Effect of remote ischemic conditioning on the immune-inflammatory profile in patients with traumatic hemorrhagic shock in a randomized controlled trial.

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.

In vivo and in vitro modulation of intercellular adhesion molecule (ICAM)-1 expression by hypertonicity.

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.

Blunt diaphragmatic and thoracic aortic rupture: an emerging injury complex.

Although both blunt diaphragmatic rupture (BDR) and thoracic aortic rupture (TAR) have been extensively discussed, the association of both injuries has been infrequently mentioned. The purpose of this study was to examine the current prevalence and clinical characteristics of combined BDR and TAR at an adult regional trauma unit. Among 3,886 trauma victims, 69 (1.8%) had a BDR and 44 (1.1%), a TAR. Seven patients (10% of all patients with a BDR) had both injuries. All 7 were victims of motor vehicle crashes and had a mean Injury Severity Score of 35. All TARs were just distal to the origin of the left subclavian artery. Five patients underwent repair of both injuries and survived, 1 patient had only the BDR repaired and survived, and 1 died during emergency thoracotomy, for a survival rate of 86%. Five patients had laparotomy and repair of the BDR in the presence of an unrepaired TAR. The TARs were repaired by the clamp-and-sew technique, three of them with primary repair and two with interposition tube grafts. Concomitant BDR and TAR appears to be an emerging injury complex with both diagnostic and therapeutic challenges. The presence of BDR demands a rigorous search for associated TAR.

Risk of complication in perforated duodenal ulcer operations according to the surgical technique employed.

We prospectively analyzed a homogeneous group of 65 patients with perforated duodenal ulcer whose medical condition (no perioperative shock, no associated disease, underwent laparotomy within 12 hours after perforation, and an APACHE II score below 11) would have little effect on the outcome of surgery to study the influence of the surgical procedure (suture closure, vagotomy, or gastrectomy) on the morbidity and mortality rate. Thirty-three patients (51%) underwent vagotomy, 25 (38%) simple suture closure, and seven (11%) gastrectomy. Five patients (8%) suffered postoperative complications, two (3%) required further operation, and one (1.5%) died of pulmonary sepsis. Statistical analyses revealed that "vagotomy" presented significantly better results than did "simple suture" and "gastrectomy" that had similar results. The type of surgery, however, was not a significant risk factor in predicting complications in this sample. This study points out the need to stratify the perforated duodenal ulcer patients for accurate investigations. It also shows that definitive operations (gastrectomy or vagotomy) do not increase surgical risk in this group of patients, and, considering the poorer results with simple suture closure compared to vagotomy, the latter is an attractive option because it also treats the underlying ulcer disease.

Injuries missed during initial assessment of blunt trauma patients.

OBJECTIVE: To determine the incidence and clinical significance of undiagnosed injuries in blunt trauma patients at our institution. DESIGN: Retrospective analysis of blunt trauma admissions over a 1-year period. Missed injury (MI) was defined as any injury recorded after the initial 24 hours. RESULTS: Of 432 patients studied, 59 (13.6%) had MI. Fractures were the most common MI. Thirty-five percent of MI were detected during repeated physical examination and 28% after patients were conscious and able to voice concerns. CONCLUSION: Over 10% of all blunt trauma patients had undiagnosed injuries. Forty percent of the MI had clinical implications. The most effective method of diagnosis consists of repeated clinical assessments. Special attention should be focused on patients with severe anatomical injuries, obtunded or intubated.

Penetrating heart wounds.

In 3 years, 26 patients were operated for penetrating heart wounds at our institution, the majority between 30 to 60 minutes after injury. Twenty-two patients with a possible heart wound were immediately taken to the operating room for thoracotomy. One patient initially underwent laparotomy while 2 were observed before operating-room thoracotomy. One patient underwent emergency-room thoracotomy. Three patients with no vital signs on admission died, 82.6% of the remainder survived. Stab wounds determined the best survival rate: 94%, whereas for gunshot wounds it was only 50%. Our experience at this Brazilian Trauma Center reveals that delay in reaching the hospital selected the patients, that clinical condition on arrival, method of injury (knife or gunshot), emergency room staffed with trauma surgeons and aggressive operating room treatment for penetrating heart wounds results in a remarkable survival rate. Emergency-room thoracotomy should be reserved for patients "in extremis" or when there is no operating room available.

Selective non-operative management of penetrating abdominal injury in Great Britain and Ireland: survey of practice.

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.

Rabbit model of uncontrolled hemorrhagic shock and hypotensive resuscitation.

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.

Occult pneumomediastinum in blunt chest trauma: clinical significance.

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.

Normal range values for thromboelastography in healthy adult volunteers.

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.

Rabbit model of uncontrolled hemorrhagic shock and hypotensive resuscitation

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.

[Acute jejunogastric intussusception]. / Invaginação jejunogástrica aguda.

