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1.
Chin J Traumatol ; 26(2): 116-120, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36357273

ABSTRACT

PURPOSE: Patients with multiple traumas are at high risk of developing respiratory complications, including pneumonia and acute respiratory distress syndrome. Many pulmonary complications are associated with systemic inflammation and pulmonary neutrophilic infiltration. Leukotriene-receptor antagonists are anti-inflammatory and anti-oxidant drugs subsiding airway inflammation. The present study investigates the effectiveness of montelukast in reducing pulmonary complications among trauma patients. METHODS: This randomized, double-blind, placebo-control trial was conducted in patients with multiple blunt traumas and evidence of lung contusion detected via CT scan. We excluded patients if they met at least one of the following conditions: < 16 years old, history of cardiopulmonary diseases or positive history of montelukast-induced hypersensitivity reactions. Patients were allocated to the treatment (10 mg of montelukast) or placebo group using permuted block randomization method. The primary measured outcome was the volume of pulmonary contusion at the end of the trial. The secondary outcomes were intensive care unit and hospital length of stay, ventilation days, multi-organ failure, and the in-hospital mortality rate. RESULTS: In total, 65 eligible patients (treatment = 31, placebo = 34) were included for the final analysis. The treatment group had more pulmonary contusion volume (mean (SD), mm3) at the right (68726.97 (93656.54) vs. 59730.27 (76551.74)) and the left side (67501.71 (91514.04) vs. 46502.21 (80604.21)), higher initial C-reactive peptide level (12.16 (10.58) vs. 10.85 (17.87)) compared to the placebo group, but the differences were not statistically significant (p > 0.05). At the end of the study, the mean (SD) of pulmonary contusion volume (mm3) (right side = 116748.74 (361705.12), left side = 64522.03 (117266.17)) of the treatment group were comparable to that of the placebo group (right side = 40051.26 (64081.56), left side = 25929.12 (47417.13), p = 0.228 and 0.082, respectively). Moreover, both groups have statistically similar hospital (mean (SD), days) (10.87 (9.83) vs. 13.05 (10.12)) and intensive care unit length of stays (mean (SD), days) (7.16 (8.15) vs. 7.82 (7.48)). Of note, the frequency of the in-hospital complications (treatment vs. control group) including acute respiratory distress syndrome (12.9% vs. 8.8%, p = 0.71), pneumonia (19.4% vs. 17.6%, p = 0.85), multi-organ failure (12.9% vs. 17.6%, p = 0.58) and the mortality rate (22.6% vs. 14.7%, p = 0.41) were comparable between the groups. CONCLUSION: Administrating montelukast has no preventive or therapeutic effects on lung contusion or its complications.


Subject(s)
Contusions , Lung Injury , Pneumonia , Respiratory Distress Syndrome , Thoracic Injuries , Thoracic Wall , Wounds, Nonpenetrating , Humans , Adolescent , Thoracic Injuries/complications , Thoracic Injuries/drug therapy , Respiratory Distress Syndrome/drug therapy , Respiratory Distress Syndrome/etiology , Inflammation , Tablets , Treatment Outcome
2.
Chinese Journal of Traumatology ; (6): 116-120, 2023.
Article in English | WPRIM (Western Pacific) | ID: wpr-970977

ABSTRACT

PURPOSE@#Patients with multiple traumas are at high risk of developing respiratory complications, including pneumonia and acute respiratory distress syndrome. Many pulmonary complications are associated with systemic inflammation and pulmonary neutrophilic infiltration. Leukotriene-receptor antagonists are anti-inflammatory and anti-oxidant drugs subsiding airway inflammation. The present study investigates the effectiveness of montelukast in reducing pulmonary complications among trauma patients.@*METHODS@#This randomized, double-blind, placebo-control trial was conducted in patients with multiple blunt traumas and evidence of lung contusion detected via CT scan. We excluded patients if they met at least one of the following conditions: < 16 years old, history of cardiopulmonary diseases or positive history of montelukast-induced hypersensitivity reactions. Patients were allocated to the treatment (10 mg of montelukast) or placebo group using permuted block randomization method. The primary measured outcome was the volume of pulmonary contusion at the end of the trial. The secondary outcomes were intensive care unit and hospital length of stay, ventilation days, multi-organ failure, and the in-hospital mortality rate.@*RESULTS@#In total, 65 eligible patients (treatment = 31, placebo = 34) were included for the final analysis. The treatment group had more pulmonary contusion volume (mean (SD), mm3) at the right (68726.97 (93656.54) vs. 59730.27 (76551.74)) and the left side (67501.71 (91514.04) vs. 46502.21 (80604.21)), higher initial C-reactive peptide level (12.16 (10.58) vs. 10.85 (17.87)) compared to the placebo group, but the differences were not statistically significant (p > 0.05). At the end of the study, the mean (SD) of pulmonary contusion volume (mm3) (right side = 116748.74 (361705.12), left side = 64522.03 (117266.17)) of the treatment group were comparable to that of the placebo group (right side = 40051.26 (64081.56), left side = 25929.12 (47417.13), p = 0.228 and 0.082, respectively). Moreover, both groups have statistically similar hospital (mean (SD), days) (10.87 (9.83) vs. 13.05 (10.12)) and intensive care unit length of stays (mean (SD), days) (7.16 (8.15) vs. 7.82 (7.48)). Of note, the frequency of the in-hospital complications (treatment vs. control group) including acute respiratory distress syndrome (12.9% vs. 8.8%, p = 0.71), pneumonia (19.4% vs. 17.6%, p = 0.85), multi-organ failure (12.9% vs. 17.6%, p = 0.58) and the mortality rate (22.6% vs. 14.7%, p = 0.41) were comparable between the groups.@*CONCLUSION@#Administrating montelukast has no preventive or therapeutic effects on lung contusion or its complications.


