Biomedical subjects

Diane Morabito

Publications and source records attributed to Diane Morabito.

17 recordsLinked to original sources

PubMed2006

Controlled cortical impact in swine: pathophysiology and biomechanics.

Investigations of the basic pathological, cellular, and molecular mechanisms of traumatic brain injury (TBI) over the past two decades have been carried out primarily in rodents. Unfortunately, these studies have not translated into improved outcome in patients with TBI. To better model human TBI, a swine model of controlled cortical impact (CCI) was developed. A CCI device was used to generate a focal lesion in 23 anesthetized male Yorkshire swine. In 10 swine, CCI parameters of velocity and dwell time were varied to achieve a consistent injury (3.5 m/sec, 400 msec, respectively). In 13 swine, depth of depression was varied from 9 to 12 mm. Physiological data, including heart rate (HR), mean arterial blood pressure (MAP), intracranial pressure (ICP), and cerebral perfusion pressure (CPP), were collected for 10 h after injury. Following injury, ICP and HR increased above baseline values in all swine, with a more pronounced elevation in animals impacted to a depth of depression of 12 mm. An 11-mm depth of depression was found to most closely mimic pathological features of human TBI with edema, infiltration of inflammatory cells, pericapillary hemorrhage, and petechial hemorrhages in the white matter. Injury to a depth of depression of 12 mm resulted in cortical laceration obscuring these features. Immunohistological staining with Neu-N, MAP-2, and Fluoro Jade B revealed evidence of degenerating neurons, axonal disruption, and impending cell death. These results indicate that the swine model of CCI results in a defined and reproducible injury with pathological features similar to human TBI. Physiological parameters after injury are readily monitored in a setting mimicking conditions of an intensive care unit, establishing a more clinically relevant experimental model for future investigations.

Animals↗

PubMed2005

Serum levels of Hsp60 correlate with the development of acute lung injury after trauma.

BACKGROUND: Previous studies have shown that heat shock protein 60 (Hsp60) is a danger signal for the immune system and appears to be a key endogenous inflammatory mediator that activates the toll-like receptors and causes the release of proinflammatory cytokines and nitric oxide by immune competent cells, but no data are available for trauma patients. The purpose of this study was to determine whether Hsp60 could be detected in the serum of patients early after severe trauma and whether its serum level might correlate with the development of acute lung injury (ALI) in trauma patients. METHODS: Clinical data were collected prospectively during a 12-month period for trauma patients who were ventilated mechanically for more than 24 h and who met the following inclusion criteria: Injury Severity Score > or =16, age >18 years. Physiological data for quantitative assessment of organ dysfunction were collected for each patient. Hsp60 levels were measured in the serum of trauma patients. RESULTS: Sixty-four patients with severe trauma were enrolled in the study. Eighteen patients developed ALI (28%). Trauma patients who later developed ALI had significantly higher serum values of Hsp60 than those who did not (4.21 +/- 2.24 ng/mL versus 0.73 +/- 0.26 ng/mL, P < 0.05, mean +/- SE). Furthermore, immature but not mature recombinant Hsp60 induced in vitro the release of nitric oxide (NO) from RAW 264.7 murine macrophages. CONCLUSION: Serum levels of Hsp60 detected within 30 min after trauma correlate with the development of ALI. Immature but mature Hsp60 causes in vitro the release of NO by macrophages, suggesting that the extracellular release of the immature Hsp60 associated with traumatic cell necrosis could be involved in the release of NO by immune competent cells, leading to an activation of the inflammatory response within the lung or other organs.

Adult↗

PubMed2005

Influence of data resolution and interpolation method on assessment of secondary brain insults in neurocritical care.

