra-arrest factors Better resuscitation Despite the dissemination of resuscitation training programmes, the quality of resuscitation performed in hospital is often suboptimal. Current guidelines for CPR recommend a chest compression rate of 100/min and a compression depth of 4 5 cm [59]. However, two recent observational studies conducted on IHCA demonstrated that both depth and rate of chest compression performed by CAT members were insufficient in about one-third of cases [60], and that chest compression rates below 80/min were associated with a significantly lower immediate survival rate [61]. The 2005 European Resuscitation Council ALS guidelines [62] emphasise the importance of minimising interruptions to chest compressions and recommend a 30:2 rate between chest compressions and ventilations (instead of the previous 15:2 rate), with the aim of increasing the number of compressions delivered in each minute of CPR. It is hoped that these new guidelines will lead to improvements in the quality of CPR and ultimately to improved survival. Since better resuscitation increases survival, CPR training could also potentially increase survival by improving resuscitation quality. There are very few studies on the effect of training on survival from IHCA. In a study performed in a 550-bed tertiary care centre [63] the survival rate of patients rescued by an ALS-trained nurse was almost four times higher (37.5% vs. 10.3%) than when resuscitation was attempted by a nurse without ALS training. Other authors [64] have demonstrated an increase in immediate survival in hospitals after the completion of a resuscitation training programme. Defibrillators with sensing capabilities are a promising tool to improve CPR quality. Current technology enables the measurement of the depth of chest compressions [60, 65], and this function has recently been incorporated into a commercial defibrillator along with

6 242 a feedback system [66] which guides and corrects the rescuer s performance. Early defibrillation Time to defibrillation is critical for survival after IHCA, but the time taken for CATs to reach the most remote wards in some hospitals can be quite long [2]. In this context, early defibrillation provided by the ward staff using automated external defibrillators (AEDs) might improve survival. AEDs are easy to use and can be operated successfully by non-medical ward staff after minimal training. Despite these positive premises, experience with in-hospital early defibrillation is still limited. The American NRCPR database [4] reports that only 1.4% of 4,071 VF/VT arrests occurring in the period were defibrillated using an AED. Few studies have investigated the impact of AED use on survival after IHCA. A pilot study [67] used AEDs in non-monitored wards in 13 episodes of VF over 17 months; the ROSC rate was 69% and survival to hospital discharge was 46%. A before-and-after single-centre study [68] reported that after the introduction of an early defibrillation programme survival from VT/VF arrest increased from 2.2% to 15.6% and the relative risk of death after the AED programme decreased to 0.86 (95% confidence interval ). Large multicentre studies are needed to assess the benefits of in-hospital early defibrillation programmes. An expected limitation of such studies will be the relatively low rate of VF/VT rhythms in IHCA. Better resuscitation, faster defibrillation and continuous training of healthcare providers are all key components of the organisation of an efficient emergency response and are likely to improve survival of IHCA. In the United Kingdom standards for clinical practice and training for cardiopulmonary resuscitation have been established [69]. Post-resuscitation care The prognosis of patients admitted to the ICU after resuscitation from cardiac arrest is poor in comparison with other ICU patients [70]. Among 14,258 patients admitted to ICU in the United Kingdom after IHCA the ICU mortality was 55% while hospital mortality was 69% (unpublished data from the Intensive Care National Audit and Research Centre, London, December 1995 October 2004). Interventions in the post-resuscitation period are likely to influence the final outcome significantly, yet there are relatively few data relating to this phase. In 2002 two distinct randomised controlled trials [71, 72] demonstrated that mild therapeutic hypothermia administered during the first h after VF cardiac arrest improves both survival and neurological recovery. Unfortunately, the study population included almost exclusively OHCAs and only VF/VT rhythms, and therefore there is some difficulty in extrapolating these results to IHCA, which more often presents as a non-vf/vt rhythm. Neurological injury is less likely to be the primary mode of death among IHCA patients than it is among OHCA patients [73]. This probably reduces the potential impact of therapeutic hypothermia in the IHCA group. One study using a historical control group has demonstrated improved neurological outcomes in comatose survivors of asystolic/pea cardiac arrest, but these were all OHCAs and the results have been presented only in abstract form [74]. The International Liaison Committee on Resuscitation recommends mild therapeutic hypothermia in OHCA when initial rhythm is VF [75]. Despite this, hypothermia after resuscitation is still underused [76]. There is a strong association between high blood glucose after resuscitation from cardiac arrest and poor neurological outcome [77]. Tight control of blood glucose ( mmol/l or mg/dl) using insulin reduces hospital mortality [78] and may protect the central and peripheral nervous system of critically ill adults [79], but this has not been demonstrated in post-cardiac arrest patients specifically. However, it is reasonable for patients admitted to an ICU after cardiac arrest to have their blood glucose monitored frequently and hyperglycaemia treated with an insulin infusion. Frequent monitoring is essential because inadvertent hypoglycaemia may cause or exacerbate brain injury. Conclusions Of every 1,000 patients admitted to hospital in Western countries between one and five sustain cardiac arrest, and only 20% survive to hospital discharge. Outcome from IHCA is determined by pre, intra- and post-arrest factors. Some pre-arrest conditions such as cancer, sepsis and renal failure are correlated with lower survival, but current pre-arrest morbidity scores do not predict a poor prognosis reliably. Many in-hospital arrests are preceded by warning signs, which should be identified early to enable treatment to prevent patient deterioration. Experience with specifically dedicated teams increased awareness of warning signs by ward personnel but their direct effect on reducing mortality is unproven. After cardiac arrest has occurred, better resuscitation and early defibrillation can improve survival. Recent evidence that better CPR is associated with increased resuscitation success should be translated into systematic training and maintenance of skills among all healthcare providers. Although not specifically evaluated on IHCA patients, mild hypothermia is a promising post-resuscitation therapy for comatose survivors of cardiac arrest.

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