A polymorphism in IRF4 affects human pigmentation through a tyrosinase-dependent MITF/TFAP2A pathway.

Sequence polymorphisms linked to human diseases and phenotypes in genome-wide association studies often affect noncoding regions. A SNP within an intron of the gene encoding Interferon Regulatory Factor 4 (IRF4), a transcription factor with no known role in melanocyte biology, is strongly associated with sensitivity of skin to sun exposure, freckles, blue eyes, and brown hair color. Here, we demonstrate that this SNP lies within an enhancer of IRF4 transcription in melanocytes. The allele associated with this pigmentation phenotype impairs binding of the TFAP2A transcription factor that, together with the melanocyte master regulator MITF, regulates activity of the enhancer. Assays in zebrafish and mice reveal that IRF4 cooperates with MITF to activate expression of Tyrosinase (TYR), an essential enzyme in melanin synthesis. Our findings provide a clear example of a noncoding polymorphism that affects a phenotype by modulating a developmental gene regulatory network.

The incidence and prevalence of proton pump inhibitor usage among internal medicine patients after hospital admission: A retrospective cohort study.

BACKGROUND: The use of proton pump inhibitors (PPIs) has increased over the past decades. One potential gateway into new PPI use is following a hospital admission. The study aimed to examine the incidence of new PPI usage following admission to internal medicine services and the ratio of new persistent users. METHODS: A retrospective descriptive study was conducted among all adults who had been admitted to internal medicine wards at the National University Hospital of Iceland from 2010-2020. Data was obtained from the Icelandic Internal Medicine Database. The proportion of patients who started treatment with PPI within 3 months of discharge (new users) and the proportion of patients who continued to use it after 3 months (persistent users) were examined. RESULTS: Among 85.942 admissions during the study period, 7238 (15.6%) became new users, and of those 4942 (68%) were new persistent users. The incidence of new PPI use was highest for patients discharged from gastroenterology (32.2%), hematology (31.8%), and oncology (29.2%). Patients with new PPI use more commonly had a history of malignancy (19.5%) and liver disease (22.7%) and more commonly were admitted to the ICU during their hospitalization. The highest ratio of persistent usage was among patients discharged from geriatric medicine (84%). CONCLUSION: One in every six patients admitted to internal medicine wards filled out a prescription for PPI within 3 months from discharge, and a large proportion of them became persistent users. The high rate of new PPI users from oncology and hematology is noteworthy and requires further research.

The epidemiology and outcomes of acute kidney injury following orthopaedic procedures: A retrospective cohort study.

BACKGROUND: Acute kidney injury (AKI) is a serious complication following major surgery. This study examined the incidence and risk factors of AKI following orthopaedic surgeries in an Icelandic cohort, as well as the association between AKI and patient- and surgery-related factors. METHODS: This retrospective cohort study comprised all patients 18 years and older who underwent orthopaedic surgeries at Landspitali - The National University Hospital in the years 2006-2018 with available serum creatinine (SCr) measurements adjacent to the surgery to stage AKI. AKI was defined according to SCr portion of the KDIGO criteria. Logistic regression was used to identify patient- and surgical factors related to progression of AKI and Poisson-regression was used to explore changes in incidence. RESULTS: A total of 222 cases of AKI following 3208 surgeries (6.9%) were identified in the study period with a rise in the incidence by about 17% per year. Higher age (odds ratio (OR), 1.02, 95% confidence interval (CI), 1.01-1.04 per year) and underlying reduction in kidney function (OR 1.93 (1.30-2.81), 3.24 (2.08-4.96) and 4.08 (2.35-6.96) for estimated glomerular filtration rate (eGFR) of 30-59, 15-29 and <15 mL/min/1.73 m2 compared with eGFR >60 mL/min/1.73 m2 ) were associated with higher risk of AKI, but female sex was associated with decreased odds (OR = 0.73; 95% CI, 0.54-0.98). After correcting for age, sex, preoperative kidney function, emergency surgery and underlying comorbidities and frailty, there was an increased risk of long-term mortality in patients with AKI (HR 1.41, 95% CI 1.08-1.85), and patients who developed AKI also had accelerated progression of chronic kidney disease compared with patients who did not develop AKI. CONCLUSIONS: The incidence of AKI following orthopaedic surgeries is increasing and is associated with adverse outcomes. It is important that elderly individuals and patients who have reduced kidney function receive adequate monitoring and surveillance in the perioperative period.

