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 ≥ $$ \ge $$ 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.

The association of degree of polypharmacy before and after among hospitalised internal medicine patients and clinical outcomes: a retrospective, population-based cohort study.

OBJECTIVES: To determine the prevalence and incidence of polypharmacy/hyperpolypharmacy and which medications are most prescribed to patients with varying burden of polypharmacy. DESIGN: Retrospective, population-based cohort study. SETTING: Iceland. PARTICIPANTS: Including patients (≥18 years) admitted to internal medicine services at Landspitali - The National University Hospital of Iceland, between 1 January 2010 with a follow-up of clinical outcomes through 17 March 2022. MAIN OUTCOMES MEASURES: Participants were categorised into medication use categories of non-polypharmacy (<5), polypharmacy (5-10) and hyperpolypharmacy (>10) based on the number of medications filled in the year predischarge and postdischarge. The primary outcome was prevalence and incidence of new polypharmacy. Secondary outcomes were mortality, length of hospital stay and re-admission. RESULTS: Among 85 942 admissions (51% male), the median (IQR) age was 73 (60-83) years. The prevalence of preadmission non-polypharmacy was 15.1% (95% CI 14.9 to 15.3), polypharmacy was 22.9% (95% CI 22.6 to 23.2) and hyperpolypharmacy was 62.5% (95% CI 62.2 to 62.9). The incidence of new postdischarge polypharmacy was 33.4% (95% CI 32.9 to 33.9), and for hyperpolypharmacy was 28.9% (95% CI 28.3 to 29.5) for patients with preadmission polypharmacy. Patients with a higher level of medication use were more likely to use multidose drug dispensing and have a diagnosis of adverse drug reaction. Other comorbidities, including responsible subspeciality and estimates of comorbidity and frailty burden, were identical between groups of varying polypharmacy. There was no difference in length of stay, re-admission rate and mortality. CONCLUSIONS: Preadmission polypharmacy/hyperpolypharmacy and postdischarge new polypharmacy/hyperpolypharmacy is common amongst patients admitted to internal medicine. A higher level of medication use category was not found to be associated with demographic, comorbidity and clinical outcomes. Medications that are frequently inappropriately prescribed were among the most prescribed medications in the group. An increased focus on optimising medication usage is needed after hospital admission. TRIAL REGISTRATION NUMBER: NCT05756400.

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.

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.

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.

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.

Physical and cognitive impact following SARS-CoV-2 infection in a large population-based case-control study.

BACKGROUND: Persistent symptoms are common after SARS-CoV-2 infection but correlation with objective measures is unclear. METHODS: We invited all 3098 adults who tested SARS-CoV-2 positive in Iceland before October 2020 to the deCODE Health Study. We compared multiple symptoms and physical measures between 1706 Icelanders with confirmed prior infection (cases) who participated, and 619 contemporary and 13,779 historical controls. Cases participated in the study 5-18 months after infection. RESULTS: Here we report that 41 of 88 symptoms are associated with prior infection, most significantly disturbed smell and taste, memory disturbance, and dyspnea. Measured objectively, cases had poorer smell and taste results, less grip strength, and poorer memory recall. Differences in grip strength and memory recall were small. No other objective measure associated with prior infection including heart rate, blood pressure, postural orthostatic tachycardia, oxygen saturation, exercise tolerance, hearing, and traditional inflammatory, cardiac, liver, and kidney blood biomarkers. There was no evidence of more anxiety or depression among cases. We estimate the prevalence of long Covid to be 7% at a median of 8 months after infection. CONCLUSIONS: We confirm that diverse symptoms are common months after SARS-CoV-2 infection but find few differences between cases and controls in objective parameters measured. These discrepancies between symptoms and physical measures suggest a more complicated contribution to symptoms related to prior infection than is captured with conventional tests. Traditional clinical assessment is not expected to be particularly informative in relating symptoms to a past SARS-CoV-2 infection.

