Is the process of withdrawal of life-sustaining measures in the intensive care unit different for deceased organ donors compared with other dying patients? A secondary analysis of prospectively collected data.

OBJECTIVE: To investigate whether observable differences exist between patterns of withdrawal of life-sustaining measures (WLSM) for patients eligible for donation after circulatory death (DCD) in whom donation was attempted compared with those patients in whom no donation attempts were made. SETTING: Adult intensive care units from 20 centres in Canada, the Czech Republic and the Netherlands. DESIGN: Secondary analysis of quantitative data collected as part of a large, prospective, cohort study (the Death Prediction and Physiology after Removal of Therapy study). PARTICIPANTS: Patients ≥18 years of age who died after a controlled WLSM in an intensive care unit. Patients were classified as not DCD eligible, DCD eligible with DCD attempted or DCD eligible but DCD was not attempted. PRIMARY AND SECONDARY OUTCOME MEASURES: The process of WLSM (timing and type and, if applicable, dosages of measures withdrawn, dosages of analgesics/sedatives) was compared between groups. RESULTS: Of the 635 patients analysed, 85% had either cardiovascular support stopped or were extubated immediately on WLSM. Of the DCD eligible patients, more were immediately extubated at the initiation of WLSM when DCD was attempted compared with when DCD was not attempted (95% vs 61%, p<0.0001). Initiation of WLSM with the immediate cessation of cardiovascular measures or early extubation was associated with earlier time to death, even after adjusting for confounders (OR 2.94, 95% CI 1.39 to 6.23, at 30 min). Other than in a few patients who received propofol, analgesic and sedative dosing after WLSM between DCD attempted and DCD eligible but not attempted patients was not significantly different. All patients died. CONCLUSIONS: Patients in whom DCD is attempted may receive a different process of WLSM. This highlights the need for a standardised and transparent process for end-of-life care across the spectrum of critically ill patients and potential organ donors.

The Assessment of Risk in Cardiothoracic Intensive Care (ARCtIC): prediction of hospital mortality after admission to cardiothoracic critical care.

The models used to predict outcome after adult general critical care may not be applicable to cardiothoracic critical care. Therefore, we analysed data from the Case Mix Programme to identify variables associated with hospital mortality after admission to cardiothoracic critical care units and to develop a risk-prediction model. We derived predictive models for hospital mortality from variables measured in 17,002 patients within 24 h of admission to five cardiothoracic critical care units. The final model included 10 variables: creatinine; white blood count; mean arterial blood pressure; functional dependency; platelet count; arterial pH; age; Glasgow Coma Score; arterial lactate; and route of admission. We included additional interaction terms between creatinine, lactate, platelet count and cardiac surgery as the admitting diagnosis. We validated this model against 10,238 other admissions, for which the c index (95% CI) was 0.904 (0.89-0.92) and the Brier score was 0.055, while the slope and intercept of the calibration plot were 0.961 and -0.183, respectively. The discrimination and calibration of our model suggest that it might be used to predict hospital mortality after admission to cardiothoracic critical care units.

The role of noninvasive positive pressure ventilation in community-acquired pneumonia.

