Fluid management of emergency department patients with sepsis-A survey of fluid resuscitation practices.

BACKGROUND: Fluid administration and resuscitation of patients with sepsis admitted through emergency departments (ED) remains a challenge, and evidence is sparse especially in sepsis patients without shock. We aimed to investigate emergency medicine physicians' and nurses' perceptions, self-reported decision-making and daily behavior, and challenges in fluid administration of ED sepsis patients. METHODS: We developed and conducted a multicenter, web-based, cross-sectional survey focusing on fluid administration to ED patients with sepsis sent to all nurses and physicians from the five EDs in the Central Denmark Region. The survey consisted of three sections: (1) baseline information; (2) perceptions of fluid administration and daily practice; and (3) clinical scenarios about fluid administration. The survey was performed from February to June, 2021. RESULTS: In total, 138 of 246 physicians (56%) and 382 of 595 nurses (64%) responded to the survey. Of total, 94% of physicians and 97% of nurses regarded fluid as an important part of sepsis treatment. Of total, 80% of physicians and 61% of nurses faced challenges regarding fluid administration in the ED, and decisions were usually based on clinical judgment. The most common challenge was the lack of guidelines for fluid administration. Of total, 96% agreed that they would like to learn more about fluid administration, and 53% requested research in fluid administration of patients with sepsis. For a normotensive patient with sepsis, 46% of physicians and 44% of nurses administered 1000 ml fluid in the first hour. Of total, 95% of physicians and 89% of nurses preferred to administer ≥1000 ml within an hour if the patients' blood pressure was 95/60 at admission. There was marked variability in responses. Blood pressure was the most commonly used trigger for fluid administration. Respondents preferred to administer less fluid if the patient in the scenario had known renal impairment or heart failure. Normal saline was the preferred fluid. CONCLUSION: Fluid administration is regarded as an important but challenging aspect of sepsis management. Responses to scenarios revealed variability in fluid volumes. Blood pressure was the most used trigger. ED nurses and physicians request evidence-based guidelines to improve fluid administration.

Twenty-four-hour fluid administration in emergency department patients with suspected infection: A multicenter, prospective, observational study.

BACKGROUND: To describe 24-hour fluid administration in emergency department (ED) patients with suspected infection. METHODS: A prospective, multicenter, observational study conducted in three Danish hospitals, January 20 to March 2, 2020. We included consecutive adult ED patients with suspected infection (drawing of blood culture and/or intravenous antibiotic administration within 6 hours of admission). Oral and intravenous fluids were registered for 24 hours. PRIMARY OUTCOME: 24-hour total fluid volume. We used linear regression to investigate patient and disease characteristics' effect on 24-hour fluids and to estimate the proportion of the variance in fluid administration explained by potential predictors. RESULTS: 734 patients had 24-hour fluids available: 387 patients had simple infection, 339 sepsis, eight septic shock. Mean total 24-hour fluid volumes were 3656 mL (standard deviation [SD]:1675), 3762 mL (SD: 1839), and 6080 mL (SD: 3978) for the groups, respectively. Fluid volumes varied markedly. Increasing age (mean difference [MD]: 60-79 years: -470 mL [95% CI: -789, -150], +80 years; -974 mL [95% CI: -1307, -640]), do-not-resuscitate orders (MD: -466 mL [95% CI: -797, -135]), and preexisting atrial fibrillation (MD: -367 mL [95% CI: -661, -72) were associated with less fluid. Systolic blood pressure < 100 mmHg (MD: 1182 mL [95% CI: 820, 1543]), mean arterial pressure < 65 mmHg (MD: 1317 mL [95% CI: 770, 1864]), lactate ≥ 2 mmol/L (MD: 655 mL [95% CI: 306, 1005]), heart rate > 120 min (MD: 566 [95% CI: 169, 962]), low (MD: 1963 mL [95% CI: 813, 3112]) and high temperature (MD: 489 mL [95% CI: 234, 742]), SOFA score > 5 (MD: 1005 mL [95% CI: 501, 510]), and new-onset atrial fibrillation (MD: 498 mL [95% CI: 30, 965]) were associated with more fluid. Clinical variables explained 37% of fluid variation among patients. CONCLUSIONS: Patients with simple infection and sepsis received equal fluid volumes. Fluid volumes varied markedly, a variation that was partly explained by clinical characteristics.

