Parameters of high-frequency jet ventilation using a mechanical lung model.

High frequency jet ventilationis a mechanical lung ventilation method which uses a relatively high flow usually through an open system. This work examined the effect of high-frequency jet ventilation on respiratory parameters of an intubated patient simulated using a high-frequency jet ventilator attached to a ventilation monitor for measurements of ventilation parameters. The series of experiments altered specific parameters each time (respiratory rate, inspiratory-expiratory (I:E) ratio, and inspiratory pressure), under different lung compliances. A reduction of minute ventilation was observed alongside a rise in respiratory rate, with low airway pressures over the entire range of lung compliances. In addition, an I:E ratio of 2:1 to 1:1; and the tidal and minute volumes were directly related to the inspiratory pressure over all compliance settings. To conclude, the respiratory mechanics in high-frequency jet ventilation are very different from those of conventional rate ventilation in a lung model. Further studies on patients and/or a biological model are needed to investigate pCO2 and end-tidal carbon-dioxide during high-frequency jet ventilation.

Early identification of acute kidney injury in the ICU with real-time urine output monitoring: a clinical investigation.

BACKGROUND: KDIGO (Kidney Disease: Improving Global Outcomes) provides two sets of criteria to identify and classify acute kidney injury (AKI): serum creatinine (SCr) and urine output (UO). Inconsistencies in the application of KDIGO UO criteria, as well as collecting and classifying UO data, have prevented an accurate assessment of the role this easily available biomarker can play in the early identification of AKI. STUDY GOAL: To assess and compare the performance of the two KDIGO criteria (SCr and UO) for identification of AKI in the intensive care unit (ICU) by comparing the standard SCr criteria to consistent, real-time, consecutive, electronic urine output measurements. METHODS: Ninety five catheterized patients in the General ICU (GICU) of Hadassah Medical Center, Israel, were connected to the RenalSense™ Clarity RMS™ device to automatically monitor UO electronically (UOelec). UOelec and SCr were recorded for 24-48 h and up to 1 week, respectively, after ICU admission. RESULTS: Real-time consecutive UO measurements identified significantly more AKI patients than SCr in the patient population, 57.9% (N = 55) versus 26.4% (N = 25), respectively (P < 0.0001). In 20 patients that had AKI according to both criteria, time to AKI identification was significantly earlier using the UOelec criteria as compared to the SCr criteria (P < 0.0001). Among this population, the median (interquartile range (IQR)) identification time of AKI UOelec was 12.75 (8.75, 26.25) hours from ICU admission versus 39.06 (25.8, 108.64) hours for AKI SCr. CONCLUSION: Application of KDIGO criteria for AKI using continuous electronic monitoring of UO identifies more AKI patients, and identifies them earlier, than using the SCr criteria alone. This can enable the clinician to set protocol goals for earlier intervention for the prevention or treatment of AKI.

Spine Surgery and Blood Loss: Systematic Review of Clinical Evidence.

Spine surgery has been growing rapidly as a neurosurgical operation, with an increase of 220% over a 15-year period. Intraoperative blood transfusion is a major outcome determinant of spine procedures. Various approaches, including pharmacologic and nonpharmacologic therapies, have been tested to decrease both intraoperative and postoperative blood loss. The aim of this systematic review is to report clinical evidence on the relationship between intraoperative blood loss (primary outcome) and on transfusion requirements and postoperative complications (secondary outcomes) in patients undergoing spine surgery. A literature search of PubMed database was performed using 5 key words: spine surgery and transfusion; spine surgery and blood loss; spine surgery and blood complications; spine surgery and deep vein thrombosis; and spine surgery and pulmonary embolism. Clinical reports (randomized controlled trials, prospective and retrospective studies, and case reports) were selected. A total of 473 articles were examined; 450 were excluded, and 24 were selected for this systematic review. Selected articles were categorized into 3 subchapters: (1) drugs active on coagulation (12 studies): tranexamic acid, aminocaproic acid, aprotinin, and recombinant activated factor VII; (2) drugs not active on coagulation (5 studies): ketorolac, epoetin alfa, magnesium sulfate, propofol/sevoflurane, and omega-3 and fish oil; (3) nonpharmacologic approaches (7 studies): surgical tips, patient positioning, and general or spinal anesthesia. Several studies have shown a significant reduction in intraoperative bleeding during spine surgery and in the requirement for blood transfusion.

