Postoperative blood pressure deficit and acute kidney injury progression in vasopressor-dependent cardiovascular surgery patients

We investigated whether, in patients who had undergone cardiovascular surgery and were receiving vasopressor support, the time-weighted difference between premorbid and in-ICU pressure-related parameters (the degree of relative hypotension) was greater among those who developed AKI progression compared with those who did not. We observed that although patients with AKI progression had equivalent MAP, DAP, and MPP to those who did not, they had significantly greater DAP, MPP, and DPP deficits.

Selection of an effective BP target to manage vasopressor-dependent patients has been a controversial issue for decades. With respect to septic shock, a large randomized clinical trial (N = 776) compared protocols targeting MAPs of either 65 mm Hg to 70 mm Hg or 80 mm Hg to 85 mm Hg for 5 days and found no significant difference in mortality [2]. However, chronic hypertension was reported in 44 % of patients, and in a predefined subgroup analysis of these patients, targeting a higher MAP was associated with a lower rate of serum creatinine doubling and renal replacement therapy requirement. A recent review of data related to MAP targets in septic shock identified seven comparative studies and suggested that a MAP target of 65 mm Hg is usually sufficient in patients with septic shock, but a MAP of approximately 75 mm Hg to 85 mm Hg may prevent AKI development in patients with chronic hypertension [11].

Fewer studies exist for types of shock other than septic shock. In a case-control study in noncritically ill ward patients, those who developed AKI were more likely to have had relative hypotension than control patients [12]. In an observational study of patients during cardiopulmonary bypass in cardiac surgery, the duration and degree to which MAP was below the cerebral autoregulation threshold was independently associated with AKI, but absolute MAP was not [13]. To the best of our knowledge, there are only two previous studies that evaluated the impact of changes from the premorbid BP level on subsequent AKI development or progression in critically ill patients with shock [3, 14]. One observational study comprised 51 consecutive heterogeneous patients requiring vasopressors and compared premorbid MPP estimated from premorbid BP and CVP with MPP during resuscitation [3]. The incidence of AKI progression was greater among patients with greater MPP deficits. The other observational study comprised 107 patients with septic shock and investigated the association of change from premorbid values with AKI progression [14]. Median MAP deficit was similar for patients with or without severe AKI; however, median MPP deficit was greater in patients with severe AKI. These results are consistent with those found in the present study.

We observed a greater DAP deficit (P = 0.027) and DPP deficit (P = 0.002) in the AKI+ group. We also observed a lower CVP deficit in the AKI+ group (P = 0.033). A recent retrospective study of 137 septic patients in the ICU showed associations between lower DAP or higher CVP and AKI but not between MAP or cardiac output and AKI [5]. The present study is the first to report an association between changes from premorbid DAP and AKI progression. In the present study, 23.8 % of the %DPP deficit was due to an increase in CVP, and 76.2 % was due to a decrease in DAP. These results suggest that a role of both DAP and back pressure (renal venous pressure) are potentially important in the development of AKI.

Previous studies have reported an association between greater premorbid MAP and a shift of the kidney’s autoregulatory range to the right [15]. Our present results imply that the autoregulation of renal blood flow may be more strongly affected by MPP and DPP than MAP because premorbid MPP and DPP were higher in AKI+ group but premorbid MAP was similar between groups. Particularly, deficit in diastolic perfusion may be the major factor responsible for decreased renal perfusion and function. Because renal vascular resistance is low, as evidenced by a positive diastolic blood flow velocity [16, 17], DPP might be a key determinant of renal perfusion. This raises the possibility that increasing diastolic blood flow and decreasing back-pressure determinants (CVP or renal venous pressure) may be important future targets for hemodynamic manipulation in these patients. This study could not assess a causal relationship between hemodynamic parameter deficits and AKI progression. Further studies are needed to clarify whether it is possible to prevent subsequent AKI progression with hemodynamic interventions, and what would be the targets of DAP, MPP and DPP deficits.

This is the first study to investigate changes from premorbid to in-ICU levels of key pressures in patients with shock after cardiovascular surgery and the first to identify which hemodynamic parameters differ in patients who develop AKI progression. We focused on patients who had undergone cardiovascular surgery for whom we could estimate premorbid CVP accurately according to preoperative echocardiography. In addition, this is the first study to demonstrate the importance not only of MPP deficit but also of DPP deficit as possible risk factors for subsequent deterioration of renal function.

There are several limitations in the present study. First, this was single center in design, with a small sample size. We excluded patients who stayed in the ICU for shorter than 48 hours, since our study design required a long observational period, enough to diagnose AKI progression. We also excluded patients who received mechanical cardiovascular support (ECMO or IABP), to avoid the impact of mechanical support on renal perfusion. However, we believe that such exclusion made our study patients more homogenous to study an association between systemic hemodynamics and AKI progression in patients receiving vasopressors. However, the incidence of AKI and outcomes in patients in our ICU are consistent with those of studies reporting the epidemiology of AKI in patients undergoing cardiovascular surgery [18, 19]. The sample size of our study was larger than that of the only previous study of patients with nonspecific shock [3]. In addition, the median achieved MAP of 74 mm Hg in our study patients was quite similar to that reported among vasopressor-dependent septic shock patients in the previous major randomized trial [20] and in a recent observational study of the association between systematic hemodynamics and septic AKI [5]. The median achieved CVP of 8 mm Hg was also the same as the lower limit level recommended in the current guidelines for septic shock [21] and slightly lower than that reported in a recent randomized trial of early goal-directed therapy [22].

It is unclear whether the methods of BP and CVP estimation used in the present study represent true premorbid BP and CVP values. However, we estimated baseline CVP by using inferior vena cava parameters according to the American Society of Echocardiography guidelines [7]. This approach might make the premorbid CVP value more accurate than that reported in previous studies [3, 14]. Finally, we studied only a cohort of patients with shock after cardiovascular surgery. Therefore, our findings may not apply to patients with shock due to other types of critical illness.