Continuous monitoring of physiologic vital signs is routine in neurocritical care. However, this patient information is usually only recorded intermittently (most often hourly) in the medical record. It is unclear whether this is sufficient to represent the occurrence of secondary brain insults (SBIs) or whether more frequent data collection will provide more comprehensive information for patient care. In 16 patients, physiologic data were acquired concurrently via two methods: per clinical routine, usually hourly, in the medical record (MR) and every minute via a custom data acquisition system (DA). SBIs were defined as a mean arterial pressure<90 mmHg, an intracranial pressure>20 mmHg or a temperature>37.5 degrees C. Number of events, cumulative duration of events and area under the curve (AUC) were compared between the two methods and 95% limits of agreement were assessed for various methods of MR data interpolation. For all three parameters, analysis of the DA and MR data frequently differed with regard to number of events, total duration of events and AUC. MR data tended to underestimate the number of total events. 95% limits of agreement were most narrow for trapezoidal interpolation of MR data, but even these limits were fairly broad. Assessment of secondary brain insults is highly dependent on (1) the temporal resolution of the method used to acquire patient data and on (2) the interpolation method if data are acquired intermittently. High frequency data acquisition may be necessary for more precise evaluation of secondary brain injury in neurocritical care.

Adult↗

PubMed2005

Profile of mothers at risk: an analysis of injury and pregnancy loss in 1,195 trauma patients.

BACKGROUND: Trauma is the number one cause of maternal death during pregnancy, but incidence of fetal loss exceeds maternal loss by more than 3 to 1. We hypothesized that we could identify women at risk for injury during pregnancy and focus our prevention efforts. STUDY DESIGN: Women of childbearing age in the American College of Surgeon's National Trauma Data Bank served as the study population. Pregnant patients were compared with nonpregnant patients with respect to age, race, mechanism of injury, injury patterns and severity, risk-taking behaviors, and outcomes. Multivariate logistic regression analysis was used to identify risk factors for loss of pregnancy in mothers who survived their trauma. RESULTS: Pregnant trauma patients (n = 1,195) were younger, less severely injured, and more likely to be African American or Hispanic as compared with the nonpregnant cohort (n = 76,126). Twenty percent of injured pregnant patients tested positive for drugs or alcohol, and approximately one-third of those involved in motor vehicle crashes were not using seatbelts. Independent risk factors for fetal loss after trauma included Injury Severity Score > 15; Adjusted Injury Score > or = 3 in the head, abdomen, thorax, or lower extremities; and Glasgow Coma Score < or = 8. CONCLUSIONS: Young, African-American, and Hispanic pregnant women are at higher risk for trauma in pregnancy and are most likely to benefit from primary trauma prevention efforts. Those with severe head, abdominal, thoracic, or lower extremity injuries are at high risk for pregnancy loss. Reduction of secondary insults and early recognition of fetal distress may improve outcomes for both the mother and fetus in this high-risk group.

Adolescent↗

PubMed2005

Posttraumatic stress symptoms in children after mild to moderate pediatric trauma: a longitudinal examination of symptom prevalence, correlates, and parent-child symptom reporting.

BACKGROUND: Full recovery from injury may be hindered by both physical ailments and psychologic distress. Little information is available on the psychologic response of children to physical trauma, although long-term dysfunction may result if psychologic needs are not identified and addressed. This study examined the prevalence and correlates of posttraumatic stress disorder (PTSD) symptoms in children and adolescents after an acute traumatic event resulting in mild to moderate physical injury. We were also interested in analyzing the discrepancies between parent/child reporting of the child's PTSD symptomatology. Because of the paucity of research evaluating interventions for pediatric PTSD, and as a secondary objective for this study, we collected preliminary data on the effectiveness of a single-session art therapy intervention designed to reduce PTSD symptoms. METHOD: From July 1998 through October 2000, 83 children/adolescents between the ages of 7 and 17 and their caregivers were interviewed within 24 hours of hospital admission and assessed for PTSD symptomatology, trauma history, and other measures of child and family functioning. Interviews were repeated at 1 month, 6 months, and 18 months after the initial hospitalization. Patients with at least mild symptomatology at the initial interview were randomized to receive either an art therapy intervention or standard hospital services alone. RESULTS: A total of 69% of children were found to have at least mild PTSD symptoms at baseline, 57% at 1 month, 59% at 6 months, and 38% at 18 months postinjury. Younger age and the severity of parental PTSD symptoms were correlated with symptom presence in children. Parents initially underreported their child's symptom severity when compared with the child's report, but assessments converged over time. The art therapy intervention showed no sustained effects on the reduction of PTSD symptoms. CONCLUSION: The presence of PTSD symptoms in children after traumatic injury is very high. Parental distress and characteristics of the family environment appear to be more relevant to the presence of child symptoms than the family make-up, course of hospitalization, or extent of the child's injuries. Parents may not initially recognize the degree to which their children experience such symptoms. The high presence of symptoms in this population underscores the need for treatment efficacy studies and parent/medical staff education in identification of PTSD.