Postoperative pain at Landspitali: A prospective study.

BACKGROUND: Moderate or severe postoperative pain is common despite advances in surgical technique and perioperative analgesia. This study aimed to assess the prevalence and severity of postoperative pain following procedures requiring anaesthesia and identify factors associated with increased risk of postoperative pain. METHODS: Surgical patients ≥18 years of age were prospectively questioned on level of current pain on a numerical rating scale (NRS) from 0 to 10 in the post-anaesthesia care unit (PACU) and on resting, active and worst pain experienced in the first 24 h postoperatively. Clinical data was obtained from medical records. Descriptive statistics were applied, and predictors of worst pain assessed as moderate/severe (NRS ≥ 5) on postoperative day one were assessed using multivariable logistic regression. RESULTS: Of 438 included participants, moderate/severe pain occurred in 29% on the day of surgery and 70% described their worst pain as moderate/severe on postoperative day one. Procedures with the highest incidence of moderate/severe pain on the day of surgery were gynaecology-, plastic-, abdominal-, breast-, and orthopaedic procedures. On postoperative day one, patients undergoing vascular-, orthopaedic-, and abdominal operations most commonly rated their worst pain as moderate/severe. Female sex (OR = 2.15, 95% Cl 1.21-3.88, p = .010), chronic preoperative pain (OR = 4.20, 95% Cl 2.41-7.51, p < .001), undergoing a major procedure (OR = 2.07, 95% Cl 1.15-3.80, p = .017), and any intraoperative remifentanil administration (OR = 2.16, 95% Cl 1.20-3.94, p = .01) had increased odds of rating the worst pain as moderate/severe. Increased age (OR = 0.66 per 10 years (95% Cl 0.55-0.78, p < .001)) and undergoing breast-, gynaecology-, otolaryngology-, and neurosurgery (OR = 0.15-0.34, p < .038) was associated with lower odds of moderate/severe pain on postoperative day one. DISCUSSION: In our cohort, patients rated their current pain in the PACU similarly to other studies. However, the ratio of patients rating the worst pain experienced as moderate/severe on postoperative day one was relatively high. The identified patient- and procedural-related factors associated with higher odds of postoperative pain highlight a subgroup of patients who may benefit from enhanced perioperative monitoring and pain management strategies.

Postoperative nausea and vomiting at Landspitali: A prospective study.

BACKGROUND: In the last decade, anaesthesia practice has changed at Landspitali, where the majority of patients now receive antiemetic prophylaxis, and the use of total intravenous anaesthesia is the dominant mode for maintenance of anaesthesia. The aim of this study was to assess the incidence of postoperative nausea and vomiting (PONV) in a prospective way, the use of PONV prophylaxis, and clinical risk factors associated with PONV during this era. METHODS: A prospective cohort study using a convenience sample of 438 patients ≥18 years old admitted to the postoperative care unit (PACU) after elective or emergency operations in May-July 2022 at Landspitali University Hospital in Iceland. Patients answered questionnaires in the PACU and 24 h after discharge from PACU. RESULTS: The incidence of self-reported moderate/severe nausea (5/10 or higher on NRS) in PACU was 4% and 3% on postoperative day 1. A total of 91% of delivered anaesthetics were with intravenous medications only, and 82% of patients received at least one prophylactic medication for PONV. When asked to rate the worst nausea experienced, this was described as moderate/severe by 7% in PACU and 17% on postoperative day 1. Risk factors associated with PONV were female gender (OR 1.90, 95% CI 1.04-3.53) and a history of motion sickness or PONV (2.74, 1.51-4.94), but increasing age was protective (0.83 per decade, 0.71-0.98). Despite a more liberal administration of antiemetics, patients with more risk factors per Apfel PONV risk classification had a higher incidence of PONV. CONCLUSION: The incidence of PONV is generally low in this diverse surgical population where anaesthesia is mostly maintained with total intravenous anaesthesia and PONV prophylaxis is common. PONV remains a predictable complication following anaesthesia, suggesting further improvement in its prevention is possible.

