Granulocyte colony-stimulating factor therapy and systemic inflammation in critically ill patients.

OBJECTIVE AND DESIGN: The effect of the granulocyte colony-stimulating factor filgrastim on systemic inflammation was investigated in a prospective, randomized, placebo-controlled, double-blind study in critically ill patients. SUBJECTS: 59 critically ill patients were recruited within 48 h of intubation due to ventilatory insufficiency. TREATMENT: Subcutaneous dosage of placebo or 300 microg filgrastim once daily. METHODS: Serum samples were collected at study entry, and 1 and 3 days after the start (Day1 and Day3, respectively). Levels of soluble E-selectin (sE-selectin) and interleukin (IL)-10 were determined by ELISA, and those of IL-6, and soluble IL-2 receptor (sIL-2R) by Immulite chemiluminescence immunoassay. RESULTS: The median sE-selectin level decreased by day 3 significantly in the control group but not in the filgrastim group. The difference in the change between the study groups was significant (p = 0.049). IL-10 levels decreased significantly in the filgrastim group, tended to decrease in controls (p = 0.052), and the difference in the change tended to be significant (p = 0.058). IL-6 levels decreased in both groups comparably. sIL-2R levels were elevated and stable. CONCLUSIONS: Filgrastim prolongs endothelial activation and possibly inhibits development of immune suppression mediated by IL-10.

Airway pressure release ventilation as a primary ventilatory mode in acute respiratory distress syndrome.

BACKGROUND: Airway pressure release ventilation (APRV) is a ventilatory mode, which allows unsupported spontaneous breathing at any phase of the ventilatory cycle. Airway pressure release ventilation as compared with pressure support (PS), another partial ventilatory mode, has been shown to improve gas exchange and cardiac output. We hypothesized whether the use of APRV with maintained unsupported spontaneous breathing as an initial mode of ventilatory support promotes faster recovery from respiratory failure in patients with acute respiratory distress syndrome (ARDS) than PS combined with synchronized intermittent ventilation (SIMV-group). METHODS: In a randomized trial 58 patients were randomized to receive either APRV or SIMV after a predefined stabilization period. Both groups shared common physiological targets, and uniform principles of general care were followed. RESULTS: Inspiratory pressure was significantly lower in the APRV-group (25.9 +/- 0.6 vs. 28.6 +/- 0.7 cmH2O) within the first week of the study (P = 0.007). PEEP-levels and physiological variables (PaO2/FiO2-ratio, PaCO2, pH, minute ventilation, mean arterial pressure, cardiac output) were comparable between the groups. At day 28, the number of ventilator-free days was similar (13.4 +/- 1.7 in the APRV-group and 12.2 +/- 1.5 in the SIMV-group), as was the mortality (17% and 18%, respectively). CONCLUSION: We conclude that when used as a primary ventilatory mode in patients with ARDS, APRV did not differ from SIMV with PS in clinically relevant outcome.

Predictive value of interleukins 6, 8 and 10, and low HLA-DR expression in acute renal failure.

AIMS: HLA-DR expression and plasma levels of pro- and anti-inflammatory cytokines (IL-6, IL-8 and IL-10) and their predictive value concerning survival of critically ill systemic inflammatory response syndrome (SIRS) patients with and without acute renal failure (ARF) were evaluated. MATERIAL: A total of 103 consecutive adult patients with SIRS from 2 university hospital intensive care units participated in the study. METHOD: Laboratory data for all patients were prospectively collected on the day of admission and 2 days thereafter. Patients with acute renal failure (ARF) and non-ARF patients were compared by Mann-Whitney U-test. Independent predictors of mortality were tested using forward stepwise logistic multiple regression analysis. The discriminative power of different variables was tested using receiver operating characteristic (ROC) curve analysis. RESULTS: ARF developed in 36 patients (35%). ARF patients showed significantly lower HLA-DR expression and higher plasma levels of IL-6, IL-8 and IL-10 than non-ARF patients. In ARF, moderate discriminative power in predicting survival was observed for day 2 IL-6 and IL-10 plasma levels (AUCs 0.703 and 0.749, respectively). CONCLUSIONS: We found no clinically significant discriminative power in predicting survival of ARF patients for monocyte HLA-DR expression or cytokine plasma levels. Therefore, our results do not support the use of HLA-DR expression or cytokine plasma levels for that purpose.

