Lutz Hannemann

Epinephrine impairs splanchnic perfusion in septic shock

OBJECTIVEnTo assess the effects of epinephrine on splanchnic perfusion and splanchnic oxygen uptake in patients with septic shock.nnnDESIGNnProspective, controlled trial.nnnSETTINGnUniversity hospital intensive care unit (ICU).nnnPATIENTSnEight 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.nnnINTERVENTIONSnWe 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.nnnMEASUREMENTS AND MAIN RESULTSnThere 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.nnnCONCLUSIONnWe conclude that undesirable splanchnic effects on patients in whom that region is particularly fragile should be considered when using epinephrine for septic shock treatment.

Influence of N-acetylcysteine on indirect indicators of tissue oxygenation in septic shock patients: results from a prospective, randomized, double-blind study.

Objectives: Deactivation of endotheliumderived 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 wholebody oxygen consumption (&OV0312;o2), gastric intramucosal pH, and veno‐arterial CO2 gradient (veno‐arterial Pco2) during septic shock. Design: Prospective, randomized, doubleblind 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 ˜90 mins. Measurements: Infusion measurements were begun 60 mins after the beginning of infusion and lasted ˜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 &OV0312;o2 >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 &OV0312;o2 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 &OV0312;o2 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. (Crit Care Med 1994; 22:1738–1746)

Dopexamine increases splanchnic blood flow but decreases gastric mucosal pH in severe septic patients treated with dobutamine

OBJECTIVEnTo assess the effects of dopexamine on splanchnic blood flow and splanchnic oxygen uptake in septic patients.nnnDESIGNnA prospective, controlled trial.nnnSETTINGnA ten-bed intensive care unit (ICU) in a university hospital.nnnPATIENTSnTwelve patients with severe sepsis (according to the criteria of the 1992 American College of Chest Physicians/Society of Critical Care Medicine consensus conference) being stabilized by volume loading and treated to an elevated oxygen delivery by dobutamine infusion.nnnINTERVENTIONSnInfusion of increasing dosages of dopexamine (0.5, 1.0, 2.0, and 4.0 microg/kg/min).nnnMEASUREMENTS AND MAIN RESULTSnSystemic and splanchnic hemodynamic and oxygen transport parameters as well as gastric mucosal pH (pHi) were measured. A hepatic venous catheter technique with indocyanine green dye dilution was used to determine splanchnic blood flow. Dopexamine increased global and splanchnic oxygen delivery without affecting oxygen consumption (VO2). Splanchnic blood flow increased proportionally to cardiac output, indicating that there was no selective effect of dopexamine on the splanchnic flow. Dopexamine decreased pHi in a dose-dependent fashion in all 12 patients.nnnCONCLUSIONSnIn hemodynamically stable, hyperdynamic septic patients being treated with dobutamine, dopexamine has no selective effect on splanchnic blood flow. In fact, a decreased pHi suggests a harmful effect on gastric mucosal perfusion.

Comparison of dopamine to dobutamine and norepinephrine for oxygen delivery and uptake in septic shock.

OBJECTIVESnTo test whether dopamine infusion improves oxygen delivery (Do2) and oxygen uptake (VO2) in hyperdynamic septic shock patients stabilized by adequate volume and dobutamine alone, or by the combination of dobutamine and norepinephrine.nnnDESIGNnProspective clinical trial of two patient groups. Group 1 (n = 15) was stabilized with dobutamine, and group 2 (n = 10) was stabilized with dobutamine and norepinephrine.nnnSETTINGnIntensive care unit in a university hospital.nnnPATIENTSnTwenty-five postoperative, hyperdynamic septic shock patients.nnnINTERVENTIONSnThe stabilizing catecholamine infusion was replaced in a stepwise manner by dopamine to achieve a similar mean arterial pressure (dopamine doses: group 1, mean 22 +/- 15 micrograms/kg/min [range 6 to 52]; and group 2, mean 57 +/- 41 micrograms/kg/min [range 15 to 130]).nnnMEASUREMENTS AND MAIN RESULTSnA complete hemodynamic profile was performed with oxygen transport-related variables at baseline, after replacement by dopamine, and after resetting to the original catecholamine infusion. The change to dopamine resulted in increases in cardiac index (group 1: 20% [p < .01]; group 2: 33% [p < .01]), and DO2 (group 1: 19% [p < .01]; group 2: 27% [p < .01]). However, VO2, whether directly measured from the respiratory gases or calculated by the cardiovascular Fick principle, did not change in both groups with dopamine, while the oxygen extraction ratio decreased significantly in both groups with dopamine. Heart rate, pulmonary artery occlusion pressure, and pulmonary shunt fraction all increased with dopamine. PaO2 decreased, but oxygen saturation remained stable in both groups with dopamine.nnnCONCLUSIONSnShort-term dopamine infusion in hyperdynamic septic shock patients, despite producing higher global DO2, was not superior to dobutamine or the combination of dobutamine and norepinephrine infusion.