Furosemide versus placebo for fluid overload in intensive care patients-The randomised GODIF trial second version: Statistical analysis plan.

BACKGROUND: Fluid overload is associated with increased mortality in intensive care unit (ICU) patients. The GODIF trial aims to assess the benefits and harms of fluid removal with furosemide versus placebo in stable adult patients with moderate to severe fluid overload in the ICU. This article describes the detailed statistical analysis plan for the primary results of the second version of the GODIF trial. METHODS: The GODIF trial is an international, multi-centre, randomised, stratified, blinded, parallel-group, pragmatic clinical trial, allocating 1000 adult ICU patients with moderate to severe fluid overload 1:1 to furosemide versus placebo. The primary outcome is days alive and out of hospital within 90 days post-randomisation. With a power of 90% and an alpha level of 5%, we may reject or detect an improvement of 8%. The primary analyses of all outcomes will be performed in the intention-to-treat population. For the primary outcome, the Kryger Jensen and Lange method will be used to compare the two treatment groups adjusted for stratification variables supplemented with sensitivity analyses in the per-protocol population and with further adjustments for prognostic variables. Secondary outcomes will be analysed with multiple linear regressions, logistic regressions or the Kryger Jensen and Lange method as suitable with adjustment for stratification variables. CONCLUSION: The GODIF trial data will increase the certainty about the effects of fluid removal using furosemide in adult ICU patients with fluid overload. TRIAL REGISTRATIONS: EudraCT identifier: 2019-004292-40 and ClinicalTrials.org: NCT04180397.

Humoral Immune Response to SARS-CoV-2 in Iceland.

BACKGROUND: Little is known about the nature and durability of the humoral immune response to infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). METHODS: We measured antibodies in serum samples from 30,576 persons in Iceland, using six assays (including two pan-immunoglobulin [pan-Ig] assays), and we determined that the appropriate measure of seropositivity was a positive result with both pan-Ig assays. We tested 2102 samples collected from 1237 persons up to 4 months after diagnosis by a quantitative polymerase-chain-reaction (qPCR) assay. We measured antibodies in 4222 quarantined persons who had been exposed to SARS-CoV-2 and in 23,452 persons not known to have been exposed. RESULTS: Of the 1797 persons who had recovered from SARS-CoV-2 infection, 1107 of the 1215 who were tested (91.1%) were seropositive; antiviral antibody titers assayed by two pan-Ig assays increased during 2 months after diagnosis by qPCR and remained on a plateau for the remainder of the study. Of quarantined persons, 2.3% were seropositive; of those with unknown exposure, 0.3% were positive. We estimate that 0.9% of Icelanders were infected with SARS-CoV-2 and that the infection was fatal in 0.3%. We also estimate that 56% of all SARS-CoV-2 infections in Iceland had been diagnosed with qPCR, 14% had occurred in quarantined persons who had not been tested with qPCR (or who had not received a positive result, if tested), and 30% had occurred in persons outside quarantine and not tested with qPCR. CONCLUSIONS: Our results indicate that antiviral antibodies against SARS-CoV-2 did not decline within 4 months after diagnosis. We estimate that the risk of death from infection was 0.3% and that 44% of persons infected with SARS-CoV-2 in Iceland were not diagnosed by qPCR.

Postoperative Acute Kidney Injury by Age and Sex: A Retrospective Cohort Association Study.

