The association between systolic blood pressure and in-hospital mortality in older emergency department patients who are hospitalised with a suspected infection.

OBJECTIVE: In existing risk stratification and resuscitation guidelines for sepsis, a hypotension threshold of systolic blood pressure (SBP) below 90-100 mmHg is typically used. However, for older patients, the clinical relevance of a SBP in a seemingly 'normal' range (>100 mmHg) is still poorly understood, as they may need higher SBP for adequate tissue perfusion due to arterial stiffening. We therefore investigated the association between SBP and mortality in older emergency department (ED) patients hospitalised with a suspected infection. METHODS: In this observational multicentre study in the Netherlands, we interrogated an existing prospective database of consecutive ED patients hospitalised with a suspected infection between 2011 and 2016. We investigated the association between SBP categories (≤100, 101-120, 121-139, ≥140 mmHg) and in-hospital mortality in patients of 70 years and older. We adjusted for demographics, comorbidity, disease severity and admission to ward/intensive care using multivariable logistic regression. RESULTS: In the 833 included older patients, unadjusted in-hospital mortality increased from 4.7% (n=359) in SBP ≥140 mmHg to 20.8% (n=96) in SBP ≤100 mmHg. SBP categories were linearly associated with case-mix-adjusted in-hospital mortality. The adjusted ORs (95% CI) for ≤100, 101-120 and 121-139 mmHgcompared with the reference of ≥140 mmHg were 3.8 (1.8 to 7.8), 2.8 (1.4 to 5.5) and 1.9 (0.9 to 3.7), respectively. CONCLUSION: In older ED patients hospitalised with a suspected infection, we found an inverse linear association between SBP and case-mix-adjusted in-hospital mortality. Our data suggest that the commonly used threshold for hypotension is not clinically meaningful for risk stratification of older ED patients with a suspected infection.

Trauma-Related Clinical Practice Variation in Dutch Emergency Departments.

Structural insights in the use of protocols and the extent of practice variation in EDs are lacking. The objective is to determine the extent of practice variation in EDs in The Netherlands, based on specified common practices. We performed a comparative study on Dutch EDs that employed emergency physicians to determine practice variation. Data on practices were collected via a questionnaire. Fifty-two EDs across The Netherlands were included. Thrombosis prophylaxis was prescribed for below-knee plaster immobilization in 27% of EDs. Vitamin C was prescribed in 50% of EDs after a wrist fracture. Splitting of applied casts to the upper or lower limb was performed in one-third of the EDs. Analysis of the cervical spine after trauma was performed by the NEXUS criteria (69%), the Canadian C-spine Rule (17%) or otherwise. The imaging modality for cervical spine trauma in adults was a CT scan (98%). The cast used for scaphoid fractures was divided between the short arm cast (46%) and the navicular cast (54%). Locoregional anaesthesia for femoral fractures was applied in 54% of the EDs. EDs in The Netherlands showed considerable practice variation in treatments among the subjects studied. Further research is warranted to gain a full understanding of the variation in practice in EDs and the potential to improve quality and efficiency.

Prehospital transdermal glyceryl trinitrate in patients with presumed acute stroke (MR ASAP): an ambulance-based, multicentre, randomised, open-label, blinded endpoint, phase 3 trial.

