Ali Y. Mejaddam

Traumatic brain injury and hemorrhagic shock: evaluation of different resuscitation strategies in a large animal model of combined insults.

ABSTRACT Traumatic brain injury (TBI) and hemorrhagic shock (HS) are the leading causes of trauma-related mortality and morbidity. Combination of TBI and HS (TBI + HS) is highly lethal, and the optimal resuscitation strategy for this combined insult remains unclear. A critical limitation is the lack of suitable large animal models to test different treatment strategies. We have developed a clinically relevant large animal model of TBI + HS, which was used to evaluate the impact of different treatments on brain lesion size and associated edema. Yorkshire swine (42–50 kg) were instrumented to measure hemodynamic parameters and intracranial pressure. A computer-controlled cortical impact device was used to create a TBI through a 20-mm craniotomy: 15-mm cylindrical tip impactor at 4 m/s velocity, 100-ms dwell time, and 12-mm penetration depth. Volume-controlled hemorrhage was started (40% blood volume) concurrent with the TBI. After 2 h of shock, animals were randomized to one of three resuscitation groups (n = 5/group): (a) normal saline (NS); (b) 6% hetastarch, Hextend (Hex); and (c) fresh frozen plasma (FFP). Volumes of Hex and FFP matched the shed blood, whereas NS was three times the volume. After 6 h of postresuscitation monitoring, brains were sectioned into 5-mm slices and stained with TTC (2,3,5-triphenyltetrazolium chloride) to quantify the lesion size and brain swelling. Combination of 40% blood loss with cortical impact and a period of shock (2 h) resulted in a highly reproducible brain injury. Total fluid requirements were lower in the Hex and FFP groups. Lesion size and brain swelling in the FFP group (2,160 ± 202.6 mm3 and 22% ± 1.0%, respectively) were significantly smaller than those in the NS group (3,285 ± 130.8 mm3 and 37% ± 1.6%, respectively) (P < 0.05). Hex treatment decreased the swelling (29% ± 1.6%) without reducing the lesion size. Early administration of FFP reduces the size of brain lesion and associated swelling in a large animal model of TBI + HS. In contrast, artificial colloid (Hex) decreases swelling without reducing the actual size of the brain lesion.

Pharmacologic resuscitation for hemorrhagic shock combined with traumatic brain injury.

BACKGROUND We have previously demonstrated that valproic acid (VPA), a histone deacetylase inhibitor, can improve survival after hemorrhagic shock (HS), protect neurons from hypoxia-induced apoptosis, and attenuate the inflammatory response. We have also shown that administration of 6% hetastarch (Hextend [Hex]) after traumatic brain injury (TBI) decreases brain swelling, without affecting size of the lesion. This study was performed to determine whether addition of VPA to Hex would decrease the lesion size in a clinically relevant large animal model of TBI + HS. METHODS Yorkshire swine (42–50 kg) were instrumented to measure hemodynamic parameters, intracranial pressure, and brain tissue oxygenation. A custom-designed, computer-controlled cortical impact device was used to create a TBI through a 20-mm craniotomy: 15-mm cylindrical tip impactor at 4-m/s velocity, 100-millisecond dwell time, and 12-mm penetration depth. Volume-controlled hemorrhage was started (40% blood volume) concurrent with the TBI. After 2 hours of shock, animals were randomized to one of three resuscitation groups (n = 7 per group) as follows: (1) isotonic sodium chloride solution; (2) 6% hetastarch, Hex; and (3) Hex and VPA 300 mg/kg (Hex + VPA). Volumes of Hex matched the shed blood, whereas that of the isotonic sodium chloride solution was three times the volume. VPA treatment was started after an hour of shock. After 6 hours of postresuscitation monitoring, brains were sectioned into 5-mm slices and stained with 2, 3, 5-Triphenyltetrazolium chloride to quantify the lesion size (mm3) and brain swelling (percent change compared with uninjured side). Levels of acetylated histone H3 were determined to quantify acetylation, and myeloperoxidase and interleukine-1&bgr; (IL-1&bgr;) levels were measured as markers of brain inflammation. RESULTS Combination of 40% blood loss with cortical impact and a period of shock (2 hours) and resuscitation resulted in a highly reproducible brain injury. Lesion size and brain swelling in the Hex + VPA group (1,989 [156.8] mm3, and 19% [1.6%], respectively) were significantly smaller than the isotonic sodium chloride solution group (3,335 [287.9] mm3 and 36% [2.2%], respectively). Hex alone treatment significantly decreased the swelling (27% [1.6%]) without reducing the lesion size. The number of CD11b-positive cells as well as myeloperoxidase and IL-1 levels in the brains were significantly reduced by the VPA treatment. CONCLUSION In a combined HS and TBI model, treatment with artificial colloid (Hex) improves hemodynamic parameters and reduces swelling, without affecting the actual size of the brain lesion. Addition of VPA effectively reduces both the size of brain lesion and associated swelling by attenuating the inflammatory response.

