Comparison of Octreotide and Vasopressors as First-Line Treatment for Intraoperative Carcinoid Crisis.

BACKGROUND: Intraoperative carcinoid crisis is typically sudden onset of profound hypotension during operations on patients with neuroendocrine tumors. The crisis was thought to be due to massive release of hormones, and perioperative octreotide was recommended as a prophylaxis against the crisis and as first-line treatment. Recent studies show that octreotide does not prevent the crisis and that no massive release of hormones occurs. Therefore, the authors hypothesized that octreotide is not effective for treating the crisis. METHODS: A prospective carcinoid anesthesia database was analyzed for occurrences of crisis. Outcomes were compared between protocols when first-line therapy was bolus octreotide and when it was vasopressors without octreotide. Significance was determined by Student's t test, the Mann-Whitney U test, and Fisher's exact test. RESULTS: Among operations performed with octreotide as first-line treatment (n = 150), crisis occurred for 45 (30 %) patients, the median crisis duration was 6 min, 12 (27 %) patients had crises longer than 10 min, 42 patients (93 %) required subsequent vasopressor administration to resolve the crisis, and 3 (2 %) operations were aborted. Among operations performed with vasopressors as the first-line treatment (n = 195), crisis occurred for 49 (25 %) patients (p = 0.31), the median crisis duration was 3 min (p < 0.001), and no crisis lasted longer than 10 min (p = 0.001). Patients treated with vasopressors were less likely to have multiple crises and had a shorter total time in crisis, a shorter anesthesia time, and no aborted operations (p < 0.05 for all). CONCLUSIONS: First-line octreotide was ineffective treatment for carcinoid crisis, with patients requiring vasopressors to resolve the crisis, and many crises lasting longer than 10 min. First-line vasopressor treatment resulted in significantly shorter crisis durations, fewer crises and aborted operations, and shorter anesthesia times. Vasopressors should be used as first-line treatment for intraoperative crisis, and treatment guidelines should be changed.

INFLUENCE OF OBESITY ON VASCULAR DYSFUNCTION AFTER TRAUMATIC HEMORRHAGE.

ABSTRACT: Background: Obesity increases the risk for morbidity and mortality after trauma. These complications are associated with profound vascular damage. Traumatic hemorrhage acutely attenuates vascular responsiveness, but the impact of obesity on this dysfunction is not known. The local inflammatory response in vascular cells is also unknown. We hypothesized that obesity potentiates trauma-induced vascular inflammation and dysfunction. Methods: Male Sprague-Dawley rats (~250 g) were fed normal chow (NC; 13.5% kcal fat, n = 20) or high-fat (HF; 60% kcal fat, n = 20) diets for 6 to 8 weeks. Under anesthesia, hemorrhage was induced by a mesenteric artery laceration, a Grade V splenic injury, and hypotension (MAP = 30-40 mm Hg) for 30 minutes. Vascular responsiveness was assessed ex vivo in isolated mesenteric arteries prehemorrhage and posthemorrhage. Gene expression for IL-1ß, and IL-6, prooxidant nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX2), and α-adrenergic receptor were assessed in carotid artery endothelial cells (ECs) and non-ECs (media + adventitia). Results: In NC rats, hemorrhage attenuated norepinephrine-induced vasoconstriction and endothelium-dependent vasodilation to acetylcholine. In HF rats, baseline norepinephrine-induced vasoconstriction was attenuated compared with NC, but vasoconstriction and endothelium-dependent vasodilation did not change prehemorrhage to posthemorrhage. Hemorrhage led to elevated IL-1ß gene expression in ECs and elevated IL1ß, IL-6, NOX2, and α-adrenergic receptor gene expression in the media + adventitia compared with sham. HF rats had greater EC IL-1 ß and NOX2 gene expression compared with NC rats. The hemorrhage-induced elevation of IL-1ß in the media + adventitia was greatest in HF rats. Conclusion: Traumatic hemorrhage attenuates vascular responsiveness and induces vascular inflammation. The attenuated vascular responsiveness after hemorrhage is absent in obese rats, while the elevated vascular inflammation persists. A HF diet amplifies the arterial inflammation after hemorrhage. Altered vascular responsiveness and vascular inflammation may contribute to worse outcomes in obese trauma patients.

The prevalence, operations, and outcomes of carcinoid heart disease.