Anesthesia reduces discharge rates in the human pallidum without changing the discharge rate ratio between pallidal segments.

Classical rate models of basal ganglia circuitry associate discharge rate of the globus pallidus external and internal segments (GPe, GPi respectively) solely with dopaminergic state and predict an inverse ratio between the discharge rates of the two pallidal segments. In contrast, the effects of other rate modulators such as general anesthesia (GA) on this ratio have been ignored. To respond to this need, we recorded the neuronal activity in the GPe and GPi in awake and anesthetized human patients with dystonia (57 and 53 trajectories respectively) and in awake patients with Parkinson's disease (PD, 16 trajectories) undergoing deep brain stimulation procedures. This triad enabled us to dissociate pallidal discharge ratio from general discharge modulation. An automatic offline spike detection and isolation quality system was used to select 1560 highly isolated units for analysis. The mean discharge rate in the GPi of awake PD patients was dramatically higher than in awake dystonia patients although the firing rate in the GPe was similar. Firing rates in dystonic patients under anesthesia were lower in both nuclei. Surprisingly, in all three groups, GPe firing rates were correlated with firing rates in the ipsilateral GPi. Thus, the firing rate ratio of ipsilateral GPi/GPe pairs was similar in awake and anesthetized patients with dystonia and significantly higher in PD. We suggest that pallidal activity is modulated by at least two independent processes: dopaminergic state which changes the GPi/GPe firing rate ratio, and anesthesia which modulates firing rates in both pallidal nuclei without changing the ratio between their firing rates.

Short term morphine exposure in vitro alters proliferation and differentiation of neural progenitor cells and promotes apoptosis via mu receptors.

BACKGROUND: Chronic morphine treatment inhibits neural progenitor cell (NPC) progression and negatively effects hippocampal neurogenesis. However, the effect of acute opioid treatment on cell development and its influence on NPC differentiation and proliferation in vitro is unknown. We aim to investigate the effect of a single, short term exposure of morphine on the proliferation, differentiation and apoptosis of NPCs and the mechanism involved. METHODS: Cell cultures from 14-day mouse embryos were exposed to different concentrations of morphine and its antagonist naloxone for 24 hours and proliferation, differentiation and apoptosis were studied. Proliferating cells were labeled with bromodeoxyuridine (BrdU) and cell fate was studied with immunocytochemistry. RESULTS: Cells treated with morphine demonstrated decreased BrdU expression with increased morphine concentrations. Analysis of double-labeled cells showed a decrease in cells co-stained for BrdU with nestin and an increase in cells co-stained with BrdU and neuron-specific class III ß-tubuline (TUJ1) in a dose dependent manner. Furthermore, a significant increase in caspase-3 activity was observed in the nestin- positive cells. Addition of naloxone to morphine-treated NPCs reversed the anti-proliferative and pro-apoptotic effects of morphine. CONCLUSIONS: Short term morphine exposure induced inhibition of NPC proliferation and increased active caspase-3 expression in a dose dependent manner. Morphine induces neuronal and glial differentiation and decreases the expression of nestin- positive cells. These effects were reversed with the addition of the opioid antagonist naloxone. Our results demonstrate the effects of short term morphine administration on the proliferation and differentiation of NPCs and imply a mu-receptor mechanism in the regulation of NPC survival.

Looking beyond discharge: clinical variables at trauma admission predict long term survival in the older severely injured patient.

