Effects of Early Altitude Exposure on the Open Abdomen After Laparotomy in Trauma.

INTRODUCTION: While damage control surgery and resuscitation techniques have revolutionized the care of injured service members who sustain severe traumatic hemorrhage, the physiologic and inflammatory consequences of hemostatic resuscitation and staged abdominal surgery in the face of early aeromedical evacuation (AE) have not been investigated. We hypothesized that post-injury AE with an open abdomen would have significant physiologic and inflammatory consequences compared to AE with a closed abdomen. MATERIALS AND METHODS: Evaluation of resuscitation and staged abdominal closure was performed using a murine model of hemorrhagic shock with laparotomy. Mice underwent controlled hemorrhage to a systolic blood pressure of 25 mmHg and received either no resuscitation, blood product resuscitation, or Hextend resuscitation to a systolic blood pressure of either 50 mmHg (partial resuscitation) or 80 mmHg (complete resuscitation). Laparotomies were either closed prior to AE (closed abdomens) or left open during AE (open abdomens) and subsequently closed. AE was simulated with a 1-hour exposure to a hypobaric hypoxic environment at 8,000 feet altitude. Mice were euthanized at 0, 4, or 24 hours following AE. Serum was collected and analyzed for physiologic variables and inflammatory cytokine levels. Samples of lung and small intestine were collected for tissue cytokine and myeloperoxidase analysis as indicators of intestinal inflammation. Survival curves were also performed. RESULTS: Unresuscitated mice sustained an 85% mortality rate from hemorrhage and laparotomy, limiting the assessment of the effect of simulated AE in these subgroups. Overall survival was similar among all resuscitated groups regardless of the presence of hypobaric hypoxia, type of resuscitation, or abdominal closure status. Simulated AE had no observed effects on acid/base imbalance or the inflammatory response as compared to ground level controls. All mice experienced both metabolic acidosis and an acute inflammatory response after hemorrhage and injury, represented by an initial increase in serum interleukin (IL)-6 levels. Furthermore, mice with open abdomens had an elevated inflammatory response with increased levels of serum IL-10, serum tumor necrosis factor alpha, intestinal IL-6, intestinal IL-10, and pulmonary myeloperoxidase. CONCLUSION: These results demonstrate the complex interaction of AE and temporary or definitive abdominal closure after post-injury laparotomy. Contrary to our hypothesis, we found that AE in those animals with open abdomens is relatively safe with no difference in mortality compared to those with closed abdomens. However, given the physiologic and inflammatory changes observed in animals with open abdomens, further evaluation is necessary prior to definitive recommendations regarding the safety or downstream effects of exposure to AE prior to definitive abdominal closure.

Lower Extremity Duplex Ultrasound Screening Protocol for Moderate- and High-Risk Trauma Patients.

BACKGROUND: Deep vein thrombosis (DVT) remains a significant cause of morbidity after injury. Lower extremity duplex ultrasound screening (LEDUS) is designed to identify early, asymptomatic DVTs in moderate and high risk patients. We sought to describe when thrombus is detected and identify which trauma patients benefit from LEDUS. MATERIALS AND METHODS: A retrospective review was conducted on trauma patients who were moderate or high risk for venous thromboembolism based on risk assessment profile (RAP) scoring. Patients with RAP scores ≥5 underwent LEDUS on hospital Day 4 and then weekly. We defined moderate venous thromboembolism risk as an RAP score of 5-9 and high risk as an RAP score of ≥10. Demographics, injury characteristics, and chemoprophylaxis type and timing were analyzed. RESULTS: A total of 579 trauma patients underwent a total of 820 ultrasounds in 1 y. Eighty-eight acute DVTs were identified. There was only one progression of a below- to above-the-knee DVT. Patients with RAP scores ≥10 had significantly higher rates of DVTs compared with patients with lower RAP scores in addition to longer lengths of stay and time to DVT prophylaxis. Moderate- and high-risk patients had similar rates of pulmonary embolism. Two-thirds of all DVTs were diagnosed on the first screening examination. The rate of DVTs in patients with RAP scores 7-9 was 15.4% compared with 6.1% of those with RAP scores of 5-6. CONCLUSIONS: LEDUS allows for early identification of asymptomatic DVTs. Moderate-risk patients with RAP scores of ≥7 should be considered for LEDUS, given higher rates of DVT.

