STOP Signs: A Population-based Interrupted Time Series Analysis of Antibiotic Duration for Complicated Intraabdominal Infection Before and After the Publication of a Landmark RCT.

OBJECTIVE: To determine if the STOP-IT randomized controlled trial changed antibiotic prescribing in patients with Complicated Intraabdominal Infection (CIAI). SUMMARY OF BACKGROUND DATA: CIAI is common and causes significant morbidity. In May 2015, the STOP-IT randomized controlled trial showed equivalent outcomes between four-day and clinically determined antibiotic duration. METHODS: This was a population-based retrospective cohort study using interrupted time series methods. The STOP-IT publication date was the exposure. Median duration of inpatient antibiotic prescription was the outcome. All adult patients admitted to four hospitals in Calgary, Canada between July 2012 and December 2018 with CIAI who survived at least four days following source control were included. Analysis was stratified by infectious source as appendix or biliary tract (group A) versus other (group B). RESULTS: Among 4384 included patients, clinical and demographic attributes were similar before vs after publication. In Group A, median inpatient antibiotic duration was 3 days and unchanged from the beginning to the end of the study period [adjusted median difference -0.00 days, 95% confidence interval (CI) -0.37 - 0.37 days]. In Group B, antibiotic duration was shorter at the end of the study period (7.87 vs 6.73 days; -1.14 days, CI-2.37 - 0.09 days), however there was no change in trend following publication (-0.03 days, CI -0.16 - 0.09). CONCLUSIONS: For appendiceal or biliary sources of CIAI, antibiotic duration was commensurate with the experimental arm of STOP-IT. For other sources, antibiotic duration was long and did not change in response to trial publication. Additional implementation science is needed to improve antibiotic stewardship.

Compassion fatigue in healthcare providers: A systematic review and meta-analysis.

BACKGROUND: Compassion fatigue is recognized as impacting the health and effectiveness of healthcare providers, and consequently, patient care. Compassion fatigue is distinct from "burnout." Reliable measurement tools, such as the Professional Quality of Life scale, have been developed to measure the prevalence, and predict risk of compassion fatigue. This study reviews the prevalence of compassion fatigue among healthcare practitioners, and relationships to demographic variables. METHODS: A systematic review was conducted using key words in MEDLINE, PubMed, and Ovid databases. Data were extracted from a total of 71 articles meeting inclusion criteria, from studies measuring compassion fatigue in healthcare providers using a validated instrument. Quantitative and qualitative data were extracted and compiled by three independent reviewers into an evidence table that included basic study characteristics, study strength and quality determination, measurements of compassion fatigue, and general findings. Meta-analysis, where data allowed, was stratified by Professional Quality of Life version, heterogeneity was quantified, and pooled means were reported with 95% confidence interval. A table of major study characteristics and results was created. ETHICAL CONSIDERATION: This paper contains no primary data obtained directly from research participants. Data obtained from previously published resources have been acknowledged within references. Psychological distress, particularly compassion fatigue, can be insidious, no health profession is immune, and may significantly impact the ability to provide care. RESULTS: A total of 71 studies were included. Compassion fatigue was reported across all practitioner groups studied. Relationships to most demographic variables such as years of experience and specialty were either not statistically significant or unclear. Variability in reporting of Professional Quality of Life results was found. INTERPRETATION: Compassion fatigue exists across diverse practitioner groups. Prevalence is highly variable, and its relationship with demographic, personal, and/or professional variables is inconsistent. Questions are raised about how to mitigate compassion fatigue.

Cost-effectiveness of dalteparin vs unfractionated heparin for the prevention of venous thromboembolism in critically ill patients.

