The Return on Investment of a Province-Wide Quality Improvement Initiative for Reducing In-Hospital Sepsis Rates and Mortality in British Columbia, Canada.

OBJECTIVES: Sepsis is a life-threatening medical emergency. There is a paucity of information on whether quality improvement approaches reduce the in-hospital sepsis caseload or save lives and decrease the healthcare system and society's cost at the provincial/national levels. This study aimed to assess the outcomes and economic impact of a province-wide quality improvement initiative in Canada. DESIGN: Retrospective population-based study with interrupted time series and return on investment analyses. SETTING: The sepsis cases and deaths averted over time for British Columbia were calculated and compared with the rest of Canada (excluding Quebec and three territories). PATIENTS: Aggregate data were obtained from the Canadian Institute for Health Information on risk-adjusted in-hospital sepsis rates and sepsis mortality in acute care sites across Canada. INTERVENTIONS: In 2012, the British Columbia Sepsis Network was formed to reduce sepsis occurrence and mortality through education, knowledge translation, and quality improvement. MEASUREMENTS AND MAIN RESULTS: A return on investment analysis compared the financial investment for the British Columbia Sepsis Network with the savings from averted sepsis occurrence and mortality. An estimated 981 sepsis cases and 172 deaths were averted in the post-British Columbia Sepsis Network period (2014-2018). The total cost, including the development and implementation of British Columbia Sepsis Network, was $449,962. Net savings due to cases averted after program costs were considered were $50.6 million in 2018. This translates into a return of $112.5 for every dollar invested. CONCLUSIONS: British Columbia Sepsis Network appears to have averted a greater number of sepsis cases and deaths in British Columbia than the national average and yielded a positive return on investment. Our findings strengthen the policy argument for targeted quality improvement initiatives for sepsis care and provide a model of care for other provinces in Canada and elsewhere globally.

Acute Cardiac Injury in Coronavirus Disease 2019 and Other Viral Infections-A Systematic Review and Meta-Analysis.

OBJECTIVES: Severe acute respiratory syndrome-related coronavirus-2 binds and inhibits angiotensin-converting enzyme-2. The frequency of acute cardiac injury in patients with coronavirus disease 2019 is unknown. The objective was to compare the rates of cardiac injury by angiotensin-converting enzyme-2-binding viruses from viruses that do not bind to angiotensin-converting enzyme-2. DATA SOURCES: We performed a systematic review of coronavirus disease 2019 literature on PubMed and EMBASE. STUDY SELECTION: We included studies with ten or more hospitalized adults with confirmed coronavirus disease 2019 or other viral pathogens that described the occurrence of acute cardiac injury. This was defined by the original publication authors or by: 1) myocardial ischemia, 2) new cardiac arrhythmia on echocardiogram, or 3) new or worsening heart failure on echocardiogram. DATA EXTRACTION: We compared the rates of cardiac injury among patients with respiratory infections with viruses that down-regulate angiotensin-converting enzyme-2, including H1N1, H5N1, H7N9, and severe acute respiratory syndrome-related coronavirus-1, to those with respiratory infections from other influenza viruses that do not bind angiotensin-converting enzyme-2, including Influenza H3N2 and influenza B. DATA SYNTHESIS: Of 57 studies including 34,072 patients, acute cardiac injury occurred in 50% (95% CI, 44-57%) of critically ill patients with coronavirus disease 2019. The overall risk of acute cardiac injury was 21% (95% CI, 18-26%) among hospitalized patients with coronavirus disease 2019. In comparison, 37% (95% CI, 26-49%) of critically ill patients with other respiratory viruses that bind angiotensin-converting enzyme-2 (p = 0.061) and 12% (95% CI, 7-22%) of critically ill patients with other respiratory viruses that do not bind angiotensin-converting enzyme-2 (p < 0.001) experienced a cardiac injury. CONCLUSIONS: Acute cardiac injury may be associated with whether the virus binds angiotensin-converting enzyme-2. Acute cardiac injury occurs in half of critically ill coronavirus disease 2019 patients, but only 12% of patients infected by viruses that do not bind to angiotensin-converting enzyme-2.

Reduced fixed dose tocilizumab 400 mg IV compared to weight-based dosing in critically ill patients with COVID-19: A before-after cohort study.

