Showing papers in "Acta Anaesthesiologica Scandinavica in 2021"

Characteristics, interventions and longer-term outcomes of COVID-19 ICU patients in Denmark - a nationwide, observational study.

Abstract: Background Most data on intensive care unit (ICU) patients with COVID-19 originate in selected populations from stressed healthcare systems with shorter term follow-up. We present characteristics, interventions and longer term outcomes of the entire, unselected cohort of all ICU patients with COVID-19 in Denmark where the ICU capacity was not exceeded. Methods We identified all patients with SARS-CoV-2 admitted to any Danish ICU from 10 March to 19 May 2020 and registered demographics, chronic comorbidities, use of organ support, length of stay, and vital status from patient files. Risk factors for death were analyzed using adjusted Cox regression analysis. Results There were 323 ICU patients with confirmed COVID-19. Median age was 68 years, 74% were men, 50% had hypertension, 21% diabetes, and 20% chronic pulmonary disease; 29% had no chronic comorbidity. Invasive mechanical ventilation was used in 82%, vasopressors in 83%, renal replacement therapy in 26%, and extra corporeal membrane oxygenation in 8%. ICU stay was median 13 days (IQR 6-22) and hospital stay 19 days (11-30). Median follow-up was 79 days. At end of follow-up, 118 had died (37%), 15 (4%) were still in hospital hereof 4 in ICU as of 16 June 2020. Risk factors for mortality included male gender, age, chronic pulmonary disease, active cancer, and number of co-morbidities. Conclusions In this nationwide, population-based cohort of ICU patients with COVID-19, longer term survival was high despite high age and substantial use of organ support. Male gender, age, and chronic co-morbidities, in particular chronic pulmonary disease, were associated with increased risk of death.

The swedish covid-19 intensive care cohort: Risk factors of ICU admission and ICU mortality.

Abstract: Background Several studies have recently addressed factors associated with severe Coronavirus disease 2019 (COVID-19); however, some medications and comorbidities have yet to be evaluated in a large matched cohort. We therefore explored the role of relevant comorbidities and medications in relation to the risk of intensive care unit (ICU) admission and mortality. Methods All ICU COVID-19 patients in Sweden until 27 May 2020 were matched to population controls on age and gender to assess the risk of ICU admission. Cases were identified, comorbidities and medications were retrieved from high-quality registries. Three conditional logistic regression models were used for risk of ICU admission and three Cox proportional hazards models for risk of ICU mortality, one with comorbidities, one with medications and finally with both models combined, respectively. Results We included 1981 patients and 7924 controls. Hypertension, type 2 diabetes mellitus, chronic renal failure, asthma, obesity, being a solid organ transplant recipient and immunosuppressant medications were independent risk factors of ICU admission and oral anticoagulants were protective. Stroke, asthma, chronic obstructive pulmonary disease and treatment with renin-angiotensin-aldosterone inhibitors (RAASi) were independent risk factors of ICU mortality in the pre-specified primary analyses; treatment with statins was protective. However, after adjusting for the use of continuous renal replacement therapy, RAASi were no longer an independent risk factor. Conclusion In our cohort oral anticoagulants were protective of ICU admission and statins was protective of ICU death. Several comorbidities and ongoing RAASi treatment were independent risk factors of ICU admission and ICU mortality.

Characteristics and outcomes of patients with COVID‐19 admitted to ICU in a tertiary hospital in Stockholm, Sweden

Abstract: Background Information on characteristics and outcomes of intensive care unit (ICU) patients with COVID-19 remains limited. We examined characteristics, clinical course and early outcomes of patients with COVID-19 admitted to ICU. Methods We included all 260 patients with COVID-19 admitted to nine ICUs at the Karolinska University Hospital (Stockholm, Sweden) between 9 March and 20 April 2020. Primary outcome was in-hospital mortality among patients with definite outcomes (discharged from ICU or death), as of 30 April 2020 (study end point). Secondary outcomes included ICU length of stay, the proportion of patients receiving mechanical ventilation and renal replacement therapy, and hospital discharge destination. Results Of 260 ICU patients with COVID-19, 208 (80.0%) were men, the median age was 59 (IQR 51-65) years, 154 (59.2%) had at least one comorbidity, and the median duration of symptoms preceding ICU admission was 11 (IQR 8-14) days. Sixty-two (23.8%) patients remained in ICU at study end point. Among the 198 patients with definite outcomes, ICU length of stay was 12 (IQR, 6-18) days, 163 (82.3%) received mechanical ventilation, 28 (14.1%) received renal replacement therapy, 60 (30.3%) died, 62 (31.3%) were discharged home, 47 (23.7%) were discharged to ward, and 29 (14.6%) were discharged to another health care facility. On multivariable logistic regression analysis, older age and admission from the emergency department was associated with higher mortality. Conclusion This study presents detailed data on clinical characteristics and early outcomes of consecutive patients with COVID-19 admitted to ICU in a large tertiary hospital in Sweden.

