Increasing mean arterial blood pressure in sepsis: effects on fluid balance, vasopressor load and renal function

Abstract

IntroductionThe objective of this study was to evaluate the effects of two different mean arterial blood pressure (MAP) targets on needs for resuscitation, organ dysfunction, mitochondrial respiration and inflammatory response in a long-term model of fecal peritonitis.MethodsTwenty-four anesthetized and mechanically ventilated pigs were randomly assigned (n = 8/group) to a septic control group (septic-CG) without resuscitation until death or one of two groups with resuscitation performed after 12 hours of untreated sepsis for 48 hours, targeting MAP 50-60 mmHg (low-MAP) or 75-85 mmHg (high-MAP).ResultsMAP at the end of resuscitation was 56 ± 13 mmHg (mean ± SD) and 76 ± 17 mmHg respectively, for low-MAP and high-MAP groups. One animal each in high- and low-MAP groups, and all animals in septic-CG died (median survival time: 21.8 hours, inter-quartile range: 16.3-27.5 hours). Norepinephrine was administered to all animals of the high-MAP group (0.38 (0.21-0.56) mcg/kg/min), and to three animals of the low-MAP group (0.00 (0.00-0.25) mcg/kg/min; P = 0.009). The high-MAP group had a more positive fluid balance (3.3 ± 1.0 mL/kg/h vs. 2.3 ± 0.7 mL/kg/h; P = 0.001). Inflammatory markers, skeletal muscle ATP content and hemodynamics other than MAP did not differ between low- and high-MAP groups. The incidence of acute kidney injury (AKI) after 12 hours of untreated sepsis was, respectively for low- and high-MAP groups, 50% (4/8) and 38% (3/8), and in the end of the study 57% (4/7) and 0% (P = 0.026). In septic-CG, maximal isolated skeletal muscle mitochondrial Complex I, State 3 respiration increased from 1357 ± 149 pmol/s/mg to 1822 ± 385 pmol/s/mg, (P = 0.020). In high- and low-MAP groups, permeabilized skeletal muscle fibers Complex IV-state 3 respiration increased during resuscitation (P = 0.003).ConclusionsThe MAP targets during resuscitation did not alter the inflammatory response, nor affected skeletal muscle ATP content and mitochondrial respiration. While targeting a lower MAP was associated with increased incidence of AKI, targeting a higher MAP resulted in increased net positive fluid balance and vasopressor load during resuscitation. The long-term effects of different MAP targets need to be evaluated in further studies.

Endotoxemic Myocardial Dysfunction

“…Thus, the CDP measurement can be helpful for identifying patients who need more elevated MAPs to improve their microcirculation. Corr<a et al (34) showed that when the MAP was increased in septic pigs, acute kidney injury was reduced; interestingly, the troponin level was slightly lower in the high-pressure group than in the low-pressure group. We previously reported that troponin elevation was correlated with nonsurvival (34).…”

“…Corr<a et al (34) showed that when the MAP was increased in septic pigs, acute kidney injury was reduced; interestingly, the troponin level was slightly lower in the high-pressure group than in the low-pressure group. We previously reported that troponin elevation was correlated with nonsurvival (34). In addition, our septic patients' data corroborated that CDP was a determinant of survival.…”

Lower Blood Pressure-Induced Renal Hypoperfusion Promotes Cisplatin-Induced Nephrotoxicity

“…Despite these approaches, incidences of cisplatin-induced AKI remain high. Previous reports indicate that decreases in mean blood pressure promote kidney ischemia and correlate with AKI in the intensive care unit [15][16][17] . However, no reports have examined the relationship between lower blood pressure and cisplatin-induced nephrotoxicity; we did this here.…”

Current concepts on hemodynamic support and therapy in septic shock

“…30 Nevertheless, targeting lower MAP levels may increase the incidence of tissue hypoperfusion and contribute to the progression of organ dysfunction. 31,32 …”