The anesthesiologist's guide to swine trauma physiology research: a report of two decades of experience from the experimental traumatology laboratory.

PURPOSE: Swine are one of the major animal species used in translational research, with unique advantages given the similar anatomic and physiologic characteristics as man, but the investigator needs to be familiar with important differences. This article targets clinical anesthesiologists who are proficient in human monitoring. We summarize our experience during the last two decades, with the aim to facilitate for clinical and non-clinical researchers to improve in porcine research. METHODS: This was a retrospective review of 337 swine with a mean (SD) weight 60 (4.2) kg at the Experimental Traumatology laboratory at Södersjukhuset (Stockholm south general hospital) between 2003 and 2023, including laboratory parameters and six CT-angiography examinations. RESULTS: Swine may be ventilated through the snout using a size 2 neonatal mask. Intubate using a 35 cm miller laryngoscope and an intubating introducer. Swine are prone to alveolar atelectasis and often require alveolar recruitment. Insert PA-catheters through a cut-down technique in the internal jugular vein, and catheters in arteries and veins using combined cut-down and Seldinger techniques. Cardiopulmonary resuscitation is possible and lateral chest compressions are most effective. Swine are prone to lethal ventricular arrhythmias, which may be reversed by defibrillation. Most vital parameters are similar to man, with the exception of a higher core temperature, higher buffer bases and increased coagulation. Anesthesia methods are similar to man, but swine require five times the dose of ketamine. CONCLUSION: Swine share anatomical and physiological features with man, which allows for seamless utilization of clinical monitoring equipment, medication, and physiological considerations.

Blast polytrauma with hemodynamic shock, hypothermia, hypoventilation and systemic inflammatory response: description of a new porcine model.

PURPOSE: In the past decade blast injuries have become more prevalent. Blast trauma may cause extensive injuries requiring improved early resuscitation and prevention of haemorrhage. Randomized prospective trials are logistically and ethically challenging, and large animal models are important for further research efforts. Few severe blast trauma models have been described, which is why we aimed to establish a comprehensive polytrauma model in accordance with the criteria of the Berlin definition of polytrauma and with a survival time of > 2 h. Multiple blast injuries to the groin and abdomen were combined with hypoperfusion, respiratory and metabolic acidosis, hypoventilation, hypothermia and inflammatory response. The model was compared to lung contusion and haemorrhage. METHODS: 16 landrace swine (mean weight 60.5 kg) were randomized to "control" (n = 5), "chest trauma/hem" by lung contusion and class II haemorrhage (n = 5), and "blast polytrauma" caused by multiple blast injuries to the groin and abdomen, class II haemorrhage, lipopolysaccharide (LPS) infusion and hypothermia 32 °C (n = 6). RESULTS: The blast polytrauma group had an Injury Severity Score of 57 which resulted in haemodynamic shock, hypothermia, respiratory and metabolic acidosis and inflammatory response. The chest trauma/hem group had an Injury Severity Score of 9 and less profound physiologic effects. Physiologic parameters presented a dose-response relationship corresponding to the trauma levels. CONCLUSION: A comprehensive blast polytrauma model fulfilling the Berlin polytrauma criteria, with a high trauma load and a survival time of > 2 h was established. A severe, but consistent, injury profile was accomplished enabling the addition of experimental interventions in future studies, particularly of immediate resuscitation efforts including whole blood administration, trauma packing and haemostasis.

Increased crystalloid fluid requirements during zone 3 Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) versus Abdominal Aortic and Junctional Tourniquet (AAJT) after class II hemorrhage in swine.

PURPOSE: Pelvic and lower junctional hemorrhage result in a significant amount of trauma related deaths in military and rural civilian environments. The Abdominal Aortic and Junctional Tourniquet (AAJT) and infra-renal (zone 3) Resuscitative Endovascular Balloon Occlusion of the Aorta (REBOA) are two options for resuscitation of patients with life threatening blood loss from and distal to the pelvis. Evidence suggest differences in the hemodynamic response between AAJT and zone 3 REBOA, but fluid management during resuscitation with the devices has not been fully elucidated. We compared crystalloid fluid requirements (Ringer's acetate) between these devices to maintain a carotid mean arterial pressure (MAP) > 60 mmHg. METHODS: 60 kg anesthetized and mechanically ventilated male pigs were subjected to a mean 1030 (range 900-1246) mL (25% of estimated total blood volume, class II) haemorrhage. AAJT (n = 6) or zone 3 REBOA (n = 6) were then applied for 240 min. Crystalloid fluids were administered to maintain carotid MAP. The animals were monitored for 30 min after reperfusion. RESULTS: Cumulative resuscitative fluid requirements increased 7.2 times (mean difference 2079 mL; 95% CI 627-3530 mL) in zone 3 REBOA (mean 2412; range 800-4871 mL) compared to AAJT (mean 333; range 0-1000 mL) to maintain target carotid MAP. Release of the AAJT required vasopressor support with norepinephrine infusion for a mean 9.6 min (0.1 µg/kg/min), while REBOA release required no vasopressor support. CONCLUSION: Zone 3 REBOA required 7.2 times more crystalloids to maintain the targeted MAP. The AAJT may therefore be considered in a situation of hemorrhagic shock to limit the need for crystalloid infusions, although removal of the AAJT caused more severe hemodynamic and metabolic effects which required vasopressor support.