Adolescent↗

PubMed2005

Recovery at one year following isolated traumatic brain injury: a Western Trauma Association prospective multicenter trial.

BACKGROUND: Age has been shown to be a primary determinant of survival following isolated traumatic brain injury (TBI). We have previously reported that patients > or =65 years who survived mild TBI have decreased functional outcome at 6 months compared with younger patients. The purpose of this study was to further investigate the effect of age on outcome at 1 year in all patients surviving isolated TBI. METHODS: The Western Trauma Association multicenter prospective study included all patients sustaining isolated TBI defined as Abbreviated Injury Scale score for Head > or = 3 with an Abbreviated Injury Scale score in any other body area < or = 1. Outcome data included discharge disposition, Glasgow Outcome Scale score (1 = dead to 5= full recovery) and modified Functional Independence Measure (FIM) score measuring feeding, expression, and locomotion (1 = total dependence to 4 = total independence) for each component at discharge and 1 year. RESULTS: In all, 295 patients were enrolled with a follow-up of 82%, resulting in 241 study patients. An additional five patients died from non-TBI causes and were excluded. The mean and median times for the last follow-up in the 236 remaining patients were 307 and 357 days, respectively. Patients were divided into four age ranges: 18 to 29 years (n = 66), 30 to 44 years (n = 54), 45 to 59 years (n = 50), and > or =60 years (n = 65). More severe TBIs, as measured by admitting Glasgow Coma Scale (GCS), were observed in the youngest group compared with all others but there were no differences in mean GCS between the remaining three groups. There were no differences in neurosurgical intervention between the groups. Age was a major determinant in the outcome at discharge and last follow-up. Patients over 60 years discharged with a GOS < or =4 were less likely to improve at 1 year than all other groups (37% versus 63 to 85%; p < or = 0.05). Patients between 18 and 29 years of age had the lowest mean Glasgow Outcome Scale and discharge FIM scores, which correlated with the low admission GCS. Despite the increased severity of TBI, this group had the best FIM score at 1 year. In contrast, patients older than 60 years had the least improvement and had a significantly lower final FIM score at 1 year compared with all other groups. CONCLUSION: Older patients following isolated TBI have poorer functional status at discharge and make less improvement at 1 year compared with all other patients. These worse outcomes occur despite what appears to be less severe TBI as measured by a higher GCS upon admission. Differences in outcome begin to appear even in patients between 45 and 59 years. Further investigations with more detailed outcome instruments are required to better understand the qualitative limitations of a patient's recovery and to devise strategies to maximize functional improvement following TBI. Age is an exceedingly important parameter affecting recovery from isolated TBI.

Adolescent↗

PubMed2005

A novel method of evaluating the impact of secondary brain insults on functional outcomes in traumatic brain-injured patients.

OBJECTIVES: Prior studies suggest that the emergency department (ED) occurrence of secondary brain insults (SBIs), such as systemic hypotension and hypoxia, worsens outcome in patients with traumatic brain injury. However, previous methods of assessing SBIs have been relatively crude, generally only determining the incidence and duration of events. The authors hypothesized that a new method that accounts for the cumulative depth and duration of SBIs would provide a more informative measure that better correlates with outcome. METHODS: The authors developed a computer algorithm to calculate the total "dose" of an SBI (in this case, hypotension and hypoxia) as the area under the curve between a cut-point value and a measured vital sign over time. To test this method, the authors used an existing data set of head trauma patients for whom occurrence in the ED of any hypotension had been shown to be associated with in-hospital mortality. The authors applied the algorithm using the cut-point values from the prior study (systolic blood pressure </=90 mm Hg and oxygen saturation </=92%). The effects of SBIs on in-hospital mortality and three-month Glasgow Outcome Scale score were evaluated. RESULTS: Of 107 patients overall, 26 had hypotension (dose range 0.2-898 mm Hg . min) and 40 had hypoxia (dose range 0.005-6.7% . min). Moderate and high doses of hypotension were more strongly associated with outcome than the measures from the initial study (any hypotension and number of hypotensive episodes). Hypoxia had no effect. CONCLUSIONS: New methods of measuring SBIs that take into account depth and duration of episodes may more accurately reflect the influence of these events on outcome after head trauma.