BACKGROUND: Acute kidney injury (AKI) after noncardiac surgery is common and has substantial health impact. Preclinical and clinical studies examining the influence of sex on AKI have yielded conflicting results, although they typically do not account for age-related changes. The objective of the study was to determine the association of age and sex groups on postoperative AKI. The authors hypothesized that younger females would display lower risk of postoperative AKI than males of similar age, and the protection would be lost in older females. METHODS: This was a multicenter retrospective cohort study across 46 institutions between 2013 and 2019. Participants included adult inpatients without pre-existing end-stage kidney disease undergoing index major noncardiac, nonkidney/urologic surgeries. The authors' primary exposure was age and sex groups defined as females 50 yr or younger, females older than 50 yr, males 50 yr or younger, and males older than 50 yr. The authors' primary outcome was development of AKI by Kidney Disease-Improving Global Outcomes serum creatinine criteria. Exploratory analyses included associations of ascending age groups and hormone replacement therapy home medications with postoperative AKI. RESULTS: Among 390,382 patients, 25,809 (6.6%) developed postoperative AKI (females 50 yr or younger: 2,190 of 58,585 [3.7%]; females older than 50 yr: 9,320 of 14,4047 [6.5%]; males 50 yr or younger: 3,289 of 55,503 [5.9%]; males older than 50 yr: 11,010 of 132,447 [8.3%]). When adjusted for AKI risk factors, compared to females younger than 50 yr (odds ratio, 1), the odds of AKI were higher in females older than 50 yr (odds ratio, 1.51; 95% CI, 1.43 to 1.59), males younger than 50 yr (odds ratio, 1.90; 95% CI, 1.79 to 2.01), and males older than 50 yr (odds ratio, 2.06; 95% CI, 1.96 to 2.17). CONCLUSIONS: Younger females display a lower odds of postoperative AKI that gradually increases with age. These results suggest that age-related changes in women should be further studied as modifiers of postoperative AKI risk after noncardiac surgery.

Haemoglobin levels and outcomes of subgroups of patients with pre-operative anaemia based on red cell size: A retrospective cohort study.

BACKGROUND: Pre-operative anaemia is common and associated with adverse outcomes. We hypothesised that pre-operative anaemia would be evident more than 1 month pre-operatively, and that peri-operative changes in haemoglobin and post-operative outcomes differed between red cell size-based subsets of anaemia. METHODS: A retrospective single-centre cohort study, including all patients 18 years and older undergoing their first surgery at Landspitali between January 2006 and December 2018 with available measurement of haemoglobin (Hb) within 30 days preceding surgery. Clinical data were compared between patients with subgroups of anaemia classified by mean corpuscular volume (MCV) into microcytic (MCV < 80 fl), normocytic (MCV 80-100 fl), and macrocytic (MCV > 100 fl) anaemia. The development of haemoglobin measurements from a nationwide database was plotted from 1 year pre-operatively to 2 years post-operatively. RESULTS: Of 40,979 patients, 10,505 (25.6%) had pre-operative anaemia, of which 1089 (10.4%) had microcytic anaemia, 9243 (88.0%) had normocytic anaemia, and 173 (1.6%) had macrocytic anaemia. Patients within all subgroups of pre-operative anaemia had a higher degree of comorbidity and frailty burden and a low haemoglobin evident for more than 100 days pre-operatively and similar changes post-operatively. Post-operative prolonged recovery of haemoglobin was slower for macrocytic anaemia than other types of anaemia. All groups of patients with anaemia had a higher incidence of 30-day mortality, acute kidney injury, and rate of readmission compared with patients without anaemia. CONCLUSIONS: Pre-operative anaemia is evident long prior to the procedure and its association with worse outcomes is similar regardless of red cell size.

Frailty assessment tools and associated postoperative outcomes in older patients undergoing elective surgery: A prospective pilot study.

BACKGROUND: There is a need for a feasible tool to assess the risk of frailty prior to surgery. We aimed to identify the ratio of abnormal results for three clinically applicable screening tools to assess the risk of frailty, and their association with adverse outcomes in a cohort of elderly surgical patients. METHODS: In this prospective pilot study, patients ≥65 years undergoing preoperative evaluation for elective surgery were included and subjected to three frailty screening tests; Program of Research to Integrate Services for the Maintenance of Autonomy 7-item questionnaire (PRISMA7), Timed Up and Go (TUG), and Clock Drawing Test (CDT). The primary outcome was the incidence of abnormal testing, and secondary outcomes were the association between abnormal tests and mortality, readmission, delirium, surgical complications and non-home discharge. RESULTS: Out of 99 patients, 41%, 37%, and 43% had abnormal PRISMA7, TUG, and CDT screening, respectively. Postoperative delirium was more likely to occur in patients with abnormal TUG screening (19% vs. 3%, p = .011) and CDT (17% vs. 2%, p = .019). When analyzing screening tool combinations, patients with abnormal PRISMA7 and TUG had a higher rate of non-home discharge (38% vs. 17%, p = .029); and patients with abnormal TUG and CDT had a higher rate of postoperative delirium (25% vs. 3%, p = .006) and any surgical complication (58% vs. 38%, p = .037); and patients with abnormal results from all three tools had a higher rate of postoperative delirium (21% vs. 5%, p = .045) and non-home discharge (42% vs. 18%, p = .034). CONCLUSION: Approximately 40% of elderly surgical patients have abnormal PRISMA7, TUG, and CDT screening tests for frailty, and they are associated individually or in combination with increased risk of adverse postoperative outcomes. The results will aid in designing studies to further risk-stratify patients at risk of frailty and attempt to modify associated outcomes.