Persistent symptoms are commonly reported after SARS-CoV-2 infection, and this is often described as long Covid. We compared different symptoms reported following SARS-CoV- 2 infection with the results obtained during various medical evaluations that are often used to assess health, such as blood tests, smell tests, taste tests, hearing tests, etc. We compared symptoms and test results between 1,706 Icelanders who had been infected previously with SARS-CoV-2 infection (cases) and 14,398 individuals who had not been infected (controls). Out of 88 assessed symptoms, 41 were more common in cases than controls. However, relatively few differences were seen in the results obtained from the various medical evaluations (cases had poorer smell and taste test results, slightly less grip strength, and slightly poorer memory recall than controls). The differences seen between symptoms and results of medical evaluations suggests that conventional clinical tests may not be informative in relating symptoms to a past SARS-CoV-2 infection.

Epidemiology and association with outcomes of polypharmacy in patients undergoing surgery: retrospective, population-based cohort study.

BACKGROUND: The aim of this study was to determine the prevalence of preoperative polypharmacy and the incidence of postoperative polypharmacy/hyper-polypharmacy in surgical patients and their association with adverse outcomes. METHODS: This was a retrospective, population-based cohort study among patients older than or equal to 18 years undergoing surgery at a university hospital between 2005 and 2018. Patients were categorized based on the number of medications: non-polypharmacy (fewer than 5); polypharmacy (5-9); and hyper-polypharmacy (greater than or equal to 10). The 30-day mortality, prolonged hospitalization (greater than or equal to 10 days), and incidence of readmission were compared between medication-use categories. RESULTS: Among 55 997 patients, the prevalence of preoperative polypharmacy was 32.3 per cent (95 per cent c.i. 33.5 to 34.3) and the prevalence of hyper-polypharmacy was 25.5 per cent (95 per cent c.i. 25.2 to 25.9). Thirty-day mortality was higher for patients exposed to preoperative hyper-polypharmacy (2.3 per cent) and preoperative polypharmacy (0.8 per cent) compared with those exposed to non-polypharmacy (0.6 per cent) (P < 0.001). The hazards ratio (HR) of long-term mortality was higher for patients exposed to hyper-polypharmacy (HR 1.32 (95 per cent c.i. 1.25 to 1.40)) and polypharmacy (HR 1.07 (95 per cent c.i. 1.01 to 1.14)) after adjustment for patient and procedural variables. The incidence of longer hospitalization (greater than or equal to 10 days) was higher for hyper-polypharmacy (11.3 per cent) and polypharmacy (6.3 per cent) compared with non-polypharmacy (4.1 per cent) (P < 0.001). The 30-day incidence of readmission was higher for patients exposed to hyper-polypharmacy (10.2 per cent) compared with polypharmacy (6.1 per cent) and non-polypharmacy (4.8 per cent) (P < 0.001). Among patients not exposed to polypharmacy, the incidence of new postoperative polypharmacy/hyper-polypharmacy was 33.4 per cent (95 per cent c.i. 32.8 to 34.1), and, for patients exposed to preoperative polypharmacy, the incidence of postoperative hyper-polypharmacy was 16.3 per cent (95 per cent c.i. 16.0 to 16.7). CONCLUSION: Preoperative polypharmacy and new postoperative polypharmacy/hyper-polypharmacy are common and associated with adverse outcomes. This highlights the need for increased emphasis on optimizing medication usage throughout the perioperative interval. REGISTRATION NUMBER: NCT04805151 (http://clinicaltrials.gov).

The incidence of new and persistent benzodiazepine use after surgery.