IMPORTANCE: Venous thromboembolism (VTE) is a common complication of acute illness, and its prevention is a ubiquitous aspect of inpatient care. A multicenter blinded, randomized trial compared the effectiveness of the most common pharmocoprevention strategies, unfractionated heparin (UFH) and the low-molecular-weight heparin (LMWH) dalteparin, finding no difference in the primary end point of leg deep-vein thrombosis but a reduced rate of pulmonary embolus and heparin-induced thrombocytopenia among critically ill medical-surgical patients who received dalteparin. OBJECTIVE: To evaluate the comparative cost-effectiveness of LMWH vs UFH for prophylaxis against VTE in critically ill patients. DESIGN, SETTING, AND PARTICIPANTS: Prospective economic evaluation concurrent with the Prophylaxis for Thromboembolism in Critical Care Randomized Trial (May 2006 to June 2010). The economic evaluation adopted a health care payer perspective and in-hospital time horizon; derived baseline characteristics and probabilities of intensive care unit and in-hospital events; and measured costs among 2344 patients in 23 centers in 5 countries and applied these costs to measured resource use and effects of all enrolled patients. MAIN OUTCOMES AND MEASURES: Costs, effects, incremental cost-effectiveness of LMWH vs UFH during the period of hospitalization, and sensitivity analyses across cost ranges. RESULTS: Hospital costs per patient were $39,508 (interquartile range [IQR], $24,676 to $71,431) for 1862 patients who received LMWH compared with $40,805 (IQR, $24,393 to $76,139) for 1862 patients who received UFH (incremental cost, -$1297 [IQR, -$4398 to $1404]; P = .41). In 78% of simulations, a strategy using LMWH was most effective and least costly. In sensitivity analyses, a strategy using LMWH remained least costly unless the drug acquisition cost of dalteparin increased from $8 to $179 per dose and was consistent among higher- and lower-spending health care systems. There was no threshold at which lowering the acquisition cost of UFH favored prophylaxis with UFH. CONCLUSIONS AND RELEVANCE: From a health care payer perspective, the use of the LMWH dalteparin for VTE prophylaxis among critically ill medical-surgical patients was more effective and had similar or lower costs than the use of UFH. These findings were driven by lower rates of pulmonary embolus and heparin-induced thrombocytopenia and corresponding lower overall use of resources with LMWH.

The Model for End-stage Liver Disease accurately predicts 90-day liver transplant wait-list mortality in Atlantic Canada.

OBJECTIVE: To determine the generalizability of the predictions for 90-day mortality generated by Model for End-stage Liver Disease (MELD) and the serum sodium augmented MELD (MELDNa) to Atlantic Canadian adults with end-stage liver disease awaiting liver transplantation (LT). METHODS: The predictive accuracy of the MELD and the MELDNa was evaluated by measurement of the discrimination and calibration of the respective models' estimates for the occurrence of 90-day mortality in a consecutive cohort of LT candidates accrued over a five-year period. Accuracy of discrimination was measured by the area under the ROC curves. Calibration accuracy was evaluated by comparing the observed and model-estimated incidences of 90-day wait-list failure for the total cohort and within quantiles of risk. RESULTS: The area under the ROC curve for the MELD was 0.887 (95% CI 0.705 to 0.978) - consistent with very good accuracy of discrimination. The area under the ROC curve for the MELDNa was 0.848 (95% CI 0.681 to 0.965). The observed incidence of 90-day wait-list mortality in the validation cohort was 7.9%, which was not significantly different from the MELD estimate of 6.6% (95% CI 4.9% to 8.4%; P=0.177) or the MELDNa estimate of 5.8% (95% CI 3.5% to 8.0%; P=0.065). Global goodness-of-fit testing found no evidence of significant lack of fit for either model (Hosmer-Lemeshow c2 [df=3] for MELD 2.941, P=0.401; for MELDNa 2.895, P=0.414). CONCLUSION: Both the MELD and the MELDNa accurately predicted the occurrence of 90-day wait-list mortality in the study cohort and, therefore, are generalizable to Atlantic Canadians with end-stage liver disease awaiting LT.

Impact of Patient and Family Involvement in Long-Term Outcomes.

Surviving a critical illness can have long-term effects on both patients and families. These effects can be physical, emotional, cognitive, and social, and they affect both the patient and the family. Family members play a key role in helping their loved one recover, and this recovery process can take considerable time. Transferring out of an intensive care unit, and discharging home from a hospital, are important milestones, but they represent only the beginning of recovery and healing after a critical illness. Recognizing that these challenges exist both for patients and families is important to improve critical illness outcomes.