A survey of preferences for respiratory support in the intensive care unit for patients with acute hypoxaemic respiratory failure.

BACKGROUND: When caring for mechanically ventilated adults with acute hypoxaemic respiratory failure (AHRF), clinicians are faced with an uncertain choice between ventilator modes allowing for spontaneous breaths or ventilation fully controlled by the ventilator. The preferences of clinicians managing such patients, and what motivates their choice of ventilator mode, are largely unknown. To better understand how clinicians' preferences may impact the choice of ventilatory support for patients with AHRF, we issued a survey to an international network of intensive care unit (ICU) researchers. METHODS: We distributed an online survey with 32 broadly similar and interlinked questions on how clinicians prioritise spontaneous or controlled ventilation in invasively ventilated patients with AHRF of different severity, and which factors determine their choice. RESULTS: The survey was distributed to 1337 recipients in 12 countries. Of these, 415 (31%) completed the survey either fully (52%) or partially (48%). Most respondents were identified as medical specialists (87%) or physicians in training (11%). Modes allowing for spontaneous ventilation were considered preferable in mild AHRF, with controlled ventilation considered as progressively more important in moderate and severe AHRF. Among respondents there was strong support (90%) for a randomised clinical trial comparing spontaneous with controlled ventilation in patients with moderate AHRF. CONCLUSIONS: The responses from this international survey suggest that there is clinical equipoise for the preferred ventilator mode in patients with AHRF of moderate severity. We found strong support for a randomised trial comparing modes of ventilation in patients with moderate AHRF.

Postoperative Acute Kidney Injury Is Associated With Progression of Chronic Kidney Disease Independent of Severity.

BACKGROUND: Both postoperative acute kidney injury (AKI) and preoperative chronic kidney disease (CKD) are associated with significantly worse outcomes following surgery. The relationship of both of these conditions with each other and with CKD progression after surgery remains poorly studied. Our objective was to assess if there was an interaction between preoperative kidney function estimated by preoperative estimated glomerular filtration rate (eGFR)/CKD stage, postoperative AKI, and eGFR/CKD progression within 1 year of surgery. Our hypothesis was that AKI severity would be associated with a faster time to eGFR/CKD stage progression within 1 year of surgery in a graded-fashion, which would be exacerbated by preoperative kidney dysfunction. METHODS: This was a retrospective cohort study at Landspitali University Hospital in Iceland, which serves about 75% of the population. Participants included adults receiving their first major anesthetic between 2005 and 2018. Patients with CKD stage 5, undergoing major urologic procedures, or having missing creatinine values for follow-up of eGFR stage were excluded from analysis. The primary exposure was postoperative AKI stage within 7 days after surgery classified by the kidney disease improving global outcome (KDIGO) criteria. The primary outcome was time to progression of CKD by at least 1 eGFR/CKD stage within 1-year following surgery. Multivariable Cox proportional hazards models were used to estimate hazard of eGFR/CKD stage progression, including an interaction between AKI and preoperative CKD on eGFR/CKD stage progression. RESULTS: A total of 5548 patients were studied. In the multivariable model adjusting for baseline eGFR/CKD stage, when compared to patients without AKI, postoperative AKI stage 1 (hazard ratio [HR], 5.91; 95% confidence interval [CI], 4.34-8.05), stage 2 (HR, 3.86; 95% CI, 1.82-8.16), and stage 3 (HR, 3.61; 95% CI, 1.49-8.74) were all independently associated with faster time to eGFR/CKD stage progression within 1 year following surgery, though increasing AKI severity did not confer additional risk. The only significant interaction between the degree of AKI and the preexisting renal function was for stage 1 AKI, where the odds of 1-year eGFR/CKD stage progression actually decreased in patients with preoperative CKD categories 3a, 3b, and 4. CONCLUSIONS: KDIGO-AKI was independently associated with eGFR/CKD stage progression within the year following surgery after adjustment for baseline eGFR/CKD stage and without an interaction between worse preoperative kidney function and higher stage AKI. Our observations suggest that further studies are warranted to test whether CKD progression could be prevented by the adoption of perioperative kidney protective practices.

