Evaluation of umbilical venous flow volume measured using ultrasound compared to circuit flow volume in the EXTra-uterine Environment for Neonatal Development (EXTEND) system in fetal sheep.

OBJECTIVE: To compare and validate umbilical venous flow volume (UVFV) measured at the intra-abdominal portion using ultrasound with actual flow volume of umbilical vein (UV) in fetal sheep sustained on the EXTrauterine Environment for Neonatal Development (EXTEND) system. METHODS: Circuit flow volume through the oxygenator was obtained using sensors. Ultrasound derived UVFV (ml/min) was calculated as (UV diameter [cm]/2)2 × 3.14 × maximum velocity (cm/s) × 0.5 × 60, measured at approximately the mid portion between its abdominal insertion and the origin of the ductus venosus. UVFV was measured by ultrasound once daily and was compared to the average of daily circuit flow volume directly measured. RESULTS: UVFV was measured 168 times in 15 fetal sheep. The ratio of circuit flow volume to combined cardiac output remained stable within the anticipated physiological range throughout. UVFV measured by ultrasound showed good correlation to directly measured circuit flow (r = 0.72). Interclass correlation coefficients for intra-observer variability was 0.991 (95% confidence interval [CI], 0.979-0.996). CONCLUSION: UVFV measured at the intra-abdominal portion using ultrasound shows a good correlation with directly measured circuit flow volume in UV of fetal sheep on the EXTEND system. Regular incorporation of such validated UVFV measures into clinical use may offer opportunities to better understand conditions of placental dysfunction.

Fetoscopic insufflation modeled in the extrauterine environment for neonatal development (EXTEND): Fetoscopic insufflation is safe for the fetus.

BACKGROUND: Minimally invasive fetal surgery, or fetoscopy, is an alternative to open fetal surgery to repair common birth defects like myelomeningocele. Although this hysterotomy-sparing approach reduces maternal morbidity, the effects of in utero insufflation on the fetus are poorly understood. Our purpose was to determine the optimal fetal insufflation conditions. METHODS: Fetal sheep at gestational age 104 to 107 days were studied under insufflation conditions in utero and ex utero. The ex utero fetuses were cannulated via their umbilical vessels into a support device, the EXTra-uterine Environment for Neonatal Development (EXTEND). EXTEND fetuses were exposed to four different insufflation conditions for four hours: untreated carbon dioxide (CO2) (n=5), warm humidified (whCO2) (n=4), whCO2 with the umbilical cord exposed (n=3), and whCO2 without amniotic fluid (skin and cord exposed) (n=3). RESULTS: In utero insufflation led to significant increases in fetal CO2 and reductions in fetal pH. Ex utero insufflation with whCO2 did not lead to changes in fetal blood gas measurements or cerebral perfusion parameters. Insufflation with whCO2 with an exposed umbilical cord led to reduced umbilical blood flow. CONCLUSIONS: Insufflation with warm humidified CO2 with an amniotic fluid covered umbilical cord is well tolerated by the fetus without significant changes in hemodynamics or cerebral perfusion parameters. TYPE OF STUDY: Basic science LEVEL OF EVIDENCE: N/A.

The EXTrauterine Environment for Neonatal Development Supports Normal Intestinal Maturation and Development.

BACKGROUND AND AIMS: The Extra-Uterine Environment for Neonatal Development (EXTEND) aims to avoid the complications of prematurity, such as NEC. Our goal was to determine if bowel development occurs normally in EXTEND-supported lambs, with specific emphasis on markers of immaturity associated with NEC. METHODS: We compared terminal ileum from 17 pre-term lambs supported on EXTEND for 2- 4 weeks to bowel from age-matched fetal lambs that developed in utero. We evaluated morphology, markers of epithelial integrity and maturation, enteric nervous system structure, and bowel motility. RESULTS: EXTEND-supported lamb ileum had normal villus height, crypt depth, density of mucin-containing goblet cells, and enteric neuron density. Expression patterns for I-FABP, activated caspase-3 and EGFR were normal in bowel epithelium. Transmural resistance assessed in Ussing chambers was normal. Bowel motility was also normal as assessed by ex vivo organ bath and video imaging. However, Peyer's patch organization did not occur normally in EXTEND ileum, resulting in fewer circulating B cells in experimental animals. CONCLUSION: EXTEND supports normal ileal epithelial and enteric nervous system maturation in pre-term lambs. The classic morphologic changes and cellular expression profiles associated with NEC are not seen. However, immune development within the EXTEND supported lamb bowel does not progress normally.

