Dopexamine Hydrochloride In Septic Shock
consumption; dobutamine; dopexamine hydrochloride; endotoxic dogs; General & Internal Medicine; heart failure; infusion; inotropic support; lactate; muscle; O-2 transport; O-2 uptake; optimal values; oxygen delivery; Respiratory System; respiratory-distress syndrome; sepsis; septic shock; tissue oxygenation; volume support
Objective: To test whether dopexamine hydrochloride, by its beta(2)-adrenoceptor and dopaminergic 1 (DA(1)) and dopaminergic 2 (DA(2)) agonistic properties, can improve oxygen consumption (V over dot O-2) in hyperdynamic patients with septic shock. Design: Prospective, single-cohort study. Setting: ICU, university hospital. Patients: Twenty-nine postoperative, hemodynamically stabilized, hyperdynamic patients with septic shock. Interventions: Short-term application (30 min) of dopexamine hydrochloride at a dose of 2 mu g/kg/min. Measurements: Complete hemodynamic profile with O-2 transport-related variables at baseline, 30 min after starting the dopexamine infusion, and 30 min after stopping the infusion. Main results: The dopexamine infusion resulted in significant increases in cardiac index (17%) (p<0.001) and O-2 delivery (DO2) (16%) (p<0.001), V over dot O-2 increased slightly but significantly about 4% (p<0.01) by respiratory gas exchange measurements and 9% (p<0.01) by cardiovascular Fick calculations. The O-2 extraction ratio decreased about 8% (0.001). Conclusions: The addition of dopexamine hydrochloride at a dose of 2 mu g/kg/min resulted in significant increases of DO2 and to a lesser extent V over dot O-2. Much of the global DO2 increase was not utilized, because O-2 extraction ratio decreased. Direct calorigenic effects of dopexamine and an increase in myocardial V over dot O-2 likely account for a large portion of the increase in global V over dot O-2. Whether any of the V over dot O-2 increase reflects improvement in regions of jeopardized tissue oxygenation remains to be clarified before the definite value of this lug in septic shock can be established.
Hannemann L; Reinhart K; Meierhellmann A; Wallenfang G; Bredle D L
Chest
1996
1996-03
Journal Article or Conference Abstract Publication
<a href="http://doi.org/10.1378/chest.109.3.756" target="_blank" rel="noreferrer noopener">10.1378/chest.109.3.756</a>
Prostacyclin In Septic Shock
critically; delivery; failure; General & Internal Medicine; ill patients; increases oxygen-consumption; infusion; lactate; norepinephrine therapy; Respiratory System; respiratory-distress syndrome; sepsis; tissue oxygenation
Objective: Investigation of the hypothesis that the infusion of 10 ng/kg/min prostacyclin (epoprostenol) (PGI(2)) improves O-2 uptake in patients with hyperdynamic septic shock. Design: Prospective, single cohort design. Setting: ICU, university hospital. Patients: Fifteen postoperative patients with septic shock. Interventions: Infusion of 10 ng/kg/min of PGI(2) for 60 min. Measurements: Complete hemodynamic profile with O-2 transport-related variables (simultaneous measurements of Vo(2) from the respiratory gases and by cardiovascular Fick) and blood lactate levels before start of the PGI(2)-infusion and 60 min thereafter. Main results: Oxygen delivery increased significantly (14 percent) from its already high value, 750+/-238 to 852+/-214 ml/min/m(2). The O-2 extraction ratio remained unchanged. When Vo(2) was measured from the respiratory gases, it was unchanged. When Vo(2) was measured by cardiovascular Fick, it increased slightly (p<0.05). Conclusions: We conclude that in this O-2 challenge test with PGI(2) in patients with septic shock, an increase in O-2 delivery was not matched by an increase in Vo(2). We believe that the adequate conventional support of these patients may have prevented the PGI(2) from revealing a ''covert'' O-2 debt. The PGI(2) test did not predict mortality by O-2 supply dependency. The small increase in Vo(2) as calculated indirectly suggests a degree of mathematical coupling of O-2 delivery and uptake.
