K. Taeger

A new pumpless extracorporeal interventional lung assist in critical hypoxemia/hypercapnia*

Objective:Pump-driven extracorporeal gas exchange systems have been advocated in patients suffering from severe acute respiratory distress syndrome who are at risk for life-threatening hypoxemia and/or hypercapnia. This requires extended technical and staff support. Design:We report retrospectively our experience with a new pumpless extracorporeal interventional lung assist (iLA) establishing an arteriovenous shunt as the driving pressure. Setting:University hospital. Patients:Ninety patients with acute respiratory distress syndrome. Interventions:Interventional lung assist was inserted in 90 patients with acute respiratory distress syndrome. Measurements and Main Results:Oxygenation improvement, carbon dioxide elimination, hemodynamic variables, and the amount of vasopressor substitution were reported before, 2 hrs after, and 24 hrs after implementation of the system. Interventional lung assist led to an acute and moderate increase in arterial oxygenation (Pao2/Fio2 ratio 2 hrs after initiation of iLA [median and interquartile range], 82 mm Hg [64–103]) compared with pre-iLA (58 mm Hg [47–78], p < .05). Oxygenation continued to improve for 24 hrs after implementation (101 mm Hg [74–142], p < .05). Hypercapnia was promptly and markedly reversed by iLA within 2 hrs (Paco2, 36 mm Hg [30–44]) in comparison with before (60 mm Hg [48–80], p < .05], which allowed a less aggressive ventilation. For hemodynamic stability, all patients received continuous norepinephrine infusion. The incidence of complications was 24.4%, mostly due to ischemia in a lower limb. Thirty-seven of 90 patients survived, creating a lower mortality rate than expected from the Sequential Organ Failure Assessment score. Conclusions:Interventional lung assist might provide a sufficient rescue measure with easy handling properties and low cost in patients with severe acute respiratory distress syndrome and persistent hypoxia/hypercapnia.

Blood irradiation for intraoperative autotransfusion in cancer surgery: demonstration of efficient elimination of contaminating tumor cells.

BACKGROUND: Intraoperative blood salvage is contraindicated in cancer surgery because of contaminating tumor cells and the risk of systemic dissemination. On the basis of the radiosensitivity of cancer cells, irradiation of salvaged blood with 50 Gy is proposed as a way to allow return of salvaged blood.

Downregulation of Angiotensin II Type 1 Receptors During Sepsis

Our study aimed to characterize the mechanisms underlying the attenuated cardiovascular responsiveness toward the renin-angiotensin system during sepsis. For this purpose, we determined the effects of experimental Gram-negative and Gram-positive sepsis in rats. We found that sepsis led to a ubiquitous upregulation of NO synthase isoform II expression and to pronounced hypotension. Despite increased plasma renin activity and plasma angiotensin (Ang) II levels, plasma aldosterone concentrations were normal, and the blood pressure response to exogenous Ang II was markedly diminished in septic rats. Mimicking the fall of blood pressure during sepsis by short-term infusion of the NO donor sodium nitroprusside in normal rats did not alter their blood pressure response to exogenous Ang II. Therefore, we considered the possibility of an altered expression of Ang II receptors during sepsis. It turned out that Ang II type 1 receptor expression was markedly downregulated in all organs of septic rats. Further in vitro studies with rat renal mesangial cells showed that NO and a combination of proinflammatory cytokines (interleukin-1&bgr;, tumor necrosis factor-&agr;, and interferon-&ggr;) downregulated Ang II type 1 receptor expression in a synergistic fashion. In summary, our data suggest that sepsis causes a systemic downregulation of Ang II type 1 receptors that is likely mediated by proinflammatory cytokines and NO. We suggest that this downregulation of Ang II type 1 receptors is the main reason for the attenuated responsiveness of blood pressure and of aldosterone formation to Ang II and, therefore, contributes to the characteristic septic shock.