Long-term survival of Icelandic women following acute myocardial infarction.

Objective. To evaluate the impact of sex on treatment and survival after acute myocardial infarction (AMI) in Iceland. Methods. A retrospective, nationwide cohort study of patients with STEMI (2008-2018) and NSTEMI (2013-2018) and obstructive coronary artery disease. Patient and procedural information were obtained from a registry and electronic health records. Survival was estimated with Kaplan-Meier method and Cox regression analysis used to identify risk factors for long-term mortality. Excess mortality from the AMI episode was estimated by comparing the survival with age- and sex-matched population in Iceland at 30-day interval. Results. A total of 1345 STEMI-patients (24% women) and 1249 NSTEMI-patients (24% women) were evaluated. Women with STEMI (mean age: 71 ± 11 vs. 67 ± 12) and NSTEMI (mean age: 69 ± 13 vs. 62 ± 12) were older and less likely to have previous cardiovascular disease. There was neither sex difference in the extent of coronary artery disease nor treatment. Although crude one-year post-STEMI survival was lower for women (88.7% vs. 93.4%, p = .006), female sex was not an independent risk factor after adjusting for age and co-morbidities after STEMI and was protective for NSTEMI (HR 0.67, 95% CI: 0.46-0.97). There was excess 30-day mortality in both STEMI and NSTEMI for women compared with sex-, age- and inclusion year-matched Icelandic population, but thereafter the mortality rate was similar. Conclusion. Women and men with AMI in Iceland receive comparable treatment including revascularization and long-term survival appears similar. Prognosis after NSTEMI is better in women, whereas higher early mortality after STEMI may be caused by delays in presentation and diagnosis.

Longitudinal changes in inflammatory biomarkers among patients with COVID-19: A nationwide study in Iceland.

OBJECTIVES: All SARS-CoV-2-positive persons in Iceland were prospectively monitored and those who required outpatient evaluation or were admitted to hospital underwent protocolized evaluation that included a standardized panel of biomarkers. The aim was to describe longitudinal changes in inflammatory biomarkers throughout the infection period of patients with COVID-19 requiring different levels of care. DESIGN: Registry-based study. SETTING: Nationwide study in Iceland. PATIENTS: All individuals who tested positive for SARS-CoV-2 by real-time polymerase chain reaction (RT-PCR) from February 28 to December 31, 2020 in Iceland and had undergone blood tests between 5 days before and 21 days following onset of symptoms. MEASUREMENTS AND MAIN RESULTS: Data were collected from the electronic medical record system of Landspitali-The National University Hospital of Iceland. Data analyses were descriptive and the evolution of biomarkers was visualized using locally weighted scatterplot smoothing curves stratified by the worst clinical outcome experienced by the patient: outpatient evaluation only, hospitalization, and either intensive care unit (ICU) admission or death. Of 571 included patients, 310 (54.3%) only required outpatient evaluation or treatment, 202 (35.4%) were hospitalized, and 59 (10.3%) were either admitted to the ICU or died. An early and persistent separation of the mean lymphocyte count and plasma C-reactive protein (CRP) and ferritin levels was observed between the three outcome groups, which occurred prior to hospitalization for those who later were admitted to ICU or died. Lower lymphocyte count, and higher CRP and ferritin levels correlated with worse clinical outcomes. Patients who were either admitted to the ICU or died had sustained higher white blood cell and neutrophil counts, and elevated plasma levels of procalcitonin and D-dimer compared with the other groups. CONCLUSIONS: Lymphocyte count and plasma CRP and ferritin levels might be suitable parameters to assess disease severity early during COVID-19 and may serve as predictors of worse outcome.