Combined effects of prone positioning and airway pressure release ventilation on gas exchange in patients with acute lung injury.

BACKGROUND: Prone positioning has been shown to improve oxygenation in 60-70% of patients with acute lung injury (ALI) or acute respiratory distress syndrome (ARDS). Another way to improve matching of ventilation to perfusion is the use of partial ventilatory support. Preserving spontaneous breathing during mechanical ventilation has been shown to improve oxygenation in comparison with controlled mechanical ventilation. However, no randomized studies are available exploring the effects of preserved spontaneous breathing on gas exchange in combination with prone positioning. Our aim was to determine whether the response of oxygenation to the prone position differs between pressure-controlled synchronized intermittent mandatory ventilation with pressure support (SIMV-PC/PS) and airway pressure release ventilation with unsupported spontaneous breathing (APRV). METHODS: We undertook a prospective randomized intervention study in a medical-surgical adult intensive care unit of a university hospital. Of 45, 33 ALI patients (acute lung injury) within 72 h after initiation of mechanical ventilation, and in whom the prone position was applied according to a predefined strategy, were included in the study. After initial stabilization the patients were randomized to receive either SIMV-PC/PS or APRV with predefined general ventilatory goals (PEEP, tidal volume, inspiratory pressure and PaCO2-level). The protocol for prone positioning was the same for both treatment arms. Prone positioning was triggered by finding a PaO2/FiO2-ratio below 200 mmHg evaluated twice per day. The duration of each prone episode was 6 h. RESULTS: The first two episodes of prone positioning were analyzed. Gas exchange was measured before and at the end of prone positioning. Of the 45 patients enrolled, 33 were turned prone once and 28 twice. No significant differences were detected in baseline characteristics. Changes in oxygenation were analyzed in response to the first and second prone episodes 5 h and 24 h after randomization and initiation of SIMV-PC/PS or APRV respectively. Before the first prone episode the PaO2/FiO2-ratio was significantly better (P = 0.02) in the APRV-group (median; interquartile range) (162; 108-192 mmHg) than in the SIMV-PC/PS-group (123; 78-154 mmHg). The response in oxygenation to the first prone episode was similar in both groups: PaO2/FiO2-ratio increased 39.5; 17.75-77.5 mmHg in the SIMV-PC/PS-group and 75.0; 9.0-125.0 mmHg in the APRV-group (P = 0.49). Before the second prone episode, the PaO2/FiO2-ratio was comparable (SIMV-PC/PS 130.5; 61.0-161.0 mmHg vs. APRV 134; 98.3-175.0 mmHg). Improvement in oxygenation was significantly (P = 0.02) greater in the APRV group (82; 37.0-141.0 mmHg) than in the SIMV-PC/PS group (50; 24.0-68.8 mmHg) during the second prone episode. General ventilatory and hemodynamic variables and use of sedatives were similar in both groups during the study. CONCLUSIONS: APRV during prone positioning is feasible in the treatment of ALI patients. APRV after 24 h appears to enhance improvement in oxygenation in response to prone positioning.

Elimination of the piperacillin/tazobactam combination during continuous venovenous haemofiltration and haemodiafiltration in patients with acute renal failure.

