Validation of the new Sepsis-3 definitions: proposal for improvement in early risk identification.

OBJECTIVES: Sepsis-3 definitions generated controversies regarding their general applicability. The Sepsis-3 Task Force outlined the need for validation with emphasis on the quick Sequential Organ Failure Assessment (qSOFA) score. This was done in a prospective cohort from a different healthcare setting. METHODS: Patients with infections and at least two signs of systemic inflammatory response syndrome (SIRS) were analysed. Sepsis was defined as total SOFA ≥2 outside the intensive care unit (ICU) or as an increase of ICU admission SOFA ≥2. The primary endpoints were the sensitivity of qSOFA outside the ICU and sepsis definition both outside and within the ICU to predict mortality. RESULTS: In all, 3346 infections outside the ICU and 1058 infections in the ICU were analysed. Outside the ICU, respective mortality with ≥2 SIRS and qSOFA ≥2 was 25.3% and 41.2% (p <0.0001); the sensitivities of qSOFA and of sepsis definition to predict death were 60.8% and 87.2%, respectively. This was 95.9% for sepsis definition in the ICU. The sensitivity of qSOFA and of ≥3 SIRS criteria for organ dysfunction outside the ICU was 48.7% and 72.5%, respectively (p <0.0001). Misclassification outside the ICU with the 1991 and Sepsis-3 definitions into stages of lower severity was 21.4% and 3.7%, respectively (p <0.0001) and 14.9% and 3.7%, respectively, in the ICU (p <0.0001). Adding arterial pH ≤7.30 to qSOFA increased sensitivity for prediction of death to 67.5% (p 0.004). CONCLUSIONS: Our analysis positively validated the use of SOFA score to predict unfavourable outcome and to limit misclassification into lower severity. However, qSOFA score had inadequate sensitivity for early risk assessment.

Change of annexin binding of monocytes as an expression of cellular response to Candida albicans: down-regulation in severe sepsis.

To study the differences of monocyte activation by albicans and non-albicans species of Candida and its change in sepsis, peripheral blood mononuclear cells were isolated from 17 healthy volunteers and 26 patients with severe sepsis/shock, and incubated in the absence/presence of heat-killed (HK) isolates of four different Candida species and purified ß-D-glucan from C.albicans. Experiments were repeated in the presence and absence of inhibitors of intracellular activation pathways. Expression of annexin V on cells membranes of monocytes and lymphocytes, cytoplasmic activity of caspase-3, and DNA fragmentation of monocytes were studied. Membrane expression of annexin V on viable monocytes of healthy volunteers decreased significantly after incubation with C.albicans but not with non-albicans species. The decrease was dose-dependent from the Candida inoculum and by the concentration of ß-D-glucan. A relationship with inhibition of apoptosis was found as the activity of caspase-3 activity, and the level of DNA fragmentation were also decreased. Incubation in the absence/presence of inhibitors showed that the decrease by annexin V expression resulted by activation of the dectin-1 pathway and Raf-1 by ß-D glucan. The decrease of annexin V(+)/PI(-) expression was not shown on monocytes of patients with severe sepsis/shock, where no effect of inhibitors was found. Decrease of annexin V binding on monocytes can be viewed as a selective response to C.albicans partly effected through activation of dectin-1. This response is down-regulated after a septic insult.

Improving outcomes of severe infections by multidrug-resistant pathogens with polyclonal IgM-enriched immunoglobulins.

