Background Severe acute pancreatitis (SAP) is a systemic inflammatory disease, and it can often complicate into acute kidney injury (AKI) and acute lung injury/acute respiratory distress syndrome (ALI/ARDS). This study aimed to evaluate the clinical effectiveness of blood purification using a polymethylmethacrylate (PMMA) hemofilter.
Methods We retrospectively examined 54 patients, who were diagnosed with SAP according to the Japanese criteria from January 2011 to December 2019.
Results Of a total of 54 SAP patients, 26 patients progressively developed AKI and required continuous hemodialysis with a PMMA membrane hemofilter (PMMA-CHD). Acute Physiology and Chronic Health Evaluation (APACHE) II score and Sequential Organ Failure Assessment (SOFA) score were significantly higher in patients requiring PMMA-CHD than in patients not requiring hemodialysis. The lung injury scores were also significantly higher in patients requiring PMMA-CHD. Of the 26 patients, 16 patients developed ALI/ARDS and required mechanical ventilation. A total of seven patients developed severe ALI/ARDS and received additional intermittent hemodiafiltration using a PMMA hemofilter (PMMA-HDF). Although the length of intensive care unit stay was significantly longer in patients with severe ALI/ARDS, blood purification therapy was discontinued in all the patients. The survival rates at the time of discharge were 92.3% and 92.9% in patients with and without PMMA-CHD, respectively. These real mortality ratios were obviously lower than the estimated mortality ratios predicted by APACHE II scores.
Conclusions These finding suggest that the blood purification using a PMMA hemofilter would be effective for the treatment of AKI and ALI/ARDS in SAP patients.
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Background Overactivation of inflammatory cells, including macrophages and neutrophils, is associated with acute lung injury. BMS-470539 is a selective agonist of melanocortin 1 receptor, which triggers the inhibition of proinflammatory responses, suppressing neutrophil infiltration and protecting tissue. This study evaluated the effects of BMS-470539 on lipopolysaccharide-induced acute lung injury in a mouse model.
Methods Mice received a subcutaneous injection of saline or BMS-470539 (18.47 mg/kg) 1 hour before an intratracheal injection of saline or lipopolysaccharide (20 μg). Mice were sacrificed to analyze the severity of pulmonary edema (lung wet-to-dry weight [W/D] ratio) and inflammatory responses (level of leukocytes, polymorphonuclear neutrophils [PMNs] and tumor necrosis factor alpha [TNF-α] in bronchoalveolar lavage fluid [BALF]), and neutrophil infiltration (myeloperoxidase activity). TNF-α activation was also measured in neutrophils from bone marrow. Survival was investigated in a second-hit sepsis mouse model.
Results BMS-470539 improved sepsis-induced pulmonary edema, as demonstrated by a decreased W/D ratio (5.76%±0.83% to 3.81%±0.86%, P<0.05). The inflammatory response also improved, as shown by decreased levels of leukocytes (551±116 to 357±86×10²/mm³, P<0.05), PMNs (51.52%±16.23% to 18.41%±7.25%, P<0.01), and TNF-α (550±338 to 128±52 pg/ml, P<0.01) in the BALF. BMS-470539 also improved the inflammatory response, as shown by TNF-α levels (850±158 to 423±59 pg/ml, P<0.01) in neutrophils. BMS-470539 downregulated neutrophil infiltration in the lung (myeloperoxidase: 654±98 to 218±89 U/g, P<0.001). Lastly, BMS improved the survival rate (0% to 70%, P<0.01) in a mice multiple organ failure model.
Conclusions BMS-470539 improved lipopolysaccharide-induced acute lung injury and mortality in mice by affecting the inflammatory response.
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Background Mesenchymal stem cells (MSCs) attenuate injury in various lung injury models through paracrine effects. We hypothesized that intratracheal transplantation of allogenic MSCs could attenuate lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice, mediated by anti-inflammatory responses.