Subject(s)
Humans , Adolescent , Thoracic Wall , Pneumonia , Wounds, Nonpenetrating , Thoracic Injuries/drug therapy , Lung Injury , Contusions , Respiratory Distress Syndrome, Newborn/etiology , Inflammation , Tablets , Treatment Outcome
3.
Drug Des Devel Ther ; 14: 2937-2943, 2020.
Article in English | MEDLINE | ID: mdl-32801635

ABSTRACT

BACKGROUND: The objective of this research was to evaluate the oxidative and histopathological effects of dexmedetomidine and ketamine on the pulmonary contusion model resulting from blunt chest trauma. METHODS: Rats were randomly assigned to 5 equal groups (n=6): control group (Group C), pulmonary contusion group (Group PC), PC-dexmedetomidine group (Group PC-D), PC-ketamine group (Group PC-K), and PC-dexmedetomidine + ketamine (Group PC-D+K). The PC was performed by dropping a weight of 500 g (2.45 Joules) from a height of 50 cm. In Group PC-D, after chest trauma, dexmedetomidine (100 µg/kg) was administered intraperitoneally. In Group PC-K, after chest trauma, ketamine (100 mg/kg) was administered intraperitoneally. In Group PC-D+K, dexmedetomidine and ketamine were administered together. At the end of the 6th hour, rats were sacrificed. Malondialdehyde (MDA) level, superoxide dismutase (SOD) enzyme activities, neutrophil infiltration/aggregation, and thickness of the alveolar wall were evaluated. RESULTS: MDA levels were significantly higher in Group PC than Groups C, PC-D, and PC-D+K. SOD enzyme activity was significantly higher in Group PC than Groups C, PC-D, and PC-D+K. In addition, neutrophil infiltration/aggregation and total pulmonary injury scores were significantly higher in Group PC than in other groups, and the thickness of the alveolar wall was significantly higher in Group PC compared to Groups C, PC-D, and PC-D+K. MDA level, SOD enzyme activities, neutrophil infiltration/aggregation, and thickness of alveolar wall were similar in PC-D and PC-D+K groups. CONCLUSION: Dexmedetomidine and dexmedetomidine+ketamine have protective effects on blunt chest trauma but no protective effect was observed when ketamine was administered alone. We concluded that the administration of dexmedetomidine and ketamine after contusion is beneficial against pulmonary injury in rats.


Subject(s)
Dexmedetomidine/pharmacology , Ketamine/pharmacology , Protective Agents/pharmacology , Thoracic Injuries/drug therapy , Wounds, Nonpenetrating/drug therapy , Animals , Disease Models, Animal , Male , Oxidative Stress/drug effects , Rats , Rats, Wistar , Thoracic Injuries/pathology , Wounds, Nonpenetrating/pathology
4.
Mol Med Rep ; 22(3): 2507-2515, 2020 09.
Article in English | MEDLINE | ID: mdl-32705267

ABSTRACT

Blunt chest trauma with hemorrhagic shock frequently induces pulmonary inflammation that leads to acute lung injury (ALI). The present study aimed to explore the protective effects of dexmedetomidine (Dex) in blunt chest trauma and hemorrhagic shock­resuscitation (THSR)­induced ALI by mediating nucleotide binding and oligomerization domain­like receptor family pyrin domain­containing protein 3 (NLRP3) inflammasome formation in rats. An ALI model in rats induced by THSR was constructed and Dex was administered intraperitoneally (5 µg/kg/h) immediately after blunt chest trauma. Blood samples were collected for the determination of proinflammatory factor levels, and lung tissue specimens were harvested for wet/dry (W/D) weight ratio, hematoxylin and eosin staining, and transmission electron microscopy analyses. Additionally, malondialdehyde (MDA), superoxide dismutase (SOD), lactate dehydrogenase (LDH) and myeloperoxidase (MPO) activity were evaluated, and the expression of protein in lung tissues was examined via western blot analysis. Compared with the sham group, pathological alterations in the ALI group and the W/D ratios were significantly increased. MDA, LDH and MPO activity, and the levels of interleukin (IL)­1ß, IL­18, IL­6 and tumor necrosis factor­α were significantly elevated. NLRP3, apoptosis­associated speck­like protein containing a caspase recruitment domain and caspase­1 expression was significantly increased. Conversely, Dex treatment significantly reversed these changes. The present study demonstrated that by reducing inflammatory responses, Dex exerted protective effects against THSR­ALI in rats, potentially via the inhibition of NLRP3 signaling pathways.


