6. However, during the first 72 hours, 158 patients did not receive a dosage of vasopressors above 0.5 ��g/kg/minute during at least two hours. Among these patients we considered as not selleck bio receiving high doses of vasopressors, 41 patients had AKI at H72 and among them, 39% (16/41) had a MAP averaged over H12 to H24 below 72 mmHg.Figure 6Vasopressors doses administered during the first 72 hours. To draw this figure we summed the hourly doses of norepinephrine and epinephrine (��g/kg/min.) administered continuously by iv infusion, considering these two catecholamines as equipotent …DiscussionThe main result of this prospective study is that in shocked patients with initial renal insult as defined by a serum creatinine above 1.

5 times the baseline value during the first 6 hours, the occurrence of AKI during the first 72 hours of care is linked to the time-averaged MAP obtained with therapy during the first 24 hours. In these patients, it appears that a MAP higher than the universally recommended level of 65 mmHg could be necessary to avoid worsening of renal function. Our subgroup analyses revealed that this is especially true in septic shock patients, whereas in patients with shock of other origins the link between MAP and AKI at H72 is less obvious.MAP level is essential to protect renal function, since below a certain MAP threshold, when autoregulation is exceeded, RBF decreases and leads to AKI [25]. In our study, the best threshold of time-averaged MAP over H6 to H24 or over H12 to H24 for predicting AKI at H72, ranged from 72 to 82 mmHg in patients with AKI at H6 and septic shock.

This result is in line with the retrospective study conducted by Dunser et al. [12], which proposed that the best MAP threshold for predicting the need of RRT in septic shock was 75 mm Hg. Altogether, these observations suggest that patients with septic shock and initial renal insult might need a higher MAP than patients with lower risk of AKI. This could be explained by the loss of autoregulation following acute renal insult. Nevertheless, up to now clinical data to support this view are still lacking. Only animal studies about ischemic acute renal failure induced by the clamping of renal artery have shown an impairment of autoregulation from the 18th hour following the renal injury [15-18].In our study, in the patients with non septic shock and/or no AKI at H6, we did not determine any MAP threshold that could predict AKI at H72.

Perhaps in these patients autoregulation was preserved. Furthermore, MAP is not the sole determinant of renal function in shock. Organ hypoperfusion and/or reperfusion lead to an important GSK-3 inflammatory reaction and inflammatory mediator systemic delivery known to be involved in renal injuries [26-30]. The recent study conducted by Lerolle et al. [31] confirms that renal lesions associated with AKI in septic shock are more complex than acute tubular injuries, involving intense capillary leukocytic infiltration and apoptosis.