Authors: Bassey Ndoma-Egba, Ahmed Al Rasheed Ahmed, Enda Hession, Etimbuk Umana / Editor: Robert Hirst / Codes: IP3, MHP1, NepC1, RP6, SLO10 / Published: 21/07/2022

This month’s TERN Top Papers is brought to you by the team at the Irish Trainee Emergency Research Network (ITERN). This month’s TERN Top Papers has looked for the most relevant papers on sepsis and infectious diseases. 

We reviewed journals published over the last year covering these topics, across multiple databases leading to a review of over six hundred articles. We hope these papers provide some valuable insights and we would really recommend reviewing the full paper.

If you or your team are interested in writing one of these, please email us at tern.education@rcem.ac.uk and we’ll talk you through the process. Enjoy!

Balanced Multielectrolyte solution versus Saline in Critically Ill Adults (PLUS Trial)

The aim of this study was to see if the use of balanced multielectrolyte  (BMES) solutions reduced the risk of death or acute kidney injury in critically ill patients. 

This multicentre, double-blind, randomized, controlled trial assigned critically ill patients to receive either balanced multielectrolyte solution (Plasma-Lyte 148) or 0.9% sodium chloride therapy in the intensive care unit for 90 days. The primary outcome was death from any cause within 90 days of randomization, with secondary outcomes of new renal replacement therapy and maximum increase in creatinine level during ICU stay.

This study was run across 53 ICUs in New Zealand and Australia over three years with a total of 5037 patients recruited with assignment to the groups equally. 42.3% of the patients had sepsis, 33% were admitted to ICU directly from the ED and primary outcome data was available for 96.2% of recruited patients (4846 patients). The median volume of trial fluid was 3.9L (range 2.0 to 6.7L) and 3.77L (range 2.0 to 6.3L) in saline group.

The primary outcome (death within 90 days) in the Plasma-Lyte group was 530/2433 (21.8%) and 530/2413 (22.0%) in the 0.9% sodium chloride group, an absolute difference of -0.15% (95% CI –3.60–3.30; p=0.90), with an odds ratio of 0.99 (95% CI 0.86–1.14). The maximum increase in serum creatinine level and the initiation of new renal replacement therapy was similar between both groups.

Bottom Line

There was no evidence that the risk of death or acute kidney among critically ill adults in the ICU was lowered by using balanced multi electrolyte solution than using saline. While there may be individual characteristics that may affect these findings, the type of fluid used appears not to affect the outcomes of mortality or renal injury in critically ill adults.

Reference

Finfer S, Micallef S, Hammond N, Navarra L, Bellomo R, Billot L et al. Balanced Multielectrolyte Solution versus Saline in Critically ill Adults. N Engl J Med. 2022; 386: 815-826. doi.10.1056/NEJMoa2114464

Effect of 12 mg vs 6 mg of Dexamethasone on the Number of Days Alive Without Life Support in Adults With COVID-19 and Severe Hypoxemia: The COVID STEROID 2 Randomized Trial 

The aim of this study was to compare the effects of 6mg to 12mg dexamethasone in patients with COVID-19 with severe hypoxemia.

This was an international, multicentre, blinded, randomized clinical trial conducted between August 2020 and May 2021 at 26 hospitals in Europe (Denmark, Switzerland, and Sweden) and India and included 1000 patients. Eligible patients were adults with confirmed COVID-19 requiring at least 10 L/m of oxygen, non-invasive ventilation or mechanical ventilation. 

The primary outcome was the number of days alive without life support (invasive mechanical ventilation, circulatory support, or renal replacement therapy) at 28 days after randomization, which was adjusted for stratification variables. The secondary outcomes were the number of days alive without life support at 90 days, the number of days alive out of the hospital at 90 days, mortality at 28 days and at 90 days, and the number of patients with 1 or more serious adverse reactions at 28 days. 

Treatment with 12 mg/d of dexamethasone compared with 6 mg/d of dexamethasone did not result in significantly more days alive without life support at 28 days. None of the analysed secondary outcomes were statistically significant. 