The emergence of infections by multidrug-resistant (MDR) Gram-negative bacteria, which is accompanied by considerable mortality due to inappropriate therapy, led to the investigation of whether adjunctive treatment with one polyclonal IgM-enriched immunoglobulin preparation (IgGAM) would improve outcomes. One hundred patients in Greece with microbiologically confirmed severe infections by MDR Gram-negative bacteria acquired after admission to the Intensive Care Unit and treated with IgGAM were retrospectively analysed from a large prospective multicentre cohort. A similar number of patient comparators well-matched for stage of sepsis, source of infection, appropriateness of antimicrobials and co-morbidities coming from the same cohort were selected. All-cause 28-day mortality was the primary end point; mortality by extensively drug-resistant (XDR) pathogens and time to breakthrough bacteraemia were the secondary end points. Fifty-eight of the comparators and 39 of the IgGAM-treated cases died by day 28 (p 0.011). The OR for death under IgGAM treatment was 0.46 (95% CI 0.26-0.85). Stepwise regression analysis revealed that IgGAM was associated with favourable outcome whereas acute coagulopathy, cardiovascular failure, chronic obstructive pulmonary disease and chronic renal disease were associated with unfavourable outcome. Thirty-nine of 62 comparators (62.9%) were infected by XDR Gram-negative bacteria and died by day 28 compared with 25 of 65 cases treated with IgGAM (38.5%) (p 0.008). Median times to breakthrough bacteraemia were 4 days and 10 days, respectively (p <0.0001). Results favour the use of IgGAM as an adjunct to antimicrobial treatment for the management of septic shock caused by MDR Gram-negative bacteria. A prospective randomized trial is warranted.

Individualized significance of the -251 A/T single nucleotide polymorphism of interleukin-8 in severe infections.

Based on the concept of the individualized nature of sepsis, we investigated the significance of the -251 A/T (rs4073) single nucleotide polymorphism (SNP) of interleukin (IL)-8 in relation to the underlying infection. Genotyping was performed in 479 patients with severe acute pyelonephritis (UTI, n = 146), community-acquired pneumonia (CAP, n = 109), intra-abdominal infections (IAI, n = 119), and primary bacteremia (BSI, n = 105) by restriction fragment length polymorphism of the polymerase chain reaction (PCR) product and compared with 104 healthy volunteers. Circulating IL-8 was measured within the first 24 h of diagnosis by an immunosorbent assay. Carriage of the AA genotype was protective from the development of UTI (odds ratio 0.38, p: 0.007) and CAP (odds ratio 0.30, p: 0.004), but not from IAI and BSI. Protection from the development of severe sepsis/septic shock was provided for carriers of the AA genotype among patients with UTI (odds ratio 0.15, p: 0.015). This was accompanied by greater concentrations of circulating IL-8 among patients with the AA genotype. It is concluded that carriage of rs4073 modifies susceptibility for severe infection in an individualized way. This is associated with a modulation of circulating IL-8.

Effect of angiotensin converting enzyme gene I/D polymorphism and its expression on clinical outcome in acute respiratory distress syndrome.

BACKGROUND: The role of the D allele of the angiotensin-converting enzyme (ACE) gene I/D polymorphism in the clinical outcomes of patients with acute lung injury and acute respiratory distress syndrome (ALI/ARDS) remains controversial. Our aim was to assess simultaneously the effect of the ACE I/D polymorphisms as well as the serum and BALF ACE levels on prognosis of patients with ARDS. METHODS: Sixty-nine mechanically ventilated patients with ALI/ARDS were recruited. ACE activity levels both in serum and BALF were assessed by chemical methods. Patients were genotyped for ACE I/D polymorphisms. Time-to-event analysis evaluated the variables associated with the 28-day and 90-day mortality. Finally, we performed a meta-analysis of studies examining the association between ACE I/D polymorphisms and mortality of ALI/ARDS patients. RESULTS: In the multivariable model, age, lung compliance, serum lactate and serum ACE levels were significantly associated with both 28- and 90-day mortality. No significant correlation was found between serum and BALF ACE levels (Spearman's rho=0.054; P=0.66). Serum ACE concentrations were significantly higher (P=0.046) in patients with D/D genotype versus the two other groups combined (I/D and I/I genotypes). The meta-analysis of 6 studies (including ours) provided evidence that D allele is significantly associated with increased mortality in ALI/ARDS patients, yielding a per-allele odds ratio of 1.76 (95% CI: 1.19, 2.59). CONCLUSION: Serum ACE levels appear to be affected by the I/D polymorphism and are correlated with prognosis in patients with ALI/ARDS indicating that further investigation of the clinical significance of the ACE in ARDS might be of value.