A multicentre controlled pre-post trial of an implementation science intervention to improve venous thromboembolism prophylaxis in critically ill patients.

PURPOSE: To test whether a multicomponent intervention would increase the use of low molecular weight heparin (LMWH) over unfractionated heparin (UFH) for venous thromboembolism (VTE) prophylaxis in critically ill patients and change patient outcomes and healthcare utilization. METHODS: Controlled pre-post trial of 12,342 adults admitted to 11 ICUs (five intervention, six control) May 1, 2015 to April 30, 2017 with no contraindication to pharmacological prophylaxis and an ICU stay longer than 24 h. Models were developed to examine temporal changes in ICU VTE prophylaxis (primary outcome), VTE, major bleeding, heparin-induced thrombocytopenia (HIT), death and hospital costs. RESULTS: The use of LMWH increased from 45.9% to 78.3% of patient days in the intervention group and from 37.9% to 53.3% in the control group, an absolute increase difference of 17.0% (32.4% vs. 15.4%, p = 0.001). Changes in the administration of UFH were inversely related to those of LMWH. There were no significant differences in the adjusted odds of VTE (ratio of odds ratios [rOR] 1.13, 95% CI 0.51-2.46) or major bleeding (rOR 1.22, 95% CI 0.97-1.54) post-implementation of the intervention (compared to pre-implementation) between the intervention group and the control group. HIT was uncommon in both groups (n = 20 patients). There were no significant changes for ICU and hospital mortality, length of stay and costs. Results were similar when stratified according to reason for ICU admission, patient weight and kidney function. CONCLUSIONS: A multicomponent intervention changed practice, but not clinical and economic outcomes. The benefit of implementing LMWH for VTE prophylaxis under real-world conditions is uncertain.

(Uncontrolled) donation after cardiac determination of death: a note of caution.

In this short article, we articulate a position that organ recovery from uncontrolled DCD (uDCD)--primarily patients who have suffered a cardiac arrest--is unlikely to result in a significant number of organs, and this small gain must be balanced against significant risk of unduly influencing resuscitation provider decision-making, and jeopardizing public trust in the propriety of organ donation and transplantation.

Derivation of a PIRO Score for Prediction of Mortality in Surgical Patients With Intra-Abdominal Sepsis.

BACKGROUND: Mortality in patients with intra-abdominal sepsis remains high. Recognition and classification of patients with sepsis are challenging; about 70% of critical care specialists find the existing definitions confusing and not clinically useful. OBJECTIVE: To assess the usefulness of the predisposition, infection/injury, response, organ dysfunction (PIRO) concept in surgical intensive care patients with severe sepsis or septic shock due to an intra-abdominal source. METHODS: Data from 2005 through 2010 of a prospective observational cohort were reviewed retrospectively. RESULTS: Among 905 patients, overall mortality was 21.3%, but patients with septic shock had a mortality of 40.6%. The variables in each PIRO subset with P ≤ .10 were entered into a stepwise backward elimination logistic regression. A PIRO score was developed that included the following variables: age greater than 65 years; comorbid conditions; leukopenia; hypothermia; and cardiovascular, renal, respiratory, and central nervous system failure. One point was given for each feature detected. The mean score was significantly higher (P < .001) in non-survivors (3.9) than in survivors (2.3). When the data were distributed according to PIRO scores, mortality rate increased (P < .001). The area under the receiver operating characteristic curve indicated consistent mortality discrimination by PIRO scores (0.80; 95% CI, 0.79-0.83), outperforming the Acute Physiology and Chronic Health Evaluation II (0.72; 95% CI, 0.68-0.75) and the Sequential Organ Failure Assessment (0.72; 95% CI, 0.68-0.76) (P < .001). CONCLUSION: The PIRO score is useful for predicting mortality in patients with surgically related intra-abdominal sepsis.

An economic evaluation of activated protein C treatment for severe sepsis.

