Denis D. Bensard

Preconditioning against myocardial dysfunction after ischemia and reperfusion by an alpha 1-adrenergic mechanism.

Preconditioning may find ready applicability in humans facing scheduled global cardiac ischemia-reperfusion (IR) during bypass or transplantation, where such a maneuver is feasible before arrest. Our objective was to delineate and exploit the endogenous preconditioning mechanism triggered by transient ischemia (TI) and thereby attenuate myocardial postischemic mechanical dysfunction by clinically acceptable means. Preconditioning by 2 minutes of TI followed by 10 minutes of normal perfusion protected isolated rat left ventricle function assessed after 20 minutes of global, 37 degrees C ischemia and 40 minutes of reperfusion. Final recovery of developed pressure (DP) was improved (91.5 +/- 1.9% of equilibration DP versus unconditioned IR control, 57.4 +/- 2.4%, P < .01) and was accompanied by increased contractility (+/- dP/dt). Norepinephrine release increased after TI, and reserpine pretreatment abolished TI preconditioning. This suggests that endogenous norepinephrine mediates functional preconditioning in rat. Brief pretreatment (2 minutes) with exogenous norepinephrine reproduced the protection (89.1 +/- 1.4%) of postischemic function. Functional protection persisted after the hemodynamic effects had resolved. Norepinephrine-induced preconditioning was simulated by phenylephrine and blocked by alpha 1-adrenergic receptor antagonist. TI preconditioning was similarly lost after selective alpha 1-adrenergic receptor blockade. We conclude that transient ischemic preconditioning is mediated by the sympathetic neurotransmitter release and alpha 1-adrenergic receptor stimulation. Although the postreceptor mechanism remains unclear, functional protection after IR does not seem related to the magnitude of ATP depletion and elevation of resting pressure during ischemia. Rather, the endogenous mechanisms facilitate both recovery of mechanical function and ATP repletion during reperfusion.

Thirty years of clinical trials in acute respiratory distress syndrome.

ObjectiveTo systematically review clinical trials in acute respiratory distress syndrome (ARDS). Data SourcesComputerized bibliographic search of published research and citation review of relevant articles. Study SelectionAll clinical trials of therapies for ARDS were reviewed. Therapies that have been compared in prospective, randomized trials were the focus of this analysis. Data ExtractionData on population, interventions, and outcomes were obtained by review. Studies were graded for quality of scientific evidence. Main ResultsLung protective ventilator strategy is supported by improved outcome in a single large, prospective trial and a second smaller trial. Other therapies for ARDS, including noninvasive positive pressure ventilation, inverse ratio ventilation, fluid restriction, inhaled nitric oxide, almitrine, prostacyclin, liquid ventilation, surfactant, and immune-modulating therapies, cannot be recommended at this time. Results of small trials using corticosteroids in late ARDS support the need for confirmatory large clinical trials. ConclusionsLung protective ventilator strategy is the first therapy found to improve outcome in ARDS. Trials of prone ventilation and fluid restriction in ARDS and corticosteroids in late ARDS support the need for large, prospective, randomized trials.

The positive predictive value of rib fractures as an indicator of nonaccidental trauma in children

BACKGROUND Rib fractures have a strong association with nonaccidental trauma (NAT) and severe trauma. The purposes of this study were to evaluate rib fractures in children to determine (1) the positive predictive value of a rib fracture in defining NAT and (2) the frequency of rib fractures as the only skeletal manifestation of NAT. METHODS We reviewed the medical records and imaging of all children with rib fractures over a 6-year period. NAT was determined by the Child Advocacy and Protection team. RESULTS In children younger than 3 years of age, the positive predictive value (PPV) of a rib fracture as an indicator of NAT was 95%. The positive predictive value increased to 100% once historical and clinical circumstance excluded all other causes for rib fractures. CONCLUSION In this study, rib fracture(s) were the only skeletal manifestation of NAT in 29% of the children.

Goal-directed Hemostatic Resuscitation of Trauma-induced Coagulopathy: A Pragmatic Randomized Clinical Trial Comparing a Viscoelastic Assay to Conventional Coagulation Assays.