BACKGROUND: Despite the increasing use of noninvasive positive pressure ventilation (NIV) in the treatment of critically ill patients with respiratory failure, its role in the treatment of severe community-acquired pneumonia (CAP) is controversial. The aim of this study was to assess the use of NIV in patients with CAP requiring ventilation who are admitted an intensive care unit. METHODS: A retrospective cohort study of all consecutive patients admitted to 3 tertiary care, university-affiliated, intensive care units from January 2007 to January 2012 with the principal diagnosis of CAP and requiring positive pressure ventilation was carried out. The primary outcome was acute hospital mortality. Univariable and multivariable analysis were performed to assess the association between mode of ventilation and death as well as factors associated with failure of NIV. RESULTS: A total of 229 patients were admitted, with 20 patients excluded from the analysis because of do-not-resuscitate orders. Fifty-six percent of patients were initially treated with NIV. Of those, 76% failed NIV and required intubation and invasive ventilation. After adjusting for confounders, no difference in mortality was seen between patients who received NIV as first-line therapy in comparison with patients who received invasive ventilation (odds ratio [OR], 1.63; 95% confidence interval [CI], 0.81-3.28; P = .17). Multivariable analysis demonstrated a trend toward increased NIV failure for the patients who had higher Acute Physiology and Chronic Health Evaluation II scores (P = .07) and vasopressor use at 2 hours after initiation of positive pressure ventilation (OR, 7.5; 95% CI, 1.8-31.3, P = .006). In an adjusted analysis, patients who failed NIV had an increased odds of death when compared with patients who were treated with invasive ventilation (OR, 2.2; 95% CI, 1.0-4.8; P = .03). CONCLUSION: Noninvasive pressure ventilation is frequently used in CAP but is associated with high failure rates. Mortality was not improved in the group of patients who received NIV as first-line therapy despite clinical characteristics that might have suggested a more favorable prognosis. Given the high rates of NIV use, high failure rates, and the hypothesis generating nature of the data in this study, further randomized studies are needed to better delineate the role of NIV in CAP.

Development and validation of a risk model for identification of non-neutropenic, critically ill adult patients at high risk of invasive Candida infection: the Fungal Infection Risk Evaluation (FIRE) Study.

BACKGROUND: There is increasing evidence that invasive fungal disease (IFD) is more likely to occur in non-neutropenic patients in critical care units. A number of randomised controlled trials (RCTs) have evaluated antifungal prophylaxis in non-neutropenic, critically ill patients, demonstrating a reduction in the risk of proven IFD and suggesting a reduction in mortality. It is necessary to establish a method to identify and target antifungal prophylaxis at those patients at highest risk of IFD, who stand to benefit most from any antifungal prophylaxis strategy. OBJECTIVES: To develop and validate risk models to identify non-neutropenic, critically ill adult patients at high risk of invasive Candida infection, who would benefit from antifungal prophylaxis, and to assess the cost-effectiveness of targeting antifungal prophylaxis to high-risk patients based on these models. DESIGN: Systematic review, prospective data collection, statistical modelling, economic decision modelling and value of information analysis. SETTING: Ninety-six UK adult general critical care units. PARTICIPANTS: Consecutive admissions to participating critical care units. INTERVENTIONS: None. MAIN OUTCOME MEASURES: Invasive fungal disease, defined as a blood culture or sample from a normally sterile site showing yeast/mould cells in a microbiological or histopathological report. For statistical and economic modelling, the primary outcome was invasive Candida infection, defined as IFD-positive for Candida species. RESULTS: Systematic review: Thirteen articles exploring risk factors, risk models or clinical decision rules for IFD in critically ill adult patients were identified. Risk factors reported to be significantly associated with IFD were included in the final data set for the prospective data collection. DATA COLLECTION: Data were collected on 60,778 admissions between July 2009 and March 2011. Overall, 383 patients (0.6%) were admitted with or developed IFD. The majority of IFD patients (94%) were positive for Candida species. The most common site of infection was blood (55%). The incidence of IFD identified in unit was 4.7 cases per 1000 admissions, and for unit-acquired IFD was 3.2 cases per 1000 admissions. Statistical modelling: Risk models were developed at admission to the critical care unit, 24 hours and the end of calendar day 3. The risk model at admission had fair discrimination (c-index 0.705). Discrimination improved at 24 hours (c-index 0.823) and this was maintained at the end of calendar day 3 (c-index 0.835). There was a drop in model performance in the validation sample. Economic decision model: Irrespective of risk threshold, incremental quality-adjusted life-years of prophylaxis strategies compared with current practice were positive but small compared with the incremental costs. Incremental net benefits of each prophylaxis strategy compared with current practice were all negative. Cost-effectiveness acceptability curves showed that current practice was the strategy most likely to be cost-effective. Across all parameters in the decision model, results indicated that the value of further research for the whole population of interest might be high relative to the research costs. CONCLUSIONS: The results of the Fungal Infection Risk Evaluation (FIRE) Study, derived from a highly representative sample of adult general critical care units across the UK, indicated a low incidence of IFD among non-neutropenic, critically ill adult patients. IFD was associated with substantially higher mortality, more intensive organ support and longer length of stay. Risk modelling produced simple risk models that provided acceptable discrimination for identifying patients at 'high risk' of invasive Candida infection. Results of the economic model suggested that the current most cost-effective treatment strategy for prophylactic use of systemic antifungal agents among non-neutropenic, critically ill adult patients admitted to NHS adult general critical care units is a strategy of no risk assessment and no antifungal prophylaxis. FUNDING: Funding for this study was provided by the Health Technology Assessment programme of the National Institute for Health Research.

