Out-of-hospital cardiac arrest (OHCA) is a sudden disease presentation where survival is tightly related to the rapid intervention delivered through an optimal teamwork. This represents the “chain of survival” concept based on prompt recognition of the cardiac arrest, call for help, bystander cardiopulmonary resuscitation (CPR), early defibrillation and standardized post-resuscitation care.1–6 The implementation of a regional lay rescue programme focused on a rapid coordinated network response7 and easy access to automatic external defibrillator (AED)8 improve OHCA survival.9 The aim is the return of spontaneous circulation (ROSC) in the first minutes following cardiac arrest (CA). In Canton Ticino, a region of Switzerland of about 350,000 inhabitants, most patients suffering from a cardiac-related OHCA are managed in a tertiary cardiac receiver centre in which an interdisciplinary team composed by cardiologists, anaesthesiologists, and intensivists is available on 24h/7 days basis. Since myocardial ischaemia is the predominant aetiology of OHCA,10 early coronary revascularisation restores myocardial perfusion and improves patient outcome.11–13 In fact, numerous observational studies have shown that patients with ST-segment elevation after OHCA benefit of urgent angiography and primary percutaneous transluminal coronary angioplasty (PTCA).14–16 Once the heart is re-perfused, the therapeutic pathway continues with the post resuscitation management in the intensive care unit (ICU). The mitigation of cerebral ischaemia–reperfusion injuries by temperature control has proven to play a role in post-OHCA neuroprotection.17–19 Other supportive strategies include optimal organ perfusion monitored by close lactate analysis,20,21 plasma glucose optimization,22 prompt correction of electrolyte imbalance, and appropriate mechanical ventilation.23 This multi-faceted ICU standardized post-cardiac arrest syndrome management combined with a well-organized extra-hospital rescue programmes have improved the survival after OHCA.9,24–26 Furthermore, some evidence suggests that patients treated in a specialized cardiac arrest centre may benefit of a better outcome.11,27–32 Therefore, a comprehensive post-cardiac arrest approach remains a pivotal step of the chain of survival, as highlighted in the last update of the 2015 ILCOR guidelines and in recent publications.1,33–37 We herewith report the data of our ten years register, collected prospectively in a cohort of post-OHCA patients admitted to our cardiovascular ICU. We analyzed independent risk factors that could have influenced patient's cerebral performance at hospital discharge after CA due to ventricular fibrillation (VF) or tachycardia (VT). The aim of the present study was to investigate survival and cerebral performance categories (CPC) in comatose patients after OHCA. Primary goal was to study the association between neurological outcome and clinical events occurring before ICU admission and during ICU stay.

Three-hundred fifty-four consecutive OHCA adult patients were admitted between 2007 and 2017 to our ICU. We enrolled 276 cases with documented sustained VT or VF as an initial resuscitation rhythm. Thirty-one patients were excluded being already conscious at the ICU admission. Two-hundred forty-five comatose patients were finally included for the analysis. The study flow diagram is showed in Fig. 1.

Figure 1.

Flow diagram of study registry.

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The average age of the cohort studied was 63.5±13.1 years with a predominance of men (84.5%); demographic features and previous cardiovascular conditions are described in Table 1. The laps from call to EMS crew arrival on OHCA scene was 8.7±4.2min in good outcome group versus 9.0±4.6min in poor outcome group, without statistically difference (p=0.66). OHCA was witnessed in 222 patients (90.6%); first responders arrived on place before EMS in 77 cases (31.4%). AED was applied by bystander in 65 (26.5%) patients, while 180 received the first shock at EMS arrival. Overall number of pre-hospital defibrillations for successful ROSC was similar in the two group, 4.1±3.2 in good outcome patients and 3.7±2.3 in poor outcome patients (p=0.61). In-ICU all patients received at least one vasoactive or inotropic drug during the first 72h. Ischaemia was the leading cause of the cardiac arrest, in fact among 245 patients 170 (69.4) were admitted with suspected diagnosis of acute myocardial infarction (Table 1), whereas in 67 (27.5) patients a culprit lesion was not visible and in 8 (3.2%) the cardiac origin was excluded (six documented hypokalaemia, one pulmonary embolism, one toxic).

