Deborah L Mueller

Low-Volume Resuscitation with a Polymerized Bovine Hemoglobin-Based Oxygen-Carrying Solution (HBOC-201) Provides Adequate Tissue Oxygenation for Survival in a Porcine Model of Controlled Hemorrhage

BACKGROUND We have shown in a previous work that HBOC-201 is able to reverse anaerobic metabolism at low volumes in a porcine model of controlled hemorrhage. On the basis of these results, we hypothesize that low-volume resuscitation with HBOC-201 in a porcine model of controlled hemorrhage provides adequate tissue oxygenation to limit end-organ damage and allow for survival of the animal. METHODS Twenty-four Yorkshire swine (55-65 kg) were rapidly hemorrhaged to a mean arterial pressure (MAP) of 30 mm Hg, maintained hypotensive for 45 minutes, and then divided into four groups. The first group, Shed Blood (BL), was resuscitated with shed blood to baseline MAP. A second group, Shed Blood (60), underwent resuscitation for four hours at an MAP of 60 mm Hg with shed blood. The third group, LR + Blood, was resuscitated with lactated Ringers (maximum, 40 mL/kg) followed by shed blood to baseline MAP. The final group, HBOC (60), underwent resuscitation for 4 hours at an MAP of 60 mm Hg with HBOC-201. Hemodynamic variables, urine output, blood gas analyses, lactate levels, and jejunal oximetry were followed throughout the experiment. Animals were allowed to survive and underwent necropsy on postinjury day 3. Histologic comparisons were made. Data were analyzed using analysis of variance/Duncans multiple range test. RESULTS All animals survived the hemorrhage/resuscitation. One animal in the LR + Blood group died on postinjury day 1. Heart rate, MAP, and arterial pH were similar between groups. Cardiac output was significantly lower throughout resuscitation in the HBOC (60) group. Jejunal oximetry was similar throughout the experiment in all groups, revealing a decline in Po2 during hemorrhage and return to baseline or near baseline during resuscitation. There was no evidence of renal dysfunction. Histologically, one animal in the LR + Blood group and four of six animals in the HBOC (60) group demonstrated mild hepatocellular damage. All other tissues examined were found to have no significant abnormalities. Elevations in serum aspartate aminotransferase levels were noted when comparing the HBOC (60) group to the Shed Blood (BL) and Shed Blood (60) groups on day 2. Significant decreases in hemoglobin levels were noted in the HBOC (60) group compared with all other groups beginning on day 2. CONCLUSION Low-volume resuscitation with HBOC-201 provides adequate tissue oxygenation for survival in a porcine model of controlled hemorrhagic shock with no long-term organ dysfunction identified. Although some animals did show mild hepatocellular damage with elevations of aspartate aminotransferase at day 2, these findings did not appear to have clinical relevance, and the enzyme elevations were trending toward normal by the third postoperative day. Decreases in hemoglobin levels at the later time points were expected, given the half-life of the product.

Pediatric radiation exposure during the initial evaluation for blunt trauma.

BACKGROUND Increased utilization of computed tomography (CT) scans for evaluation of blunt trauma patients has resulted in increased doses of radiation to patients. Radiation dose is relatively amplified in children secondary to body size, and children are more susceptible to long-term carcinogenic effects of radiation. Our aim was to measure radiation dose received in pediatric blunt trauma patients during initial CT evaluation and to determine whether doses exceed doses historically correlated with an increased risk of thyroid cancer. METHODS A prospective cohort study of patients aged 0 years to 17 years was conducted over 6 months. Dosimeters were placed on the neck, chest, and groin before CT scanning to measure surface radiation. Patient measurements and scanning parameters were collected prospectively along with diagnostic findings on CT imaging. Cumulative effective whole body dose and organ doses were calculated. RESULTS The mean number of scans per patient was 3.1 ± 1.3. Mean whole body effective dose was 17.43 mSv. Mean organ doses were thyroid 32.18 mGy, breast 10.89 mGy, and gonads 13.15 mGy. Patients with selective CT scanning defined as ≤2 scans had a statistically significant decrease in radiation dose compared with patients with >2 scans. CONCLUSIONS Thyroid doses in 71% of study patients fell within the dose range historically correlated with an increased risk of thyroid cancer and whole body effective doses fell within the range of historical doses correlated with an increased risk of all solid cancers and leukemia. Selective scanning of body areas as compared with whole body scanning results in a statistically significant decrease in all doses.