Procalcitonin and sepsis: recent data on diagnostic utility prognostic potential and therapeutic implications in critically ill patients.

Procalcitonin (PCT) has emerged as the most specific biomarker for bacterial infection. As clinicians become more familiar with its use, a multitude of observational studies have reported on its diagnostic potential in distinct types of infections and various clinical situations, such as in neutropenia or in the postoperative period. In the Intensive Care Unit setting, however, the prognostic value of a single PCT measurement at the time of admission on a patient with sepsis is suboptimal. Especially in cases of community-acquired pneumonia, cardiovascular biomarkers, such as mid-regional proadrenomedullin, seem to carry stronger prognostic potential than PCT. Nevertheless, the study of PCT kinetics may still be of use as a risk assessment tool for the general population of critically ill patients with sepsis syndrome. The most recent significant development in the field of PCT monitoring, is the publication of several randomized controlled trials that investigated its use as a decision making tool for the initiation and/or the duration of antibiotic treatment. Currently, the available evidence suggests that the incorporation of PCT measurements to assist with the duration of antibiotic stewardship programs may decrease antibiotic use without compromising clinical outcomes. Nevertheless, this strategy still needs further validation in large prospective studies.

Procalcitonin as an early indicator of outcome in sepsis: a prospective observational study.

This study explores the role of procalcitonin (PCT) in predicting the outcome of sepsis. In a prospective multicentre observational investigation, blood was sampled within 24 h of onset of sepsis in 1156 hospitalised patients; 234 were in the intensive care unit (ICU) at the point of presentation of sepsis while 922 were not. PCT was estimated in serum by the ultrasensitive Kryptor assay in a double-blinded fashion. Among patients outside the ICU, mortality was 8% in those with PCT ≤0.12 ng/mL but 19.9% in those with PCT >0.12 ng/mL [P<0.0001, odds ratio (OR) for death: 2.606; 95% confidence interval (CI): 1.553-4.371]. Among patients whose sepsis presented in ICU, mortality was 25.6% in those with PCT ≤0.85 ng/mL but 45.3% in those with PCT >0.85 ng/mL (P=0.002; OR for death: 2.404; 95% CI: 1.385-4.171). It is concluded that PCT cut-off concentrations can contribute to predicting the outcome of sepsis and might be of particular value in identifying patients who would benefit from ICU admission.

The effect of homocysteine on the clinical outcomes of ventilated patients with severe sepsis.

BACKGROUND: There is considerable evidence that elevated plasma homocysteine levels are associated with a prothrombotic milieu, whereas activation of the coagulation cascade is an important component of the pathogenesis of sepsis. The protein C pathway has been reported to play a central role both in the propagation of sepsis and a hyperhomocysteinemia-induced hypercoagulable state. Our primary aim was to measure plasma homocysteine levels in mechanically ventilated patients with severe sepsis/septic shock and to assess the association of these levels with relevant clinical outcomes. METHODS: The study cohort included 102 mechanically ventilated patients with severe sepsis or septic shock. Demographics, comorbidities, clinical data and severity scores were recorded. Plasma homocysteine, vitamin B12, folate, creatinine, and protein C levels were measured in all study subjects upon enrollment, and genotyping for the C677T and A1298C polymorphisisms of the methylenetetrahydrofolate reductase (MTHFR) gene and for factor V Leiden (FVL) mutations was performed as well. The primary outcomes were mortality at 28 and 90 days; secondary outcomes included the number of days without renal or cardiovascular failure and the ventilator-free days during the study period. RESULTS: Homocysteine levels were not significantly associated with any primary or secondary outcomes in the multivariable analysis. In addition, a synergistic effect of homocysteine with protein C levels was not detected. CONCLUSION: Our data suggest that plasma homocysteine levels may not inform the prognosis of mechanically ventilated patients with severe sepsis/septic shock.