Background: Interleukin-6 inhibitors reduce mortality in severe COVID-19. British Columbia began using tocilizumab 8 mg/kg (maximum 800 mg) in January 2021 in critically ill patients with COVID-19, but due to drug shortages, decreased dosing to 400 mg IV fixed dose in April 2021. The aims of this study were twofold: to compare physiological responses and clinical outcomes of these two strategies, and examine the cost-effectiveness of treating all patients with 400 mg versus half the patients with 8 mg/kg and the other half without tocilizumab. Methods: This was a single-centre, before-after cohort study of critically ill COVID-19 patients treated with tocilizumab, and a control cohort treated with dexamethasone only. Physiological responses and clinical outcomes were compared between patients receiving both doses of tocilizumab and those receiving dexamethasone only. We built a decision tree model to examine cost-effectiveness. Findings: 152 patients were included; 40 received tocilizumab 8 mg/kg, 59 received 400 mg and 53 received dexamethasone only. Median CRP fell from 103 mg/L to 5.2 mg/L, 96 mg/L to 6.8 mg/L and from 81.3 mg/L to 48 mg/L in the 8 mg/kg, 400 mg tocilizumab, and dexamethasone only groups, respectively. 28-day mortality was 5% (n=2) vs 8% (n=5) vs 13% (n=7), with no significant difference in all pair-wise comparison. At an assumed willingness-to-pay threshold of $50,000 Canadian per life-year, utilizing 400 mg for all patients rather than 8 mg/kg for half the patients is cost-effective in 51.6% of 10,000 Monte Carlo simulations. Interpretation: Both doses of tocilizumab demonstrated comparable reduction of inflammation with similar 28-day mortality. Without consideration of equity, the net monetary benefits of providing 400 mg tocilizumab to all patients are comparable to 8 mg/kg to half the patients. In the context of ongoing drug shortages, fixed-dose 400 mg tocilizumab may be a practical, feasible and economical option. Funding: This work was supported by a gift donation from Hsu & Taylor Family to the VGH Foundation, and the Yale Bernard G. Forget Scholarship.

The effect of a bolus dose of etomidate on cortisol levels, mortality, and health services utilization: a systematic review.

STUDY OBJECTIVE: To synthesize the evidence on the effect of a bolus dose of etomidate on adrenal function, mortality, and health services utilization compared with other induction agents used for rapid sequence intubation. METHODS: We developed a systematic search strategy and applied it to 10 electronic bibliographic databases. We hand searched journals; reviewed conference proceedings, gray literature, and bibliographies of relevant literature; and contacted content experts for studies comparing a bolus dose of etomidate with other induction agents. Retrieved articles were reviewed and data were abstracted with standardized forms. Data were pooled with the random-effects model if at least 4 clinically homogenous studies of the same design reported the same outcome measure. All other data were reported qualitatively. RESULTS: From 3,083 titles reviewed, 20 met our inclusion criteria. Pooled mean cortisol levels were lower in elective surgical patients induced with etomidate compared with those induced with other agents between 1 and 4 hours postinduction. The differences varied from 6.1 microg/dL (95% confidence interval [CI] 2.4 to 9.9 microg/dL; P=.001) to 16.4 microg/dL (95% CI 9.7 to 23.1 microg/dL; P<.001). Two studies in critically ill patients reported significantly different cortisol levels up to 7 hours postinduction. None of the studies reviewed, nor our pooled estimate (odds ratio 1.14; 95% CI 0.81 to 1.60), showed a statistically significant effect on mortality. Only one study reported longer ventilator, ICU, and hospital lengths of stay in patients intubated with etomidate. CONCLUSION: The available evidence suggests that etomidate suppresses adrenal function transiently without demonstrating a significant effect on mortality. However, no studies to date have been powered to detect a difference in hospital, ventilator, or ICU length of stay or in mortality.

The Association of Inflammatory Cytokines in the Pulmonary Pathophysiology of Respiratory Failure in Critically Ill Patients With Coronavirus Disease 2019.