One-hundred fifty-two patients (62%) survived at hospital discharge, 131 (86.2%) of them with favourable neurologic outcome (CPC≤2). The cause of death was circulatory failure 17.2%,16 neurological injury 67.7%,47 multi-organ failure 15.1%.14 Among patients with good neurologic outcome one-year survival rate was 95.9% (117 alive at 1-year, 9 missed, 5 deceased). ICU length of stay (LOS) was respectively 6.4±5.8 days for a good and 5.9±6.7 days for a poor neurologic outcome (p=0.21). Among patients with CPC 1 or 2, the time to the first signs of neurologic recovery was 75±60h after admission (time of “awakening” defined as the best motor response with Glasgow Coma Scale=6).

The patients directly admitted to the tertiary centre had shorter time of access to the catheter laboratory, in comparison to those previously admitted to other hospitals; the time lapsed from ROSC to the beginning of coronary procedure was 67±29min vs 188±52min (p<0.01), nevertheless the lapse was not associated with the outcome (p=0.06). Moreover, this group of patients had earlier target temperature management, since time from ROSC to the activation of the intravascular cooling device was shorter (197±55min vs 220±67min, p=0.04).

All variables (before ICU and in-ICU) related to the primary outcome with a statistically significant value (p<0.05) (Tables 1 and 2), were run in the finally multivariable analysis (Table 3). The final stepwise multivariable logistic regression showed that an age >70 years old (OR 2.0; 95%CI 1.1–4.1), previous myocardial infarction (OR 2.7; 95%CI 1.2–6.1), shock at hospital admission (OR 2.9; 95%CI 1.3–6.2), time from call to ROSC >25min (OR 3.1; 95%CI 1.6–6.0), and anticonvulsant therapy (OR 18.2; 95%CI 5.5–60) were independent predictors of poor neurologic outcome. Direct admission to the cardiac arrest centre (OR 0.5; 95%CI 0.3–0.9) and positive lactate clearance reaching lactate plasma level <2.5mmol/l at 12h (OR 0.4; 95%CI 0.2–0.8), were independent predictors of a more favourable outcome.

The performance of the models to predict poor neurologic outcome was assessed (Fig. 2). The model considering pre-ICU factors (green dashed line) explained 34.4% of the variance in CPC and correctly classified 71.8% of cases, whereas the model including ICU factors (red dotted curve) explained 34.6% of the variance in CPC, and correctly classified 74.7% of cases. The robustness of the predictive model increased when pre-ICU and ICU variables, from above mentioned analyses, were considered in a combined model (blue continuous line). When all variables (pre-ICU and ICU) were pooled, the Nagelkerke's R2 value increased the variance in neurological outcome to 45.5% and the AUC's predictive value improved up to 77.9%. The better performance of this combined model confirms the importance of a global approach in order to increase the precision in predicting neurological outcome at hospital discharge of OHCA survivors. The pattern of lactate kinetics was also found to correlate to neurological outcome (Fig. 3). A progressive clearance of lactate after ICU admission was associated with an increased probability of CPC ≤2. Conversely, a progressive increase in lactatemia raised the likelihood of poor neurologic outcome. During these ten years the proportion of patients suffering from unfavourable outcome (CPC 3-4 and mortality) were 54% (2007), 63% (2008), 57% (2009), 48% (2010), 47% (2011), 36% (2012), 32% (2013), 54% (2014), 47% (2015), 27% (2016) and 48% (2017), respectively (Fig. 4). The Cochran–Armitage test of trend did not show a statistically significant linear trend between years and the proportion of patients with poor neurological outcome (CPC>2), p=0.08.

Figure 2.

ROCs of three logistic regression models.

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Figure 3.

Clearance lactate at 12h and probability of CPC >2 with 95% confidence intervals. The lactate reduction index used in this analysis was expressed in percentage as follows: (ICU admission lactate−lactate levels at 12h)/ICU admission lactate*100.

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Figure 4.

Mortality and CPC trend.