BACKGROUND: Carcinoid heart disease (CHD) is a sequela of carcinoid liver metastases (LM). The true prevalence of CHD is unknown due to infrequent screening by transthoracic echocardiography (TTE). Octreotide is believed to protect against new and recurrent CHD, but supporting data are scant. This study determined CHD prevalence and outcomes in patients screened by TTE and treated with octreotide. METHODS: Records of carcinoid patients from 2001 to 2021 were reviewed. Survival was estimated by Kaplan-Meyer curves and compared by log-rank. RESULTS: Among 282 patients screened by TTE, overall survival was lower in CHD (n = 40) versus non-CHD (n = 242) patients (p < 0.001). Despite octreotide therapy, 21 patients developed CHD. Among patients with inoperable LM, survival was lower in CHD patients without valve replacement (VR) (p < 0.001), but similar between CHD patients with VR and non-CHD patients. CHD patients with VR and hepatic cytoreduction had survival similar to CHD patients without VR. CONCLUSION: VR improves survival in CHD patients with inoperable LM. Hepatic cytoreduction after VR should be reserved for carefully selected cases. Our data do not support a protective effect of octreotide.

A prospective study of carcinoid crisis with no perioperative octreotide.

BACKGROUND: Carcinoid crises, defined as the sudden onset of hemodynamic instability in patients with neuroendocrine tumors undergoing operation, are associated with significantly increased risk of postoperative complications. Octreotide has been used prophylactically to reduce crisis rates as well as therapeutically to treat crises that still occur. However, studies using octreotide still report crisis rates of 3.4% to 35%, leading to the questioning of its efficacy. METHODS: Patients with neuroendocrine tumors undergoing operation between 2017 to 2020 with no perioperative octreotide were prospectively studied. Clinicopathologic data were compared by χ2 test for discrete variables and by Mann-Whitney U test for continuous variables. RESULTS: One hundred and seventy-one patients underwent 195 operations. Crisis was documented in 49 operations (25%), with a mean duration of 3 minutes. Crisis was more likely to occur in patients with small bowel primary tumors (P = .012), older age (P = .015), and carcinoid syndrome (P < .001). Those with crises were more likely to have major postoperative complications (P = .003). CONCLUSION: Completely eliminating perioperative octreotide resulted in neither increased rate nor duration compared with previous studies using octreotide. We conclude perioperative octreotide use may be safely stopped, owing to inefficacy, though the need for an effective medication is clear given continued higher rates of complications.

Temporal profile of the pro- and anti-inflammatory responses to severe hemorrhage in patients with venous thromboembolism: Findings from the PROPPR trial.

BACKGROUND: The Pragmatic Randomized Optimal Platelet and Plasma Ratios (PROPPR) trial showed that 15% of patients developed venous thromboembolism (VTE) following hemorrhage, but the mechanisms are unknown. Since inflammation is associated with hypercoagulability and thrombosis, our goal was to compare the temporal inflammatory profile following hemorrhagic shock in patients with and without VTE. STUDY DESIGN: Secondary analysis was performed on data collected from PROPPR. Blood samples collected at 0 hour, 2 hours, 4 hours, 6 hours, 12 hours, 24 hours, 48 hours, and 72 hours following admission were assayed on a 27-target cytokine panel, and compared between VTE (n = 83) and non-VTE (n = 475) patients. p < 0.05 indicated significance. RESULTS: Over time, both groups exhibited elevations in proinflammatory mediators interleukin (IL)-6, IL-8, IL-10, granulocyte colony-stimulating factor 57, monocyte chemoattractant protein 1 and macrophage inflammatory protein 1ß, and anti-inflammatory mediators IL-1ra and IL-10 (p < 0.05 vs. admission). Venous thromboembolism patients showed amplified responses for IL-6 (6-72 hours) and IL-8 (6-24 hours), which peaked at later time points, and granulocyte colony-stimulating factor 57 (12-24 hours), monocyte chemoattractant protein 1 (6-72 hours), and macrophage inflammatory protein-1 ß (2-12 hours) (p < 0.05 vs. non-VTE per time point) that peaked at similar time points to non-VTE patients. The anti-inflammatory responses were similar between groups, but the interleukin-mediated proinflammatory responses continued to rise after the peak anti-inflammatory response in the VTE group. The occurrence rate of adverse events was higher in VTE (97%) versus non-VTE (87%, p = 0.009) and was associated with higher inflammation. CONCLUSION: Patients with VTE following hemorrhagic shock exhibited a prolonged and amplified proinflammatory responses mediated by select interleukin, chemotactic, and glycoprotein cytokines that are not antagonized by anti-inflammatory mediators. This response is not related to randomization group, injury severity or degree of shock, but may be linked to adverse events. LEVEL OF EVIDENCE: Prognostic, level III.