Self-expanding polyurethane polymer improves survival in a model of noncompressible massive abdominal hemorrhage.

BACKGROUND Intracavitary noncompressible hemorrhage remains a significant cause of preventable death on the battlefield. Two dynamically mixed and percutaneously injected liquids were engineered to create an in situ self-expanding polymer foam to facilitate hemostasis in massive bleeding. We hypothesized that intraperitoneal injection of the polymer could achieve conformal contact with sites of injury and improve survival in swine with lethal hepatoportal injury. METHODS High grade hepatoportal injury was created in a closed abdominal cavity, resulting in massive noncoagulopathic, noncompressible hemorrhage. Animals received either standard battlefield fluid resuscitation (control, n = 12) or fluid resuscitation plus intraperitoneal injection of hemostatic foam (polymer, n = 15) and were monitored for 3 hours. Blood loss was quantified, and all hepatoportal injuries were inspected for consistency. RESULTS Before intervention, all animals initially experienced severe, profound hypotension and near-arrest (mean arterial pressure at 10 minutes, 21 [5.3] mm Hg). Overall survival at 3 hours was 73% in the polymer group and 8% in the control group (p = 0.001). Median survival time was more than 150 minutes in the polymer group versus 23 minutes (19–41.5 minutes) in the control group (p < 0.001), and normalized blood loss in the polymer group was 0.47 (0.30) g/kg per minute versus 3.0 (1.3) g/kg per minute in the controls (p = < 0.001). All hepatoportal injuries were anatomically similar, and the polymer had conformal contact with injured tissues. CONCLUSION Intraperitoneal polymer injection during massive noncompressible hemorrhage reduces blood loss and improves survival in a lethal, closed-cavity, hepatoportal injury model. Chronic safety and additional efficacy studies in other models are needed.

Development of a lethal, closed-abdomen grade V hepato-portal injury model in non-coagulopathic swine

BACKGROUND Hemorrhage within an intact abdominal cavity remains a leading cause of preventable death on the battlefield. Despite this need, there is no existing closed-cavity animal model to assess new hemostatic agents for the preoperative control of intra-abdominal hemorrhage. METHODS We developed a novel, lethal liver injury model in non-coagulopathic swine by strategic placement of two wire loops in the medial liver lobes including the hepatic and portal veins. Distraction resulted in grade V liver laceration with hepato-portal injury, massive bleeding, and severe hypotension. Crystalloid resuscitation was started once mean arterial pressure (MAP) fell below 65 mm Hg. Monitoring continued for up to 180 min. RESULTS We demonstrated 90% lethality (9/10) in swine receiving injury and fluid resuscitation, with a mean survival time of 43 min. Previous efforts in our laboratory to develop a consistently lethal swine model of abdominal solid organs, including preemptive anticoagulation, a two-hit injury with controlled hemorrhage prior to liver trauma, and the injury described above without resuscitation, consistently failed to result in lethal injury. CONCLUSION This model can be used to screen other interventions for pre hospital control of noncompressible.

Emergent cricothyroidotomies for trauma: training considerations

BACKGROUND Emergent cricothyroidotomy remains an uncommon, but life-saving, core procedural training requirement for emergency medicine (EM) physician training. We hypothesized that although most cricothyroidotomies for trauma occur in the emergency department (ED), they are usually performed by surgeons. METHODS We conducted a retrospective analysis of all emergent cricothyroidotomies for trauma presentations performed at 2 large level I trauma centers over 10 years. Operators and assistants for all procedures were identified, as well as mechanism of injury and patient demographics were examined. RESULTS Fifty-four cricothyroidotomies were analyzed. Patients had a mean age of 50 years, 80% were male, and 90% presented as a result of blunt trauma. The most common primary operator was a surgeon (n = 47, 87%), followed by an emergency medical services (EMS) provider (n = 6, 11%) and an EM physician (n = 1, 2%). In all cases, except those performed by EMS, the operator or assistant was an attending surgeon. All EMS procedures resulted in serious complications compared with in-hospital procedures (P < .0001). CONCLUSIONS (1) Prehospital cricothyroidotomy results in serious complications. (2) Despite the ubiquitous presence of EM physicians in the ED, all cricothyroidotomies were performed by a surgeon, which may present opportunities for training improvement.

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.

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.

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.

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.