Pulse palpation is an effective method for population-based screening to exclude peripheral arterial disease.

OBJECTIVE: There is a strong association between peripheral arterial disease (PAD) and future cardiovascular events. Therefore, intensive atherosclerotic risk factor reduction is recommended for people with PAD, and early detection is essential. This study assessed whether systematic pedal pulse palpation is an effective screening method for PAD in population-based screening programs. METHODS: As part of a randomized screening project, The Viborg Vascular Screening trial, 18,681 men (mean age, 69.3 years; range, 65-74 years) participated in a screening program, which included bilateral pulse palpation and ankle-brachial index (ABI) measurement. PAD was defined as ABI ≤0.9 or ≥1.4. Analysis was conducted on sensitivity, specificity, positive predictive value, and negative predictive value for PAD and for the number of pedal pulses. RESULTS: PAD was present in 2215 participants (12.1%). The pedal pulse palpation test was set to be positive for having PAD if one or more pulses were missing. Sensitivity was 71.7% and specificity was 72.3%. No palpable pulses were associated with a 50% chance of ABI-verified PAD or with a false finding. Four palpable pulses were associated with 5% false-negative PAD cases. CONCLUSIONS: Pedal pulse palpation is was shown to be a reliable initial screening tool for PAD in population-based programs but only when four pedal pulses were present. Therefore, ABI measurement should routinely be measured in patients with fewer than four palpable pedal pulses so cardiovascular preventive actions can be initiated if PAD is confirmed.

Abdominal aortic aneurysm, arterial stiffening and the role of the intraluminal thrombus.

BACKGROUND: Measure of arterial stiffness could be affected by the presence of abdominal aortic aneurysm (AAA) and especially an intraluminal thrombus (ILT). We, therefore, sought to study this possible connection by measuring pulse wave velocity (PWV) and pulse wave analysis (PWA) including augmentation index adjusted to heart rate 75 (Aix75) in patients with AAA ± ILT. PATIENTS AND METHODS: PWV and PWA were measured in male patients with AAA from an ongoing Danish AAA screening trial. Information on blood pressure, medications, BMI and smoking status was obtained at inclusion. RESULTS: In total, 157 patients were included. Mean age was 73 years. Mean AAA size was 42.2 mm. Fifty-six of the patients had an intraluminal thrombus, and patients with AAA and ILT had a significantly higher Aix75 than patients with AAA but without ILT (Mean = 28.3 ± 1.4 SEM vs. 24.9 ± 0.81, p=0.027), a difference that was also significant when adjusting for AAA size, blood pressure and age. There was no difference in PWV between the groups. CONCLUSIONS: Haemodynamic properties of the aorta are affected by the presence of ILT in patients with AAA that is not explained by aortic size. Alternatively, these findings could be explained by associations between ILT and properties of the left ventricle.

A tandem chemoenzymatic methylation by S-adenosyl-L-methionine.

Keep 'em methylated: The in situ preparation of the cofactor AdoMet was achieved by allowing the biosynthetic enzyme SalL to operate in the reverse direction by presentation of 5'-chloro-5'-deoxyadenosine at low salt concentrations. This reaction was readily coupled with DNA and small molecule methyltransferases to afford a regioselective method for chemo-enzymatic methylation and isotope incorporation.

Chemoenzymatic synthesis and in situ application of S-adenosyl-L-methionine analogs.

Analogs of S-adenosyl-L-methionine (SAM) are increasingly applied to the methyltransferase (MT) catalysed modification of biomolecules including proteins, nucleic acids, and small molecules. However, SAM and its analogs suffer from an inherent instability, and their chemical synthesis is challenged by low yields and difficulties in stereoisomer isolation and inhibition. Here we report the chemoenzymatic synthesis of a series of SAM analogs using wild-type (wt) and point mutants of two recently identified halogenases, SalL and FDAS. Molecular modelling studies are used to guide the rational design of mutants, and the enzymatic conversion of L-Met and other analogs into SAM analogs is demonstrated. We also apply this in situ enzymatic synthesis to the modification of a small peptide substrate by protein arginine methyltransferase 1 (PRMT1). This technique offers an attractive alternative to chemical synthesis and can be applied in situ to overcome stability and activity issues.