The elimination of the piperacillin/tazobactam combination was studied in six patients with acute renal failure undergoing either continuous venovenous haemofiltration (CVVH) or continuous venovenous haemodiafiltration (CVVHDF) at 1 L/h and 2 L/h for 12 h. Piperacillin 4 g/tazobactam 0.5 g was given iv on three successive treatment periods and their concentrations in plasma, ultrafiltrate/dialysate and urine were determined for 12 h after each dose. The elimination half-life of piperacillin during CVVH (7.7 +/- 2.3 h; mean +/- s.d.) was significantly longer than during CVVHDF 1 L/h (6.7 +/- 1.9 h) or 2 L/h (6.1 +/- 2.0 h) (P< 0.05). Corresponding values for tazobactam were 13.9 +/- 3.9, 11.6 +/- 3.3 and 9.4 +/- 2.4 h, respectively (P< 0.05). Total piperacillin clearance during CVVH (3.89 +/- 1.23 L/h) was significantly lower than during CVVHDF 1 L/h (5.06 +/- 1.68 L/h) or 2 L/h (5.48 +/- 2.11 L/h) (P< 0.05). The corresponding tazobactam clearance values were 2.42 +/- 0.75, 3.13 +/- 0.66 and 3.75 +/- 1.43 L/h, respectively. The mean 12 h elimination of piperacillin and tazobactam in ultrafiltrate/dialysate was 29% and 37% during CVVH, 42% and 57% during CVVHDF (1 L/h), and 46% and 69% during CVVHDF (2 L/h). We recommend 8 hourly dosing of patients with renal failure on CVVH or CVVHDF with dialysis flow rates of 1 or 2 L/h treated with piperacillin 4 g/tazobactam 0.5 g.

Airway pressure release ventilation and prone positioning in severe acute respiratory distress syndrome.

BACKGROUND: Implementation of lung protective strategy in the treatment of severe Acute Respiratory Distress Syndrome (ARDS) has been reported to be associated with improved outcome. To fulfil this approach, sedation, neuromuscular blocking agents and full mechanical ventilatory support are often used in critical failure of gas exchange. CASE REPORT: We present a patient who developed multiple organ failure, including severe ARDS, after severe skin injuries and septic shock. Ventilatory strategy consisted of lung protective approach, permissive hypercapnia and prone positioning. Airway pressure release ventilation (APRV) with the patient's superimposed spontaneous breathing was implemented and maintained, also during prone episodes. Improvement of gas exhange occurred after application of combined use of APRV and prone positioning. CONCLUSION: APRV and maintenance of patients' spontaneous ventilation is feasible during prone positioning, and this approach may have beneficial synergistic effects on gas exhange in patients with severe acute lung injury.

Safety of granulocyte colony-stimulating factor (filgrastim) in intubated patients in the intensive care unit: interim analysis of a prospective, placebo-controlled, double-blind study.

OBJECTIVE: To investigate the safety of the granulocyte colony-stimulating factor filgrastim in the prevention of nosocomial infections in intubated patients in the intensive care unit (ICU), with special emphasis on the possible deleterious effect on acute respiratory distress syndrome (ARDS) and the development of multiple organ dysfunction (MOD). DESIGN: Predetermined, interim analysis of a prospective, randomized, placebo-controlled, double-blind trial. SETTING: University hospital medical-surgical ICU. PATIENTS: A total of 59 consecutive ICU patients, aged >18 yrs, admitted to the ICU no more than 12 hrs before the study, intubated because of ventilatory insufficiency no more than 48 hrs before the study, expected to stay in the ICU for >48 hrs, and had informed consent from the next relative. INTERVENTIONS: Patients were randomized to receive either placebo or 300 microg of filgrastim subcutaneously once daily for 7 days. MEASUREMENTS AND MAIN RESULTS: No significant differences were found in the number of patients developing ARDS (2 of 20 in the placebo group vs. 0 of 22 in the filgrastim group), disseminated intravascular coagulation (3 of 27 vs. 3 of 29), acute renal failure (1 of 27 vs. 1 of 23), or change in MOD. Data analysis showed nosocomial infections in 11 of 29 patients in the placebo group and in 7 of 30 patients in the filgrastim group (p = .266). The median (range) length of ICU stay was 8 (1-34) days in the placebo group and 6 days (1-28) in the filgrastim group. The day 28 mortality rate was 17% (5 of 29) in the placebo group and 13% (4 of 30) in the filgrastim group. No drug-related adverse events occurred. CONCLUSION: Filgrastim is safe in intubated ICU patients, with no excess risk for development of ARDS or MOD.