Adenomyosis: MRI of the uterus treated with uterine artery embolization.

OBJECTIVE: The purpose of this study was to determine the MRI features seen after uterine artery embolization and to evaluate the clinical response in patients with adenomyosis. MATERIALS AND METHODS: Thirty women with adenomyosis underwent uterine artery embolization and follow-up MRI for 1 year. Of the 30, 27 patients were diagnosed with uterine fibroids and adenomyosis on the basis of MRI before uterine artery embolization. In six of the 27 patients, the dominant disease was adenomyosis. Three of the 30 patients had adenomyosis alone. The distribution, thickness, and enhancement of adenomyosis were analyzed in each patient. Patients completed a symptom questionnaire. RESULTS: After uterine artery embolization, the junctional zone-myometrial ratio did not change significantly. There were regions of devascularization of adenomyosis on contrast-enhanced images in 12 patients, all with a junctional zone thickness before uterine artery embolization of more than 20 mm (mean thickness, 39.2 mm). Eleven of the 12 patients had focal or asymmetric distribution patterns of adenomyosis. All three patients with pure adenomyosis and all six patients with dominant adenomyosis reported an improvement in symptoms. CONCLUSION: In patients treated with uterine artery embolization, MRI shows changes in areas of adenomyosis with a decrease in junctional zone vascularity in patients with thickening of the junctional zone greater than 20 mm. Devascularization may be related to the distribution of adenomyosis. The presence of adenomyosis should not be used as a contraindication to uterine artery embolization because most patients show clinical improvement after undergoing this procedure.

MR angiography and preoperative evaluation for laparoscopic donor nephrectomy.

OBJECTIVE: The purpose of our study was to evaluate the effectiveness of gadolinium-enhanced MR imaging in imaging arterial, venous, and ureteric anatomy in a group of potential laparoscopic renal donors and to compare our findings with those established at surgery. SUBJECTS AND METHODS: Sixty-four consecutive patients underwent successful laparoscopic donor nephrectomy. Imaging of the kidneys was performed before surgery with MR imaging and breath-hold three-dimensional gadolinium-enhanced MR angiography. All studies were reviewed prospectively by one of two attending radiologists. Results were compared with findings at the time of laparoscopic nephrectomy. RESULTS: Of the 64 patients, MR imaging and MR angiography identified 30 patients with normal arterial, venous, and ureteric anatomy, and concordance was found at surgery in 29 of these patients. Vascular anomalies were depicted on MR imaging in 34 patients, with complete concordance at surgery in 29 patients. The use of MR angiography for revealing arterial anomalies had a sensitivity of 89.4%, specificity of 94.1%, and accuracy of 90.6%. For venous anomalies, there was a sensitivity of 98.3%, specificity of 100%, and accuracy of 98.4%. No important utereric anomalies were identified at surgery or on MR imaging. CONCLUSION: Renal MR imaging and gadolinium-enhanced MR angiography provide a safe, accurate, and minimally invasive means of comprehensive assessment of the potential living renal donor.

Time and force dependence of the rupture of glycoprotein IIb-IIIa-fibrinogen bonds between latex spheres.

