Lavage Effluent Research Articles

α-bisabolol-loaded lipid-core nanocapsules reduce lipopolysaccharide-induced pulmonary inflammation in mice.

Acute respiratory distress syndrome (ARDS) is a severe clinical condition of respiratory failure due to an intense inflammatory response with different etiologies. Despite all efforts, therapy remains limited, and ARDS is still associated with high mortality and morbidity. Plants can provide a vast source of active natural products for the discovery of new drugs. α-bisabolol (α-bis), a constituent of the essential oil from chamomile, has elicited pharmacological interest. However, the molecule has some limitations to its biological application. This study was conducted to develop a drug delivery system using lipid-core nanocapsules (LNCs) to improve the anti-inflammatory effects of orally administered α-bis. α-bis-loaded LNCs (α-bis-LNCs) were prepared by interfacial deposition of poly(ε-caprolactone) and orally administered in a mouse model of ARDS triggered by an intranasal administration of lipopolysaccharide (LPS). We found that α-bis-LNCs (30, 50, and 100 mg kg−1) significantly reduced airway hyperreactivity (AHR), neutrophil infiltration, myeloperoxidase activity, chemokine levels (KC and MIP-2), and tissue lung injury 18 hours after the LPS challenge. By contrast, free α-bis failed to modify AHR and neutrophil accumulation in the bronchoalveolar lavage effluent and lung parenchyma and inhibited elevation in the myeloperoxidase and MIP-2 levels only at the highest dose. Furthermore, only α-bis-LNCs reduced LPS-induced changes in mitogen-activated protein kinase signaling, as observed by a significant reduction in phosphorylation levels of ERK1/2, JNK, and p38 proteins. Taken together, our results clearly show that by using LNCs, α-bis was able to decrease LPS-induced inflammation. These findings may be explained by the robust increase of α-bis concentration in the lung tissue that was achieved by the LNCs. Altogether, these results indicate that α-bis-LNCs should further be investigated as a potential alternative for the treatment of ARDS.

Impact of Pathogen-Directed Antimicrobial Therapy for Ventilator-Associated Pneumonia in Trauma Patients on Charges and Recurrence

Ventilator-associated pneumonia (VAP) represents one of the driving forces behind antibiotic use in the ICU. In a previous study, we established a defined algorithm for treatment of hospital-acquired VAP dictated by the causative pathogen. The purpose of the current study was to evaluate the impact of this algorithm for hospital-acquired VAP on recurrence and charges in trauma patients. Patients with VAP secondary to MRSA, Acinetobacter baumannii, Pseudomonas aeruginosa, Stenotrophomonas maltophilia, or Enterobacteriaceae during 5 years subsequent to the previous study were evaluated. All VAP were diagnosed using quantitative cultures of the bronchoalveolar lavage effluent. Duration of antimicrobial therapy was dictated by the causative pathogen. If microbiologic resolution, defined as <10(3) colony-forming units/mL, was achieved, therapy was stopped by day 10. The remainder received 14 days of therapy. Recurrence was defined as >10(5) colony-forming units/mL on subsequent bronchoalveolar lavage performed within 2 weeks after completion of appropriate therapy. Five hundred and twenty-nine VAP episodes were identified in 381 patients. Overall recurrence was unchanged compared with the previous study (1.5% vs 2%; p = 0.3). There was a decrease in the number of bronchoalveolar lavages performed per patient compared with the previous study (1.6 vs 2.3; p = 0.24) and a reduction of 4.8 antibiotic days per VAP episode compared with the previous study. Both changes resulted in a cumulative reduction of $3,535.04 per patient, for a savings of $1.35 million during the study period. Hospital-acquired VAP can be managed effectively by a defined course of therapy dictated by the causative pathogen. Adherence to an established algorithm simplified the management of VAP and contributed to a cumulative reduction in patient charges without impacting recurrence.

Diagnostic peritoneal lavage in hemodynamically stable patients with lower chest or anterior abdominal stab wounds.