Strengths of this trial included the pragmatic protocol, inclusion of most eligible patients, blinding, and a high percentage of follow-up at 28 days. Including patients from both Europe (62%) and India (38%) results in a high degree of generalisability across different populations and healthcare systems. 

Limitations were that it was likely underpowered trial to detect statistically significant outcome differences. Additionally, the effect of the intervention may have been reduced in some patients who had been treated with steroids prior to enrolment. Finally, changes in the treatment of COVID-19 during the trial (such as increased use of IL-6 receptor antagonists) may have influenced the results. 

Bottom Line

Compared with 6mg of dexamethasone, 12mg of dexamethasone did not statistically significantly increase the number of days alive without life support at 28 days. 

Reference

The COVID STEROID 2 Trial Group authors. Effect of 12 mg vs 6 mg of Dexamethasone on the Number of Days Alive Without Life Support in Adults With COVID-19 and Severe Hypoxemia: The COVID STEROID 2 Randomized Trial. JAMA. 2021; 326(18): 1807-17. doi:10.1001/jama.2021.18295

The impact of Age on Predictive Performance of National Early Warning Score at Arrival to Emergency Departments: Development and External Validation

This international multicenter retrospective cohort study aimed to investigate how age affects the National Early Warning Score (NEWS) at arrival to the emergency department and to validate the predictive performance externally.

The study was run across 2 hospitals in Denmark (a development cohort) and 3 hospitals in the Netherlands (an external validation cohort). The development cohort used data from the Danish Civil Registration System and Danish National Patient Register and collected blood pressure, oxygen saturation, use of supplemental oxygen, pulse, temperature, oxygen, consciousness and basic demographic information, and included all patients aged >18 years of age. The external validation cohort used data from the Netherlands Emergency Evaluation Database (NEED) and collected the same data. The primary outcome was in-hospital mortality and secondary outcome was ICU admission. 

A multivariable logistic regression was performed to form NEWS + Age. Age showed a non-linear association with the risk of in-hospital mortality, and was the strongest predictor compared to NEWS sum-score for in-hospital mortality. Using NEWS alone resulted in underestimating the risk pf mortality for patients over the age of 80. The Area Under Receiver Operating Characteristics (AUROC) was 0.82 (95% CI 0.80–0.84) in the Danish multi-centre cohort and 0.75 (95% CI 0.75–0.77) in the NEED. 

When NEWS was combined with age, there was elimination of the underestimation of risk for patients over 80. There was a significant increase in the AUROC to 0.86 (95% CI 0.85–0.88) in the Danish multicenter Cohort and 0.82 (95% CI 0.81–0.83) in the NEED group. The same model did not result in improved prediction for ICU admission. 

There were limitations to the study regarding selection bias; patients with missing data was excluded from analysis, and these patients had less favourable outcomes. In addition, the model appeared to be miscalibrated for patients with a high predicted risk of mortality (≥20%). In addition, frailty as a factor was not explored.

Bottom Line

Combining age with the NEWS improved the prediction performance for in-hospital mortality, mostly for patients over the age of 80. There was no effect on the prediction of intensive care admission. 

Reference

Nissen SK, Candel BGJ, Nickel CH, Jonge E, Ryg J, Bogh SB et al. The Impact of Age on Predictive Performance of National Early Warning Score at Arrival to Emergency Departments: Development and External Validation. Ann Emerg Med. 2022; 79(4): 354-363. doi:10.1016/j.annemergmed.2021.09.434

Comparison of qSOFA, SIRS and NEWS scoring systems for diagnosis, mortality and morbidity of sepsis in emergency department.

Sepsis is a condition characterised by high mortality and early diagnosis and treatment is thought essential to improve outcomes. Various scoring systems have been developed to aid the early recognition and management of the condition.