Early signs of critical illness polyneuropathy in ICU patients with systemic inflammatory response syndrome or sepsis.

OBJECTIVE: To evaluate with electromyography the incidence and the time of appearance of neuromuscular abnormality in patients with systemic inflammatory response syndrome (SIRS) and/or sepsis. DESIGN: Follow-up study. SETTING: Intensive care unit of Helsinki University Hospital, Finland. PATIENTS: Nine mechanically ventilated patients with SIRS and/or sepsis. INTERVENTIONS: Electromyography and conduction velocity measurements on the 2nd-5th day after admission to the intensive care unit. MEASUREMENTS AND RESULTS: In all nine patients electromyography revealed signs of neuromuscular abnormality. The means of compound muscle action potential amplitudes of the median and ulnar nerves were decreased. Fibrillation was observed in four patients out of nine. CONCLUSION: Because neuromuscular abnormalities seem to develop earlier than previously reported, electroneuromyography should be used more frequently as a diagnostic test.

Left ventricular calcification following resuscitation.

In this paper we report a case of 34-year-old man with a severe septic shock. Because of profound hypotension he was given massive amounts of catecholamines for 10 days. After a short recovery the function of his heart started to deteriorate again and clear calcification around the left ventricle was disclosed by computer tomography. Catecholamines are known to induce myocardial injury resulting in a special form of cardiomyopathy with eventual calcification, but there are no previous reports of myocardial calcification to this extent.

Late steroid therapy in primary acute lung injury.

OBJECTIVE: To investigate the effect of steroid treatment in the late phase of primary acute lung injury (ALI) with special emphasis on pneumococcal pneumonia. DESIGN: Retrospective study. SETTING: Multidisciplinary intensive care unit (ICU) in a university hospital. PATIENTS: Of 31 patients with primary ALI requiring mechanical ventilation for more than 10 days, 16 were treated with methylprednisolone and 15 served as controls. MEASUREMENTS AND RESULTS: Steroid and control groups were comparable regarding demographic data, APACHE II score, Multiple Organ Dysfunction Score (MODS), and PaO2/FiO2-ratio on admission to ICU. The mean start of steroid therapy was 9.7 days after establishment of respiratory failure, and values for control patients were registered on day 10. The PaO2/FiO2 ratio improved significantly within 3 days after the start of steroid therapy, and MODS and C-reactive protein decreased concurrently. No differences in mortality, in length of ICU stay, or in length of mechanical ventilation were detectable. In a subgroup analysis, for patients with Streptococcus pneumoniae pneumonia, beneficial change in physiological variables was evident. CONCLUSIONS: In patients with primary ALI, steroid therapy, started 10 days after the start of mechanical ventilation, improves gas exchange and is associated with a decrease in multiorgan dysfunction.

Zinc chloride smoke inhalation: a rare cause of severe acute respiratory distress syndrome.

Zinc chloride smoke inhalation is a rare cause of slowly progressive and often fatal acute respiratory distress syndrome (ARDS). The conventional treatment includes intravenous N-acetylcysteine, L-3, 4-dehydroproline, methylene blue, and respiratory support according to the lung protective strategy. This report presents the cases of three patients with serious zinc chloride inhalation and ARDS, the last of whom survived after prolonged intensive care, videothoracoscopic excision of emphysema bullae, and recurrent chemical pleurodesis.

Intramucosal pH and endotoxin and cytokine release in severe acute pancreatitis.