The authors present one case of type III jejunogastric intussusception that occurred on the 9th post-gastrectomy day. They compare this case to five others seen at the same hospital in the last nine years. They discuss the rarity of this complication that can only be resolved surgically, the importance of early diagnosis for the favorable clinical evolution, and the surgical technique used. They stress the need to include jejunogastric intussusception in the differential diagnosis of high intestinal obstruction in gastrectomized patients both in the early and in the late post-operative period.

Exclusive jejunal and ileal lesions due to blunt trauma.

The exclusive jejunal and ileal lesion due to blunt trauma is a rare and potentially lethal condition. The small intestine is the most damaged organ in penetrating abdominal injuries, although its isolated injury in blunt abdominal trauma is rare and difficult to diagnosed. There are no characteristic signs nor symptoms in the exclusive jejunal and ileal lesions due to abdominal contusions which result in high morbidity and mortality rates since a late diagnosis is done despite advanced auxiliary diagnostic methods available. Considering these facts, the aim of the present work is to study the prognosis of patients suffering from this type of injury due to abdominal trauma, taking into consideration the time elapsed between the trauma and its diagnosis and the importance of its early surgical correction.

Abbreviated laparotomy for damage control: a case report.

During the initial operation on victims of multisystem trauma, life-threatening hypothermia, metabolic acidosis and coagulopathy occasionally develop. Without the immediate control of active bleeding and correction of these abnormalities, the intraoperative death rate is high. A patient with severe abdominal trauma was successfully managed with staged laparotomies. The patient's initial surgery was abbreviated to allow the aggressive correction of hypothermia and coagulopathy before definitive reconstruction of bowel injuries. Abbreviated laparotomy for damage control should be a part of the surgical armamentarium in the management of severe abdominal trauma.

Advances in fluid resuscitation of hemorrhagic shock.

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.

Cell volume-dependent regulation of L-selectin shedding in neutrophils. A role for p38 mitogen-activated protein kinase.

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.

Insertion of a transpyloric feeding tube during laparotomy in the critically injured: rationale and plea for routine use.

Although clinical and experimental evidence favours early enteral feeding in the critically injured, provision of such enteral feeds can be difficult. Gastric feeds are often not tolerated and may lead to aspiration. An intolerance of gastric feeds leads to a cumulative energy and protein deficit and may result in the initiation of expensive parenteral nutrition (TPN). An alternative and under-utilized technique to ensure enteral access in trauma victims is the insertion of a transpyloric (nasojejunal) feeding tube during emergent laparotomy. We have employed this method of enteral access with success. In the following report, we describe this technique, provide an illustrative case with a cost comparison between nasojejunal feeds and TPN, present the rationale for such a mode of enteral access and outline the indications and contraindications. Enteral access by the intra-operative insertion of a transpyloric feeding tube allows immediate/early enteral feeding that is easy, safe, reliable and inexpensive.

What are the clinical determinants of early energy expenditure in critically injured adults?

The clinical determinants of energy expenditure in critically injured adults require definition. Among adult blunt trauma victims who required mechanical ventilation, the resting energy expenditure was calculated with the Harris-Benedict equation (HBEE) and the early (< or = 5 days postinjury) energy expenditure was measured by indirect calorimetry (MEE) (n = 115). The MEE was 2052 +/- 531 kcal/day and MEE/HBEE ("stress factor") was 1.24 +/- 0.2. The MEE was correlated with HBEE, age, height, weight, sex, temperature, and paralytic agents (p < 0.01). However, MEE did not correlate with ISS, admission GCS score, admission base deficit, initial systolic blood pressure, or the number of units of packed red blood cells transfused in the first 24 hours after injury (p = NS). Temperature and paralysis correlated with MEE/HBEE (p < 0.01). A regression model of MEE was developed with the clinical variables HBEE, temperature, and the presence or absence of paralytic agents (r2 = 0.62; p < 0.001): MEE (kcal/d) = 1.4(HBEE) + 71.4(temperature) + 274(paralytics; + = 1, - = 2) - 3485. In mechanically ventilated trauma victims, both the early energy expenditure and the stress factor are determined by host factors but are independent of the severity of the anatomic and physiologic insult. The degree of hypermetabolism observed in this population was less than previously reported.

[Ogilvie syndrome in 2 cases of pseudo-pseudo-obstruction of the colon]. / Considerações sobre a síndrome de Ogilvie a partir de dois casos de pseudo-pseudo-obstrução do cólon.

Ogilvie's syndrome is defined as a pseudo-obstruction of the colon of unknown cause. A review of recent literature shows a proliferation of reports of such cases associated to multiple conditions. The authors present two cases of perforated peptic ulcers with peritonitis that mimicked Ogilvie's syndrome in the clinical, radiological, and colonoscopic presentations. They propose that pseudo-obstruction cases obviously caused by adynamic ileus be excluded from the Ogilvie's syndrome classification, for a better understanding of its pathogenesis.