The Bradykinin Response and Early Hypotension at the Introduction of Continuous Renal Replacement Therapy in the Intensive Care Unit

Abstract

We assessed the relationship of certain clinical variables (including bradykinin [BK] release and dialysis membrane) to initial mean arterial pressure (MAP) reduction in 47 patients requiring continuous renal replacement therapy (CRRT) in an intensive care unit. The pretreatment MAP was 84 +/- 14 mm Hg for the group as a whole. The initial MAP reduction was 11.5 (7-20) mm Hg, occurring 4 to 8 min after connection. MAP reduction was 9 (6-15) mm Hg with polyacryonitrile (PAN) membranes versus 14 (5-19) mm Hg with polysulfone (PS) (not significant). There were positive correlations between MAP reduction and BK concentration at 3 (BK3; r = 0.58, p < 0.01) and 6 (BK6; r = 0.67, p < 0.001) min with PAN but not with PS. A greater reduction in MAP was seen in patients who were not receiving inotropic support (Mann-Whitney test, p < 0.01). BK3 and BK6 values for the PAN and PS groups were not significantly different. However, BK concentrations greater than 1,000 pg/ml were only seen with PAN (6 patients, MAP reduction 27 [17-31] mm Hg). There were positive (albumin) and negative (age; acute physiology, age, and chronic health evaluation score; C-reactive protein [CRP]; calcium) correlations with BK3/BK6 in the PAN and PS groups, some of which (albumin, CRP) reached statistical significance. In summary, MAP reduction at the start of CRRT correlates with BK concentration. The similarity of response with PAN and PS suggests an importance for other clinical factors. In this study, hemodynamic instability was more likely in patients with evidence of a less severe inflammatory or septic illness.

Contact System Activation in Patients with HAE and Normal C1 Inhibitor Function

“…50 The KK-kinin system can also be activated by contact with artificial surface in extracorporeal circulations with subsequent kininformation and hypotension. 51 …”

Clinical Application of Bioartificial Liver Support Systems

“…Along the same lines, bradykinin has been shown to cause a drop in mean arterial pressure within 10 minutes after the start of continuous renal dialysis. 123 Except for this transient hypotension, no other important BAL-related adverse events have been reported. In addition, no clinically manifest adverse immunologic reactions have been observed during short-term treatment with BAL systems charged with allogeneic or xenogeneic hepatocytes.…”

Dialytic Treatment for Septic Patients with Acute Kidney Injury

“…However, septic patients with AKI are much more susceptible to intradialytic hypotension due to systemic vasodilatation, coupled with a cardiac output which, although increased, is suboptimal for the degree of vasodilatation due to the presence of cardiodepressant factors. As part of the inflammatory milieu background, plasma concentrations of nitric oxide and bradykinin are increased with increased complement activation [7] . At the start of the dialysis, the passage of dilute blood across the dialyser can generate bradykinin and the anaphylatoxins C3a and C5a.…”

“…In the chronic dialysis patients, this reaction with the extracorporeal circuit is greater for patients prescribed angiotensin-converting enzyme inhibitors, which prevent bradykinin degradation, dialyser membranes with negatively charged surfaces, use of heparins which have increased negative charge, priming the circuit with normal saline or blood due to the negatively charged chloride or citrate, respectively, and endotoxinor peptidoglycan-contaminated dialysate. However, in the patients with systemic sepsis, bradykinin generation is more dependent upon the severity of the systemic inflammatory response syndrome response rather than dialyser choice [7] . Even so, the risk of early hypotension during treatment ( fig.…”