It has been postulated that in severely ill patients splanchnic hypoperfusion may cause endotoxin release from the gut, and this leakage of endotoxin into the circulation can trigger the cascade of inflammatory cytokines. We tested this hypothesis in 9 patients with acute severe pancreatitis by monitoring gastric intramucosal pH (pHi) as measure of splanchnic hypoperfusion at 12-h intervals trying to correlate it to endotoxin and cytokine release. Only 3 of 59 samples, obtained from 3 patients contained circulating endotoxin. Thirteen of 15 plasma samples drawn at pHi <7.20 did not contain endotoxin. The pHi was significantly lower in patients who subsequently developed 3 or more organ failures (P = 0.0017, analysis of variance). Although endotoxemia was only occasionally found, most patients had measurable interleukin 1beta (IL-1beta), interleukin 6 (IL-6), interleukin 8 (IL-8), and interleukin 10 (IL-10) in their plasma. Concentrations of IL-6, IL-8, and IL-10 on admission correlated to degree of organ dysfunction as measured by the multiple organ system failure score (P = 0.035, r = 0.74; P = 0.010, r = 0.91; P = 0.021, r = 0.82, respectively). In conclusion, patients with acute, severe pancreatitis often have splanchnic hypoperfusion and produce a wide array of cytokines despite a rare occurrence of endotoxemia.

Markers of systemic inflammation predicting organ failure in community-acquired septic shock.

To obtain predictors of organ failure (OF), we studied markers of systemic inflammation [circulating levels of interleukin-6 (IL-6), IL-8, soluble IL-2 receptor (sIL-2R), soluble E-selectin and C-reactive protein, and neutrophil and monocyte CD11b expression] and routine blood cell counts in 20 patients with systemic inflammatory response syndrome and positive blood culture. Eight patients with shock due to community-acquired infection developed OF, whereas 11 normotensive patients and one patient with shock did not (NOF group). The first blood sample was collected within 48 h after taking the blood culture (T1). OF patients, as compared with NOF patients, had at T1 a lower monocyte count, a lower platelet count, higher levels of CD11b expression on both neutrophils and monocytes, and higher concentrations of IL-6, IL-8 and sIL-2R. C-reactive protein and soluble E-selectin concentrations did not differ between groups. No parameter alone identified all patients that subsequently developed OF. However, a sepsis-related inflammation severity score (SISS), developed on the basis of the presence or absence of shock and on the levels of markers at T1, identified each patient that developed OF. The maximum SISS value was 7. The range of SISS values in OF patients was 2-5, and that in NOF patients was 0-1. In conclusion, high levels of CD11b expression, depressed platelet and monocyte counts, and high concentrations of IL-6, IL-8 and sIL-2R predict OF in patients with community-acquired septic shock, and the combination of these markers may provide the means to identify sepsis patients who will develop OF.

Interleukin 1 receptor antagonist and E-selectin concentrations: a comparison in patients with severe acute pancreatitis and severe sepsis.

PURPOSE: This prospective clinical study was designed to compare interleukin 1 receptor antagonist (IL-1ra) and E-selectin concentrations in patients with severe acute pancreatitis to those with severe sepsis. MATERIALS AND METHODS: Nine consecutive patients with severe acute pancreatitis and 11 consecutive patients with severe sepsis admitted to a medical/surgical intensive care unit were included in the study. Plasma concentrations of IL-1ra and E-selectin were serially measured daily for 7 days or throughout their stay in the intensive care unit if shorter. RESULTS: The concentrations of IL-1ra were significantly higher on admission in patients with severe sepsis compared with the patients with severe pancreatitis (median levels 10,500 and 2,600 pg/mL, respectively, P = .007). When the data from the first 3 days were analyzed using analysis of variance (ANOVA), the levels of IL-1ra and E-selectin were similar in both groups. The concentrations of IL-1ra and E-selectin correlated to the development of multiorgan dysfunction as assessed by sequential organ failure assessment (SOFA) score (P = .032 and .043, respectively). CONCLUSION: This study shows that IL-1ra and E-selectin are released in acute severe pancreatitis, and the levels seem to be comparable to those in patients with severe sepsis. Concentrations of IL-1ra and E-selectin correlate to the development of multiorgan failure as indicated by high SOFA scores during the first week of disease.

Systemic inflammatory response syndrome without systemic inflammation in acutely ill patients admitted to hospital in a medical emergency.