BACKGROUND: It is possible that a portion of new and new persistent use of benzodiazepines is among individuals who start using the medications before or after surgery. We studied the incidence of new and new persistent benzodiazepine use among patients undergoing surgery. METHODS: Retrospective, single-center, population-based cohort of all individuals ≥18 years undergoing first surgery between January 2, 2006 and December 31, 2018 with a year of follow-up for filled medications. Benzodiazepine-naïve patients were defined as not filling a prescription from a year to 31 days before surgery. Patients with new use were naïve patients who filled a prescription between 30 days before and 14 days after surgery, and patients with new persistent use were patients with new use who filled a prescription between 15 days and a year after surgery. Patient and procedural characteristics and prescription filling patterns between the groups were compared. RESULTS: A total of 55,997 patients (32,136 women [57.4%]; median [interquartile range] age, 55 [39, 69] years) were included. The incidence of new use among naïve patients was 2.7% (95% confidence interval, 2.6%-2.8%; n = 1,311), and, of those, 43.7% (95% confidence interval, 41.0%-46.5%; n = 571) had new persistent benzodiazepine use. Approximately 10% of patients with new use filled a prescription for benzodiazepine in every 30-day window during the follow-up period. CONCLUSION: A small portion of surgical patients begin benzodiazepine use perioperatively, but subsequently half fill criteria for persistent use. This highlights the importance of identifying strategies to minimize both new use and the progression of new use into persistent use in surgical patients.

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.

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.

Nordic survey on assessment and treatment of fluid overload in intensive care.

Introduction: Fluid overload in patients in the intensive care unit (ICU) is associated with higher mortality. There are few randomized controlled trials to guide physicians in treating patients with fluid overload in the ICU, and no guidelines exist. We aimed to elucidate how ICU physicians from Nordic countries define, assess, and treat fluid overload in the ICU. Materials and methods: We developed an online questionnaire with 18 questions. The questions were pre-tested and revised by specialists in intensive care medicine. Through a network of national coordinators. The survey was distributed to a wide range of Nordic ICU physicians. The distribution started on January 5th, 2022 and ended on May 6th, 2022. Results: We received a total of 1,066 responses from Denmark, Norway, Finland, Sweden, and Iceland. When assessing fluid status, respondents applied clinical parameters such as clinical examination findings, cumulative fluid balance, body weight, and urine output more frequently than cardiac/lung ultrasound, radiological appearances, and cardiac output monitoring. A large proportion of the respondents agreed that a 5% increase or more in body weight from baseline supported the diagnosis of fluid overload. The preferred de-resuscitation strategy was diuretics (91%), followed by minimization of maintenance (76%) and resuscitation fluids (71%). The majority declared that despite mild hypotension, mild hypernatremia, and ongoing vasopressor, they would not withhold treatment of fluid overload and would continue diuretics. The respondents were divided when it came to treating fluid overload with loop diuretics in patients receiving noradrenaline. Around 1% would not administer noradrenaline and diuretics simultaneously and 35% did not have a fixed upper limit for the dosage. The remaining respondents 63% reported different upper limits of noradrenaline infusion (0.05-0.50 mcg/kg/min) when administering loop diuretics. Conclusion: Self-reported practices among Nordic ICU physicians when assessing, diagnosing, and treating fluid overload reveals variability in the practice. A 5% increase in body weight was considered a minimum to support the diagnosis of fluid overload. Clinical examination findings were preferred for assessing, diagnosing and treating fluid overload, and diuretics were the preferred treatment modality.

Development of a prognostic model of COVID-19 severity: a population-based cohort study in Iceland.