Failure of tigecycline to treat severe Clostridium difficile infection.

Clostridium difficile infection is an emerging and often difficult-to-treat iatrogenic complication. Recent data suggest that tigecycline, a novel antibiotic with broad-spectrum antibacterial activity, can be used successfully to treat patients with severe Clostridium difficile infection. We report a 70-year-old man who developed severe Clostridium difficile infection, was admitted to the intensive care unit and eventually succumbed to complications of his illness despite receiving tigecycline for approximately three weeks in combination with vancomycin, metronidazole and intravenous immunoglobulin. Additionally, we discuss the unique challenges that emerged during tigecycline treatment, such as the development of Proteus mirabilis bacteraemia and of colonisation with Acinetobacter baumannii resistant to tigecycline. Finally, we review data on other cases reported in the medical literature. Even though tigecycline looks promising for the treatment of Clostridium difficile infection, we urge caution against its indiscriminate use for off label indications.

Malfunction of SynchroMed II baclofen pump delivers a near-lethal baclofen overdose.

INTRODUCTION: Intrathecal baclofen therapy using implantable pumps is an established treatment for spasticity. The pumps occasionally experience serious malfunction. CASE REPORT: A 12-year-old girl suffering from spastic diplegia was implanted with a Medtronic SynchroMed II pump (Medtronic Inc., Minneapolis, Minn., USA). During a refill at 3 months 19 ml of baclofen were still in the pump. It was assumed that there was a lumbar catheter obstruction and a revision was performed. At 11 months she was receiving 180 microg/day. When she presented for refill, there were again 19 ml of baclofen in the reservoir. The pump was refilled, stopped and restarted at a lower dose. Ten minutes after restart the patient was complaining that she could not move her legs. Within the next 50 min she lapsed into coma, from a presumed baclofen overdose. She was intubated and ventilated. The reservoir was emptied of baclofen and the pump stopped. Seventeen hours after the baclofen overdose, the patient woke up gradually with no new neurological deficits. The pump was removed a week later. Medtronic laboratories examined the pump and reported no technical fault. DISCUSSION: The implanted Medtronic SynchroMed II pump suffered an unusual malfunction. It is postulated that the pump had suffered a motor stall, and when it was restarted, it gave an unusually high, potentially lethal, dose to the patient. CONCLUSION: Physicians who implant pumps for intrathecal baclofen administration need to be aware that these devices may suffer unheralded catastrophic failure that can lead to potentially lethal overdose administration.

Population pharmacokinetic analysis of colistin methanesulfonate and colistin after intravenous administration in critically ill patients with infections caused by gram-negative bacteria.

Colistin is used to treat infections caused by multidrug-resistant gram-negative bacteria (MDR-GNB). It is administered intravenously in the form of colistin methanesulfonate (CMS), which is hydrolyzed in vivo to the active drug. However, pharmacokinetic data are limited. The aim of the present study was to characterize the pharmacokinetics of CMS and colistin in a population of critically ill patients. Patients receiving colistin for the treatment of infections caused by MDR-GNB were enrolled in the study; however, patients receiving a renal replacement therapy were excluded. CMS was administered at a dose of 3 million units (240 mg) every 8 h. Venous blood was collected immediately before and at multiple occasions after the first and the fourth infusions. Plasma CMS and colistin concentrations were determined by a novel liquid chromatography-tandem mass spectrometry method after a rapid precipitation step that avoids the significant degradation of CMS and colistin. Population pharmacokinetic analysis was performed with the NONMEM program. Eighteen patients (6 females; mean age, 63.6 years; mean creatinine clearance, 82.3 ml/min) were included in the study. For CMS, a two-compartment model best described the pharmacokinetics, and the half-lives of the two phases were estimated to be 0.046 h and 2.3 h, respectively. The clearance of CMS was 13.7 liters/h. For colistin, a one-compartment model was sufficient to describe the data, and the estimated half-life was 14.4 h. The predicted maximum concentrations of drug in plasma were 0.60 mg/liter and 2.3 mg/liter for the first dose and at steady state, respectively. Colistin displayed a half-life that was significantly long in relation to the dosing interval. The implications of these findings are that the plasma colistin concentrations are insufficient before steady state and raise the question of whether the administration of a loading dose would benefit critically ill patients.