COVID-19 patients in intensive care develop predominantly oliguric acute kidney injury.

Abstract: BACKGROUND: Acute kidney injury (AKI) is a syndrome of reduced glomerular filtration rate and/or reduced urine flow associated with mortality in corona virus disease 2019 (COVID-19). AKI is often associated with renal tissue damage, which may lead to chronic kidney disease. Biomarkers of tissue damage may identify patients of particular risk. METHODS: In a prospective observational study of 57 patients admitted to intensive care, AKI incidence and characteristics was evaluated according to KDIGO criteria and related to days after admission. Urinary albumin, Neutrophil Gelatinase-Associated Lipocalin (NGAL), Kidney Injury Molecule 1 (KIM-1) and Plasma Tissue Inhibitor of MetalloProteinase 2 (TIMP-2) were analysed in 52 patients at admission. The majority (n = 51, 89%) of patients developed AKI, and 27 (47%) patients had predominantly oliguric AKI where oliguria was more severe than plasma Creatinine increase. Severe oliguria within first 2 days after admission was common (n = 37, 65%), whereas stage 2 and 3 AKI due to Creatinine occurred later than day 2 in 67% (12/18) of cases. Renal replacement therapy was started in 9 (16%) patients, and 30-day mortality was 28%. Urinary biomarkers were increased in a majority of patients, but did not robustly predict KDIGO stage. Most patients had microalbuminuria, and severe albuminuria (albumin Creatinine ratio > 30 mg/mmol) was found in n = 9 (17%) patients. CONCLUSIONS: A majority of patients with COVID-19 admitted to the ICU develop AKI. The functional deficit is often low urinary volume, and initial levels of biomarkers are generally increased without clear relation to final AKI stage.

Human glycocalyx shedding: Systematic review and critical appraisal.

Abstract: BACKGROUND The number of studies measuring breakdown products of the glycocalyx in plasma has increased rapidly during the past decade. The purpose of the present systematic review was to assess the current knowledge concerning the association between plasma concentrations of glycocalyx components and structural assessment of the endothelium. METHODS We performed a literature review of Pubmed to determine which glycocalyx components change in a wide variety of human diseases and conditions. We also searched for evidence of a relationship between plasma concentrations and the thickness of the endothelial glycocalyx layer as obtained by imaging methods. RESULTS Out of 3,454 publications, we identified 228 that met our inclusion criteria. The vast majority demonstrate an increase in plasma glycocalyx products. Sepsis and trauma are most frequently studied, and comprise approximately 40 publications. They usually report 3-4-foldt increased levels of glycocalyx degradation products, most commonly of syndecan-1. Surgery shows a variable picture. Cardiac surgery and transplantations are most likely to involve elevations of glycocalyx degradation products. Structural assessment using imaging methods show thinning of the endothelial glycocalyx layer in cardiovascular conditions and during major surgery, but thinning does not always correlate with the plasma concentrations of glycocalyx products. The few structural assessments performed do not currently support that capillary permeability is increased when the plasma levels of glycocalyx fragments in plasma are increased. CONCLUSIONS Shedding of glycocalyx components is a ubiquitous process that occurs during both acute and chronic inflammation with no sensitivity or specificity for a specific disease or condition.

Low-dose hydrocortisone in patients with COVID-19 and severe hypoxia: the COVID STEROID randomised, placebo-controlled trial.

Abstract: Background In the early phase of the pandemic, some guidelines recommended the use of corticosteroids for critically ill patients with COVID-19, whereas others recommended against the use despite lack of firm evidence of either benefit or harm. In the COVID STEROID trial, we aimed to assess the effects of low-dose hydrocortisone on patient-centred outcomes in adults with COVID-19 and severe hypoxia. Methods In this multicentre, parallel-group, placebo-controlled, blinded, centrally randomised, stratified clinical trial, we randomly assigned adults with confirmed COVID-19 and severe hypoxia (use of mechanical ventilation or supplementary oxygen with a flow of at least 10 L/min) to either hydrocortisone (200 mg/d) vs a matching placebo for 7 days or until hospital discharge. The primary outcome was the number of days alive without life support at day 28 after randomisation. Results The trial was terminated early when 30 out of 1000 participants had been enrolled because of external evidence indicating benefit from corticosteroids in severe COVID-19. At day 28, the median number of days alive without life support in the hydrocortisone vs placebo group were 7 vs 10 (adjusted mean difference: -1.1 days, 95% CI -9.5 to 7.3, P = .79); mortality was 6/16 vs 2/14; and the number of serious adverse reactions 1/16 vs 0/14. Conclusions In this trial of adults with COVID-19 and severe hypoxia, we were unable to provide precise estimates of the benefits and harms of hydrocortisone as compared with placebo as only 3% of the planned sample size were enrolled. Trial registration ClinicalTrials.gov: NCT04348305. European Union Drug Regulation Authorities Clinical Trials (EudraCT) Database: 2020-001395-15.