Neurologic outcomes of the premature lamb in an extrauterine environment for neonatal development.

BACKGROUND/PURPOSE: Neurologic injury remains the most important morbidity of prematurity. Those born at the earliest gestational ages can face a lifetime of major disability. Perinatal insults result in developmental delay, cerebral palsy, and other profound permanent neurologic impairments. The EXTracorporeal Environment for Neonatal Development (EXTEND) aims to transition premature neonates through this sensitive period, but it's impact on neurologic development requires analysis. METHODS: Fetal sheep were maintained in a fluid-filled environment for up to 28 days. Physiologic parameters were measured continuously; tissues were subsequently fixed and preserved for myelin quantification, glial cell staining, and structural assessment via magnetic resonance. Surviving animals were functionally assessed. RESULTS: No evidence of fetal brain ischemia or white matter tract injury associated with the EXTEND system was detected, and the degree of myelination was regionally appropriate and consistent with age matched controls. No evidence of neurologic injury or immaturity was visible on magnetic resonance; animals that transitioned from the system had no persistent neurologic deficits. CONCLUSIONS: No evidence of major neurologic morbidity was found in animals supported on the EXTEND system, though more work needs to be done in order to verify its safety during critical periods of neurologic development.

Ex Utero Extracorporeal Support as a Model for Fetal Hypoxia and Brain Dysmaturity.

BACKGROUND: Congenital heart disease (CHD) is associated with abnormal fetal brain development, a phenomenon that may be related to decreased cerebral oxygen delivery in utero. We used an artificial womb model to test the hypothesis that decreasing fetal oxygen delivery would reproduce physiologic changes identified in fetuses with CHD. METHODS: Experimental (hypoxemic) fetal lambs (mean gestational age, 111 ± 3 days; n = 4) and control animals (112 days; n = 5) were maintained in the artificial womb for a mean of 22 ± 6 days. Oxygen delivery was reduced to 15.6 ± 1.0 mL/kg/min in the hypoxemia animals versus 21.6 ± 2.0 mL/kg/min in the control animals. Blood chemistry analysis and sonographic evaluation were performed daily. An additional control group (n = 7) was maintained in utero and harvested for analysis at gestational age 134 ± 4 days. RESULTS: Physiologic variables were monitored continuously, and no statistical differences between the groups were identified. Fetal oxygen delivery and arterial partial pressure of oxygen were remarkably lower in the experimental group longitudinally. Increased umbilical artery and decreased middle cerebral artery resistance resulted in a lower cerebral to umbilical resistance ratio, similar to the brain sparing effect observed in human fetuses with CHD. Experimental brains were smaller than control brains in relation to the calvarium on magnetic resonance. CONCLUSIONS: Sustained hypoxemia in fetal sheep leads to altered cerebrovascular resistances and loss of brain mass, similar to human fetuses with CHD. This unique model provides opportunities to investigate the pathologic process underlying CHD-associated brain dysmaturity and to evaluate potential fetal neuroprotective therapies.

The Effects of Nitric Oxide in Oxygenator Sweep Gas During Extracorporeal Circulation in a Neonatal Ovine Model.

