Innate immune response after resuscitation with hemoglobin-based oxygen carrier and recombinant factor VIIA in uncontrolled hemorrhagic shock in a swine model.

BACKGROUND: Rapid resuscitation with oxygen-carrying fluids is critically important in hemorrhagic shock (HS) combat casualties in remote areas where blood is not available. Hemoglobin-based oxygen carrier-201 (HBOC-201) has been shown to increase survival and reduce immune activation following HS in animal models. Recombinant factor VIIa (rfVIIa), a systemic hemostatic agent, is Food and Drug Administration approved for use in acute hemorrhage in hemophilic patients. The combination of HBOC-201 and rfVIIa may form the basis of a prospective multifunctional blood substitute and provide benefits in the rapid restoration of hemostasis, decreased inflammation and improved survival of HS combat casualties. In the present study, we evaluated innate immune responses in a swine model of uncontrolled HS following resuscitation with HBOC-201 +/- rfVIIa. MATERIALS: Thirty-two pigs underwent uncontrolled hemorrhage/liver crush injury, followed by resuscitation with five doses of HBOC-201 or HBOC + rfVIIa (90 microg/kg, or 180 microg/kg, or 360 microg/kg) and simulated 4 hours hospital arrival. Immune parameters were evaluated by flow cytometry and enzyme-linked immunosorbent assay. RESULTS: Survival differences to 72 hours of animals resuscitated with HBOC, HBOC + rfVIIa (90), (180), and (360) were not statistically significant and resulted in survival of 25%, 63%, 63% and 50%, respectively. At the prehospital phase all groups exhibited minimal immunomodulation, characterized by stable CD4/CD8 ratio, marginal increase of apoptosis and insignificant fluctuations of adhesion markers; increase of plasma cytokines was comparable across all groups, except tumor necrosis factor-alpha, that was significantly elevated in the HBOC group. CONCLUSION: HBOC-201 + rfVIIa triggered minimum immune activation in an uncontrolled HS swine and there was a nonsignificant survival benefit.

Innate immune responses in Swine resuscitated from severe traumatic hemorrhagic shock with hemoglobin-based oxygen carrier-201.

Hemoglobin-based oxygen carrier-201 transports oxygen and improves survival in swine with hemorrhagic shock, but has potential to be immune activating. Herein, we evaluated HBOC-201's immune effects in swine with more severe hemorrhagic shock due to soft tissue injury and 55% blood volume catheter withdrawal over 15 minutes followed by fluid resuscitation at 20 minutes with HBOC-201, Hextend, or no treatment (NON) before hospital arrival. Survival rates were similar with HBOC-201 and Hextend (p > 0.05), but were higher than in (p = 0.007). There were no significant group differences in blood cell count, percentages of leukocyte sub-populations and immunophenotype (CD4:CD8 ratio), adhesion markers expression (neutrophil CD11b; monocyte or neutrophil CD49d) and apoptosis. There was a trend to higher plasma IL-10 in HBOC-201 and groups vs. Hextend. We conclude that in swine with severe controlled HS and soft tissue injury, immune responses are similar with resuscitation with HBOC-201 and Hextend.

Coagulation patterns following haemoglobin-based oxygen carrier resuscitation in severe uncontrolled haemorrhagic shock in swine.

Massive blood loss due to penetrating trauma and internal organ damage can cause severe haemorrhagic shock (HS), leading to a severely compromised haemostatic balance. This study evaluated the effect of bovine polymerized haemoglobin (Hb) (Hb-based oxygen carrier, HBOC) resuscitation on haemostasis in a swine model of uncontrolled HS. Following liver injury/HS, swine received HBOC (n= 8), Hextend (HEX) (n= 8) or no resuscitation (NON) (n= 8). Fluids were infused to increase mean arterial pressure above 60 mmHg and to reduce heart rate to baseline. At 4 h, the animals were eligible for blood transfusions. Prothrombin time (PT), activated partial thromboplastin time, fibrinogen, thromboelastography (TEG) and platelet function analyser closure time (PFA-CT) were compared by using mixed statistical model. At 4 h, blood loss (% estimated blood volume) was comparable for HBOC (65.5 +/- 18.5%) and HEX (80.8 +/- 14.4%) and less for NON (58.7 +/- 10.1%; P < 0.05). Resuscitation-induced dilutional coagulopathy was observed with HBOC and HEX, as indicated by reduced haematocrit, platelets and fibrinogen (P < 0.05). At 4 h, PT was higher in HEX than in HBOC groups (P < 0.01). In the early hospital phase, a trend to increased TEG reaction time and PFA-CT indicates that dilutional effects persist in HBOC and HEX groups. PFA-CT returned to baseline later with HBOC than with HEX (48 vs. 24 h) following blood transfusion. At 4 h, all surviving HEX animals (n= 3) required transfusion, in contrast to no HBOC (n= 7) or NON (n= 1) animals. In this severe uncontrolled HS model, successful resuscitation with HBOC produced haemodilutional coagulopathy less than or similar to that produced by resuscitation with HEX.

Diagnostic procedures for the urogenital system.