The swine as a vehicle for research in trauma-induced coagulopathy: Introducing principal component analysis for viscoelastic coagulation tests.

BACKGROUND: Uncontrolled bleeding is the leading cause of potentially preventable deaths among trauma patients. Tissue injury and shock result in trauma-induced coagulopathy (TIC). There are still uncertainties regarding detection methods and best practice management for TIC, and a deeper understanding of the pathophysiology requires robust animal models. The applicability of swine in coagulation studies, particularly after trauma has not been sufficiently elucidated. We, therefore, evaluated the swine as a vehicle for TIC research in a selection of trauma modalities. METHODS: Twenty-six landrace swine (3 females/23 males) (mean weight, 60.0 kg) were anesthetized and randomized to negative controls, receiving no manipulation (n = 5), positive controls by hemodilution (n = 5), pulmonary contusion without hemorrhage (n = 5), pulmonary contusion with hemorrhage (n = 5), and blast polytrauma with hypothermia, hypoperfusion, hypoventilation, and systemic inflammation (n = 6). A comprehensive coagulation panel was analyzed at baseline, 20 minutes and 120 minutes after trauma. RESULTS: PT(INR), aPTT, thrombocytes, and fibrinogen did not change after trauma. D-dimer increased (p < 0.0001), prothrombin decreased (p < 0.05) and aPC decreased (p < 0.01) after polytrauma. PAI-1 decreased after pulmonary contusion with hemorrhage (p < 0.05). Positive controls displayed changes in PT(INR), thrombocytes, fibrinogen, prothrombin, aPC (p < 0.05). Principal Component Analysis of rotational thromboelastometry presented pathologic coagulation profiles in both polytrauma and positive control groups with vectors extending outside the 95% confidence interval, which were not detected in negative controls. CONCLUSION: Coagulopathy was induced after severe porcine blast polytrauma, specifically detected in rotational thromboelastometry. A novel method for principal component analysis of viscoelastic tests was introduced which may increase the detection sensitivity and differentiation of TIC phenotypes and should be further investigated in trauma populations.

Transition from abdominal aortic and junctional tourniquet to zone 3 resuscitative endovascular balloon occlusion of the aorta is feasible with hemodynamic support after porcine class IV hemorrhage.

BACKGROUND: Traumatic hemorrhage remains a major cause of death in rural civilian and combat environments. Potential interventions to control hemorrhage from the pelvis and lower junctional regions include the abdominal aortic and junctional tourniquet (AAJT) and resuscitative endovascular balloon occlusion of the aorta (REBOA). The AAJT requires low technical skills and may thus be used by nonmedical professionals, but is associated with time-dependent ischemic complications. In combination with delayed patient evacuation, it may therefore be deleterious. Transition to zone 3 REBOA in higher levels of care may be a possibility to maintain hemostasis, mitigate adverse effects and enable surgery in patients resuscitated with the AAJT. It is possible that a transition between the interventions could lead to hemodynamic penalties. Therefore, we investigated the feasibility of replacing the AAJT with zone 3 REBOA in a porcine model of uncontrolled femoral hemorrhage. METHODS: Domestic pigs (n = 12) averaging 57 kg were exposed to a class IV uncontrolled hemorrhage from the common femoral artery. The animals were randomized to 60-minute AAJT (n = 6) or 30-minute AAJT with transition to 30-minute zone 3 REBOA. Hemodynamic and metabolic parameters and ultrasonographic measurements of the common femoral artery were collected. RESULTS: Transition from AAJT to zone 3 REBOA caused a significant decrease in mean arterial pressure (25 mm Hg). Hemostasis was maintained. The common femoral artery diameter decreased by 1.8 mm (38%) after hemorrhage and further 0.7 mm (23%) after aortic occlusion. CONCLUSION: Transition from AAJT to zone 3 REBOA after a class IV bleeding is feasible with hemodynamic support. Vascular access to the femoral artery for REBOA insertion poses a technical challenge after hemorrhage and AAJT application. LEVEL OF EVIDENCE: Laboratory animal study, level IV.