Managing hemodynamically stable patients with thoracoabdominal stab wounds is still under dispute. This study aimed at discussing cut-off points of red blood cell (RBC) count in diagnostic peritoneal lavage (DPL) effluent in these patients. Three hundred and eighty-eight patients with thoracoabdominal stab wounds and hemodynamically stable status were enrolled. In cases without a clear indication of laparotomy, the peritoneal cavity was washed out with 1000 ml of normal saline and the effluent fluid was analyzed for RBC count. RBC counts of >100,000/mm3 in abdominal wounds and of >10,000/mm3 in lower chest wounds were considered as indications for exploratory laparotomy (conventional approach). New cut-off points for RBC count were calculated in backward analysis. Sensitivity and specificity of the conventional approach were 90% and 84%, respectively. RBC counts >15,000/mm3 in abdominal wounds and >25,000/mm3 in lower chest wounds were the best cut-off points in distinguishing patients with and without need of operation, with a sensitivity and specificity of 94% and 96%, respectively. New cut-off points of RBC count in DPL effluent may promote management of patients with thoracoabdominal stab wounds and no obvious indication for operation.

Anatomical association of fluid yielding ducts with location of the breast cancer affected segment in screen detected and symptomatic breast cancer

The concept of the intraductal approach to evaluating the breast microenvironment assumes direct access to the breast cancer containing duct. Previous studies on duct anatomy infusing a dye or contrast found fluid-yielding ducts to be associated with the cancer containing duct in approximately 50% of fluid-yielding breasts with cancer. A concordant anatomical relationship between accessible ductal sytems and the cancer-affected lobe is essential if cytology or other cell markers are to be successfully identified as indicators of cancer or of early cancerous change. The concordant relationship is less important if field change effects are considered to predictors of malignant change. The aim of this study was to determine how often duct lavage effluent drains the breast cancer affected segment.

Use of CT Morphometry To Detect Changes in Lung Weight and Gas Volume

CT estimates of lung density have been used to estimate the extent and severity of emphysema. The present study was designed to test the hypothesis that quantitative CT can track the changes that occur in diffuse lung disease. The study was based on five patients with pulmonary alveolar proteinosis (PAP) who underwent lung lavage. Pulmonary function was measured before and after each individual lung lavage, and the CT scans before and after lavage were used to compare total lung volume, airspace volume, lung weight, and regional lung inflation. The dry weight of proteinaceous material lavaged from the lung was measured and compared to the change in CT lung weight. All the patients showed improvements in dyspnea, percentage of predicted diffusion capacity of the lung for carbon monoxide, and FVC. There was no change in CT-measured total lung volume or airspace volume, but there was a reduction in lung weight following lavage (p = 0.001), which correlated with the dry weight of the lavage effluent (R(2) = 0.73). Therefore, there was a shift in the regional lung inflation toward a more inflated lung with a corresponding increase in the mean lung inflation (p = 0.001). These data show that quantitative CT can objectively track the changes in lung weight and airspace inflation produced by a standard intervention in PAP, and we postulate that it can provide similar information about the progression of other diffuse lung diseases.

Ductal Lavage for Early Detection--What Doesn't Come Out in the Wash

Ductal Lavage for Early Detection--What Doesn't Come Out in the Wash

Is Ventilator-Associated Pneumonia in Trauma Patients an Epiphenomenon or a Cause of Death?

