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


METHODS
Twenty-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).


RESULTS
MAP 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).


CONCLUSIONS
The 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.
Thiago Domingos
TD
Corrêa
Madhusudanarao
M
Vuda
Jukka
J
Takala
Siamak
S
Djafarzadeh
Eliézer
E
Silva
Stephan Mathias
SM
Jakob
D000818:Animals; D062186:Arterial Pressure / Q000187:drug effects / Q000502:physiology*; D005260:Female; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology*; D018836:Inflammation Mediators / Q000378:metabolism; D007668:Kidney / Q000187:drug effects / Q000502:physiology*; D008297:Male; D011897:Random Allocation; D012151:Resuscitation / Q000379:methods; D018805:Sepsis / Q000378:metabolism* / Q000503:physiopathology* / Q000628:therapy; D013552:Swine; D014662:Vasoconstrictor Agents / Q000494:pharmacology / Q000627:therapeutic use; D014882:Water-Electrolyte Balance / Q000502:physiology*
D018836:Inflammation Mediators; D014662:Vasoconstrictor Agents