Indicators of the need for ICU admission following suicide bombing attacks

<p>Abstract</p> <p>Introduction</p> <p>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.</p> <p>Methods</p> <p>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.</p> <p>Results</p> <p>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, <it>p </it>= 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 (<it>p </it>= 0.014), peripheral vascular injury (<it>p </it>= 0.015), injury ≥ 4 body areas (<it>p </it>= 0.002) and skull fractures (<it>p </it>= 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.</p> <p>Conclusions</p> <p>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.</p

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

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.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.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 β-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.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

Morphine increases the levels of active caspase-3 in proliferating cells.

<p>Addition of morphine to the cultures of NPCs results in an increase in apoptosis of BrdU-positive cells with increased morphine concentrations. (*p<0.05, **p<0.01, ***p<0.001 vs. untreated) (<b>2A, 2B</b>).</p

Naloxone reverses morphine increased-caspase-3 activity, neuronal differentiation and decreased NPC expression.

<p>Morphine results in increased apoptosis of BrdU- positive cells, decreases Nestin- positive- BrdU- positive cell expression and enhances neuronal differentiation as demonstrated in TUJ1- positive-BrdU- positive cell co-staining. Naloxone reverses these effects (*p<0.05, **p<0.01, ***p<0.001 vs. Morphine 13 µM). Morphine 13 =  Morphine 13 µM; Naloxone 50 =  Naloxone 50 µM (<b>6A, 6B</b>).</p

Morphine decreases proliferation of NPCs and induces the apoptotic enzyme active caspase-3 in a dose dependent manner.

<p>NPCs were exposed to increasing doses of morphine. This increase caused a decrease in the number of cells expressing BrdU and an increase in the number of apoptotic cells expressing active caspase-3 (<b>1A</b>). Bar graph showing, in a dose-dependent manner, the decrease in BrdU and increase in active caspase-3 expression in NPCs exposed to a single-dose of morphine (***p<0.001 different morphine doses vs. untreated in BrdU and caspase-3; ^###p<0.001 0.13 µM and 1.3 µM vs. 13 µM in caspase-3; ⁺⁺⁺p<0.001 0.13 µM vs. 13 µM in BrdU) (<b>1B</b>).</p

Morphine causes increased caspase-3 activity in NPCs and astrocytes but not in TUJ1-expressing neurons.

<p>NPCs expressing caspase-3 were co-stained with nestin, GFAP or TUJ1. Most of the cells expressing active caspase-3 were nestin- positive cells and GFAP- positive cells while relatively low levels of the cells were TUJ1- positive cells. The percentage of nestin- positive and GFAP- positive cells expressing caspase-3 increased in a dose dependent manner (***p<0.001 vs. untreated) (<b>4A, 4B</b>).</p

Morphine increases neuronal differentiation and inhibits self-renewal of NPCs.

<p>NPCs exposed to increasing levels of morphine demonstrated a decrease in BrdU- positive- nestin-positive cell expression while TUJ1- positive- BrdU- positive co-staining was enhanced with increased morphine concentrations (*p<0.05, **p<0.01, ***p<0.001 vs. untreated; ⁺p<0.05, ⁺⁺⁺p<0.001 vs. 13 µM) (<b>3A, 3B</b>).</p

Naloxone reverses the anti-proliferative and pro-apoptotic effects of morphine on NPCs.

<p>Both the anti-proliferative and the pro-apoptotic effects of morphine were diminished by naloxone. The addition of naloxone to NPCs treated with morphine demonstrated a proliferative effect on NPCs and a reduced apoptotic effect compared with the morphine-treated groups (***p<0.001 vs. morphine 13 µM). Morphine 13 =  Morphine 13 µM; Naloxone 50 =  Naloxone 50 µM (<b>5A, 5B</b>).</p