Total opioid-free general anaesthesia can improve postoperative outcomes after surgery, without evidence of adverse effects on patient safety and pain management: A systematic review and meta-analysis.

Abstract: BACKGROUND Opioid-based treatment is used to manage stress responses during surgery and postoperative pain. However, opioids have both acute and long-term side effects, calling for opioid-free anaesthetic strategies. This meta-analysis compares adverse events, postoperative recovery, discharge time from post-anaesthesia care unit, and postoperative pain, nausea, vomiting, and opioid consumption between strict opioid-free and opioid-based general anaesthesia. METHODS We conducted a systematic review and meta-analysis. We searched PubMed, Embase, Cinahl, Cochrane Library, selected reference lists, and Google Scholar. We included randomised controlled trials (RCTs) published between January 2000 and February 2021 with at least one opioid-free study arm, i.e. no opioids administered preoperatively, during anaesthesia induction, before skin closure, or before emergence from anaesthesia. RESULTS The study comprised 1934 patients from 26 RCTs. Common interventions included laparoscopic gynaecological surgery, upper gastrointestinal surgery, and breast surgery. There is firm evidence that opioid-free anaesthesia significantly reduced adverse postoperative events (OR 0.32, 95% CI 0.22 to 0.46, I2 = 56%, p < 0.00001), mainly driven by decreased nausea (OR 0.27, (0.17 to 0.42), p < 0.00001) and vomiting (OR 0.22 (0.11 to 0.41), p < 0.00001). Postoperative opioid consumption was significantly lower in the opioid-free group (-6.00 mg (-8.52 to -3.48), p < 0.00001). There was no significant difference in length of post-anaesthesia care unit stay and overall postoperative pain between groups. CONCLUSIONS Opioid-free anaesthesia can improve postoperative outcomes in several surgical settings without evidence of adverse effects on patient safety and pain management. There is a need for more evidence-based non-opioid anaesthetic protocols for different types of surgery as well as postoperative phases.

Two-months quality of life of COVID-19 invasively ventilated survivors; an Italian single-center study.

Abstract: BACKGROUND: COVID-19 disease can lead to severe functional impairments after discharge. We assessed the quality of life of invasively ventilated COVID-19 ARDS survivors. METHODS: We carried out a prospective follow-up study of the patients admitted to the Intensive Care Units (ICUs) of a teaching hospital. Patients affected by COVID-19 ARDS who required invasive ventilation and were successfully discharged home were assessed through the telephone administration of validated tests. We explored survival, functional outcomes, return to work, quality of life, cognitive and psychological sequelae. The main variables of interest were the following: demographics, severity scores, laboratory values, comorbidities, schooling, working status, treatments received during ICU stay, complications, and psychological, cognitive, functional outcomes. RESULTS: Out of 116 consecutive invasively ventilated patients, overall survival was 65/116 (56%) with no death occurring after hospital discharge. Forty-two patients were already discharged home with a median follow-up time of 61 (51-71) days after ICU discharge and 39 of them accepted to be interviewed. Only one patient (1/39) experienced cognitive decline. The vast majority of patients reported no difficulty in walking (32/35:82%), self-care (33/39:85%), and usual activities (30/39:78%). All patients were either malnourished (15/39:38%) or at risk for malnutrition (24/39:62%). Exertional dyspnea was present in 20/39 (51%) patients. 19/39 (49%) reported alterations in senses of smell and/or taste either before or after hospitalization. CONCLUSIONS: Invasively ventilated COVID-19 ARDS survivors have an overall good recovery at a 2-months follow-up which is better than what was previously reported in non-COVID-19 ARDS patients.

Prone positioning in mechanically ventilated patients with severe acute respiratory distress syndrome and coronavirus disease 2019.

Abstract: BACKGROUND: The management of COVID-19 ARDS is debated. Although current evidence does not suggest an atypical acute respiratory distress syndrome (ARDS), the physiological response to prone positioning is not fully understood and it is unclear which patients benefit. We aimed to determine whether proning increases oxygenation and to evaluate responders. METHODS: This case series from a single, tertiary university hospital includes all mechanically ventilated patients with COVID-19 and proning between 17 March 2020 and 19 May 2020. The primary measure was change in PaO2 :FiO2 . RESULTS: Forty-four patients, 32 males/12 females, were treated with proning for a total of 138 sessions, with median (range) two (1-8) sessions. Median (IQR) time for the five sessions was 14 (12-17) hours. In the first session, median (IQR) PaO2 :FiO2 increased from 104 (86-122) to 161 (127-207) mm Hg (P < .001). 36/44 patients (82%) improved in PaO2 :FiO2 , with a significant increase in PaO2 :FiO2 in the first three sessions. Median (IQR) FiO2 decreased from 0.7 (0.6-0.8) to 0.5 (0.35-0.6) (<0.001). A significant decrease occurred in the first three sessions. PaO2 , tidal volumes, PEEP, mean arterial pressure (MAP), and norepinephrine infusion did not differ. Primarily, patients with PaO2 :FiO2 approximately < 120 mm Hg before treatment responded to proning. Age, sex, BMI, or SAPS 3 did not predict success in increasing PaO2 :FiO2 . CONCLUSION: Proning increased PaO2 :FiO2 , primarily in patients with PaO2 :FiO2 approximately < 120 mm Hg, with a consistency over three sessions. No characteristic was associated with non-responding, why proning may be considered in most patients. Further study is required to evaluate mortality.

