Catecholamines in cardiogenic shock - dosis fecit venenum

Despite catecholamines being routinely used around the world in the treatment of patients in shock, the evidence on the association with mortality is scarce with some trials being biased by high dosages and concomitant use of multiple adrenergic drugs.

We sought to investigate the association of catecholamine, their dosages and drugs combination with mortality in all comers with cardiogenic shock (CS).

Cardiogenic shock was defined according to latest recommendation as well as the SCAI stratification. Only patients with baseline use of adrenergic drugs were included; patients with cardiac arrest at clinical presentation and with an implanted mechanical circulatory support at any time during admission were excluded. The primary endpoint of the study was in-hospital mortality according to adrenergic drugs use and dosage. Binary logistic regression analysis was applied with adjustment variables selected on univariate stepwise approach: age, positive pressure ventilation, CRRT, MAP, lactate, SCAI. Likelihood ratio test comparing a model with the spline function of the covariate vs a null model was used to test the association between the covariate and the event.

Amongst 1056, 240 patients (age 65 ±14.2; gender female 27.7%) were considered for analysis.

35% were ischemic CS, 65% HF – CS. SCAI distribution was as follow: SCAI B 19.8% C 54.9; D 16.3; E 1.1%. Mean systolic pressure was 98.6 mmHg (± 22); MAP 72.2 (±16) mmHg; HR 94.5 (±27); bpm RAP 14 (±6) mmHg; lac 4.9 (±4) mmol/L; eGFR 47.3 (±32).

Ninety-seven patients used adrenaline as first inotropes (41.6%), 124 (53%) used noradrenaline and 56% used dobutamine as first inotrope. The average dosages were adrenaline 0.09 [0.05-0.1] mgc/Kg/min; noradrenaline 0.14 [0.1 – 0.27] mgc/Kg/min; dobutamine 5 [3.8 – 5.85] mgc/Kg/min.

The use of adrenaline was not associated with in hospital mortality, conversely both the use of noradrenaline and dobutamine was associated with mortality (Table 1). Additionally, the combination of multiple drugs demonstrated a further increase association with worsen outcome. These results were confirmed when adjusted for relevant variables in the multivariate model. Interestingly the dosages of adrenaline and dobutamine were both associated with increased mortality.

The result of the preliminary analysis show that adrenaline was not associated with mortality when used as inotrope at clinical dosages (< 0.1 mcg/Kg/min); while higher dosages are associated with mortality likely because they induced the known detrimental metabolic effect. The combination of multiple inotropes also exposes to worsen outcome.Table 1  Figure 1