Extracorporeal membrane oxygenation is a life-saving intervention, but bleeding complications are frequent. Given that the combination of platelet loss and dysfunction is a major contributor to this acquired bleeding diathesis, efforts to combat these phenomena are of great clinical importance. In this study, we investigated the effects of nitric oxide (NO) added to the sweep gas of an extracorporeal circuit in a neonatal ovine model. Eight lambs (age 9.6 ± 1.9 days) were cannulated via the neck vessels and maintained on a pumpless arteriovenous extracorporeal membrane oxygenation circuit with blood flow restricted to 100 ml/min for 72 hours. All animals were heparinized, and a subset (n = 4) also received NO in the sweep gas at a concentration of 200 ppm. We observed no adverse effects from NO administration, and methemoglobin levels remained unchanged. Platelet counts significantly declined in all animals over the course of the study; however, mean counts were higher in the NO-treated group, and this difference was statistically significant at 24 hours (62 ± 3% vs. 32 ± 7% of baseline, P < 0.01). Likewise, mean plasma levels of beta-thromboglobulin, a marker of platelet activation, were lower in the NO-treated group, and this difference was also significant at the 24 hour time point (9.5 ± 2.2 vs. 19.7 ± 6.5 pg/mL/10 platelets, P < 0.05). We conclude that 200 ppm NO can be safely blended into the oxygenator sweep gas of a low-flow extracorporeal circuit and that it may transiently attenuate platelet consumption and activation.

Technical feasibility of umbilical cannulation in midgestation lambs supported by the EXTra-uterine Environment for Neonatal Development (EXTEND).

EXTEND (EXTra-uterine Environment for Neonatal Development) is a novel system for supporting extremely premature infants that replicates in utero conditions by maintaining a sterile fluid environment and providing gas exchange via a pumpless arteriovenous oxygenator circuit connected to the umbilical vessels. Target gestational age (GA) for EXTEND support in human infants is 23-27 weeks, when immature lungs are most susceptible to injury in the setting of air ventilation. We previously demonstrated physiologic support of premature lambs cannulated at 105-117 days GA (lungs developmentally analogous to the 23-27 week GA human infant) for up to 28 days on EXTEND. In the present study, we sought to determine the technical feasibility of umbilical vessel cannulation in 85-96 days GA lambs delivered to EXTEND at weights equivalent to the 23-27 week GA human infant (500-850 g). Five preterm lambs were cannulated at 85-96 days GA (term 145 days) and supported on EXTEND for 4-7 days. All lambs underwent umbilical artery and umbilical vein cannulation. Circuit flows and pressures were monitored continuously, and blood gases were obtained at regular intervals for assessment of oxygen parameters. Systemic pH and lactate were measured at least once daily. Mean body weight at cannulation was 641 ± 71 g (range 480-850 g). All lambs were cannulated successfully (cannula size varied from 8 to 12 Fr), and mean survival on EXTEND was 140 ± 7 hours. Mean circuit flow was 213 ± 15 mL/kg*min, mean pH was 7.37 ± 0.01, and mean lactate was 1.6 ± 0.2 mmol/L. During the initial 120 hours after EXTEND cannulation, there were no significant differences between 85-96 days GA lambs and 105-117 days GA lambs in weight-adjusted circuit flows, oxygen delivery, pH, or lactate levels. This study demonstrates successful umbilical cord cannulation and adequate circuit flows and oxygen delivery in midgestation lambs size-matched to the 23-27 week GA human fetus, which represents an important step in the translation of EXTEND to clinical practice.

Premature Lambs Exhibit Normal Mitochondrial Respiration after Long-Term Extrauterine Support.

BACKGROUND: In an effort to mitigate the major morbidities and mortality associated with extreme prematurity, we have developed an EXTrauterine Environment for Neonatal Development (EXTEND) designed to provide physiologic support of extremely premature infants. OBJECTIVES: We have previously shown that long-term, physiologic support of premature fetal lambs is possible with EXTEND, but in this study, we sought to demonstrate bioenergetic equipoise at the tissue level. METHODS: Four premature fetal lambs were delivered by hysterotomy at gestational ages (GA) of 105-107 days (term ∼145 days), cannulated via the umbilical vessels, and transitioned to support on EXTEND for 3-4 weeks. Five control fetuses were age-matched to the GA of experimental fetuses at the time of study end (128-134 days GA) and immediately sacrificed after hysterotomy. Mitochondria were isolated from the heart, liver, kidney, and skeletal muscle of fetuses at the time of sacrifice, and oxygen consumption rates (OCRs) were measured. RESULTS: There were no differences in basal mitochondrial OCR between EXTEND and control fetuses for heart, kidney, or skeletal muscle. For liver, the basal OCR was higher in EXTEND fetuses compared to controls. There were no differences in physiologic maximal OCR or reserve capacity for any tissue analyzed. CONCLUSIONS: Fetal lambs supported by EXTEND demonstrate physiologic mitochondrial function as evidenced by adequate basal and physiologic maximal cellular respiration as well as preserved reserve capacity.

