Association of Corticosteroid Treatment With Outcomes in Adult Patients With Sepsis A Systematic Review and Meta-analysis

Fang, F. et al| 2018| Association of Corticosteroid Treatment With Outcomes in Adult Patients With SepsisA Systematic Review and Meta-analysis|  JAMA Intern Med| Published online December 21, 2018|  doi:10.1001/jamainternmed.2018.5849

This systematic review with meta-analysis of 37 RCTs considers the research question: Are corticosteroids associated with a reduction in 28-day mortality in patients with sepsis? 

It reports in its study of over 9500 patients with sepsis, that the administration of arteriosclerosis was  associated with reduced 28-day mortality. Administration of corticosteroids were also linked to a increased shock reversal at day 7, as well as vasopressor-free days and with decreased intensive care unit length of stay. 

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The authors of the research suggest that administration of corticosteroid treatment in patients with sepsis is associated with significant improvement in health care outcomes and thus with reduced 28-day mortality.

Abstract

Importance  Although corticosteroids are widely used for adults with sepsis, both the overall benefit and potential risks remain unclear.

Objective  To conduct a systematic review and meta-analysis of the efficacy and safety of corticosteroids in patients with sepsis.

Data Sources and Study Selection  MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials were searched from inception until March 20, 2018, and updated on August 10, 2018. The terms corticosteroidssepsisseptic shockhydrocortisonecontrolled trials, and randomized controlled trialwere searched alone or in combination. Randomized clinical trials (RCTs) were included that compared administration of corticosteroids with placebo or standard supportive care in adults with sepsis.

Data Extraction and Synthesis  Meta-analyses were conducted using a random-effects model to calculate risk ratios (RRs) and mean differences (MDs) with corresponding 95% CIs. Two independent reviewers completed citation screening, data abstraction, and risk assessment.

Main Outcomes and Measures  Twenty-eight–day mortality.

Results  This meta-analysis included 37 RCTs (N = 9564 patients). Eleven trials were rated as low risk of bias. Corticosteroid use was associated with reduced 28-day mortality  and intensive care unit (ICU) mortality. Corticosteroids were significantly associated with increased shock reversal at day 7 and vasopressor-free days ( and with ICU length of stay, the sequential organ failure assessment score at day 7, and time to resolution of shock. However, corticosteroid use was associated with increased risk of hyperglycemia  and hypernatremia.

Conclusions and Relevance  The findings suggest that administration of corticosteroids is associated with reduced 28-day mortality compared with placebo use or standard supportive care. More research is needed to associate personalized medicine with the corticosteroid treatment to select suitable patients who are more likely to show a benefit.

This article is available to Rotherham NHS staff through NHS Athens (one month embargo) or a paper copy of this article is available in the Library

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Sepsis: Raising awareness

Sepsis is a serious complication triggered by an infection, and it can lead to multiple organ failure and death if not treated quickly.

Sepsis kills 44,000 people in the UK each year but many people have never heard of it. They certainly don’t know how to spot the signs and symptoms. We can all help prevent sepsis deaths if we’re aware of early symptoms in adults & older children and can get people treated immediately:

  • High temperature (fever) or low body temperature
  • Chills and shivering
  • Severe breathlessness
  • Confusion or slurred speech
  • Pale or mottled skin

In support their educational programmes to improve knowledge and management of sepsis, the UK Sepsis Trust and NHS England have developed ‘The Sepsis Game’ which helps health professionals learn how to spot and treat sepsis quickly and effectively.

The game is based around the Sepsis Six care bundle and supports the Survive Sepsis training programme. A simplified online version of the Sepsis Game  can be tried here.

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Image source: http://www.sepsisgame.com/

A Role for Antimicrobial Stewardship in Clinical Sepsis Pathways

The aim of this study was to evaluate the impact of early infectious diseases (ID) antimicrobial stewardship (AMS) intervention on inpatient sepsis antibiotic management | Infection Control & Hospital Epidemiology

All patients reviewed by an ID Fellow within 24 hours of sepsis pathway trigger underwent case review and clinic file documentation of recommendations. Those not reviewed by an ID Fellow were considered controls and received standard sepsis pathway care. The primary outcome was antibiotic appropriateness 48 hours after sepsis trigger.

In total, 164 patients triggered the sepsis pathway: 6 patients were excluded (previous sepsis trigger); 158 patients were eligible; 106 had ID intervention; and 52 were control cases. Of these 158 patients, 91 (58%) had sepsis, and 15 of these 158 (9.5%) had severe sepsis. Initial antibiotic appropriateness, assessable in 152 of 158 patients, was appropriate in 80 (53%) of these 152 patients and inappropriate in 72 (47%) of these patients. In the intervention arm, 93% of ID Fellow recommendations were followed or partially followed, including 53% of cases in which antibiotics were de-escalated. ID Fellow intervention improved antibiotic appropriateness at 48 hours by 24% (adjusted risk ratio, 1.24; 95% confidence interval, 1.04–1.47; P=.035). The appropriateness agreement among 3 blinded ID staff opinions was 95%. Differences in intervention and control group mortality (13% vs 17%) and median length of stay (13 vs 17.5 days) were not statistically significant.

Sepsis overdiagnosis and delayed antibiotic optimization may reduce sepsis pathway effectiveness. Early ID AMS improved antibiotic management of non-ICU inpatients with suspected sepsis, predominantly by de-escalation.