Ventilator-associated pneumonia (VAP) is a common infection among patients in trauma intensive care units (ICUs). It has been suggested by different investigators that VAP is an indicator of injury severity and not necessarily associated with mortality. Crude mortality rates approximating 20% have been reported for trauma patients with VAP. Most studies have involved the most severely injured patients, making it difficult to determine the relative contribution of either VAP or injury severity to death. If VAP is independently associated with mortality, this relationship should be most evident in less severely injured patients. We studied patients with less severe injuries (Injury Severity Score, ISS < 25) to determine the impact of VAP on outcomes. Patients admitted to the trauma ICU with ISS < 25 were identified from the trauma registry of a level I trauma center. Patients with penetrating injuries and those who died within 48 h of injury were excluded. Pneumonia was diagnosed using quantitative cultures of bronchoalveolar lavage effluent (>/= 10(5) colony forming units/mL). Risk factors for VAP, including age, transfusions with 24 h of admission, brain injury, and chest injury severity were analyzed. Logistic regression analysis was then performed to determine independent factors for death.Results: There were 15,492 blunt admissions over a 5.5 year study period who survived >48 h. Of these, 5,860 (38%) were admitted to the ICU, and 4,111 (70% of ICU admissions) had ISS < 25. The incidence of VAP in this group was 8%. Patients with VAP were older (47 vs 39 years), had more transfusions within 24 h (2.5 vs 0.9 units of red blood cell concentrates) and had greater injury severity by ISS (16.7 vs 12.6 points), GCS (Glasgow Coma Scale) score (11.8 vs. 13.7 points) and chest AIS (Abbreviated Injury Scale) (1.7 vs 0.9 points; all p < 0.001). Overall mortality was 4%. Mortality was 16% in patients with VAP compared to 3% in those without VAP (p < 0.0001). Logistic regression analysis identified transfusions, age, and VAP as independent predictors of mortality. Other descriptors of injury severity (ISS, GCS, or chest AIS) were not associated with death. There were 15,492 blunt admissions over a 5.5 year study period who survived . 48 h. Of these, 5,860 (38%) were admitted to the ICU, and 4,111 (70% of ICU admissions) had ISS , 25. The incidence of VAP in this group was 8%. Patients with VAP were older (47 vs 39 years), had more transfusions within 24 h (2.5 vs 0.9 units of red blood cell concentrates) and had greater injury severity by ISS (16.7 vs 12.6 points), GCS (Glasgow Coma Scale) score (11.8 vs. 13.7 points) and chest AIS (Abbreviated Injury Scale) (1.7 vs 0.9 points; all p , 0.001). Overall mortality was 4%. Mortality was 16% in patients with VAP compared to 3% in those without VAP (p , 0.0001). Logistic regression analysis identified transfusions, age, and VAP as independent predictors of mortality. Other descriptors of injury severity (ISS, GCS, or chest AIS) were not associated with death. Ventilator-associated pneumonia is independently associated with death in less severely injured trauma patients. This demonstrates the need for effective diagnostic techniques so that adequate therapy may be initiated. Prevention of VAP in less severely injured trauma patients should increase survival.

Diagnostic peritoneal lavage in the evaluation of abdominal trauma using the dipstick.

To determine the accuracy and sensitivity of diagnostic peritoneal lavage in the assessment of intra-abdominal injury using the dipstick method. Prospective study, involving the performance of diagnostic peritoneal lavage in the out patient department and surgical wards prior to surgical intervention. Kenyatta National Hospital-General Surgical and Orthopaedic wards and outpatient department. The study was conducted over a duration of six months, starting from January 1995 to July 1995. Ninety six patients with penetrating (68) and blunt (28) abdominal trauma underwent diagnostic peritoneal lavage as evaluation of the severity of abdominal trauma. Dipstick (combur 9 strips) was used to evaluate lavage effluent for red blood cells, white blood cells, protein and bilirubin. Forty three patients had positive diagnostic peritoneal lavage (DPL) results, of which 40 (93%) had positive findings at laparatomy and three (7%) had negative findings at laparatomy. The remaining 53 patients had negative DPL results and were managed conservatively. One patient with a negative DPL result became symptomatic and had a positive laparatomy. Conservatively managed patients were discharged after 24 hours observations without any complications. DPL had an accuracy and sensitivity of 93% and specificity of 98%. Diagnostic peritoneal lavage is a cheap, safe and reliable method for assessment of abdominal trauma. The method is easy to perform by trained junior doctors in the OPD, or as a bedside procedure. Use of this method reduced negative laparotomy rate from 50% to 6.9% and average duration of stay from 6.5 days to 1.9 days. This method is recommended as a basic tool in the assessment of abdominal trauma patients.