Erythropoietin Prevents Anemia and Transfusions in Extremely Premature Lambs Supported by an EXTrauterine Environment for Neonatal Development (EXTEND).

BACKGROUND: We recently developed an EXTrauterine Environment for Neonatal Development (EXTEND) that provides physiologic support for premature lambs. Here, we assess the efficacy of exogenous erythropoietin (EPO) to prevent anemia and transfusions on EXTEND. MATERIALS AND METHODS: Lambs were cannulated at 0.7 gestation and supported on EXTEND for up to 4 weeks. The lambs were divided into three groups: (1) No EPO, (2) Low EPO (300 U kg-1 per day), and (3) High EPO (800 U kg-1 per day). Daily hematocrit and weekly complete blood count were assessed. RESULTS: The mean percentage change in hematocrit from baseline was significantly different between the groups (No EPO -23.6 ± 7.8% vs. Low EPO -16.6 ± 6.4% vs. High EPO +2.6 ± 6.6%; p = 0.02). This occurred despite a greater median number of blood transfusions in the No EPO group (5 vs. 1 vs. 0; p = 0.02). EPO administration was associated with a higher mean corpuscular volume (MCV; p < 0.01) and reticulocyte count (p = 0.02). The High EPO group was comparable to in utero control fetuses with respect to hematocrit (p = 0.49), MCV (p = 0.24), and reticulocyte count (p = 0.68). CONCLUSIONS: EPO (800 U kg-1 per day) prevents anemia, eliminates transfusions, and restores normal red blood cell indices in premature lambs supported by EXTEND.

Chronically Hypoxic Fetal Lambs Supported by an Extra-Uterine Device Exhibit Mitochondrial Dysfunction and Elevations of Hypoxia Inducible Factor 1-Alpha.

INTRODUCTION: We have recently developed an extra-uterine environment for neonatal development (EXTEND) capable of supporting premature fetal lambs and have been able to replicate hypoxic in utero conditions by controlling fetal oxygen delivery. In this study, we investigated the fetal mitochondrial response to hypoxia. METHODS: Eight premature fetal lambs were delivered via hysterotomy and transitioned to extra-uterine support for 3 weeks. The lambs were divided into 2 groups: normoxic fetuses which maintained physiologic oxygen delivery and hypoxic fetuses in which oxygen delivery was significantly reduced. Control fetuses were delivered via hysterotomy but not cannulated. Measurements of mitochondrial membrane potential (MMP) were performed in peripheral blood mononuclear cells. RESULTS: There were no significant differences in MMP between normoxic EXTEND fetuses and controls. Hypoxic fetuses had significantly more depolarized mitochondria compared to normoxic fetuses overall, and these changes were specifically appreciated in weeks 1 and 2, but not by week 3. Hypoxic fetuses had significantly elevated levels of HIF-1α compared to normoxic fetuses in the first 2 weeks. DISCUSSION: Normoxic fetal lambs supported by EXTEND demonstrate normal mitochondrial function as evidenced by equivalent membrane potentials compared to control fetuses. Hypoxic fetuses exhibit mitochondrial dysfunction, though they do show evidence of adaptation after 3 weeks of hypoxic exposure.

Fetal hypoxemia causes abnormal myocardial development in a preterm ex utero fetal ovine model.