BACKGROUND: Recombinant human activated protein C was shown in the Recombinant Human Activated Protein C Worldwide Evaluation in Severe Sepsis (PROWESS) study to reduce mortality among patients with severe sepsis. A post hoc reanalysis by the Food and Drug Administration (FDA) of data from this study suggested that the reduction in mortality was restricted to patients with Acute Physiology and Chronic Health Evaluation (APACHE II) scores of 25 or more. METHODS: We estimated the cost effectiveness of activated protein C as compared with conventional care for patients with severe sepsis. We performed an economic analysis involving all patients, as well as analyses of subgroups defined according to age and severity of illness. The probabilities of transition between clinical states and the estimates of resource use were derived from a population-based cohort of patients with severe sepsis. We used data on the effectiveness of activated protein C from the PROWESS study and analyses by the FDA. RESULTS: The cost per life-year gained by treating all patients with activated protein C was $27,936. It was more cost effective to treat patients with an APACHE II score of 25 or more ($24,484 per life-year gained) than those with a lower APACHE II score ($35,632 per life-year gained). The cost effectiveness of treating patients with an APACHE II score of 24 or less increased to $575,054 per life-year gained when the FDA's estimates of effectiveness were considered. For patients with an APACHE II score of 25 or more, the cost per life-year gained increased with age ($16,309 for patients less than 40 years of age; $28,100 for those 80 years of age or older). CONCLUSIONS: Activated protein C is relatively cost effective when targeted to patients with severe sepsis, greater severity of illness (an APACHE II score of 25 or more), and a reasonable life expectancy if they survive the episode of sepsis. Further research is needed to determine the cost effectiveness of activated protein C for patients with sepsis and less severe illness.

The epidemiology of severe sepsis syndrome and its treatment with recombinant human activated protein C.

Severe sepsis syndrome has important consequences to healthcare systems as the incidence is increasing, there is significant attributed morbidity and mortality and there is a substantial cost for in-hospital and post-discharge care. Current treatment includes the use of antimicrobials, local source control and aggressive physiological support, usually in an intensive care unit setting. Drotrecogin-alpha (activated) or recombinant human activated protein C (rhAPC) is the only biological agent approved for use in severe sepsis syndrome that has demonstrated efficacy in reducing 28-day all-cause mortality and new data suggests a trend towards longer term survival. However, given the evidence of a variable effect on survival rates in patient subgroups and its acquisition cost, controversy has arisen concerning its appropriate use. This review discusses the epidemiology of sepsis, preclinical and clinical evidence supporting the use of rhAPC use, controversies about the evidence of efficacy in severe sepsis syndrome and cost-effectiveness data.

Economic evaluation of the prophylaxis for thromboembolism in critical care trial (E-PROTECT): study protocol for a randomized controlled trial.

BACKGROUND: Venous thromboembolism (VTE) is a common complication of critical illness with important clinical consequences. The Prophylaxis for ThromboEmbolism in Critical Care Trial (PROTECT) is a multicenter, blinded, randomized controlled trial comparing the effectiveness of the two most common pharmocoprevention strategies, unfractionated heparin (UFH) and low molecular weight heparin (LMWH) dalteparin, in medical-surgical patients in the intensive care unit (ICU). E-PROTECT is a prospective and concurrent economic evaluation of the PROTECT trial. METHODS/DESIGN: The primary objective of E-PROTECT is to identify and quantify the total (direct and indirect, variable and fixed) costs associated with the management of critically ill patients participating in the PROTECT trial, and, to combine costs and outcome results to determine the incremental cost-effectiveness of LMWH versus UFH, from the acute healthcare system perspective, over a data-rich time horizon of ICU admission and hospital admission. We derive baseline characteristics and probabilities of in-ICU and in-hospital events from all enrolled patients. Total costs are derived from centers, proportional to the numbers of patients enrolled in each country. Direct costs include medication, physician and other personnel costs, diagnostic radiology and laboratory testing, operative and non-operative procedures, costs associated with bleeding, transfusions and treatment-related complications. Indirect costs include ICU and hospital ward overhead costs. Outcomes are the ratio of incremental costs per incremental effects of LMWH versus UFH during hospitalization; incremental cost to prevent a thrombosis at any site (primary outcome); incremental cost to prevent a pulmonary embolism, deep vein thrombosis, major bleeding event or episode of heparin-induced thrombocytopenia (secondary outcomes) and incremental cost per life-year gained (tertiary outcome). Pre-specified subgroups and sensitivity analyses will be performed and confidence intervals for the estimates of incremental cost-effectiveness will be obtained using bootstrapping. DISCUSSION: This economic evaluation employs a prospective costing methodology concurrent with a randomized controlled blinded clinical trial, with a pre-specified analytic plan, outcome measures, subgroup and sensitivity analyses. This economic evaluation has received only peer-reviewed funding and funders will not play a role in the generation, analysis or decision to submit the manuscripts for publication. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT00182143 . Date of registration: 10 September 2005.