BACKGROUND: The severity of SARS-CoV-2 infection varies from asymptomatic state to severe respiratory failure and the clinical course is difficult to predict. The aim of the study was to develop a prognostic model to predict the severity of COVID-19 in unvaccinated adults at the time of diagnosis. METHODS: All SARS-CoV-2-positive adults in Iceland were prospectively enrolled into a telehealth service at diagnosis. A multivariable proportional-odds logistic regression model was derived from information obtained during the enrollment interview of those diagnosed between February 27 and December 31, 2020 who met the inclusion criteria. Outcomes were defined on an ordinal scale: (1) no need for escalation of care during follow-up; (2) need for urgent care visit; (3) hospitalization; and (4) admission to intensive care unit (ICU) or death. Missing data were multiply imputed using chained equations and the model was internally validated using bootstrapping techniques. Decision curve analysis was performed. RESULTS: The prognostic model was derived from 4756 SARS-CoV-2-positive persons. In total, 375 (7.9%) only required urgent care visits, 188 (4.0%) were hospitalized and 50 (1.1%) were either admitted to ICU or died due to complications of COVID-19. The model included age, sex, body mass index (BMI), current smoking, underlying conditions, and symptoms and clinical severity score at enrollment. On internal validation, the optimism-corrected Nagelkerke's R2 was 23.4% (95%CI, 22.7-24.2), the C-statistic was 0.793 (95%CI, 0.789-0.797) and the calibration slope was 0.97 (95%CI, 0.96-0.98). Outcome-specific indices were for urgent care visit or worse (calibration intercept -0.04 [95%CI, -0.06 to -0.02], Emax 0.014 [95%CI, 0.008-0.020]), hospitalization or worse (calibration intercept -0.06 [95%CI, -0.12 to -0.03], Emax 0.018 [95%CI, 0.010-0.027]), and ICU admission or death (calibration intercept -0.10 [95%CI, -0.15 to -0.04] and Emax 0.027 [95%CI, 0.013-0.041]). CONCLUSION: Our prognostic model can accurately predict the later need for urgent outpatient evaluation, hospitalization, and ICU admission and death among unvaccinated SARS-CoV-2-positive adults in the general population at the time of diagnosis, using information obtained by telephone interview.

HLA alleles, disease severity, and age associate with T-cell responses following infection with SARS-CoV-2.

Memory T-cell responses following SARS-CoV-2 infection have been extensively investigated but many studies have been small with a limited range of disease severity. Here we analyze SARS-CoV-2 reactive T-cell responses in 768 convalescent SARS-CoV-2-infected (cases) and 500 uninfected (controls) Icelanders. The T-cell responses are stable three to eight months after SARS-CoV-2 infection, irrespective of disease severity and even those with the mildest symptoms induce broad and persistent T-cell responses. Robust CD4+ T-cell responses are detected against all measured proteins (M, N, S and S1) while the N protein induces strongest CD8+ T-cell responses. CD4+ T-cell responses correlate with disease severity, humoral responses and age, whereas CD8+ T-cell responses correlate with age and functional antibodies. Further, CD8+ T-cell responses associate with several class I HLA alleles. Our results, provide new insight into HLA restriction of CD8+ T-cell immunity and other factors contributing to heterogeneity of T-cell responses following SARS-CoV-2 infection.

Identifying Patients Vulnerable to Inadequate Pain Resolution After Cardiac Surgery.

Acute postoperative pain (APOP) is often evaluated through granular parameters, though monitoring postoperative pain using trends may better describe pain state. We investigated acute postoperative pain trajectories in cardiac surgical patients to identify subpopulations of pain resolution and elucidate predictors of problematic pain courses. We examined retrospective data from 2810 cardiac surgical patients at a single center. The k-means algorithm for longitudinal data was used to generate clusters of pain trajectories over the first 5 postoperative days. Patient characteristics were examined for association with cluster membership using ordinal and multinomial logistic regression. We identified 3 subgroups of pain resolution after cardiac surgery: 37.7% with good resolution, 44.2% with moderate resolution, and 18.2% exhibiting poor resolution. Type I diabetes (2.04 [1.00-4.16], p = 0.05), preoperative opioid use (1.65 [1.23-2.22], p = 0.001), and illicit drug use (1.89 [1.26-2.83], p = 0.002) elevated risk of membership into worse pain trajectory clusters. Female gender (1.72 [1.30-2.27], p < 0.001), depression (1.60 [1.03-2.50], p = 0.04) and chronic pain (3.28 [1.79-5.99], p < 0.001) increased risk of membership in the worst pain resolution cluster. This study defined 3 APOP resolution subgroups based on pain score trend after cardiac surgery and identified factors that predisposed patients to worse resolution. Patients with moderate or poor pain trajectory consumed more opioids and received them for longer before discharge. Future studies are warranted to determine if altering postoperative pain monitoring and management improve postoperative course of patients at risk of moderate or poor pain resolution.

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.