Microvesicles generated following traumatic brain injury induce platelet dysfunction via adenosine diphosphate receptor.

BACKGROUND: Traumatic brain injury (TBI) can result in an acute coagulopathy including platelet dysfunction that can contribute to ongoing intracranial hemorrhage. Previous studies have shown adenosine diphosphate (ADP)-induced platelet aggregation to be reduced after TBI. In addition, circulating microvesicles (MVs) are increased following TBI and have been shown to play a role in post-TBI coagulopathy and platelet function. We hypothesized that post-TBI MVs would affect platelet aggregation in a murine head injury model. METHODS: Moderate TBI was performed using a weight-drop method in male C57BL6 mice. Whole blood, plasma, MVs, and MV-poor plasma were isolated from blood collected 10 minutes following TBI and were mixed separately with whole blood from uninjured mice. Platelet aggregation was measured with Multiplate impedance platelet aggregometry in response to ADP. The ADP P2Y12 receptor inhibitor, R-138727, was incubated with plasma and MVs from TBI mice, and platelet inhibition was again measured. RESULTS: Whole blood taken from 10-minute post-TBI mice demonstrated diminished ADP-induced platelet aggregation compared with sham mice. When mixed with normal donor blood, post-TBI plasma and MVs induced diminished ADP-induced platelet aggregation compared with sham plasma and sham MVs. By contrast, the addition of post-TBI MV-poor plasma to normal blood did not change ADP-induced platelet aggregation. The observed dysfunction in post-TBI ADP platelet aggregation was prevented by the pretreatment of post-TBI plasma with R-138727. Treatment of post-TBI MVs with R-138727 resulted in similar findings of improved ADP-induced platelet aggregation compared with nontreated post-TBI MVs. CONCLUSION: Adenosine diphosphate-induced platelet aggregation is inhibited acutely following TBI in a murine model. This platelet inhibition is reproduced in normal blood by the introduction of post-TBI plasma and MVs. Furthermore, observed platelet dysfunction is prevented when post-TBI plasma and MVs are treated with an inhibitor of the P2Y12 ADP receptor. Clinically observed post-TBI platelet dysfunction may therefore be partially explained by the presence of the ADP P2Y12 receptor within post-TBI MVs. LEVEL OF EVIDENCE: Level III.

Proximal penetrating extremity injuries-An opportunity to decrease overtriage?

BACKGROUND: Penetrating injuries to the extremity proximal to the elbow or knee are anatomic criteria for full trauma team activation (FFTA) by the American College of Surgeon's Committee on Trauma standards. This criterion lacks objective evidence-based support. Overtriage of trauma team activation may result in excessive costs and resource burden at trauma centers. We hypothesized that FFTA for penetrating injuries to the proximal extremities by anatomic criteria alone may lead to significant overtriage. METHODS: A 3-year retrospective review (2013-2015) was completed of all patients evaluated at an urban Level I trauma center with isolated penetrating extremity injuries. Data included the number of full and limited trauma team activations as well as criterion met, Injury Severity Score (ISS), injury, limb characteristics, and disposition. Overtriage was defined as FFTA for an ISS of 15 or less, with a goal rate less than 50%. RESULTS: We identified 6,335 total trauma team activations with 795 isolated penetrating extremity injuries. Of these injuries, 413 (51.9%) were injuries proximal to the joint. Within this subgroup, 71.2% of patients were discharged from the emergency department with a median ISS of 1 and no additional intervention. Only 5.3% of patients that did not meet additional FFTA criteria underwent immediate operative intervention. By comparison, 21% of FFTAs and 5.8% of limited trauma team activations underwent immediate operative intervention during the 3-year period. Of the 413 isolated penetrating proximal-extremity injuries, only one had an ISS of 15 or greater, resulting in a 99.7% overtriage rate. CONCLUSION: Penetrating injuries to the extremities are common in urban trauma centers. Full trauma team activation based on anatomic, rather than physiologic, criteria may lead to a significant overtriage rate. Further distinction in the level of trauma team activation may be made based on hard signs of neurovascular injury. LEVEL OF EVIDENCE: Epidemiological study, level III; Care Management, level IV.