BACKGROUND: Long term follow up is difficult to obtain in most trauma settings, these data are essential for assessing outcomes in the older (≥60) patient. We hypothesized that clinical data obtained during initial hospital stay could accurately predict long term survival. STUDY DESIGN: Using our trauma registry and hospital database, we reviewed all trauma admissions (age ≥60, ISS > 15) to our Level 1 center over the most recent 7 years. Mechanism of injury, co-morbidities, ICU admission, and ultimate disposition were assessed for 2-7 years post-discharge. Primary outcome was defined as long term survival to the end of the last year of the study. RESULTS: Of 342 patients discharged following initial admission, mean age was 76.2 ± 9.7, and ISS was 21.5 ± 6.9. 119 patients (34.8%) died (mean follow up 18.8 months; range 1.1-66.2 months). For 233 survivors, mean follow-up was 50.2 months (range 24.8-83.8 months). Univariate analysis disclosed post-discharge mortality was associated with age (80.1 ± 9.64 vs. 74.2 ± 9.07), mean number of co-morbidities (1.6 ± 1.1 vs. 1.0 ± 1.2), fall as a mechanism, lower GCS upon arrival (11.85 ± 4.21 vs. 13.73 ± 2.89), intubation at the scene and discharge to an assisted living facility (p < 0.001 for all). Cox regression analysis hazard ratio showed that independent predictors of mortality on long term follow-up included: older age, fall as mechanism, lower GCS at admission and discharge to assisted living facility (all = p < 0.0001). CONCLUSIONS: Nearly two-thirds of patients ≥60 who were severely injured survived >4 years following discharge; furthermore, admission data, including younger age, injury mechanism other than falls, higher GCS and home discharge predicted a favorable long term outcome. These findings suggest that common clinical data at initial admission can predict long term survival in the older trauma patient.

N-arachidonoyl-L-serine (AraS) possesses proneurogenic properties in vitro and in vivo after traumatic brain injury.

N-arachidonoyl-L-serine (AraS) is a novel neuroprotective endocannabinoid. We aimed to test the effects of exogenous AraS on neurogenesis after traumatic brain injury (TBI). The effects of AraS on neural progenitor cells (NPC) proliferation, survival, and differentiation were examined in vitro. Next, mice underwent TBI and were treated with AraS or vehicle. Lesion volumes and clinical outcome were evaluated and the effects on neurogenesis were tested using immunohistochemistry. Treatment with AraS led to a dose-dependent increase in neurosphere size without affecting cell survival. These effects were partially reversed by CB1, CB2, or TRPV1 antagonists. AraS significantly reduced the differentiation of NPC in vitro to astrocytes or neurons and led to a 2.5-fold increase in expression of the NPC marker nestin. Similar effects were observed in vivo in mice treated with AraS 7 days after TBI. These effects were accompanied by a reduction in lesion volume and an improvement in neurobehavioral function compared with controls. AraS increases proliferation of NPCs in vitro in cannabinoid-receptor-mediated mechanisms and maintains NPC in an undifferentiated state in vitro and in vivo. Moreover, although given at 7 days post injury, these effects are associated with significant neuroprotective effects leading to an improvement in neurobehavioral functions.

Indicators of the need for ICU admission following suicide bombing attacks.

INTRODUCTION: Critical hospital resources, especially the demand for ICU beds, are usually limited following mass casualty incidents such as suicide bombing attacks (SBA). Our primary objective was to identify easily diagnosed external signs of injury that will serve as indicators of the need for ICU admission. Our secondary objective was to analyze under- and over-triage following suicidal bombing attacks. METHODS: A database was collected prospectively from patients who were admitted to Hadassah University Hospital Level I Trauma Centre, Jerusalem, Israel from August 2001-August 2005 following a SBA. One hundred and sixty four victims of 17 suicide bombing attacks were divided into two groups according to ICU and non-ICU admission. RESULTS: There were 86 patients in the ICU group (52.4%) and 78 patients in the non-ICU group (47.6%). Patients in the ICU group required significantly more operating room time compared with patients in the non-ICU group (59.3% vs. 25.6%, respectively, p=0.0003). For the ICU group, median ICU stay was 4 days (IQR 2 to 8.25 days). On multivariable analysis only the presence of facial fractures (p=0.014), peripheral vascular injury (p=0.015), injury≥4 body areas (p=0.002) and skull fractures (p=0.017) were found to be independent predictors of the need for ICU admission. Sixteen survivors (19.5%) in the ICU group were admitted to the ICU for one day only (ICU-LOS=1) and were defined as over-triaged. Median ISS for this group was significantly lower compared with patients who were admitted to the ICU for >1 day (ICU-LOS>1). This group of over-triaged patients could not be distinguished from the other ICU patients based on external signs of trauma. None of the patients in the non-ICU group were subsequently transferred to the ICU. CONCLUSIONS: Our results show that following SBA, injury to ≥4 areas, and certain types of injuries such as facial and skull fractures, and peripheral vascular injury, can serve as surrogates of severe trauma and the need for ICU admission. Over-triage rates following SBA can be limited by a concerted, focused plan implemented by dedicated personnel and by the liberal utilization of imaging studies.

