RESUMEN
Resuscitation induced ischemia/reperfusion predisposes trauma patients to systemic inflammation and organ dysfunction. We investigated the effect of remote ischemic conditioning (RIC), a treatment shown to prevent ischemia/reperfusion injury in experimental models of hemorrhagic shock/resuscitation, on the systemic immune-inflammatory profile in trauma patients in a randomized trial. We conducted a prospective, single-centre, double-blind, randomized, controlled trial involving trauma patients sustaining blunt or penetrating trauma in hemorrhagic shock admitted to a Level 1 trauma centre. Patients were randomized to receive RIC (four cycles of 5-min pressure cuff inflation at 250 mmHg and deflation on the thigh) or a Sham intervention. The primary outcomes were neutrophil oxidative burst activity, cellular adhesion molecule expression, and plasma levels of myeloperoxidase, cytokines and chemokines in peripheral blood samples, drawn at admission (pre-intervention), 1 h, 3 h, and 24 h post-admission. Secondary outcomes included ventilator, ICU and hospital free days, incidence of nosocomial infections, 24 h and 28 day mortality. 50 eligible patients were randomized; of which 21 in the Sham group and 18 in the RIC group were included in the full analysis. No treatment effect was observed between Sham and RIC groups for neutrophil oxidative burst activity, adhesion molecule expression, and plasma levels of myeloperoxidase and cytokines. RIC prevented significant increases in Th2 chemokines TARC/CCL17 (P < 0.01) and MDC/CCL22 (P < 0.05) at 24 h post-intervention in comparison to the Sham group. Secondary clinical outcomes were not different between groups. No adverse events in relation to the RIC intervention were observed. Administration of RIC was safe and did not adversely affect clinical outcomes. While trauma itself modified several immunoregulatory markers, RIC failed to alter expression of the majority of markers. However, RIC may influence Th2 chemokine expression in the post resuscitation period. Further investigation into the immunomodulatory effects of RIC in traumatic injuries and their impact on clinical outcomes is warranted.ClinicalTrials.gov number: NCT02071290.
Asunto(s)
Precondicionamiento Isquémico , Choque Hemorrágico , Humanos , Choque Hemorrágico/complicaciones , Peroxidasa , Precondicionamiento Isquémico/efectos adversos , Estudios Prospectivos , Isquemia/etiología , Choque Traumático , Citocinas , Resultado del TratamientoRESUMEN
BACKGROUND: The selective non-operative management of penetrating abdominal injury is gaining increasing acceptance. In Great Britain and Ireland, the management of trauma remains the responsibility of general surgeons. This study appraises the acceptance and utilisation of selective non-operative management strategies by British and Irish general surgeons, compared with trauma surgeons in the United States of America. METHODS: Electronic questionnaire survey of British and Irish consultant general surgeons and trauma surgeons in the United States of America. RESULTS: 139 British and Irish general surgeons and 75 US trauma surgeons completed the survey. 84.3% of British and Irish general surgeons and 94.4% of US trauma surgeons practise selective non-operative management of abdominal stab wounds, and 14.0% and 74.3% practise selective non-operative management of abdominal gunshot wounds. The management of those British and Irish surgeons who do practise selective non-operative management is broadly similar to that of US trauma surgeons, with the exception of the use of laparoscopy to examine the left hemidiaphragm following thoracoabdominal injuries, which is employed by fewer British and Irish general surgeons than US trauma surgeons. CONCLUSIONS: The selective non-operative management of abdominal stab wounds is generally accepted by British and Irish general surgeons. In contrast, few British and Irish surgeons are comfortable with non-operatively managing patients with abdominal gunshot wounds, reflecting both the rarity of this type of injury, and surgeons' training and experience. This proportion is unlikely to change until the management of torso trauma is recognised as a specialty, and services are concentrated in regional centres.