The effect of exogenous surfactant in patients with lung contusions and acute lung injury.

OBJECTIVE: To investigate the acute effect of surfactant replacement in multiple-trauma patients with lung contusion and acute lung injury. DESIGN AND SETTING: Prospective randomized clinical trial in the 14-bed ICU of a 750-bed university hospital. PATIENTS AND PARTICIPANTS: Sixteen ventilated trauma patients with severe refractory hypoxemia (PaO(2)/FIO(2)<150 mmHg) and lung contusions. INTERVENTIONS: Patients were randomly assigned to either surfactant administration (n=8) or standard treatment (n=8). A single dose of natural bovine surfactant was instilled bronchoscopically in the involved lung areas; each segmental bronchus received (200/19) mg/kg body weight. MEASUREMENTS AND RESULTS: The surfactant group demonstrated an acute improvement in oxygenation after surfactant replacement compared both to control group and to baseline values. In the surfactant group PaO(2)/FIO(2) increased from 100+/-20 mmHg at baseline to 140+/-20 (6 h), 163+/-26 (12 h), and 187+/-30 mmHg (24h). Compliance increased from 30 to 36 ml/cmH(2)O at 6 h after administration, and this increase remained significant at the 24, 48, and 72 h time points. The surfactant group demonstrated a higher response to recruitment maneuvers than the control group at 6 h. The mean duration of ventilatory support was 5.6 +/-2.6 days in the surfactant group and 8.1+/-2.4 days in the control group. CONCLUSIONS: Surfactant replacement was well tolerated in patients with lung contusions and severe hypoxemia and resulted in improved oxygenation and compliance.

Coronary sinus venoarterial CO2 difference in different hemodynamic states.

Myocardial metabolic rate and coronary flow are closely related limiting thus the diagnostic value of coronary sinus saturation monitoring as an indicator of flow. Regional venoarterial CO2 gradient was found elevated during low flow in various clinical and experimental conditions, in animals and humans. This study was undertaken to examine the impact of the variations of cardiac mechanical work on veno-arterial CO2 content and partial pressure difference (deltaPCO2) of the coronary sinus blood. Twenty-seven patients of either sex (m/f = 21/6), undergoing coronary artery bypass grafting under extracorporeal circulation, were studied. Monitoring included a Swan-Ganz catheter and a coronary sinus line. The correct position of the late was verified by the waveform displayed in the monitor. Immediately after cannulae placement, a hemodynamic profile was obtained and simultaneous arterial and coronary sinus sampling for blood gas analysis was done in an ABL 720 (Radiometer Copenhagen) analyzer. A second collection of the same data was obtained five minutes later with the patients in a slight "head-down" position. Conditions for exclusion was intersample variation of hemoglobin's concentration greater than 15% and sodium ion concentration difference greater than 10% of the greater value. Arteriovenous oxygen partial pressure difference (deltaP(a-cs)O2), veno-arterial carbon dioxide partial pressure difference (deltaP(cs-a)CO2), O2 & CO2 content difference and heart's respiratory quotient were calculated and correlated to cardiac output (CO) and the other hemodynamic parameters. Statistical analysis employed t-paired test and linear regression. No ischemia was detected during sampling. "Head-down" position had a significant impact to all hemodynamic parameters except heart rate. In both data rows, although CO ranged widely and altered significantly, coronary sinus oxygen saturation and arteriovenous O2 content difference were stable and showed insignificant correlations to all the hemodynamic parameters that were studied. Carbon dioxide content difference (coronary sinus-arterial) showed a trending of decrease with higher flow. DeltaP(cs-a)CO2 appeared stable and independent of flow. Finally, respiratory quotient decreased significantly from 0.91 +/- 0.4 to 0.86 +/- 0.4 (mean +/- SD; p < 0.05). The heart's high basal oxygen consumption and the almost near hemoglobin's desaturation transcoronary extraction of oxygen limits the value of coronary sinus saturation monitoring as indicator of coronary flow. Heart's little extraction reserve is faced with coronary flow reserve. In the physiologic range and under the conditions of anesthesia, elevated CO2 production is accompanied with increased coronary flow. Under these circumstances, deltaP(cs-a)CO2 appears stable and is not suitable for clinical decisions concerning heart's coronary flow.