Safety and efficacy of brain injury guidelines at a Level III trauma center.

BACKGROUND: Patients with mild to moderate traumatic brain injury (TBI) are often primarily managed by emergency medicine and trauma/acute care physicians. The Brain Injury Guidelines (BIG) were developed at an American College of Surgeons-accredited Level 1 trauma center to triage mild to moderate TBI patients and help identify patients who warrant neurosurgical consultation. The BIG have not been validated at a Level III trauma center. We hypothesized that BIG criteria can be safely adapted to an American College of Surgeons-accredited Level III trauma center to guide transfers to a higher echelon of care. METHODS: We reviewed the trauma registry at a Level III trauma center to identify TBI patients who presented with an Abbreviated Injury Severity-Head score greater than zero. Demographic data, injury details, and clinical outcomes were abstracted with primary outcome measures of worsening on second computed tomography of the head, neurosurgical intervention, transfer to a Level I trauma center, and in-hospital mortality. Patients were classified using the BIG criteria. After validating the BIG in our cohort, we reclassified patients using updated BIG criteria. Updated criteria included mechanism of injury, reclassification of anticoagulation or antiplatelet use, and replacement of the neurologic examination component with stratification by admission Glasgow Coma Scale (GCS) score. RESULTS: From July 2013 to June 2016, 332 TBI patients were identified: 115 BIG-1, 25 BIG-2, and 192 BIG-3. Patients requiring neurosurgical intervention (n = 30) or who died (n = 29) were BIG-3 with one exception. Patients with GCS score of less than 12 had worse outcomes than those with a GCS score of 12 or greater, regardless of BIG classification. Anticoagulant or antiplatelet use was not associated with worsened outcomes in patients not meeting other BIG-3 criteria. The updated BIG resulted in more patients in BIG-1 (n = 109) and BIG-2 (n = 100) without negatively affecting outcomes. CONCLUSION: The BIG can be applied in the Level III trauma center setting. Updated BIG criteria can aid triage of mild to moderate TBI patients to a Level I trauma center and may reduce secondary overtriage. LEVEL OF EVIDENCE: Care management, level IV.

Platelet Function Changes in a Time-Dependent Manner Following Traumatic Brain Injury in a Murine Model.

Traumatic brain injury (TBI) results in systemic changes in coagulation and inflammation that contribute to post-traumatic morbidity and mortality. The potential interaction of platelets and pro-inflammatory cytokines in the modulation of coagulation, microthrombosis, and venous thromboembolic events after moderate TBI has not been determined. Using a murine model, we hypothesized that the degree of platelet-induced coagulation varies depending on the platelet aggregation agonist platelet-induced coagulation changes in a time-dependent manner following TBI, and changes in platelet-induced coagulation are mirrored by changes in the levels of circulating pro-inflammatory cytokines. An established weight-drop model was used to induce TBI in anesthetized mice. Blood samples were collected at intervals after injury for measurements of platelet count, serum fibrinogen, pro-inflammatory cytokines, and determination of soluble P-selectin levels. Thromboelastometry was used to evaluate changes in hemostasis. Platelet function was determined using whole blood impedance aggregometry. Ten minutes following TBI, adenosine diphosphate-induced platelet aggregation decreased as measured by platelet aggregometry. Despite no changes in platelet counts and serum fibrinogen, platelet aggregation, pro-inflammatory cytokines, and soluble P-selectin were increased at 6 h after TBI. Rotation thromboelastometry demonstrated increased maximal clot firmness at 6 h. Platelet function and coagulability returned to baseline levels 24 h following head injury. Our data demonstrate that after TBI, acute platelet dysfunction occurs followed by rebound platelet hyperaggregation. Alterations in post-TBI platelet aggregation are reflected in whole blood thromboelastometry and are temporally associated with the systemic pro-inflammatory response.

Variability of fluid administration during exploratory laparotomy for abdominal trauma.