Long-term consequences in critically ill COVID-19 patients: A prospective cohort study.

Abstract: BACKGROUND: COVID-19 can cause severe disease with need of treatment in the intensive care unit (ICU) for several weeks. Increased knowledge is needed about the long-term consequences. METHODS: This is a single-center prospective follow-up study of COVID-19 patients admitted to the ICU for respiratory organ support between March and July 2020. Patients with invasive ventilation were compared with those with high-flow nasal oxygen (HFNO) or non-invasive ventilation (NIV) regarding functional outcome and health-related qualify of life. The mean follow-up time was 5 months after ICU discharge and included clinical history, three well-validated questionnaires about health-related quality of life and psychological health, pulmonary function test, 6-minute walk test (6MWT) and work ability. Data were analyzed with multivariable general linear and logistic regression models with 95% confidence intervals. RESULTS: Among 248 ICU patients, 200 patients survived. Of these, 113 patients came for follow-up. Seventy patients (62%) had received invasive ventilation. Most patients reported impaired health-related quality of life. Approximately one-third suffered from post-traumatic stress, anxiety and depression. Twenty-six percent had reduced total lung capacity, 34% had reduced 6MWT and 50% worked fulltime. The outcomes were similar regardless of ventilatory support, but invasive ventilation was associated with more bodily pain (MSD -19, 95% CI: -32 to -5) and <80% total lung capacity (OR 4.1, 95% CI: 1.3-16.5). CONCLUSION: Among survivors of COVID-19 who required respiratory organ support, outcomes 5 months after discharge from ICU were largely similar among those requiring invasive compared to non-invasive ventilation.

Characteristics, management and survival of ICU patients with coronavirus disease-19 in Norway, March-June 2020. A prospective observational study.

Abstract: Background Norwegian hospitals have operated within capacity during the COVID-19 pandemic. We present patient and management characteristics, and outcomes for the entire cohort of adult (> 18 years) COVID-19 patients admitted to Norwegian intensive care units (ICU) from 10 March to 19 June 2020. Methods Data were collected from The Norwegian intensive care and pandemic registry (NIPaR). Demographics, co-morbidities, management characteristics and outcomes are described. ICU length of stay (LOS) was analysed with linear regression, and associations between risk factors and mortality were quantified using Cox regression. Results In total, 217 patients were included. The male to female ratio was 3:1 and the median age was 63 years. A majority (70%) had one or more co-morbidities, most frequently cardiovascular disease (39%), chronic lung disease (22%), diabetes mellitus (20%), and obesity (17%). Most patients were admitted for acute hypoxaemic respiratory failure (AHRF)(91%) and invasive mechanical ventilation (MV) was used in 86%, prone ventilation in 38% and 25% of patients received a tracheostomy. Vasoactive drugs were used in 79% and renal replacement therapy in 15%. Median ICU LOS and time of MV was 14.0 and 12.0 days. At end of follow-up 45 patients (21%) were dead. Age, co-morbidities and severity of illness at admission were predictive of death. Severity of AHRF and male gender were associated with LOS. Conclusions In this national cohort of COVID-19 patients, mortality was low and attributable to known risk factors. Importantly, prolonged length-of-stay must be taken into account when planning for resource allocation for any next surge.

Acute pulmonary hypertension and short-term outcomes in severe Covid-19 patients needing intensive care.

Abstract: INTRODUCTION: Critically ill Covid-19 pneumonia patients are likely to develop the sequence of acute pulmonary hypertension, right ventricular (RV) strain, and eventually RV failure due to known pathophysiology (endothelial inflammation plus thrombo-embolism) that promotes increased pulmonary vascular resistance and pulmonary artery pressure. This study aimed to investigate the occurrence of acute pulmonary hypertension (aPH) as per established trans-thoracic echocardiography (TTE) criteria in Covid-19 patients receiving intensive care and to explore whether short-term outcomes are affected by the presence of aPH. METHODS: Medical records were reviewed for patients treated in the intensive care units at a tertiary university hospital over a month. The presence of aPH on the TTE was noted, and plasma NTproBNP and troponin were measured as markers of cardiac failure and myocardial injury, respectively. Follow-up data were collected 21 d after the performance of TTE. RESULTS: In total, 26 of 67 patients (39%) had an assessed systolic pulmonary artery pressure of > 35 mmHg (group aPH), meeting the TTE definition of aPH. NTproBNP levels (median [range]: 1430 [102-30 300] vs. 470 [45-29 600] ng L-1 ; P = .0007), troponin T levels (63 [22-352] vs. 15 [5-407] ng L-1 ; P = .0002), and the 21-d mortality rate (46% vs. 7%; P < .001) were substantially higher in patients with aPH compared to patients not meeting aPH criteria. CONCLUSION: TTE-defined acute pulmonary hypertension was frequently observed in severely ill Covid-19 patients. Furthermore, aPH was linked to biomarker-defined myocardial injury and cardiac failure, as well as an almost sevenfold increase in 21-d mortality.