Bronchoalveolar lavage alterations during prolonged ventilation of patients without acute lung injury.

Mechanical ventilation deteriorates previously injured lung, but little is known about its effect on healthy human lung. This work was designed to assess the effect of prolonged mechanical ventilation on bronchoalveolar lavage (BAL) fluid composition of patients without acute lung injury. Twenty-two ventilated patients (tidal volume 8-10 mL x kg(-1), positive end-expiratory pressure 3-5 cmH2O) without lung injury, who did not develop any complication from the respiratory system during the 2-week study period, were studied. They were subjected to three consecutive BALs, the first during 36 h from intubation, the second at the end of the first week of mechanical ventilation and the third at the end of the second week of mechanical ventilation. Total BAL protein increased during mechanical ventilation (148 +/- 62, 381 +/- 288, 353 +/- 215 microg x mL(-1) BAL for the first, second and third BAL, respectively). In contrast, BAL phospholipids decreased (2.7 +/- 1.1, 1.4 +/- 0.6, 1.2 +/- 0.7 microg x mL(-1) BAL, respectively). Large surfactant aggregates were reduced and inflammatory markers, such as platelet activating factor (PAF), PAF-acetylhydrolase and neutrophils, significantly increased after 1 week, but partially remitted after 2 weeks of mechanical ventilation. In summary, this study demonstrates that prolonged mechanical ventilation even of patients without acute lung injury is associated with the presence of inflammatory markers and surfactant alterations.

Effect of the prone position on patients with hydrostatic pulmonary edema compared with patients with acute respiratory distress syndrome and pulmonary fibrosis.

This study examined the effect of the prone position on mechanically ventilated patients with hydrostatic pulmonary edema (HPE). Eight patients with acute HPE and mechanically ventilated in the prone position (Group 1) were studied. Six patients with acute HPE and mechanically ventilated in the supine position (Group 2), 20 patients with ARDS (Group 3), and 5 patients with pulmonary fibrosis (PF) (Group 4) served as control patients. Patients with HPE, who after being mechanically ventilated for at least 6 h needed an FI(O(2)) >/= 0.6 to achieve an Sa(O(2)) of approximately 90%, and did not respond to recruitment maneuvers, were turned to the prone position. Parameters of oxygenation, lung mechanics, and hemodynamics were determined in both the supine and prone positions. All patients with HPE exhibited improvement of oxygenation when they were placed in the prone position. The Pa(O(2))/FI(O(2)) ratio increased from 72 +/- 16 in the supine position to 208 +/- 61 after 6 h in the prone position (p < 0.001); the rise in Pa(O(2)) was persistent, without detrimental effect on hemodynamics. Fifteen of 20 patients with ARDS (75%) improved oxygenation when in the prone position. The Pa(O(2))/FI(O(2)) ratio increased from 83 +/- 14 in the supine position to 189 +/- 34 after 6 h in the prone position (p < 0.001). In contrast, 5 of 20 patients with ARDS (25%) and none of the patients with PF responded favorably to prone positioning. Patients with HPE and early ARDS responded better to prone positioning than did patients with late ARDS and PF. Patients with HPE and ventilated in the supine position had a lower Pa(O(2))/FI(O(2)) ratio and the duration of mechanical ventilation was longer compared with that of patients in the prone position. Our results show that the prone position may be a useful maneuver in treating patients with severe hypoxemia due to pulmonary edema. The presence of pulmonary edema, as in early ARDS and HPE predicts a beneficial effect of the prone position on gas exchange. In contrast, the presence of fibrosis, as in late ARDS and pulmonary fibrosis, predisposes to nonresponsiveness to prone positioning.