BACKGROUND: Pooled analyses of previous randomised studies have suggested that very early treatment with glyceryl trinitrate (also known as nitroglycerin) improves functional outcome in patients with acute ischaemic stroke or intracerebral haemorrhage, but this finding was not confirmed in a more recent trial (RIGHT-2). We aimed to assess whether patients with presumed acute stroke benefit from glyceryl tr initrate started within 3 h after symptom onset. METHODS: MR ASAP was a phase 3, randomised, open-label, blinded endpoint trial done at six ambulance services serving 18 hospitals in the Netherlands. Eligible participants (aged ≥18 years) had a probable diagnosis of acute stroke (as assessed by a paramedic), a face-arm-speech-time test score of 2 or 3, systolic blood pressure of at least 140 mm Hg, and could start treatment within 3 h of symptom onset. Participants were randomly assigned (1:1) by ambulance personnel, using a secure web-based electronic application with random block sizes stratified by ambulance service, to receive either transdermal glyceryl trinitrate 5 mg/day for 24 h plus standard care (glyceryl trinitrate group) or to standard care alone (control group) in the prehospital setting. Informed consent was deferred until after arrival at the hospital. The primary outcome was functional outcome assessed with the modified Rankin Scale (mRS) at 90 days. Safety outcomes included death within 7 days, death within 90 days, and serious adverse events. Analyses were based on modified intention to treat, and treatment effects were expressed as odds ratios (ORs) or common ORs, with adjustment for baseline prognostic factors. We separately analysed the total population and the target population (ie, patients with intracerebral haemorrhage, ischaemic stroke, or transient ischaemic attack). The target sample size was 1400 patients. The trial is registered as ISRCTN99503308. FINDINGS: On June 24, 2021, the MR ASAP trial was prematurely terminated on the advice of the data and safety monitoring board, with recruitment stopped because of safety concerns in patients with intracerebral haemorrhage. Between April 4, 2018, and Feb 12, 2021, 380 patients were randomly allocated to a study group. 325 provided informed consent or died before consent could be obtained, of whom 170 were assigned to the glyceryl trinitrate group and 155 to the control group. These patients were included in the total population. 201 patients (62%) had ischaemic stroke, 34 (10%) transient ischaemic attack, 56 (17%) intracerebral haemorrhage, and 34 (10%) a stroke-mimicking condition. In the total population (n=325), the median mRS score at 90 days was 2 (IQR 1-4) in both the glyceryl trinitrate and control groups (adjusted common OR 0·97 [95% CI 0·65-1·47]). In the target population (n=291), the 90-day mRS score was 2 (2-4) in the glyceryl trinitrate group and 3 (1-4) in the control group (0·92 [0·59-1·43]). In the total population, there were no differences between the two study groups with respect to death within 90 days (adjusted OR 1·07 [0·53-2·14]) or serious adverse events (unadjusted OR 1·23 [0·76-1·99]). In patients with intracerebral haemorrhage, 12 (34%) of 35 patients allocated to glyceryl trinitrate versus two (10%) of 21 allocated to the control group died within 7 days (adjusted OR 5·91 [0·78-44·81]); death within 90 days occurred in 16 (46%) of 35 in the glyceryl trinitrate group and 11 (55%) of 20 in the control group (adjusted OR 0·87 [0·18-4·17]). INTERPRETATION: We found no sign of benefit of transdermal glyceryl trinitrate started within 3 h of symptom onset in the prehospital setting in patients with presumed acute stroke. The signal of potential early harm of glyceryl trinitrate in patients with intracerebral haemorrhage suggests that glyceryl trinitrate should be avoided in this setting. FUNDING: The Collaboration for New Treatments of Acute Stroke consortium, the Brain Foundation Netherlands, the Ministry of Economic Affairs, Stryker, Medtronic, Cerenovus, and the Dutch Heart Foundation.

The association between intravenous fluid resuscitation and mortality in older emergency department patients with suspected infection.

OBJECTIVE: Recent studies suggest that hypotension thresholds in current guidelines might be too low for older patients due to arterial stiffening, possibly leading to insufficient fluid resuscitation. We compared intravenous (IV) fluid volumes that older (≥ 70 years) and younger (< 70 years) patients with suspected infection with similar initial systolic blood pressure (SBP) received in the emergency department (ED) and investigated whether this was associated with in-hospital mortality in older patients. METHODS: This was an observational multicenter study using an existing database in which consecutive ED patients hospitalized with suspected infection were prospectively included. We first compared the fluid volumes older and younger ED patients received per initial SBP category. Patients were then stratified into two SBP categories (≤ or > 120 mmHg; 120 has been suggested to be a better threshold) and thereafter into three fluid volume categories: 0-1 L, 1-2 L, or > 2 L. In each SBP and fluid category, case-mix-adjusted in-hospital mortality was compared between older and younger patients, using multivariable logistic regression analysis. RESULTS: The included 981 (37%) older and 1678 (63%) younger ED patients received similar IV fluid volumes per initial SBP category. Older patients with an initial SBP > 120 mmHg had a higher adjusted OR of 2.06 (95% CI 1.02-4.16), in the 0-1 L category, while this association was not found in the higher fluid categories of 1-2 L or > 2 L. In the SBP ≤ 120 mmHg category, this association was also absent. CONCLUSION: This hypothesis-generating study suggests that older patients with suspected infection may need higher fluid volumes than younger patients, when having a seemingly normal initial SBP.

The most commonly used disease severity scores are inappropriate for risk stratification of older emergency department sepsis patients: an observational multi-centre study.

