This study reviewed the data of the SOS-KANTO 2012 study, a multicenter, retrospective, cohort population-based study, and revealed the interrelationship between the outcome of paediatric patients with OHCA and the number of doses of adrenaline that was administered during resuscitation. The results revealed that the median number of adrenaline doses in paediatric OHCA patients with ROSC was three, and none of the OHCA paediatric patients with good neurological outcome had received more than three doses of adrenaline.
The predictors of survival to hospital discharge included a shorter interval between the OHCA and hospital arrival, a palpable pulse on presentation, comparatively fewer doses of adrenaline, and a relatively shorter duration of resuscitation in the ED (18). In the present study, the rate of successful ROSC was 23% (62/267), and 11.3% (7/62) of the survivors had a favourable neurological outcome. In previous reports, survival rates of paediatric OHCA patients have ranged from 2% to 22%, and 5-10% have survived to hospital discharge, with a good neurological outcome in 0-12% of the survivors (7, 10, 19). Multivariate logistic regression analysis of the ROSC and adrenaline administration showed that fewer adrenaline doses were associated with an improved rate of ROSC. Therefore, similarly as in the previous reports, shorter duration of resuscitation and fewer doses of adrenaline were related to the rate of successful ROSC (18).
Previous reports have described a specific number of adrenaline doses wherein the outcome was universally poor, such that that the futility of the resuscitative intervention could be assured. More than two or three doses of adrenaline have been previously reported as cutoff points (18, 19). In 1996, Schindler reported that there were no survivors of paediatric cardiac arrest if more than two doses of adrenaline were required (18). Young et al more recently reported in 2004 greater than 3 adrenaline doses to be universally associated with poor survival outcome (19, 20). In Moler’s cohort, 46 patients received more than three doses of adrenaline, and only seven of these 46 children survived to hospital discharge, and only one of these seven children was discharged from the hospital with a good neurological outcome. Overall, 45/46 (98%) of their patients had a poor outcome, defined as death or PCPC >2. Therefore, the cutoff point of four of more doses of adrenaline is usually, but not always, associated with a poor clinical outcome (10). In another report, patients who needed comparatively fewer doses of resuscitative drugs had improved survival outcomes. However, none of the patients who were given more than three doses of adrenaline survived to hospital discharge (10, 18). The results of the present study are similar to those mentioned in previous reports, and none of the children who were received more than three doses of adrenaline had a good neurological outcome.
Several observational studies have demonstrated that the effects of adrenaline may be time dependent, with earlier adrenaline administration associated with improved outcomes in OHCA with a shockable initial cardiac rhythm (21-23). Adrenaline is thought to be beneficial for patients in cardiac arrest through increased coronary perfusion pressure, which potentially enhances cardiac function; however, adrenaline may reduce cerebral blood flow and can cause increased myocardial oxygen demand (24, 25). Previous studies have consistently found that adrenaline improves the rate of ROSC during cardiac arrest (21, 26-29). The primary physiological mechanism for the improved rate of ROSC is attributed to the alpha-adrenergic effect of adrenaline to improve the aortic diastolic pressure, which leads to an increased blood flow to the left ventricle that is mediated by an increase in the coronary perfusion pressure (30-33). However, vital organs such as the brain and heart sustain more ischaemic amage with longer CPR times and frequent administration of adrenaline, and the beneficial effects of adrenaline on the left ventricular blood flow may be countered by a reduction in the cerebral blood flow, worsening of brain ischarmia, reduction of microcirculatory flow, and an increased myocardial oxygen demand (24, 25). In this study, the patients with prolonged resuscitation or more than three doses of adrenaline were unable to achieve a favourable neurological outcome. Similarly as in a previous report, the results of this study suggest that the rate of successful ROSC and favoruable neurological outcome in paediatric OHCA patients are related to fewer doses of adrenaline and the duration of resuscitation time (10, 19, 20). Thus, it is important to discuss the termination criteria with regard to the resuscitation time or doses of adrenaline in the paediatric OHCA patient, because the rates of ROSC and favourable neurological outcome do not change with an increasing number of adrenaline doses. Moreover, resuscitative efforts that involve many doses of adrenaline do not produce survivors with good neurological outcomes.
Several limitations should be considered when interpreting the results of the present study. First, a major limitation of this study concerns the long-term neurological outcome of survivors. In this study, neurological outcome could only be ascertained at 1 month after the OHCA with the simple clinical score of the PCPC. Optimally, outcome should be assessed at follow-up periods for at least a year and with a more extensive range of neurobehavioral assessment tools. Second, this study is a secondary analysis of the SOS-KANTO study 2012 and, because the original study was not specifically designed for the stated purpose of the present study, some of the study patients were missing data for the specific parameters evaluated in this study. Therefore, we are only able to comment on the association rather than the causation. Third, we do not have information on specific hospital factors, such as staff ratios or the presence of an intensivist in the intensive care unit or the paediatric intensive care unit. Furthermore, the emergency medical system and the procedures which are permissible for EMS personnel to carry out differs in the various subareas. The prehospitalisation procedures performed at the scene of the OHCA differed by the emergency medical system or patient’s age, and they might have affected the outcome to some extent. Fourth, these results may not be generalisable to different paediatric populations who suffer an OHCA. An important limitation of this study is the number of paediatric patients includeed in the study. In the original SOS-KANTO 2012 study, the OHCA paediatric patients compared only 1.6% of the total study population. this constitutes a very small proportion of the study sample compared with the population of adult patients. Finally, this study is also limited by its retrospective nature. Demographic and clinical data were obtained from medical records, which may have been incompletely or erroneously filled out, and there were several patients withmissing data.