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.

Principal component analysis of a swine injury model identifies multiple phenotypes in trauma.

BACKGROUND: Trauma is the third leading cause of death in the United States and the primary cause of death for people between the ages of 1 year and 44 years. In addition to tissue damage, trauma may also activate an inflammatory state known as trauma-induced coagulopathy (TIC) that is associated with clotting malfunctions, acidemia, and end-organ dysfunction. Prior work has also demonstrated benefit to acknowledging the type and severity of endothelial injury, coagulation derangements, and systemic inflammation in the management of trauma patients. This study builds upon prior work by combining laboratory, metabolic, and clinical metrics into an analysis of trauma phenotypes, evolution of phenotypes over time after trauma, and significance of trauma phenotype on mortality. METHODS: Seventy 3-month-old female Yorkshire crossbred swine were randomized to injury and resuscitation groups. Principal component analysis (PCA) of longitudinal swine TEG data (Reaction time, Alpha-Angle, Maximum Amplitude, and Clot Lysis at 30 minutes), pH, lactate, and MAP was completed in R at baseline, 1 hour postinjury, 3 hours postinjury, 6 hours postinjury, and 12 hours postinjury. Subjects were compared by principal component factor scores to assess differences in survival, injury severity, and treatment group. RESULTS: Among injured animals, three phenotypes were observed at each time point. Five phenotypes were associated with differences in survival, and of these, four were associated with differences in injury severity. Phenotype alignment was not significantly different by treatment group. CONCLUSION: This application of PCA to a set of coagulation, hemodynamic, and organ perfusion variables has identified multiple evolving phenotypes after trauma. Some of these phenotypes may correlate with injury severity and may have implications for survival. Next steps include validating these findings over greater numbers of subjects and exploring other machine-learning techniques for phenotype identification. LEVEL OF EVIDENCE: Level IV, Therapeutic/Care Management.

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.

FFP maintains normal coagulation while Kcentra induces a hypercoagulable state in a porcine model of pulmonary contusion and hemorrhagic shock.

BACKGROUND: Moderate injury can lead to a coagulopathy. Fresh frozen plasma (FFP) corrects coagulopathy by means of a balanced array of clotting factors. We sought to compare the late effects of FFP and a prothrombin complex concentrate (PCC) on the coagulopathy of trauma using a porcine model of pulmonary contusion (PC) and hemorrhagic shock (HS) designed to evaluate the organ protective effects of these treatments. METHODS: Female Yorkshire swine (40-50 kg) were randomized to receive PC + HS or control (instrumented and uninjured). A blunt PC was created using a captive bolt gun. To induce HS, a liver crush injury was performed. Eighty minutes after injury, swine were treated with 25 U·kg-1 PCC, 1 U FFP, or 50 mL lactated Ringer's vehicle in a blinded manner. Arterial blood samples were drawn every 6 hours. Swine were euthanized 48 hours postinjury. Data were analyzed by Pearson χ2, analysis of variance and Kruskal-Wallis tests with Tukey's or Mann-Whitney U tests for post hoc analysis. RESULTS: Twenty-seven swine received PC + HS, 3 groups of 9 per group received PCC, FFP, or vehicle. Nine were noninjured controls. When compared with control, PC + HS swine had significantly shortened R time at 6 hours, 36 hours, and 42 hours, decreased LY30 at 12 hours, shortened K time at 30 hours and reduced α angle at 42 hours. PC + HS swine showed significant differences between treatment groups in K and α angle at 3 hours, LY30 at 12 hours and 18 hours, and MA at 12 hours, 18 hours, and 30 hours. Post hoc analysis was significant for higher α angle in PCC versus vehicle at 3 hours, higher MA in vehicle versus PCC at 12 hours and 18 hours, and higher LY30 in PCC versus vehicle at 18 hours (p < 0.012) with no significant differences between FFP and vehicle. CONCLUSION: Severe injury with HS induced a coagulopathy in swine. While FFP maintained normal coagulation following injury, PCC induced more rapid initial clot propagation in injured animals.

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.

Fibrinolytic Activation in Patients with Progressive Intracranial Hemorrhage after Traumatic Brain Injury.

Progression of intracranial hemorrhage (PICH) is a significant cause of secondary brain injury in patients with traumatic brain injury (TBI). Previous studies have implicated a variety of mediators that contribute to PICH. We hypothesized that patients with PICH would display either a hypocoagulable state, hyperfibrinolysis, or both. We conducted a prospective study of adult trauma patients with isolated TBI. Blood was obtained for routine coagulation assays, platelet count, fibrinogen, thrombelastography, markers of thrombin generation, and markers of fibrinolysis at admission and 6, 12, 24, and 48 h. Univariate analyses were performed to compare baseline characteristics between groups. Linear regression models were created, adjusting for baseline differences, to determine the relationship between individual assays and PICH. One hundred forty-one patients met entry criteria, of whom 71 had hemorrhage progression. Patients with PICH had a higher Injury Severity Score and Abbreviated Injury Scale score (head), a lower Glasgow Coma Scale score, and lower plasma sodium on admission. Patients with PICH had higher D-dimers on admission. After adjusting for baseline differences, elevated D-dimers remained significantly associated with PICH compared to patients without PICH at admission. Hypocoagulation was not significantly associated with PICH in these patients. The association between PICH and elevated D-dimers early after injury suggests that fibrinolytic activation may contribute to PICH in patients with TBI.

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.

The effects of human prothrombin complex concentrate on hemorrhagic shock-induced lung injury in rats: Implications for testing human blood products in rodents.