Adult↗

PubMed2005

Brain tissue oxygen monitoring in intracerebral hemorrhage.

INTRODUCTION: Brain tissue oxygen (PbrO2) monitoring is an emerging technique for detection of secondary brain injury in neurocritical care. Although it has been extensively reported in traumatic brain injury and aneurysmal subarachnoid hemorrhage, its use in nontraumatic intracerebral hemorrhage (ICH) has not been well described. We report complementary preliminary studies in a large animal model and in patients that demonstrate the feasibility of PbrO2 monitoring after ICH. METHODS: To assess early events after ICH, Licox Clark-type oxygen probes were inserted in the bilateral frontal white matter of four anesthetized swine that subsequently underwent right parietal hematoma formation in an experimental model of ICH. Intracranial pressure (ICP) was monitored as well. Seven patients with acute ICH, who were undergoing ICP monitoring as part of standard neurocritical care, had placement of a frontal oxygen probe, with subsequent monitoring for up to 7 days. RESULTS: In the swine ICH model, a rise in ICP early after hematoma formation was accompanied by a decrease in ipsilateral and contralateral PbrO2. Secondary increases in hematoma volume resulted in further decreases in PbrO2 over the first hour after ICH. In patients undergoing oxygen monitoring, low PbrO2 (<15 mmHg) was common. In these patients, changes in FiO2, mean arterial pressure, and cerebral perfusion pressure (but not ICP) predicted subsequent change in PbrO2. CONCLUSION: Brain tissue oxygen monitoring is feasible in ICH patients, as well as in a swine model of ICH. Translational research that emphasizes complementary information derived from human and animal studies may yield additional insights not available from either alone.

Animals↗

PubMed2005

Relationship between brain tissue oxygen tension and CT perfusion: feasibility and initial results.

BACKGROUND AND PURPOSE: Monitoring of intraparenchymal brain tissue oxygen tension (P(br)O(2)) is an emerging tool in neurocritical care. The purpose of this study was to determine if there is a relationship between CT perfusion (CTP) imaging parameters and P(br)O(2). METHODS: Nineteen patients underwent continuous P(br)O(2) monitoring with probes placed to target white matter in the cerebral hemisphere. Twenty-two CTP studies were performed at the level of the oxygen electrode, as identified on concurrent nonenhanced CT. CTP analysis software was used to measure mean transit time (MTT) and cerebral blood volume (CBV) and to derive cerebral blood flow (CBF) for a region of interest (ROI) surrounding the oxygen probe. For correlation, P(br)O(2) levels and other physiologic parameters were recorded at the time of CTP. RESULTS: P(br)O(2) values at the time of CTP were 2.7-54.4 mm Hg, MTT was 1.86-5.79 seconds, CBV was 1.18-8.76 mL/100 g, and CBF was 15.2-149.2 mL/100 g/min. MTT but not CBV or CBF was correlated with P(br)O(2) (r = -0.50, P = .017). MTT, CBV, or CBF were not correlated with other physiologic parameters, including mean arterial pressure, cerebral perfusion pressure, intracranial pressure, and fraction of inspired oxygen. On multivariable analysis, only P(br)O(2) was independently associated with MTT. CONCLUSION: CTP assessment of ROI surrounding an oxygen probe in the intraparenchymal brain tissue is feasible and showed a significant correlation between P(br)O(2) and MTT. Further studies are warranted to determine the role of CTP in assessing acute brain injury and whether it can be used to prospectively identify brain regions at risk for tissue hypoxia that should be targeted for advanced neuromonitoring.

Adult↗

PubMed2004

Thromboembolism after trauma: an analysis of 1602 episodes from the American College of Surgeons National Trauma Data Bank.