Brief review: history, concept and controversies in the neurological determination of death.

PURPOSE: Despite general worldwide acceptance of the concept of neurological determination of death (NDD), inconsistencies in clinical criteria and ancillary testing requirements remain. Numerous guidelines for NDD may be applied in clinical practice by a variety of medical practitioners, but the scientific rationale for specific guideline recommendations often remains unclear. This review examines the evolution of NDD, and seeks to provide scientific validation for existing NDD criteria. SOURCE: English language peer-reviewed medical journals and established contemporary medical texts. PRINCIPAL FINDINGS: Currently published guidelines appear to have evolved from the work of the ad hoc Committee of the Harvard Medical School to Examine the Definition of Brain Death. The Conference of the Royal Colleges and Faculties of the United Kingdom refined the criteria and subsequently adopted the principal of brainstem death. While the fundamentals of NDD guidelines are remarkably consistent worldwide, specific criteria and requirements are often inconsistent. CONCLUSION: Numerous controversies regarding NDD continue to exist, necessitating further scientific clarification of these issues. More recently published guidelines representing the collective opinion of world experts in NDD based upon best current scientific evidence are available in current medical journals.

Brief survey: determining brain death in Canadian intensive care units.

PURPOSE: Criteria for brain death were first described in 1968, and Canadian guidelines were published in 1988. However, international inconsistency persists in the process of determining brain death. We sought to determine self-reported practices and processes in the determination of brain death amongst Canadian intensive care unit (ICU) physicians. METHODS: An email survey of members of the Canadian Critical Care Society was undertaken. A survey instrument was developed, then face and content validated prior to distribution. RESULTS: Eighty eight responded (response rate = 49%), including adult and pediatric ICU physicians working in both tertiary referral (academic) and community hospitals. Most respondents admit patients with brain death to their ICUs. However, 9% reported refusing to admit this type of patient for reasons including inappropriate utilization of ICU resources (36%), and lack of either space or staff (32% and 29% of respondents, respectively). Community hospital-based ICU physicians were less likely to report a hospital policy on the determination of brain death (46% vs 78% of physicians in tertiary care hospitals). Nearly all physicians (96%) reported that a revised national standard and checklist for the determination of death would be useful. CONCLUSIONS: Nearly one quarter, and over one half of tertiary care and community hospitals (respectively) in Canada lack an institutional policy on neurological determination of brain death. Canadian ICU physicians are interested in a national standard for the determination of death, and establishment of processes that may improve the clinical determination of death by neurological criteria.

Brief review: the role of ancillary tests in the neurological determination of death.

PURPOSE: The acceptance of brain death by society has allowed for the discontinuation of "life support" and the transplantation of organs. In Canada we accept the clinical criteria for brain death (essentially brain stem death) when they can be legitimately applied. Ancillary tests are needed when these clinical criteria cannot be applied or when there are confounders. Ancillary tests include tests of intracranial blood circulation, electrophysiological tests, metabolic studies and tests for residual vagus nerve function. The ideal confirmatory test is one which, when positive, would be incompatible with recoverable brain function (i.e., has no false positives), is not influenced by drugs or metabolic disturbances and which can be readily applied. A critical review of the various ancillary tests used to support the neurological determination of death (brain death) was undertaken. METHODS: A literature review based on a MEDLINE search of relevant articles published between January 1966 to January 2005 was undertaken. RESULTS: Tests of whole brain perfusion/intracranial blood circulation are the only ones that meet stated criteria. CONCLUSIONS: At present only cerebral angiography and nuclear medicine tests of perfusion are accepted by Canadian standards, but computed tomography and magnetic resonance angiography should prove to be suitable. Transcranial Doppler studies may be suitable for specific cases once appropriate guidelines are established.