Asunto(s)
Traumatismos Abdominales/cirugía , Cirugía General/estadística & datos numéricos , Laparoscopía/estadística & datos numéricos , Heridas por Arma de Fuego/cirugía , Heridas Punzantes/cirugía , Traumatismos Abdominales/epidemiología , Adulto , Anciano , Femenino , Cirugía General/métodos , Encuestas Epidemiológicas , Humanos , Irlanda/epidemiología , Masculino , Persona de Mediana Edad , Guías de Práctica Clínica como Asunto , Pautas de la Práctica en Medicina , Encuestas y Cuestionarios , Reino Unido/epidemiología , Estados Unidos/epidemiología , Heridas por Arma de Fuego/epidemiología , Heridas Punzantes/epidemiologíaRESUMEN
Clinically relevant animal models capable of simulating traumatic hemorrhagic shock are needed. We developed a hemorrhagic shock model with male New Zealand rabbits (2200-2800 g, 60-70 days old) that simulates the pre-hospital and acute care of a penetrating trauma victim in an urban scenario using current resuscitation strategies. A laparotomy was performed to reproduce tissue trauma and an aortic injury was created using a standardized single puncture to the left side of the infrarenal aorta to induce hemorrhagic shock similar to a penetrating mechanism. A 15-min interval was used to simulate the arrival of pre-hospital care. Fluid resuscitation was then applied using two regimens: normotensive resuscitation to achieve baseline mean arterial blood pressure (MAP, 10 animals) and hypotensive resuscitation at 60 percent of baseline MAP (10 animals). Another 10 animals were sham operated. The total time of the experiment was 85 min, reproducing scene, transport and emergency room times. Intra-abdominal blood loss was significantly greater in animals that underwent normotensive resuscitation compared to hypotensive resuscitation (17.1 ± 2.0 vs 8.0 ± 1.5 mL/kg). Antithrombin levels decreased significantly in normotensive resuscitated animals compared to baseline (102 ± 2.0 vs 59 ± 4.1 percent), sham (95 ± 2.8 vs 59 ± 4.1 percent), and hypotensive resuscitated animals (98 ± 7.8 vs 59 ± 4.1 percent). Evidence of re-bleeding was also noted in the normotensive resuscitation group. A hypotensive resuscitation regimen resulted in decreased blood loss in a clinically relevant small animal model capable of reproducing hemorrhagic shock caused by a penetrating mechanism.
Asunto(s)
Animales , Masculino , Conejos , Fluidoterapia/métodos , Resucitación/métodos , Choque Hemorrágico/terapia , Choque Traumático/terapia , Modelos Animales de Enfermedad , Hematócrito , Choque Hemorrágico/sangre , Choque Hemorrágico/etiología , Choque Traumático/sangre , Choque Traumático/complicacionesRESUMEN
Clinically relevant animal models capable of simulating traumatic hemorrhagic shock are needed. We developed a hemorrhagic shock model with male New Zealand rabbits (2200-2800 g, 60-70 days old) that simulates the pre-hospital and acute care of a penetrating trauma victim in an urban scenario using current resuscitation strategies. A laparotomy was performed to reproduce tissue trauma and an aortic injury was created using a standardized single puncture to the left side of the infrarenal aorta to induce hemorrhagic shock similar to a penetrating mechanism. A 15-min interval was used to simulate the arrival of pre-hospital care. Fluid resuscitation was then applied using two regimens: normotensive resuscitation to achieve baseline mean arterial blood pressure (MAP, 10 animals) and hypotensive resuscitation at 60% of baseline MAP (10 animals). Another 10 animals were sham operated. The total time of the experiment was 85 min, reproducing scene, transport and emergency room times. Intra-abdominal blood loss was significantly greater in animals that underwent normotensive resuscitation compared to hypotensive resuscitation (17.1 ± 2.0 vs 8.0 ± 1.5 mL/kg). Antithrombin levels decreased significantly in normotensive resuscitated animals compared to baseline (102 ± 2.0 vs 59 ± 4.1%), sham (95 ± 2.8 vs 59 ± 4.1%), and hypotensive resuscitated animals (98 ± 7.8 vs 59 ± 4.1%). Evidence of re-bleeding was also noted in the normotensive resuscitation group. A hypotensive resuscitation regimen resulted in decreased blood loss in a clinically relevant small animal model capable of reproducing hemorrhagic shock caused by a penetrating mechanism.
Asunto(s)
Fluidoterapia/métodos , Resucitación/métodos , Choque Hemorrágico/terapia , Choque Traumático/terapia , Animales , Modelos Animales de Enfermedad , Hematócrito , Masculino , Conejos , Choque Hemorrágico/sangre , Choque Hemorrágico/etiología , Choque Traumático/sangre , Choque Traumático/complicacionesRESUMEN
INTRODUCTION: Thoracic injuries are potentially responsible for 25% of all trauma deaths. Chest X-ray is commonly used to screen patients with chest injury. However, the use of computed tomography (CT) scan for primary screening is increasing, particularly for blunt trauma. CT scans are more sensitive than chest X-ray in detecting intra-thoracic abnormalities such as pneumothoraces and pneumomediastinums. Pneumomediastinum detected by chest X-ray or "overt pneumomediastinum", raises the concern of possible aerodigestive tract injuries. In contrast, there is scarce information on the clinical significance of pneumomediastinum diagnosed by CT scan only or "occult pneumomediastinum". Therefore we investigated the clinical consequences of occult pneumomediastinum in our blunt trauma population. METHODS: A 2-year retrospective chart review of all blunt chest trauma patients with initial chest CT scan admitted to a level I trauma centre. Data extracted from the medical records include; demographics, occult, overt, or no pneumomediastinum, the presence of intra-thoracic aerodigestive tract injuries (trachea, bronchus, and/or esophagus), mechanism and severity of injury, endotracheal intubation, chest thoracostomy, operations and radiological reports by an attending radiologist. All patients with intra-thoracic aerodigestive tract injuries from 1994 to 2004 were also investigated. RESULTS: Of 897 patients who met the inclusion criteria 839 (93.5%) had no pneumomediastinum. Five patients (0.6%) had overt pneumomediastinum and 53 patients (5.9%) had occult pneumomediastinum. Patients with occult pneumomediastinum had significantly higher ISS and AIS chest (p<0.0001) than patients with no pneumomediastinum. A chest thoracostomy tube was more common (p<0.0001) in patients with occult pneumomediastinum (47.2%) than patients with no pneumomediastinum (10.4%), as well as occult pneumothorax. None of the patients with occult pneumomediastinum had aerodigestive tract injuries (95%CI 0-0.06). Follow up CT scan of patients with occult pneumomediastinum showed complete resolution in all cases, in average 3 h after the initial exam. CONCLUSION: Occult pneumomediastinum occurred in approximately 6% of all trauma patients with blunt chest injuries in our institution. Patients who had occult pneumomediastinum were more severely injured than those who without. However, none of the patients with occult pneumomediastinum had aerodigestive tract injuries and follow up chest CT scans demonstrated their complete and spontaneous resolution.
