A Multifunctional, Low-Volume Resuscitation Cocktail Improves Vital Organ Blood Flow and Hemostasis in a Pig Model of Polytrauma with Traumatic Brain Injury

The resuscitation of polytrauma with hemorrhagic shock and traumatic brain injury (TBI) is a balance between permissive hypotension and maintaining vital organ perfusion. There is no current optimal solution. This study tested whether a multifunctional resuscitation cocktail supporting hemostasis and perfusion could mitigate blood loss while improving vital organ blood flow during prolonged limited resuscitation. Anesthetized Yorkshire swine were subjected to fluid percussion TBI, femur fracture, catheter hemorrhage, and aortic tear. Fluid resuscitation was started when lactate concentration reached 3–4 mmol/L. Animals were randomized to one of five groups. All groups received hydroxyethyl starch solution and vasopressin. Low- and high-dose fibrinogen (FBG) groups additionally received 100 and 200 mg/kg FBG, respectively. A third group received TXA and low-dose FBG. Two control groups received albumin, with one also including TXA. Animals were monitored for up to 6 h. Blood loss was decreased and vital organ blood flow was improved with low- and high-dose fibrinogen compared to albumin controls, but survival was not improved. There was no additional benefit of high- vs. low-dose FBG on blood loss or survival. TXA alone decreased blood loss but had no effect on survival, and combining TXA with FBG provided no additional benefit. Pooled analysis of all groups containing fibrinogen vs. albumin controls found improved survival, decreased blood loss, and improved vital organ blood flow with fibrinogen delivery. In conclusion, a low-volume resuscitation cocktail consisting of hydroxyethyl starch, vasopressin, and fibrinogen concentrate improved outcomes compare to controls during limited resuscitation of polytrauma.

Percutaneous treatment of severe retroperitoneal hematoma after percutaneous coronary intervention

We describe a patient who developed severe retroperitoneal and intraperitoneal bleeding complicating femoral arterial catheterization for Percutaneous coronary intervention. Balloon tamponade of the actively bleeding femoral artery was effective in sealing off the leakage. This management strategy for this problem emphasizing an anatomical based interventional approach if the patient does not stabilize with volume resuscitation.

Volume Resuscitation in the Acutely Hemorrhaging Patient: Historic Use to Current Applications

Acute hemorrhage in small animals results from traumatic and non-traumatic causes. This review seeks to describe current understanding of the resuscitation of the acutely hemorrhaging small animal (dog and cat) veterinary patient through evaluation of pre-clinical canine models of hemorrhage and resuscitation, clinical research in dogs and cats, and selected extrapolation from human medicine. The physiologic dose and response to whole blood loss in the canine patient is repeatable both in anesthetized and awake animals and is primarily characterized clinically by increased heart rate, decreased systolic blood pressure, and increased shock index and biochemically by increased lactate and lower base excess. Previously, initial resuscitation in these patients included immediate volume support with crystalloid and/or colloid, regardless of total volume, with a target to replace lost vascular volume and bring blood pressure back to normal. Newer research now supports prioritizing hemorrhage control in conjunction with judicious crystalloid administration followed by early consideration for administration of platelets, plasma and red blood during the resuscitation phase. This approach minimizes blood loss, ameliorates coagulopathy, restores oxygen delivery and correct changes in the glycocalyx. There are many hurdles in the application of this approach in clinical veterinary medicine including the speed with which the bleeding source is controlled and the rapid availability of blood component therapy. Recommendations regarding the clinical approach to volume resuscitation in the acutely hemorrhaging veterinary patient are made based on the canine pre-clinical, veterinary clinical and human literature reviewed.

Learning to Treat Hypotensive Episodes in Sepsis Patients Using a Counterfactual Reasoning Framework

The optimal treatment strategy for volume resuscitation and vasopressor dosing to combat hypotensive episodes in septic patients remains a subject of ongoing controversy and can vary from clinician to clinician. We develop a machine learning approach to guide a fluid and vasopressor dosing strategy that adapts to patient-specific clinical states to improve the survival of septic patients. We adopt a model-free reinforcement learning (RL) framework in a continuous action space with a clinically significant reward function, and use a Switching Generalized Linear Model (SGLM) to characterize patient-specific clinical states. We use retrospective data from the MIMIC III database to train this model to learn volume resuscitation and vasopressor dosing strategies among the 5,366 patients (totalling 352,328 unique hourly measurements) with ICU-onset sepsis or septic shock, as diagnosed by the Sepsis-3 definition. The RL agent receives short- and long-term rewards associated with optimizing in-hospital survival and avoiding end-organ damage to learn volume resuscitation and vasopressor dosing strategies. On average, the RL agent learns to resuscitate patients earlier than clinicians with a fluid bolus (one hour vs. four hours after the diagnosis of sepsis), and improves the expected survival by ≈ 3%. Our preliminary results indicate that adherence to RL-based individualized fluid and vasopressor dosing recommendations is associated with a significant mortality reduction in septic patients, even after adjusting for severity of illness.

Shenfu injection improves cerebral microcirculation and reduces brain injury in a porcine model of hemorrhagic shock; SFI reduces brain injury after hemorrhagic shock

BACKGROUND: Shenfu injection (SFI) is a traditional Chinese herbal medicine which has been clinically used for treatment of septic shock and cardiac shock. The aim of this study was to clarify effects of SFI on cerebral microcirculation and brain injury after hemorrhagic shock (HS). METHODS: Twenty-one domestic male Beijing Landrace pigs were randomly divided into three groups: SFI group (SFI, n = 8), saline group (SA, n = 8) or sham operation group (SO, n = 5). In the SFI group, animals were induced to HS by rapid bleeding to a mean arterial pressure of 40 mmHg within 10 minutes and maintained at 40±3 mmHg for 60 minutes. Volume resuscitation (shed blood and crystalloid) and SFI were given after 1 hour of HS. In the SA group, animals received the same dose of saline instead of SFI. In the SO group, the same surgical procedure was performed but without inducing HS and volume resuscitation. The cerebral microvascular flow index (MFI), nitric oxide synthase (NOS) expression, aquaporin-4 expression, interleukin-6, tumor necrosis factor-α (TNF-α) and ultrastructural of microvascular endothelia were measured. RESULTS: Compared with the SA group, SFI significantly improved cerebral MFI after HS. SFI up regulated cerebral endothelial NOS expression, but down regulated interleukin-6, TNF-α, inducible NOS and aquaporin-4 expression compared with the SA group. The cerebral microvascular endothelial injury and interstitial edema in the SFI group were lighter than those in the SA group. CONCLUSIONS: Combined application of SFI with volume resuscitation after HS can improve cerebral microcirculation and reduce brain injury.

Intra-abdominal Inferior Vena Cava Injuries: Operative Strategies and Outcomes

Visceral vascular injuries are relatively uncommon even in busy urban trauma centers. The inferior vena cava (IVC) is the most frequently injured visceral vein and can be a complex operative challenge. Despite advances in early volume resuscitation, improved transport times, prompt operative intervention, and hemorrhage control, mortality rates have remained largely unchanged. This article conducts an in-depth review of the literature surrounding IVC injuries and a detailed discussion of operative strategies and management as survivability is ultimately dependent on the grade of injury, location, and the presence of hemorrhagic shock.