Hannemann L; Reinhart K; Meierhellmann A; Bredle D L
Chest
1994
1994-05
Journal Article or Conference Abstract Publication
<a href="http://doi.org/10.1378/chest.105.5.1504" target="_blank" rel="noreferrer noopener">10.1378/chest.105.5.1504</a>
Epinephrine impairs splanchnic perfusion in septic shock
sepsis; oxygen consumption; General & Internal Medicine; epinephrine; agents; septic shock; norepinephrine; oxygen delivery; critically ill patients; intramural ph; tissue oxygenation; blood flow; oxygen consumption; gastric-mucosal ph; indocyanine green; splanchnic; splanchnic oxygen delivery; dobutamine; hepatic blood-flow; splanchnic oxygen consumption; vasoactive
Objective: To assess the effects of epinephrine on splanchnic perfusion and splanchnic oxygen uptake in patients with septic shock. Design: Prospective, controlled trial. Setting: University hospital intensive care unit (ICU). Patients: Eight patients with septic shock, according to the criteria of the 1992 American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference, requiring treatment with vasopressors. Interventions: We compared in crossover design a 2-hr infusion of epinephrine with dobutamine plus norepinephrine in eight ICU patients with septic shock, Systemic and splanchnic hemodynamics and oxygen transport were measured before and during treatment with epinephrine. Measurements and Main Results: There was essentially no effect of epinephrine on the global parameters, except for increased lactate concentrations, There were marked effects on the regional variables; epinephrine caused lower splanchnic flow and oxygen uptake, lower mucosal pH, and higher hepatic vein lactate. Conclusion: We conclude that undesirable splanchnic effects on patients in whom that region is particularly fragile should be considered when using epinephrine for septic shock treatment.
MeierHellmann A; Reinhart K; Bredle D L; Specht M; Spies C D; Hannemann L
Critical Care Medicine
1997
1997-03
Journal Article or Conference Abstract Publication
<a href="http://doi.org/10.1097/00003246-199703000-00005" target="_blank" rel="noreferrer noopener">10.1097/00003246-199703000-00005</a>
Endothelial NOS activity and myocardial oxygen metabolism define the salvageable ischemic time window for ischemic postconditioning
cardioprotection; mice; inhibition; Physiology; Cardiovascular System & Cardiology; activation; dysfunction; reperfusion injury; tissue oxygenation; consumption; blood flow; electron paramagnetic resonance; infarct size; ischemia and reperfusion; mitochondrial enzyme activity; mitochondrial permeability transition; rabbit hearts; regional
Cai M, Li Y, Xu Y, Swartz HM, Chen C, Chen Y, He G. Endothelial NOS activity and myocardial oxygen metabolism define the salvageable ischemic time window for ischemic postconditioning. Am J Physiol Heart Circ Physiol 300: H1069-H1077, 2011. First published January 7, 2011; doi: 10.1152/ajpheart.00694.2010.-Ischemic postconditioning (IPOC) could be ineffective or even detrimental if the index ischemic duration is either too short or too long. The present study is to demonstrate that oxygen supply and metabolism defines a salvageable ischemic time window of IPOC in mice. C57BL/6 mice underwent coronary artery occlusion followed by reperfusion (I/R), with or without IPOC by three cycles of 10 s/10 s R/I. In vivo myocardial tissue oxygenation was monitored with electron paramagnetic resonance oximetry. Regional blood flow (RBF) was measured with a laser Doppler monitor. At the end of 60 min reperfusion, tissue from the risk area was collected, and mitochondrial enzyme activities were assayed. Tissue oximetry demonstrated that I/R induced a reperfusion hyperoxygenation state in the 30- and 45-min but not 15- and 60-min ischemia groups. IPOC attenuated the hyperoxygenation with 45 but not 30 min ischemia. RBF, eNOS phosphorylation, and mitochondrial enzyme activities were suppressed after I/R with different ischemic time, and IPOC afforded protection with 30 and 45 but not 60 min ischemia. Infarct size measurement indicated that IPOC reduced infarction with 30 and 45 min but not 60 min ischemia. Clearly, IPOC protected mouse heart with a defined ischemic time window between 30 and 45 min. This salvageable time window was accompanied by the improvement of RBF due to increased phosphorylated eNOS and the preservation of mitochondrial oxygen consumption due to conserved mitochondrial enzyme activities. Interestingly, this salvageable ischemic time window was mirrored by tissue hyperoxygenation status in the postischemic heart.