Hypertonic saline in stabilized hyperdynamic sepsis.

Hypertonic saline with or without colloidal solution has been successfully used for treating hemorrhagic shock in animal experiments and clinical studies. Due to its various effects at systemic, organ, and microcirculatory levels, the substance appears to be a promising candidate for improving tissue oxygenation in sepsis. We therefore investigated the hypothesis that infusion of hypertonic saline would further improve O2 delivery, O2 extraction, and O2 uptake in hyperdynamic septic shock patients already stabilized by adequate volume and catecholamine infusion. Twenty-one patients received 2–4 mL/kg body weight of hypertonic saline in hydroxyethyl starch within 15 min. This hypertonic saline infusion caused a rapid significant increase in O2 delivery by 14% but only a marginal increase in O2 consumption (7% by cardiovascular Fick [p < .05], 4% by respiratory gases [n.s.]). Hypertonic saline increased the already elevated cardiac output by 24%. The pulmonary capillary wedge pressure increased from 14 ± 3 to 23 ± 3 mmHg and pulmonary shunt fraction increased 15%, but arterial PO2 did not fall. Except for the increase in pulmonary capillary wedge pressure, none of the cardiovascular changes lasted longer than 60 min. Plasma sodium levels increased from 138 ± 25 to 163 ± 38 mmol/L and normalized within 24 h. In these hyperdynamic septic patients, hypertonic saline infusion produced a transient increase in circulation, but no evidence of a substantial increase in O2 consumption. Either there was no significant O2 debt due to the already elevated O2 delivery levels at baseline (700 mL/min/m2) or the global O2 measurements we used were not able to detect discrete regional hypoxia.

Relevance of Carbohydrate-deficient Transferrin as a Predictor of Alcoholism in Intensive Care Patients following Trauma

Every second traumatized patient is a chronic alcoholic. Chronic alcoholics are at risk due to an increased morbidity and mortality. Reliable and precise diagnostic methods for detecting alcoholism are mandatory to prevent posttraumatic complications by adequate prophylaxis. The patients history, however, is often not reliable, and conventional laboratory markers are not sensitive or specific enough. The aim of this study was to investigate whether carbohydrate-deficient transferrin (CDT) is a sensitive and specific marker to detect alcoholism in traumatized patients. One hundred and five male traumatized patients or their relatives gave their written informed consent to participate in this institutionally approved study. All patients were transferred to the intensive care unit after admission to the emergency room, followed by surgical treatment. Diagnostics included an alcoholism-related questionnaire, conventional laboratory markers (mean corpuscular volume, gamma-glutamyltransferase, aspartate aminotransferase, and alanine aminotransferase), and CDT sampling (microanion-exchange chromatography, turbidimetry, and radioimmunoassay, respectively). Only patients in whom a reliable history could be obtained were included. Alcoholism was diagnosed if the patients met the Diagnostic and Statistical Manual of Mental Disorders criteria for chronic alcohol abuse or dependence. The administration of fluids before CDT sampling was carefully documented. Patients did not differ significantly regarding age, Trauma and Injury Severity Score, and Acute Physiology and Chronic Health Evaluation score. The sensitivity of the CDT research kit was 70% and of the commercially available kit CDTect was 65%. Early sampling in the emergency room and before administration of large volumes of fluid increased the sensitivity to 83% for the CDT research kit and 74% for CDTect, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Reliability of Carbohydrate-Deficient Transferrin to Detect Chronic Alcohol Misuse in Carcinoma Patients

The patients’ history and conventional laboratory markers are often not sensitive or specific enough to detect chronic alcohol misuse, preoperatively. We investigated whether carbohydrate-deficient tr