Comparison of a new hemostatic agent to current combat hemostatic agents in a Swine model of lethal extremity arterial hemorrhage.

BACKGROUND: Gaining hemostatic control of lethal vascular injuries sustained in combat using topical agents remains a challenge. Recent animal testing using a lethal arterial injury model has demonstrated that QuikClot zeolite granules (QCG) and the HemCon chitosan bandage (HC) are not capable of providing hemostasis and improving survival over the Army gauze field bandage (AFB). We have developed a new hemostatic agent consisting of a granular combination of a smectite mineral and a polymer (WoundStat) capable of producing hemostasis in the face of high-pressure arterial bleeding. We compared the performance of WoundStat (WS) to QCG, HC, AFB, and the new QuikClot zeolite Advance Clotting Sponge (ACS) in a lethal vascular injury model. METHODS: Hemostatic agents were tested using a lethal femoral artery vascular injury model. Twenty-five (5 per group) male swine (42 kg +/- 3 kg) were anesthetized, instrumented, and splenectomized. A lethal femoral artery injury was produced by creating a 6-mm arteriotomy in the vessel. After 45 seconds of hemorrhage, animals were randomized to be treated with AFB (control group), HC, QCG, ACS, or WS. Pressure (200 mm Hg) was applied over the product in the wound for 3 minutes. A second application and 3 additional minutes of pressure was provided if hemostasis was not achieved. Fluid resuscitation was begun at the time of application with 500 mL of Hextend, followed by lactated Ringer's solution at 100 mL/min to achieve and maintain a postapplication mean arterial blood pressure of 65 mm Hg. Animals were observed for 180 minutes or until death. Primary endpoints were survival, survival time, post-treatment blood loss, and amount of resuscitation fluid. RESULTS: All animals treated with WS survived to 180 minutes and required only a single application. No animal in the AFB, QCG, or ACS group survived. One animal in the HC group survived. Survival (p < 0.05) and survival times (p < 0.0001) for WS animals were significantly greater than for all other groups. No significant difference in survival or survival time existed between the AFB, QCG, ACS, or HC groups. Post-treatment blood loss (p = 0.0099) and postresuscitation fluid volume (p = 0.006) was significantly less for animals treated with WS than for all other groups. No significant difference in these parameters existed between the AFB, QCG, ACS, and HC groups. CONCLUSION: WS was superior to the other hemostatic agents tested in this study of lethal arterial vascular injury. Additional study is warranted on this agent to determine its potential for use in combat and civilian trauma.

Dynamic Limb Bioimpedance and Inferior Vena Cava Ultrasound in Patients Undergoing Hemodialysis.

Assessment of volume status in critically ill patients poses a challenge to clinicians. Measuring changes in the inferior vena cava (IVC) diameter using ultrasound is becoming a standard tool to assess volume status. Ultrasound requires physicians with significant training and specialized expensive equipment. It would be of significant value to be able to obtain this measurement continuously without physician presence. We hypothesize that dynamic changes in limb's bioimpedance in response to respiration could be used to predict changes in IVC. Forty-six subjects were tested a hemodialysis session. Impedance was measured via electrodes placed on the arm. Simultaneously, the IVC diameter was assessed by ultrasound. Subjects were asked to breathe spontaneously and perform respiratory maneuvers using a respiratory training device. Impedance (dz) was determined and compared with change in IVC diameter (dIVC; r = 0.76, p < 0.0001). There was significant relationship between dz and dIVC (p< 0.0001). Receiver-operator curves for dz at thresholds of dIVC (20% to70%) demonstrated high predictive power with areas under the curves (0.87-0.99, p < 0.0001). This evaluation suggests that real-time dynamic changes in limb impedance are capable of tracking a wide range of dynamic dIVC. This technique might be a suitable surrogate for monitoring real-time changes in dIVC to assess intravascular volume status.

Use of pelvic hemostasis belt to control lethal pelvic arterial hemorrhage in a swine model.

BACKGROUND: Hemorrhage is the leading cause of death for both civilian and battlefield injuries. Hemorrhage from pelvic vascular wounds is of concern since it is difficult to control before surgical intervention. This has resulted in renewed interest in developing presurgical endovascular approaches to hemorrhage control. However, it is likely that other short-term techniques may be needed as a bridge to such approaches. We tested a prototype device called the pelvic hemostasis belt (PHB) for its ability to reduce or halt blood flow in a lethal model of pelvic arterial injury. METHODS: Seventeen male swine, 42 (5.2)kg were anesthetized, instrumented, and then randomized into three groups (control, military antishock trousers [MAST], and PHB). Animals underwent laparotomy with placement of a 4-0 stainless steel monofilament suture through the right iliac artery. The laparotomy was closed, and the iliac suture was exteriorized. Hemorrhage was produced by pulling the suture through the iliac artery. In both PHB and MAST groups, the devices were applied over the pelvis and lower abdomen for 60 minutes, followed by release and monitoring for 30 minutes or until the animal expired. Hetastarch (500 mL) was infused immediately after commencement of hemorrhage. RESULTS: All PHB group animals and only two from the MAST group survived for 60 minutes. Mean (SD) survival time for the control group was 13 (12.3) minutes. Log-rank (Mantel-Cox) survival analysis demonstrated a significant difference in survival time when comparing all groups (p < 0.0001) as well as when comparing PHB and MAST groups (p = 0.018). Significant differences were noted between groups in mean arterial pressure, lactate, and central venous hemoglobin oxygen saturation levels. CONCLUSION: The PHB was successful in improving survival for 60 minutes after a lethal vascular injury. Such a device may be helpful to bridge endovascular methods of hemorrhage control.