Full reference: Burston, J. et al. (2017) A Role for Antimicrobial Stewardship in Clinical Sepsis Pathways: a Prospective Interventional Study. Infection Control & Hospital Epidemiology. Vol. 38 (Issue 9) pp. 1032-1038

Giving immediate antibiotics reduces deaths from sepsis

Giving immediate antibiotics (defined as within one hour) when people present to emergency departments with suspected sepsis reduces their risk of dying by a third compared with later administration. 

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This meta-analysis of observational data from 23,596 people in emergency department settings confirmed that giving antibiotics within one hour was linked to a lower risk of in-hospital mortality compared with giving antibiotics later.

This adds weight to recommendations from NICE and other organisations that antibiotics should be administered straight away in people with suspected sepsis. However, in practice up to a third of people in the UK do not receive antibiotics within the hour.

NHS England and the UK Sepsis Trust have recently launched a campaign to encourage all healthcare professionals to act quickly when they recognise sepsis.

Full reference: Johnston AN, Park J, Doi SA, et al. Effect of immediate administration of antibiotics in patients with sepsis in tertiary care: a systematic review and meta-analysis. Clinical Therapeutics.  2017;39(1):190-202.e6.

Reducing the impact of serious infections CQUIN

Resources to support delivery of the ‘Reducing the impact of serious infections (antimicrobial resistance and sepsis)’ CQUIN, parts 2c and 2d | NHS Improvement

  • Reducing the impact of serious infections CQUIN, parts 2c and 2d – questions and answersPDF, 185.4 KB – Questions and answers relating to parts 2c and 2d of the ‘Reducing the impact of serious infections’ CQUIN.
  • Part 2c data collection and submissionXLSX, 236.1 KB – PHE has developed this submission tool (and sample data collection form) to facilitate the submission of part 2c (antibiotic review). All data submitted will be available on AMR Fingertips.
  • Part 2d antibiotic consumption submission toolXLSM, 91.4 KB – The data submitted as part of this year’s antimicrobial resistance (AMR) CQUIN has been used to develop this baseline data. Providers that did not take part in the 2016/17 AMR CQUIN or submitted previous annual data should submit quarterly data from January to December 2016, using the antibiotic consumption spreadsheets available on the NHS England AMR CQUIN webpage. Without this data a baseline cannot be calculated for your provider.
  • Part 2d baseline dataXLS, 259.5 KB – Use this to submit quarterly antibiotic consumption data to PHE. All data once submitted will be available via AMR Fingertips after an eight week data cleaning period.

Supporting better decision making for acute infection management in secondary care

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Background

The inappropriate use of antimicrobials drives antimicrobial resistance. We conducted a study to map physician decision-making processes for acute infection management in secondary care to identify potential targets for quality improvement interventions.

Methods

Physicians newly qualified to consultant level participated in semi-structured interviews. Interviews were audio recorded and transcribed verbatim for analysis using NVIVO11.0 software. Grounded theory methodology was applied. Analytical categories were created using constant comparison approach to the data and participants were recruited to the study until thematic saturation was reached.

Results

Twenty physicians were interviewed. The decision pathway for the management of acute infections follows a Bayesian-like step-wise approach, with information processed and systematically added to prior assumptions to guide management. The main emerging themes identified as determinants of the decision-making of individual physicians were (1) perceptions of providing ‘optimal’ care for the patient with infection by providing rapid and often intravenous therapy; (2) perceptions that stopping/de-escalating therapy was a senior doctor decision with junior trainees not expected to contribute; and (3) expectation of interactions with local guidelines and microbiology service advice. Feedback on review of junior doctor prescribing decisions was often lacking, causing frustration and confusion on appropriate practice within this cohort.

Conclusion

Interventions to improve infection management must incorporate mechanisms to promote distribution of responsibility for decisions made. The disparity between expectations of prescribers to start but not review/stop therapy must be urgently addressed with mechanisms to improve communication and feedback to junior prescribers to facilitate their continued development as prudent antimicrobial prescribers.

Full reference: Timothy Miles Rawson, T. M. et al: Mapping the decision pathways of acute infection management in secondary care among UK medical physicians: a qualitative study BMC Medicine 2016 14:208

Helping parents spot the signs of sepsis

Sepsis awareness campaign will help parents and carers of young children recognise the symptoms of sepsis.

A nationwide campaign has been launched to help parents spot the symptoms of sepsis to protect young children and save lives.The campaign is principally aimed at parents and carers of young children aged 0 to 4.

The campaign, delivered by Public Health England and the UK Sepsis Trust, follows a number of measures already taken by the NHS to improve early recognition and timely treatment of sepsis. This includes a national scheme to make sure at-risk patients are screened for sepsis as quickly as possible and receive timely treatment on admission to hospital.

Leaflets and posters are being sent to GP surgeries and hospitals across the country. These materials, developed with experts, will urge parents to call 999 or take their child to A&E if they display any of the following signs:

  • looks mottled, bluish or pale
  • is very lethargic or difficult to wake
  • feels abnormally cold to touch
  • is breathing very fast
  • has a rash that does not fade when you press it
  • has a fit or convulsion

The UK Sepsis Trust estimates that there are more than 120,000 cases of sepsis and around 37,000 deaths each year in England.

Click Here to Download Sepsis Symptoms Poster

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Image source: http://sepsistrust.org/