Subject(s)
Acute Lung Injury/prevention & control , Dexmedetomidine/administration & dosage , Resuscitation/adverse effects , Shock, Hemorrhagic/therapy , Thoracic Injuries/drug therapy , Wounds, Nonpenetrating/drug therapy , Acute Lung Injury/etiology , Acute Lung Injury/metabolism , Animals , Cytokines/metabolism , Dexmedetomidine/pharmacology , Disease Models, Animal , Gene Expression Regulation/drug effects , Injections, Intraperitoneal , L-Lactate Dehydrogenase/metabolism , Male , Malondialdehyde/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Peroxidase/metabolism , Rats , Shock, Hemorrhagic/etiology , Shock, Hemorrhagic/metabolism , Signal Transduction , Superoxide Dismutase , Thoracic Injuries/complications , Thoracic Injuries/metabolism , Wounds, Nonpenetrating/complications , Wounds, Nonpenetrating/metabolism
5.
Biotech Histochem ; 94(6): 442-448, 2019 Aug.
Article in English | MEDLINE | ID: mdl-30929510

ABSTRACT

We investigated the effects of caffeic acid phenethyl ester (CAPE) on cardiac damage after blunt chest injury. Forty male adult Wistar albino rats were divided into four groups; control, cardiac contusion, cardiac contusion + CAPE, and CAPE. CAPE, 10 mmol/kg, was administered intraperitoneally for 7 days following cardiac contusion. Heart tissue and blood were obtained at the end of the experimental period. Cardiac histopathology was determined using hematoxylin & eosin (H & E) staining. Expression of tumor necrosis factor-alpha (TNF-α) in cardiomyocytes was determined using immunohistochemistry. Cardiac apoptosis was determined using the TUNEL method. Serum creatine kinase (CK), creatine kinase-muscle/brain (CK-MB) and lactate dehydrogenase (LDH) levels were determined using spectrophotometric methods. The serum cardiac troponin I (C-TI) level was measured using the ELISA method. Myofibril loss was detected in the cardiomyocytes of the cardiac contusion group. Increased apoptosis and TNF-α expression were observed in the cardiac contusion group compared to the control group. Increased CK, CK-MB, LDH and C-TI levels were found in the cardiac contusion group. We found that CAPE administration improved myocardial function. Compared to the cardiac contusion group, CK, CK-MB, LDH and C-TI levels decreased significantly in the cardiac contusion + CAPE group. Administration of CAPE significantly inhibited apoptosis and cardiac TNF-α expression. Our findings demonstrate the therapeutic effects of CAPE for cardiac contusion damage after blunt chest trauma.


Subject(s)
Caffeic Acids/pharmacology , Myocardial Contusions/drug therapy , Myocardium/metabolism , Phenylethyl Alcohol/analogs & derivatives , Wounds, Nonpenetrating/drug therapy , Animals , Antioxidants/pharmacology , Apoptosis/drug effects , Heart/drug effects , Male , Phenylethyl Alcohol/pharmacology , Rats, Wistar , Thoracic Injuries/drug therapy
6.
Shock ; 52(2): 230-239, 2019 08.
Article in English | MEDLINE | ID: mdl-29927788

ABSTRACT

Hemorrhagic shock (HS) accounts for 30% to 40% of trauma-induced mortality, which is due to multi-organ-failure subsequent to systemic hyper-inflammation, triggered by hypoxemia and tissue ischemia. The slow-releasing, mitochondria-targeted H2S donor AP39 exerted beneficial effects in several models of ischemia-reperfusion injury and acute inflammation. Therefore, we tested the effects of AP39-treatment in a murine model of combined blunt chest trauma (TxT) and HS with subsequent resuscitation. METHODS: After blast wave-induced TxT or sham procedure, anesthetized and instrumented mice underwent 1 h of hemorrhage followed by 4 h of resuscitation comprising an i.v. bolus injection of 100 or 10 nmol kg AP39 or vehicle, retransfusion of shed blood, fluid resuscitation, and norepinephrine. Lung mechanics and gas exchange were assessed together with hemodynamics, metabolism, and acid-base status. Blood and tissue samples were analyzed for cytokine and chemokine levels, western blot, immunohistochemistry, mitochondrial oxygen consumption (JO2), and histological changes. RESULTS: High dose AP39 attenuated systemic inflammation and reduced the expression of inducible nitric oxide synthase (iNOS) and IκBα expression in lung tissue. In the combined trauma group (TxT + HS), animals treated with high dose AP39 presented with the lowest mean arterial pressure and thus highest norepinephrine requirements and higher mortality. Low dose AP39 had no effects on hemodynamics, leading to unchanged norepinephrine requirements and mortality rates. CONCLUSION: AP39 is a systemic anti-inflammatory agent. In our model of trauma with HS, there may be a narrow dosing and timing window due to its potent vasodilatory properties, which might result in or contribute to aggravation of circulatory shock-related hypotension.


Subject(s)
Mitochondria/metabolism , Organophosphorus Compounds/therapeutic use , Shock, Hemorrhagic/drug therapy , Shock, Hemorrhagic/metabolism , Thiones/therapeutic use , Thoracic Injuries/drug therapy , Thoracic Injuries/metabolism , Wounds and Injuries/drug therapy , Wounds and Injuries/metabolism , Animals , Body Temperature , Chemokines/metabolism , Cytokines/metabolism , Disease Models, Animal , Hemodynamics/drug effects , Immunoblotting , Immunohistochemistry , Male , Mice , Mice, Inbred C57BL , Wounds, Nonpenetrating/drug therapy , Wounds, Nonpenetrating/metabolism
7.
Inflammation ; 42(2): 690-701, 2019 Apr.
Article in English | MEDLINE | ID: mdl-30411212