Enhanced Alveolar Clearance With Chest Percussion Therapy and Positional Changes During Whole-Lung Lavage for Alveolar Proteinosis

Pulmonary alveolar proteinosis has traditionally been treated with whole-lung lavage (WLL). The literature describes a variety of techniques used in performing the WLL, including mechanical vs manual chest percussion, use of prone positioning, and variances in lavage volume. We have quantified and compared the effective alveolar clearance for each component of the lavage by measuring the dry weight of material in the lavage effluent. We measured this in five patients who underwent six consecutive WLLs at the University of Pittsburgh Medical Center. We performed the lavage in the following three stages: stage I, passive drainage; stage II, assisted clearance; and stage III, positional clearance. Aliquots of lavage effluent were centrifuged to determine the dry weight of material present in sequentially recorded bottles within each stage. At the initiation of each augmentation, there was a statistically significant improvement in the clearance of material (stage II, p = 0.009; stage III, p = 0.012). Furthermore, we show that lipoproteinaceous material is present in the lavage effluent in all stages of latter portions of the lavage. The effective removal of material would be expected to have an impact on the physiologic and clinical response to WLL. This finding emphasizes the importance of performing an adequate and standardized lavage.

The appropriate diagnostic threshold for ventilator-associated pneumonia using quantitative cultures.

The use of quantitative cultures of the bronchoalveolar lavage (BAL) effluent to distinguish between posttraumatic inflammatory response and ventilator-associated pneumonia (VAP) is becoming more common. However, the diagnostic threshold of either 10 or 10 colonies/mL remains debatable. Because mortality from VAP is related to treatment delay, some have chosen a lower diagnostic threshold (>10 colonies/mL). This may result in unnecessary antibiotic use with its sequelae: increased resistant organisms, antibiotic-related complications, and increased costs. The purpose of this study is to determine the optimal diagnostic threshold for VAP diagnosis using quantitative cultures of the BAL effluent. Data on patients with fiberoptic bronchoscopy with BAL are maintained in a prospectively collected database at our Level I trauma center. This database was reviewed for timing and frequency of BAL and the colony counts of each organism identified. Indication for bronchoscopy was clinical evidence of VAP. VAP was defined as >10 colonies/mL in the BAL effluent. A false-negative BAL was defined as any patient who had <10 colonies/mL and developed VAP with the same organism up to 7 days after the previous culture. Over a 46-month period, 526 patients underwent 1,372 fiberoptic bronchoscopy procedures with BAL. Of these, 72% were male patients, 91% followed blunt injury, and mean age and Injury Severity Score were 43 years and 30, respectively. Overall mortality was 14%. There were 1,898 organisms identified (42% were gram-positive and 58% were gram-negative). VAP was diagnosed in 38% of BAL. Overall, there were 43 episodes in 38 patients defined as false-negative (3%). The false-negative rate was 9% in patients with 10 organisms. The most common false-negative organisms were Pseudomonas and Acinetobacter species. The VAP diagnostic threshold for quantitative BAL in trauma patients should be >10 colonies/mL. One may consider a threshold of >10 colonies/mL in severely injured patients with Pseudomonas or Acinetobacter species.

Novel broad-spectrum chemokine inhibitor protects against lung ischemia-reperfusion injury

Background: Functional roles for chemokines have been demonstrated in several models of ischemia-reperfusion injury. The redundancy inherent to chemokine pathways makes administration of neutralizing antibodies to any single chemokine ineffective in ameliorating injury. This study was undertaken to define the pattern of chemokine expression in lung ischemia-reperfusion injury (LIRI), and to determine whether a broad-spectrum chemokine inhibitor, NR58-3.14.3, could confer significant protection against LIRI. Methods: Left lungs of rats were rendered ischemic for 90 minutes and then reperfused for 4 hours. Chemokine secretion into the alveolar space was quantified by enzyme-linked immunoassay. Treated animals received NR58-3.14.3 prior to reperfusion. Vascular injury was measured by lung permeability index, neutrophil accumulation in lung parenchyma was determined by myeloperoxidase (MPO) activity, and alveolar leukocyte counts were quantified in bronchoalveolar lavage (BAL) effluent. A ribonuclease protection assay evaluated mRNA expression of various chemokines. Results: Lavage effluent in untreated animals demonstrated significant increases in the secretion of cytokine-induced neutrophil chemoattractant (CINC), tumor necrosis factor-alpha (TNF-α), macrophage inflammatory protein-2 (MIP-2), MIP-1α and monocyte chemoattractant protein-1 (MCP-1). Animals receiving NR58-3.14.3 demonstrated a 37% ( p < 0.001) reduction in vascular injury and a marked reduction in lung MPO activity ( p < 0.001) and alveolar cell counts ( p = 0.005). Chemokine inhibition decreased mRNA expression of a number of early response cytokines when compared with positive control animals, and caused a significant decrease ( p < 0.04) in the secretion of TNF-α. Conclusions: These studies demonstrate that chemokines are expressed after lung ischemia and reperfusion, and that broad-spectrum chemokine inhibition ameliorates reperfusion injury. mRNA expression of early response cytokines was modulated, and the secretion of TNF-α was decreased.

