Relationship Between Serum Norepinephrine Levels at ICU Admission and the Risk of ICU-Acquired Delirium: Secondary Analysis of the Melatonin Evaluation of Lowered Inflammation of ICU Trial

Abnormal secretion of catecholamines is well known to cause delirium. In particular, disturbances of catecholamine balance can cause ICU-acquired delirium. The aim of this study was to evaluate the association between the serum levels of catecholamines and the risk of occurrence of ICU-acquired delirium separately in patients who had/had not received exogenous catecholamines before ICU admission. DESIGN: A secondary analysis of the data of 81 patients enrolled in our previous randomized clinical trial. SETTING: ICU of an academic hospital. PATIENTS: ICU patients in whom the serum levels of catecholamines were measured at ICU admission. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We evaluated the association between the serum levels of catecholamines measured at ICU admission and the risk of ICU-acquired delirium separately in patients who had received exogenous catecholamines at ICU admission (Ex[+] group) and those who had not received exogenous catecholamines (Ex[–] group). The serum levels of norepinephrine measured at ICU admission were significantly associated with the risk of ICU-acquired delirium in the Ex(–) group (odds ratio, 2.58; 95% CI, 1.02–6.52; p = 0.046), but not in the Ex(+) group (odds ratio, 1.02; 95% CI, 0.88–1.18; p = 0.823). Furthermore, there was a statistically significant interaction effect between the serum levels of norepinephrine and the use/nonuse of exogenous catecholamines at ICU admission in relation to the risk of occurrence of ICU-acquired delirium (p(interaction) = 0.017). CONCLUSIONS: The serum levels of norepinephrine measured at admission were associated with the risk of occurrence of ICU-acquired delirium in patients who had not received exogenous catecholamines at ICU admission, whereas no such association was observed in those who had received exogenous catecholamines previously. Thus, the association between the serum levels of catecholamines measured at admission and the risk of ICU-acquired delirium differed between patients who had/had not received exogenous catecholamines at ICU admission.