BACKGROUND: Approximately 8% of traumatically injured patients require transfusion with packed red blood cells (pRBC) and only 1% to 2% require massive transfusion. Intraoperative massive transfusion was defined as requiring greater than 5 units (u) of pRBC in 4 hours. Despite the majority of patients not requiring transfusion, the appropriate amount and type of crystalloid administered during the era of damage control resuscitation have not been analyzed. We sought to determine the types of crystalloid used during trauma laparotomies and the potential effects on resuscitation. METHODS: Patients who underwent laparotomy after abdominal trauma from January 2014 to December 2016 at the University of Cincinnati Medical Center were identified. Patients were grouped based on requiring 0u, 1u to 4u, and ≥5u pRBC during intraoperative resuscitation. Demographic, physiologic, pharmacologic, operative, and postoperative data were collected. Statistical analysis was performed with Kruskal-Wallis test and Pearson's correlation coefficient. RESULTS: Lactated Ringer's (LR) solution was the most used crystalloid type received in the 0u and 1u to 4u pRBC cohorts, whereas normal saline (NS) was the most common in the ≥5u pRBC cohort. Most patients received two types of crystalloid intraoperatively. NS and LR were most frequently the first crystalloids administered, with Normosol infusion occurring later. The amount of crystalloid received correlated with operative length, but did not correlate with the estimated blood loss. Neither the type of crystalloid administered nor the anesthesia provider type was associated with changes in postoperative resuscitation parameters or electrolyte concentrations. DISCUSSION: There is a wide variation in the amount and types of crystalloids administered during exploratory laparotomy for trauma. Interestingly, the amount or type of crystalloid given did not affect resuscitation parameters regardless of blood product requirement. LEVEL OF EVIDENCE: Level IV.

Laparoscopic subtotal cholecystectomy compared to total cholecystectomy: a matched national analysis.

BACKGROUND: Laparoscopic subtotal cholecystectomy (LSC) is considered a safe alternative to laparoscopic cholecystectomy (LC) if biliary anatomy is obscured by inflammation. While case series studies have observed low morbidity rates with LSC, the impact of operative conversion on patient outcomes is poorly understood. METHODS: A national analysis of all patients who underwent LC or LSC from 2009 to 2013 was performed using the University HealthSystem Consortium database. A 1:1 propensity score match was used to compare procedural outcomes accounting for clinical and demographic factors. Matched samples had <10% standardized differences of each baseline covariate. RESULTS: A total of 131,082 LC and 487 LSC were performed during the study period. Compared with LC, patients undergoing LSC were more likely to be older (56 versus 48 years), male (54.2% versus 32.3%), and have higher severity of illness scores on admission (9.2% versus 3.5% extreme severity of illness; P < 0.001 each). LSC patients had a prolonged hospital length of stay (LOS, 4 versus 3 days), greater total direct cost ($9053 versus $6398), higher readmission rates (11.9% versus 7.0%), and higher mortality rates (0.82% versus 0.28%, P < 0.05 each). After matching, the difference in total direct cost persisted ($9053 versus $7,581, P < 0.001), but there were no differences in hospital LOS, readmission rates, or overall mortality. CONCLUSIONS: LSC is an important alternative to LC for the difficult gallbladder. Conversion to LSC is associated with increased patient morbidity and resource utilization leading to perceived poor outcomes, but this is due to patient factors at initial presentation. Health care providers should consider LSC if the patient may be at risk for iatrogenic injury to the biliary tract.

Sphingosine's role in epithelial host defense: A natural antimicrobial and novel therapeutic.

Sphingosine is a natural sphingolipid found in membranes of all eukaryotic cells. In addition to its functions in cell signaling, sphingosine has broad-spectrum antimicrobial properties. Sphingosine's role as an antimicrobial is important in tissues such as the skin and respiratory epithelium. Reduction in the normal sphingosine level is associated with problems related to infection susceptibility. Therefore, exogenous sphingosine may be an effective antimicrobial therapeutic. Inhaled nebulized sphingosine has been shown to be effective at both preventing and treating pneumonia in multiple mouse models. We now show that inhaled sphingosine has low toxicity to the respiratory system, strengthening its case as an excellent candidate for a novel inhaled antimicrobial drug.