ABSTRACT

Blunt chest (thoracic) trauma (TxT) and hemorrhagic shock (HS)-induced local and systemic inflammation with increased neutrophil activity often result in an impaired organ function. Next to increasing the trauma risk, binge drinking causes anti-inflammatory effects due to immunomodulatory properties of alcohol (ethanol, EtOH). The impact of clinically relevant acute binge drinking scenario on local and systemic inflammatory changes, notably regarding the activity and longevity of leukocytes, has been analyzed in a combinatory trauma model of TxT + H/R. Twenty-four female Lewis rats (190-240 g) received alcohol (5 g/kg, 30%) or saline gavage. Two hours after alcohol gavage, TxT with subsequent HS (60 min) and resuscitation (TxT + H/R) were induced. Sham-operated animals underwent surgical procedures. Bronchoalveolar lavage fluid (BAL), lung tissue, and blood were harvested 2 h after resuscitation. Pulmonary infiltration with PMN, IL-6 gene expression, systemic PMN activation, neutrophil and monocyte apoptosis (caspase-3/7), and pyroptosis/inflammasome activation (caspase-1) were evaluated. Lung damage was evaluated by hematoxylin-eosin (H/E) staining and determination of the total protein content in BAL (ANOVA, p < 0.05 was significant). TxT + H/R-induced increases in IL-6, PMN infiltration and BAL-protein concentration were significantly reduced by EtOH; however, histological morphology changes after trauma remained unaltered by EtOH. TxT + H/R-induced systemic leukocyte activation (increased CD11b and CD31, reduced CD62L expression) as well as inflammasome activation in monocytes were significantly diminished by EtOH. Apoptosis was prolonged only in PMN after TxT + H/R and was further prolonged by EtOH, an effect that was observed in sham animals as a trend as well. Acute EtOH exposure inhibits the activation of circulating leukocytes after trauma compared to controls. These EtOH-driven systemic changes may be associated with reduced infiltration with PMN after trauma as well as reduced local tissue inflammation.


Subject(s)
Binge Drinking , Ethanol/pharmacology , Lymphocyte Activation/drug effects , Neutrophil Infiltration/drug effects , Shock, Hemorrhagic/drug therapy , Thoracic Injuries/drug therapy , Animals , Apoptosis/drug effects , Disease Models, Animal , Ethanol/therapeutic use , Female , Inflammation/drug therapy , Leukocytes/drug effects , Lung/pathology , Rats , Rats, Inbred Lew , Thoracic Injuries/pathology , Wounds, Nonpenetrating
8.
Unfallchirurg ; 121(8): 634-641, 2018 Aug.
Article in German | MEDLINE | ID: mdl-29907900

ABSTRACT

The management of anesthesia plays a central role in the treatment of thoracic trauma, both in the initial phase when safeguarding the difficult airway and in the intensive care unit. A rapid transfer to a trauma center should be considered in order to recognize and treat organ dysfunction in time. Development of atelectasis, pneumonia and acute lung failure are common pulmonary complications. Non-invasive ventilation combined with physiotherapy and respiratory training can help to minimize these pulmonary complications. If single lung ventilation is necessary as part of the operative patient care, a double-lumen tube, a bronchial blocker and the Univent®-Tubus (Fuji Systems Corporation, Tokyo, Japan) can be used. Special attention should be paid to the hypoxic pulmonary vasoconstriction that occurs in this maneuver. Pain therapy is ideally carried out patient-adapted with epidural anesthesia. In addition, intraoperatively inserted catheters in the sense of a continuous intercostal block or serratus plane block are good alternatives. The aim of these therapies should be early mobilization and transfer of the patient to rehabilitation.


Subject(s)
Anesthesia , Pain Management , Thoracic Injuries , Analgesics/therapeutic use , Humans , Respiration, Artificial , Thoracic Injuries/drug therapy , Thoracic Injuries/surgery
9.
Immunobiology ; 223(3): 310-318, 2018 03.
Article in English | MEDLINE | ID: mdl-29102048

ABSTRACT

OBJECTIVE: After blunt thoracic trauma (TxT) and hemorrhagic shock with resuscitation (H/R) intense local inflammatory response and cell loss frequently impair the pulmonary function. Ethyl pyruvate (EP) has been reported to improve the pathophysiologic derangements in models of acute inflammation. Here, we studied the effects of EP on inflammation and lung damage after TxT+H/R. METHODS: Twenty four female Lewis rats (180-240g) were randomly divided into 3 groups: two groups underwent TxT followed by hemorrhagic shock (35±3mmHg) for 60min and resuscitation with either Ringers-Lactat (RL) alone or RL supplemented with EP (EP, 50mg/kg). Sham operated animals underwent surgical procedures. Two hours later bronchoalveolar lavage fluid (BAL), lung tissue and blood were collected for analyses. RESULTS: EP significantly improved pO2 levels compared to RL after TxT+H/R. TxT+H/R induced elevated levels of lactate dehydrogenase, total protein concentration in BAL and lung damage as evidenced by lung histology; these effects were significantly reduced by EP. Local inflammatory markers, lung TNF-alpha protein levels and infiltration with polymorphonuclear leukocytes (PMNL) significantly decreased in EP vs. RL group after TxT+H/R. Indicators of apoptosis as reduced BCL-2 and increased FAS gene expression after TxT+H/R were significantly increased or decreased, respectively, by EP after TxT+H/R. EP reduced TxT+H/R-induced p65 phosphorylation, which was concomitant with reduced HMGB1 levels in lung sections. CONCLUSIONS: Taken together, TxT+H/R induced strong inflammatory response and apoptotic changes as well as lung injury which were markedly diminished by EP. Our results suggest that this might be mediated via NF-κB and/or HMGB1 dependent mechanism.


