The management of sepsis has substantially improved over the past 15 years. In this study, early, goal-directed therapy, which focuses on the initial resuscitation efforts, was compared with usual ...care for the management of severe sepsis in the United Kingdom.
The incidence of severe sepsis and septic shock in adults is estimated to range from 56 to 91 per 100,000 population per year.
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Affected patients have high rates of death, complications, and resource utilization.
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Since 2002, the Surviving Sepsis Campaign (SSC) has promoted best practice, including early recognition, source control, appropriate and timely antibiotic administration, and resuscitation with intravenous fluids and vasoactive drugs.
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Resuscitation guidance is largely based on a 2001 single-center, proof-of-concept study by Rivers et al., which indicated that protocolized delivery of 6 hours of early, goal-directed therapy (EGDT) to patients presenting to the emergency department . . .
In this study comparing the delivery of early nutritional support through the parenteral route with delivery through the enteral route in critically ill adults, there was no significant difference in ...30-day mortality between the groups.
Nutritional support is standard for critically ill patients and requires a complex calculus of timing, route of delivery, and the amount and type of nutrients that are administered — all of which may affect patient outcomes. The interpretation of published meta-analyses of trials comparing nutritional support through the parenteral route versus the enteral route in critically ill patients
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is complicated by small sample sizes, variable quality, selection bias, lack of standardized definitions, and interventions that combine multiple elements of nutritional support (e.g., timing and route). Currently, the enteral route is the mainstay, largely on the grounds of physiological rationale . . .
To determine whether patients admitted to an ICU during times of unprecedented ICU capacity strain, during the COVID-19 pandemic in the United Kingdom, experienced a higher risk of death.
...Multicenter, observational cohort study using routine clinical audit data.
Adult general ICUs participating the Intensive Care National Audit & Research Centre Case Mix Programme in England, Wales, and Northern Ireland.
One-hundred thirty-thousand six-hundred eighty-nine patients admitted to 210 adult general ICUs in 207 hospitals.
Multilevel, mixed effects, logistic regression models were used to examine the relationship between levels of ICU capacity strain on the day of admission (typical low, typical, typical high, pandemic high, and pandemic extreme) and risk-adjusted hospital mortality.
In adjusted analyses, compared with patients admitted during periods of typical ICU capacity strain, we found that COVID-19 patients admitted during periods of pandemic high or pandemic extreme ICU capacity strain during the first wave had no difference in hospital mortality, whereas those admitted during the pandemic high or pandemic extreme ICU capacity strain in the second wave had a 17% (odds ratio OR, 1.17; 95% CI, 1.05-1.30) and 15% (OR, 1.15; 95% CI, 1.00-1.31) higher odds of hospital mortality, respectively. For non-COVID-19 patients, there was little difference in trend between waves, with those admitted during periods of pandemic high and pandemic extreme ICU capacity strain having 16% (OR, 1.16; 95% CI, 1.08-1.25) and 30% (OR, 1.30; 95% CI, 1.14-1.48) higher overall odds of acute hospital mortality, respectively.
For patients admitted to ICU during the pandemic, unprecedented levels of ICU capacity strain were significantly associated with higher acute hospital mortality, after accounting for differences in baseline characteristics. Further study into possible differences in the provision of care and outcome for COVID-19 and non-COVID-19 patients is needed.
By describing trends in intensive care for patients with coronavirus disease (COVID-19) we aim to support clinical learning, service planning, and hypothesis generation.
To describe variation in ICU ...admission rates over time and by geography during the first wave of the epidemic in England, Wales, and Northern Ireland; to describe trends in patient characteristics on admission to ICU, first-24-hours physiology in ICU, processes of care in ICU and patient outcomes; and to explore deviations in trends during the peak period.
A cohort of 10,741 patients with COVID-19 in the Case Mix Program national clinical audit from February 1 to July 31, 2020, was used. Analyses were stratified by time period (prepeak, peak, and postpeak periods) and geographical region. Logistic regression was used to estimate adjusted differences in 28-day in-hospital mortality between periods.
Admissions to ICUs peaked almost simultaneously across regions but varied 4.6-fold in magnitude. Compared with patients admitted in the prepeak period, patients admitted in the postpeak period were slightly younger but with higher degrees of dependency and comorbidity on admission to ICUs and more deranged first-24-hours physiology. Despite this, receipt of invasive ventilation and renal replacement therapy decreased, and adjusted 28-day in-hospital mortality was reduced by 11.8% (95% confidence interval, 8.7%-15.0%). Many variables exhibited u-shaped or n-shaped curves during the peak.