Evaluation of the prognosis for N2 status in patients with small bowel neuroendocrine tumors.

BACKGROUND: The 8th edition AJCC Staging for small bowel neuroendocrine tumors created a novel N2 classification. This study investigates if it is independently prognostic. METHODS: Records of patients from 2008 to 2019 were reviewed. Survival rates were estimated by Kaplan-Meier method and compared by log-rank. The Cox Proportional Hazards model was used to determine factors associated with overall survival (OS) via multivariate analysis. RESULTS: Among 300 patients, 225 were N2 and 60 were N1. No differences were seen in pathologic markers for N1 compared to N2. N2 were more likely to have liver metastases (LM) (p = 0.048) but rates of resectability were similar. Median OS for N1 with >70% liver cytoreduction was not yet reached compared to 121 months for N2 (p = 0.005). On multivariate analysis, LM was associated with shorter survival (p = 0.028), but nodal status was not. CONCLUSIONS: Unlike LM, N2 status is not independently prognostic, but a marker for aggressive LM.

Outcomes of cytoreductive operations for peritoneal carcinomatosis with or without liver cytoreduction in patients with small bowel neuroendocrine tumors.

BACKGROUND: This study determines how much cytoreduction for small bowel neuroendocrine tumors with peritoneal carcinomatosis and liver metastases can be achieved and the corresponding survival benefits of different levels of clearance. METHODS: Records of patients with small bowel neuroendocrine tumors with peritoneal carcinomatosis were reviewed and scored using the Lyon Stage system. Kaplan-Meier survival was calculated and compared by log-rank analysis. RESULTS: Among 323 patients with small bowel neuroendocrine tumors identified, 98 (30%) had peritoneal carcinomatosis. At laparotomy, 82% had Lyon Stage ≥3 compared with 78% who had Lyon Stage ≤2 after debulking (P < .00001). Median overall survival for Lyon Stage = 0 was 132 months and 51 months for Lyon Stage ≥1 (P = .026). For incomplete clearance, overall survival was 76 months for Lyon Stage ≤1 compared with 32 months for Lyon Stage ≥3 (P = .037). Seventy-nine (81%) patients had liver metastases, and 57 underwent >70% liver metastases cytoreduction. Overall survival was 76 months for Lyon Stage ≤1 and >70% liver metastases cytoreduction, 38.5 months for Lyon Stage ≥3 and >70% liver metastases cytoreduction, 22 months for Lyon Stage ≤1 and liver metastases not cytoreduced, and 20 months for Lyon Stage ≥3 and liver metastases not cytoreduced (P = .018). CONCLUSION: A majority of patients with peritoneal carcinomatosis from small bowel neuroendocrine tumors can be cytoreduced. Best survival times are seen with complete clearance; however, there are improved survival times for Lyon Stage ≤1. In patients with liver metastases, best survival after cytoreduction is seen when both Lyon Stage ≤1 and liver metastases >70% are achieved.

Tranexamic acid administration in the field does not affect admission thromboelastography after traumatic brain injury.

BACKGROUND: No Food and Drug Administration-approved medication improves outcomes following traumatic brain injury (TBI). A forthcoming clinical trial that evaluated the effects of two prehospital tranexamic acid (TXA) dosing strategies compared with placebo demonstrated no differences in thromboelastography (TEG) values. We proposed to explore the impact of TXA on markers of coagulation and fibrinolysis in patients with moderate to severe TBI. METHODS: Data were extracted from a placebo-controlled clinical trial in which patients 15 years or older with TBI (Glasgow Coma Scale, 3-12) and systolic blood pressure of ≥90 mm Hg were randomized prehospital to receive placebo bolus/placebo infusion (placebo), 1 g of TXA bolus/1 g of TXA infusion (bolus maintenance), or 2 g of TXA bolus/placebo infusion (bolus only). Thromboelastography was performed, and coagulation measures including prothrombin time, activated partial thromboplastin time, international ratio, fibrinogen, D-dimer, plasmin-antiplasmin (PAP), thrombin antithrombin, tissue plasminogen activator, and plasminogen activator inhibitor 1 were quantified at admission and 6 hours later. RESULTS: Of 966 patients receiving study drug, 700 had laboratory tests drawn at admission and 6 hours later. There were no statistically significant differences in TEG values, including LY30, between groups (p > 0.05). No differences between prothrombin time, activated partial thromboplastin time, international ratio, fibrinogen, thrombin antithrombin, tissue plasminogen activator, and plasminogen activator inhibitor 1 were demonstrated across treatment groups. Concentrations of D-dimer in TXA treatment groups were less than placebo at 6 hours (p < 0.001). Concentrations of PAP in TXA treatment groups were less than placebo on admission (p < 0.001) and 6 hours (p = 0.02). No differences in D-dimer and PAP were observed between bolus maintenance and bolus only. CONCLUSION: While D-dimer and PAP levels reflect a lower degree of fibrinolysis following prehospital administration of TXA when compared with placebo in a large prehospital trial of patients with TBI, TEG obtained on admission and 6 hours later did not demonstrate any differences in fibrinolysis between the two TXA dosing regimens and placebo. LEVEL OF EVIDENCE: Diagnostic test, level III.