Asunto(s)
Enfisema Mediastínico/etiología , Traumatismos Torácicos/complicaciones , Heridas no Penetrantes/complicaciones , Adulto , Esófago/lesiones , Femenino , Humanos , Masculino , Enfisema Mediastínico/diagnóstico por imagen , Enfisema Mediastínico/epidemiología , Persona de Mediana Edad , Radiografía Torácica , Sistema de Registros , Estudios Retrospectivos , Traumatismos Torácicos/diagnóstico por imagen , Traumatismos Torácicos/epidemiología , Toracostomía/estadística & datos numéricos , Tomografía Computarizada por Rayos X , Tráquea/lesiones , Heridas no Penetrantes/diagnóstico por imagen , Heridas no Penetrantes/epidemiologíaRESUMEN
Thromboelastography (TEG®) provides a functional evaluation of coagulation. It has characteristics of an ideal coagulation test for trauma, but is not frequently used, partially due to lack of both standardized techniques and normal values. We determined normal values for our population, compared them to those of the manufacturer and evaluated the effect of gender, age, blood type, and ethnicity. The technique was standardized using citrated blood, kaolin and was performed on a Haemoscope 5000 device. Volunteers were interviewed and excluded if pregnant, on anticoagulants or having a bleeding disorder. The TEG® parameters analyzed were R, K, á, MA, LY30, and coagulation index. All volunteers outside the manufacturers normal range underwent extensive coagulation investigations. Reference ranges for 95 percent for 118 healthy volunteers were R: 3.8-9.8 min, K: 0.7-3.4 min, á: 47.8-77.7 degrees, MA: 49.7-72.7 mm, LY30: -2.3-5.77 percent, coagulation index: -5.1-3.6. Most values were significantly different from those of the manufacturer, which would have diagnosed coagulopathy in 10 volunteers, for whom additional investigation revealed no disease (81 percent specificity). Healthy women were significantly more hypercoagulable than men. Aging was not associated with hypercoagulability and East Asian ethnicity was not with hypocoagulability. In our population, the manufacturers normal values for citrated blood-kaolin had a specificity of 81 percent and would incorrectly identify 8.5 percent of the healthy volunteers as coagulopathic. This study supports the manufacturers recommendation that each institution should determine its own normal values before adopting TEG®, a procedure which may be impractical. Consideration should be given to a multi-institutional study to establish wide standard values for TEG®.
Asunto(s)
Adulto , Femenino , Humanos , Masculino , Coagulación Sanguínea/fisiología , Antígenos de Grupos Sanguíneos , Grupos Raciales , Valores de Referencia , TromboelastografíaRESUMEN
Thromboelastography (TEG) provides a functional evaluation of coagulation. It has characteristics of an ideal coagulation test for trauma, but is not frequently used, partially due to lack of both standardized techniques and normal values. We determined normal values for our population, compared them to those of the manufacturer and evaluated the effect of gender, age, blood type, and ethnicity. The technique was standardized using citrated blood, kaolin and was performed on a Haemoscope 5000 device. Volunteers were interviewed and excluded if pregnant, on anticoagulants or having a bleeding disorder. The TEG parameters analyzed were R, K, alpha, MA, LY30, and coagulation index. All volunteers outside the manufacturer's normal range underwent extensive coagulation investigations. Reference ranges for 95% for 118 healthy volunteers were R: 3.8-9.8 min, K: 0.7-3.4 min, alpha: 47.8-77.7 degrees, MA: 49.7-72.7 mm, LY30: -2.3-5.77%, coagulation index: -5.1-3.6. Most values were significantly different from those of the manufacturer, which would have diagnosed coagulopathy in 10 volunteers, for whom additional investigation revealed no disease (81% specificity). Healthy women were significantly more hypercoagulable than men. Aging was not associated with hypercoagulability and East Asian ethnicity was not with hypocoagulability. In our population, the manufacturer's normal values for citrated blood-kaolin had a specificity of 81% and would incorrectly identify 8.5% of the healthy volunteers as coagulopathic. This study supports the manufacturer's recommendation that each institution should determine its own normal values before adopting TEG, a procedure which may be impractical. Consideration should be given to a multi-institutional study to establish wide standard values for TEG.