Cytokines down-regulate α1-adrenergic receptor expression during endotoxemia

ObjectiveThe reduced pressure response to norepinephrine in septic patients has directed our interest to the regulation of &agr;1-adrenergic receptors in vitro and in vivo during conditions mimicking acute sepsis. DesignProspective animal trial followed by a controlled cell culture study. SettingLaboratory of the Department of Anesthesiology. SubjectsMale Sprague-Dawley rats weighing 200 to 250 g and a mesangial cell line. InterventionsExperimental endotoxemia was induced in rats with lipopolysaccharide, and blood pressure dose-response studies with norepinephrine were performed. &agr;1-Receptor gene expression was determined in various organs by a specific RNase protection assay, and tissue concentrations of the proinflammatory cytokines interleukin-1&bgr; and tumor necrosis factor-&agr; were measured. Rat renal mesangial cells were incubated with these cytokines or with nitric oxide donors to investigate the regulation of &agr;1-adrenergic receptors during severe inflammation on a cellular level. Measurements and Main ResultsThe pressor effect of norepinephrine was markedly diminished during endotoxemia. The animals showed down-regulated mRNA levels of &agr;1A-, &agr;1B- and &agr;1D-receptors in all organs investigated, and the tissue concentrations of interleukin-1&bgr; and tumor necrosis factor-&agr; were highly increased during experimental endotoxemia. Incubation of cultured rat renal mesangial cells with the cytokines resulted in diminished &agr;1B-receptor gene expression and [H]prazosin binding capacity, whereas incubation of the cells with nitric oxide donors did not affect &agr;1B-receptor expression. In line, blocking of cytokine-induced nitric oxide synthesis by coincubation of mesangial cells with NG-nitro-l-arginine methyl ester did not influence cytokine-induced down-regulation of &agr;1B-receptors. ConclusionsOur data show that endotoxemia causes a systemic down-regulation of &agr;1-receptors on the level of gene expression and suggest that this effect is likely mediated by proinflammatory cytokines in a synergistic but nitric oxide-independent fashion. We propose that this down-regulation of &agr;1-adrenergic receptors contributes to the attenuated blood pressure response to norepinephrine and, therefore, to septic circulatory failure in patients.

Monitoring of Cerebral Oxygen Metabolism in the Jugular Bulb: Reliability of Unilateral Measurements in Severe Head Injury

To investigate the reliability of unilateral jugular venous monitoring and to determine the appropriate side, we performed bilateral jugular venous monitoring in 22 head-injured patients. Fiberoptic catheters were placed in both jugular bulbs. Arterial and bilateral jugular venous blood samples were obtained simultaneously for in vitro determination of jugular venous oxygen saturation (SJO2), arterial minus jugular venous lactate content difference (AJDL), and modified lactate-oxygen index (mLOI). Ischemia was assumed if one of the following pathologic values occurred at least unilaterally: SJO2 <54%, AJDL <−0.37 mmol/L, mLOI >0.08. The sensitivity of calculated unilateral monitoring in detecting ischemia was evaluated by comparing the incidence detected unilaterally with that disclosed bilaterally. The mean and maximum bilateral SJO2 differences varied between 1.4% and 21.0%, and 8.1% and 44.3%, respectively. The bias and limits of agreement (mean differences ± 2 SD) between paired samples were 0.4% ± 12.8%. There was no significant variation in bilateral SJO2 differences with time. Decreasing cerebral perfusion pressure (r = −0.559, P < 0.001) and arterial Pco2 (r = −0.342, P < 0.001) were associated with increasing bilateral SJO2 differences. Regarding AJDL, the maximum bilateral differences varied between 0.04 mmol/L and 1.52 mmol/L. The bias and limits of agreement were −0.01 ± 0.18 mmol/L. At best, 87% of ischemic events were disclosed by monitoring on the side of predominant lesion or, in diffuse injuries, on the side of the larger jugular foramen (computed tomographic [CT] approach). We conclude that in severe head injury, even calculated unilateral jugular venous monitoring has an unpredictable risk for misleading or missing data. Therefore, the reliability of unilateral jugular venous monitoring appears suspicious. For diagnosing ischemia the CT approach is recommended.