Restrictive fluids versus standard care in adults with sepsis in the emergency department (REFACED): A multicenter, randomized feasibility trial.

BACKGROUND: Fluid treatment in sepsis is a challenge and clinical equipoise exists regarding intravenous (IV) volumes. We aimed to determine whether a 24-h protocol restricting IV fluid was feasible in adult patients with sepsis without shock presenting to the emergency department (ED). METHODS: The REFACED Sepsis trial is an investigator-initiated, multicenter, randomized, open-label, feasibility trial, assigning sepsis patients without shock to 24 h of restrictive, crystal IV fluid administration or standard care. In the IV fluid restriction group fluid boluses were only permitted if predefined criteria for hypoperfusion occurred. Standard care was at the discretion of the treating team. The primary outcome was total IV crystalloid fluid volumes at 24 h after randomization. Secondary outcomes included total fluid volumes, feasibility measures, and patient-centered outcomes. RESULTS: We included 123 patients (restrictive 61 patients and standard care 62 patients) in the primary analysis. A total of 32% (95% confidence interval [CI] 28%-37%) of eligible patients meeting all inclusion criteria and no exclusion criteria were included. At 24 h, the mean (±SD) IV crystalloid fluid volumes were 562 (±1076) ml versus 1370 (±1438) ml in the restrictive versus standard care group (mean difference -801 ml, 95% CI -1257 to -345 ml, p = 0.001). Protocol violations occurred in 21 (34%) patients in the fluid-restrictive group. There were no differences between groups in adverse events, use of mechanical ventilation or vasopressors, acute kidney failure, length of stay, or mortality. CONCLUSIONS: A protocol restricting IV crystalloid fluids in ED patients with sepsis reduced 24-h fluid volumes compared to standard care. A future trial powered toward patient-centered outcomes appears feasible.

Restrictive Fluid Administration vs. Standard of Care in Emergency Department Sepsis Patients (REFACED Sepsis)-protocol for a multicenter, randomized, clinical, proof-of-concept trial.

BACKGROUND: Intravenous fluids are often used in the treatment of sepsis. The better strategy regarding fluid volume is debated, but preliminary data in patients with septic shock or sepsis-related hypotension favor restrictive fluid administration. We describe the protocol and statistical analysis plan for the Restrictive Fluid Administration vs. Standard of Care in Emergency Department Sepsis Patients (REFACED Sepsis)-a multicenter, randomized clinical proof-of-concept trial. The aim of the REFACED Sepsis trial is to test if a restrictive intravenous fluid protocol in emergency department patients with sepsis without shock is feasible and decreases the intravenous fluid volume administered in comparison to standard care. METHODS: This is an investigator-initiated, multicenter, randomized, parallel-group, open-labeled, feasibility trial investigating volumes of crystalloid fluid within 24 h in 124 patients with sepsis without shock enrolled at three emergency departments in the Central Denmark Region. Patients are allocated to two different intravenous fluid regimens: a restrictive approach using four trigger criteria for fluid administration vs. standard care. The primary, feasibility outcome is total intravenous, crystalloid fluid volume within 24 h, and key secondary outcomes include protocol violations, total fluids (intravenous and oral) within 24 h, and serious adverse reactions and suspected unexpected serious adverse reactions. Status: The trial started in November 2021, and the last patient is anticipated to be included in January 2022. DISCUSSION: Sepsis is very common in emergency department patients and fluid administration is very frequently administered in these patients. However, the evidence to guide fluid administration is very sparse. This feasibility trial will be the foundation for a potential future large-scale trial investigating restrictive vs. standard fluid administration in patients with sepsis. TRIAL REGISTRATION: EudraCT number: 2021-000224-35 (date: 2021 May 03), ClinicalTrials.gov number: NCT05076435 (date: 2021 October 13), Committee on Health Research Ethics - Central Denmark Region: 1-10-72-163-21 (date: 2021 June 28).