Selective aortic arch perfusion with fresh whole blood or HBOC-201 reverses hemorrhage-induced traumatic cardiac arrest in a lethal model of noncompressible torso hemorrhage.

BACKGROUND: Hemorrhage-induced traumatic cardiac arrest (HiTCA) has a dismal survival rate. Previous studies demonstrated selective aortic arch perfusion (SAAP) with fresh whole blood (FWB) improved the rate of return of spontaneous circulation (ROSC) after HiTCA, compared with resuscitative endovascular balloon occlusion of the aorta and cardiopulmonary resuscitation (CPR). Hemoglobin-based oxygen carriers, such as hemoglobin-based oxygen carrier (HBOC)-201, may alleviate the logistical constraints of using FWB in a prehospital setting. It is unknown whether SAAP with HBOC-201 is equivalent in efficacy to FWB, whether conversion from SAAP to extracorporeal life support (ECLS) is feasible, and whether physiologic derangement post-SAAP therapy is reversible. METHODS: Twenty-six swine (79 ± 4 kg) were anesthetized and underwent HiTCA which was induced via liver injury and controlled hemorrhage. Following arrest, swine were randomly allocated to resuscitation using SAAP with FWB (n = 12) or HBOC-201 (n = 14). After SAAP was initiated, animals were monitored for a 20-minute prehospital period prior to a 40-minute damage control surgery and resuscitation phase, followed by 260 minutes of critical care. Primary outcomes included rate of ROSC, survival, conversion to ECLS, and correction of physiology. RESULTS: Baseline physiologic measurements were similar between groups. ROSC was achieved in 100% of the FWB animals and 86% of the HBOC-201 animals (p = 0.483). Survival (t = 320 minutes) was 92% (11/12) in the FWB group and 67% (8/12) in the HBOC-201 group (p = 0.120). Conversion to ECLS was successful in 100% of both groups. Lactate peaked at 80 minutes in both groups, and significantly improved by the end of the experiment in the HBOC-201 group (p = 0.001) but not in the FWB group (p = 0.104). There was no significant difference in peak or end lactate between groups. CONCLUSION: Selective aortic arch perfusion is effective in eliciting ROSC after HiTCA in a swine model, using either FWB or HBOC-201. Transition from SAAP to ECLS after definitive hemorrhage control is feasible, resulting in high overall survival and improvement in lactic acidosis over the study period.

Efficacy of the Abdominal Aortic Junctional Tourniquet-Torso Plate in a Lethal Model of Noncompressible Torso Hemorrhage.

BACKGROUND: The Abdominal Aortic Junctional Tourniquet, when modified with an off-label, prototype, accessory pressure distribution plate (AAJT-TP), has the potential to control noncompressible torso hemorrhage in prolonged field care. METHODS: Using a lethal, noncompressible torso hemorrhage model, 24 male Yorkshire swine (81kg-96kg) were randomly assigned into two groups (control or AAJT-TP). Anesthetized animals were instrumented and an 80% laparoscopic, left-side liver lobe transection was performed. At 10 minutes, the AAJT-TP was applied and inflated to an intraabdominal pressure of 40mmHg. At 20 minutes after application, the AAJT-TP was deflated, but the windlass was left tightened. Animals were observed for a prehospital time of 60 minutes. Animals then underwent damage control surgery at 180 minutes, followed by an intensive care unit-phase of care for an additional 240 minutes. Survival was the primary end point. RESULTS: Compared with Hextend, survival was not significantly different in the AAJT-TP group (ρ = .564), nor was blood loss (3.3L ± 0.5L and 3.0L ± 0.5L, respectively; p = .285). There was also no difference in all physiologic parameters between groups at the end of the study or end of the prehospital phase. Three of 12 AAJT-TP animals had an inferior vena cava thrombus. CONCLUSION: The AAJT-TP did not provide any survival benefit compared with Hextend alone in this model of noncompressible torso hemorrhage.