BACKGROUND: Sepsis recognition in older emergency department (ED) patients is difficult due to atypical symptom presentation. We therefore investigated whether the prognostic and discriminative performance of the five most commonly used disease severity scores were appropriate for risk stratification of older ED sepsis patients (≥70 years) compared to a younger control group (<70 years). METHODS: This was an observational multi-centre study using an existing database in which ED patients who were hospitalized with a suspected infection were prospectively included. Patients were stratified by age < 70 and ≥70 years. We assessed the association with in-hospital mortality (primary outcome) and the area under the curve (AUC) with receiver operator characteristics of the Predisposition, Infection, Response, Organ dysfunction (PIRO), quick Sequential Organ Failure Assessment (qSOFA), Mortality in ED Sepsis (MEDS), and the Modified and National Early Warning (MEWS and NEWS) scores. RESULTS: In-hospital mortality was 9.5% ((95%-CI); 7.4-11.5) in the 783 included older patients, and 4.6% (3.6-5.7) in the 1497 included younger patients. In contrast to younger patients, disease severity scores in older patients associated poorly with mortality. The AUCs of all disease severity scores were poor and ranged from 0.56 to 0.64 in older patients, significantly lower than the good AUC range from 0.72 to 0.86 in younger patients. The MEDS had the best AUC (0.64 (0.57-0.71)) in older patients. In older and younger patients, the newly proposed qSOFA score (Sepsis 3.0) had a lower AUC than the PIRO score (sepsis 2.0). CONCLUSION: The prognostic and discriminative performance of the five most commonly used disease severity scores was poor and less useful for risk stratification of older ED sepsis patients.

Initial disease severity and quality of care of emergency department sepsis patients who are older or younger than 70 years of age.

OBJECTIVE: Due to atypical symptom presentation older patients are more prone to delayed sepsis recognition. We investigated whether initial disease severity before emergency department (ED) treatment (including treatable acute organ dysfunction), quality of ED sepsis care and the impact on mortality was different between patients older and younger than 70 years. If differences exist, improvements are needed for ED management of older patients at risk for sepsis. METHODS: In this observational multicenter study, ED patients who were hospitalized with a suspected infection were stratified by age <70 and ≥70 years. The presence of treatable and potentially reversible acute organ dysfunction was measured by the RO components of the Predisposition, Infection, Response and Organ dysfunction (PIRO) score, reflecting acute sepsis-related organ dysfunction developed before ED presentation. Quality of care, as assessed by the full compliance with nine quality performance measures and the standardized mortality ratio (SMR: observed/expected in-hospital mortality), was compared between older and younger patients. RESULTS: The RO-components of the PIRO score were 8 (interquartile range; 4-9) in the 833 older patients, twice as high as the 4 (2-8; P<0.001) in the 1537 younger patients. However, full compliance with all nine quality performance measures was achieved in 34.2 (31.0-37.4)% of the older patients, not higher than the 33.0 (30.7-35.4)% in younger patients (P = 0.640). In-hospital mortality was 9.2% (95%-CI, 7.3-11.2) in patients ≥70, twice as high as the 4.6% (3.6-5.6) in patients <70 years, resulting in an SMR (in study period) of ~0.7 in both groups (P>0.05). CONCLUSION: Older sepsis patients are sicker at ED presentation but are not treated more expediently or reliably despite their extra acuity The presence of twice as much treatable acute organ dysfunction before ED treatment suggests that acute organ dysfunction is recognized relatively late by general practitioners or patients in the out of hospital setting.

Lactate ≥2 mmol/L plus qSOFA improves utility over qSOFA alone in emergency department patients presenting with suspected sepsis.

OBJECTIVE: The Sepsis-3 task force recommends the use of the quick Sequential Organ Failure Assessment (qSOFA) score to identify risk for adverse outcomes in patients presenting with suspected infection. Lactate has been shown to predict adverse outcomes in patients with suspected infection. The aim of the study is to investigate the utility of a post hoc lactate threshold (≥2 mmol/L) added qSOFA score (LqSOFA(2) score) to predict primary composite adverse outcomes (mortality and/or ICU stay ≥72 h) in patients presenting to ED with suspected sepsis. METHODS: Retrospective cohort study was conducted on a merged dataset of suspected or proven sepsis patients presenting to ED across multiple sites in Australia and The Netherlands. Patients are identified as candidates for quality improvement initiatives or research studies at respective sites based on local screening procedures. Data-sharing was performed across sites of demographics, qSOFA, SOFA, lactate thresholds and outcome data for included patients. LqSOFA(2) scores were calculated by adding an extra point to qSOFA score in patients who met lactate thresholds of ≥2 mmol/L. RESULTS: In a merged dataset of 12 555 patients where a full qSOFA score and outcome data were available, LqSOFA(2) ≥2 identified more patients with an adverse outcome (sensitivity 65.5%, 95% confidence interval 62.6-68.4) than qSOFA ≥2 (sensitivity 47.6%, 95% confidence interval 44.6- 50.6). The post hoc addition of lactate threshold identified higher proportion of patients at risk of adverse outcomes. CONCLUSIONS: The lactate ≥2 mmol/L threshold-based LqSOFA(2) score performs better than qSOFA alone in identifying risk of adverse outcomes in ED patients with suspected sepsis.