We have investigated the occurrence and severity of AKI in OHCA patients with early compared with deferred coronary angiography. This study did not show a higher incidence or grade of AKI in patients undergoing early angiography after OHCA. These findings suggest that coronary angiography can be performed safely either early or delayed in patients after OHCA with regard to the development of AKI. This outcome is an important addition to the results of the randomized COACT trial, which showed a similar survival for immediate and delayed angiography in OHCA patients without STEMI and also showed no difference in AKI between groups(16). Also, the present data are in line with findings from smaller retrospective cohort studies(15–18).
The reported incidence of AKI after cardiac arrest is up to 80% and depends on population and definition criteria(19). The incidence of AKI of 17.4% in our population is in line with previous results(15). Baseline risk factors for AKI, such as older age and chronic kidney disease, that were found more frequently in patients with deferred angiography, might have contributed to the decision for deferral. Patients in the early angiography group more frequently had a shockable rhythm and subsequently ST-elevation on the electrocardiogram, while patients with deferred angiography were more frequently comatose. During hospitalization, intra-aortic balloon pumps were used more frequently in the early angiography group compared to the deferred angiography group. This may reflect differences in cardiovascular performance between the groups, although the use of inotropics or vasopressors did not differ. Other baseline patient characteristics were balanced between the groups. Furthermore, in a patient-matched analysis no higher incidence of AKI was found in the early angiography group.
Previous, smaller studies focusing on the association between timing of coronary angiography and AKI found no difference between early or delayed angiography(15, 17, 18). With additional patient matching we accordingly did not find a higher incidence of AKI with early angiography; we even found a trend towards a higher incidence of AKI in the deferred angiography group. Considering that early angiography does not seem to aggravate the development of AKI, this may support treating physicians to choose either early or delayed coronary angiography. Remarkably, patients without angiography developed more AKI than patients that did undergo angiography. This can be explained by the fact that in patients with an overall worse condition, angiography is more often delayed. This group was older and had more comorbidities. However, mortality in the delayed angiography group was not higher than in the early angiography group.
We observed an association between the development of severe AKI after OHCA and increased mortality, which is in agreement with previous reports(2, 5, 20–24). Patients who developed AKI more frequently had hypotension and treatment with an inotropic or vasopressor. The optimal balance between level of perfusion and vasoactive support with regard to renal function after cardiac arrest is unknown. On the one hand, increasing mean arterial pressure improves renal function in OHCA patients, but on the other hand higher level of vasoactive support may increase the incidence of AKI(25). This aspect of clinical management after cardiac arrest must be studied in future research. Targeted temperature management was used as much in the early as in the deferred angiography group, however, patients who developed AKI were more frequently treated with targeted temperature management than patients without AKI. In a substudy of the TTM trial no difference in the incidence of AKI was found between temperature management at 33°C or 36°C degrees(24). Patients who received targeted temperature management in our study may be in a worse clinical condition. Intended targeted temperature management may be a factor in the timing of coronary angiography, as in the COACT trial patients undergoing immediate angiography reached target temperature later than the delayed angiography group(16). Although the optimal strategy for targeted temperature management is still unclear(26, 27), potential benefit from early cooling may be a reason to postpone angiography in comatose OHCA patients without STEMI.
Patients who developed AKI had more unfavorable characteristics and arrest factors. In accordance with other studies, early coronary angiography and amount of contrast were not associated with the development of AKI(15, 24). Only a higher baseline creatinine level and prolonged time to ROSC were independent predictors for AKI. The latter may reflect the intensity of ischemia-reperfusion injury after OHCA, of which the association with AKI has been noted in several studies(5, 20, 22, 24). Also increased creatinine on admission has been associated with development of AKI(5, 19, 22, 24).
One might question whether modern iodinated contrast media are nephrotoxic at all. Several studies concluded that early intervention is not harmful with regard to AKI(16–18, 20, 28). A meta-analysis of three matched cohort studies suggested that no association between AKI and iodinated contrast exposure in critically ill patients exists at all(15, 29). Iodinated contrast is thought to cause acute tubular necrosis through hypoxia from renal vasoconstriction and by direct cytotoxic effects within the nephron(30–32). Oxidative free radicals have been presumed to cause direct endothelial dysfunction during ischemia/reperfusion, such as after cardiac arrest(33, 34). Although nephrotoxicity from iodinated contrast has been well established, little is known about the pathophysiology of AKI after cardiac arrest. Furthermore, according to a meta-analysis of 52 studies, renal function does not substantially change after renal denervation with the use of contrast agents as a treatment to lower blood pressure(35).
The aim of this study was to investigate the effects of early angiography in a condition in which the renal system is already in distress after discontinuation of the circulation. The absence of augmented renal injury in this setting can be a contribution to management of patients after OHCA without STEMI, especially in the light of the newest international guidelines(36). At present, delayed as opposed to immediate angiography is recommended to be considered in OHCA patients without ST-elevation. In the decision process when to perform angiography, the lack of increased AKI incidence permits both strategies. So decision-making regarding management of OHCA patients should be individualized according to clinical status as well as to logistical circumstances.
To the best of our knowledge, this study is the first multicenter retrospective study to evaluate the association between timing of coronary angiography and AKI in a sizeable patient cohort. Nevertheless, several limitations of our study should be noted. First, causality of the results is difficult to determine and therefore the results should be interpreted with caution. Second, data on pre-admission renal function were not available. The use of the first serum creatinine values on arrival might have underestimated prior renal function, resulting in a lower AKI incidence. However, we note that it may take 24\(-\)36 h for serum creatinine to rise after a definite renal insult(37). Therefore, it is likely that the creatinine concentrations measured rapidly after OHCA are reasonably representative of pre-existing renal function. Third, we cannot exclude that performance of early angiography was influenced by a history of chronic kidney disease and creatinine level upon admission, as chronic kidney disease was less frequently present in the early angiography group and baseline creatinine was lower. Finally, exclusion of patients who died within two days may have produced an unknown bias.