Bronchoalveolar lavage fluid characteristics of early intermediate and late phases of ARDS. Alterations in leukocytes, proteins, PAF and surfactant components.

OBJECTIVE: To determine the concentration of proteins and phospholipids, markers of inflammatory reaction such as platelet-activating factor (PAF), and cell alterations in bronchoalveolar lavage (BAL) fluid during the evolution of the acute respiratory distress syndrome (ARDS). DESIGN: Prospective controlled study. SETTING: 14-bed medical-surgical intensive care unit in a 750-bed university teaching hospital. PATIENTS: 19 mechanically ventilated patients, 9 patients with ARDS and 10 patients without cardiopulmonary disease (controls), were eligible for this study. INTERVENTIONS: BAL was performed during the early, intermediate, and late phases of ARDS. MEASUREMENTS AND RESULTS: Total phospholipids and individual phospholipid classes of the surfactant, proteins, PAF, and cells were measured. High levels of PAF, an increase in neutrophils and proteins, and quantitative as well as qualitative alterations in phospholipids in BAL fluid were observed in ARDS patients compared to the control group. PAF, proteins, and neutrophils were higher in early ARDS than in intermediate or late ARDS. The surfactant pool increased in the early phase and decreased in the intermediate or late phase of the syndrome. The qualitative alterations of surfactant consist of reduced phospholipid content in the surfactant structures with good surface properties; moreover, there was a considerable decrease in the percentage of phosphatidylcholine and phosphatidylglycerol, followed by an increase in phosphatidylethanolamine, phosphatidylserine, phosphatidylinositol, and sphingomyelin in all three phases of ARDS compared to the control group. Lysophosphatidylcholine was detectable only in late ARDS. CONCLUSION: Total surfactant phospholipids, surfactant components, and inflammatory markers such as PAF, cells, and proteins were affected in patients with ARDS. These factors, undergoing quantitative alterations during the course of ARDS, could have a significant role in the pathogenesis and evolution of ARDS.

Proteins and phospholipids in BAL from patients with hydrostatic pulmonary edema.

The purpose of the present study is twofold: to evaluate alterations in total phospholipid content and individual phospholipid classes of the surfactant, and to detect markers of inflammatory reaction in bronchoalveolar lavage (BAL) from patients with hydrostatic pulmonary edema (HPE). Mechanically ventilated patients with HPE (Group 1) were compared with mechanically ventilated patients without cardiopulmonary disease (Group 2), considered as the control group. Group 3, including patients with high-permeability pulmonary edema, was used for further comparison. BAL was obtained and immediately cooled at 4 degrees C. Total proteins, albumin, and platelet-activating factor--acetylhydrolase (PAF-AcH) were measured. Total lipids were extracted and analyzed after thin-layer chromatographic separation. PAF was determined with bioassay. Total BAL proteins and albumin were found significantly higher in patients with HPE compared with control, but were lower compared with adult respiratory distress syndrome (ARDS). PAF was elevated in patients with HPE and ARDS, whereas in the control group it was actually in nondetectable levels. PAF was significantly higher in ARDS than in HPE patients. BAL neutrophils concentration was higher in HPE compared with control, but lower compared with ARDS. There was an inverse correlation between PAF-AcH and PAF. Quantitative reduction of total BAL phospholipids (PL) and qualititative deficiency was observed in both patients with HPE and ARDS. The findings of this study suggest that there is evidence of inflammation in the airspaces of patients with HPE.