Tissue oxygenation monitoring using resonance Raman spectroscopy during hemorrhage.

BACKGROUND: The ability to monitor the patient of hemorrhage noninvasively remains a challenge. We examined the ability of resonance Raman spectroscopy to monitor tissue hemoglobin oxygenation (RRS-StO2) during hemorrhage and compared its performance with conventional invasive mixed venous (SmvO2) and central venous (ScvO2) hemoglobin oxygen saturation as well as with near-infrared spectroscopy tissue hemoglobin oxygenation (NIRS-StO2). METHODS: Five male swine were anesthetized and instrumented followed by hemorrhage at a rate of 30 mL/min for 60 minutes. RRS-StO2 was continuously measured from the buccal mucosa, and NIRS-StO2 was continuously measured from the forelimb. Paired interval measures of SmvO2, ScvO2, and lactate were made. Pearson correlation was used to quantify the degree to which any two variables are related. Receiver operating characteristic (ROC) area under the curve values were used for pooled data for RRS-StO2, NIRS-StO2, SmvO2, and ScvO2 to compare performance in the ability of tissue oxygenation methods to predict the presence of an elevated arterial blood lactate level. RESULTS: Sequential RRS-StO2 changes tracked changes in SmvO2 (r = 0.917; 95% confidence interval [CI], 0.867-0.949) and ScvO2 (r = 0.901; 95% CI, 0.828-0.944) during hemorrhage, while NIRS-StO2 failed to do so for SmvO2 (r = 0.283; 95% CI, 0.04919-0.4984) and ScvO2 (r = 0.142; 95% CI, -0.151 to 0.412). ROC curve performance of oxygenation measured to indicate lactate less than or greater than 3 mM yielded the following ROC area under the curve values: SmvO2 (1.0), ScvO2 (0.994), RRS-StO2 (0.972), and NIRS-StO2 (0.611). CONCLUSION: RRS-StO2 seems to have significantly better ability to track central oxygenation measures during hemorrhage as well as to predict shock based on elevated lactate levels when compared with NIRS-StO2.

Effects of a combination hemoglobin based oxygen carrier-hypertonic saline solution on oxygen transport in the treatment of traumatic shock.

BACKGROUND: Logistics complicate fluid resuscitation of traumatic shock on the battlefield. Traumatic shock can result in oxygen debt (O(2)D) accumulation that is fatal. However, the ability of fluid strategies to repay O(2)D are not commonly reported. This pilot study examined various resuscitation fluids, including a combination of PEGylated bovine hemoglobin and hypertonic saline (AfterShock™) on their ability to repay O(2)D in traumatic shock. METHODS: 41 anesthetized swine underwent hemorrhage to an O(2)D of 80 mL/kg. Animals received one of the following: 500 mL whole blood, 500 mL AfterShock™, 500 mL hypertonic (7.2%) saline, 250 mL hypertonic (7.2%) saline, 500 mL Hetastarch (6%), or 500 mL lactated Ringer's. Oxygen transport variables (O(2)D, oxygen consumption, oxygen delivery, central venous hemoglobin oxygen saturation, oxygen extraction ratios), lactate clearance, and survival were monitored for 3h after treatment. Data were analyzed using mixed-model ANOVA and comparisons were made to the performance of whole blood. RESULTS: Only animals receiving AfterShock™, 500 mL hypertonic saline, and 500 mL Hetastarch survived to 180 min. While not statistically significant AfterShock™ demonstrated trends in improving the repayment of O(2)D and in improving oxygen transport variables despite having lower levels of global oxygen delivery compared to whole blood, Hetastarch and 500 mL hypertonic saline groups. CONCLUSION: Use of 500 mL AfterShock™, 500 mL of 7.2% saline or 500 mL of Hetastarch resulted in improved short-term survival. While not statistically significant, AfterShock™ demonstrated trends in improving O(2)D. These findings may have implications for designing resuscitation fluids for combat casualty care.

A novel noninvasive impedance-based technique for central venous pressure measurement.

Knowledge of central venous pressure (CVP) is considered valuable in the assessment and treatment of various states of critical illness and injury. We tested a noninvasive means of determining CVP (NICVP) by monitoring upper arm blood flow changes in response to externally applied circumferential pressure to the upper arm veins. Thirty-six patients who were undergoing CVP monitoring as part of their care had NICVP determined and compared with CVP. Volume changes were measured in the upper arm using tetra-polar impedance plethysmography underneath a blood pressure cuff. The cuff was inflated over 5 s to a pressure greater than CVP but less than diastolic arterial pressure. After 45 to 60 s, the cuff was rapidly deflated. Noninvasive CVP was determined as the cuff pressure noted at the maximum derivative of the volume increase under the cuff during deflation. Noninvasive CVP was then compared with invasively measured CVP taken during the same period by Bland-Altman analysis. A total of 108 trials (three per subject) were performed on 36 patients. Mean bias was -0.26 mmHg (95% confidence interval [CI]: -0.67, 0.15). Limits of agreement were -2.7 and 2.2 mmHg with the 95% CI for the lower limit of agreement (-3.4, -2.0 mmHg) and for the upper limit of agreement (1.5, 2.9 mmHg). Correlation between CVP and NICVP was 0.95 (95% CI: 0.93 to 0.97; P < 0.0001). Noninvasive CVP as determined in this study may be a clinically useful substitute for traditional CVP measurement and may offer a tool for early diagnosis and treatment of acute states in which knowledge of CVP would be helpful.