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
Murder mystery' for student practice of pulmonary physiology calculations.
Education; Blood Gas Analysis; Teaching Methods; Games; Oxygen Saturation; Respiratory Rate; Respiratory Tract Physiology; Lung – Physiology; Carbon Monoxide Poisoning – Diagnosis; Oxygen Consumption – Evaluation; Partial Pressure – Evaluation; Respiratory Therapy
Maron M B; Bosso F J
Respiratory Care
1992
1992-10
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1152/advances.1991.261.6.s3" target="_blank" rel="noreferrer noopener">10.1152/advances.1991.261.6.s3</a>
Acid-base interpretation: part 1: applying five rules in everyday cases.
Female; Male; Aged; Outpatients; Reference Values; Blood Gas Analysis; Inpatients; Middle Age; Cations; Anions; Acid-Base Imbalance – Diagnosis; Acidosis – Diagnosis; Alkalosis – Diagnosis; Acid-Base Equilibrium – Physiology; Carbon Dioxide – Analysis; Hydrogen-Ion Concentration – Evaluation
The interpretation of acid-base data can be greatly facilitated by applying five rules: (1) use the blood gas to identify acidemia or alkalemia, (2) determine whether the underlying cause of acidemia or alkalemia is respiratory or metabolic, (3) calculate the anion gap, (4) check for the degree of compensation, and (5) assess the relationship between anions (there should be a 1:1 relationship of acid to base). Alkalemia has an underlying respiratory cause if the partial pressure of carbon dioxide (PCO2) is substantially less than 40 min Hg. It has a metabolic cause if the bicarbonate content is greater than 25 mEq/L Acidemia has a respiratory cause if the PC02 is greater than 40/min Hg. It has a metabolic cause if the bicarbonate content is less than 25 mEq/L.Calculating the acidbase ratio may reveal a metabolic alkalosis not detected by rules 1 through 4.
Rutecki G W; Whittier F C
Consultant (00107069)
1997
1997-12
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
Edema development and recovery in neurogenic pulmonary edema.
Animals; Atrial Function; Blood Gas Analysis; Blood Volume; Dogs; Extravascular Lung Water/drug effects/*physiology; Female; Hemodynamics; Left; Male; Pulmonary Artery/physiopathology; Pulmonary Circulation/drug effects/physiology; Pulmonary Edema/chemically induced/*physiopathology; Radio-Iodinated; Serum Albumin; Sympathetic Nervous System/physiopathology
We determined the time course of changes in extravascular lung water (EVLW) that occur after massive sympathetic activation produced by intracisternal veratrine administration in chloralose-anesthetized dogs. Three groups of dogs were studied. In the first group (n = 9), acute increases in EVLW (occurring within minutes) were determined both by measuring extravascular thermal volume and by gravimetric analysis. In the second (n = 6) and third (n = 7) groups, changes in EVLW were followed for 2-3 h after veratrine administration. Extravascular thermal volume was measured in the second group. In the third group, right atrial injections of a vascular indicator (125I-labeled serum albumin) and an extravascular indicator (3HOH) were made while blood was sampled from the pulmonary artery (PA) and left atrium, and EVLW was determined by deconvolution of the left atrial and PA concentration-time curves. Indicator-dilution and gravimetric EVLW increased acutely only in dogs in which PA pressure exceeded 60 Torr, with two- to four-fold increases in EVLW being observed in dogs that developed the highest PA pressures (maximum 94 Torr). Thus, severe edema can develop rapidly after massive sympathetic nervous system activation but requires extreme degrees of pulmonary hypertension. In several dogs after the acute increase in EVLW associated with the pulmonary hypertension, the indicator-dilution EVLW decreased with time. These decreases appear to effect clearance of edema fluid rather than alterations in perfusion.
Maron M B; Holcomb P H; Dawson C A; Rickaby D A; Clough A V; Linehan J H
Journal of applied physiology (Bethesda, Md. : 1985)
1994
1994-09
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1152/jappl.1994.77.3.1155" target="_blank" rel="noreferrer noopener">10.1152/jappl.1994.77.3.1155</a>