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>
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
N-ACETYLCYSTEINE PRESERVES OXYGEN-CONSUMPTION AND GASTRIC-MUCOSAL PH DURING HYPEROXIC VENTILATION
cardiac-output; critically-ill patients; endotoxin; gas-exchange; General & Internal Medicine; l-arginine; nitric-oxide synthesis; relaxing factor; Respiratory System; septic patients; skeletal-muscle; superoxide
Hyperoxic ventilation, used to prevent hypoxemia during potential periods of hypoventilation, has been reported to paradoxically decrease whole body oxygen consumption (Vo(2)). Reduction in nutritive blood flow due to oxygen radical production is one possible mechanism. We investigated whether pretreatment with the sulfhydryl group donor and O-2 radical scavenger N-acetylcysteine (NAG) would preserve whole body Vo(2) and prevent deterioration of oxygenation in gastric mucosal tissue during hyperoxia. Thirty-eight patients, requiring hemodynamic monitoring (radial and pulmonary artery catheters) due to sepsis syndrome, were included in this randomized experiment. All patients exhibited stable clinical conditions (hemodynamics, body temperature, hemoglobin, Flo(2) < 0.5). A gastric tonometer was placed to measure the gastric intramucosal pH (pH(i)), which indirectly assesses nutritive blood flow to the mucosa. Cardiac output was determined by thermodilution and Vo(2) by cardiovascular Fick. After baseline measurements, patients randomly received either 150 mg . kg(-1) NAC (n = 19) or placebo (n = 19) in 250 ml 5% dextrose intravenously over a period of 15 min. Measurements were repeated 30 min after starting NAC or placebo infusion, 30 min after starting hyperoxia (Flo(2) = 1.0), and 60 min after resetting the original Flo(2). There were no significant differences between groups in any of the measurements before treatment and after the return to baseline Flo(2) at the end of the study. NAG, but not placebo infusion, caused a slight but significant increase in cardiac output and decrease in systemic vascular resistance. Significant differences between groups during hyperoxia were: Vo(2) (NAG: 114 +/- 9 mi min(-1) m(-2) versus placebo: 81 +/- 31 ml . min(-1) m(-2); p = 0.008) and oxygen extraction ratio (NAG: 21 +/- 6% versus placebo: 14 +/- 5%; p = 0.003). The mean decrease of Vo(2) was 11% in the NAC group versus 34% in the placebo group. The mean decrease of the oxygen extraction ratio was 12% in the NAC group versus 34% in the placebo group. NAC prevented a decrease in pH(i) in hyperoxia (NAG: 7.28 +/- 0.10 versus placebo: 7.14 +/- 0.18; p = 0.012). NAC helped preserve whole body oxygen uptake, oxygen extraction ratio, and pH(i) during brief hyperoxia in these septic patients. This suggests that pretreatment with NAC can attenuate impaired tissue oxygenation during hyperoxia.
Reinhart K; Spies C D; Meierhellmann A; Bredle D L; Hannemann L; Specht M; Schaffartzik W
American Journal of Respiratory and Critical Care Medicine
1995
1995-03
Journal Article
n/a