Asunto(s)
Coagulación Sanguínea/fisiología , Adulto , Antígenos de Grupos Sanguíneos , Femenino , Humanos , Masculino , Grupos Raciales , Valores de Referencia , TromboelastografíaRESUMEN
The optimal fluid for resuscitation in hemorrhagic shock would combine the volume expansion and oxygen-carrying capacity of blood without the need for cross-matching or the risk of disease transmission. Although the ideal fluid has yet to be discovered, current options are discussed in this review, including crystalloids, colloids, blood and blood substitutes. The future role of blood substitutes is not yet defined, but the potential advantages in trauma or elective surgery may prove to be enormous.
Asunto(s)
Sustitutos Sanguíneos , Transfusión Sanguínea , Sustitutos del Plasma , Resucitación , Choque Hemorrágico/terapia , HumanosRESUMEN
Hepatic ischemia-reperfusion (I/R) is an important cause of organ dysfunction in the critically ill. With reperfusion, Kupffer cells release pro-inflammatory cytokines that promote endothelial cell (EC) expression of adhesion molecules such as intercellular adhesion molecule (ICAM)-1, facilitating neutrophil (PMN) infiltration. Studies suggest hypertonic saline (HTS) might exert beneficial effects on development of organ injury following shock on the basis of reduced PMN-EC interactions. We hypothesized that HTS alters expression of EC ICAM-1 and thus minimizes PMN-mediated injury. To test our hypothesis, we used an in vivo model of hepatic I/R and an in vitro model of activated EC. Rats underwent 30 min of hepatic ischemia after pretreatment with HTS (7.5% NaCl, 4cc/kg ia) or normal saline (NS). At 4 h reperfusion, plasma was taken for aspartate aminotransferase (AST) and liver tissue was harvested for assessment of hepatic ICAM-1 mRNA by Northern blot analysis. Human umbilical vein endothelial cells (HUVECs) were activated by lipopolysaccharide (LPS) and exposed to hypertonic medium (350-500 mOsM). HUVEC ICAM-1 protein was measured by cell ELISA and ICAM-1 mRNA by Northern blot analysis. HTS prevented hepatic I/R injury as measured by AST. AST of shams was 282.6+/-38.1 IU/L. I/R following NS pretreatment caused significant injury (AST 973.8+/-110.9 IU/L) compared to sham (SM) (P < 0.001). Pretreatment with HTS exerted significant protection following I/R with an AST of 450.9+/-56.3 IU/L (P < 0.05). There was no significant difference in AST levels between SM and HTS groups. Reduced hepatic injury after HTS and I/R was accompanied by inhibition of I/R-induced hepatic ICAM-1 mRNA expression compared to NS treated animals (P < 0.01). Similarly, hypertonicity inhibited HUVEC LPS-induced ICAM-1 protein (LPS: 1.86+/-0.19 absorbance units; 400 mOsM +/- LPS: 1.45+/-0.14 absorbance units; 450 mOsM + LPS: 1.02+/-0.19 absorbance units, P < 0.001) and mRNA expression. Thus, hypertonicity modulates endothelial ICAM-1 expression as one possible protective mechanism against I/R injury.
Asunto(s)
Molécula 1 de Adhesión Intercelular/efectos de los fármacos , Molécula 1 de Adhesión Intercelular/genética , Hígado/irrigación sanguínea , Hígado/metabolismo , Solución Salina Hipertónica/farmacología , Animales , Presión Sanguínea , Células Cultivadas , Relación Dosis-Respuesta a Droga , Endotelio Vascular/citología , Endotelio Vascular/efectos de los fármacos , Endotelio Vascular/metabolismo , Humanos , Molécula 1 de Adhesión Intercelular/metabolismo , Isquemia/tratamiento farmacológico , Isquemia/metabolismo , L-Lactato Deshidrogenasa/efectos de los fármacos , L-Lactato Deshidrogenasa/metabolismo , Lipopolisacáridos/farmacología , Hígado/efectos de los fármacos , Masculino , Ratas , Ratas Sprague-Dawley , Daño por Reperfusión/tratamiento farmacológico , Daño por Reperfusión/metabolismoRESUMEN
Hypertonicity suppresses neutrophil functions by unknown mechanisms. We investigated whether osmotically induced cytoskeletal changes might be related to the hypertonic inhibition of exocytosis. Hyperosmolarity abrogated the mobilization of all four granule types induced by diverse stimuli, suggesting that it blocks the process of exocytosis itself rather than individual signaling pathways. Concomitantly, osmotic stress provoked a twofold increase in F-actin, induced the formation of a submembranous F-actin ring, and abolished depolymerization that normally follows agonist-induced actin assembly. Several observations suggest a causal relationship between actin polymerization and inhibition of exocytosis: 1) prestimulus actin levels were inversely proportional to the stimulus-induced degranulation, 2) latrunculin B (LB) prevented the osmotic actin response and restored exocytosis, and 3) actin polymerization induced by jasplakinolide inhibited exocytosis under isotonic conditions. The shrinkage-induced tyrosine phosphorylation and the activation of the Na(+)/H(+) exchanger were not affected by LB. Inhibition of osmosensitive kinases failed to prevent the F-actin change, suggesting that the osmotic tyrosine phosphorylation and actin polymerization are independent phenomena. Thus cytoskeletal remodeling appears to be a key component in the neutrophil-suppressive, anti-inflammatory effects of hypertonicity.