Cai M; Li Y J; Xu Y; Swartz H M; Chen C L; Chen Y R; He G L
American Journal of Physiology-Heart and Circulatory Physiology
2011
2011-03
Journal Article or Conference Abstract Publication
<a href="http://doi.org/10.1152/ajpheart.00694.2010" target="_blank" rel="noreferrer noopener">10.1152/ajpheart.00694.2010</a>
INFLUENCE OF N-ACETYLCYSTEINE ON INDIRECT INDICATORS OF TISSUE OXYGENATION IN SEPTIC SHOCK PATIENTS - RESULTS FROM A PROSPECTIVE, RANDOMIZED, DOUBLE-BLIND-STUDY
blood gas analysis; critical illness; critically-ill patients; endotoxin; gastric mucosa; General & Internal Medicine; glutathione; intramural ph; l-arginine; multiple organ failure; n-acetylcysteine; nitric-oxide synthesis; organ failure; oxygen consumption; ph; relaxing factor; sepsis; septic; shock; skeletal-muscle; tissue oxygenation
Objectives: Deactivation of endothelium-derived relaxing factor due to an increased oxygen radical load during sepsis may contribute to an impairment in microcirculatory blood flow. We investigated whether treatment with the sulfhydryl donor and oxygen radical scavenger, N-acetylcysteine, would improve whole-body oxygen consumption (Vo(2)), gastric intramucosal pH, and veno-arterial CO2 gradient (veno-arterial PCO2) during septic shock. Design: Prospective, randomized, double-blind study conducted over 2 yrs. Setting: Septic shock patients admitted to the intensive care unit. Patients: Fifty-eight patients requiring hemodynamic monitoring (radial and pulmonary artery catheters) due to septic shock, were included in this study. All patients were examined within 72 hrs after the onset of sepsis. They were optimally resuscitated by conventional means with volume and inotropic agents, and exhibited stable clinical conditions (hemodynamic values, body temperature, hemoglobin, FIO2). Interventions: A gastric tonometer was inserted to measure the gastric intramucosal pH. Subjects randomly received either 150 mg/kg of intravenous N-acetylcysteine or placebo over a 15-min period, then a continuous infusion of 12.5 mg/hr of N-acetylcysteine or placebo over similar to 90 mins. Measurements: Infusion measurements were begun 60 mins after the beginning of infusion and lasted similar to 30 mins. The infusion was then discontinued and 2 hrs later the final measurements were taken. Main Results: Basic patient characteristics (age, sex, Acute Physiology and Chronic Health Evaluation [APACHE] II scores, Multiple Organ Failure scores) did not differ significantly, nor did pre- and 2-hr postinfusion measurements differ between any of the groups. Thirteen (45%) patients responded (i.e., showed an increase in Vo(2) >10%, reaching a mean of 19%) to the N-acetylcysteine infusion. The N-acetylcysteine responders also showed an increase in gastric intramucosal pH, a decrease in veno-arterial PCO2, an increase in oxygen delivery, cardiac index, stroke index, and left ventricular stroke work index, as well as a significant decrease in systemic vascular resistance in comparison to baseline. The N-acetylcysteine nonresponders, as well as the patients in the placebo group, did not show any significant changes in any of these variables. The N-acetylcysteine responders had a higher survival rate (69%) than the nonresponders (19%) and were studied earlier after onset of sepsis (37 hrs) than the nonresponders (61 hrs). The only significant difference between the entire N-acetylcysteine group (which included responders plus nonresponders) and the placebo group was an increased 30, in the entire N-acetylcysteine group during infusion measurements. Conclusions: N-acetylcysteine provided a transient improvement in tissue oxygenation in about half of the septic shock patients, as indicated by an increase in Vo(2) and gastric intramucosal pH and a decrease in veno-arterial PCO2. The higher survival rate in the N-acetylcysteine responders and the fact that half of the patients receiving N-acetylcysteine did not respond, suggests that, in some patients, sepsis irreversibly damages the microvasculature to the extent that N-acetylcysteine has no effect. If analyzed by intention to treat, the N-acetylcysteine did not produce effects that were significantly different from the placebo. Whether the N-acetylcysteine challenge was merely diagnostic or whether N-acetylcysteine can be effective in the treatment of sepsis deserves further investigation.
Spies C D; Reinhart K; Witt I; Meierhellmann A; Hannemann L; Bredle D L; Schaffartzik W
Critical Care Medicine
1994
1994-11
Journal Article
n/a