In utero hypoxia is a major cause of neonatal morbidity and mortality and predisposes to adult cardiovascular disease. No therapies exist to correct fetal hypoxia. In a new ex utero fetal support system, we tested the hypothesis that hypoxemic support of the fetus impairs myocardial development, whereas normoxic support allows normal myocardial development. Preterm fetal lambs were connected via umbilical vessels to a low-resistance oxygenator and placed in a sterile-fluid environment. Control normoxic fetuses received normal fetal oxygenation, and hypoxemic fetuses received subphysiologic oxygenation. Fetuses with normal in utero development served as normal controls. Hypoxemic fetuses exhibited decreased maximum cardiac output in both ventricles, diastolic function, myocyte and myocyte nuclear size, and increased myocardial capillary density versus control normoxic fetuses. There were no differences between control normoxic fetuses in the fetal support system and normal in utero controls. Chronic fetal hypoxemia resulted in significant abnormalities in myocyte architecture and myocardial capillary density as well as systolic and diastolic cardiac function, whereas control fetuses showed no differences. This ex utero fetal support system has potential to become a significant research tool and novel therapy to correct fetal hypoxia.

Umbilical cannulation optimizes circuit flows in premature lambs supported by the EXTra-uterine Environment for Neonatal Development (EXTEND).

KEY POINTS: Bronchopulmonary dysplasia is a disease of extreme prematurity that occurs when the immature lung is exposed to gas ventilation. We designed a novel 'artificial womb' system for supporting extreme premature lambs (called EXTEND) that obviates gas ventilation by providing oxygen via a pumpless arteriovenous circuit with the lamb submerged in sterile artificial amniotic fluid. In the present study, we compare different arteriovenous cannulation strategies on EXTEND, including carotid artery/jugular vein (CA/JV), carotid artery/umbilical vein (CA/UV) and umbilical artery/umbilical vein (UA/UV). Compared to CA/JV and CA/UV cannulation, UA/UV cannulation provided significantly higher, physiological blood flows to the oxygenator, minimized flow interruptions and supported significantly longer circuit runs (up to 4 weeks). Physiological circuit blood flow in UA/UV lambs made possible normal levels of oxygen delivery, which is a critical step toward the clinical application of artificial womb technology. ABSTRACT: EXTEND (EXTra-uterine Environment for Neonatal Development) is a novel system that promotes physiological development by maintaining the premature lamb in a sterile fluid environment and providing gas exchange via a pumpless arteriovenous oxygenator circuit. During the development of EXTEND, different cannulation strategies evolved with the aim of improving circuit flow. The present study examines how different cannulation strategies affect EXTEND circuit haemodynamics in extreme premature lambs. Seventeen premature lambs were cannulated at gestational ages 105-117 days (term 145-150 days) and supported on EXTEND for up to 4 weeks. Experimental groups were distinguished by cannulation strategy: carotid artery outflow and jugular vein inflow (CA/JV; n = 4), carotid artery outflow and umbilical vein inflow (CA/UV; n = 5) and double umbilical artery outflow and umbilical vein inflow (UA/UV; n = 8). Circuit flows and pressures were measured continuously. As we transitioned from CA/JV to CA/UV to UA/UV cannulation, mean duration of circuit run and weight-adjusted circuit flows increased (P < 0.001) and the frequency of flow interruptions declined (P < 0.05). Umbilical vessels generally accommodated larger-bore cannulas, and cannula calibre was directly correlated with circuit pressures and indirectly correlated with flow:pressure ratio (a measure of post-membrane resistance). We conclude that UA/UV cannulation in fetal lambs on EXTEND optimizes circuit flow dynamics and flow stability and also supports circuit flows that closely approximate normal placental flow.

Corrigendum: An extra-uterine system to physiologically support the extreme premature lamb.

This corrects the article DOI: 10.1038/ncomms15112.

An extra-uterine system to physiologically support the extreme premature lamb.