The effects of cryopreserved red blood cell transfusion on tissue oxygenation in obese trauma patients.

BACKGROUND: Low tissue oxygenation (StO2) is associated with poor outcomes in obese trauma patients. A novel treatment could be the transfusion of cryopreserved packed red blood cells (CPRBCs), which the in vitro biochemical profile favors red blood cell (RBC) function. We hypothesized that CPRBC transfusion improves StO2 in obese trauma patients. METHODS: Two hundred forty-three trauma patients at five Level I trauma centers who required RBC transfusion were randomized to receive one to two units of liquid packed RBCs (LPRBCs) or CPRBCs. Demographics, injury severity, StO2, outcomes, and biomarkers of RBC function were compared in nonobese (body mass index [BMI] < 30) and obese (BMI ≥ 30) patients. StO2 was also compared between obese patients with BMI of 30 to 34.9 and BMI ≥ 35. StO2 was normalized and expressed as % change after RBC transfusion. A p value less than 0.05 indicated significance. RESULTS: Patients with BMI less than 30 (n = 141) and BMI of 30 or greater (n = 102) had similar Injury Severity Score, Glasgow Coma Scale, and baseline StO2. Plasma levels of free hemoglobin, an index of RBC lysis, were lower in obese patients after CPRBC (125 [72-259] µg/mL) versus LPRBC transfusion (230 [178-388] µg/mL; p < 0.05). StO2 was similar in nonobese patients regardless of transfusion type, but improved in obese patients who received CPRBCs (104 ± 1%) versus LPRPCs (99 ± 1%, p < 0.05; 8 hours after transfusion). Subanalysis showed improved StO2 after CPRBC transfusion was specific to BMI of 35 or greater, starting 5 hours after transfusion (p < 0.05 vs. LPRBCs). CPRBCs did not improve clinical outcomes in either group. CONCLUSION: CPRBC transfusion is associated with increased StO2 and lower free hemoglobin levels in obese trauma patients, but did not improve clinical outcomes. Future studies are needed to determine if CPRBC transfusion in obese patients attenuates hemolysis to improve StO2. LEVEL OF EVIDENCE: Therapeutic, level IV.

Transfusion of cryopreserved packed red blood cells is safe and effective after trauma: a prospective randomized trial.

OBJECTIVES: To determine the safety and efficacy of cryopreserved packed red blood cell (CPRBC) transfusion in trauma patients. BACKGROUND: Liquid packed red blood cells (LPRBCs) have an abbreviated shelf-life and worsening storage lesion with age. CPRBCs are frozen 2 to 6 days after donation, stored up to 10 years, and are available for 14 days after thawing and washing. CPRBCs can be utilized in diverse settings, but the effect on clinical outcomes is unknown. METHODS: We performed a prospective, randomized, double-blind study at 5 level 1 trauma centers. Stable trauma patients requiring transfusion were randomized to young LPRBCs (≤14 storage days), old LPRBCs (>14 storage days), or CPRBCs. Tissue oxygenation (StO2), biochemical and inflammatory mediators were measured, and clinical outcomes were determined. RESULTS: Two hundred fifty-six patients with well-matched injury severity and demographics (P > 0.2) were randomized (84 young, 86 old, and 86 CPRBCs). Pretransfusion and final hematocrits were similar (P > 0.68). Patients in all groups received the same number of units postrandomization (2 [1-4]; P > 0.05). There was no difference in the change in tissue oxygenation between groups. CPRBCs contained less α2-macrogobulin, haptoglobin, C-reactive protein, and serum amyloid P (P < 0.001). Organ failure, infection rate, and mortality did not differ between groups (P > 0.2). CONCLUSIONS: Transfusion of CPRBCs is as safe and effective as transfusion of young and old LPRBCs and provides a mechanism to deliver PRBCs in a wide variety of settings.

Effect of ascorbic acid concentrations on hemodynamics and inflammation following lyophilized plasma transfusion.