Early activation of the alveolar macrophage is critical to the development of lung ischemia-reperfusion injury

Objectives Activation of the alveolar macrophage is critical to the development of nonischemic inflammatory lung injury. The present studies were undertaken to determine whether the alveolar macrophage plays a similarly important role in lung ischemia-reperfusion injury. Methods The left lungs of male rats were rendered ischemic for 90 minutes and reperfused for up to 4 hours. Treated animals received liposome-encapsulated clodronate, which depletes alveolar macrophages. Injury was quantitated in terms of vascular permeability, tissue neutrophil accumulation, and bronchoalveolar lavage fluid leukocyte, chemokine, and cytokine content. Lung homogenates were also analyzed for nuclear translocation of the transcription factors nuclear factor κB and activator of protein 1. Results Depletion of alveolar macrophages reduced lung vascular permeability by 53% compared with that seen in control animals (permeability indices: 0.88 ± 0.07 to 0.46 ± 0.04, P < .001). The protective effects of alveolar macrophage depletion correlated with a 50% reduction in tissue myeloperoxidase content (0.62 ± 0.07 to 0.33 ± 0.03, P < .006) and marked reductions in bronchoalveolar lavage fluid leukocyte accumulation. Alveolar macrophage–depleted animals also demonstrated marked reductions of the elaboration of multiple proinflammatory chemokines and cytokines in the lavage effluent and nuclear transcription factors in lung homogenates. Conclusion It is likely that the alveolar macrophage is the key early source of multiple proinflammatory mediators that orchestrate lung ischemia-reperfusion injury. Depleting alveolar macrophages is protective against injury, supporting its central role in oxidant stress–induced cytokine and chemokine release and the subsequent development of lung injury.

Endogenous interleukin-4 and interleukin-10 regulate experimental lung ischemia reperfusion injury

Background Regulatory cytokines play functional roles in experimental heart, hindlimb, and liver ischemia reperfusion injury. However, little is known about their involvement in direct lung ischemia reperfusion injury (LIRI). These studies were undertaken to investigate the role of two regulatory cytokines, interleukin-4 (IL-4) and IL-10, in an in vivo model of LIRI. Methods Left lungs of Long-Evans rats underwent normothermic ischemia for 90 minutes and reperfusion for up to 4 hours. Treated animals received either recombinant IL-4 or recombinant IL-10, or antibodies to IL-4 or IL-10 immediately before reperfusion. Lung injury was quantitated by permeability indices, lung parenchymal neutrophil sequestration (myeloperoxidase [MPO] content), and alveolar leukocyte content in bronchoalveolar lavage (BAL) effluent. Expression of IL-4 and IL-10 was determined by immunoblotting, and mRNA expression for early response cytokines was evaluated by ribonuclease protection assays. Results IL-4 and IL-10 protein expression was significant after 2 hours of reperfusion. Animals receiving anti-IL-4 ( p = 0.05) and anti-IL-10 ( p = 0.01) antibodies demonstrated increased permeabilities compared with positive controls. Lung tissue neutrophil accumulation ( p < 0.004) and BAL leukocyte content ( p < 0.04) were also significantly increased in animals receiving anti-IL-10 antibodies. Conversely, animals receiving recombinant IL-4 and recombinant IL-10 demonstrated reduced permeabilities and lung MPO content. Both anti-IL-4 and anti-IL-10 treatment increased mRNA expression for a number of early response cytokines, including TNF-α and IL-1β. Conclusions IL-4 and IL-10 are expressed in response to LIRI and function to decrease injury severity. These effects are partly due to modulated expression of early proinflammatory cytokines.