Therapeutics and COVID-19-A living WHO guideline: Endorsement by the Scandinavian Society of Anaesthesiology and Intensive Care Medicine.

The Clinical Practice Committee of the Scandinavian Society of Anaesthesiology and Intensive Care Medicine endorses the Living WHO guideline on therapeutics and COVID-19. This trustworthy continuously updated guideline serves as a highly useful decision aid for Nordic anaesthesiologists caring for patients with COVID-19.

Utilization and outcomes of tracheostomies in the intensive care unit in Iceland in 2007-2020: A descriptive study.

BACKGROUND: Tracheostomies are commonly utilized in ICU patients due to prolonged mechanical ventilation, upper airway obstruction, or surgery in the face/neck region. However, practices regarding the timing of placement and utilization vary. This study provides a nationwide overview of tracheostomy utilization and outcomes in the ICU over a 14-year period. METHODS: A retrospective study including all patients that received a tracheostomy during their ICU stay in Iceland between 2007 and 2020. Data were retrieved from hospital records on admission cause, comorbidities, indication for tracheostomy insertion, duration of mechanical ventilation before and after tracheostomy placement, extubation attempts, complications, length of ICU and hospital stay and survival. Descriptive statistics were provided, and survival analysis was performed using Cox regression. RESULTS: A total of 336 patients (median age 64 years, 33% females) received a tracheostomy during the study period. The most common indication for tracheostomy insertion was respiratory failure, followed by neurological disorders. The median duration of mechanical ventilation prior to tracheostomy insertion was 9 days and at least one extubation had been attempted in 35% of the cases. Percutaneous tracheostomies were 32%. The overall rate of complications was 25% and the most common short-term complication was bleeding (5%). In-hospital mortality was 33%. The one- and five-year survival rate was 60% and 44%, respectively. CONCLUSIONS: We describe a whole-nation practice of tracheostomies. A notable finding is the relatively low rate of extubation attempts prior to tracheostomy insertion. Future work should focus on standardization of assessing the need for tracheostomy and the role of extubation attempts prior to tracheostomy placement.

Management of acute atrial fibrillation in the intensive care unit: An international survey.

BACKGROUND: Atrial fibrillation (AF) is common in intensive care unit (ICU) patients and is associated with poor outcomes. Different management strategies exist, but the evidence is limited and derived from non-ICU patients. This international survey of ICU doctors evaluated the preferred management of acute AF in ICU patients. METHOD: We conducted an international online survey of ICU doctors with 27 questions about the preferred management of acute AF in the ICU, including antiarrhythmic therapy in hemodynamically stable and unstable patients and use of anticoagulant therapy. RESULTS: A total of 910 respondents from 70 ICUs in 14 countries participated in the survey with 24%-100% of doctors from sites responding. Most ICUs (80%) did not have a local guideline for the management of acute AF. The preferred first-line strategy for the management of hemodynamically stable patients with acute AF was observation (95% of respondents), rhythm control (3%), or rate control (2%). For hemodynamically unstable patients, the preferred strategy was observation (48%), rhythm control (48%), or rate control (4%). Overall, preferred antiarrhythmic interventions included amiodarone, direct current cardioversion, beta-blockers other than sotalol, and magnesium in that order. A total of 67% preferred using anticoagulant therapy in ICU patients with AF, among whom 61% preferred therapeutic dose anticoagulants and 39% prophylactic dose anticoagulants. CONCLUSION: This international survey indicated considerable practice variation among ICU doctors in the clinical management of acute AF, including the overall management strategies and the use of antiarrhythmic interventions and anticoagulants.

A descriptive study of the surge response and outcomes of ICU patients with COVID-19 during first wave in Nordic countries.