In making clinical decisions concerning the urogenital system, the emergency department physician has many different diagnostic tools at his or her disposal. Choosing the appropriate diagnostic study can often be difficult. For well over a thousand years, the initial step in assessing almost any urologic condition has been to examine the urine. Thankfully, this has progressed from a gustatory approach to the modern urinalysis. There is certainly a great deal of information that may be gleaned from the urinalysis, but the physician must also be mindful of its limitations. Overuse of the urinalysis can result in unwanted and unhelpful information. Although IVP is still the study of choice in assessing the functional status of the kidney, the introduction of CT and ultrasound technology to clinical medicine has revolutionized the emergency department assessment of the urogenital tract. CT and ultrasound can help differentiate between the urologic emergencies and the various surgical conditions that can mimic them.

Emergency medical services in the reconstruction phase following a major earthquake: a case study of the 1988 Armenia earthquake.

STUDY OBJECTIVE: To use the clinical activities of an ambulance service as a tool to assess the residual and unmet medical needs of a city in the aftermath of a major earthquake and to apply that assessment to the development of a training curriculum for the prehospital personnel. METHODS: The researchers conducted structured interviews with health care workers at all levels of the emergency health care delivery system in Gyumrii, Armenia, and carried out a retrospective frequency analysis of 29,010 ambulance runs for an 11-month period from February through December 1992. Runs first were assigned into the broad categories of: 1) Adult Medical; 2) Pediatric Medical; or 3) Trauma, and then, according to diagnosis. The runs then were classified further as: 1) Primary Care; 2) Basic Life Support (BLS); or 3) Advanced Life Support (ALS). RESULTS: Adult Medical calls represented 24,684 (85%), Pediatric Medical calls 459 (1.6%), and Trauma calls 3,867 (13%). Only 12% of all ambulance calls resulted in transport to a medical facility, although this percentage was higher in children. Thirty percent of Adult Medical patients were diagnosed by the emergency medical providers as having exclusively a psychiatric problem. CONCLUSION: In the late aftermath of a devastating earthquake, the ambulance service in Gyumrii, Armenia has been delivering a substantial proportion of non-emergency, primary care services. They have adopted this unconventional role to compensate for the deficit in health care facilities and personnel created by the disaster. The training program that the investigators developed reflected the actual work activities of the prehospital personnel demonstrated in their assessment.

Factors and methodology in achieving ideal delivery temperatures for intravenous and lavage fluid in hypothermia.

A study was undertaken to determine the relationship between temperature and delivery rate of warmed intravenous fluid using standard intravenous infusion equipment and tubing. One-liter bags of 0.9% NaCl were warmed to 60 degrees C and run through standard microdrip tubing for 1 hour at rates of 1,000, 800, 600, and 400 mL/h. Thermistor probes were placed into the bag and into the tubing at 0, 100, 180, 230, and 280 cm from the intravenous bag. Separate fluid bags were also warmed to 39.3 degrees and 75 degrees C, and the fluid was run through the same apparatus at 1,000 mL/h and 200 mL/h, respectively. Temperatures were recorded at each site at the start of the infusion and every 10 minutes thereafter for 1 hour, Subsequently, 60-mL syringes of fluid warmed to 39.5 degrees C were eluted through 50 cm tubing over 10 minutes at 300 mL/h and 360 mL/h. Mean delivery temperature over each 10-minute infusion was determined. Fluid preheated to 39.3 degrees C approached room temperature at delivery even at a flow rate of 1,000 mL/h and tubing lengths as short as 100 cm. Fluid preheated to 60 degrees C was delivered at near 37 degrees C using tubing lengths as long as 280 cm when eluted at 1,000 mL/h. Fluid preheated to 39 degrees C in 60-mL syringes and eluted through 50 cm of tubing over a period of 10 minutes at 300 mL/h or 360 mL/h was delivered near a mean temperature of 37 degrees C. These results show that warmed fluid can be delivered through standard intravenous tubing at or near 37 degrees C if the fluid is preheated to 60 degrees C and eluted through long tubing (280 cm) at high flow rates (1,000 mL/h). Alternatively, fluid warmed to 37 degrees C to 42 degrees C can be delivered at or near 37 degrees C via intermittent bolus through short tubing (50 cm) either by hand or syringe pump. The latter approach would be particularly beneficial in the pediatric population, in whom it is not advisable to administer fluid at flow rates as high as 1,000 mL/h.

Signs and symptoms of patients with brain tumors presenting to the emergency department.

This retrospective chart review was conducted to determine the presenting signs and symptoms of patients with primary brain tumors diagnosed in the emergency department. There were 101 patients (65 males and 36 females) identified with a hospital discharge diagnosis of primary brain tumor who were admitted through the emergency department. The presenting symptoms included headache (56 patients), altered mental status (51 patients), ataxia (41 patients), nausea or vomiting (37 patients), weakness (27 patients), speech deficits (21 patients), and sensory abnormalities (18 patients). The presenting signs included motor weakness (37 patients), ataxia (37 patients), papilledema (28 patients), cranial nerve palsies (26 patients), visual deficits (20 patients), and speech deficits (12 patients). The average age was 42.8 years, with a range of 3 days to 88 years. The majority of tumors were malignant astrocytomas. Tumor location was cortical in 68 patients, subcortical in 9 patients, and brainstem or cerebellum in 24 patients. In conclusion, patients of all ages may present to the emergency department with a variety of symptoms resulting from a primary brain tumor. Headache and altered mental status were common in our series of patients, but symptoms will depend on the size, location, and type of tumor. A complete neurologic examination is essential, including evaluation for papilledema.