Methods Six-week-old male mice were randomized to either the control or the ALI group. ALI was induced by intratracheal LPS instillation. Four hours after LPS instillation, MSCs or phosphate-buffered saline was randomly intratracheally administered. Neutrophil count and protein concentration in bronchoalveolar lavage fluid (BALF); lung histology; levels of interleukin (IL)-1β, IL-6, tumor necrosis factor (TNF)-α, and macrophage inflammatory protein-2; and the expression of proliferation cell nuclear antigen (PCNA), caspase-3, and caspase-9 were evaluated at 48 hours after injury.
Results Treatment with MSCs attenuated lung injury in ALI mice by decreasing protein level and neutrophil recruitment into the BALF and improving the histologic change. MSCs also decreased the protein levels of proinflammatory cytokines including IL-1β, IL-6, and TNF-α, but had little effect on the protein expression of PCNA, caspase-3, and caspase-9.
Conclusions Intratracheal injection of bone marrow-derived allogenic MSCs attenuates LPSinduced ALI via immunomodulatory effects.
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Although the incidence is not high in the general surgical population, pulmonary aspiration of gastric contents can result in serious long-term morbidity and mortality. We report a case of early use of extracorporeal membrane oxygenation (ECMO) to correct severe hypoxemia refractory to conventional mechanical ventilation in a patient with massive aspiration of gastric contents immediately followed by acute lung injury during general anesthesia induction.
A 64-year-old woman diagnosed with stomach cancer was scheduled for elective diagnostic laparoscopy. Although there was no sign of gastrointestinal tract obstruction and midnight Nil per Os (NPO) was performed before the operation, pulmonary aspiration occurred during the induction of anesthesia. Despite the endotracheal intubation with mechanical ventilation, severe hypoxemia with hypercapnea persisted. Medical team agreed with applying veno-venous (VV) ECMO, and her blood gas analysis results became stable. ECMO was weaned successfully 9 days after the first aspiration event had occurred. Based on this case, early application of extracorporeal life support can have survival benefits.
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BACKGROUND Hypothermia is known to suppress inflammation in various experimental and clinical settings. We wanted to investigate how the suppressed inflammation by hypothermia is affected during rewarming. METHODS Mice were being assigned to normothermia (37degrees C) or hypothermia (32degrees C). After 30 minutes at the assigned temperature, lipopolysaccharide was administered intratracheally. The mice were then randomly grouped and subjected to 4 hours of normothermia (N), 24 hours of normothermia (NN), 4 hours of hypothermia (H), or 4 hours of hypothermia followed by normothermia for the next 20 hours (HN). In another experiment, other HN mice were treated with varying doses of anti-TNF-alpha or anti-IL-1beta antibodies (0, 6.25, 12.5, 25, and 50 microg/250 microl) immediately prior to rewarming. RESULTS The neutrophil counts of BAL fluid (x104/ml) were 23.0 +/- 13.1 in the N, 6.4 +/- 3.1 in the H (p = 0.002 vs N), 20.4 +/- 10.2 in the NN, and 49.7 +/- 21.0 in the HN (p = 0.005 vs H; p < 0.001 vs NN). Myeloperoxidase activity of the lung (unit/microg) was 6.7 +/- 2.9, 7.9 +/- 1.9, 17.8 +/- 4.0 (p < 0.001 vs N), and 12.9 +/- 5.9 (p = 0.034 vs H, p = 0.028 vs NN), respectively. Compared with control HN, total WBC and neutrophil counts of mice treated with anti-TNF-alpha antibody or anti-IL-1beta antibody prior to rewarming were lower at all tested doses. The combination of both anti-TNF-alpha or anti-IL-1beta antibodies was not increasingly reducing the neutrophilic sequestration. CONCLUSIONS Rewarming from induced hypothermia resulted in augmentation of neutrophilic sequestration of endotoxin-injured lung. Treatment with antibodies against TNF-alpha or IL-1beta prevented this rebound of neutrophilic infiltration.
Transfusion-related acute lung injury (TRALI) is the leading cause of transfusion-related mortalities. Each type of blood product is likely to cause TRALI. Patients with TRALI present with dyspnea/respiratory distress and fever. The symptoms, signs and chest radiological findings in TRALI are similar to transfusion associated circulatory overload.