BACKGROUND: We sought to provide a description of surge response strategies and characteristics, clinical management and outcomes of patients with severe COVID-19 in the intensive care unit (ICU) during the first wave of the pandemic in Denmark, Finland, Iceland, Norway and Sweden. METHODS: Representatives from the national ICU registries for each of the five countries provided clinical data and a description of the strategies to allocate ICU resources and increase the ICU capacity during the pandemic. All adult patients admitted to the ICU for COVID-19 disease during the first wave of COVID-19 were included. The clinical characteristics, ICU management and outcomes of individual countries were described with descriptive statistics. RESULTS: Most countries more than doubled their ICU capacity during the pandemic. For patients positive for SARS-CoV-2, the ratio of requiring ICU admission for COVID-19 varied substantially (1.6%-6.7%). Apart from age (proportion of patients aged 65 years or over between 29% and 62%), baseline characteristics, chronic comorbidity burden and acute presentations of COVID-19 disease were similar among the five countries. While utilization of invasive mechanical ventilation was high (59%-85%) in all countries, the proportion of patients receiving renal replacement therapy (7%-26%) and various experimental therapies for COVID-19 disease varied substantially (e.g. use of hydroxychloroquine 0%-85%). Crude ICU mortality ranged from 11% to 33%. CONCLUSION: There was substantial variability in the critical care response in Nordic ICUs to the first wave of COVID-19 pandemic, including usage of experimental medications. While ICU mortality was low in all countries, the observed variability warrants further attention.

Goal directed fluid removal with furosemide versus placebo in intensive care patients with fluid overload: A trial protocol for a randomised, blinded trial (GODIF trial).

BACKGROUND: Fluid overload is a risk factor for mortality in intensive care unit (ICU) patients. Administration of loop diuretics is the predominant treatment of fluid overload, but evidence for its benefit is very uncertain when assessed in a systematic review of randomised clinical trials. The GODIF trial will assess the benefits and harms of goal directed fluid removal with furosemide versus placebo in ICU patients with fluid overload. METHODS: An investigator-initiated, international, randomised, stratified, blinded, parallel-group trial allocating 1000 adult ICU patients with fluid overload to infusion of furosemide versus placebo. The goal is to achieve a neutral fluid balance. The primary outcome is days alive and out of hospital 90 days after randomisation. Secondary outcomes are all-cause mortality at day 90 and 1-year after randomisation; days alive at day 90 without life support; number of participants with one or more serious adverse events or reactions; health-related quality of life and cognitive function at 1-year follow-up. A sample size of 1000 participants is required to detect an improvement of 8% in days alive and out of hospital 90 days after randomisation with a power of 90% and a risk of type 1 error of 5%. The conclusion of the trial will be based on the point estimate and 95% confidence interval; dichotomisation will not be used. CLINICALTRIALS: gov identifier: NCT04180397. PERSPECTIVE: The GODIF trial will provide important evidence of possible benefits and harms of fluid removal with furosemide in adult ICU patients with fluid overload.

Sepsis after elective surgery - Incidence, aetiology and outcome.

BACKGROUND: Sepsis requiring admission to intensive care (ICU) is a rare complication of elective surgery, but is associated with high morbidity and mortality. The aim of this study was to describe the incidence and outcome of sepsis following elective surgery. METHODS: This was a retrospective, observational study where all admissions to Icelandic ICUs during calendar years 2006, 2008, 2010, 2012, 2014 and 2016 were screened, identifing patients with sepsis following elective surgery (ACCP/SCCM criteria). The number of elective operations performed at the largest center (Landspitali) during the study years were collected. Descriptive statistics were used to assess the incidence and outcome of patients with sepsis after elective surgery. RESULTS: During the study years, 88 patients were admitted to Icelandic ICUs with sepsis following elective surgery. Of those, 80 were operated at Landspitali, where the incidence of sepsis was 0.19% per elective procedure, highest following pancreaticoduodenectomies (14%, CI 6-25) and esophagectomies (13%, CI 4-27), but the greatest number of patients (30% (26/88)) developed sepsis after a colorectal procedure. The most common infection sources were the abdomen (65% (57/88)) and lungs/mediastinum (22% (19/88)), frequently polymicrobial (58% (36/62) of patients with cultures). The incidence of insufficient empirical antibiotics was high (50% (30/60)). The median ICU and hospital length-of-stay were 5.5 and 26 days and the 28-day and 1-year mortality rates were 16% (14/88) and 41% (36/87), respectively. CONCLUSIONS: Incidence of sepsis following elective surgery is low in Iceland but mortality is high. Initial antimicrobial therapy needs careful consideration in these hospital-acquired, often polymicrobial infections.