A Comparison of the Hemoglobin-Based Oxygen Carrier HBOC-201 to Other Low-Volume Resuscitation Fluids in a Model of Controlled Hemorrhagic Shock

BACKGROUND The ideal resuscitation fluid for military applications would be effective at low volumes, thereby reducing logistical constraints. We have previously shown that the bovine hemoglobin-based oxygen carrier HBOC-201 is an effective low-volume resuscitation fluid. The goal of this experiment was to evaluate the effectiveness of HBOC-201 in comparison with other low-volume resuscitation fluids in a swine model of controlled hemorrhagic shock. METHODS Forty-two immature female Yorkshire swine (55-70 kg) were divided into seven groups of six. Animals were hemorrhaged to a mean arterial pressure of 30 mm Hg. After 45 minutes, animals were resuscitated to a mean arterial pressure of 60 mm Hg with one of the following agents: hypertonic saline 7.5% (HTS), hypertonic saline 7.5%/Dextran-70 6% (HSD), pentastarch 6%, hetastarch 6%, or HBOC-201. Lactated Ringers (LR) solution was used as a standard resuscitation control. Another group of animals received no resuscitation. Resuscitation was continued for 4 hours. Hemodynamic variables and oxygen consumption were measured continuously. Arterial and mixed venous blood gases and serum lactate levels were measured at intervals throughout the experiment. Data were analyzed using analysis of variance with Tukeys post hoc test when appropriate. Significance was defined as p < 0.05. RESULTS Five of six animals in the no-resuscitation control group, six of six in the HTS group, and one animal in the HSD group died before completion of the study. All other animals survived to completion. Animals receiving resuscitation with HBOC-201 had significantly lower cardiac output, mixed venous oxygen saturation levels, and urinary output throughout the resuscitation period; however, there were no differences with regard to lactate, base excess, or oxygen consumption. Animals receiving HBOC-201 required significantly less fluid than any other group. CONCLUSION In this model, hypotensive resuscitation with HBOC-201 restores tissue oxygenation and reverses anaerobic metabolism at significantly lower volumes when compared with HTS, HSD, pentastarch, or hetastarch solutions. These data suggest that HBOC-201 would be an effective primary resuscitation fluid for far-forward military or rural trauma settings where logistic constraints and prolonged transport times are common. However, when HBOC-201 is administered as a primary resuscitation fluid in hypotensive protocols, common clinical markers for determining adequacy of resuscitation may not be useful.

Malpractice risk and cost are significantly reduced after tort reform

BACKGROUND Rising medical malpractice premiums have reached a crisis point in many areas of the United States. In 2003 the Texas legislature passed a comprehensive package of tort reform laws that included a cap at

The Effect of the Bovine Hemoglobin Oxygen Therapeutic HBOC-201 on Human Neutrophil Activation In Vitro

250,000 on noneconomic damages in most medical malpractice cases. We hypothesized that tort reform laws significantly reduce the risk of malpractice lawsuit in an academic medical center. We compared malpractice prevalence, incidence, and liability costs before and after comprehensive state tort reform measures were implemented. STUDY DESIGN Two prospectively maintained institutional databases were used to calculate and characterize malpractice risk: a surgical operation database and a risk management and malpractice database. Risk groups were divided into pretort reform (1992 to 2004) and post-tort reform groups (2004 to the present). Operative procedures were included for elective, urgent, and emergency general surgery procedures. RESULTS During the study period, 98,513 general surgical procedures were performed. A total of 28 lawsuits (25 pre-reform, 3 postreform) were filed, naming general surgery faculty or residents. The prevalence of lawsuits filed/100,000 procedures performed is as follows: before reform, 40 lawsuits/100,000 procedures, and after reform, 8 lawsuits/100,000 procedures (p < 0.01, relative risk 0.21 [95% CI 0.063 to 0.62]). Virtually all of the liability and defense cost was in the pretort reform period:

Natural history and clinical implications of nondepressed skull fracture in young children

595,000/year versus

Absence of clinical findings reliably excludes unstable cervical spine injuries in children 5 years or younger

515/year in the postreform group (p < 0.01). CONCLUSIONS Implementation of comprehensive tort reform in Texas was associated with a significant decrease in the prevalence and cost of surgical malpractice lawsuits at one academic medical center.

