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 . . .
Patients in intensive care units (ICUs) suffer from sleep deprivation arising from nursing interventions and ambient noise. This may exacerbate confusion and ICU-related delirium. The World Health ...Organization (WHO) suggests that average hospital sound levels should not exceed 35 dB with a maximum of 40 dB overnight. We monitored five ICUs to check compliance with these guidelines.
Sound levels were recorded in five adult ICUs in the UK. Two sound level monitors recorded concurrently for 24 hours at the ICU central stations and adjacent to patients. Sample values to determine levels generated by equipment and external noise were also recorded in an empty ICU side room.
Average sound levels always exceeded 45 dBA and for 50% of the time exceeded between 52 and 59 dBA in individual ICUs. There was diurnal variation with values decreasing after evening handovers to an overnight average minimum of 51 dBA at 4 AM. Peaks above 85 dBA occurred at all sites, up to 16 times per hour overnight and more frequently during the day. WHO guidelines on sound levels could be only achieved in a side room by switching all equipment off.
All ICUs had sound levels greater than WHO recommendations, but the WHO recommended levels are so low they are not achievable in an ICU. Levels adjacent to patients are higher than those recorded at central stations. Unit-wide noise reduction programmes or mechanical means of isolating patients from ambient noise, such as earplugs, should be considered.
Purpose
Discharge from an intensive care unit (ICU) out of hours is common. We undertook a systematic review and meta-analysis to explore the association between time of discharge and mortality/ICU ...readmission.
Methods
We searched Medline, Embase, Web of Knowledge, CINAHL, the Cochrane Library and OpenGrey to June 2017. We included studies reporting in-hospital mortality and/or ICU readmission rates by ICU discharge “out-of-hours” and “in-hours”. Inclusion was limited to patients aged ≥ 16 years discharged alive from a non-specialist ICU to a lower level of hospital care. Studies restricted to specific diseases were excluded. We assessed study quality using the Newcastle Ottowa Scale. We extracted published data, summarising using a random-effects meta-analysis.
Results
Our searches identified 1961 studies. We included unadjusted data from 1,191,178 patients from 18 cohort studies (presenting data from 1994 to 2014). “Out of hours” had multiple definitions, beginning between 16:00 and 22:00 and ending between 05:59 and 09:00. Patients discharged out of hours had higher in-hospital mortality relative risk (95% CI) 1.39 (1.24, 1.57)
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< 0.0001 and readmission rates 1·30 (1.19, 1.42),
p
< 0.001 than patients discharged in hours. Heterogeneity was high (
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90.1% for mortality and 90.2% for readmission), resulting from differences in effect size rather than the presence of an effect.
Conclusions
Out-of-hours discharge from an ICU is strongly associated with both in-hospital death and ICU readmission. These effects persisted across all definitions of “out of hours” and across healthcare systems in different geographical locations. Whether these increases in mortality and readmission result from patient differences, differences in care, or a combination remains unclear.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
There is conflicting evidence on harm related to exposure to supraphysiologic Pa
(hyperoxemia) in critically ill patients.
To examine the association between longitudinal exposure to hyperoxemia and ...mortality in patients admitted to ICUs in five United Kingdom university hospitals.
A retrospective cohort of ICU admissions between January 31, 2014, and December 31, 2018, from the National Institute of Health Research Critical Care Health Informatics Collaborative was studied. Multivariable logistic regression modeled death in ICU by exposure to hyperoxemia.
Subsets with oxygen exposure windows of 0 to 1, 0 to 3, 0 to 5, and 0 to 7 days were evaluated, capturing 19,515, 10,525, 6,360, and 4,296 patients, respectively. Hyperoxemia dose was defined as the area between the Pa
time curve and a boundary of 13.3 kPa (100 mm Hg) divided by the hours of potential exposure (24, 72, 120, or 168 h). An association was found between exposure to hyperoxemia and ICU mortality for exposure windows of 0 to 1 days (odds ratio OR, 1.15; 95% compatibility interval CI, 0.95-1.38;
= 0.15), 0 to 3 days (OR 1.35; 95% CI, 1.04-1.74;
= 0.02), 0 to 5 days (OR, 1.5; 95% CI, 1.07-2.13;
= 0.02), and 0 to 7 days (OR, 1.74; 95% CI, 1.11-2.72;
= 0.02). However, a dose-response relationship was not observed. There was no evidence to support a differential effect between hyperoxemia and either a respiratory diagnosis or mechanical ventilation.