The population of patients with COVID-19 admitted to ICUs, and the processes of care in ICUs, changed over the first wave of the epidemic. After adjustment for important risk factors, there was a substantial improvement in patient outcomes.
Despite Canada's investment of hundreds of millions of dollars into researching coronavirus disease 2019 (COVID-19), contributions from other countries have greatly exceeded Canada's research ...productivity. Additional research funds in Canada have been leveraged during the pandemic, and more may be needed. However, it will take more than just funding to fulfill Canada's health research potential; a culture change is required, along with the will to forge a partnership among the provincial and territorial health systems and the various research institutes and organizations. Here, Lamontagne et al discuss the limitations of the existing clinical research infrastructure in Canada, describe the mechanisms implemented to successfully embed clinical research in the UK health system and provide a roadmap to a Canadian version of the UK system.
OBJECTIVES:To determine whether patients admitted to an ICU during times of strain, when compared with its own norm (i.e. accommodating a greater number of patients, higher acuity of illness, or ...frequent turnover), is associated with a higher risk of death in ICUs with closed models of intensivist staffing.
DESIGN:We conducted a large, multicenter, observational cohort study. Multilevel mixed effects logistic regression was used to examine relationships for three measures of ICU strain (bed census, severity-weighted bed census, and activity-weighted bed census) on the day of admission with risk-adjusted acute hospital mortality.
SETTING:Pooled case mix and outcome database of adult general ICUs participating in the Intensive Care National Audit and Research Centre Case Mix Programme.
MEASUREMENTS AND MAIN RESULTS:The analysis included 149,310 patients admitted to 215 adult general ICUs in 213 hospitals in United Kingdom, Wales, and Northern Ireland. A relative lower strain in ICU capacity as measured by bed census on the calendar day (daytime hours) of admission was associated with decreased risk-adjusted acute hospital mortality (odds ratio, 0.94; 95% CI, 0.90–0.99; p = 0.01), whereas a nonsignificant association was seen between higher strain and increased acute hospital mortality (odds ratio, 1.04; 95% CI, 1.00–1.10; p = 0.07). The relationship between periods of high ICU strain and acute hospital mortality was strongest when bed census was composed of higher acuity patients (odds ratio, 1.05; 95% CI, 1.01–1.10; p = 0.03). No relationship was seen between high strain and ICU mortality.
CONCLUSIONS:In closed staffing models of care, variations in bed census within individual ICUs was associated with patient’s predicted risk of acute hospital mortality, particularly when its standardized bed census consisted of sicker patients.
OBJECTIVES:Sepsis generates significant global acute illness burden. The international variations in sepsis epidemiology (illness burden) have implications for region specific health policy. We ...hypothesised that there have been changes over time in the sepsis definitional elements (infection and organ dysfunction), and these may have impacted on hospital mortality.
DESIGN:Cohort study.
SETTING:We evaluated a high quality, nationally representative, clinical ICU database including data from 181 adult ICUs in England.
PATIENTS:Nine hundred sixty-seven thousand five hundred thirty-two consecutive adult ICU admissions from January 2000 to December 2012.
INTERVENTIONS:None.
MEASUREMENTS AND MAIN RESULTS:To address the proposed hypothesis, we evaluated a high quality, nationally representative, clinical, ICU database of 967,532 consecutive admissions to 181 adult ICUs in England, from January 2000 to December 2012, to identify sepsis cases in a robust and reproducible way. Multinomial logistic regression was used to report unadjusted trends in sepsis definitional elements and in mortality risk categories based on organ dysfunction combinations. We generated logistic regression models and assessed statistical interactions with acute hospital mortality as outcome and cohort characteristics, sepsis definitional elements, and mortality risk categories as covariates. Finally, we calculated postestimation statistics to illustrate the magnitude of clinically meaningful improvements in sepsis outcomes over the study period. Over the study period, there were 248,864 sepsis admissions (25.7%). Sepsis mortality varied by infection sources (19.1% for genitourinary to 43.0% for respiratory; p < 0.001), by number of organ dysfunctions (18.5% for 1 to 69.9% for 5; p < 0.001), and organ dysfunction combinations (18.5% for risk category 1 to 58.0% for risk category 4). The rate of improvement in adjusted hospital mortality was significant (odds ratio, 0.939 0.934–0.945 per year; p < 0.001), but showed different secular trends in improvement between infection sources.