Thrombocytopenia in intensive care unit patients: A scoping review.

Abstract: Background Thrombocytopenia is frequent in intensive care unit (ICU) patients and may be associated with adverse outcomes. We aimed to assess the incidence, risk factors, and outcomes associated with thrombocytopenia in adult ICU patients. Methods We conducted a scoping review in accordance with the Preferred Reporting Items for Systematic Review and Meta-analyses extension for Scoping Reviews (PRISMA-ScR) and the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. We included study reports on adult ICU patients with thrombocytopenia and assessed patient-important outcomes, including mortality and health-related quality-of-life. Results We included a total of 70 studies comprising a total of 215 098 patients; 57 were cohort studies. The incidence of thrombocytopenia varied from 8 to 56 per 100 admissions (very low quality of evidence). We identified several risk factors including age, sepsis, and higher disease severity (low quality of evidence). Thrombocytopenia was associated with bleeding, use of life support, length of stay in the ICU, and increased mortality (low/very low quality of evidence). Data on platelet transfusion before invasive procedures and transfusion thresholds were limited. No studies assessed the benefits and harms of thromboprophylaxis in ICU patients with thrombocytopenia. Conclusions Thrombocytopenia is common and associated with increased morbidity and mortality in adult ICU patients. Several risk factors for thrombocytopenia exists, but the evidence-base on management strategies, including transfusion thresholds and thromboprophylaxis in ICU patients is very limited.

Higher vs lower doses of dexamethasone in patients with COVID-19 and severe hypoxia (COVID STEROID 2) trial: Protocol and statistical analysis plan.

Abstract: Background The coronavirus disease 2019 (COVID-19) pandemic has resulted in millions of deaths and overburdened healthcare systems worldwide. Systemic low-dose corticosteroids have proven clinical benefit in patients with severe COVID-19. Higher doses of corticosteroids are used in other inflammatory lung diseases and may offer additional clinical benefits in COVID-19. At present, the balance between benefits and harms of higher vs. lower doses of corticosteroids for patients with COVID-19 is unclear. Methods The COVID STEROID 2 trial is an investigator-initiated, international, parallel-grouped, blinded, centrally randomised and stratified clinical trial assessing higher (12 mg) vs. lower (6 mg) doses of dexamethasone for adults with COVID-19 and severe hypoxia. We plan to enrol 1,000 patients in Denmark, Sweden, Switzerland and India. The primary outcome is days alive without life support (invasive mechanical ventilation, circulatory support or renal replacement therapy) at day 28. Secondary outcomes include serious adverse reactions at day 28; all-cause mortality at day 28, 90 and 180; days alive without life support at day 90; days alive and out of hospital at day 90; and health-related quality of life at day 180. The primary outcome will be analysed using the Kryger Jensen and Lange test adjusted for stratification variables and reported as adjusted mean differences and median differences. The full statistical analysis plan is outlined in this protocol. Discussion The COVID STEROID 2 trial will provide evidence on the optimal dosing of systemic corticosteroids for COVID-19 patients with severe hypoxia with important implications for patients, their relatives and society.

Cardiac arrhythmias in critically ill patients with coronavirus disease 2019: A retrospective population-based cohort study.

Abstract: Background Coronavirus disease 2019 (COVID-19) may be associated with cardiac arrhythmias in hospitalized patients, but data from the ICU setting are limited. We aimed to describe the epidemiology of cardiac arrhythmias in ICU patients with COVID-19. Methods We conducted a multicenter, retrospective cohort study including all ICU patients with an airway sample positive for severe acute respiratory syndrome corona-virus 2 from March 1st to June 1st in the Capital Region of Denmark (1.8 million inhabitants). We registered cardiac arrhythmias in ICU, potential risk factors, interventions used in ICU and outcomes. Results From the seven ICUs we included 155 patients with COVID-19. The incidence of cardiac arrhythmias in the ICU was 57/155 (37%, 95% confidence interval 30-45), and 39/57 (68%) of these patients had this as new-onset arrhythmia. Previous history of tachyarrhythmias and higher disease severity at ICU admission were associated with cardiac arrhythmias in the adjusted analysis. Fifty-four of the 57 (95%) patients had supraventricular origin of the arrhythmia, 39/57 (68%) received at least one intervention against arrhythmia (eg amiodarone, IV fluid or magnesium) and 38/57 (67%) had recurrent episodes of arrhythmia in ICU. Patients with arrhythmias in ICU had higher 60-day mortality (63%) as compared to those without arrhythmias (39%). Conclusion New-onset supraventricular arrhythmias were frequent in ICU patients with COVID-19 and were related to previous history of tachyarrhythmias and severity of the acute disease. The mortality was high in these patients despite the frequent use of interventions against arrhythmias.