We studied the shear-induced breakup of doublets of aldehyde/sulfate (A/S) latex spheres covalently linked with purified platelet GPIIb-IIIa receptor, and cross-linked by fibrinogen. Flow cytometry with fluorescein isothiocyanate-fibrinogen showed than an average of 22,500 molecules of active GPIIb-IIIa were captured per sphere, with a mean K(d) = 56 nM for fibrinogen binding. The spheres, suspended in buffered 19% Ficoll 400 containing 120 or 240 pM fibrinogen, were subjected to Couette flow in a counter-rotating cone-plate rheoscope. Doublets, formed by two-body collisions at low shear rate (G = 8 s(-1)) for < or =15 min, were subjected to shear stress from 0.6 to 2.9 Nm(-2), their rotations recorded until they broke up or were lost to view. Although breakup was time dependent, occurring mostly in the first 2 rotations after the onset of shear, the percentage of doublets broken up after 10 rotations were almost independent of normal hydrodynamic force, F(n): at 240 pN, 15.6, 16.0, and 17.0% broke up in the force range 70-150 pN, 150-230 pN, and 230-310 pN. Unexpectedly, at both [fibrinogen], the initial rate of breakup was highest in the lowest force range, and computer simulation using a stochastic model of breakup was unable to simulate the time course of breakup. When pre-sheared at low G for >15 min, no doublets broke up within 10 rotations at 70 < F(n) < 310 pN; it required >3 min shear (>1110 rotations) at F(n) = 210 pN for significant breakup to occur. Other published work has shown that binding of fibrinogen to GPIIb-IIIa immobilized on plane surfaces exhibits an initial fast reversible process with relative low affinity succeeded by transformation of GPIIb-IIIa to a stable high-affinity complex. We postulate that most doublet breakups observed within 10 rotations were from a population of young doublets having low numbers of bonds, by dissociation of the initial receptor complex relatively unresponsive to force. The remaining, older doublets with GPIIb-IIIa in the high-affinity complex were not broken up in the time or range of forces studied.

Pulmonary edema possibly developing secondary to the intravenous administration of oxytocin.

Oxytocin, a posterior pituitary hormone, is commonly used for induction of labor, stimulation or reinforcement of labor, management of incomplete or inevitable abortion and control of post partum bleeding. We describe a case of acute pulmonary edema possibly developing secondary to the administration of iv oxytocin. Clinicians should be aware of the potential for pulmonary edema secondary to iv oxytocin. Close hemodynamic monitoring should be done during oxytocin therapy.

Quinidine-induced hepatotoxicity revisited.

Although quinidine has been widely used since the beginning of the century, quinidine-induced hepatotoxicity has been recently reported in the literature. We describe a reversible case of quinidine-induced hepatotoxicity. A 62-y-old male with a past medical history of atrial flutter and adult onset diabetes was admitted to the hospital with a 3-d history of diarrhea, nausea, fever, chills and palpitations. Past medications included 7.5 mg glyburide daily for 4 y, 0.25 mg digoxin daily for 3 w, 324 mg quinidine gluconate 3 times daily for 2 w, and 150 mg papaverine daily for 2 y. On admission, liver enzyme levels were elevated (SGOT 606, SGPT 1104). Quinidine was considered an etiologic agent and was discontinued after administration of 1 dose. The patient became afebrile within 48 h, liver enzyme levels gradually decreased, and the patient was discharged on day 6 of hospitalization. Repeat enzyme levels obtained 12 d after discharge were mostly within normal limits. The symptoms were atypical as described in the literature. We conclude that unexplained fever or elevated liver enzyme levels should alert the clinician to the possibility of quinidine-induced hepatotoxicity.

Orbital complications of acute sinusitis.

Although the association of sinusitis and inflammation of the orbits has been known for centuries, and the incidence widespread until the introduction of antibiotics, there has been a marked decline in the number of case reports in the medical literature since the 1940s. In this paper three recent cases are presented, with a review of the anatomy, clinical features and the authors' approach to the management of the problem, along with a literature search of this topic.