CONCLUSIONS:Within a sepsis cohort, we illustrate case-mix heterogeneity using definitional elements (infection source and organ dysfunction). In the context of improving outcomes, we illustrate differential secular trends in impact of these variables on adjusted mortality and propose this as a valid reason for international variations in sepsis epidemiology. Our article highlights the need to determine standardized reporting elements for optimal comparisons of international sepsis epidemiology.
This study presents a patient-level meta-analysis of three recent trials of early, goal-directed therapy for septic shock. Results showed that EGDT did not improve outcomes and increased ...hospitalization costs across a broad range of patient and hospital characteristics.
In 2001, Rivers and colleagues reported on a 263-patient, single-center, randomized, controlled trial of early, goal-directed therapy (EGDT) versus usual care in patients presenting with septic shock to an urban emergency department in the United States.
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EGDT is a 6-hour resuscitation protocol for the administration of intravenous fluids, vasopressors, inotropes, and red-cell transfusion to achieve prespecified targets for arterial blood pressure, central venous pressure, central venous oxygen saturation, and hemoglobin level. EGDT reduced hospital mortality from 46.5% to 30.5%,
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prompting many institutions worldwide to adopt EGDT.
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Three subsequent, government-funded, multicenter, randomized, controlled trials from the United States (Protocolized Care for . . .
IMPORTANCE: Vasopressors are commonly administered to intensive care unit (ICU) patients to raise blood pressure. Balancing risks and benefits of vasopressors is a challenge, particularly in older ...patients. OBJECTIVE: To determine whether reducing exposure to vasopressors through permissive hypotension (mean arterial pressure MAP target, 60-65 mm Hg) reduces mortality at 90 days in ICU patients aged 65 years or older with vasodilatory hypotension. DESIGN, SETTING, AND PARTICIPANTS: A multicenter, pragmatic, randomized clinical trial was conducted in 65 ICUs in the United Kingdom and included 2600 randomized patients aged 65 years or older with vasodilatory hypotension (assessed by treating clinician). The study was conducted from July 2017 to March 2019, and follow-up was completed in August 2019. INTERVENTIONS: Patients were randomized 1:1 to vasopressors guided either by MAP target (60-65 mm Hg, permissive hypotension) (n = 1291) or according to usual care (at the discretion of treating clinicians) (n = 1307). MAIN OUTCOME AND MEASURES: The primary clinical outcome was all-cause mortality at 90 days. RESULTS: Of 2600 randomized patients, after removal of those who declined or had withdrawn consent, 2463 (95%) were included in the analysis of the primary outcome (mean SD age 75 years 7 years; 1387 57% men). Patients randomized to the permissive hypotension group had lower exposure to vasopressors compared with those in the usual care group (median duration 33 hours vs 38 hours; difference in medians, –5.0; 95% CI, –7.8 to –2.2 hours; total dose in norepinephrine equivalents median, 17.7 mg vs 26.4 mg; difference in medians, –8.7 mg; 95% CI, –12.8 to −4.6 mg). At 90 days, 500 of 1221 (41.0%) in the permissive hypotension compared with 544 of 1242 (43.8%) in the usual care group had died (absolute risk difference, −2.85%; 95% CI, −6.75 to 1.05; P = .15) (unadjusted relative risk, 0.93; 95% CI, 0.85-1.03). When adjusted for prespecified baseline variables, the odds ratio for 90-day mortality was 0.82 (95% CI, 0.68 to 0.98). Serious adverse events were reported for 79 patients (6.2%) in the permissive care group and 75 patients (5.8%) in the usual care group. The most common serious adverse events were acute renal failure (41 3.2% vs 33 2.5%) and supraventricular cardiac arrhythmia (12 0.9% vs 13 1.0%). CONCLUSIONS AND RELEVANCE: Among patients 65 years or older receiving vasopressors for vasodilatory hypotension, permissive hypotension compared with usual care did not result in a statistically significant reduction in mortality at 90 days. However, the confidence interval around the point estimate for the primary outcome should be considered when interpreting the clinical importance of the study. TRIAL REGISTRATION: isrctn.org Identifier: ISRCTN10580502
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