This single-center prospective study conducted in a tertiary university hospital emergency department aimed to evaluate the effectiveness of these scoring systems in the diagnosis, mortality, and morbidity of sepsis. The National Early Warning Score (NEWS), Sequential Organ Failure Assessment (SOFA, with qSOFA for out of ICU use) and Systemic Inflammatory Response Syndrome (SIRS) were evaluated. The primary outcomes were the sensitivity and specificity of scoring systems for 30-day mortality of sepsis. Secondary outcomes included prediction of the scoring systems for diagnosis of sepsis, sepsis-related morbidity and ICU admission. 

The Inclusion criteria were patients over 18 with highly suspicious for infectious disease given parental antibiotics with culture samples taken, while patients with trauma, intoxication, pregnant women, epilepsy, cardiorespiratory arrest were excluded. The study ran for one year.

There were 525 patients evaluated and 62 excluded, with 463 patients analysed. 62% of patients were diagnosed with sepsis and 13.8% with septic shock. 17.2% of patients were admitted to ICU. Seven-day mortality rate was 8.4% and 30-day mortality rate was 18.1%. The sensitivity for qSOFA, SIRS and NEWS for diagnosis of sepsis was 23%, 77%, 58% and specificity was 99%, 35%, 81% respectively. The sensitivity of the qSOFA, SIRS and NEWS scoring systems for mortality was 39%, 82%, 77% and specificity 91%, 29% and 64% respectively. ROC analysis was done with the SIRS criteria found to be significantly less useful than qSOFA and NEWS in the diagnosis of sepsis and predicting mortality.

Limitations of the study include it being from a single tertiary centre which may include a sicker patient cohort, lack of a gold standard method of diagnosis, and the sample size does not appear to be powered to detect a difference between the different scoring systems.

Bottom Line

Accounting for the limitations of the study, there is no single consistently reliable scoring tool that can be applied at the bedside for diagnosis of sepsis. However, the NEWS and qSOFA scoring systems would appear to perform better in line with previous studies.

Reference

Oduncu AF, Kıyan GS, Yalçınlı S. Comparison of qSOFA, SIRS, and NEWS scoring systems for diagnosis, mortality and morbidity of sepsis in emergency department. American Journal of Emergency Medicine. 2021; 48: 54-59. doi:10.1016/j.ajem.2021.04.006.

Retrospective single-center descriptive study of the characteristics, management and outcomes of adult patients with suspected sepsis in the emergency department

The management of sepsis hinges on early recognition and diagnosis to improve patient outcomes. Various scoring systems based on physiological parameters are used to aid in the management of sepsis.

This study aimed to look at the characteristics, management and outcomes of adults attending the ED with suspected sepsis and specifically describe the prevalence of comorbidities, functional impairment, and escalations of care.

It was a retrospective observational study of adults presenting to a type 1 ED over a one-year period. Patients were identified from positive blood cultures as a screening method for suspected sepsis. Power calculation was performed, and chart review performed by two clinicians. Retrospective evaluation of the qSOFA and NEWS score was performed. The outcome measures were descriptive, describing the characteristics of these patients, with a focus on prevalence of comorbidities, functional impairment and ceilings of care. Incomplete electronic records and direct referrals to specialties were excluded.

There were 509 patients included in the study, with a median age of 74 years. 49.3% met the Sepsis-3 criteria (defined by evidence of infection and a change in baseline SOFA score equation.pdf2). 42.5% of patients were living at home, 41.5% could walk independently, 19.3% were care home residents and 89.2% had more than one co-morbidity. 22% had a pre-existing do not attempt resuscitation order, 13.2% died in hospital and 34.3% of these had an escalation plan explicitly documented.

The notable limitations of the study were the use of blood cultures as a screening tool which could miss a number of relevant cases, and the investigators were aware of all outcomes and the hypothesis of the study leading to risk of observer bias.

Bottom Line

Patients with suspected sepsis have many significant non-physiological parameters which have a role to play in the morbidity and mortality. These should be considered in the development of guidelines and treatment plans for patients with sepsis.

Reference

Sabir L, Wharton L, Goodacre S. Retrospective single-centre descriptive study of the characteristics, management and outcomes of adult patients with suspected sepsis in the emergency department. Emerg Med J. 2022; 39: 272-8. doi:10.1136/emermed-2020-211111.