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Alharfi I.M.,University of Western Ontario | Charyk Stewart T.,University of Western Ontario | Charyk Stewart T.,London Health Sciences Center | Al Helali I.,University of Western Ontario | And 5 more authors.
Journal of Neurotrauma | Year: 2014

Infections can increase medical costs and worsen patient outcomes. Our aims in pediatric severe traumatic brain injury (sTBI) patients were to determine the infection and fever rates, and to report on associated clinical, imaging, treatment, and outcome factors. We included 180 sTBI patients (presedation Glasgow Coma Scale ≤8 and Maximum Abbreviated Injury Scale ≥4) admitted to our pediatric intensive care unit. Overall, 17% of sTBI patients (n=30 of 180) developed 36 infections, consisting primarily of urinary tract infections (UTIs; n=13 of 36) and ventilator-associated pneumonias (n=11 of 36). Most infections were nosocomial, occurring >2 days after admission. Fever was found in 36% of sTBI patients during the first few hospital days, but fewer than 7% of patients had infections. Infections occurred more frequently in sTBI patients who were older, heavier, and with a higher injury severity score (ISS; p<0.05). Admission head computed tomography imaging abnormalities (subarachnoid hemorrhage, intraventricular hemorrhage, and diffuse axonal injury), placement of an intracranial pressure (ICP) monitor, and administration of ICP-lowering therapies (hypertonic saline, mannitol, and thiopental) were associated with infections (p<0.05). Those with infections had fewer ventilator-free days, greater hospital lengths of stays, and were less likely to be discharged home. Logistic regression demonstrated that infections were independently associated with use of hypertonic saline (odds ratio [OR], 4.46; p=0.001) and higher ISS (OR, 1.05; p=0.028). In summary, infections were prevalent in sTBI patients and were associated with greater head-imaging abnormalities and use of ICP-lowering therapies. Hypertonic saline administration was strongly associated with infection, but further analyses are required to determine the nature of this relationship. Fever was a poor indicator of infection after sTBI. © Mary Ann Liebert, Inc.

Alharfi I.M.,University of Western Ontario | Stewart T.C.,University of Western Ontario | Stewart T.C.,London Health Sciences Center | Kelly S.H.,University of Western Ontario | And 5 more authors.
Journal of Neurotrauma | Year: 2013

Acquired hypernatremia in hospitalized patients is often associated with poorer outcomes. Our aim was to evaluate the relationship between acquired hypernatremia and outcome in children with severe traumatic brain injury (sTBI). We performed a retrospective cohort study of all severely injured trauma patients (Injury Severity Score ≥12) with sTBI (Glasgow Coma Scale [GCS] ≤8 and Maximum Abbreviated Injury Scale [MAIS] ≥4) admitted to a Pediatric Critical Care Unit ([PCCU]; 2000-2009). In a cohort of 165 patients, 76% had normonatremia (135-150 mmol/L), 18% had hypernatremia (151-160 mmol/L), and 6% had severe hypernatremia (>160 mmol/L). The groups were similar except for lower GCS (p=0.002) and increased incidence of fixed pupil(s) on admission in both hypernatremia groups (p<0.001). Mortality rate was four-fold and six-fold greater with hypernatremia and severe hypernatremia, respectively (p<0.001), and mortality rates were unchanged when patients with fixed pupils or those with central diabetes insipidus were excluded (p<0.001). Hypernatremic patients had fewer ventilator-free days (p<0.001). Survivors with hypernatremia had greater PCCU (p=0.001) and hospital (p=0.031) lengths of stays and were less frequently discharged home (p=0.008). Logistic regression analyses of patient characteristics and sTBI interventions demonstrated that hypernatremia was independently associated with the presence of fixed pupil(s) on admission (odds ratio [OR] 5.38; p=0.003); administration of thiopental (OR 8.64; p=0.014), and development of central diabetes insipidus (OR 5.66; p=0.005). Additional logistic regression analyses demonstrated a significant association between hypernatremia and mortality (OR 6.660; p=0.034). In summary, acquired hypernatremia appears to signal higher risk of mortality in pediatric sTBI and is associated with a higher discharge level of care in sTBI survivors. © 2013, Mary Ann Liebert, Inc. 2013.

Stewart T.C.,University of Western Ontario | Stewart T.C.,London Health Sciences Center | Alharfi I.M.,King Fahad Medical City | Fraser D.D.,University of Western Ontario | And 3 more authors.
Journal of Trauma and Acute Care Surgery | Year: 2013