Subject(s)
Acute Lung Injury/drug therapy , Anti-Inflammatory Agents/therapeutic use , Lung/drug effects , Pyruvates/therapeutic use , Shock, Hemorrhagic/diet therapy , Thoracic Injuries/drug therapy , Animals , Disease Models, Animal , Gene Expression Regulation , HMGB1 Protein/metabolism , Humans , Lung/physiology , NF-kappa B/metabolism , Proto-Oncogene Proteins c-bcl-2/genetics , Proto-Oncogene Proteins c-bcl-2/metabolism , Rats , Rats, Inbred Lew , Signal Transduction/drug effects , Tumor Necrosis Factor-alpha/metabolism
10.
Arch Toxicol ; 92(1): 323-336, 2018 Jan.
Article in English | MEDLINE | ID: mdl-28924833

ABSTRACT

Bacterial protein toxins became valuable molecular tools for the targeted modulation of cell functions in experimental pharmacology and attractive therapeutics because of their potent and specific mode of action in human cells. C2IN-C3lim, a recombinant fusion toxin (~50 kDa) of the Rho-inhibiting C3lim from Clostridium (C.) limosum and a non-toxic portion of the C. botulinum C2 toxin (C2IN), is selectively internalized into the cytosol of monocytic cells where C3lim specifically ADP-ribosylates Rho A and -B, thereby inhibiting Rho-mediated signaling. Thus, we hypothesized that these unique features make C2IN-C3lim an attractive molecule for the targeted pharmacological down-regulation of Rho-mediated functions in monocytes. The analysis of the actin structure and the Rho ADP-ribosylation status implied that C2IN-C3lim entered the cytosol of primary human monocytes from healthy donors ex vivo within 1 h. Moreover, it inhibited the fMLP-induced chemotaxis of human monocytes in a Boyden chamber model ex vivo. Similarly, in a 3-dimensional ex vivo model of extravasation, single cell analysis revealed that C2IN-C3lim-treated cells were not able to move. In a clinically relevant mouse model of blunt chest trauma, the local application of C2IN-C3lim into the lungs after thorax trauma prevented the trauma-induced recruitment of monocytes into the lungs in vivo. Thus, C2IN-C3lim might be an attractive lead compound for novel pharmacological strategies to avoid the cellular damage response caused by monocytes in damaged tissue after trauma and during systemic inflammation. The results suggest that the pathophysiological role of clostridial C3 toxins might be a down-modulation of the innate immune system.


Subject(s)
ADP Ribose Transferases/genetics , Botulinum Toxins/genetics , Chemotaxis/drug effects , Monocytes/drug effects , Recombinant Fusion Proteins/pharmacology , rho GTP-Binding Proteins/antagonists & inhibitors , Animals , Cell Movement/drug effects , Cells, Cultured , Disease Models, Animal , Humans , Lung/drug effects , Lung/pathology , Macrophages/drug effects , Male , Mice, Inbred C57BL , Monocytes/cytology , Recombinant Fusion Proteins/genetics , Thoracic Injuries/drug therapy , Wounds, Nonpenetrating/drug therapy , rho GTP-Binding Proteins/metabolism
11.
Ulus Travma Acil Cerrahi Derg ; 23(5): 368-376, 2017 Sep.
Article in English | MEDLINE | ID: mdl-29052821

ABSTRACT

BACKGROUND: Blunt thoracic injury often leads to pulmonary contusion and the development of acute respiratory distress syndrome, which carries a high risk of morbidity and mortality, originating from the local and systemic inflammatory states. This study aimed to investigate the local and systemic antiinflammatory effects of levosimendan in rat models of blunt chest trauma. METHODS: A total of 32 Wistar albino rats were randomly assigned to one of the following four groups: control, sham, low-dose levosimendan (LDL) (5 µg/kg loading dose for 10 min and 0.05 µg/kg/min intravenous infusion), and high-dose levosimendan (HDL) (10 µg/kg loading dose for 10 min and 0.1 µg/kg/min intravenous infusion). Blunt chest trauma was induced, and after 6 h, the contused pulmonary tissues were histopathologically and immunohistopathologically evaluated, serum TNF-α, IL-1ß, IL-6, and NO levels were biochemically evaluated. RESULTS: The mean arterial pressure was low throughout the experiment in the LDL and HDL groups, with no statistically difference between the groups. Levosimendan reduced the alveolar congestion and hemorrhage, which developed after inducing trauma. Neutrophil infiltration to the damaged pulmonary tissue was also reduced in both the LDL and HDL groups. In rats in which pulmonary contusion (PC) was observed, increased activation of nuclear factor kappa B was observed in the pulmonary tissue, and levosimendan did not reduce this activation. Both high and low doses of levosimendan reduced serum IL-1ß levels, and high doses of levosimendan reduced IL-6 and NO levels. TNF-α levels were not reduced. CONCLUSION: In conclusion, the results showed that in a rat model of PC, the experimental agent levosimendan could reduce neutrophil cell infiltration to damaged pulmonary tissues and the systemic expressions of some cytokines (IL-1ß, IL-6, and NO), thereby partially reducing and/or correcting pulmonary damage. Systemic inflammatory response that occurs after trauma could also be reduced.