OBJECTIVES: The majority of coronavirus disease 2019 mortality and morbidity is attributable to respiratory failure from severe acute respiratory syndrome coronavirus 2 infection. The pathogenesis underpinning coronavirus disease 2019-induced respiratory failure may be attributable to a dysregulated host immune response. Our objective was to investigate the pathophysiological relationship between proinflammatory cytokines and respiratory failure in severe coronavirus disease 2019. DESIGN: Multicenter prospective observational study. SETTING: ICU. PATIENTS: Critically ill patients with coronavirus disease 2019 and noncoronavirus disease 2019 critically ill patients with respiratory failure (ICU control group). INTERVENTIONS: Daily measurement of serum inflammatory cytokines. MEASUREMENTS AND MAIN RESULTS: Demographics, comorbidities, clinical, physiologic, and laboratory data were collected daily. Daily serum samples were drawn for measurements of interleukin-1ß, interleukin-6, interleukin-10, and tumor necrosis factor-α. Pulmonary outcomes were the ratio of Pao2/Fio2 and static lung compliance. Twenty-six patients with coronavirus disease 2019 and 22 ICU controls were enrolled. Of the patients with coronavirus disease 2019, 58% developed acute respiratory distress syndrome, 62% required mechanical ventilation, 12% underwent extracorporeal membrane oxygenation, and 23% died. A negative correlation between interleukin-6 and Pao2/Fio2 (rho, -0.531; p = 0.0052) and static lung compliance (rho, -0.579; p = 0.033) was found selectively in the coronavirus disease 2019 group. Diagnosis of acute respiratory distress syndrome was associated with significantly elevated serum interleukin-6 and interleukin-1ß on the day of diagnosis. CONCLUSIONS: The inverse relationship between serum interleukin-6 and Pao2/Fio2 and static lung compliance is specific to severe acute respiratory syndrome coronavirus 2 infection in critically ill patients with respiratory failure. Similar observations were not found with interleukin-ß or tumor necrosis factor-α.

Missed opportunities for noninvasive positive pressure ventilation: a utilization review.

BACKGROUND: Although noninvasive positive pressure ventilation (NPPV) improves outcomes in patients who have acute respiratory failure due to chronic obstructive pulmonary disease (COPD) or congestive heart failure (CHF), it may be underutilized outside the controlled trial setting. PURPOSE: The purpose of this study is to determine the proportion of patients who met criteria for a trial of NPPV but were emergently intubated and mechanically ventilated without receiving a trial of NPPV. METHODS: We retrospectively reviewed charts of patients who were intubated and ventilated or who received NPPV on admission to one intensive care unit and who had an intensive care unit admitting diagnosis of either exacerbation of COPD or CHF during the period from November 1998 to July 2003. RESULTS: Of the 243 patients who had an admitting diagnosis of COPD or CHF, 59 (24.3%) met explicit criteria for a trial of NPPV. Only 20 (33.9%) of 59 had a trial of NPPV. The remaining 39 (66%) of 59 did not receive a trial of NPPV and were intubated. INTERPRETATION: Nearly two thirds of patients who appeared to meet criteria for NPPV did not receive a trial of this intervention. There is an opportunity to improve the use of NPPV in these patients. Systematic knowledge translation strategies such as guideline implementation and interactive educational interventions may optimize the appropriate use of NPPV.

Purulent pericarditis in a patient with rheumatoid arthritis treated with etanercept and methotrexate.

Purulent pericarditis is rarely seen in this post-antibiotic era. We report a case of spontaneous purulent pericarditis in a patient with rheumatoid arthritis being treated with etanercept, a tumour necrosis factor-alpha (TNF-alpha) antagonist, and methotrexate, an immunosuppressant. Both are disease-modifying anti-rheumatic drugs. We discuss the pathophysiology of purulent pericarditis and the recent literature on the infectious complications of TNF-alpha antagonists.

Prevalence of advance directives among elderly patients attending an urban Canadian emergency department.

INTRODUCTION: To date, there has been minimal research on advance directives (ADs) among elderly patients in Canadian emergency departments (EDs). The purpose of this study was to determine the prevalence of ADs among elderly patients visiting an urban ED. We also explored whether there were factors associated with the existence of an AD and possible barriers to having one. METHODS: This prospective study ran between October and December 2008. Individuals over the age of 70 who presented to the ED between 7 am and 7 pm, 7 days a week, were considered for enrollment. Exclusion criteria included previous enrollment and inability to provide informed consent. A team of nurses who specialize in assessment of geriatric patients administered a study instrument consisting of 28 questions. Topics included demographics, level of education, medical information, and knowledge of and attitudes toward ADs. RESULTS: The results from 280 participants, with an average age of 80.6 years, were analyzed. Thirty-five percent of participants reported that they knew what an AD was; 19.3% of participants said they had an AD, but only 5.6% brought it to the hospital; 50.7% were interested in further information regarding ADs; and 67.9% of participants felt that it was important for physicians to know their wishes about life support. CONCLUSION: Knowledge of ADs among elderly patients visiting an urban Canadian ED is limited and is likely a significant factor precluding wider prevalence of ADs. There is interest in further discussion about ADs in this population group.