Residual lung damage following ARDS in COVID-19 ICU survivors.

Abstract: Background COVID-19 ARDS is a disease that often requires invasive ventilation. Little is known about COVID-19 ARDS sequelae. We assessed mid-term lung status of COVID-19 survivors and investigated factors associated with pulmonary sequelae. Methods All adult COVID-19 patients admitted to the intensive care unit from February 25th to April 27th 2020 were included. Lung function was evaluated through chest CT scan and pulmonary function tests (PFT). Logistic regression was used to identify predictors of persisting lung alterations. Results Forty-nine patients (75%) completed lung assessment. Chest CT scan was performed after a median (interquartile range) time of 97 (89-105) days, while PFT after 142 (133-160) days. Median age was 58 (52-65) years and most patients were male (90%). Median duration of mechanical ventilation was 11 (6-16) days. Median tidal volume/ideal body weight (TV/IBW) was 6.8 (5.71-7.67) ml/Kg. 59% and 63% of patients showed radiological and functional lung sequelae, respectively. Diffusion capacity of carbon monoxide (DLCO ) was reduced in 59%, with a median percent of predicted DLCO of 72.1 (57.9-93.9) %. Mean TV/IBW during invasive ventilation emerged as an independent predictor of persistent CT scan abnormalities, while duration of mechanical ventilation was an independent predictor of both CT and PFT abnormalities. The extension of lung involvement at hospital admission (evaluated through Radiographic Assessment of Lung Edema, RALE score) independently predicted the risk of persistent alterations in PFTs. Conclusions Both the extent of lung parenchymal involvement and mechanical ventilation protocols predict morphological and functional lung abnormalities months after COVID-19.

Training non-intensivist doctors to work with COVID-19 patients in intensive care units.

Abstract: Background Due to an expected surge of COVID-19 patients in need of mechanical ventilation, the intensive care capacity was doubled at Rigshospitalet, Copenhagen, in March 2020 This resulted in an urgent need for doctors with competence in working with critically ill COVID-19 patients A training course and a theoretical test for non-intensivist doctors were developed The aims of this study were to gather validity evidence for the theoretical test and explore the effects of the course Methods The one-day course was comprised of theoretical sessions and hands-on training in ventilator use, haemodynamic monitoring, vascular access and use of personal protective equipment Validity evidence was gathered for the test by comparing answers from novices and experts in intensive care Doctors who participated in the course completed the test before (pre-test), after (post-test) and again within eight weeks following the course (retention-test) Results Fifty-four non-intensivist doctors from 15 different specialties with a wide range in clinical experience level completed the course The test consisted of 23 questions and demonstrated a credible pass-fail standard at 16 points Mean pre-test score was 119 (SD 30), mean post-test score 206 (18) and mean retention-test score 174 (22) All doctors passed the post-test Conclusion Non-intensivist doctors, irrespective of experience level, can acquire relevant knowledge for working in the ICU through a focused one-day evidence-based course This knowledge was largely retained as shown by a multiple-choice test supported by validity evidence The test is available in appendix and online

Risk factors for emergence agitation in adults after general anesthesia: A systematic review and meta-analysis.

Abstract: Background Emergence agitation (EA) is an adverse post-operative complication that increases the risk for injury, self-extubation, hemorrhages, and prolonged hospitalization. This meta-analysis aims to define the risk factors for adult EA after general anesthesia and provide recommendations for clinical practice. Methods Embase, PubMed, Medline, and the Cochrane Library databases were comprehensive retrieved. Observational studies that reported the risk factors for adult EA were enrolled. Review Manager 5.4 was used to analyze the extracted data. Results Eighteen observational studies involving 16, 678 adult patients were enrolled in this study. Eighteen pre-operative and nineteen intraoperative factors with unadjusted data, and five pre-operative and five intraoperative factors with adjusted data were meta-analyzed separately. Among them, seven factors (age, male, smoking, history of substance misuse, inhalational anesthesia, urinary catheter, complain of pain, or need analgesic drug use in post-anesthetic care unit) were the risk factors no matter meta-analyzed by unadjusted data or adjusted data. Intraoperative use of benzodiazepines was the risk factor when meta-analyzed by adjusted data, but not unadjusted data. Moreover, age and inhalational anesthesia were not the risk factors when omitted one study for sensitivity analysis, and history of substance misuse could not do sensitivity analysis. Conclusion Based on this meta-analysis, male, smoking, urinary catheter, and post-operative pain are the risk factors, while age, inhalational anesthesia, history of substance misuse, and intraoperative use of benzodiazepines are the possible risk factors for adult EA. Editorial comment This systematic review and meta-analysis identify risk factors associated with the occurrence of agitation during emergence from general anesthesia. As might be expected, the strongest factors are generally things which are irritating or painful for patients, but cannot necessarily be avoided.