In the developed world, extreme prematurity is the leading cause of neonatal mortality and morbidity due to a combination of organ immaturity and iatrogenic injury. Until now, efforts to extend gestation using extracorporeal systems have achieved limited success. Here we report the development of a system that incorporates a pumpless oxygenator circuit connected to the fetus of a lamb via an umbilical cord interface that is maintained within a closed 'amniotic fluid' circuit that closely reproduces the environment of the womb. We show that fetal lambs that are developmentally equivalent to the extreme premature human infant can be physiologically supported in this extra-uterine device for up to 4 weeks. Lambs on support maintain stable haemodynamics, have normal blood gas and oxygenation parameters and maintain patency of the fetal circulation. With appropriate nutritional support, lambs on the system demonstrate normal somatic growth, lung maturation and brain growth and myelination.

Admissions for isolated nonoperative mild head injuries: Sharing the burden among trauma surgery, neurosurgery, and neurology.

BACKGROUND: Isolated nonoperative mild head injuries (INOMHI) occur with increasing frequency in an aging population. These patients often have multiple social, discharge, and rehabilitation issues, which far exceed the acute component of their care. This study was aimed to compare the outcomes of patients with INOMHI admitted to three services: trauma surgery, neurosurgery, and neurology. METHODS: Retrospective case series (January 1, 2009 to August 31, 2013) at an academic Level I trauma center. According to an institutional protocol, INOMHI patients with Glasgow Coma Scale (GCS) of 13 to 15 were admitted on a weekly rotational basis to trauma surgery, neurosurgery, and neurology. The three populations were compared, and the primary outcomes were survival rate to discharge, neurological status at hospital discharge as measured by the Glasgow Outcome Score (GOS), and discharge disposition. RESULTS: Four hundred eighty-eight INOMHI patients were admitted (trauma surgery, 172; neurosurgery, 131; neurology, 185). The mean age of the study population was 65.3 years, and 58.8% of patients were male. Seventy-seven percent of patients has a GCS score of 15. Age, sex, mechanism of injury, Charlson Comorbidity Index, Injury Severity Score, Abbreviated Injury Scale in head and neck, and GCS were similar among the three groups. Patients who were admitted to trauma surgery, neurosurgery and neurology services had similar proportions of survivors (98.8% vs 95.7% vs 94.7%), and discharge disposition (home, 57.0% vs 61.6% vs 55.7%). The proportion of patients with GOS of 4 or 5 on discharge was slightly higher among patients admitted to trauma (97.7% vs 93.0% vs 92.4%). In a logistic regression model adjusting for Charlson Comorbidity Index CCI and Abbreviated Injury Scale head and neck scores, patients who were admitted to neurology or neurosurgery had significantly lower odds being discharged with GOS 4 or 5. While the trauma group had the lowest proportion of repeats of brain computed tomography (61.6%), the neurosurgery group had the highest proportion of intensive care unit admission (29.8%), and the neurology group had the longest emergency department stay (7.5 hours), there were no significant differences in duration of hospital stay, in-hospital complications, and readmission within 30 days. CONCLUSIONS: Although there were differences in use of health care resources, and the proportion of patients with GOS of 4 or 5 on discharge was slightly higher among patients admitted to trauma, most clinical outcomes were similar in INOMHI patients admitted to trauma surgery, neurosurgery, or neurology in our institution. A rotational policy of admitting INOMHI patients is feasible among services with expertise in and commitment to the care of these patients. LEVEL OF EVIDENCE: Therapeutic/care management study, level IV.

Additional Imaging in Alert Trauma Patients with Cervical Spine Tenderness and a Negative Computed Tomographic Scan: Is it Needed?