BACKGROUND: Compared with lyophilized plasma (LP) buffered with other acids, LP with ascorbic acid (AA) attenuates systemic inflammation and DNA damage in a combat relevant polytrauma swine model. We hypothesize that increasing concentrations of AA in transfused LP will be safe, will be hemodynamically well tolerated, and will attenuate systemic inflammation following polytraumatic injury and hemorrhage in swine. METHODS: This prospective, randomized, blinded study involved 52 female swine. Forty animals were subjected to our validated polytrauma model and resuscitated with LP. Baseline control sham (n = 6), operative control sham (n = 6), low-AA (n = 10), medium-AA (n = 10), high-AA (n = 10) groups, and a hydrochloric acid control (HCL, n = 10) were randomized. Hemodynamics, thrombelastography, and blood chemistries were assessed. Inflammatory cytokines (tumor necrosis factor α, interleukin 6 [IL-6], C-reactive protein, and IL-10) and DNA damage were measured at baseline, 2 hours, and 4 hours after liver injury. Significance was set at p < 0.05, with a Bonferroni correction for multiple comparisons. RESULTS: Hemodynamics, shock, and blood loss were similar between groups. All animals had robust procoagulant activity 2 hours following liver injury. Inflammation was similar between groups at baseline, and AA groups remained similar to HCL following liver injury. IL-6 and tumor necrosis factor α were increased at 2 hours and 4 hours compared with baseline within all groups (p < 0.008). DNA damage increased at 2 hours compared with baseline in all groups (p < 0.017) and further increased at 4 hours compared with baseline in HCL, low-, and high-AA groups (p < 0.005). C-reactive protein was similar between and within groups. IL-10 increased at 2 hours compared with baseline in low- and high-AA groups and remained elevated at 4 hours compared with baseline in the low-AA group (all, p < 0.017). CONCLUSION: Concentrations of AA were well tolerated and did not diminish the procoagulant activity of LP. Within our tested range of concentrations, AA can safely be used to buffer LP.

A controlled resuscitation strategy is feasible and safe in hypotensive trauma patients: results of a prospective randomized pilot trial.

BACKGROUND: Optimal resuscitation of hypotensive trauma patients has not been defined. This trial was performed to assess the feasibility and safety of controlled resuscitation (CR) versus standard resuscitation (SR) in hypotensive trauma patients. METHODS: Patients were enrolled and randomized in the out-of-hospital setting. Nineteen emergency medical services (EMS) systems in the Resuscitation Outcome Consortium participated. Eligible patients had an out-of-hospital systolic blood pressure (SBP) of 90 mm Hg or lower. CR patients received 250 mL of fluid if they had no radial pulse or an SBP lower than 70 mm Hg and additional 250-mL boluses to maintain a radial pulse or an SBP of 70 mm Hg or greater. The SR group patients received 2 L initially and additional fluid as needed to maintain an SBP of 110 mm Hg or greater. The crystalloid protocol was maintained until hemorrhage control or 2 hours after hospital arrival. RESULTS: A total of 192 patients were randomized (97 CR and 95 SR). The CR and SR groups were similar at baseline. The mean (SD) crystalloid volume administered during the study period was 1.0 L (1.5) in the CR group and 2.0 L (1.4) in the SR group, a difference of 1.0 L (95% confidence interval [CI], 0.6-1.4). Intensive care unit-free days, ventilator-free days, renal injury, and renal failure did not differ between the groups. At 24 hours after admission, there were 5 deaths (5%) in the CR group and 14 (15%) in the SR group (adjusted odds ratio, 0.39; 95% CI, 0.12-1.26). Among patients with blunt trauma, 24-hour mortality was 3% (CR) and 18% (SR) with an adjusted odds ratio of 0.17 (0.03-0.92). There was no difference among patients with penetrating trauma (9% vs. 9%; adjusted odds ratio, 1.93; 95% CI, 0.19-19.17). CONCLUSION: CR is achievable in out-of-hospital and hospital settings and may offer an early survival advantage in blunt trauma. A large-scale, Phase III trial to examine its effects on survival and other clinical outcomes is warranted. LEVEL OF EVIDENCE: Therapeutic study, level I.

Reconstitution fluid type does not affect pulmonary inflammation or DNA damage following infusion of lyophilized plasma.