Criteria of the systemic inflammatory response syndrome (SIRS) are known to include patients without systemic inflammation. Our aim was to explore additional markers of inflammation that would distinguish SIRS patients with systemic inflammation from patients without inflammation. The study included 100 acutely ill patients with SIRS. Peripheral blood neutrophil and monocyte CD11b expression, serum interleukin-6, interleukin-1beta, tumour necrosis factor-alpha and C-reactive protein were determined, and severity of inflammation was evaluated by systemic inflammation composite score based on CD11b expression, C-reactive protein and cytokine levels. Levels of CD11b expression, C-reactive protein and interleukin-6 were higher in sepsis patients than in SIRS patients who met two criteria (SIRS2 group) or three criteria of SIRS (SIRS3 group). The systemic inflammation composite score of SIRS2 patients (median 1.5; range 0-8, n=56) was lower than that of SIRS3 patients (3.5; range 0-9, n=14, P=0.013) and that of sepsis patients (5.0; range 3-10, n=19, P<0.001). The systemic inflammation composite score was 0 in 13/94 patients. In 81 patients in whom systemic inflammation composite scores exceeded 1, interleukin-6 was increased in 64 (79.0%), C-reactive protein in 59 (72.8%) and CD11b in 50 (61.7%). None of these markers, when used alone, identified all patients but at least one marker was positive in each patient. Quantifying phagocyte CD11b expression and serum interleukin-6 and C-reactive protein concurrently provides a means to discriminate SIRS patients with systemic inflammation from patients without systemic inflammation.

Plasma interleukin-8, interleukin-10, and E-selectin levels in neutropenic and non-neutropenic bacteremic patients.

Plasma interleukin-8 (IL-8) interleukin-10 (IL-10), and E-selectin concentrations were studied in 39 neutropenic and 30 non-neutropenic bacteremic patients; 54 nonbacteremic patients were analyzed as controls. Interleukin-8 concentrations were significantly higher in neutropenic than in non-neutropenic bacteremic patients (median 475 vs. 0 pg/ml, p < 0.0001). Median IL-8 and IL-10 levels were higher in bacteremic than in non-bacteremic patients (330 vs. 0 pg/ml, p < 0.0001 and 20 vs. 0 pg/ml, p = 0.04, respectively). In contrast, concentrations of IL-10 were similar in neutropenic and non-neutropenic patients. Median levels of E-selectin were not increased in any of the patient groups. Neutropenic bacteremic patients showed significantly lower concentrations of E-selectin than did non-neutropenic bacteremic patients (p < 0.0001). In conclusion, neutropenic bacteremic patients had significantly higher concentrations of IL-8 than non-neutropenic bacteremic patients. Levels of IL-10 were higher in bacteremic than in nonbacteremic patients, but neutropenic and non-neutropenic patients had similar levels of IL-10. Increased levels of E-selectin were not found in any of the patient groups, although neutropenic patients with bacteremia had lower concentrations than did non-neutropenic patients.

Validation of air tonometric measurement of gastric regional concentrations of CO2 in critically ill septic patients.