BACKGROUND: The value of additional imaging in clearing the cervical spine (C-spine) of alert trauma patients with tenderness on clinical exam and a negative computed tomographic (CT) scan is still unclear. METHODS: All adult trauma patients with a Glasgow Coma Scale of 15, C-spine tenderness in the absence of neurologic signs, and a negative C-spine CT were included. The study period extended from September 2011 to June 2012. C-spine CT scans were interpreted in detail and considered negative in the absence of any findings indicating bony, ligamentous, or soft tissue injury around the C-spine. The incidence of C-spine injury was evaluated using early (<24 h) repeat physical examination, MRI, and/or flexion-extension films. RESULTS: Of 2015 patients with a C-spine CT, 383 (19 %) fulfilled the inclusion criteria. The median age was 43 (IQR: 30-53) and 44.7 % were female. Thirty-six patients (9.4 %) underwent MRI (3.7 %), flexion-extension imaging (5.2 %), or both (0.5 %), with no significant injuries identified and subsequent removal of the collar allowed. The remaining patients were clinically cleared within 24 h of presentation. None of the patients developed neurological signs following removal of the collar. On bivariate analysis, no variable except for evaluation by trauma surgery was associated with performance of additional imaging. CONCLUSION: C-spine precautions can be withdrawn without additional imaging in most blunt trauma patients with C-spine tenderness but negative neurologic evaluation and C-spine CT. Focus should be placed on the detailed and comprehensive interpretation of the C-spine CT.

The clinical significance of isolated loss of lordosis on cervical spine computed tomography in blunt trauma patients: a prospective evaluation of 1,007 patients.

BACKGROUND: A negative computed tomographic (CT) scan may be used to rule out cervical spine (c-spine) injury after trauma. Loss of lordosis (LOL) is frequently found as the only CT abnormality. We investigated whether LOL should preclude c-spine clearance. METHODS: All adult trauma patients with isolated LOL at our Level I trauma center (February 1, 2011 to May 31, 2012) were prospectively evaluated. The primary outcome was clinically significant injury on magnetic resonance imaging (MRI), flexion-extension views, and/or repeat physical examination. RESULTS: Of 3,333 patients (40 ± 17 years, 60% men) with a c-spine CT, 1,007 (30%) had isolated LOL. Among 841 patients with a Glasgow Coma Scale score of 15, no abnormalities were found on MRI, flexion-extension views, and/or repeat examinations, and all collars were removed. Among 166 patients with Glasgow Coma Scale less than 15, 3 (.3%) had minor abnormal MRI findings but no clinically significant injury. CONCLUSION: Isolated LOL on c-spine CT is not associated with a clinically significant injury and should not preclude c-spine clearance.

Real-time heart rate entropy predicts the need for lifesaving interventions in trauma activation patients.

BACKGROUND: Heart rate complexity (HRC), commonly described as a "new vital sign," has shown promise in predicting injury severity, but its use in clinical practice has been precluded by the absence of real-time data. This study was conducted to evaluate the utility of real-time, automated, instantaneous, hand-held heart rate entropy analysis in predicting the need for lifesaving interventions (LSIs). We hypothesized that real-time HRC would predict LSIs. METHODS: Prospective enrollment of patients who met criteria for trauma team activation was conducted at a Level I trauma center (September 2011 to February 2012). A novel, hand-held, portable device was used to measure HRC (by sample entropy) and time-domain heart rate variability continuously in real time for 2 hours after the moment of presentation. Electric impedance cardiography was used to determine cardiac output. Patients who received an LSI were compared with patients without any intervention (non-LSI). Multivariable analysis was performed to control for differences between the groups. RESULTS: Of 82 patients enrolled, 21 (26%) received 67 LSIs within 24 hours of hospital arrival. Initial systolic blood pressure was similar in both groups. LSI patients had a lower Glasgow Coma Scale (GCS) score (9.2 [5.1] vs. 14.9 [0.2], p < 0.0001). The mean (SD) HRC value on presentation was 0.8 (0.6) in the LSI group compared with 1.5 (0.6) in the non-LSI group (p < 0.0001). With the use of logistic regression, initial HRC was the only significant predictor of LSI. A cutoff value for HRC of 1.1 yields sensitivity, specificity, negative predictive value, and positive predictive value of 86%, 74%, 94%, and 53%, respectively, with an accuracy of 77% for predicting an LSI. CONCLUSION: Decreased HRC on hospital arrival is an independent predictor of the need for LSI in trauma activation patients. Real-time HRC may be a useful adjunct to standard vital signs monitoring and predicts LSIs. LEVEL OF EVIDENCE: Prognostic and diagnostic study, level III.