Subject(s)
Anti-Inflammatory Agents/therapeutic use , Hydrazones/therapeutic use , Inflammation , Pyridazines/therapeutic use , Thoracic Injuries , Wounds, Nonpenetrating , Animals , Disease Models, Animal , Inflammation/drug therapy , Inflammation/physiopathology , Interleukin-1beta , Random Allocation , Rats , Rats, Wistar , Simendan , Thoracic Injuries/drug therapy , Thoracic Injuries/physiopathology , Wounds, Nonpenetrating/drug therapy , Wounds, Nonpenetrating/physiopathology
12.
Medicine (Baltimore) ; 95(2): e2374, 2016 Jan.
Article in English | MEDLINE | ID: mdl-26765412

ABSTRACT

Effective analgesia in the early stages after any major traumatic event remains pivotal to optimal trauma management. For patients with significant thoracic injuries, this is paramount to ensure ongoing efficient respiratory function. The aim of this study was to investigate the use of analgesic modes in the management of patients with a primary thoracic injury and blunt mechanism of injury. By understanding variables that influence the use of varying analgesic modes and influence the development of pulmonary complications, there should be more uniform evidence-based prescription in the future.This retrospective study considered analgesic use in patients admitted after blunt thoracic injuries at one major trauma center over a 2-year period. Pulmonary complications measured included both infective and ventilator-associated failure. Univariate and multivariate analyses were used to identify patient and injury severity characteristics and their association with respiratory complications.A total of 401 cases were reviewed and analyzed: 159 received Patient Controlled Analgesia (PCA), 32 received PCA and epidural analgesia (EA), 6 received EA alone, and 204 received interval-administered analgesia. There were no significant differences in the rates of complication when compared between analgesic modes. Patients who developed pneumonia had significantly increased number of thoracic fractures and underlying organ injury (P < 0.05). Logistic regression analysis highlighted duration of intercostal drain insertion (OR 1.377, P = 0.001) and premorbid cardiac disease (OR 2.624, P = 0.042) and ICU length of stay (OR: 1.146, P < 0.001) as significant predictors of developing pneumonia in this patient group.Examining the different analgesic modes, this study failed to identify a particular analgesic mode that was more effective in preventing pulmonary complications in blunt thoracic injuries. However, variables that may influence usage of different analgesic modes and high-risk groups for the development of pneumonia were identified. Further work is warranted to consider the long-term benefits of analgesia in patients post-blunt thoracic injuries.


Subject(s)
Analgesia, Epidural , Analgesia, Patient-Controlled , Lung Diseases/etiology , Thoracic Injuries/drug therapy , Wounds, Nonpenetrating/drug therapy , Adult , Aged , Female , Humans , London/epidemiology , Lung Diseases/epidemiology , Lung Diseases/prevention & control , Male , Middle Aged , Retrospective Studies , Thoracic Injuries/complications , Wounds, Nonpenetrating/complications
13.
Klin Khir ; (12): 46-8, 2016.
Article in Ukrainian | MEDLINE | ID: mdl-30272871

ABSTRACT

Results of treatment of 242 patients, to whom 697 оperative interventions were done, including 492 (70.6%) ­with restoration of the injured soft tissues and other trunk and extremities structures ­were analyzed. Choice of the correcting intervention method and closure of the covering tissues defect have depended on the wound dimensions and depth, peculiarities of hemodynamics in the area injured. Application of Lacert preparation for the traumatic injury consequences made spectrum of treatment options in patients, suffering covering tissues defect,broader. Differential approach to choice of procedure for the wound surface closure have permitted to achieve satisfactory results in 98.75% of patients.


Subject(s)
Arm Injuries/surgery , Dermatologic Surgical Procedures/methods , Leg Injuries/surgery , Soft Tissue Injuries/surgery , Thoracic Injuries/surgery , Adult , Arm Injuries/drug therapy , Arm Injuries/pathology , Female , Fractures, Bone/drug therapy , Fractures, Bone/pathology , Fractures, Bone/surgery , Hemodynamics , Humans , Hyaluronic Acid/therapeutic use , Leg Injuries/drug therapy , Leg Injuries/pathology , Male , Middle Aged , Multiple Trauma/pathology , Multiple Trauma/surgery , Precision Medicine , Retrospective Studies , Skin/drug effects , Skin/injuries , Skin Transplantation , Soft Tissue Injuries/drug therapy , Soft Tissue Injuries/pathology , Surgical Flaps , Thoracic Injuries/drug therapy , Thoracic Injuries/pathology , Trauma Severity Indices
14.
PLoS One ; 9(3): e91284, 2014.
Article in English | MEDLINE | ID: mdl-24609084

ABSTRACT

INTRODUCTION: The difficulties in the management of the blunt chest wall trauma patient in the Emergency Department due to the development of late complications are well recognised in the literature. Pre-injury anti-platelet therapy has been previously investigated as a risk factor for poor outcomes following traumatic head injury, but not in the blunt chest wall trauma patient cohort. The aim of this study was to investigate pre-injury anti-platelet therapy as a risk factor for the development of complications in the recovery phase following blunt chest wall trauma. METHODS: A retrospective study was completed in which the medical notes were analysed of all blunt chest wall trauma patients presenting to a large trauma centre in Wales in 2012 and 2013. Using univariate and multivariable logistic regression analysis, pre-injury platelet therapy was investigated as a risk factor for the development of complications following blunt chest wall trauma. Previously identified risk factors were included in the analysis to address the influence of confounding. RESULTS: A total of 1303 isolated blunt chest wall trauma patients presented to the ED in Morriston Hospital in 2012 and 2013 with complications recorded in 144 patients (11%). On multi-variable analysis, pre-injury anti-platelet therapy was found to be a significant risk factor for the development of complications following isolated blunt chest wall trauma (odds ratio: 16.9; 95% confidence intervals: 8.2-35.2). As in previous studies patient age, number of rib fractures, chronic lung disease and pre-injury anti-coagulant use were also found to be significant risk factors. CONCLUSIONS: Pre-injury anti-platelet therapy is being increasingly used as a first line treatment for a number of conditions and there is a concurrent increase in trauma in the elderly population. Pre-injury anti-platelet therapy should be considered as a risk factor for the development of complications by clinicians managing blunt chest wall trauma.


