16 Feb 06
Posted in Critical Care, Inotropic support, Splanchnic perfusion at 18:44 by Laci
By P Seguin, B Laviolle, Pk Guinet, I Morel, Y Mallédant and E Bellissant
Critical care 2006, 10:R32, http://ccforum.com/content/10/1/R32
Introduction
Microcirculatory blood flow, and notably gut perfusion, is important in the development of multiple organ failure in septic shock. We compared the effects of dopexamine and norepinephrine (noradrenaline) with those of epinephrine (adrenaline) on gastric mucosal blood flow (GMBF) in patients with septic shock. The effects of these drugs on oxidative stress were also assessed.
Methods
This was a prospective randomized study performed in a surgical intensive care unit among adults fulfilling usual criteria for septic shock. Systemic and pulmonary hemodynamics, GMBF (laser-Doppler) and malondialdehyde were assessed just before catecholamine infusion (T0), as soon as mean arterial pressure (MAP) reached 70 to 80 mmHg (T1), and 2 hours (T2) and 6 hours (T3) after T1. Drugs were titrated from 0.2 µg kg-1 min-1 with 0.2 µg kg-1 min-1 increments every 3 minutes for epinephrine and norepinephrine, and from 0.5 µg kg-1 min-1 with 0.5 µg kg-1 min-1 increments every 3 minutes for dopexamine.
Results
Twenty-two patients were included (10 receiving epinephrine, 12 receiving dopexamine–norepinephrine). There was no significant difference between groups on MAP at T0, T1, T2, and T3. Heart rate and cardiac output increased significantly more with epinephrine than with dopexamine–norepinephrine, whereas. GMBF increased significantly more with dopexamine–norepinephrine than with epinephrine between T1 and T3 (median values 106, 137, 133, and 165 versus 76, 91, 90, and 125 units of relative flux at T0, T1, T2 and T3, respectively). Malondialdehyde similarly increased in both groups between T1 and T3.
Conclusion
In septic shock, at doses that induced the same effect on MAP, dopexamine–norepinephrine enhanced GMBF more than epinephrine did. No difference was observed on oxidative stress.
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14 Feb 06
Posted in Critical Care, Inotropic support, Sepsis at 19:33 by Laci
By SM Hollenberg, TS Ahrens, D Annane, ME Astiz, DB Chalfin, et al
Crit Care Med 2004; 32:1928-1948
Objective
To provide the American College of Critical Care Medicine with updated guidelines for hemodynamic support of adult patients with sepsis.
Data Source
Publications relevant to hemodynamic support of septic patients were obtained from the medical literature, supplemented by the expertise and experience of members of an international task force convened from the membership of the Society of Critical Care Medicine.
Study Selection
Both human studies and relevant animal studies were considered.
Data Synthesis
The experts articles reviewed the literature and classified the strength of evidence of human studies according to study design and scientific value. Recommendations were drafted and graded levels based on an evidence-based rating system described in the text. The recommendations were debated, and the task force chairman modified the document until <10% of the experts disagreed with the recommendations.
Conclusions
An organized approach to the hemodynamic support of sepsis was formulated. The fundamental principle is that clinicians using hemodynamic therapies should define specific goals and end points, titrate therapies to those end points, and evaluate the results of their interventions on an ongoing basis by monitoring a combination of variables of global and regional perfusion. Using this approach, specific recommendations for fluid resuscitation, vasopressor therapy, and inotropic therapy of septic in adult patients were promulgated.
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Posted in Acid-Base disorders, Critical Care, Inotropic support, Sepsis, Splanchnic perfusion at 19:29 by Laci
By B Levy, PE Bollaert, C Charpentier, L Nace, G Audibert, P Bauer, P Nabet, A. Larcan
Intensive Car Med 1997; 23:282-287
Objectives
To compare the effects of norepinephrine and dobutamine to epinephrine on hemodynamics, lactate metabolism, and gastric tonometric variables in hyperdynamic dopamine-resistant septic shock.
Design
A prospective, intervention, randomized clinical trial.
Setting
Adult medical/surgical intensive care unit in a university hospital.
Patients
30 patients with a cardiac index (CI) > 3.5 l · min-1 · m-2 and a mean arterial pressure (MAP) h 60 mmHg after volume loading and dopamine 20 ug/kg/min and either oliguria or hyperlactatemia.
Interventions
Patients were randomized to receive an infusion of either norepinephrine-dobutamine or epinephrine titrated to obtain an MAP greater than 80 mmHg with a stable or increased CI.
Measurements and main results
Baseline measurements included: hemodynamic and tonometric parameters, arterial and mixed venous gases, and lactate and pyruvate blood levels. These measurements were repeated after 1, 6, 12, and 24 h. All the patients fulfilled the therapeutic goals. No statistical difference was found between epinephrine and norepinephrine-dobutamine for systemic hemodynamic measurements. Considering metabolic and tonometric measurements and compared to baseline values, after 6 h, epinephrine infusion was associated with an increase in lactate levels (from 3.1 - 1.5 to 5.9 - 1.0 mmol/l; p < 0.01), while lactate levels decreased in the norepinephrine-dobutamine group (from 3.1 - 1.5 to 2.7 - 1.0 mmol/l). The lactate/pyruvate ratio increased in the epinephrine group (from 15.5 - 5.4 to 21 - 5.8; p < 0.01) and did not change in the norepinephrine-dobutamine group (13.8 - 5 to 14 - 5.0). Gastric mucosal pH (pHi) decreased (from 7.29 - 0.11 to 7.16 - 0.07; p < 0.01) and the partial pressure of carbon dioxide (PCO2) gap (tonometer PCO2 – arterial PCO2) increased (from 10 - 2.7 to 14 - 2.7 mmHg; p < 0.01) in the epinephrine group. In the norepinephrine-dobutamine group pHi (from 7.30 - 0.11 to 7.35 - 0.07) and the PCO2 gap (from 10 - 3.0 to 4 - 2.0 mmHg) were normalized within 6 h (p < 0.01). The decrease in pHi and the increase in the lactate/pyruvate ratio in the epinephrine group was transient, since it returned to normal within 24 h.
Conclusions
Considering the global hemodynamic effects, epinephrine is as effective as norepinephrine-dobutamine. Nevertheless, gastric mucosal acidosis and global metabolic changes observed in epinephrine-treated patients are consistent with a markedly inadequate, although transient, splanchnic oxygen utilization. The metabolic and splanchnic effects of the combination of norepinephrine and dobutamine in hyperdynamic dopamine-resistant septic shock appeared to be more predictable and more appropriate to the current goals of septic shock therapy than those of epinephrine alone.
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10 Feb 06
Posted in Critical Care, Sepsis, rhAPC at 21:38 by Laci
By RP Dellinger
Critical Care Medicine 34(2): 530-531
“There are two tragedies in life. One is not to get your heart’s desire. The other is to get it.” – George Bernard Shaw
…
So where do we stand? In my opinion we stand right where the FDA recommends, that is, administering rhAPC in situations of high risk of death, while considering counterbalancing effects of risk for life-threatening hemorrhage. When you have high risk of death from severe sepsis, then it is worth giving an expensive drug with a significant side effect profile, when that drug has satisfied the a priori end point for beneficial effect in a single large randomized placebo-controlled clinical trial. What is high risk of death? I believe that in general, high risk of death remains the four considerations as recommended by the Surviving Sepsis Campaign guidelines: acute respiratory distress syndrome, septic shock, multiple organ failure, and APACHE II ≥25. One caveat is that the ADDRESS trial results would suggest that an APACHE II ≥25 in and of itself may not represent high risk of death.
…
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