Potential organ donors referred to Ontario neurosurgical centres.

PURPOSE: Eleven hospitals in Ontario are adult neurosurgical centres (ONCs). Patients transferred to ONCs from community hospitals with acute intracranial emergencies often have non-survivable injuries, and may be returned to the referring hospital for end-of-life care. These referring hospitals may not be familiar with neurological determination of death, or organ donation. Our objective was to determine the number of patients with severe brain injuries assessed in ONC emergency departments where progression to brain death may be reasonably expected, and to determine their outcome. METHODS: A one-year retrospective cohort study was undertaken using a convenience sample of patients transferred to eight ONCs for neurosurgical assessment, with evidence of either (a) brain death in the emergency department, or (b) severe brain injury who met criteria of a reasonable likelihood of progression to brain death. The outcome of these patients to disposition from the ONC was determined by chart review. RESULTS: Three thousand four hundred and forty-seven patients were identified of whom 141 met inclusion criteria. Eleven patients (7.8%) were pronounced dead in the emergency department, 96 (68.1%) patients were admitted, and 34 (24.1%) were transferred back to their referring hospital. Fourteen patients (9.9%) became organ donors: two died in the emergency department and 12 died following admission. CONCLUSIONS: A significant number of patients transferred to ONCs have an injury with a likelihood of progressing to brain death, but only a small proportion of these patients become organ donors. Emergency department triage, assessment and admission decisions for patients with intracranial catastrophes should consider diagnostic criteria for brain death and recognition of donor potential as part of end-of-life care.

Retrieving organs from non-heart-beating organ donors: a review of medical and ethical issues.

PURPOSE: The increasing gap between numbers of individuals awaiting organ replacement surgery and the supply of organs available for transplant underpins attempts to increase the number of organs available. One practice, used in other countries, is the recovery of organs from non-heart-beating organ donors (NHBD). The purpose of this review is to discuss ethical issues surrounding the use of organs from these donors. SOURCE: Narrative review from selected Medline references, and other published reports. PRINCIPAL FINDINGS: NHBD protocols have been established in many countries including the United States. Despite numerous publications, and extensive debate in the literature, significant ethical issues remain unresolved in the retrieval of organs from donors that have died from cessation of cardiac activity. The ethical concerns primarily arise in the determination of death, the tension between the time constraints on recovering organs viable for transplantation, and procedures to enhance organ viability. Despite a concerted effort in the United States, less than half of the organ procurement organizations have NHBD protocols. CONCLUSION: Canadian centres can learn from the difficulties encountered in other centres that have developed NHBD protocols. A moratorium on Canadian NHBD protocols should be considered until a National consensus reflecting Canadian values has been undertaken.

Brain death: resolving inconsistencies in the ethical declaration of death.

PURPOSE: The first criteria for the determination of brain death were developed in 1968 in part to address concerns that had arisen with the retrieval of organs for transplantation. Despite over 30 years of application, some professional and public doubt persists over the validity of the theoretical construct underlying this method of determining death. Our review will address historical perspectives on the development of brain death criteria, and inconsistencies in current clinical criteria. METHOD: Narrative review from selected MEDLINE references and other published sources. PRINCIPLE FINDINGS: The primary construct of the determination of death is that either cardiopulmonary or neurological function irreversibly ceases. However, there is inconsistency in the neurological criteria for death between jurisdictions, between patient populations, and in the use of confirmatory tests. These inconsistencies may cause concern in the public or profession about the validity of the determination of death by neurological criteria. CONCLUSIONS: Organ transplantation is premised on professional and public acceptance that the donor is dead. Given that the criteria for brain death or their application remain variable, we suggest that it is reasonable to consider a national consensus to address these inconsistencies. Alternatively, the standard use of confirmatory radiographic testing prior to the retrieval of organs from donors who meet clinical brain death criteria should be considered to provide conclusive evidence of permanent and irreversible loss of brain function.