OBJECTIVE: Venous thromboembolic events (VTE) are potentially preventable causes of morbidity and mortality after injury. We hypothesized that the current clinical incidence of VTE is relatively low and that VTE risk factors could be identified. METHODS: We queried the ACS National Trauma Data Bank for episodes of deep venous thrombosis (DVT) and/or pulmonary embolism (PE). We examined demographic data, VTE risk factors, outcomes, and VTE prophylaxis measures in patients admitted to the 131 contributing trauma centers. RESULTS: From a total of 450,375 patients, 1602 (0.36%) had a VTE (998 DVT, 522 PE, 82 both), for an incidence of 0.36%. Ninety percent of patients with VTE had 1 of the 9 risk factors commonly associated with VTE. Six risk factors found to be independently significant in multivariate logistic regression for VTE were age > or = 40 years (odds ratio [OR] 2.01; 95% confidence interval [CI] 1.74 to 2.32), lower extremity fracture with AIS > or = 3 (OR 1.92; 95% CI 1.64 to 2.26), head injury with AIS > or = 3 (OR 1.24; 95% CI 1.05 to 1.46), ventilator days >3 (OR 8.08; 95% CI 6.86 to 9.52), venous injury (OR 3.56; 95% CI 2.22 to 5.72), and a major operative procedure (OR 1.53; 95% CI 1.30 to 1.80). Vena cava filters were placed in 3,883 patients, 86% as PE prophylaxis, including in 410 patients without an identifiable risk factor for VTE. CONCLUSIONS: Patients who need VTE prophylaxis after trauma can be identified based on risk factors. The use of prophylactic vena cava filters should be re-examined.

Adolescent↗

PubMed2004

The effect of age on functional outcome in mild traumatic brain injury: 6-month report of a prospective multicenter trial.

OBJECTIVE: Elderly patients (aged 60 years and older) have been demonstrated to have an increased mortality after isolated traumatic brain injury (TBI); however, the prognosis of those patients surviving their hospitalization is unknown. We hypothesized that surviving elderly patients would also have decreased functional outcome, and this study examined the functional outcome of patients with isolated TBI at discharge and at 6 months posthospitalization. METHODS: This was a multicenter prospective study of all patients with isolated moderate to severe TBI defined as Head Abbreviated Injury Scale score of 3 with an Abbreviated Injury Scale score in any other body area of 1. Patients surviving to discharge gave their consent and were enrolled. Data collected included demographics, Glasgow Coma Scale (GCS) score at admission, and neurosurgical interventions. Outcome data included discharge disposition and Glasgow Outcome Scale score and modified Functional Independence Measure (FIM) score at discharge and at 6 months. RESULTS: Two hundred thirty-five patients were enrolled, with 44 (19%) aged greater than or equal to 65 years. Mechanisms of injury were falls (34%), assaults (28%), motor vehicle collisions (14%), pedestrian (11%), and other (12%). Falls were more common in the older patients and assaults in the younger group. The mean admitting GCS score was 12.8 (95% confidence interval [CI], 12.4-13.3), with older patients having a higher mean GCS score, 14.1 (95% CI, 13.6-14.6) versus 12.5 (95% CI, 12.0-13.1; p = 0.03). There were no differences in the percentage of patients admitted to the intensive care unit or requiring neurosurgical intervention between younger and older patients. Because there were few elderly patients with low GCS scores who survived to discharge, outcome measures focused on those patients with GCS scores of 13 to 15. A greater percentage of elderly were discharged to rehabilitation (28% vs. 16%, p =0.08). The mean discharge FIM score was 10.4 (95% CI, 9.8-11.0) for the elderly versus 11.4 (95% CI, 11.1-11.7) for the young (p =0.001), with 68% elderly and 89% young discharged with total independent scores of 11 to 12. At 6 months, the difference narrowed, but the mean FIM score was still greater for the young group, 11.7 (95% CI, 11.6-11.9) versus 11.0 (95% CI, 10.6-11.4; p < 0.001). CONCLUSION: Functional outcome after isolated mild TBI as measured by the Glasgow Outcome Scale and modified FIM is generally good to excellent for both elderly and younger patients. Older patients required more inpatient rehabilitation and lagged behind their younger counterparts but continued to recover and improve after discharge. Although there were statistically significant differences in the FIM score at both discharge and 6 months, the clinical importance of these small differences in the mean FIM score to the patient's quality of life is less clear. Measurable improvement in functional status during the first 6 months after injury is observed in both groups. Aggressive management and care of older patients with TBI is warranted, and efforts should be made to decrease inpatient mortality. Continued follow-up is ongoing to determine whether these outcomes persist at 12 months.