BACKGROUND: Dysfunctional inflammation following traumatic hemorrhage can lead to multiple-organ failure and death. In our polytrauma swine model, lyophilized plasma (LP) reconstituted with sterile water and ascorbic acid suppressed systemic inflammation and attenuated DNA damage. However, it remains unknown whether the inflammatory response is affected by the type of fluid used to reconstitute LP. We hypothesized that common resuscitation fluids such as normal saline (LP-NS), lactated Ringer's solution (LP-LR), Hextend (LP-HX), or sterile water (LP-SW) would yield similar inflammation profiles and DNA damage following LP reconstitution and transfusion. METHODS: This was a randomized, prospective, blinded animal study. LP was reconstituted to 50% of original volume with NS, LR, HX, or SW buffered with 15-mM ascorbic acid. Forty swine were subjected to a validated model of polytrauma, hemorrhagic shock, and Grade V liver injury and resuscitated with LP. Serum interleukin 6 (IL-6), IL-10, plasma C-reactive protein, and 8-hydroxy-2-deoxyguanosine concentrations were assessed for systemic inflammation and DNA damage at baseline, 2 hours, and 4 hours following liver injury. Lung inflammation was evaluated by Real Time Polymerize Chain Reaction (RT-PCR). RESULTS: Reconstituted LP pH was similar between groups before resuscitation. IL-6 and IL-10 increased at 2 hours and 4 hours compared with baseline in all groups (p < 0.017). DNA damage increased at 2 hours and 4 hours compared with baseline and from 2 hours to 4 hours in the LP-NS, LP-LR, and LP-SW groups (all p < 0.017). Animals resuscitated with LP-HX not only demonstrated increased DNA damage at 4 hours versus baseline but also had the lowest C-reactive protein level at 2 hours and 4-hours (p < 0.017). Overall, differences between groups were similar for DNA damage and lung inflammation. CONCLUSION: Reconstitution fluid type does not affect inflammatory cytokine profiles or DNA damage following LP transfusion in this swine polytrauma model. Based on universal availability, these data suggest that sterile water is the most logical choice for LP reconstitution in humans. LEVEL OF EVIDENCE: Prognostic, level II.

Diet-induced obesity prevents the development of acute traumatic coagulopathy.

BACKGROUND: Obesity and hemorrhagic shock following trauma are predictors of mortality but have conflicting effects on coagulation. Following hemorrhage, tissue injury and hypoperfusion lead to acute traumatic coagulopathy (ATC), producing a hypocoagulable state. Inversely, obesity promotes clotting and impairs fibrinolysis to yield a hypercoagulable state. High rates of venous thromboembolism, organ failure, and early mortality may be caused by hypercoagulability in obese patients. We hypothesize that obesity prevents the development of ATC following injury-induced hemorrhagic shock. METHODS: Male Sprague-Dawley rats (250-275 g) were fed a high-fat diet (32%kcal from fat) for 4 weeks to 6 weeks and diverged into obesity-resistant (OR, n = 9) and obesity-prone (OP, n = 9) groups. Age-matched control (CON) rats were fed normal diet (10% kcal from fat, n = 9). Anesthetized rats were subjected to an uncontrolled hemorrhage by a Grade V splenic injury to a mean arterial pressure (MAP) of 40 mm Hg. Hypotension (MAP, 30-40 mm Hg) was maintained for 30 minutes to induce shock. MAP, heart rate, lactate, base excess, cytokines, blood loss, and thrombelastography (TEG) parameters were measured before and after hemorrhagic shock. RESULTS: At baseline, OP rats exhibited a shorter time to 20-mm clot (K), and higher rate of clot formation (α angle), clot strength (maximal amplitude), and coagulation index, compared with the CON rats (p < 0.05), indicating enhanced coagulation. Physiologic parameters following shock were similar between groups. In the CON and OR rats, shock prolonged the time to clot initiation (R) and K and decreased α angle and coagulation index (all p < 0.05 vs. baseline). In contrast, shock had no effect on these TEG parameters in the OP rats. Maximal amplitude was the only TEG parameter affected by shock in the OP rats, which was decreased in all groups. CONCLUSION: Obesity prevents the development of ATC following hemorrhage shock. Complications associated with obesity following hemorrhagic shock may be attributed to the preserved hypercoagulable state.

Complete cervical spinal cord injury above C6 predicts the need for tracheostomy.