Therefore, it is difficult to distinguish such from circulatory overloads. We report a case of TRALI in a 49-year-old woman after stored packed red blood cell transfusion. The patient developed hypoxemia and pulmonary edema after packed red blood cell transfusion during postoperative period. The patient completely recovered after an oxygen support for 3 days.
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Acute respiratory distress syndrome (ARDS) is a common disorder associated with significant mortality and morbidity. The American-European Consensus Conference (AECC) definition of ARDS, established in 1994, has advanced the knowledge of ARDS by allowing the acquisition of clinical and epidemiological data, which in turn have led to improvements in care for patients with ARDS. However, after 18 years of applied research, a number of issues regarding various criteria of AECC definition have emerged. For these reason, and because all disease definitions should be reviewed periodically, the European Society of Intensive Care Medicine convened an international expert panel to revise the ARDS definition from September 30 to October 2, 2011, Berlin, Germany, with endorsement from American Thoracic Society and the Society of Critical Care Medicine.
This consensus discussion, following empirical evaluation and consensus revision, addressed some of the limitations of the AECC definition by incorporating current data, physiologic concepts, and clinical trials to develop a new definition of ARDS (Berlin definition). The Berlin definition should facilitate case recognition and better match treatment options to severity in both the research trials and clinical practice.
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Transfusion-related acute lung injury (TRALI) is a significant cause of iatrogenic injuries in patients. It is also the major cause of transfusion-associated fatalities.
Pathophysiologic mechanism is an implicated donor of HLA.
Neutrophil antibodies and biologic response modifiers are accumulated in the stored blood products. Pulmonary endothelial activation of the host may be the response from these mediators. Treatment is supportive and will be subjected to other forms of ALL/ARDS. Diverting donors at high risk for alloimmunization may decrease the incidence of such cases.
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Transfusion-related acute lung injury (TRALI) is a serious complication following the transfusion of blood products.
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Severe acute lung injury (ALI), leading to respiratory failure caused by H1N1 infection, developed in a 34-year-old man during a work-up for non-small cell lung cancer.
Although he fully recovered through instant treatment with oseltamivir, mechanical ventilation was required again, 7 days later, due to subsequent diffuse alveolar hemorrhage (DAH). Finally, his condition improved and he was able to move out of the intensive care unit. However, multiple pulmonary metastatic nodules appeared over a period of one month, suggesting the aggressive nature of lung cancer.
Although he was discharged after chemotherapy, his prognosis seemed poor, considering the rapidity of growth of the lung cancer. It is important to recognize that DAH can occur after acute lung injury caused by influenza virus.
BACKGROUND Despite the fact that a randomized controlled trial did not support the use of ketoconazole for treatment of acute lung injury (ALI), there is evidence that pretreatment with ketoconazole might prevent ALI in critically ill patients. An in vitro study showed, however, that itraconazole was a more potent inhibitor of thromboxane and leukotriene formation than was ketoconazole. We investigated the effect of itraconazole pretreatment in lipopolysaccharide (LPS)-induced ALI in rats. METHODS Twenty-one pathogen free, male Sprague-Dawley rats were administered either saline or LPS (5 mg/kg of body weight) intratracheally, with or without intraperitoneal pretreatment of itraconazole (2.5 mg/kg). Six hours after saline or LPS treatment (7 h after itraconazole pretreatment), samples were obtained. RESULTS Compared with the saline group, LPS group had increased total cell count, polymorphonuclear leukocyte differential count, protein, lactate dehydrogenase (LDH) and cytokines in BAL fluid. Itraconazole pretreatment decreased polymrphonuclear leukocyte differential count, protein and LDH in BAL fluid compared with those of LPS-treated rats without itraconazole pretreatment. Itraconazole pretreatment also decreased the elevated BAL fluid levels of interleukin-1beta (IL-1beta) and cytokine-induced neutrophil chemoattractant (CINC) by LPS. There was, however, no difference in the BAL fluid tumor necrosis factor alpha (TNF-alpha) level in terms of itraconazole pretreatment in LPS-treated rats. Histopathologic features of LPS-induced ALI were attenuated by itraconazole pretreatment. CONCLUSIONS These results suggest that itraconazole pretreatment attenuated LPS-induced ALI in rats. Decreases in levels of IL-1beta and CINC would likely be associated with attenuation of LPS-induced ALI in rats by itraconazole pretreatment.