Abbreviated Injury Scale↗

PubMed2003

Small-volume resuscitation with the hemoglobin substitute HBOC-201: effect on brain tissue oxygenation.

OBJECTIVES: To investigate the effects of small-volume resuscitation with a hemoglobin based oxygen carrier on brain tissue oxygen tension (PbrO2) in hemorrhaged swine. METHODS: Clark-type electrodes were inserted into the brain tissue of 6 swine to measure PbrO2 directly. Swine were hemorrhaged to a MAP of 40 mm Hg for 20 minutes. Resuscitation was performed with a bolus infusion of HBOC-201 (6 cc/kg; Biopure Corp.) and high-flow oxygen (100%). Swine were observed for an additional 2 hours. RESULTS: PbrO2 prior to hemorrhage was 48.7 +/- 4.7 mm Hg with 100% inspired oxygen. PbrO2 rapidly declined to 7.6 +/- 5.3 mm Hg in response to hemorrhage. Small-volume resuscitation with HBOC-201 and high-flow oxygen resulted in a significant increase (p < 0.001) in PbrO2 to 44.6 +/- 8.1 mm Hg. MAP was also significantly increased to 84% of baseline. These elevations were sustained during the observation period. CONCLUSIONS: Resuscitation with HBOC-201 can restore and sustain cerebral oxygenation and MAP. These results suggest that a small-volume bolus of HBOC-201 may provide adequate oxygen and pressure support during the initial management of hemorrhage.

Animals↗

PubMed2003

Trauma assessment training with a patient simulator: a prospective, randomized study.

BACKGROUND: Patient simulators are computer-controlled mannequins that may increase realism during trauma training by providing real-time changes in vital signs and physical findings during trauma scenarios. We hypothesized that trauma assessment training on a patient simulator would be as effective as training with a more traditional moulage patient/actor. METHODS: This study was conducted during a surgery intern orientation at two academic trauma centers. Interns (n = 60) attended a basic trauma course, and were then randomized to trauma assessment practice sessions with either the patient simulator (n = 30) or a moulage patient (n = 30). After practice sessions, interns were randomized a second time to an individual trauma assessment test on either the simulator or the moulage patient. Two surgeon-judges rated each intern live and on video for completion of 50 predetermined assessment objectives (total score) divided into sections (primary and secondary survey, general performance, diagnostic studies/procedures, and plan) and the identification and management of an acute neurologic deterioration in the test patient (event score). Multiple linear regression with random student effects was used to estimate the independent effects of all study variables. RESULTS: Within randomized groups, mean trauma assessment test scores for all simulator-trained interns were higher when compared with all moulage-trained interns (71 +/- 8 vs. 66 +/- 8, respectively; p = 0.02). Simulator training independently showed a small but statistically significant improvement in both the total score and the event score (+4.6 and +8.6, respectively; p < 0.05). CONCLUSION: Use of a patient simulator to introduce trauma assessment training is feasible and compares favorably to training in a moulage setting. Continued research in this area of physician education is warranted.

Educational Measurement↗

PubMed2003

Tissue oxygen monitoring during hemorrhagic shock and resuscitation: a comparison of lactated Ringer's solution, hypertonic saline dextran, and HBOC-201.