A formula for prediction of posttraumatic pneumonia based on early anatomic and physiologic parameters.

Identification of risks for development of ventilator-associated pneumonia (VAP), which might be identified early after injury, would allow for prognostic estimates and targeting of high-risk cohorts for clinical trials of preventive strategies. This study was performed to develop an equation that can be applied to estimate the probability of pneumonia based on parameters collected in the early postinjury interval. Over a 28-month period, patient admissions were reviewed for mechanism and severity of injury, patterns of injury, shock, and need for emergent intubation. Early deaths (<48 hours) were excluded. VAP diagnosis required > or = 10(5) colony-forming units/mL organisms in the bronchoalveolar lavage effluent. Multiple logistic regression analysis was used to develop the prediction equation and estimate odds ratios. The equation was then tested on consecutive patients admitted over a 2-month period. We reviewed 9,721 admissions (77% blunt, 23% penetrating). VAP incidence was 5.6%. Overall mortality was 2% (21% for patients with VAP vs. 1% for no VAP; p < 0.0001). Multiple logistic regression analysis for all patients produced the following equation: f(x) = -3.08 - 1.56 (MOI) - 0.12 (GCS) + 1.37 (SCI) + 0.30 (chest AIS) + 1.87 (lap) + 0.67 (tx) + 0.05 (ISS) + 0.66 (int), where MOI is mechanism of injury (penetrating = 1, blunt = 0), GCS is Glasgow Coma Scale score, SCI is spinal cord injury (yes = 1, no = 0), lap is emergent laparotomy (yes = 1, no = 0), ISS is Injury Severity Score, tx is units of blood transfused in the resuscitation room, and int is intubation in either the field or the resuscitation room (yes = 1, no = 0). The probability of VAP was calculated as follows: P(VAP) = e(f)(x)/1 + e(f)(x). This formula was concordant in 95% and discordant in 5%. It is possible to accurately predict risk for VAP in trauma patients based on data available early after injury. This calculation could be useful for counseling families relative to prognosis and research protocols, and addressing hospitalization issues with third-party payors.

Does gender difference influence outcome?

Recent laboratory studies have demonstrated that immune responses differ between male and female rodents, and some clinical studies have suggested gender differences regarding incidence and mortality from sepsis. The differences appear because of both deleterious testosterone and beneficial estrogen effects; clinical trials of testosterone blockage and/or estrogen administration for male subjects have been suggested. We evaluated the effect of gender on various outcomes in trauma patients. Trauma patients over a 52-month period were identified from the trauma registry. Early deaths were excluded. Outcomes included mortality, pneumonia (> or = 10 colony-forming units/mL in bronchoalveolar lavage effluent), acute respiratory distress syndrome, bacteremia, ventilator days, and intensive care unit and hospital length of stay. Patients were stratified by injury mechanism, gender, age (assuming women < or = 40 were premenopausal and those > 50 were postmenopausal), and injury severity. There were 18,133 patients identified, and 544 were excluded because of early death. There were 12,756 (73%) men and 4,833 (27%) women. There were no outcome differences after penetrating injury with respect to gender and age group. There was a survival advantage for women < or = 40 in the Injury Severity Score 16 to 24 group, but these patients had statistically less severe injury. Overall, men tended to have more infectious complications, but women had lower survival in the face of infection. Logistic regression did not identify gender as an independent predictor of mortality. Although there was a survival advantage for women in subgroup analysis, there was no overall difference in mortality. Women with pneumonia, however, had a higher mortality than men. Further understanding of potential mechanisms is necessary before hormonal manipulation studies.