Background:Massive transfusion protocols (MTPs) have become standard of care in the management of bleeding injured patients, yet strategies to guide them vary widely. We conducted a pragmatic, randomized clinical trial (RCT) to test the hypothesis that an MTP goal directed by the viscoelastic assay thrombelastography (TEG) improves survival compared with an MTP guided by conventional coagulation assays (CCA). Methods:This RCT enrolled injured patients from an academic level-1 trauma center meeting criteria for MTP activation. Upon MTP activation, patients were randomized to be managed either by an MTP goal directed by TEG or by CCA (ie, international normalized ratio, fibrinogen, platelet count). Primary outcome was 28-day survival. Results:One hundred eleven patients were included in an intent-to-treat analysis (TEG = 56, CCA = 55). Survival in the TEG group was significantly higher than the CCA group (log-rank P = 0.032, Wilcoxon P = 0.027); 20 deaths in the CCA group (36.4%) compared with 11 in the TEG group (19.6%) (P = 0.049). Most deaths occurred within the first 6 hours from arrival (21.8% CCA group vs 7.1% TEG group) (P = 0.032). CCA patients required similar number of red blood cell units as the TEG patients [CCA: 5.0 (2–11), TEG: 4.5 (2–8)] (P = 0.317), but more plasma units [CCA: 2.0 (0–4), TEG: 0.0 (0–3)] (P = 0.022), and more platelets units [CCA: 0.0 (0–1), TEG: 0.0 (0–0)] (P = 0.041) in the first 2 hours of resuscitation. Conclusions:Utilization of a goal-directed, TEG-guided MTP to resuscitate severely injured patients improves survival compared with an MTP guided by CCA and utilizes less plasma and platelet transfusions during the early phase of resuscitation.

Recurrent inflammatory pseudotumors in children

BACKGROUND/PURPOSE pulmonary (PPT) and extrapulmonary pseudotumors (EPPT) are uncommon benign tumors, which, in general, do not recur after complete resection. Recurrence rates for both types of pseudotumors are undocumented in a large population of children, and the salient features of potential recurrences are unspecified. METHODS This is a report of 15 children with PPT and EPPT; 3 children had a recurrence. These pseudotumors recurred despite adequate primary resection of all gross disease at first presentation. The literature was reviewed to determine rate of recurrence for PPT and EPPT and also to document features common to recurrent pseudotumors. RESULTS Overall recurrence rate for pseudotumors was 14%. PPT and EPPT, which were not confined to a single organ, had a high chance of recurrence (46% and 30%, respectively) compared with PPT and EPPT, which were confined to a single organ (1.5% and 8%, respectively). Recurrences have appeared between 3 months and 7 years. Intraabdominal EPPT accounts for more than 75% of the EPPT recurrences. CONCLUSIONS PPT and EPPT recur more frequently than anticipated. All pseudotumors, which on initial presentation extend beyond the confines of a single organ, have a high chance of recurrence despite what appears to be adequate resection. Children with pseudotumors that extend beyond a single organ, require frequent postoperative evaluation for recurrence and may be candidates for chemotherapy or radiotherapy at the time of initial resection.

Small Bowel Injury in Children after Blunt Abdominal Trauma: Is Diagnostic Delay Important?

OBJECTIVE To assess the incidence and consequences of small bowel injury (SBI) in children suffering blunt abdominal trauma managed with the intent to treat nonoperatively. DESIGN Retrospective chart review. MATERIALS AND METHODS A total of 168 consecutive hemodynamically stable children admitted to a Level I pediatric trauma center during a 24-month period. RESULTS Nine of 168 children (5%) sustained SBI: three underwent early (< 4 hours) operation for recognized SBI (identified on computed tomographic scan); and six had delayed (36 +/- 16 hours) operation for missed SBI (not identified on computed tomographic scan). Increased temperature and heart rate, or decreased urine output at 24 hours suggested occult SBI. The hospital course was unaltered by delayed diagnosis. Fifty-seven percent of the children (95) suffered intra-abdominal injury; 10% required laparotomy for SBI (9) or solid organ injury (7); 90% (152) were discharged without laparotomy. CONCLUSIONS SBI is uncommon in children suffering blunt abdominal trauma. The diagnosis can be made using clinical and radiographic findings. Limited diagnostic delay does not seem to affect outcome. We conclude that clinical diagnosis of SBI is safe, permits the nonoperative treatment of most blunt abdominal injuries, and reduces the risk of unnecessary laparotomy associated with alternate approaches.

