22 May 06

Effects of epinephrine, norepinephrine, and phenylephrine on microcirculatory blood flow in the gastrointestinal tract in sepsis

Posted in Inotropic support, Sepsis, Splanchnic perfusion at 18:37 by Laci

By V Krejci, L Hiltebrand, G Sigurdsson

Critical Care Medicine 2006;34:1456-1463

Objective
The use of vasopressors for treatment of hypotension in sepsis may have adverse effects on microcirculatory blood flow in the gastrointestinal tract. The aim of this study was to measure the effects of three vasopressors, commonly used in clinical practice, on microcirculatory blood flow in multiple abdominal organs in sepsis.

Design
Random order, cross-over design.

Setting
University laboratory.

Subjects
Eight sedated and mechanically ventilated pigs.

Interventions
Pigs were exposed to fecal peritonitis-induced septic shock. Mesenteric artery flow was measured using ultrasound transit time flowmetry. Microcirculatory flow was measured in gastric, jejunal, and colon mucosa; jejunal muscularis; and pancreas, liver, and kidney using multiple-channel laser Doppler flowmetry. Each animal received a continuous intravenous infusion of epinephrine, norepinephrine, and phenylephrine in a dose increasing mean arterial pressure by 20%. The animals were allowed to recover for 60 mins after each drug before the next was started.

Measurements and Main Results
During infusion of epinephrine (0.8 +/- 0.2 [mu]g/kg/hr), mean arterial pressure increased from 66 +/- 5 to 83 +/- 5 mm Hg and cardiac index increased by 43 +/- 9%. Norepinephrine (0.7 +/- 0.3 [mu]g/kg/hr) increased mean arterial pressure from 70 +/- 4 to 87 +/- 5 mm Hg and cardiac index by 41 +/- 8%. Both agents caused a significant reduction in superior mesenteric artery flow (11 +/- 4%, p < .05, and 26 +/- 6%, p < .01, respectively) and in microcirculatory blood flow in the jejunal mucosa (21 +/- 5%, p < .01, and 23 +/- 3%, p < .01, respectively) and in the pancreas (16 +/- 3%, p < .05, and 8 +/- 3%, not significant, respectively). Infusion of phenylephrine (3.1 +/- 1.0 [mu]g/kg/min) increased mean arterial pressure from 69 +/- 5 to 85 +/- 6 mm Hg but had no effects on systemic, regional, or microcirculatory flow except for a 30% increase in jejunal muscularis flow (p < .01). Conclusions
Administration of the vasopressors phenylephrine, epinephrine, and norepinephrine failed to increase microcirculatory blood flow in most abdominal organs despite increased perfusion pressure and-in the case of epinephrine and norepinephrine-increased systemic blood flow. In fact, norepinephrine and epinephrine appeared to divert blood flow away from the mesenteric circulation and decrease microcirculatory blood flow in the jejunal mucosa and pancreas. Phenylephrine, on the other hand, appeared to increase blood pressure without affecting quantitative blood flow or distribution of blood flow.

16 Feb 06

Dopexamine and norepinephrine versus epinephrine on gastric perfusion

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.

14 Feb 06

Comparison of norepinephrine and dobutamine to epinephrine in septic shock

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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