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Norepinephrine is a standard of care in the hemodynamic management of septic shock concomitantly to fluid administration. However, no guidelines exist concerning norepinephrine weaning. Further more, norepinephrine may rapidly restore macrocirculatory hemodynamics through stressed volume without treating the underlying volume deficit, especially in the absence of optimal volume expansion. Norepinephrine weaning may reveal latent/persisting need for volume expansion in apparently stable patients.
Observational study of norepinephrine weaning in seven resuscitated SICU septic shock patients. Weaning was performed in 0.1 mg/hour decrements every 5 to 15 minutes until hemodynamic instability, defined as a mean arterial pressure (MAP) ≤70 mmHg, interrupted the process, at which point pulse pressure variation (PPV) was measured and transthoracic echocardiography (TTE) performed as per standard procedures. Upon instability with PPV ≥13%, 250 ml fluid challenge was performed and the MAP increase allowed pursuit of weaning, whereas instability with PPV <13% halted weaning. Nonparametric correlations were sought between norepinephrine decrements and variations over weaning (and fluid challenge) in PPV, arterial compliance, and indexed systolic ejection volume (iSEV). Global resuscitation endpoints (serum lactate, ScvO2) were compared before and after the entire weaning process.
Two behaviors were observed. First, norepinephrine weaning unmasked latent preload dependency in steps characterized by marked PPV increase (16.5%, 8 to 36), correlated to norepinephrine decrements (ρ = 0.971; r2 = 0.745; P = 0.005) resulting in PPV ≥13% and fluid challenge increasing the MAP and allowing pursuit of weaning. Second, weaning revealed norepinephrine dependency in steps halted by instability and characterized by slight PPV increases (3.9%, 0.3 to 8.4), resulting in PPV <10%, and a decrease in iSEV that was correlated to norepinephrine decrements (ρ = 0.943; r2 = 0.830; P = 0.001). Globally, weaning decreased serum lactate to under 2 mmol/l with ScvO2 maintained above 70%.
Hemodynamic stability through norepinephrine use in septic shock might be at the cost of occulting residual fluid requirements which can be revealed during norepinephrine weaning.