The Intersection of Death Investigation and Organ Donation Systems: A Scoping Review.

Introduction: Death investigators (DIs) such as coroners, medical examiners, and forensic pathologists play important and evolving roles in deceased organ donation. DIs communicate with organ donation organizations (ODOs) to gather case-specific information and release or restrict organs depending on the medicolegal requirements. This scoping review aims to identify the breadth of roles and decision-making processes that may facilitate or hinder deceased donation in DI cases. Methods: This study was conducted using a scoping literature review and subsequent thematic analysis. Results: Thirty-one eligible papers described 8 common themes with region-specific nuances. These include: 1) shared (ODO and DI) protocols for early communication around each case; 2) shared standards and education for death investigation practices related to organ donation; 3) DI support staff or teams to facilitate organ donation; 4) DI authority to order additional testing and imaging before organ recovery; 5) donation-specific legislation to enhance DI and/or ODO operations; 6) legally trained DI authority to veto medical decisions to proceed with organ donation; 7) DI attendance at organ recovery; and 8) surgeons recording specific DI evidence during organ recovery. Conclusion: These findings have cultural and resource-allocation implications and expose gaps in the international literature describing practices at the intersection of deceased organ donation and death investigation. A better understanding of the rationale and execution of various systems for DI and ODO cooperation may serve to advance both organ donation and death investigation.

Utility of the physical examination in detecting pulmonary hypertension. A mixed methods study.

INTRODUCTION: Patients with pulmonary hypertension (PH) often present with a variety of physical findings reflecting a volume or pressure overloaded right ventricle (RV). However, there is no consensus regarding the diagnostic utility of the physical examination in PH. METHODS: We conducted a systematic review of publications that evaluated the clinical examination and diagnosis of PH using MEDLINE (1946-2013) and EMBASE (1947-2013). We also prospectively evaluated the diagnostic utility of the physical examination findings. Patients who underwent right cardiac catheterization for any reason were recruited. After informed consent, participants were examined by 6 physicians (3 "specialists" and 3 "generalists") who were unaware of the results of the patient's hemodynamics. Each examiner independently assessed patients for the presence of a RV lift, loud P2, jugular venous distension (JVD), tricuspid insufficiency murmur and right-sided 4th heart sound at rest and during a slow inspiration. A global rating (scale of 1-5) of the likelihood that the patient had pulmonary hypertension was provided by each examiner. RESULTS: 31 articles that assessed the physical examination in PH were included in the final analysis. There was heterogeneity amongst the studies and many did not include control data. The sign most associated with PH in the literature was a loud pulmonic component of the second heart sound (P2). In our prospective study physical examination was performed on 52 subjects (25 met criteria for PH; mPAP ≥ 25 mmHg). The physical sign with the highest likelihood ratio (LR) was a loud P2 on inspiration with a LR +ve 1.9, 95% CrI [1.2, 3.1] when data from all examiners was analyzed together. Results from the specialist examiners had higher diagnostic utility; a loud P2 on inspiration was associated with a positive LR of 3.2, 95% CrI [1.5, 6.2] and a right sided S4 on inspiration had a LR +ve 4.7, 95% CI [1.0, 15.6]. No aspect of the physical exam, could consistently rule out PH (negative LRs 0.7-1.3). CONCLUSIONS: The presence of a loud P2 or audible right-sided 4th heart sound are associated with PH. However the physical examination is unreliable for determining the presence of PH.

Role of endothelin-1 in the hyper-responsiveness to nitrovasodilators following acute NOS inhibition.

BACKGROUND AND PURPOSE: Acute NOS inhibition in humans and animals is associated with hypersensitivity to NO donors. The mechanisms underlying this phenomenon have not been fully elucidated. The purpose of the present study was to assess whether hypersensitivity to NOS-blockade is linked to endothelin-1 (ET-1) signalling. EXPERIMENTAL APPROACH: Sprague Dawley rats were instrumented with indwelling arterial and venous catheters for continuous assessments of haemodynamic parameters and drug delivery, respectively. Mesenteric arteries were isolated and tested for reactivity by wire myography. KEY RESULTS: NOS blockade with L-N(G)-nitroarginine methyl ester (L-NAME) caused a pronounced increase in arterial blood pressure (BP) (∼40 mmHg). In L-NAME-treated animals, the dose of sodium nitroprusside (SNP) required to cause a significant reduction in arterial BP was lower than in vehicle-treated rats (P < 0.001), and the magnitude of the reduction in BP was greater. Similar results were obtained with other NO mimetics, but not isoprenaline; moreover, decreasing the BP back to baseline levels with prazosin after L-NAME treatment did not attenuate the hyper-responsiveness to NO donors. The increased responsiveness to NO donors was abolished by pretreatment with the ET(A/B) receptor antagonist, PD145065, or the ET(A) receptor-specific antagonist ABT627. Ex vivo, L-NAME treatment potentiated the constriction induced by big endothelin-1 (bET-1), the precursor to active ET-1, but had no effect on the ET-1-mediated constriction. CONCLUSIONS AND IMPLICATIONS: These data suggest that the increased sensitivity to NO donors is mediated, at least in part, by ET-1 in vivo, and the mechanism may involve the conversion of bET-1 to ET-1.