Profound metabolic acidosis from pyroglutamic acidemia: an underappreciated cause of high anion gap metabolic acidosis.

The workup of the emergency patient with a raised anion gap metabolic acidosis includes assessment of the components of "MUDPILES" (methanol; uremia; diabetic ketoacidosis; paraldehyde; isoniazid, iron or inborn errors of metabolism; lactic acid; ethylene glycol; salicylates). This approach is usually sufficient for the majority of cases in the emergency department; however, there are many other etiologies not addressed in this mnemonic. Organic acids including 5-oxoproline (pyroglutamic acid) are rare but important causes of anion gap metabolic acidosis. We present the case of a patient with profound metabolic acidosis with raised anion gap, due to pyroglutamic acid in the setting of malnutrition and chronic ingestion of acetaminophen.

Effect of an emergency department sepsis protocol on the care of septic patients admitted to the intensive care unit.

OBJECTIVE: We sought to determine whether the implementation of a sepsis protocol in a Canadian emergency department (ED) improves care for the subset of patients admitted to the intensive care unit (ICU). METHODS: After implementing a sepsis protocol in our ED we used an ICU database and chart review to compare various time-dependent end points and outcomes between a historical control year and the first year after implementation. We re-viewed the charts of all patients admitted to the ICU within 24 hours of ED admission with a primary or other diagnosis of sepsis, severe sepsis or septic shock, who met criteria for early goal-directed therapy within the first 6 hours of their ED stay. RESULTS: We compared 29 patients from the control year with 30 patients from the year after implementation of our sepsis protocol. We found that patients treated during the postintervention year had improvements in time to antibiotics (4.2 v. 1.0 h, difference = -3.2 h, 95% CI -4.8 to -2.0), time to central line placement (above the diaphragm) (11.6 v. 3.2 h, difference = -8.4 h, 95% CI -12.1 to -4.7), time to arterial line placement (7.5 v. 2.3 h, difference = -5.2 h, 95% CI -7.4 to -3.0), and achievement of central venous pressure and central venous oxygen saturation goals (11.1 v. 5.1 h, difference = -6.0 h, 95% CI -11.03 to -1.71, and 13.1 v. 5.5 h, difference = -7.6 h, 95% CI -11.97 to -3.16, respectively). There were no statistically significant differences in ICU length of stay, hospital length of stay or mortality (31.0% v. 20.0%, difference = -11.0%, 95% -33.1% to 11.1%). CONCLUSION: Implementation of an ED sepsis protocol im-proves care for patients with severe sepsis and septic shock.

Effect of early achievement of physiologic resuscitation goals in septic patients admitted from the ward on the kidneys.

PURPOSE: The aim of the study was to evaluate if early achievement of physiologic goals of resuscitation in critically ill septic patients admitted from the ward may prevent acute kidney injury (AKI). MATERIALS AND METHODS: Patients admitted to the intensive care unit (ICU) with a diagnosis of sepsis were retrospectively identified. Mean arterial pressure greater than 65 mm Hg, central venous pressure greater than 8 mm Hg, and central venous oxygenation greater than 70% achieved within 6 hours after ICU consultation at the ward was considered early achievement. Acute kidney injury was defined by the RIFLE criteria. RESULTS: Of 85 patients, 29% achieved all goals within 6 hours, 42% had late or no achievement of goals, and 28% had incomplete documentation of goals. Of these, 52% developed AKI. Patients who eventually developed AKI had a significantly higher creatinine level at ICU consultation before resuscitation. Delay in achievement of goals results in a 3.4% creatinine level rise per hour in multivariate analysis (P = .03). The development of AKI was significantly influenced by delayed achievement of physiologic goals on the ICU (P = .02). CONCLUSIONS: Although most of AKI occurred before ICU consultation, early physiologic resuscitation and achievement of hemodynamic goals on the ICU is associated with a decrease in development of AKI of septic patients admitted from the ward.