A single-centre, prospective cohort study of COVID-19 patients admitted to ICU for mechanical ventilatory support.

Abstract: Background Mortality rates in COVID-19 patients in need of mechanical ventilation are high, with wide variations between countries. Most studies were retrospective, and results may not be generalizable due to differences in demographics, healthcare organization and surge capacity. We present a cohort of mechanically ventilated COVID-19 patients from a resource-rich, publicly financed healthcare system. Methods Prospective study from a tertiary hospital. Consecutive SARS-CoV-2 positive adult patients admitted to the ICU for mechanical ventilation from 10 March 2020 to 04 May 2020 were included. Triage and treatment were protocolized. High-dose dalteparin was adjusted by D-dimer. Demographics, treatments and high-resolution physiological variables were collected. Outcomes were 30-day and hospital mortality. Data are medians (quartiles). Results Of the 1484 persons in the hospital catchment area testing positive for SARS-CoV-2, 201 (13.5%) were hospitalized. Thirty-eight (19%) patients were mechanically ventilated, of whom five (13%) died. Of the 163 patients treated with supplemental oxygen, eight (5%) died. In ventilated patients (75% males, age 61 (53-70) years), severe, moderate and mild ARDS was present in 25%, 70% and 5%. Tidal volume ≤8 mL/kg ideal bodyweight was achieved in 34 (94%) patients. Proning and neuromuscular blockers were used in 19 (54%) and 20 (61%) patients. Duration of ventilation was 12 days (8-23). D-dimer peaked at 3.8 mg/L (2.1-5.3), and maximum dalteparin dose was 15 000 IU/24 h (10 000-15 000). Despite organizational changes, a high degree of adherence to treatment protocols was achieved. Conclusion In a prospective cohort study of mechanically ventilated COVID-19 patients treated in a resource-rich, publicly financed healthcare system, mortality was considerably lower than previously reported in retrospective studies.

Hemodynamic monitoring with Hypotension Prediction Index versus arterial waveform analysis alone and incidence of perioperative hypotension

Abstract: BACKGROUND Intraoperative hypotension is associated with increased morbidity and mortality. The Hypotension Prediction Index (HPI) is an advancement of the arterial waveform analysis to predict intraoperative hypotension minutes before episodes occur enabling preventive treatments. We tested the hypothesis that the HPI combined with a personalized treatment protocol reduces intraoperative hypotension when compared to arterial waveform analysis alone. METHODS We conducted a retrospective analysis of 100 adult consecutive patients undergoing moderate- or high-risk noncardiac surgery with invasive arterial pressure monitoring using either index guidance (HPI) or arterial waveform analysis (FloTrac) depending on availability (FloTrac, n = 50; HPI, n = 50). A personalized treatment protocol was applied in both groups. The primary endpoint was the incidence and duration of hypotensive events defined as MAP <65 mmHg evaluated by time-weighted average of hypotension. RESULTS In the FloTrac group, 42 patients (84%) experienced a hypotension while in the HPI group 26 patients (52%) were hypotensive (p = 0.001). The median (IQR) time-weighted average of hypotension in the FloTrac group was 0.27 (0.42) mmHg versus 0.10 (0.19) mmHg in the HPI group (p = 0.001). Finally, the median duration of each hypotensive event (IQR) was 2.75 (2.40) min in the FloTrac group compared to 1.00 (2.06) min in the HPI group (p = 0.002). CONCLUSIONS The application of the HPI combined with a personalized treatment protocol can reduce incidence and duration of hypotension when compared to arterial waveform analysis alone. This study therefore provides further evidence of the transition from prediction to actual prevention of hypotension using HPI.

Higher vs Lower Doses of Dexamethasone in Patients with COVID-19 and Severe Hypoxia (COVID STEROID 2) trial: Protocol for a secondary Bayesian analysis.

Abstract: Background Coronavirus disease 2019 (COVID-19) can lead to severe hypoxic respiratory failure and death. Corticosteroids decrease mortality in severely or critically ill patients with COVID-19. However, the optimal dose remains unresolved. The ongoing randomised COVID STEROID 2 trial investigates the effects of higher vs lower doses of dexamethasone (12 vs 6 mg intravenously daily for up to 10 days) in 1,000 adult patients with COVID-19 and severe hypoxia. Methods This protocol outlines the rationale and statistical methods for a secondary, pre-planned Bayesian analysis of the primary outcome (days alive without life support at day 28) and all secondary outcomes registered up to day 90. We will use hurdle-negative binomial models to estimate the mean number of days alive without life support in each group and present results as mean differences and incidence rate ratios with 95% credibility intervals (CrIs). Additional count outcomes will be analysed similarly and binary outcomes will be analysed using logistic regression models with results presented as probabilities, relative risks and risk differences with 95% CrIs. We will present probabilities of any benefit/harm, clinically important benefit/harm and probabilities of effects smaller than pre-defined clinically minimally important differences for all outcomes analysed. Analyses will be adjusted for stratification variables and conducted using weakly informative priors supplemented by sensitivity analyses using sceptic priors. Discussion This secondary, pre-planned Bayesian analysis will supplement the primary, conventional analysis and may help clinicians, researchers and policymakers interpret the results of the COVID STEROID 2 trial while avoiding arbitrarily dichotomised interpretations of the results. Trial registration ClinicalTrials.gov: NCT04509973; EudraCT: 2020-003363-25.