BACKGROUND: The study objective was to describe the epidemiology of serious concomitant injuries and their effects on outcome in pediatric severe traumatic brain injury (sTBI). METHODS: A retrospective cohort of all severely injured (Injury Severity Score [ISS] ≥ 12) pediatric patients (G18 years) admitted to our pediatric intensive care unit, between 2000 and 2011, after experiencing an sTBI (Glasgow Coma Scale [GCS] score ≤ 8 and head Abbreviated Injury Scale [AIS] ≥ 4) were included. Two groups were compared based on the presence of serious concomitant injuries (maximum AIS score ≥ 3). Multivariate logistic regression was undertaken to determine variable associations with mortality. RESULTS: Of the 180 patients with sTBI, 113 (63%) sustained serious concomitant injuries. Chest was the most commonly injured extracranial body region (84%), with lung being the most often injured. Patients with serious concomitant injuries had increased age, weight, and injury severity (p < 0.001) and were more likely injured in a motor vehicle collision (91% vs. 48%, p < 0.001). Those with serious concomitant injuries had worse sTBI, based on lower presedation GCS (p = 0.031), higher frequency of fixed pupils (p = 0.006), and increased imaging abnormalities (SAH and DAI, p ≤ 0.01). Non-neurosurgical operations and blood transfusions were more frequent in the serious concomitant injury group (p < 0.01). The differences in mortality for the two groups failed to reach statistical significant (p = 0.053), but patients with serious concomitant injuries had higher rates of infection and acute central diabetes insipidus, fewer ventilator-free days, and greater length of stays (p < 0.05). Multivariate analyses revealed fixed pupillary response (odd ratio [OR], 63.58; p < 0.001), presedation motor GCS (OR, 0.23; p = 0.001), blood transfusion (OR, 5.80; p = 0.008), and hypotension (OR, 4.82; p = 0.025) were associated with mortality, but serious concomitant injuries was not (p = 0.283). CONCLUSION: Head injury is the most important prognostic factor in mortality for sTBI pediatric patients, but the presence of serious concomitant injuries does contribute to greater morbidity, including longer stays, more infections, fewer ventilator-free days, and a higher level of care required on discharge from hospital. Copyright © 2013 by Lippincott Williams & Wilkins.

Stewart T.C.,London Health Sciences Center | Gilliland J.,University of Western Ontario | Gilliland J.,Childrens Health Research Institute | Fraser D.D.,Childrens Health Research Institute | Fraser D.D.,Center for Critical Illness Research
Journal of Trauma and Acute Care Surgery | Year: 2014

BACKGROUND: The objective of this study was to describe the epidemiology of concussions presenting to the emergency department (ED). METHODS: A retrospective cohort of concussions for pediatric (age < 18 years) patients treated in the ED of a regional pediatric Level 1 trauma center from 2006 to 2011 was examined. Descriptive and geographic analyses were completed, with comparisons by age groups and residence (urban/rural). RESULTS: There were a total of 2,112 treated pediatric concussions. Two thirds of the concussions occurred in males (67%), with a median age of 13 years (interquartile range [IQR], 6). Nearly half of the pediatric concussions were sports related (48%); 36% of these concussions were from hockey. Significant differences were found in the distribution of the mechanism of injury across age groups (p < 0.001). Falls were most prevalent among young children, and sports concussions, for children 10 years and older. Two fifths of concussions occurred during winter months. Discharge disposition significantly differed by age (p < 0.001), with home discharge increasing with age up to 14 years. There were a total of 387 rural (19%) and 1,687 urban (81%) concussed patients, for a mean ED concussion visit rate of 2.2 per 1,000 and 3.5 per 1,000, respectively. Rural patients were older (14 [IQR, 6] vs. 13 [IQR, 6], p = 0.019] and sustained 2.5 times more concussions from a motor vehicle crash compared with urban youth patients (p < 0.001). CONCLUSION: Males in early adolescence are at highest risk for concussion, particularly from sport-related activities. Urban and rural children have differences in their etiology and severity of concussions. Concussions are predictable, and their prevention should be targeted based on epidemiologic and environmental data. Copyright © 2014 Lippincott Williams & Wilkins.

Patterson E.K.,Center for Critical Illness Research | Fraser D.D.,Center for Critical Illness Research | Fraser D.D.,Lawson Health Research Institute | Fraser D.D.,University of Western Ontario | And 4 more authors.
Free Radical Biology and Medicine | Year: 2014

Polymorphonuclear leukocyte (PMN)-derived myeloperoxidase (MPO) contributes to the pathophysiology of numerous systemic inflammatory disorders through: (1) direct peroxidation of targets and (2) production of strong oxidizing compounds, e.g., hypohalous acids, particularly hypochlorous acid, which furthers oxidant damage and contributes to the propagation of inflammation and tissue injury/dysfunction. Carbon monoxide-releasing molecules (CORMs) offer potent anti-inflammatory effects; however, the mechanism(s) of action is not fully understood. This study assessed the potential of MPO activity inhibition by a water-soluble CORM, CORM-3. To this end, we used in vitro assays to study CORM-3-dependent modulation of MPO activity with respect to: (1) the inhibition of MPO's catalytic activity generally and (2) the specific inhibition of MPO's peroxidation and halogenation (i.e., production of hypochlorous acid) reactions. Further, we employed primary human umbilical vein endothelial cells (HUVECs) to investigate MPO-dependent cellular activation and dysfunction by measuring intracellular oxidant stress (DHR-123 oxidation) and HUVEC permeability (flux of Texas red-dextran), respectively. The results indicate that CORM-3 significantly inhibits MPO activity as well as MPO's peroxidation and hypohalous acid cycles specifically (p<0.05 vs uninhibited MPO). In addition, CORM-3 significantly decreases PMN homogenate- or rhMPO-induced intracellular DHR-123 oxidation in HUVECs and rhMPO-induced HUVEC monolayer permeability (p<0.05 vs untreated). In all assays the inactivated CORM-3 was significantly less effective than CORM-3 (p<0.05). Taken together our findings indicate that CORM-3 is a novel MPO inhibitor and mitigates inflammatory damage at least in part through a mechanism involving the inhibition of neutrophilic MPO activity. © 2014 Elsevier Inc.

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