An association between hyperoxemia and mortality was observed in our large, unselected multicenter cohort. The absence of a dose-response relationship weakens causal interpretation. Further experimental research is warranted to elucidate this important question.
Somatic mutations in UBA1 cause vacuoles, E1 ubiquitin-activating enzyme, X-linked, autoinflammatory somatic (VEXAS) syndrome, an adult-onset inflammatory disease with an overlap of hematologic ...manifestations. VEXAS syndrome is characterized by a high mortality rate and significant clinical heterogeneity. We sought to determine independent predictors of survival in VEXAS and to understand the mechanistic basis for these factors. We analyzed 83 patients with somatic pathogenic variants in UBA1 at p.Met41 (p.Met41Leu/Thr/Val), the start codon for translation of the cytoplasmic isoform of UBA1 (UBA1b). Patients with the p.Met41Val genotype were most likely to have an undifferentiated inflammatory syndrome. Multivariate analysis showed ear chondritis was associated with increased survival, whereas transfusion dependence and the p.Met41Val variant were independently associated with decreased survival. Using in vitro models and patient-derived cells, we demonstrate that p.Met41Val variant supports less UBA1b translation than either p.Met41Leu or p.Met41Thr, providing a molecular rationale for decreased survival. In addition, we show that these 3 canonical VEXAS variants produce more UBA1b than any of the 6 other possible single-nucleotide variants within this codon. Finally, we report a patient, clinically diagnosed with VEXAS syndrome, with 2 novel mutations in UBA1 occurring in cis on the same allele. One mutation (c.121 A>T; p.Met41Leu) caused severely reduced translation of UBA1b in a reporter assay, but coexpression with the second mutation (c.119 G>C; p.Gly40Ala) rescued UBA1b levels to those of canonical mutations. We conclude that regulation of residual UBA1b translation is fundamental to the pathogenesis of VEXAS syndrome and contributes to disease prognosis.
•p.Met41Val genotype and transfusion dependence are risks for decreased survival in VEXAS syndrome; ear chondritis confers better prognosis.•Differences in disease severity of VEXAS syndrome are linked with residual translation of the cytoplasmic isoform of UBA1 (UBA1b).
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
To determine the prevalence of post traumatic stress disorder in survivors of intensive care treatment.
Systematic literature review including Medline, Embase, CINAHL, PsycINFO and references from ...identified papers.
Studies determining the prevalence of PTSD in adult patients who had at least 24Symbol: see texth treatment on an intensive care unit. Independent duplicate data extraction. Study quality was evaluated in terms of study design and method and timing of PTSD assessment. DATA SYNTHESIS AND RESULTS: Of the 1472 citations identified, 30 studies meeting the selection criteria were reviewed. PTSD was diagnosed by standardised clinical interview alone in 2 studies. A self-report measure alone was used in 19 studies to measure PTSD symptomatology. The remaining 9 studies applied both standardised clinical interview and a self-report measure. The reported prevalence of PTSD was 0-64% when diagnosed by standardised clinical interview and 5-64% by self-report measure. PTSD assessments occurred 7 days to 8 years after intensive care discharge.
The true prevalence of PTSD and the optimum timing and method of PTSD assessment have not yet been determined in intensive care unit survivors. Deficiencies in design, methodology and reporting make interpretation and comparison of quoted prevalence rates difficult, and rigorous longitudinal studies are needed.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
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
This study was performed to systematically review the available evidence for the risk factors for new-onset atrial fibrillation (NOAF) on the general adult intensive care unit (ICU) and provide a ...semi-quantitative evidence synthesis.
We searched the MEDLINE, EMBASE, Cochrane Database of Systematic Reviews and the CENTRAL databases from 1970 to 2018.
We included studies of adults based in general ICUs that evaluated potential risk factors for NOAF. We excluded studies involving patients with a history of atrial fibrillation (AF).
We semi-qualitatively evaluated the strength of evidence for each identified variable.