A multifaceted strategy to reduce inappropriate use of frozen plasma transfusions in the intensive care unit.

PURPOSE: The purpose of this study is to determine the effect of a multifaceted behavior-change strategy on inappropriate use of frozen plasma (FP) transfusions in the intensive care unit (ICU). MATERIALS AND METHODS: A prospective, time-series study was conducted in a 15-bed medical-surgical ICU in 3 phases: (1) baseline observation; (2) educational campaign, audit and feedback to prescribers, and implementation of an FP request form; and (3) FP request form only. Independently, in triplicate and blinded to study phase, appropriateness of each FP request was adjudicated based on published guidelines and clinical context. RESULTS: Over the 15-month study period, 626 FP transfusions (210 FP requests) were administered to 88 patients. Inappropriate FP requests decreased slightly from phases I to III (60% vs 46%; P = .09), FP requests that were consistent with the guidelines did not change (23% vs 22%; P = .86), and FP requests that were appropriate for the ICU yet inconsistent with the guidelines increased (17% vs 32%; P = .04). Although uptake of the FP request form decreased in phase III, it was associated with fewer inappropriate transfusions. CONCLUSIONS: The behavior-change strategy modestly improved appropriate use of FP transfusions in the ICU. Improving FP request form accuracy, completeness, and compliance may be required to achieve maximum effect and ensure sustainability.

Necrotizing pneumonia and septic shock: suspecting CA-MRSA in patients presenting to Canadian emergency departments.

We report a case of fatal necrotizing pneumonia and sepsis caused by community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) in an otherwise well, 48-year-old Canadian man with type 2 diabetes mellitus who had travelled to Texas. Despite therapy that included intravenous antibiotics, intravenous immune globulin and other supportive measures, the patient succumbed to his illness. Recently, CA-MRSA pneumonia has been reported in several countries. The virulence of this organism may in part be related to its ability to produce toxins, such as Panton-Valentine leukocidin. As rates of CA-MRSA increase worldwide, physicians should be aware of the potential for MRSA to cause life-threatening infections in patients presenting to Canadian emergency departments (EDs). Necrotizing pneumonia caused by MRSA must be considered in the differential diagnosis of acute, severe respiratory illness. Early recognition of this syndrome in the ED may help physicians initiate appropriate antibiotic therapy in a timely manner.

The use of noninvasive ventilation in emergency department patients with acute cardiogenic pulmonary edema: a systematic review.

STUDY OBJECTIVE: Acute cardiogenic pulmonary edema is a common cause of respiratory distress in emergency department (ED) patients. Noninvasive ventilation by noninvasive positive pressure ventilation or continuous positive airway pressure has been studied as a treatment strategy. We critically evaluate the evidence for the use of noninvasive ventilation on rates of hospital mortality and endotracheal intubation. METHODS: We searched the databases of MEDLINE, EMBASE, and the Cochrane Library from 1980 to 2005. Additional sources included key journals, bibliographies of selected articles, and expert contact. We included studies that incorporated a randomized design; patients older than 18 years and with acute cardiogenic pulmonary edema; diagnosis and treatment initiated in the ED; noninvasive ventilation in addition to standard medical therapy compared to standard medical therapy alone, or noninvasive positive pressure ventilation compared to continuous positive airway pressure (both in addition to standard medical therapy); and data on hospital mortality or intubation. A random-effects model was used to obtain the summary risk ratios (RRs) and 95% confidence intervals (CIs) for hospital mortality and intubation. RESULTS: A pooled analysis of 494 patients suggested that noninvasive ventilation in addition to standard medical therapy significantly reduced hospital mortality compared to standard medical therapy alone (RR 0.61; [95% CI 0.41, 0.91]). Similarly, a meta-analysis of 436 patients suggested that noninvasive ventilation was associated with a significant decrease in intubation rates (RR 0.43; [95% CI 0.21, 0.87]). CONCLUSION: Our results suggest that noninvasive ventilation with standard medical therapy is advantageous over standard medical therapy alone in ED patients with acute cardiogenic pulmonary edema. Future studies, powered appropriately for mortality and intubation rates, are necessary to confirm these findings.

Effects of intravascular cryotherapy on vessel wall repair in a balloon-injured rabbit iliac artery model.