Mitral valve perforation appearing years after radiofrequency ablation.

The case is reported of a young adult with Wolff-Parkinson-White (WPW) syndrome who, three years after a complicated radiofrequency (RF) catheter ablation procedure, developed dyspnea on exertion. Echocardiography revealed severe mitral valve regurgitation caused by a perforation of the posterior leaflet. Echocardiographic follow up is recommended after a complicated course of left-sided catheter ablation.

Spontaneous pneumothorax as a clinical manifestation of neurofibromatosis type 1.

Neurofibromatosis type 1 (NF1) is a genetic disorder affecting the skin, nervous system, eyes and bones. Pulmonary involvement is unknown to many physicians. Yet, patients may be affected by lung bullae and cysts, which represent an increased risk for secondary spontaneous pneumothorax (SSP). We present a 56-year-old patient with a pathogenic variant of the NF1 gene, who suffered from NF1 with lung manifestations and recurrent SSP. It is essential to identify the patients having an increased risk of developing SSP as preventive surgery seem to decrease the risk of new events. Pneumothorax can be a clinical manifestation of NF1 but is not yet widely acknowledged as such.

An evolutionarily young defense metabolite influences the root growth of plants via the ancient TOR signaling pathway.

To optimize fitness a plant should monitor its metabolism to appropriately control growth and defense. Primary metabolism can be measured by the universally conserved TOR (Target of Rapamycin) pathway to balance growth and development with the available energy and nutrients. Recent work suggests that plants may measure defense metabolites to potentially provide a strategy ensuring fast reallocation of resources to coordinate plant growth and defense. There is little understanding of mechanisms enabling defense metabolite signaling. To identify mechanisms of defense metabolite signaling, we used glucosinolates, an important class of plant defense metabolites. We report novel signaling properties specific to one distinct glucosinolate, 3-hydroxypropylglucosinolate across plants and fungi. This defense metabolite, or derived compounds, reversibly inhibits root growth and development. 3-hydroxypropylglucosinolate signaling functions via genes in the ancient TOR pathway. If this event is not unique, this raises the possibility that other evolutionarily new plant metabolites may link to ancient signaling pathways.

Self-reported knowledge and awareness about blood pressure and hypertension: a cross-sectional study of a random sample of men and women aged 60-74 years.

BACKGROUND: In general, it is assumed that patient education, by increasing knowledge, may change behavior and lifestyle and promote health. In this context, it is a surprise that knowledge and awareness about blood pressure and hypertension among elderly people is poor. We hypothesized that knowledge about blood pressure and hypertension would be better among individuals with self-reported hypertension compared with subjects without self-reported hypertension. METHODS: We mailed a questionnaire to a random sample of 1,000 subjects living in the municipality of Silkeborg, Denmark. The study sample was drawn from the Central Person Registry. RESULTS: The response rate was 72%. Of these, 43% of responders had self-reported hypertension. The people with self-reported hypertension were older, less educated, had higher self-reported blood cholesterol levels, had higher body weight, and more often had a family history of hypertension. More than 80% reported that overweight and obesity increases blood pressure. More than 60% reported that untreated hypertension may cause heart disease or stroke. More than half of the responders did not know their blood pressure, and only 21% knew that hypertension can occur without symptoms. Knowledge about hypertension was independent of self-reported hypertension status, but awareness about blood pressure was most prominent among those with self-reported hypertension. CONCLUSION: General knowledge about blood pressure and hypertension was reasonable, but there is still room for improvement in elderly people's knowledge and awareness of blood pressure.

[Hymen imperforatus with atypical symptom presentation]. / Hymen imperforatus med atypisk symptomdebut.

One in every 2,000 girls has hymen imperforatus. A few are recognized at birth because of mucocolpos. The rest are not detected before puberty. Typical symptoms are abdominal pain and distension of the lower abdomen, and half of the girls present with acute urinary retention. A case is presented where the symptoms started after a minor trauma. Diagnosis and treatment are easy. Complications can be infertility, endometriosis and adhesions.