BACKGROUND: Failed extubation and delayed tracheostomy contribute to poor outcomes in patients with a traumatic spinal cord injury (SCI). We determined if the level and completeness of SCI predict the need for tracheostomy. METHODS: Data from 256 patients with SCI between C1 and T3 with or without tracheostomy were retrospectively analyzed. Logistic regression identified predictors for tracheostomy. Data are presented as raw percentage or odds ratio (OR) with 95% confidence interval. P < .05 indicates significance. RESULTS: Complete spinal cord injuries were common in patients requiring tracheostomy (55% vs 18%, P < .05), and predicted the need for tracheostomy (OR: 6.4 (3.1 to 13.5), P < .05). An injury above C6 predicted the need for tracheostomy in patients with complete injury (OR: 3.7 (1 to 11.9), P < .05), but not incomplete injury (OR: .7 (.3 to 1.9); P = .53). CONCLUSION: Tracheostomy is unlikely in patients with incomplete SCI, regardless of the level of injury. Patients with complete SCI above C6 are likely to require tracheostomy.

Comparison of the hemostatic efficacy of low-volume lyophilized plasma reconstituted using sterile water, lactated Ringer's, normal saline, and Hextend solutions.

BACKGROUND: Low-volume ascorbic acid-buffered reconstituted lyophilized plasma (LP) provides logistic advantages, reduces the risks for large-volume resuscitation, modulates inflammation, and is equally effective for hemostatic resuscitation as full-volume LP. We compared the physiologic effects of resuscitation using LP reconstituted with sterile water (LP-SW), lactated Ringer's solution (LP-LR), normal saline (LP-NS), and Hextend (LP-Hx). METHODS: Plasma was collected from swine, lyophilized, and then reconstituted into four test solutions: LP-SW, LP-LR, LP-NS, or LP-Hx. Forty swine were anesthetized and subjected to a validated model of polytrauma and hemorrhagic shock (including a Grade V liver injury), then randomized to receive one of the four test solutions. Physiologic parameters, blood loss, lactate, and hematocrit were followed up. Coagulation status was evaluated using thrombelastography. Inflammatory mediator expression was evaluated by multiplex serum assay. RESULTS: Forty animals were included in the study (10 animals per group). One animal died following LP-Hx resuscitation. There was less blood loss in the LP-SW and LP-LR groups compared with the LP-NS and LP-Hx groups (p < 0.05). The LP-SW group exhibited less early coagulopathic changes by thrombelastography, and the LP-Hx group had persistently elevated international normalized ratios at the end of the study period (p < 0.05). Serum interleukin 6 was lower after 4 hours in the LP-SW group compared with LP-NS (p < 0.05). CONCLUSION: Resuscitation using low-volume LP-SW and LP-LR buffered with ascorbic acid confers an anti-inflammatory benefit and results in less blood loss. Sterile water is a safe, cost-effective, and universally available fluid for creating a low-volume hemostatic LP resuscitation solution.

Correlation of conventional thrombelastography and rapid thrombelastography in trauma.

BACKGROUND: Conventional thrombelastography has been in use for over 6 decades and provides a functional assay of coagulation. Rapid thrombelastography was developed to provide more rapid comprehensive analysis of coagulation status in an emergency setting. The purpose of this study was to determine the correlation of rapid thrombelastographic values with conventional thrombelastographic values in trauma patients. METHODS: We performed a prospective study on trauma patients at a university level 1 trauma center. Conventional thrombelastography and rapid thrombelastography were performed on 190 consecutive major trauma patients upon admission between 2010 and 2012. Conventional thrombelastographic and rapid thrombelastographic parameters were analyzed using bivariate analysis with Pearson correlation. Group comparisons were performed using the Mann-Whitney U test. RESULTS: Patients were predominantly male (71.6%, P < .05) with a median Injury Severity Score of 17 (range 10 to 29) and a median age of 43 years (range 29 to 53 years). There were significantly more patients with blunt trauma than penetrating trauma (72% vs 28%, P < .05). There was a strong correlation between the rapid thrombelastographic and conventional thrombelastographic maximal amplitude value, which represents platelet function (r = .80). There was a moderate correlation between the G (overall clot strength, r = .70), k (speed of clot formation, r = .66), and α-angle (r = .38), which reflects the degree of fibrin cross-linking. Lysis at 30 minutes correlated poorly (r = .19). CONCLUSIONS: Overall, there is a strong correlation between rapid thrombelastography and conventional thrombelastography in terms of overall clot strength and platelet function. There is a moderate correlation in assessing the degree of fibrin cross-linking and a poor correlation in evaluating thrombolysis. These correlations should be considered when evaluating coagulation status using rapid thrombelastography.