Asunto(s)
Actinas/fisiología , Citoesqueleto/fisiología , Exocitosis/efectos de los fármacos , Soluciones Hipertónicas/farmacología , Neutrófilos/efectos de los fármacos , Neutrófilos/fisiología , Gránulos Citoplasmáticos/fisiología , Exocitosis/fisiología , Humanos , Iones , Soluciones Isotónicas , Neutrófilos/citología , Presión Osmótica , Polímeros/metabolismo , Tirosina/metabolismoRESUMEN
Neutrophil-mediated organ damage is a common feature of many disease states. We previously demonstrated that resuscitation with hypertonic salt solutions prevented the endotoxin-induced leukosequestration and consequent lung injury, and this effect was partially attributed to an altered surface expression of adhesion molecules, CD11b and L-selectin. In this study we investigated the mechanisms whereby osmotic stress evokes L-selectin shedding. The metalloprotease inhibitor RO 31-9790 prevented the osmotic down-regulation of L-selectin, indicating that this process was catalyzed by the same "sheddase" responsible for L-selectin cleavage induced by diverse inflammatory stimuli. The trigger for hypertonic shedding was cell shrinkage and not increased osmolarity, ionic strength, or intracellular pH. Volume reduction caused robust tyrosine phosphorylation and its inhibition by genistein and erbstatin abrogated shedding. Shrinkage stimulated tyrosine kinases Hck, Syk, and Pyk2, but prevention of their activation by the Src-family inhibitor PP1 failed to affect the L-selectin response. Hypertonicity elicited the Src family-independent activation of p38, and the inhibition of this kinase by SB203580 strongly reduced shedding. p38 was also essential for the N-formyl-methionyl-leucyl-phenylalanine- and lipopolysaccharide-induced shedding but not the phorbol ester-induced shedding. Thus, cell volume regulates L-selectin surface expression in a p38-mediated, metalloprotease-dependent manner. Moreover, p38 has a central role in shedding induced by many inflammatory mediators.
Asunto(s)
Proteínas Quinasas Dependientes de Calcio-Calmodulina/sangre , Ácidos Hidroxámicos , Selectina L/sangre , Proteínas Quinasas Activadas por Mitógenos , Neutrófilos/citología , Neutrófilos/fisiología , Tamaño de la Célula/efectos de los fármacos , Citosol/fisiología , Inhibidores Enzimáticos/farmacología , Genisteína/farmacología , Humanos , Concentración de Iones de Hidrógeno , Soluciones Hipertónicas , Imidazoles/farmacología , Técnicas In Vitro , Selectina L/genética , Antígeno de Macrófago-1/sangre , Metaloendopeptidasas/antagonistas & inhibidores , Neutrófilos/efectos de los fármacos , Fosfotirosina/sangre , Inhibidores de Proteasas/farmacología , Piridinas/farmacología , Proteínas Quinasas p38 Activadas por MitógenosRESUMEN
BACKGROUND: In a two-hit model of hemorrhagic shock and lipopolysaccharide (LPS), we previously showed that hypertonic saline (HTS) resuscitation reduced lung sequestration of neutrophils and the accompanying injury. This effect was partially attributed to suppressed expression of the surface adhesion molecule CD11b. This study investigates the duration of this protective effect after a single HTS dose and the usefulness of repeated infusions. MATERIAL AND METHODS: The previous two-hit rodent model was used. Neutrophil lung sequestration was measured by bronchoalveolar fluid cell count. CD11b expression was followed by flow cytometry. In vitro studies used isolated human neutrophils. RESULTS: Eighteen hours following resuscitation, the protective effect of HTS was lost. At this time, LPS caused an increase in both neutrophil lung sequestration and CD11b expression, regardless of the resuscitation regimen used. A second infusion of HTS prevented these changes and restored the lung protection observed earlier. In vitro studies showed that the duration of hypertonic pretreatment is an important determinant of cell responsiveness under the isotonic conditions: Four but not 2 h hypertonic exposure was able to prevent upregulation of CD11b induced by LPS added immediately after reestablishing isotonicity. CONCLUSIONS: This study demonstrates that HTS resuscitation lessens lung neutrophil sequestration and CD11b surface expression induced by LPS. This protective effect is transient but can be restored by a second HTS infusion suggesting that maintenance of beneficial effect necessitates repeated HTS addition. The reversibility ensures rapid modulation of neutrophil functions, thereby preventing acute tissue damage without causing long-lasting immunosuppression.
