Treatment of sepsis: what changed during the last decades?
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Adjuvants, Immunologic↗
Biomedical subjects
W Karzai
Publications and source records attributed to W Karzai.
Dobutamine increases oxygen consumption during constant flow cardiopulmonary bypass.
We have studied the effects of flow and dobutamine on systemic haemodynamic variables, oxygen delivery (DO2) and oxygen consumption (VO2) in 20 patients during cardiopulmonary bypass (CPB) with mild hypothermia (34 degrees C). In a subgroup of seven patients, we also studied the effects on gastric microcirculatory blood flow (MCF) using laser Doppler flowmetry. During CPB, measurements were made before and after two interventions: the first consisted of increasing flow from 2.4 to 3.0 litre min-1 m-2 for 10 min; the second consisted of an infusion of dobutamine at a rate of 6 micrograms kg-1 min-1 for 10 min during constant flow CPB. There were no significant differences in DO2, VO2 or haemodynamic variables between the two baseline measurements. The increase in flow raised DO2 (27%, P < 0.001), mean arterial pressure (P < 0.01) and MCF (P < 0.01), but failed to increase VO2. In contrast, dobutamine infusion increased VO2 (11%, P < 0.001) during constant flow CPB without significant changes in DO2, systemic haemodynamic variables or MCF. These results indicate that increases in VO2 during dobutamine may be flow-independent.
Aged↗
Effects of dopamine on oxygen consumption and gastric mucosal blood flow during cardiopulmonary bypass in humans.
We investigated the effects of flow rate and dopamine on systemic oxygen delivery (DO2) oxygen consumption (VO2) and gastric mucosal microcirculatory blood flow (gMCF), measured by laser Doppler flowmetry in 12 patients undergoing mild hypothermic (34 degrees C) cardiopulmonary bypass (CPB). The first intervention comprised increasing CPB flow rates from 2.4 to 3.0 litre min-1 m-2, and the second intervention administering dopamine 6 micrograms kg-1 min-1. Measurements were made before and 10 min after the start of one of the two interventions. The heart remained in cardioplegic arrest throughout the study. There were no significant differences in variables between the two baseline measurements preceding the interventions. The increase in CPB flow rate increased DO2 and gMCF without affecting VO2. At constant flow rate, dopamine also increased gMCF with no change in VO2, DO2 or mean arterial pressure. Our data suggested that dopamine had no flow-independent effect on VO2 and that it increased gMCF during constant flow hypothermic CPB.
Aged↗
Controlled trials of rG-CSF and CD11b-directed MAb during hyperoxia and E. coli pneumonia in rats.
We studied the effects of inhibiting and augmenting neutrophil function by using an immunocompetent rat model of infectious and hyperoxic lung injury. After intrabronchial Escherichia coli challenge at all fractional inspired O2 (FIO2) values studied (FIO2 = 0.21, 0.60, and 0.95) and after lethal O2 exposure alone (FIO2 = 0.90), lung injury, as measured by histological and physiological changes, was reduced by a CD11b/CD18-directed monoclonal antibody (MAb 1B6, P < 0.05 vs. controls) but was increased by recombinant granulocyte colony-stimulating factor (rG-CSF; P < 0.05 vs. control; MAb 1B6 vs. rG-CSF, P < 0.004). Pulmonary neutrophil counts were reduced by MAb 1B6 (P < 0.04) and increased by rG-CSF (P < 0.0004) compared with control animals. However, despite antibiotics, MAb 1B6 and rG-CSF both significantly increased the relative risk of death, independent of O2 concentration, during E. coli pneumonia (1.74 [symbol: see text] 1.20 and 2.39 [symbol: see text] 1.19, respectively, each P < 0.01). During lethal hyperoxia, MAb 1B6 increased the relative risk of death (1.76 [symbol: see text] 1.28, P < 0.16), whereas rG-CSF had no effect on survival (0.97 [symbol: see text] 1.28, P = 0.89). Thus inhibition of neutrophil function attenuated and enhancement worsened lung injury in response to infectious and hyperoxic challenges, supporting a pathophysiological role of the neutrophil in these processes. However, it is problematic that MAb 1B6 therapy, despite preventing lung damage, ultimately worsened host defenses and survival. Furthermore, rG-CSF also adversely affected survival during infectious lung injury, demonstrating the inherent risks of inhibiting or augmenting neutrophil function in an immunocompetent host during infection.
Animals↗
Hemodynamic effects of dopamine, norepinephrine, and fluids in a dog model of sepsis.