Urine flow is a novel hemodynamic monitoring tool for the detection of hypovolemia.

BACKGROUND: Noticeable changes in vital signs indicating hypovolemia occur only after 15% of the blood volume is lost. More sensitive variables (e.g., cardiac output, systolic pressure variation and its Δdown component) are invasive and difficult to obtain in the early phase of bleeding. Lately, a new technology for continuous optical measurements of minute-to-minute urine flow rates has become available. We performed a preliminary evaluation to determine whether urine flow can act as an early and sensitive warning of hypovolemia. METHODS: Eleven patients (ASA physical status I-II) undergoing posterior spine fusion surgery were studied prospectively. Study variables included heart rate, blood pressure (systolic and diastolic), systolic pressure variation and Δdown, minute urinary flow, hemoglobin, blood and urinary sodium, and creatinine in the blood and urine. Urine flow rate was measured using URINFO 2000™ (FlowSense Medical, Misgav, Israel). After recording baseline variables, 10 mL/kg of the patient's blood was shed and a second set of variables was recorded. Subsequently, hypovolemia was reversed by infusing colloid solution (hetastarch 6%) followed by recording a third set of variables. These 3 observations were then compared. RESULTS: An average of 614 ± 143 mL (mean ± SD) of blood was shed. During phlebotomy, the mean urine flow rate decreased from 5.7 ± 8 mL/min to 1.07 ± 2.5 mL/min. Systolic blood pressure and hemoglobin also decreased. Δdown increased. After rehydration, urine flow, blood pressure, and Δdown values returned to baseline. The hemoglobin concentration decreased whereas other variables did not change significantly. CONCLUSION: Urine flow rate is a dynamic variable that seems to be a reliable indicator of changes in blood volume. These results justify further investigation.

Multiple casualty terror events: the anesthesiologist's perspective.

UNLABELLED: In a 28-mo period 14 multiple-casualty terror events occurred in Jerusalem, challenging the Department of Anesthesiology and Critical Care Medicine of the city's sole Level 1 trauma center. We performed a retrospective review of the response of the department to evaluate staff activities, resource use (emergency department, operating rooms, and intensive care unit [ICU]), and patient flow. A total of 1062 people were injured in the 14 multi-casualty terror incidents. The emergency department treated 355 victims; 108 of them were hospitalized, and 58 underwent surgery during the first 8 h. Only two surgeries were performed during the first hour, and the average time to the first surgery was 124 min. Fifty-one patients were admitted to the ICU an average of 5.5 h after the terror event. After a terrorist act, multiple, simultaneous efforts were required of the anesthesiology department, including taking part in the initial resuscitation in the emergency department, anesthetizing victims for surgery and angiographies, and caring for them in the recovery room and ICU. Therefore, anesthesiology departments are greatly impacted by such events and must plan for them to maximize the use of available personnel and to have the appropriate equipment and supplies available. IMPLICATIONS: Anesthesiologists provide essential care to patients injured in terror events, from the initial resuscitation through therapeutic/diagnostic procedures and surgeries. Operational issues faced by a department of anesthesiology during the initial 8 h after terrorist actions were examined. Multiple, and often parallel, efforts were required of the department.