Outcomes following "rescue" superselective angioembolization for gastrointestinal hemorrhage in hemodynamically unstable patients.

BACKGROUND: Therapeutic angioembolization is a relatively new "rescue treatment" modality for gastrointestinal hemorrhage (GIH) for unstable patients who fail primary treatment approaches; however, the effectiveness of this treatment and the incidence of ischemic necrosis following embolization for acute GIH are poorly described. The purpose of this study was to evaluate the effectiveness and safety of "rescue" transcatheter superselective angioembolization (SSAE) for the treatment of hemodynamically unstable patients with GIH. METHODS: A 10-year retrospective review of all hemodynamically unstable patients (systolic blood pressure < 90 mm Hg and ongoing transfusion requirement) who underwent "rescue" SSAE for GIH after failed endoscopic management was performed. All patients with evidence of active contrast extravasation were included. Data were collected on demographics, comorbidities, clinical presentation, and type of intravascular angioembolic agent used. Outcomes included technical success (cessation of extravasation), clinical success (no rebleeding requiring intervention within 30 days), and incidence of ischemic complications. RESULTS: Ninety-eight patients underwent SSAE for GIH during the study period; 47 were excluded owing to lack of active contrast extravasation. Of the remaining 51 patients, 22 (43%) presented with a lower GIH and 29 (57%) with upper GIH. The majority underwent embolization with a permanent agent (71%), while the remaining patients received either a temporary agent (16%) or a combination (14%). The overall technical and clinical success rates were 98% and 71%, respectively. Of the 14 patients with technical success but clinical failure (rebleeding within 30 days) and the 1 patient with technical failure, 4 were managed successfully with reembolization, while 2 underwent successful endoscopic therapy, and 9 had surgical resections. Only one patient had an ischemic complication (small bowel necrosis) requiring resection. CONCLUSION: SSAE, with reembolization if necessary, is an effective rescue treatment modality for hemodynamically unstable patients with active GIH. Of the patients, 20% will fail SSAE and require additional intervention. Ischemic complications are extremely rare. LEVEL OF EVIDENCE: Therapeutic study, level IV.

Prolonged emergency department length of stay is not associated with worse outcomes in traumatic brain injury.

BACKGROUND: Data suggest that prolonged Emergency Department length of stay (EDLOS) has a detrimental effect on outcomes in some critically ill patients. However, the relationship between EDLOS and outcomes in traumatic brain injury (TBI) has not been examined. OBJECTIVE: Our objective was to determine the effect of EDLOS on neurologic outcomes in TBI patients. METHODS: We performed a retrospective analysis of a prospectively identified cohort of patients with moderate (Glasgow Coma Scale [GCS] score 9-13) and severe (GCS ≤ 8) TBI who presented to a Level 1 trauma center (2006-2010). Inclusion criteria were transfer to the intensive care unit (ICU) or operating room (OR) from the ED. Primary outcome was Glasgow Outcome Scale (GOS) score, a measure of neurologic function, at discharge. We used a proportional odds model to control for significant predictors of GOS in univariate analysis. RESULTS: Two hundred and twenty-four patients were included in the analysis, 77 (34%) of which were transferred to the OR. Median EDLOS was 3.3 h and 81.2% of patients had a GOS score ≤3 (e.g., severe disability, vegetative, or deceased). In multivariable analyses, EDLOS was not associated with GOS score in either ICU bound (p = 0.57) or OR bound (p = 0.11) patients. Younger age, pupil reactivity, and absence of intubation were independent predictors of good outcomes in the ICU group. In OR patients, predictors of higher GOS score included presence of an epidural hemorrhage, absence of midline shift, and pupil reactivity. CONCLUSIONS: Our study demonstrates that EDLOS was not associated with poor outcomes in patients with moderate to severe TBI who required intensive care or early operative intervention in an academic Level 1 trauma center.