Subject(s)
Blood Platelets/pathology , Platelet Aggregation Inhibitors/therapeutic use , Thoracic Injuries/complications , Thoracic Injuries/drug therapy , Thoracic Wall/pathology , Wounds, Nonpenetrating/complications , Wounds, Nonpenetrating/drug therapy , Blood Platelets/drug effects , Demography , Female , Humans , Male , Middle Aged , Odds Ratio , Platelet Aggregation Inhibitors/pharmacology , Retrospective Studies , Risk Factors , Thoracic Wall/drug effects
15.
J Mol Histol ; 45(4): 463-71, 2014 Aug.
Article in English | MEDLINE | ID: mdl-24442604

ABSTRACT

The aim of this study was to investigate the protective effects of N-acetylcysteine (NAC) on peroxidative and apoptotic changes in the contused lungs of rats following blunt chest trauma. The rats were randomly divided into three groups: control, contusion, and contusion + NAC. All the rats, apart from those in the control group, performed moderate lung contusion. A daily intramuscular NAC injection (150 mg/kg) was given immediately following the blunt chest trauma and was continued for two additional days following cessation of the trauma. Samples of lung tissue were taken in order to evaluate the tissue malondialdehyde (MDA) level, histopathology, and epithelial cell apoptosis using terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay and active caspase-3 immunostaining. In addition, we immunohistochemically evaluated the expression of surfactant protein D (SP-D) in the lung tissue. The blunt chest trauma-induced lung contusion resulted in severe histopathological injury, as well as an increase in the MDA level and in the number of cells identified on TUNEL assay together with active caspase-3 positive epithelial cells, but a decrease in the number of SP-D positive alveolar type 2 (AT-2) cells. NAC treatment effectively attenuated histopathologic, peroxidative, and apoptotic changes, as well as reducing alterations in SP-D expression in the lung tissue. These findings indicate that the beneficial effects of NAC administrated following blunt chest trauma is related to the regulation of oxidative stress and apoptosis.


Subject(s)
Acetylcysteine/therapeutic use , Contusions/drug therapy , Epithelial Cells/cytology , Epithelial Cells/drug effects , Lung Injury/drug therapy , Oxidative Stress/drug effects , Pulmonary Alveoli/cytology , Thoracic Injuries/drug therapy , Animals , Apoptosis/drug effects , Female , Rats , Rats, Sprague-Dawley
16.
J Pak Med Assoc ; 63(1): 32-7, 2013 Jan.
Article in English | MEDLINE | ID: mdl-23865129

ABSTRACT

OBJECTIVES: To investigate the effects of aprotinin, on blood gasses, oxidant-antioxidant status, and lung histopathology in an experimental bilateral blunt chest trauma model. METHODS: Conducted at the Experimental Animal Laboratory of Meram Medical School at Selcuk University, Konya, Turkey, the study comprised 21 New Zealand female albino rabbits who were divided into three groups.Trauma was applied on the sham and aprotinin groups, which was administered intravenous Aprotinin 20.000 U/kg. Arterial blood samples were obtained from all rabbits at hours 0, 3, 24, and 96. At hour 96 after trauma, all rabbits were sacrificed using the decapitation method, and then blood and lung tissue samples were obtained. Blood nitric oxide, malondialdehyde and blood gas measurements were made. Histopathological changes in the lung were examined with a light microscope. RESULTS: While no positive effect of aprotinin was observed on nitric oxide malondialdehyde and partial pressure of carbon dioxide values, it was seen to have an increasing effect on partial oxygen pressure level. Aprotinin had a partial effect on lung histopathology. CONCLUSION: Aprotinin was determined to have a positive effect on PO2 levels. We could not find any positive effects especially on alveolar haemorrhage.


Subject(s)
Aprotinin/therapeutic use , Hemostatics/therapeutic use , Thoracic Injuries/drug therapy , Wounds, Nonpenetrating/drug therapy , Animals , Disease Models, Animal , Female , Rabbits , Thoracic Injuries/etiology , Thoracic Injuries/pathology , Wounds, Nonpenetrating/etiology , Wounds, Nonpenetrating/pathology
17.
Eur J Cardiothorac Surg ; 43(1): 163-7, 2013 Jan.
Article in English | MEDLINE | ID: mdl-22733840

ABSTRACT

OBJECTIVES: In our study, we aimed to investigate the anti-inflammatory mediator effects of budesonide (BS), an inhaled corticosteroid and interleukin-10 (IL-10) on a pulmonary contusion in an experimental rat model in which an isolated bilateral pulmonary contusion was created by blunt thoracic trauma. METHODS: Fifty-five male Sprague-Dawley rats were used in the study. Sham, control, BS and IL-10 groups were created. A pulmonary contusion was created by performing isolated blunt thoracic trauma in all groups except for the sham group. The trauma's severity was determined as 1.45 J. BS and IL-10 were administered orogastrically to the respective groups 30 min before trauma, and orogastrically and intraperitoneally, respectively, on the first and second days after the trauma. Only the blunt thoracic trauma was performed for the control group. SatO(2), PaO(2) and PaCO(2), blood glutathione, malondialdehyde (MDA) and tumour necrosis factor-α (TNFα) values were recorded on the zeroth, first, second and third days. The histopathological examination and the bronchoalveolar lavage cell count were performed on pulmonary tissues. RESULTS: Blood gas analysis revealed that SatO(2) and PaO(2) values on the first and second days were significantly lower in the control, BS and IL-10 groups compared with the sham group (P < 0.05). The SatO(2) and PaO(2) values on the third day in the BS and IL-10 groups were higher than in the control group (P < 0.05). The mean MDA in the control group was higher than in the sham, BS and IL-10 groups (P < 0.05). The mean TNFα in the control group was higher than in the sham, BS and IL-10 groups (P < 0.05). Pulmonary pathology scoring in the control group was observed to be higher than in the sham, BS and IL-10 groups (P < 0.05). CONCLUSION: In this rat experiment model in which an isolated pulmonary contusion was created by blunt trauma, BS and IL-10 were observed to reduce contusion severity in the lung and minimize the inflammatory reaction.