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Antígeno de Macrófago-1/genética , Neutrófilos/fisiología , Solución Salina Hipertónica/uso terapéutico , Choque Hemorrágico/fisiopatología , Choque Hemorrágico/terapia , Animales , Antígenos CD/sangre , Antígenos CD/genética , Líquido del Lavado Bronquioalveolar/citología , Recuento de Células , Escherichia coli , Citometría de Flujo , Regulación de la Expresión Génica , Humanos , Lipopolisacáridos/toxicidad , Antígeno de Macrófago-1/sangre , Masculino , Neutrófilos/citología , Neutrófilos/inmunología , Ratas , Ratas Sprague-Dawley , Resucitación , Choque Hemorrágico/inmunologíaRESUMEN
BACKGROUND: Neutrophil sequestration in the lungs plays an important role in the development of acute respiratory distress syndrome. We previously reported that hypertonic saline resuscitation attenuated lung injury after hemorrhagic shock and lipopolysaccharide (LPS) by abolishing neutrophil CD11b up-regulation. We investigated the mechanism underlying this effect. METHODS: Human neutrophils were exposed to LPS in the presence or absence of hypertonicity or SB203580 (p38 inhibitor). CD11b and CD14 were studied by immunofluorescence and p38 phosphorylation by immunoblotting. RESULTS: Hypertonicity had no effect on CD11b or CD14, caused a weak p38 phosphorylation, and completely prevented the LPS-induced p38 phosphorylation and CD11b up-regulation. p38 inhibition also abrogated CD11b up-regulation by LPS. CONCLUSION: MAPKp38 is important in CD11b regulation by LPS. The inhibitory effect of hypertonicity on the LPS-mediated effect may contribute to its protective anti-inflammatory effect observed in vivo. Transient hypertonicity might minimize organ injury in diseases characterized by neutrophil-mediated damage such as ARDS.
Asunto(s)
Antígenos CD18/metabolismo , Soluciones Hipertónicas/farmacología , Lipopolisacáridos/farmacología , Antígeno de Macrófago-1/metabolismo , Proteínas Quinasas Activadas por Mitógenos , Neutrófilos/metabolismo , Western Blotting , Proteínas Quinasas Dependientes de Calcio-Calmodulina/antagonistas & inhibidores , Proteínas Quinasas Dependientes de Calcio-Calmodulina/metabolismo , Supervivencia Celular , Inhibidores Enzimáticos/farmacología , Escherichia coli , Técnica del Anticuerpo Fluorescente , Humanos , Imidazoles/farmacología , Técnicas In Vitro , Receptores de Lipopolisacáridos/metabolismo , Fosforilación , Piridinas/farmacología , Regulación hacia Arriba , Proteínas Quinasas p38 Activadas por MitógenosRESUMEN
Hypertonic resuscitation fluids are known to be effective in restoring circulating volume in the hypovolemic trauma patient. Previous studies have suggested that hypertonicity might exert effects on immune cells leading to an altered host response. The present studies evaluated the effect of hypertonic resuscitation on the development of lung injury in a hemorrhagic shock model in which antecedent shock primes for increased lung neutrophil sequestration in response to intratracheal LPS. Resuscitation with hypertonic saline significantly reduced albumin leak, bronchoalveolar lavage fluid neutrophil counts, and the degree of histopathologic injury compared with resuscitation with Ringer's lactate. Both in vivo and in vitro data suggest that this beneficial effect may be related to altered adhesion molecule expression by the neutrophil. Specifically, hypertonicity induced shedding of L-selectin and prevented LPS-stimulated expression and activation of CD11b, both of which might contribute to reduced sequestration in the lung. Impaired up-regulation of lung ICAM-1 may have also participated, although ex vivo studies suggest that alterations in neutrophils were sufficient to account for the effect. Lung cytokine-induced neutrophil chemoattractant did not differ between animals resuscitated with hypertonic saline vs Ringer's lactate. Considered together, these studies demonstrate a possible novel approach to inhibiting organ injury in disease processes characterized by neutrophil-mediated damage.