To study how sepsis affects hemodynamic responses to catecholamines and fluids, either Escherichia coli-infected (septic, n = 8) or sterile (controls, n = 6) fibrin clots were implanted intraperitoneally into 2-yr-old beagles. Hemodynamics were measured at each of four doses of dopamine (0, 5, 10, and 20 micrograms.kg-1.min-1) and norepinephrine (0, 10, 20, and 40 micrograms.min-1), before and after infusion of fluid (Ringer 40 ml.kg-1). Septic animals had lower mean arterial pressure (MAP, P = 0.04), stroke volume index (SVI, P = 0.0001), and left ventricular (LV) ejection fraction (LVEF) (P = 0.0001) than controls. During this time, increasing doses of dopamine and norepinephrine produced corresponding increases (P < 0.001) in LVEF, SVI, and MAP. However, during sepsis, the ability of dopamine to increase MAP diminished, while its ability to increase LVEF and SVI was maintained. Conversely, the ability of norepinephrine to increase LVEF and SVI diminished, but its ability to increase MAP was maintained. During sepsis, fluids alone increased (P < 0.05) MAP, LVEF, SVI, and cardiac index (CI). Fluids with catecholamines also significantly increased (P < 0.05) MAP with only minimal increases in LVEF, SVI, and CI. These data demonstrate that during sepsis without catecholamines, fluids improve cardiac performance and systemic pressures, but with catecholamines, fluids have minimal effects on cardiac performance and augment MAP. Furthermore, during sepsis dopamine is more effective than norepinephrine in increasing LV performance, but norepinephrine is more effective than dopamine in increasing systemic pressures.
Animals↗
The effects of beta-adrenoreceptor blockade on oxygen consumption during cardiopulmonary bypass.
The effect of chronic beta-adrenoreceptor blockade (beta-blockade) on hemodynamics and oxygen consumption (VO2) during cardiopulmonary bypass (CPB) in mild hypothermia (34 degrees C) was studied in 34 patients. The study group included 17 patients who received beta-adrenergic blocking drugs for at least 1 mo prior to the study. Seventeen patients who did not receive beta-adrenergic blockers served as controls. Demographic data in the two groups were comparable. Prior to induction of anesthesia, the heart rate was slower in the beta-adrenergic blocker group as compared to the control group. During CPB, measurements were made at two pump flow rates: 2.4 L.min-1.m-2 and 3.0 L.min-1.m-2. Oxygen delivery was similar in the two groups (beta-adrenergic blocker vs control) but the oxygen consumption was significantly lower in the beta-adrenergic blocker group as compared to the control group at both flow rates (P = 0.009). Increasing the flow rate from 2.4 L.min-1.m-2 to 3.0 L.min-1.m-2 produced a similar increase (P = 0.0001) in oxygen consumption in both groups. Increasing flow rate increased mean arterial pressure (MAP) and central venous pressure (CVP) and decreased systemic vascular resistance index (SVRI) and reservoir volume similarly in both groups. Thus, compared to the control group, patients on chronic beta-adrenergic blocker medication have a lower VO2 during CPB.
Adrenergic beta-Antagonists↗
[The concentration of atrial natriuretic peptides (ANP). ANP in different sections of the circulation during atrial volume load with and without anesthesia].
We studied the effect of a volume load induced by a 45 degrees Trendelenburg position on atrial natriuretic peptide (ANP) secretion in awake and anaesthetized patients with coronary artery disease undergoing aortocoronary bypass surgery. ANP was measured in different parts of the circulation before and after induction of high dose fentanyl anaesthesia at fixed times prior to and after extracorporeal circulation. METHOD. In eight patients with coronary artery disease (NYHA classification II-III), who received neither diuretic nor positive inotropic therapy, ANP was measured in the various parts of the circulation: in a peripheral vein, a radial artery, in the pulmonary artery and in the coronary sinus. The measurements were made in the supine and 45 degrees Trendelenburg position. Measurements of mean arterial pressure (MAP), central venous pressure (RAP), pulmonary arterial pressure (PAP), pulmonary capillary wedge pressure (PCWP), cardiac index (CI) and heart rate (HR) were taken simultaneously. The measurements were taken in the awake patient, during steady-state high-dose fentanyl anaesthesia with 50% O2 in N2O and after extracorporeal circulation. RESULTS. Compared to measurements in a control group, ANP levels were significantly higher in all parts of the circulation in patients with coronary artery disease, although clinical symptoms of heart failure were absent. After extracorporeal circulation, significantly higher levels of ANP were found at all measurement sites; however the concentration gradient of ANP between coronary sinus and arterial or venous blood was reduced. In awake and anaesthetized patients a change in body position, causing a significant increase in filling pressures, did not produce an increase in ANP levels at all measurement sites. The induction of high-dose fentanyl anaesthesia did not have an influence on plasmatic ANP levels. CONCLUSION. The results of this study lead to the following conclusions: 1. ANP levels in patients with CAD are increased, even if clinical heart failure symptoms are absent. 2. ANP is secreted in the coronary vessels. Following dilution in the atrial blood, it is metabolized to inactive compounds in the periphery. 3. Basic ANP levels are not changed by high-dose fentanyl anaesthesia. Marked increases of the filling pressures do not correlate with atrial ANP levels either before or after induction of anaesthesia. 4. After extracorporeal circulation ANP levels are significantly increased in all parts of the circulation. The concentration gradient between coronary sinus blood, on the one hand, and arterial and venous blood on the other hand is reduced. This phenomenon is probably caused by an alteration in the metabolism of ANP during hypothermic extracorporeal circulation.
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Procalcitonin--a new indicator of the systemic response to severe infections.
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C-Reactive Protein↗