OBJECTIVE: To evaluate the accuracy of continuous air tonometry (Tonocap, Tonometric Division, Instrumentarium, Helsinki, Finland). DESIGN: The accuracy of air tonometry was tested by comparing it with conventional saline tonometry in mechanically ventilated, critically ill septic patients and in vitro determining the partial pressure of carbon dioxide (PCO2) of humidified gases with known concentrations of CO2. SETTING: A mixed intensive care unit in a university hospital. PATIENTS: 16 mechanically ventilated patients with sepsis. MEASUREMENTS AND RESULTS: Two gastric tonometer catheters (TRIP NGS catheter, Tonometric Division, Instrumentarium, Helsinki, Finland) were introduced into the patients' stomachs. The control catheter was used as a conventional saline tonometer and the other catheter was used with the Tonocap monitoring device. A total of 153 paired measurements was made and analysed according to Bland and Altman. The mean difference between air PCO2 and saline PCO2 values (bias), the standard deviation of the differences (precision), and the Pearson correlation coefficient between air PCO2 and saline PCO2 were calculated. The data on patients were pooled and calculated for different cycle times. The mean bias (kPa) was-0.02 with a 10-min cycle time, 0.31 with 15 min, 0.56 with 30 min and 0.21 with 60-min. The precisions were 0.39, 0.54, 0.44 and 0.76, respectively. Pearson correlation coefficients were 0.93, 0.97, 0.95 and 0.82, respectively (p < 0.0001). In vitro tonometry with the Tonocap was performed in a gas chamber fully saturated with known CO2 concentrations. The clinically important 10-min cycle time was tested with 5 Tonocap monitors. Except for the first 10-min cycle time, PCO2 values determined by the Tonocap monitoring systems were comparable to known CO2 concentrations. CONCLUSIONS: The accuracy of Tonocap continuous air tonometry is close to that of conventional saline tonometry. Moreover, the clinically important 10-min cycle time with air tonometry correlated very well with saline tonometry and the time response with air tonometry was short.

Time course of beta 2-integrin CD11b/CD18 (Mac-1, alpha M beta 2) upregulation on neutrophils and monocytes after coronary artery bypass grafting. CD11b upregulation after CABG surgery.

Although upregulation of CD11b/CD18 receptor, i.e. activation of neutrophils and monocytes, during cardiopulmonary bypass is well documented, the duration of the active state after uncomplicated operation is less understood. We therefore investigated CD11b expression of phagocytes in blood samples collected 2-4, 24, 48 and 72 h after coronary artery bypass grafting. CD11b expression on neutrophils was significantly elevated at 2-4 and 24 hours after operation as compared with baseline. On monocytes, expression peaked at 24 h and returned to baseline by 72 h. Because CD11b is a sensitive marker, effects of different sampling techniques on its expression were also studied. CD11b expression was similar in samples collected with a syringe from arterial or central venous catheter or with open technique from cubital vein. On neutrophils from healthy subjects, sampling with syringe caused small (10%) but statistically significant increase of expression. We conclude that activated neutrophils disappear from circulation within hours after CABG surgery while activated monocytes may continue circulating for 2-3 days, and that CD11b sampling can be done with a syringe.

Plasma endotoxin and cytokine levels in neutropenic and non-neutropenic bacteremic patients.

Plasma endotoxin, tumor necrosis factor-alpha (TNF-alpha), interleukin 1 beta (IL-1 beta), interleukin 1 receptor antagonist (IL-1ra), and interleukin 6 (IL-6) concentrations in 69 bacteremic patients were compared with those in 54 nonbacteremic patients suffering from suspected bacterial infections. Only three (11%) of the 27 patients with gram-negative bacteremia showed detectable levels of endotoxin. TNF-alpha was detected in 6% of the bacteremic patients and in none of the nonbacteremic patients. Median IL-6 levels were significantly higher in bacteremic than in nonbacteremic patients (55 vs. 0 pg/ml, p = 0.0008). IL-6 concentrations were similar in neutropenic and non-neutropenic bacteremic patients (median 55 vs. 74 pg/ml). In contrast, neutropenic bacteremic patients had significantly lower concentrations of IL-1ra than non-neutropenic bacteremic patients (250 vs. 1,950 pg/ml, p < 0.0001). Patients with fatal bacteremia had significantly higher concentrations of IL-6 and IL-1ra than the survivors (median, 450 vs. 40, p = 0.012 and 7,600 vs. 420 pg/ml, p = 0.0075, respectively). Determinations of endotoxin or TNF-alpha in patients with suspected bacteremia failed to offer clinically relevant data on the prognosis of these patients. IL-6 levels correlated with both the presence of bacteremia and the risk of death. Granulocytopenic patients with bacteremia had lower levels of circulating IL-1ra than patients with normal granulocyte counts, and these levels correlated with poor outcome.