Effects of extreme lateral posture on hemodynamics and plasma atrial natriuretic peptide levels in critically ill patients

ObjectiveTo quantify the hemodynamic effects of turning critically ill, mechanically ventilated patients to the extreme left and right lateral postures.DesignProspective investigation.SettingEight-bed intensive care unit in a university hospital.PatientsTwelve consecutive patients presenting with severe respiratory failure and requiring continuous positive inotropic support.InterventionsAll patients were mechanically ventilated and placed in a kinetic treatment system. They were positioned in the supine, left dependent, and right dependent postures, resting for 15 min in each position.Measurements and resultsHemodynamic measurements, assessments of right ventricular function, and determinations of intrathoracic blood volume were performed in three different positions. Concentrations of atrial natriuretic peptide in plasma were quantified. In three patients, the findings were controlled by transesophageal echocardiography.Cardiac index [median (range) 5.5 (3.2–8.1) vs 4.3 (3.2–7.5) l/min per m2,p<0.01], intrathoracic blood volume [1125 (820–1394) vs 1037 (821–1267) ml/m2,p<0.01], and right ventricular end-diastolic volume [130 (83–159) vs 114 (79–155) ml/m2,p<0.05] increased significantly in the left dependent position compared to supine. Mean arterial pressure did not change. Atrial natriuretic peptide levels rose from 140 to 203 pg/ml. In the right dependent position, we found a marked decrease in the mean arterial pressure [85 mmHg (supine) to 72 mmHg (right dependent),p<0.01]. Cardiac index and intrathoracic blood volume were unchanged, but right ventricular enddiastolic volume decreased from 114 to 102 ml/m2 (p<0.05) Additionally, atrial natriuretic peptide levels decreased significantly (median Δ value: 37 pg/ml). In echocardiographic controls we found an increase in right ventricular end-diastolic diameters in the left dependent position and shortened diameters in the right dependent position.ConclusionsExtreme lateral posture affects the cardiovascular system in critically ill, mechanically ventilated patients: in the left dependent position a “hyperdynamic state” is reinforced, while the right decubitus position impairs right ventricular preload and predisposes to hypotension. Echocardiography and changes in plasma atrial natriuretic peptide values indicate that these findings are due to altered distensibility of the right ventricle caused by regional intrathoracic gravitational changes. We conclude that the duration and the angle of lateral posture should be restricted in hemodynamically unstable patients.

Mild hyperthermia down-regulates receptor-dependent neutrophil function

Mild hypothermia impairs resistance to infection and, reportedly, impairs phagocytosis and oxidative killing of unopsonized bacteria. We evaluated various functions at 33°–41°C in neutrophils taken from volunteers. Adhesion on endothelial cells was determined using light microscopy. Adhesion molecule expression and receptors, phagocytosis, and release of reactive oxidants were assessed using flow cytometric assays. Adhesion protein CD11b expression on resting neutrophils was temperature-independent. However, up-regulation of CD11b with tumor necrosis factor (TNF)-&agr; was increased by hypothermia and decreased with hyperthermia. Neutrophil adhesion to either resting or activated endothelial cells was not temperature-dependent. Bacterial uptake was inversely related to temperature, more so with Escherichia coli than Staphylococcus aureus. Temperature dependence of phagocytosis occurred only with opsonized bacteria. Hypothermia slightly increased N-formyl-l-methionyl-l-leucyl-phenylalanine receptors on neutrophils: hyperthermia decreased expression, especially with TNF-&agr;. N-formyl-l-methionyl-l-leucyl-phenylalanine-induced H2O2 production was inversely related to temperature, especially in the presence of TNF-&agr;. Conversely, phorbol-13-myristate-12-acetate, an activator of protein kinase C, induced an extreme and homogenous release of reactive oxidants that increased with temperature. In contrast to nonreceptor-dependent phagocytosis and oxidative killing, several crucial receptor-dependent neutrophil activities show temperature-dependent regulation, with hypothermia increasing function. The temperature dependence of neutrophil function is thus more complicated than previously appreciated.

The correlation of the Narcotrend® Index and classical electroencephalographic parameters with endtidal desflurane concentrations and hemodynamic parameters in different age groups

Background : The Narcotrend® Index (NI) for assessment of depth of anesthesia by analysis of the electroencephalogram (EEG), is potentially a pharmacodynamic measure of the effects of desflurane on the brain.

Waste gas exposure during desflurane and isoflurane anaesthesia

Background: Currently, there are no data available concerning the occupational exposure to desflurane during general anaesthesia. This prospective, randomized study reports on occupational exposure to desflurane, compared to isoflurane, in a modern operation theatre (OT).

Continuous Intraarterial Measurement of Oxygenation during Aerosolized Prostacyclin Administration in Severe Respiratory Failure

To the Editor: A recent report1 stimulated us to use aerosolized prostaglandin I2 (PGI2; also called prostacyclin or epoprostenol) to improve arterial oxygenation by producing selective pulmonary v...