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This study investigated the impact of continuity of care, on patients presenting OHCA due to shockable rhythm. We assessed the effectiveness of our local chain of survival and the post-resuscitation management in our centre collecting data in conformity to the Utstein register recommendations.48 In our cohort 2007–2017 we found a survival rate of 62% and a favourable neurologic recovery in 86.2% of them (CPC≤2). These encouraging results compared to a survival rate of 33% in 20054 suggest that the continuity of care after OHCA in a dedicated cardiac centre ICU, could be pivotal in increasing the likelihood of good neurologic outcome.27 We investigated factors occurring before ICU admission and during ICU management that can influence the outcome of patients after OHCA. Prolonged call time to ROSC (>25min), previous myocardial infarction, age >75 years and circulatory failure at hospital admission are independent factors associated with poor outcome. While direct admission to a specialized cardiac centre and positive lactate clearance reaching plasma level <2.5mmol/l at 12h are linked with increased survival rate and better neurological performances. The present study and previous publications performed in other environments support the concept that victims of cardiac arrest should be directly admitted to a tertiary centre in where an experienced and multidisciplinary staff is on call 24/7.25,27,29–31,49–52 The large proportion of cardiovascular predisposing factors found in our cohort justifies the direct admission in a cardiac centre with prompt interventional cardiac approach in patients suffering from OHCA due to shockable rhythm. In fact, acute myocardial ischaemia was the primary cause of 69.4% of OHCAs in the studied population. Emergent coronary angiography was thus performed in 94.7% of cases and 66.5% of them were treated by percutaneous coronary intervention (PCI).53–55 After rapid myocardial revascularisation with restoration of an adequate organ driving blood pressure56 ICU treatment should continue with haemodynamic support and neuroprotection.57 This targeted management may improve survival and reduce secondary brain injury.19,25,34,58 Unfortunately, direct admission in a cardiac receiver centre is not yet a reality in several Western countries since two surveys on organization and post-resuscitation care indicate a large discrepancy between published guidelines and the daily clinical practice.35,59–61

In our cohort, a progressive increase of plasma lactates or a negative lactate clearance index in the first hours of ICU stay are likely to be caused by the prolongation of circulatory failure which increases the risk of poor outcome.20,21,42,62,63 The finding of our study suggests that a positive lactate clearance index (i.e. decrease in lactate level) could be an indicator of a proper and timely haemodynamic resuscitation potentially limiting ischaemic damage. Therefore, in our centre, lactate clearance reaching normal plasma levels in the firsts 12h was used as a marker of optimal organ reperfusion and potential favourable outcome.

Myoclonus and sub-clinical epileptic EEG patterns still remain a frequent manifestations of global brain ischaemia.47,64 In our study, we considered the prescription of anticonvulsant therapy as a surrogate marker for post OHCA ischaemic brain injury. From our analysis anticonvulsant therapy appears the strongest indicator of poor neurologic outcome. This result stress the importance of early EEG monitoring to detect clinically silent epileptic activity.65 The time elapsed between OHCA and the first signs of neurological recovery is rarely reported in the literature and therefore in our work we defined the awakening when the patient followed simple verbal orders (best motor response, GCS=6). This finding documents that patients admitted to our ICU after OHCA with a positive neurological prognosis needed approximately 3–6 days of clinical observation.66,67 In our opinion this insight demonstrates the importance to avoid prognostication before a week from OHCA has elapsed.68 The final analysis combining all independent predictors yields a model with a better predictive value. This result suggests that neurological outcome after OHCA depends from a complex multifaceted post-resuscitation pathway based on continuity of care.

Our study has limitations. Firstly, our results report the experience a single cardiac centre experience. In order to reduce the impact of this bias we performed a data collection based on published standards and recommendations in cardiac arrest research. This standardized approach should permit the comparison of our results with other centres using the same criteria for the assessment of quality of care in patients who have survived to OHCA. The second limitation concerns patient's selection since our register includes only shockable rhythms. Thirdly, the outcome after OHCA could be influenced by the local rescue protocols applied in each emergency system. Our study focused on post resuscitation care; therefore, in order to decrease the impact of the pre-hospital phase on our analysis, we adjusted the ICU events for the main unbiased extra-hospital factors. Lastly, we defined CPC <2, as primary end-point, since we considered neurologic outcome as a valid surrogate of survival.

Direct admission to a cardiac referral centre and targeted haemodynamic ICU management monitored by positive lactate clearance during the first 12h seem both to increase the likelihood of good neurological outcome. Additionally, the time between OHCA and the first signs of neurological recovery suggests the need for further investigations focused on the correct timing of prognostication after OHCA.

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  Study design: Tiziano Cassina, Gabriele Casso;

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  Study conduct: Tiziano Cassina, Sara Clivio, Alessandro Putzu, Michele Villa;

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  Data analysis: Tiziano Cassina, Sara Clivio, Alessandro Putzu, Michele Villa, Daniela Fortuna;

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  Data interpretation: Tiziano Cassina, Sara Clivio, Alessandro Putzu, Michele Villa, Tiziano Moccetti, Daniela Fortuna, Gabriele Casso;

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  Writing and revising paper: Tiziano Cassina, Sara Clivio, Alessandro Putzu, Michele Villa, Tiziano Moccetti, Daniela Fortuna, Gabriele Casso.

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  All authors read and approved the final manuscript.

The study was supported by department funds only.

The authors declare no conflicts of interests.