We screened 1447 studies. Seventeen studies were included in the final analysis. We identified strong evidence for age, male sex, preceding cardiovascular disease, acute renal failure, acute respiratory failure, APACHE score and the use of vasopressors as risk factors for the development of NOAF on the ICU. Modifiable risk factors had not been studied in detail.
We provide the first systematic review with evidence synthesis of risk factors for NOAF on the general adult ICU. Evidence for modifiable risk factors was limited. Further research is therefore required and may contribute towards the evidence-based prevention and management of this important condition.
•Limited data exists for modifiable risk factors for new-onset atrial fibrillation in ICU patients.•Demographic/comorbid risk factors include age, male sex and preceding cardiovascular disease.•Acute risk factors include renal failure, respiratory failure, APACHE score and vasopressor use.•Further research should focus on standardised definitions and core outcome measures.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Abstract Objective To compare outcomes in critically ill patients undergoing artificial ventilation who received a tracheostomy early or late in their treatment. Data sources The Cochrane Central ...Register of Clinical Trials, Medline, Embase, CINAHL, the National Research Register, the NHS Trusts Clinical Trials Register, the Medical Research Council UK database, the NHS Research and Development Health Technology Assessment Programme, the British Heart Foundation database, citation review of relevant primary and review articles, and expert informants. Study selection Randomised and quasi-randomised controlled studies that compared early tracheostomy with either late tracheostomy or prolonged endotracheal intubation. From 15 950 articles screened, 12 were identified as “randomised or quasi-randomised” controlled trials, and five were included for data extraction. Data extraction Five studies with 406 participants were analysed. Descriptive and outcome data were extracted. The main outcome measure was mortality in hospital. The incidence of hospital acquired pneumonia, length of stay in a critical care unit, and duration of artificial ventilation were also recorded. Random effects meta-analyses were performed. Results Early tracheostomy did not significantly alter mortality (relative risk 0.79, 95% confidence interval 0.45 to 1.39). The risk of pneumonia was also unaltered by the timing of tracheostomy (0.90, 0.66 to 1.21). Early tracheostomy significantly reduced duration of artificial ventilation (weighted mean difference –8.5 days, 95% confidence interval –15.3 to –1.7) and length of stay in intensive care (–15.3 days, –24.6 to –6.1). Conclusions In critically ill adult patients who require prolonged mechanical ventilation, performing a tracheostomy at an earlier stage than is currently practised may shorten the duration of artificial ventilation and length of stay in intensive care.
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BFBNIB, CMK, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
OBJECTIVES:To identify characteristics that predict 30-day mortality among patients critically ill with coronavirus disease 2019 in England, Wales, and Northern Ireland.
DESIGN:Observational cohort ...study.
SETTING:A total of 258 adult critical care units.
PATIENTS:A total of 10,362 patients with confirmed coronavirus disease 2019 with a start of critical care between March 1, 2020, and June 22, 2020, of whom 9,990 were eligible (excluding patients with a duration of critical care less than 24 hr or missing core variables).
MEASUREMENTS AND MAIN RESULTS:The main outcome measure was time to death within 30 days of the start of critical care. Of 9,990 eligible patients (median age 60 yr, 70% male), 6,027 died within 30 days of the start of critical care. As of July 22, 2020, 189 patients were still receiving critical care and a further 446 were still in acute hospital. Data were missing for between 0.1% and 7.2% of patients across prognostic factors. We imputed missing data ten-fold, using fully conditional specification and continuous variables were modeled using restricted cubic splines. Associations between the candidate prognostic factors and time to death within 30 days of the start of critical care were determined after adjustment for multiple variables with Cox proportional hazards modeling. Significant associations were identified for age, ethnicity, deprivation, body mass index, prior dependency, immunocompromise, lowest systolic blood pressure, highest heart rate, highest respiratory rate, PaO2/FIO2 ratio (and interaction with mechanical ventilation), highest blood lactate concentration, highest serum urea, and lowest platelet count over the first 24 hours of critical care. Nonsignificant associations were found for sex, sedation, highest temperature, and lowest hemoglobin concentration.
CONCLUSIONS:We identified patient characteristics that predict an increased likelihood of death within 30 days of the start of critical care for patients with coronavirus disease 2019. These findings may support development of a prediction model for benchmarking critical care providers.
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