Individualized early goal-directed therapy in systemic inflammation: is full utilization of preload reserve the optimal strategy?
OBJECTIVE
In severe acute pancreatitis, the administration of fluids in the presence of positive fluid responsiveness is associated with better outcome when compared to guiding therapy on central venous pressure. We compared the effects of such consequent maximization of stroke volume index with a regime using individual values of stroke volume index assessed prior to severe acute pancreatitis induction as therapeutic hemodynamic goals.


METHODS
Prospective, randomized animal study.


METHODS
University animal research laboratory.


METHODS
Thirty domestic pigs.


METHODS
After randomization, fluid resuscitation was started 2 hours after severe acute pancreatitis induction and continued for 6 hours according to the respective treatment algorithms. In the control group, fluid therapy was directed by maximizing stroke volume index, and in the study group, stroke volume index assessed prior to severe acute pancreatitis served as primary hemodynamic goal.


RESULTS
Within the first 6 hours of severe acute pancreatitis, the study group received a total of 1,935.8 ± 540.7 mL of fluids compared with 3,462.8 ± 828.2 mL in the control group (p < 0.001). Pancreatic tissue oxygenation did not differ significantly between both groups. Vascular endothelial function, measured by flow-mediated vasodilation before and 6 hours after severe acute pancreatitis induction, revealed less impairment in the study group after treatment interval (-90.76% [study group] vs -130.89% [control group]; p = 0.046). Further, lower levels of heparan sulfate (3.41 ± 5.6 pg/mL [study group] vs 43.67 ± 46.61 pg/mL [control group]; p = 0.032) and interleukin 6 (32.18 ± 8.81 pg/mL [study group] vs 77.76 ± 56.86 pg/mL [control group]; p = 0.021) were found in the study group compared with control group. Histopathological examination of the pancreatic head and corpus at day 7 revealed less edema for the study group compared with the control group (1.82 ± 0.87 [study group] vs 2.89 ± 0.33 [control group, pancreatic head]; p = 0.03; 2.2 ± 0.92 [study group] vs 2.91 ± 0.3 [control group, pancreatic corpus]; p = 0.025).


CONCLUSIONS
Individualized optimization of intravascular fluid status during the early course of severe acute pancreatitis, compared with a treatment strategy of maximizing stroke volume by fluid loading, leads to less vascular endothelial damage, pancreatic edema, and inflammatory response.
1Department of Anesthesiology, Center of Anesthesiology and Intensive Care Medicine, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. 2Department of General, Visceral and Thoracic Surgery, Center of Surgical Sciences, University Medical Center Hamburg-Eppendorf, Hamburg, Germany. 3Laboratory of Pathology, Lübeck, Germany.
Karin H
KH
Wodack
Annika M
AM
Poppe
Lena
L
Tomkötter
Tomköetter
T
Lena
Kai A
KA
Bachmann
Cilly M
CM
Strobel
Sarah
S
Bonk
Jan
J
Havel
Kai
K
Heckel
Andreas
A
Gocht
Bernd
B
Saugel
Oliver
O
Mann
Jakob R
JR
Izbicki
Alwin E
AE
Goetz
Constantin J C
CJ
Trepte
Daniel A
DA
Reuter
D000208:Acute Disease; D000818:Animals; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000503:physiopathology; D004797:Enzyme-Linked Immunosorbent Assay; D005440:Fluid Therapy / Q000379:methods*; D019276:Glycocalyx / Q000378:metabolism; D006439:Hemodynamics; D006497:Heparan Sulfate / Q000097:blood; D007249:Inflammation / Q000503:physiopathology / Q000628:therapy*; D010195:Pancreatitis / Q000628:therapy*; D011446:Prospective Studies; D011897:Random Allocation; D012720:Severity of Illness Index; D013318:Stroke Volume / Q000502:physiology*; D013552:Swine; D053668:Syndecan-1 / Q000097:blood
D006497:Heparan Sulfate; D053668:Syndecan-1