BACKGROUND: The ideal resuscitation fluid for the trauma patient would be readily available to prehospital personnel, universally compatible, effective when given in small volumes, and capable of reversing tissue hypoxia in critical organ beds. Recently developed hemoglobin-based oxygen-carrying solutions possess many of these properties, but their ability to restore tissue oxygen after hemorrhagic shock has not been established. We postulated that a small-volume resuscitation with HBOC-201 (Biopure) would be more effective than either lactated Ringer's (LR) solution or hypertonic saline dextran (HSD) in restoring baseline tissue oxygen tension levels in selected tissue beds after hemorrhagic shock. We further hypothesized that changes in tissue oxygen tension measurements in the deltoid muscle would reflect the changes seen in the liver and could thus be used as a monitor of splanchnic resuscitation. METHODS: This study was a prospective, blinded, randomized resuscitation protocol using anesthetized swine (n = 30), and was modeled to approximate an urban prehospital clinical time course. After instrumentation and splenectomy, polarographic tissue oxygen probes were placed into the liver (liver PO2) and deltoid muscle (muscle PO2) for continuous tissue oxygen monitoring. Swine were hemorrhaged to a mean arterial pressure (MAP) of 40 mm Hg over 20 minutes, shock was maintained for another 20 minutes, and then 100% oxygen was administered. Animals were then randomized to receive one of three solutions: LR (12 mL/kg), HSD (4 mL/kg), or HBOC-201 (6 mL/kg). Physiologic variables were monitored continuously during all phases of the experiment and for 2 hours postresuscitation. RESULTS: At a MAP of 40 mm Hg, tissue PO2 was 20 mm Hg or less in both the liver and muscle beds. There were no significant differences in measured liver or muscle PO2 values after resuscitation with any of the three solutions in this model of hemorrhagic shock. When comparing the hemodynamic effects of resuscitation, the cardiac output was increased from shock values in all three animal groups with resuscitation, but was significantly higher in the animals resuscitated with HSD. Similarly, MAP was increased by all solutions during resuscitation, but remained significantly below baseline except in the group of animals receiving HBOC-201 (p < 0.01). HBOC-201 was most effective in both restoring and sustaining MAP and systolic blood pressure. There was excellent correlation between liver and deltoid muscle tissue oxygen values (r = 0.8, p < 0.0001). CONCLUSION: HBOC-201 can be administered safely in small doses and compared favorably to resuscitation with HSD and LR solution in this prehospital model of hemorrhagic shock. HBOC-201 is significantly more effective than HSD and LR solution in restoring MAP and systolic blood pressure to normal values. Deltoid muscle PO2 reflects liver PO2 and thus may serve as an index of the adequacy of resuscitation in critical tissue beds.

Animals↗

PubMed2003

The development of acute lung injury is associated with worse neurologic outcome in patients with severe traumatic brain injury.

OBJECTIVE: The purpose of this study was to determine the incidence of acute lung injury (ALI) in trauma patients with severe traumatic brain injury (TBI), to evaluate the impact of ALI on mortality and neurologic outcome after severe traumatic brain injury (TBI), and to identify whether the development of ALI correlates with the severity of TBI. METHODS: Clinical data were collected prospectively over a 4-year period in a Level I trauma center. Patients included in the study met the following criteria: mechanical ventilation > 24 hours, head Abbreviated Injury Scale score >or= 3, no other body region Abbreviated Injury Scale score >or= 3, and age between 18 and 54 years. ALI was defined using international consensus criteria. Glasgow Outcome Scale scores were assessed at 3 and 12 months. Bivariate comparisons were made between ALI and non-ALI groups. Multivariate analysis with stepwise logistical regression was used to assess independent factors on mortality. The patient's admission head computed tomographic (CT) scan was graded using the Marshall system, and the presence and size of specific intracranial abnormality was noted. Glasgow Coma Scale (GCS) score, Marshall CT scan score, and intracranial abnormality were correlated with the development of ALI. RESULTS: One hundred thirty-seven patients with isolated head trauma were enrolled in the study over a 4-year period. Thirty-one percent of patients with severe TBI developed ALI. Head trauma patients with ALI had a significantly higher ISS, a greater number of days on the ventilator, and a worse neurologic outcome for those who survived their hospitalization. Mortality was 38% in the ALI group and 15% in the non-ALI group (p = 0.004). Only 3 of 16 (19%) of the deaths within the ALI group were directly related to ALI. By multivariate analysis, only the presence of ALI, older age, and lower initial GCS score were associated with higher mortality. There was no association between ISS, the presence of arterial hypotension (arterial systolic pressure < 90 mm Hg) at admission to the hospital, or the amount of blood transfused and mortality. No correlation was found between the severity of head injury (GCS score, Marshall score, or intracranial abnormality) and development of ALI. CONCLUSION: The development of ALI is a critical independent factor affecting mortality in patients suffering traumatic brain injury and is associated with a worse long-term neurologic outcome in survivors. The risk of developing ALI is not associated with specific anatomic lesions diagnosed by cranial CT scanning.

Abbreviated Injury Scale↗

PubMed2002

Serum levels of Hsp 72 measured early after trauma correlate with survival.