Identification of Early Predictors for Post-Traumatic Pneumonia

We demonstrated that the standard clinical criteria of fever, leukocytosis, purulent sputum, and infiltrate on chest radiograph are nonspecific for the diagnosis of post-traumatic pneumonia, and only approximately 50 per cent of patients with these conditions have pneumonia. Quantitative cultures of bronchoalveolar lavage effluent will differentiate pneumonia (requiring antibiotic therapy) from systemic inflammatory response syndrome (not requiring antibiotics). Early identification of patients at risk for pneumonia can target populations for clinical research. Because risk factors for pneumonia when diagnosed by quantitative cultures have not been defined we reviewed our recent experience to identify variables predictive of pneumonia. Patients over a 22-month period who survived > 48 hours were identified from the trauma registry. Pneumonia was defined as growth of > or = 10(5) organisms per milliliter in the bronchoalveolar lavage effluent. Risk factors evaluated included injury severity and severity of shock. There were 7503 patients (75% with blunt and 25% with penetrating injuries). The incidence of pneumonia was 6 per cent (7% of patients with blunt and 2% of patients with penetrating injuries). Logistic regression analysis identified age; Glasgow Coma Scale score; Injury Severity Score; transfusion requirements during resuscitation; spinal cord injury; chest injury severity; and emergent femur fixation, craniotomy, and laparotomy as being independent predictors of pneumonia. We conclude that multiple risk factors, which are all able to be determined early after injury, are predictive of post-traumatic pneumonia. Prompt identification of this high-risk group of patients allows prognostic considerations relative to patient management schemes and targets populations for prophylactic measures or immunomodulation.

Postoperative Pneumonia

Despite the advances made in surgical critical care, the diagnosis of one of the most common infections seen in critically ill patients remains a challenge. Ventilator-associated pneumonia is associated with a 20 to 25 per cent mortality rate. There are numerous risk factors for ventilator-associated pneumonia, including underlying disease, prolonged mechanical ventilation, direct lung injury, and shock. The standard clinical criteria for pneumonia are inaccurate. Quantitative cultures of bronchoalveolar lavage effluent are accurate for the diagnosis, and it is safe to base antibiotic therapy on the results of the quantitative cultures.

Early and late acute respiratory distress syndrome: two distinct clinical entities.

Despite numerous advances in surgical critical care and ventilatory management, mortality rates for acute respiratory distress syndrome (ARDS) have remained relatively constant. Pressure-limited and non-pressure-limited ventilatory techniques have been advocated with disparate results. We hypothesized that there are two forms of ARDS, which may account for the conflicting clinical reports. Patients with posttraumatic ARDS were identified and reviewed. ARDS was defined as PaO2/FiO2 ratio less than 200 with diffuse bilateral infiltrates on chest radiograph and no congestive heart failure. Patients were analyzed relative to injury mechanism, transfusions, fluid balance, presence of pneumonia (defined as > or =10(5) colony-forming units/mL in bronchoalveolar lavage effluent), and outcome. All were managed with a non-pressure-limited strategy. During a 5.5-year period, 178 patients with posttraumatic ARDS were identified. Mean Injury Severity Score and age were 29 and 40 years, respectively. Patients were stratified by time of ARDS diagnosis. Eighty-two patients (46%) had early ARDS (within 48 hours after admission), and 96 patients (54%) had late ARDS (>48 hours between admission and diagnosis). There were no differences in Injury Severity Score, but the late group was significantly older. The early ARDS group was characterized by profound hemorrhagic shock and had significant differences from the late group in incidence of penetrating injury (30 vs. 10%; p<0.001), admission base deficit (-7.7 vs. -4.2 mEq/L; p<0.001), 48-hour transfusions (19.7 vs. 9.4; p<0.0001), initial 5-day fluid balance (19.9 vs. 10.1 L; p<0.0001), and initial PaO2/FiO2 (121 vs. 141; p<0.007). Pneumonia before ARDS was significantly associated with late ARDS (38 vs. 9%; p<0.001). ARDS-related mortality was primarily caused by hemorrhagic shock in the early group and progressive multiple organ failure in the late group. There are two distinct forms of posttraumatic ARDS. Early ARDS is characterized by hemorrhagic shock with capillary leak. Late ARDS frequently follows pneumonia and is associated with multiple system injury. Further studies should differentiate between these two distinct syndromes.

