Translational research in sepsis - an ultimate challenge?

Kampmeier, Tim; Ertmer, Christian; Rehberg, Sebastian

doi:10.1186/2040-7378-3-14

Cited by 5 publications

(4 citation statements)

References 32 publications

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“…Furthermore, species related differences in (receptor-)physiology may also play a role in this context 25 . AVP and its synthetic analogues (especially TP) are potent vasopressors, causing vasoconstriction by activation of vasopressin (V)-receptors.…”

Section: Discussionmentioning

confidence: 99%

Comparison of first-line and second-line terlipressin versus sole norepinephrine in fulminant ovine septic shock

Kampmeier

Arnemann

Heßler

et al. 2018

Sci Rep

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The Surviving Sepsis Guidelines suggest the use of vasopressin in case of catecholamine-refractory septic shock. Terlipressin (TP) as a V1-selective AVP analogue is a potential alternative, though data regarding the first-line administration in septic shock are scarce. The present study explored and compared the effects of first-line vs. second-line infusion of TP or sole norepinephrine regarding organ function, fluid and norepinephrine requirements and survival in fulminant ovine septic shock. Peritoneal sepsis was induced in 23 ewes after laparotomy and faecal withdrawal from the caecum. After onset of shock, causal and supportive sepsis therapy (antibiotics, peritoneal lavage, fluids and open-label norepinephrine) was performed in all animals. Concurrently, animals were randomized to receive 0.9% sodium chloride (control group) or TP (2 µg∙kg−1∙h−1, first-line group) after shock onset. In the second-line TP group, TP (2 µg∙kg−1∙h−1) was started once norepinephrine requirements exceeded 0.5 µg∙kg−1∙min−1. No significant differences were found between groups regarding survival, haemodynamics as well as fluid- and catecholamine-requirements. Kidney function and electron microscopic kidney injury were comparable between groups. In the present model of fulminant ovine septic shock, first-line TP infusion had no significant effect on fluid and norepinephrine requirements or organ dysfunction as compared to second-line TP infusion or placebo.

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Section: Discussionmentioning

confidence: 99%

Comparison of first-line and second-line terlipressin versus sole norepinephrine in fulminant ovine septic shock

Kampmeier

Arnemann

Heßler

et al. 2018

Sci Rep

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“…Since this is a model in sheep, the results of this and similar studies should be transferred to human medicine with caution. Though especially sheep models show similar hemodynamic development compared to human beings, results from animal models often differ from clinical trial data for a variety of reasons (3,23). Moreover, the impact of sole hemodynamic without causal therapy was not investigated and may be a focus of future studies.…”

Section: Limitationsmentioning

confidence: 99%

“…Sepsis and septic shock are among the most common causes of death in intensive care units (1,2). To investigate and establish new therapeutic agents and strategies, preclinical sepsis models are necessary that implement current treatment guidelines thereby allowing the most reliable translational research (3).…”

Section: Introductionmentioning

confidence: 99%

Sole causal therapy worsens outcome as compared to no therapy and combined causal and goal-directed supportive therapy in ovine septic shock

et al. 2018

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Background: There is clear evidence that early causal therapy improves outcome in sepsis and septic shock, whereas recent studies on supportive hemodynamic therapy have produced very conflictive results. The objective of the present study was to determine whether a supportive hemodynamic therapy guided by clinically relevant invasive monitoring improves survival and organ function in a high-lethality model of septic shock in sheep as compared to sole causal therapy including surgical and antimicrobial treatment. Methods: Twenty healthy ewes were anaesthetized and instrumented for hemodynamic surveillance. After laparotomy and fecal withdrawal from the caecum, animals were randomly assigned to one of four groups: sham, control, causal and combined therapy. In all groups but the sham group, feces were injected into the peritoneal cavity. Septic shock was defined as mean arterial pressure (MAP) ≤60 mmHg and arterial lactate concentration ≥1.8 mmol•L −1. Animals of the control group received no therapy, while the causal group received broad-spectrum antibiotic therapy and peritoneal lavage. The combined therapy group received causal therapy plus supportive hemodynamic therapy. Results: The sham animals showed no signs of systemic infection, while all other animals developed septic shock with arterial hypotension and lactic acidosis within 4.0 (4.0-6.8) hours. Induction of causal therapy did not impact on haemodynamics as compared to the control group. Notably, 50% of the control animals and none of the causal therapy animals survived the study. Combined therapy stabilized haemodynamics and improved organ function and survival as compared to control and causal therapy groups. Conclusions: The present data suggest that sole causal sepsis therapy without hemodynamic support worsens outcome even more than natural evolution of sepsis and combined causal and supportive therapy. This underlines the importance of early hemodynamic stabilization in parallel with antibiotic and surgical treatment of the sepsis focus.

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“…Furthermore, use of a suitable control group is crucial for result analysis and study integrity however suitable control interventions and investigator "blinding" make defining control group criteria difficult. Defining strict inclusion criteria for sepsis RCTs may overcome some obstacles posed by patient heterogenicity but the trial may then be faced with slow recruitment and smaller sample sizes yielding low specificity results (22). This idea of precision medicine versus a population-based approach in ICU medicine is key.…”

Section: Defining Patients For Inclusionmentioning

confidence: 99%