BACKGROUND: Experimental studies have shown that hemorrhagic shock is associated with the expression of inducible heat proteins, especially heat shock protein (Hsp) 72, in liver, brain, heart, and kidney. Moreover, induction of Hsp 72 by various stressors before the onset of shock has been associated with the attenuation of organ injury caused by hemorrhage. However, it is not known whether Hsp 72 is expressed after severe trauma in humans. The purpose of this study was therefore to determine whether Hsp 72 could be detected in the serum of patients early after severe trauma and whether serum levels of Hsp 72 might correlate with survival of trauma patients or the severity of the postinjury inflammatory response. METHODS: Clinical data were collected prospectively over a 3-year period for trauma patients mechanically ventilated for more than 2 days who met the following inclusion criteria: Injury Severity Score > or = 16, and age > 18 years. Physiologic data for quantitative assessment of organ dysfunction were collected for each patient. Hsp 72 and nitrate and nitrite levels were measured in the serum of trauma patients collected at or 12 to 48 hours after the admission to the emergency department. RESULTS: Sixty-seven patients with severe trauma were enrolled in the study. Hsp 72 was detected in the serum of all trauma patients. All patients with high initial serum levels of Hsp 72 (serum levels > 15 ng/mL) survived, whereas 29% of the patients with low Hsp 72 serum levels died from their traumatic injuries (p = 0.01). The overall mortality was 21%, occurring within 5 to 7 days. Patients who died were older (mean age, 54 +/- 15 years) than those who survived (mean age, 36 +/- 15 years) (p < 0.0.05). The cause of death was attributable to head injury in 79%, although the severity of head injury (Abbreviated Injury Scale score) was not statistically different between survivors with high serum values of Hsp 72 and patients who died. There was no correlation between the initial serum Hsp 72 values and the severity of organ dysfunction or clinical indicators of the inflammatory response. CONCLUSION: Hsp 72 can be detected in the serum of severely traumatized patients within 30 minutes after injury. Elevated initial serum levels of Hsp 72 (serum levels > 15 ng/mL) are associated with survival after severe trauma, but are not related to the incidence or severity of the postinjury inflammatory response or organ dysfunction.

Analysis of Variance↗

PubMed2002

Small-volume resuscitation with HBOC-201: effects on cardiovascular parameters and brain tissue oxygen tension in an out-of-hospital model of hemorrhage in swine.

OBJECTIVE: Hemoglobin-based oxygen carriers, such as HBOC-201, offer several potential advantages over conventional resuscitation solutions or banked blood in the acute treatment of hemorrhagic shock. While previous studies with some hemoglobin solutions revealed vasoactive effects resulting in decreased oxygen delivery, these investigations were performed without directly measuring vital tissue oxygenation. The authors tested the hypothesis that a small-volume bolus of HBOC-201 would improve and sustain brain tissue oxygen tension (PbrO(2)) without adverse effects on cardiovascular end-points, when used in an acute out-of-hospital hemorrhage model. METHODS: Male Yorkshire swine (n = 7) were hemorrhaged to a mean arterial pressure (MAP) of 40 mm Hg while monitoring standard hemodynamic parameters. In addition, Clark-type polarographic probes were directly inserted into brain tissue to measure PbrO(2). Following institution of high-flow oxygen (FiO(2) = 1.0), resuscitation was performed with a bolus infusion of HBOC-201 (6 mL/kg). Swine were observed for two hours. RESULTS: Cardiac output (CO), MAP, pulmonary artery diastolic pressure (PAD), and PbrO(2) all decreased significantly with hemorrhage (p < 0.05). Immediately following resuscitation with HBOC-201 (mean volume = 239 mL), MAP and CO were restored to 83% and 84% of baseline levels, respectively. PbrO(2) increased significantly after treatment with HBOC-201, surpassing baseline levels by 66%. PAD rose above baseline levels during observation, but this increase was not significantly different from baseline levels (24.0 mm +/- 4.1 vs. 22.7 mm +/- 7.4). CONCLUSIONS: Small-volume resuscitation with HBOC-201 rapidly restored hemodynamic parameters and PbrO(2) following severe hemorrhage without detrimental vasoactive effects and without compromise to directly monitored brain tissue oxygenation. The results of this preliminary study demonstrate that HBOC-201 could potentially improve current resuscitation measures and that further investigations with HBOC-201 are warranted.

Animals↗