OBJECTIVE: Although the application of cold energy, cryotherapy, has been shown to cause selective damage to cellular components with preservation of matrix structure resulting in less fibrosis in a variety of tissues, the effects of intravascular cryotherapy on vessel wall repair after balloon angioplasty are unknown. We sought to characterize the effects of cryotherapy application on vessel wall repair after balloon angioplasty and study the relationship between collagen accumulation in the vessel wall and late lumen loss as assessed by serial intravascular ultrasound. METHODS: The immediate, early (72 h) and late (10 weeks) effects of three intravascular cryotherapy application time periods (60, 120 and 240 s) after iliac artery balloon angioplasty ('cryotherapy') were compared with balloon angioplasty alone ('control') in 59 rabbits. Arterial lumen area was measured by intravascular ultrasound immediately after the procedure, at 72 h and at 10 weeks. Collagen content was calculated separately for intima and media/adventitia layers and correlated with late lumen loss. RESULTS: Cryotherapy produced average vessel wall temperature of -26 degrees C (range, -20 to -45 degrees C) and resulted in significantly larger lumen cross-sectional area (CSA) immediately after application (5.74+/-1.18 vs. 4.14+/-0.75 mm(2), P=0.008) but was not different than control arteries at 10 weeks. At 72 h, there was extensive cell loss in the medial and adventitial layers accompanied by increased macrophage infiltration in cryotherapy treated arteries compared to control. At 10 weeks, intimal hyperplasia was increased 2-fold in cryotherapy treated arteries. Collagen content was increased 2-fold in the medial/adventitial layers, and nearly 3-fold in the intima of cryotherapy treated arteries. Collagen content in arterial intima (P=0.01) as well as media/adventitia (P=0.005) positively correlated with late lumen loss. Foci of chondro- and osseous metaplasia and calcification were evident at the medial-adventitial junction in cryotherapy treated arteries at 10 weeks. CONCLUSION: Intravascular cryotherapy induced early arterial wall cell loss and late intimal hyperplasia, vascular fibrosis and chondro- and osseous metaplastic changes with no late beneficial effects on lumen area compared to balloon angioplasty alone. Collagen accumulation in all three layers of the vessel wall contributes to the development of late inward remodeling after balloon angioplasty.

Late effects of low-energy gamma-emitting stents in a rabbit iliac artery model.

PURPOSE: To determine the long-term dose response of novel low-dose gamma-emitting stents in a rabbit iliac artery model. METHODS AND MATERIALS: Control stents (n=24) and 103Pd stents 1.0 to 4.0 mCi (n=36) were implanted in the iliac arteries of 30 New Zealand rabbits. Stents were evaluated by intravascular ultrasound (immediately post procedure and before killing) and by histomorphometry. RESULTS: At 26 weeks, 28 rabbits were killed, with no evidence of stent thrombosis. In the body of the stent there was a dose-response relationship with 50% inhibition of intimal hyperplasia at the highest activity compared to control stents (p=0.07) and a significant increase in intimal hyperplasia at the lowest activity (p < 0.01). At the stent edges, there was a significant reduction of lumen area at all activity levels compared to control stents, which was most prominent at the proximal stent edge. Higher-activity stents demonstrated incomplete endothelialization and immature neointimal formation. CONCLUSIONS: Continuous low-dose-rate irradiation by gamma-emitting 103Pd stents is feasible with reduction of in-stent hyperplasia in a dose-related manner. However, significant narrowing at the stent edges, increased in-stent hyperplasia at lower activities, and incomplete vascular healing with persistence of immature neointima at higher activities are significant limitations.

Arterial repair after stenting and the effects of GM6001, a matrix metalloproteinase inhibitor.

OBJECTIVES: This study compared the extracellular matrix (ECM) and cellular responses after stenting to balloon angioplasty (BA) and to determine the late effects of matrix metalloproteinase (MMP) inhibition on arterial repair after stenting. BACKGROUND: Although stenting is the predominant form of coronary intervention, there is limited understanding of the early and late arterial response. METHODS: In a double-injury rabbit model, adjacent iliac arteries in 87 animals received BA (3.0 mm diameter) or stenting (3.0 mm NIR). Rabbits were treated for 1 week postprocedure with either GM6001 (100 mg/kg per day), an MMP inhibitor or placebo and sacrificed at 1 week or at 10 weeks' postprocedure. Arteries were analyzed for morphometry, collagen content, gelatinase activity, cell proliferation and DNA content. RESULTS: Stented arteries had significant increases in collagen content (2-fold) at 10 weeks compared to BA-treated arteries. At one week, overall gelatinase activity was increased >2-fold in stented arteries, with both 72 kD and 92 kD gelatinase activity. Stented arteries also had increases in both intimal DNA content (1.5-fold) and absolute cell proliferation (4-fold). Compared to placebo, GM6001 significantly inhibited intimal hyperplasia and intimal collagen content, and it increased lumen area in stented arteries without effects on proliferation rates. CONCLUSIONS: Stenting causes a more vigorous ECM and MMP response than BA, which involves all layers of the vessel wall. Inhibition by MMP blocks in-stent intimal hyperplasia and offers a novel approach to prevent in-stent restenosis.