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BACKGROUND Nutrition delivery is frequently interrupted or delayed by physicians' ordering patterns. We conducted this study to investigate the effect of physician compliance with tube feeding (TF) protocol on the nutritional and clinical outcomes in acute lung injury (ALI) patients. METHODS After implementing a TF protocol, 71 ALI patients with mechanical ventilation (MV) for > or = 7 days were observed. A dietician assessed the nutritional status of the patients and established individualized nutrition plans according to the protocol. If the physicians followed the dietician's recommendation within 48 hours, the patients were classified under the compliant group (Group 1). RESULTS Forty patients (56.3%) were classified into Group 1. Prealbumin was comparable in both groups at ICU admission but higher in Group 1 at the time of discharge from the ICU (228 +/- 81 vs 157 +/- 77 mg/dl, p = 0.025). Nitrogen balance was only improved in Group 1. The time to reach calorie goal was shorter and non-feeding days were reduced in Group 1. The proportion of parenteral nutrition to nutritional support days was lower and delivered calories on the 4th and 7th day of TF were higher in Group 1 (p < 0.001). ICU mortality/stay and hospital mortality failed to show differences but hospital stay was prolonged in the noncompliant group (Group 2) (p = 0.023). Arterial oxygen tension and PaO2/FiO2 were maintained during the 1st week of ICU stay in Group 1 but were decreased in Group 2. CONCLUSIONS Physicians' compliance with the TF protocol contributed to the likelihood of nutritional improvement and a shorter hospital stay in ALI patients with prolonged MV.
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BACKGROUND Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) are the leading causes of death after lungresection. Neutrophil elastase is thought to be an important mediator in the pathogenesis of ALI. Sivelestat is a new neutrophil elastase inhibitor which may improve the outcome in patients with ALI/ARDS after lung resection. The objective of this study was to determine whether or not sivelestat can reduce mortality in patients with ALI after pulmonary resection for lung cancer. METHODS This study was a retrospective case-control study of twenty three patients who developed ALI/ARDS within seven days of lung resection for lung cancer. The control group (n = 12) received standard care, while the sivelestat group (n = 11) received a continuous infusion of sivelestat (0.2 mg/kg/hr) for seven days in addition to standard care. RESULTS There was no significant difference in the baseline characteristics between the control and sivelestat groups, except for heart rate. Six of twelve patients (50%) in the control group survived, while seven of twelve patients (64%) survived in the sivelestat group (p = 0.34). There was also no significant difference between the two groups in the progression to ARDS. In the sivelelestat group, survivors had lower APACHE II and SOFA scores than the patients in the control group. CONCLUSIONS There was no additional effect of a neutrophil elastase inhibitor in the treatment of ALI after pulmonary resection for lung cancer.
Acute lung injury (ALI) is a common, life-threatening cause of acute respiratory failure, which is ultimately caused by a variety of local and systemic insults. Alterations in the coagulation and fibrinolysis profiles are present in almost all the patients suffering with ALI. The classic histologic findings in ALI patients include alveolar fibrin formation and microthrombi in the pulmonary vasculature. Decreased circulating levels of protein C and increased concentrations of thrombomodulin are present in patients with septic and nonseptic ALI. The circulating and pulmonary concentrations of plasminogen activator inhibitor-1 (PAI-1) are increased in the setting of ALI, and the degree of elevation in the PAI-1 level directly correlates with mortality. The need for new specific therapies has led a number of investigators to examine the role of altered coagulation and fibrinolysis in the pathogenesis of ALI. This review summarizes the current understanding of coagulation and fibrinolysis in ALI with an emphasis on the pathways that could be potential therapeutic targets, including the tissue factor pathway, the protein C pathway and the modulation of fibrinolysis via plasminogen activator inhibitor-1.