Time and degree of glycemic derangement are associated with increased mortality in trauma patients in the setting of tight glycemic control

BACKGROUND We previously demonstrated that HBOC-201 is an efficient resuscitation fluid. However, little is known about its immunomodulatory effects. The goal of this study was to investigate human neutrophil activation after exposure to HBOC-201 and other low-volume resuscitation fluids. METHODS Whole blood from 10 healthy volunteers was serially diluted with HBOC-201, 7.5% hypertonic saline (HTS), 7.5% hypertonic saline-6% dextran 70 (HSD), Hextend, or PentaLyte. After an incubation period, samples were analyzed for oxidative burst and CD11b expression using flow cytometry. RESULTS Increases in both CD11b and oxidative burst activity were noted in samples diluted with HBOC-201, Hextend, PentaLyte, and lactated Ringers solution. Samples maximally diluted with HBOC-201 demonstrated increased CD11b expression when compared with lactated Ringers solution and Hextend (196.11% vs. 22.68% and 33.97%; p = 0.018 and p = 0.033). CONCLUSION Although differences were noted only at the highest dilutions, further studies investigating the effects of HBOC-201 are warranted.

SU‐GG‐I‐75: Calculating the Effective Dose for Pediatric Patients from Multi‐Detector CT Studies: New vs. Old ICRP Recommendations

BACKGROUND Head injury is the most common cause of neurologic disability and mortality in children. Previous studies have demonstrated that depressed skull fractures (SFs) represent approximately one quarter of all SFs in children and approximately 10% percent of hospital admissions after head injury. We hypothesized that nondepressed SFs (NDSFs) in children are not associated with adverse neurologic outcomes. METHODS Medical records were reviewed for all children 5 years or younger with SFs who presented to our Level I trauma center during a 4-year period. Data collected included patient demographics, Glasgow Coma Scale (GCS) score at admission, level of consciousness at the time of injury, type of SF (depressed SF vs. NDSF), magnitude of the SF depression, evidence of neurologic deficit, and the requirement for neurosurgical intervention. RESULTS We evaluated 1,546 injured young children during the study period. From this cohort, 563 had isolated head injury, and 223 of them had SF. Of the SF group, 163 (73%) had NDSFs, of whom 128 (78%) presented with a GCS score of 15. None of the NDSF patients with a GCS score of 15 required neurosurgical intervention or developed any neurologic deficit. Of the remaining 35 patients with NDSF and GCS score less than 15, 7 (20%) had a temporary neurologic deficit that resolved before discharge, 4 (11%) developed a persistent neurologic deficit, and 2 died (6%). CONCLUSION Children 5 years or younger with NDSFs and a normal neurologic examination result at admission do not develop neurologic deterioration. LEVEL OF EVIDENCE Epidemiological study, level III.

A prospective randomized pilot study of near-infrared spectroscopy-directed restricted fluid therapy versus standard fluid therapy in patients undergoing elective colorectal surgery.

BACKGROUND Increased accessibility and rapidity of computed tomography (CT) have led to increased use and radiation exposure to pediatric trauma patients. The thyroid is radiosensitive and therefore at risk for developing malignancy from radiation exposure during cervical spine CT. This analysis aimed to determine which preelementary trauma patients warrant cervical spine CT by defining incidence and clinical characteristics of preelementary cervical spine injury. METHODS This was a retrospective review of pre-elementary trauma patients from 1998 to 2010 with cervical spine injury admitted to a Level I trauma center. Patients were identified from the trauma registry using DRG International Classification of Diseases—9th Rev. codes and reviewed for demographics, mechanism of injury, clinical presentation, injury location, injury type, treatment, and outcome. RESULTS A total of 2,972 preelementary trauma patients were identified. Twenty-two (0.74%) had confirmed cervical spine injuries. Eleven (50%) were boys, and the mean (SD) age was 3 (1.7) years. The most common mechanism of injury was motor vehicle collision (n = 16, 73%). The majority (59%) were in extremis, and 12 (55%) arrived intubated. The median Glasgow Coma Scale (GCS) score was 3 (interquartile range, 3–10); the median Injury Severity Score (ISS) was 33 (interquartile range, 17–56). Nineteen injuries (76%) were at the level of C4 level and higher. The mortality rate was 50%. All patients had clinical findings suggestive of or diagnostic for cervical spine injury; 18 (82%) had abnormal neurologic examination result, 2 (9%) had torticollis, and 2 (9%) had neck pain. CONCLUSION The incidence of cervical spine injury in preelementary patients was consistent with previous reports. Missing a cervical spine injury in asymptomatic preelementary patients is extremely low. Reserving cervical spine CT to symptomatic preelementary patients would decrease unnecessary radiation exposure to the thyroid. LEVEL OF EVIDENCE Therapeutic study, level IV.