IL-1 regulates in vivo C—X—C chemokine induction and neutrophil sequestration following endotoxemia

The influx of neutrophils into tissues in response to inflammatory stimuli involves C—X—C chemokines. Interleukin-1 (IL-1) stimulates chemokine production in vitro , but its role in vivo on chemokine production is not as clearly understood. We hypothesized that IL-1 mediates in vivo tissue C—X—C chemokine production induced by systemic lipopolysaccharide (LPS). IL-1 activity was blockedbyIL-1 receptor antagonist (IL-1Ra). Rats were injected with Salmonella typhi LPS (0.5 mg/kg) with and without prior administration of IL-1Ra. Cytokine-induced neutrophil chemoattractant-1 (CINC-1) and macrophage inflammatory protein-2 (MIP-2) protein and mRNA levels, tissue neutrophil accumulation, and indices of organ injury were measured. LPS administration resulted in increased plasma, lung, and liver IL-1β that was decreased by IL-1Ra. LPS also induced an increase in plasma, lung, and liver CINC-1 and MIP-2 protein and mRNA. However, IL-1Ra had no effect on LPS-induced plasma or lung tissue CINC-1 levels. In contrast, IL-1Ra pretreatment did significantly decrease CINC-1 protein expression in the liver (45% decrease) and MIP-2 protein expression in plasma (100% decrease), lung (72% decrease) and liver (100% decrease) compared to LPS-treated controls. Steady-state mRNA levels by Northern blot analysis of both CINC-1 and MIP-2 in lung and liver were similar to the protein findings. Pretreatment with IL-1Ra also resulted in a 47% and 59% decrease in lung and liver neutrophil accumulation, respectively, following LPS. In addition, indices of both lung and liver injury were decreased in animals pretreated with IL-1Ra. In summary, LPS induces IL-1β and MIP-2 expression in the lung and liver, both of which are IL-1 dependent. Although lung neutrophil accumulation in both lung and liver after LPS is also IL-1 mediated, lung CINC-1 levels were unaffected by IL-1Ra. These data suggest that IL-1 regulates tissue chemokine expression and neutrophil accumulation after LPS.

Blunt cerebrovascular injuries: redefining screening criteria in the era of noninvasive diagnosis.

Background: Screening for blunt cerebrovascular injuries (BCVIs) and early treatment has virtually eliminated injury-related strokes. Screening protocols developed in the 1990s captured ∼80% of ultimately identified BCVI. With the availability of noninvasive diagnosis with computed tomographic angiography, broader indications for screening seem warranted. The purpose of this study was to identify injury patterns of patients with BCVI that are not currently recommended screening criteria. Methods: Our prospective BCVI database, initiated in 1997, was queried through December 2010. Indications for screening, injury mechanism, and outcomes were analyzed. Patients younger than 18 years were excluded. Results: During the 14-year study period, 585 BCVIs were identified in 418 patients (66% men; age, 40 years ± 0.7 years). Eighty-three (20%) patients with BCVI did not have standard screening criteria; 66% were asymptomatic at diagnosis. Injury patterns in these patients included mandible fracture (27 patients), complex skull fractures (21 patients), traumatic brain injury with thoracic trauma (6 patients), scalp degloving (6 patients), and great vessel or cardiac injuries (4 patients). Other injuries (11 patients) and no injuries (8 patients) were identified in the remainder. Of the 307 asymptomatic patients who received antithrombotic treatment, one patient suffered stroke (0.3%) and one patient a transient ischemic attack (0.3%). Conclusions: A significant number of patients suffering BCVI are not captured by current screening guidelines. Screening for BCVI should be considered in patients with mandible fractures, complex skull fractures, traumatic brain injury with thoracic injuries, scalp degloving, and thoracic vascular injuries. Level of Evidence: II, prognostic study.

Ultrasound is an effective triage tool to evaluate blunt abdominal trauma in the pediatric population

BACKGROUND Although computed tomography has been considered the diagnostic modality of choice for pediatric patients with blunt abdominal trauma (BAT), it is costly, time-consuming, requires sedation, and may be associated with complications in young children. Abdominal ultrasonography (US) is a promising modality in the evaluation of BAT that is quick, noninvasive, repeatable, and cost-effective. We hypothesized that emergency department US, performed by trauma surgeons, is a useful triage tool for pediatric BAT that reduces the need for computed tomography. METHODS The 230 children (<18 years old) with suspected BAT were initially evaluated with US in the emergency department by surgeons. Subsequent computed tomographic scan or exploratory laparotomy was performed as indicated by the key clinical pathway. RESULTS Twelve children (5.2%) had documented intra-abdominal injuries. All five injured children with significant intraperitoneal fluid were identified by US. Of the seven patients who had intra-abdominal injury not detected by US, six sustained solid organ injuries that were managed nonoperatively. Extrapolated reductions in hospital charges due to the decreased number of computed tomographic scans total

A critical analysis of acutely injured children managed in an adult level I trauma center.

130,000. CONCLUSIONS Using US as a triage tool may dramatically reduce the cost of pediatric BAT evaluation while being able to quickly identify significant intraperitoneal fluid that requires further evaluation and possible laparotomy.