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Adyuvantes Inmunológicos/farmacología , Pulmón/inmunología , Pulmón/patología , Resucitación , Solución Salina Hipertónica/farmacología , Choque Hemorrágico/inmunología , Animales , Presión Sanguínea/inmunología , Quimiocinas/biosíntesis , Humanos , Inflamación/inmunología , Inflamación/metabolismo , Inflamación/fisiopatología , Molécula 1 de Adhesión Intercelular/biosíntesis , Selectina L/biosíntesis , Lipopolisacáridos/toxicidad , Pulmón/metabolismo , Antígeno de Macrófago-1/biosíntesis , Masculino , Neutrófilos/efectos de los fármacos , Neutrófilos/inmunología , Neutrófilos/trasplante , Ratas , Ratas Sprague-Dawley , Resucitación/métodos , Choque Hemorrágico/metabolismo , Choque Hemorrágico/fisiopatologíaRESUMEN
OBJECTIVE: Trauma victims with hypotension require a rapid and reliable localization of bleeding and expedient surgical triage. Our hypothesis is that emergent abdominal sonography (EAS) is a rapid and accurate test of the need for urgent laparotomy in blunt trauma victims with hypotension. METHODS: Among 400 blunt trauma victims entered in a prospective blind study of EAS, a subgroup of 69 (17%) patients had a systolic blood pressure < or = 90 mm Hg during their initial assessment. Although the EAS results [(+) = fluid, (-) = no fluid] were not used in clinical decision making, the potential contribution of EAS to patient care was examined. RESULTS: The mean Injury Severity Score was 32. Twenty-two (32%) patients were EAS (+), of which 19 required an acute laparotomy. No laparotomies were performed in the 47 EAS (-) patients. The EASs required 19 +/- 5 seconds in the EAS (+) group and 154 +/- 13 seconds in the EAS (-) group. Twenty of the 22 positive EASs had free fluid in Morison's pouch. All 13 patients with an ultrasound score > or = 3 had a laparotomy. The primary etiology of hypotension was blood loss in 42 patients, hemoperitoneum in 18, and retroperitoneal hemorrhage in 12. CONCLUSION: EAS is a rapid and accurate indicator of the need for urgent laparotomy in the hypotensive blunt trauma victim. Further, a negative EAS can hasten the search for other causes of hypotension. Diagnostic peritoneal lavage may become obsolete in centers with EAS capabilities.
Asunto(s)
Traumatismos Abdominales/complicaciones , Traumatismos Abdominales/diagnóstico por imagen , Hemorragia/diagnóstico por imagen , Hipotensión/etiología , Triaje , Heridas no Penetrantes/complicaciones , Heridas no Penetrantes/diagnóstico por imagen , Adolescente , Adulto , Servicios Médicos de Urgencia , Femenino , Hemoperitoneo/diagnóstico por imagen , Hemoperitoneo/etiología , Hemorragia/etiología , Humanos , Puntaje de Gravedad del Traumatismo , Laparotomía , Masculino , Persona de Mediana Edad , Lavado Peritoneal , Estudios Prospectivos , Tomografía Computarizada por Rayos X , UltrasonografíaRESUMEN
OBJECTIVE: To determine the pattern and severity of injury and the outcome of front seat motor vehicle occupants after lateral impact crashes. DESIGN: Retrospective review undertaken in a Regional Trauma Unit (Sunnybrook Health Science Centre). MATERIALS AND METHODS: Review of seriously injured front seat motor vehicle occupants admitted to a Regional Trauma Unit over a 46-month period (September 15, 1989, to July 15, 1993) for whom vehicle crash information and occupant seat belt use were known. MEASUREMENTS AND MAIN RESULTS: Three hundred forty-eight front seat vehicle occupants were available for study; one hundred forty-one (41%) were involved in a lateral impact motor vehicle crash. Driver side lateral crashes (57%) were more common than passenger side impacts. Victims of lateral impact crashes had a significantly higher mean Injury Severity Score (25 compared with 20 for nonlateral crashes: p < 0.05), and the direction of impact was strongly associated with injury severity (p < 0.05). Lateral impact crashes resulted in substantially more significant chest (p < 0.01) and intra-abdominal (p < 0.0001) injuries. Type of injury was significantly different between the lateral and nonlateral impact groups for facial, chest, abdominal, and musculoskeletal injuries. CONCLUSIONS: The direction of impact in motor vehicle crashes is strongly associated with the pattern and severity of organ injuries. Further attention to automobile safety design is necessary to better protect occupants involved in lateral impact crashes.
