The Effects of Ex Vivo Administration of Granulocyte-Macrophage Colony-Stimulating Factor and Endotoxin on Cytokine Release of Whole Blood Are Determined by Priming Conditions.

BACKGROUND: Lipopolysaccharide- (LPS-) induced tumour necrosis factor alpha (TNFα) secretion in critically ill patients can be considered as a measure of immune responsiveness. It can be enhanced by granulocyte-macrophage colony stimulating factor (GM-CSF). We investigated the effect of GM-CSF on ex vivo stimulated cytokine production using various preincubation regimens in healthy donors and patients with sepsis. RESULTS: The maxima for the stimuli occurred 3 hours after stimulation. In donors, there was an increase (p < 0.001) of LPS-induced TNFα levels following incubation with GM-CSF. The simultaneous incubation with GM-CSF and LPS caused an inhibition of TNFα production (p < 0.001). Postincubation with GM-CSF did not yield any difference. In patients, preincubation with GM-CSF yielded an enhanced ex vivo TNFα-response when TNFα levels were low. Patients with increased TNFα concentrations did not show a GM-CSF stimulation effect. The GM-CSF preincubation yielded an increase of IL-8 production in patients and donors. CONCLUSIONS: This study demonstrates the immune-modulating properties of GM-CSF depending on the absence or presence of LPS or systemic TNFα. The timing of GM-CSF administration may be relevant for the modulation of the immune system in sepsis. The lack of stimulation in patients with high TNFα may represent endotoxin tolerance.

Interventional lung assist enables lung protective mechanical ventilation in acute respiratory distress syndrome.

BACKGROUND: The feasibility and safety of a pumpless arteriovenous extracorporeal lung assist system (pECLA) has been demonstrated in previous studies of patients with severe respiratory insufficiency. The aim of this report was to examine whether pECLA is feasible in a center that is new to the technology and to determine the positive and adverse effects associated with its use. METHODS: This was a retrospective case series of 13 consecutive patients with established acute respiratory distress syndrome (ICU patients with ARDS or ALI) at a university hospital. Management consisted of transcutaneous placement of a femoral arteriovenous pECLA to allow lung-protective ventilation. Nonparametric statistics were applied; all data are values and standard deviations (SD). RESULTS: Mean simplified acute physiology score (SAPS) II was 49.5 (26); ICU mortality was 54% (7/13). Mean length of ICU stay was 34.5 (65.3) days for survivors (S) and 36 (32.8) days for non-survivors (NS). Total time on arteriovenous pECLA was 12.0 (22.2) days (S) and 7.0(7.8) days (NS), total time on mechanical ventilation was 31.0 (28.2) (S) and 32.0 (15.2) days (NS). Hypercapnia was significantly (P<0.05) reduced from 80.0 (23.0) (pre-pECLA) to 48.0 (13.0) mmHg (day 7), as were minute ventilation and inspiratory pressure. pECLA was accompanied by a significant (P<0.05) increase in the PaO2/fraction of inspired oxygen (P/F) ratio from 100.0 (28.9) (pre-pECLA) to 191.1 (114.3) mmHg after 7 days of treatment. Major complications were two inadvertent decannulations in the first two patients treated; there was one minor bleeding event in a patient seen subsequently. CONCLUSION: pECLA is an effective and manageable technique to support gas exchange in ARDS patients. This retrospective case series demonstrates the feasibility of pECLA in a center that did not have prior experience with this technique. pECLA may decrease further lung injury by minimizing the amount of time for which the lung is exposed to high stress and/or strain.

Inhalational induction of anaesthesia with 8% sevoflurane in children: conditions for endotracheal intubation and side-effects.

BACKGROUND AND OBJECTIVE: This study was designed to assess the conditions for endotracheal intubation or insertion of a laryngeal mask airway following an inhalational induction using 8% sevoflurane and nitrous oxide without the use of muscle relaxants or opioids. METHODS: There were two groups: 30 children had endotracheal intubation and 30 children had a laryngeal mask airway inserted. Induction of anaesthesia was accomplished using an inspiratory concentration of sevoflurane 8% in a nitrous oxide and oxygen mixture. After an end-expiratory concentration of sevoflurane of at least 4% had been reached, when the pupils were miotic and centred, the trachea was intubated or a laryngeal mask inserted. The time to loss of consciousness and successful airway management was recorded. Jaw relaxation, movements, visibility, and position of the vocal cords and vital parameters were monitored. RESULTS: Jaw relaxation was complete in all children. The vocal cords were completely visible in all patients of the tracheal intubation group, whereas vocal cord relaxation was incomplete in five children. Nevertheless, all children had an atraumatic intubation or insertion of the laryngeal mask without the use of a muscle relaxant. Vital signs were stable in both groups. There were no cases of restlessness and/or postoperative shivering. Four patients in the endotracheal group (13.3%) were nauseous and three (10%) vomited, while two children (6.6%) in the laryngeal mask group experienced nausea and vomiting. CONCLUSIONS: Induction with sevoflurane in nitrous oxide and oxygen leads to fast loss of consciousness and provides ideal conditions for managing the airway without supplemental opioids or muscle relaxants. Furthermore, sevoflurane using this technique was very well tolerated, indicated by high haemodynamic stability and a reduced rate of postoperative restlessness, shivering, nausea and vomiting.