BACKGROUND: Hemorrhagic shock (HS) and trauma can result in an endotheliopathy of trauma, characterized by endothelial compromise, inflammation, and aberrant coagulation. Kcentra, a prothrombin concentrate, has been demonstrated to mitigate pulmonary vascular leak in a murine model of HS. We investigated the effects of Kcentra in a rat model of HS, to achieve physiologic endpoints of relevance. METHODS: Rats subjected to a grade intravenous splenic injury and controlled hemorrhage for 60 minutes were resuscitated with shed volumes of (1) Lactated Ringer's (LR) solution, (2) LR + 20 IU/kg Kcentra, (3) LR + 50 IU/kg Kcentra, (4) rat fresh frozen plasma (RFFP), or (5) human fresh frozen plasma (HFFP). Blood was harvested for monitoring metabolic and coagulation function. Rat lungs were evaluated for lung injury and permeability. RESULTS: Animals resuscitated with LR displayed a significant increase in pulmonary vascular permeability (sham, 407.9 ± 122.4; shock + LR, 2040 ± 1462). Resuscitation with RFFP (606.5 ± 169.3) reduced leak; however, treatment with Kcentra (HS + Kcentra [20 IU/kg]: 1792 ± 903.4, HS + Kcentra [50 IU/kg]: 1876 ± 1103), and HFFP (1450 ± 533.2) had no significant effect on permeability. Kcentra modestly altered clotting parameters. Metabolic measures, such as lactate, pH, and base deficit, were restored to baseline levels by both RFFP and HFFP, but not Kcentra or LR. CONCLUSION: Kcentra did not alter pulmonary vascular permeability, but modestly increased clotting potential in injured rats. This suggests that there may be a xenogenic reaction of human products in rats and that the effects of Kcentra on vascular stability may be distinct from its ability to modulate clotting. Our data indicate that the species chosen and utilized for in vivo preclinical testing of human derived blood products is of critical importance in determining their efficacy in animal models and is the primary impetus to communicate these results.

Use of bilobed partial resuscitative endovascular balloon occlusion of the aorta is logistically superior in prolonged management of a highly lethal aortic injury.

BACKGROUND: Resuscitative endovascular balloon occlusion of the aorta (REBOA) is a viable technique for management of noncompressible torso hemorrhage. The major limitation of the current unilobed fully occlusive REBOA catheters is below-the-balloon ischemia-reperfusion complications. We hypothesized that partial aortic occlusion with a novel bilobed partial (p)REBOA-PRO would result in the need for less intraaortic balloon adjustments to maintain a distal goal perfusion pressure as compared with currently available unilobed ER-REBOA. METHODS: Anesthetized (40-50 kg) swine randomized to control (no intervention), ER-REBOA, or pREBOA-PRO underwent supraceliac aortic injury. The REBOA groups underwent catheter placement into zone 1 with initial balloon inflation to full occlusion for 10 minutes followed by gradual deflation to achieve and subsequently maintain half of the baseline below-the-balloon mean arterial pressure (MAP). Physiologic data and blood samples were collected at baseline and then hourly. At 4 hours, the animals were euthanized, total blood loss and urine output were recorded, and tissue samples were collected. RESULTS: Baseline physiologic data and basic laboratories were similar between groups. Compared with control, interventions similarly prolonged survival from a median of 18 minutes to over 240 minutes with comparable mortality trends. Blood loss was similar between partial ER-REBOA (41%) and pREBOA-PRO (51%). Partial pREBOA-PRO required a significantly lower number of intraaortic balloon adjustments (10 ER-REBOA vs. 3 pREBOA-PRO, p < 0.05) to maintain the target below-the-balloon MAP. The partial ER-REBOA group developed significantly increased hypercapnia, fibrin clot formation on TEG, liver inflammation, and IL-10 expression compared with pREBOA-PRO. CONCLUSION: In this highly lethal aortic injury model, use of bilobed pREBOA-PRO for a 4-hour partial aortic occlusion was logistically superior to unilobed ER-REBOA. It required less intraaortic balloon adjustments to maintain target MAP and resulted in less inflammation.

Aggressive treatment of acute kidney injury and hyperkalemia improves survival in a combat relevant trauma model in swine.

INTRODUCTION: Our swine model of pulmonary contusion (PC) and hemorrhagic shock (HS) was initially complicated by renal failure, hyperkalemia, and premature death. To study the effects of novel therapies on organ failure, improved survival was necessary requiring the design of an aggressive treatment regimen. METHODS: Anesthetized swine sustained either PC or PC with grade V liver injury to induce HS (PC + HS). After injury, animals were resuscitated followed by either standard care (SC) with maintenance intravenous fluids (IVF) and treatment at potassium level of 6.0 mmol/L (n = 7; 3 PC, 4 PC + HS) or aggressive care (AC) with increased initial IVF, early and frequent potassium monitoring, and treatment at potassium level of 5.0 mmol/L (n = 15, 8 PC, 7 PC + HS). Hyperkalemia was treated with calcium, insulin, and glucose in both groups. RESULTS: Survival to 48 h was achieved in 13/15 (87%) in the AC group and 2/7 (29%) in the SC group (p = 0.014). Compared to SC, AC improved median survival (48 vs. 18 h, p = 0.008) and lowered potassium (5.0 vs. 7.5 mmol/L), creatinine (2.4 vs. 4.0 mg/dL), BUN (27.5 vs. 39.0 mg/dL), and lactate (0.97 vs. 3.57 mmol/L) at the last observed time-point prior to death. For PC + HS animals, survival to 48 h was achieved in 6/7 in the AC group and 0/4 in the SC group with an improved median survival in the AC group (48 vs. 18 h, p = 0.011) DISCUSSION: Aggressive and early hyperkalemia treatment prolongs survival while reducing kidney injury and potassium levels in a combat relevant injury model in swine.

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.