Asunto(s)
Accidentes de Tránsito , Heridas y Lesiones , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Canadá , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Índices de Gravedad del Trauma , Heridas y Lesiones/epidemiologíaRESUMEN
Although there is an interest in emergent abdominal sonography (EAS), the clinical utilization of EAS in North America is minimal. The purpose of this study was to develop a new diagnostic algorithm for blunt abdominal injury based on a prospective blinded comparison of EAS, diagnostic peritoneal lavage (DPL), and computed tomography (CT). EAS (+ = fluid, - = no fluid) was performed before the DPL or CT, in 400 patients with a mean Injury Severity Score of 26; 293 had a CT and 107 had a DPL. The EASs required 2.6 +/- 1.2 minutes with 82% < or = 3 minutes. The accuracy of EAS for free fluid was 94% with a positive and negative predictive value of 82 and 96%, respectively. Only 1 of 338 patients with EAS- had an acute therapeutic laparotomy. Three patients with EAS- had a delayed laparotomy based on evolving clinical findings. The radiologists interpretation of the EAS video disagreed with the clinician sonographer in only 3% of cases. Based on these results, a diagnostic algorithm was developed using EAS as a screening test with selective use of DPL and CT. Emergent abdominal sonography performed by clinician sonographers is a rapid and accurate test for peritoneal fluid in blunt trauma victims, and the need for laparotomy in patients with a negative EAS is rare. Our study supports the routine use of EAS as a screening test in a diagnostic algorithm for the evaluation of blunt abdominal trauma.
Asunto(s)
Traumatismos Abdominales/diagnóstico por imagen , Algoritmos , Heridas no Penetrantes/diagnóstico por imagen , Traumatismos Abdominales/diagnóstico , Traumatismos Abdominales/cirugía , Adolescente , Adulto , Reacciones Falso Negativas , Femenino , Humanos , Masculino , Persona de Mediana Edad , Lavado Peritoneal , Estudios Prospectivos , Método Simple Ciego , Tomografía Computarizada por Rayos X , Ultrasonografía , Heridas no Penetrantes/diagnóstico , Heridas no Penetrantes/cirugíaRESUMEN
The use of lap seat belts has recently been recognized as a mechanism of blunt injury to the small bowel. Patients usually present immediately after injury and require urgent laparotomy. An unusual case of delayed small-bowel stricture after conservative management of an injury resulting from blunt trauma is reported. A 37-year-old woman involved in a high-speed motor vehicle accident was managed in hospital by observation. She had abdominal distension and pain, which gradually decreased and allowed slow introduction of a liquid diet. She was discharged from hospital but returned 6 weeks after injury with pain, abdominal distension, vomiting and obstipation. Stricture of an 8-cm segment of distal jejunum was found. Resection of the involved segment with primary anastomosis was curative.
Asunto(s)
Obstrucción Intestinal/etiología , Enfermedades del Yeyuno/etiología , Cinturones de Seguridad/efectos adversos , Heridas no Penetrantes/etiología , Adulto , Constricción Patológica , Femenino , HumanosRESUMEN
The classification of liver injuries is important for clinical practice, clinical research and quality assurance activities. The Organ Injury Scaling (OIS) Committee of the American Association for the Surgery of Trauma proposed the OIS for liver trauma in 1989. The purpose of the present study was to apply this scale to a cohort of liver trauma patients managed at a single Canadian trauma centre from January 1987 to June 1992. 170 study patients were identified and reviewed. The mean age was 30, with 69% male and a mean ISS of 33. 90% had a blunt mechanism of injury. The 170 patients were categorized into the 6 OIS grades of liver injury. The number of units of blood transfused, the magnitude of the operative treatment required, the liver-related complications and the liver-related mortality correlated well with the OIS grade. The OIS grade was unable to predict the need for laparotomy or the length of stay in hospital. We conclude that the OIS is a useful, practical and important tool for the categorization of liver injuries, and it may prove to be the universally accepted classification scheme in liver trauma.
Asunto(s)
Hígado/lesiones , Adolescente , Adulto , Anciano , Niño , Femenino , Humanos , Puntaje de Gravedad del Traumatismo , Masculino , Persona de Mediana Edad , Heridas y Lesiones/clasificaciónRESUMEN
In North America, the role of emergent abdominal sonography [ultrasonography (US)] after blunt trauma requires further definition. The purpose of this prospective study was to compare US to the gold standards, diagnostic peritoneal lavage (DPL), and computed tomography (CT), in a population of adults after blunt trauma. In 206 adults who required either CT or DPL to assess possible abdominal injury, US was performed, before DPL or CT, and was aimed at the detection of intraperitoneal fluid. The mean Injury Severity Score and Glasgow Coma Scale score were 24.0 and 11.9, respectively. One hundred thirty-seven patients (67%) had CT and 69 (33%) had DPL. The positive and negative predictive values of US for intraperitoneal fluid were 90% and 97%, respectively. The sensitivity, specificity, and accuracy of US for free fluid were 81%, 98%, and 96%, respectively. Of the six false-negative USs, only one required surgery. The US examinations required 2.6 +/- 1.4 min. Emergent abdominal sonography is an accurate, rapid test for the presence of intraperitoneal fluid in adult blunt trauma victims and in these patients may prove valuable as a screening test for abdominal injury.