Utility of Gram's stain and efficacy of quantitative cultures for posttraumatic pneumonia: a prospective study.

This prospective trial examined the efficacy of using bronchoalveolar lavage (BAL) for the diagnosis of pneumonia (PN) and the utility of Gram's stain (GS) for dictating empiric therapy. Posttraumatic nosocomial PN remains a significant cause of morbidity and mortality. However, its diagnosis is elusive, especially in multiply injured patients. The systemic inflammatory response syndrome of fever, leukocytosis, and a hyperdynamic state is common in trauma patients, especially patients with pulmonary contusion. Bronchoscopy with BAL with quantitative cultures of the lavage effluent may distinguish between PN and systemic inflammatory response syndrome, and GS of the lavage effluent may guide empiric therapy before quantitative culture results. Mechanically ventilated trauma patients with a clinical diagnosis of PN (fever, leukocytosis, purulent sputum, and new or changing infiltrate on chest radiograph) underwent bronchoscopy with BAL. Effluent was sent for GS and quantitative cultures. The diagnostic threshold for PN was > or =10(5) colony-forming units (CFU)/mL, and antibiotics were continued. Antibiotics were stopped for < 10(5) CFU/mL and the diagnosis of systemic inflammatory response syndrome was made. Causative organisms for PN were compared to GS. Over a 2-year period, 232 patients underwent 443 bronchoscopies with BAL (71% men, 29% women; mean age, 41). The mean injury severity score was 30. Sixty percent of the patients had pulmonary contusion, and 59% were cigarette smokers. The overall incidence of PN was 39% and was no different regardless of the number of BALs a patient had. The false-negative rate of BAL was 7%. GS identified gram-positive organisms in 80% of patients with gram-positive PN and 40% of patients with gram-negative PN. GS identified gram-negative organisms in 52% of patients with gram-positive PN and 77% with gram-negative PN. The duration of the intensive care unit stay relative to the timing of BAL was beneficial for guiding empiric therapy. BAL in week 1 primarily identified Haemophilus influenzae and gram-positive organisms; Acinetobacter sp. and Pseudomonas sp. were more common after week 1. Bronchoscopy with BAL is an effective method to diagnose PN and avoids prolonged, unnecessary antibiotic therapy. Empiric therapy should be adjusted to the duration of the intensive care unit stay because the causative bacteria flora changes over time. GS of BAL effluent correlates poorly with quantitative cultures and is not reliable for dictating empiric therapy.

Validity of pulmonary artery catheter-derived hemodynamic information during bronchopulmonary lavage

Critical Care Systems, Chicago, IL), and urine output. For the left BPL, the position of the PAC in the fight pulmonary artery (PA) was confirmed fluoroscopically. For the right BPL, the position of the PAC in the right PA was confirmed by TEE (Two-Dimensional Orrmiplane, Hewlett-Packard, Andover, MA). After placing the patient in a slight lateral decubitus position (ie, left decubitus-left lung lavage, right decubitus-right lung lavage), the lung undergoing lavage was degassed by clamping the appropriate lumen of the endobronchial tube for 5 minutes. The nonlavaged lung was ventilated with a tidal volume of approximately 10 mL/kg, F102 of 1.0, inspiratory pressure (plateau) of 35 cmH20, and respiratory rate aimed at maintenance of end-tidal CO2 of 35 to 40 mmHg. Lavage was initiated with 0.9% saline solution warmed to 37.0°C, optimized by chest percussion, and instilled from a height approximately 30 cm above the midaxillary line. The fluid drained to a collection reservoir at ground level passively by gravity through a Y-piece in the tubing. For the left BPL, 17 L of 0.9% saline were lavaged until the lavage effluent was almost clear, whereas the right BPL required 9 liters. Mean arterial pressure (MAP) was maintained above 80 mmHg during lavage by alteration of depth of isoflurane and administration of crystalloid, as necessary. During both left and right BPL, PAC-derived hemodynamic data were recorded for three lavage cycles; namely, on completion of the lung filling and emptying. The thermodilution method was used to measure CO, which was obtained by calculation of the mean of two saline (room temperature)