Subject(s)
Anti-Inflammatory Agents/pharmacology , Budesonide/pharmacology , Contusions/drug therapy , Interleukin-10/pharmacology , Thoracic Injuries/drug therapy , Wounds, Nonpenetrating/drug therapy , Analysis of Variance , Animals , Bronchoalveolar Lavage Fluid/chemistry , Carbon Dioxide/blood , Contusions/blood , Disease Models, Animal , Glutathione/blood , Histology , Lung/chemistry , Male , Malondialdehyde/blood , Oxygen/blood , Rats , Rats, Sprague-Dawley , Thoracic Injuries/blood , Tumor Necrosis Factor-alpha/blood , Wounds, Nonpenetrating/blood
18.
Emerg Med J ; 30(12): 1024-8, 2013 Dec.
Article in English | MEDLINE | ID: mdl-23221457

ABSTRACT

OBJECTIVES: To determine if complications from blunt thoracic trauma are reduced with patient-controlled analgesia (PCA) compared with interval analgesic dosing given as needed. Secondary aims were to investigate the influence of PCA on hospital length of stay (LOS) and cost. METHODS: In this retrospective cohort study, patients were identified using the hospital trauma registry and clinical information department. Data on analgesic method, outcomes and confounders were obtained from the medical record. Costing data were obtained from the case-mix department. The analysis used logistic regression for the primary outcome and a generalised linear model for the secondary outcomes to adjust for potential confounders. RESULTS: 227 patients were included. In the PCA group, 17/52 (33%) patients had a complication compared with 26/175 (15%) in the interval dosing group. The adjusted odds for a complication in patients receiving PCA was not significantly different from the adjusted odds in those receiving interval dosing (OR=1.2, 95% CI 0.3 to 4.6, p=0.83). The median LOS was 8.9 days in the PCA group and 4.6 days in the interval dosing group. The adjusted LOS for patients receiving PCA was 10% shorter than those receiving interval dosing (relative difference 0.9, 95% CI 0.6 to 1.3, p=0.52). The median hospital cost was $A11 107 in the PCA group (IQR $A7520-$A15 744) and $A4511 (IQR $A2687-$A8248) in the interval dosing group. The adjusted total hospital costs for patients receiving PCA was 10% higher than for those receiving interval dosing (relative difference 1.1, 95% CI 0.8 to 1.5, p=0.44). CONCLUSIONS: PCA did not reduce complications, hospital LOS or costs compared with interval analgesic dosing.


Subject(s)
Analgesia, Patient-Controlled , Analgesics, Opioid/administration & dosage , Pain/drug therapy , Thoracic Injuries/complications , Wounds, Nonpenetrating/complications , Adult , Aged , Analgesia, Patient-Controlled/economics , Analgesics, Opioid/economics , Emergency Service, Hospital/economics , Emergency Service, Hospital/statistics & numerical data , Female , Hospital Costs/statistics & numerical data , Humans , Length of Stay , Logistic Models , Male , Middle Aged , Pain/etiology , Retrospective Studies , Thoracic Injuries/drug therapy , Wounds, Nonpenetrating/drug therapy , Young Adult
19.
J Trauma Acute Care Surg ; 73(5 Suppl 4): S341-4, 2012 Nov.
Article in English | MEDLINE | ID: mdl-23114491

ABSTRACT

BACKGROUND: Antibiotic use in injured patients requiring tube thoracostomy (TT) to reduce the incidence of empyema and pneumonia remains a controversial practice. In 1998, the Eastern Association for the Surgery of Trauma (EAST) developed and published practice management guidelines for the use of presumptive antibiotics in TT for patients who sustained a traumatic hemopneumothorax. The Practice Management Guidelines Committee of EAST has updated the 1998 guidelines to reflect current literature and practice. METHODS: A systematic literature review was performed to include prospective and retrospective studies from 1997 to 2011, excluding those studies published in the previous guideline. Case reports, letters to the editor, and review articles were excluded. Ten acute care surgeons and one statistician/epidemiologist reviewed the articles under consideration, and the EAST primer was used to grade the evidence. RESULTS: Of the 98 articles identified, seven were selected as meeting criteria for review. Two questions regarding presumptive antibiotic use in TT for traumatic hemopneumothorax were addressed: (1) Do presumptive antibiotics reduce the incidence of empyema or pneumonia? And if true, (2) What is the optimal duration of antibiotic prophylaxis? CONCLUSION: Routine presumptive antibiotic use to reduce the incidence of empyema and pneumonia in TT for traumatic hemopneumothorax is controversial; however, there is insufficient published evidence to support any recommendation either for or against this practice.


Subject(s)
Antibiotic Prophylaxis/standards , Chest Tubes/standards , Hemopneumothorax/surgery , Thoracic Injuries/surgery , Thoracostomy/standards , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/therapeutic use , Antibiotic Prophylaxis/methods , Empyema, Pleural/prevention & control , Hemopneumothorax/drug therapy , Hemopneumothorax/etiology , Humans , Pneumonia/prevention & control , Thoracic Injuries/complications , Thoracic Injuries/drug therapy , Thoracostomy/methods
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