Glycemic lability index and mortality in critically ill patients - a multicenter cohort study.

Abstract: BACKGROUND: Emerging evidence indicates a relationship between glycemic variability during intensive care unit (ICU) admission and death. We assessed whether mean glucose, hypoglycemia occurrence, or premorbid glycemic control modified this relationship. METHODS: In this retrospective, multicenter cohort study, we included adult patients admitted to five ICUs in Australia and Sweden with available preadmission glycated hemoglobin A1c (HbA1c) and three or more glucose readings. We calculated the glycemic lability index (GLI), a measure of glycemic variability, and the time-weighted average blood glucose (TWA-BG) from all glucose readings. We used logistic regression analysis with adjustment for hypoglycemia and admission characteristics to assess the independent association of GLI (above vs. below cohort median) and TWA-BG (above vs. below cohort median) with hospital mortality. RESULTS: Among 2305 patients, 859 (37%) had diabetes, median GLI was 40 [mmol/L]2 /h/week, median TWA-BG was 8.2 mmol/L, 171 (7%) developed hypoglycemia, and 371 (16%) died. The adjusted odds ratio for death was 1.61 (95% CI, 1.19-2.15; P = .002) for GLI above versus below median and 1.06 (95% CI, 0.80-1.41; P = .67) for TWA-BG above versus below median. The relationship between GLI and mortality was not modified by TWA-BG (P [interaction] = 0.66), a history of diabetes (P [interaction] = 0.89) or by HbA1c ≥52 mmol/mol (vs. <52 mmol/mol) (P [interaction] = 0.29). CONCLUSION: In adult patients admitted to an ICU in Sweden and Australia, a high GLI was associated with increased hospital mortality irrespective of the level of mean glycemia, hypoglycemia occurrence, or premorbid glycemic control. These findings support the assessment of interventions to reduce glycemic variability during critical illness.

Early post-operative nausea and vomiting: A retrospective observational study of 2030 patients.

Abstract: BACKGROUND The overall risk of post-operative nausea and vomiting (PONV) after general anaesthesia is reportedly 20%-40%. The first episode of PONV may occur early in the post-anaesthesia care unit (PACU) or later at the ward or after discharge at home in an ambulatory setting. This study aimed to investigate and describe the risk of early PONV in a PACU, and we hypothesised that patients and perioperative factors were associated with early PONV. METHODS This single-centre retrospective observational study was conducted in a Swedish county hospital from January to June 2017 and included adult patients who underwent surgical procedures under general anaesthesia. Perioperative data were obtained by reviewing the local registry for surgical procedures, medical records and anaesthesia and post-operative charts. Early PONV was defined as PONV occurring up to 4 hours post-operatively at the PACU. Any notification in the medical records, perioperative charts or the registry regarding nausea, vomiting or PONV treatment was regarded as PONV. Univariate and multivariate analyses were performed for factors associated with early PONV. RESULTS A total of 2030 patients were included in the study, of which 9.6% (n = 194) experienced early PONV. Factors associated with a high risk of early PONV were suboptimal PONV prophylaxis, need for opioids, female sex, body mass index >35 kg m-2 and major surgery and anaesthesia time ≥60 minutes. CONCLUSION We found that every 10th patient under general anaesthesia experienced early PONV. Suboptimal PONV prophylaxis and previously acknowledged risk factors for PONV were associated with early PONV.

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

Abstract: 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.

Chronic post-operative opioid use after open cardiac surgery: A Danish population-based cohort study.

Abstract: Background Knowledge of chronic opioid use after cardiac surgery is sparse. We therefore aimed to describe the proportion of new chronic post-operative opioid use after open cardiac surgery. Methods We used prospectively registered data from a national prescription registry and a clinical registry of 29 815 first-time cardiac surgeries from three Danish university hospitals. Data collection spanned from 2003 to 2016. The main outcome was chronic post-operative opioid use, defined as at least one opioid dispensing in the fourth post-operative quarter. Data were assessed for patient-level predictors of chronic post-operative opioid use, including pre-operative opioid use, opioid use at discharge, comorbidities, and procedural related variables. Results The overall proportion of post-operative opioid use was 10.6% (95% CI: 10.2-10.9). The proportion of new chronic post-operative opioid use was 5.7% (95% CI: 5.5-6.0) among pre-operative opioid naive patients. The corresponding proportions among patients, who pre-operatively used low or high dose opioid (1-500 mg or > 500 mg cumulative morphine equivalent opioid), were 68.3% (95% CI: 66.1-70.4) and 76.3% (95% CI: 74.0-78.5) respectively. Risk factors associated with new chronic post-operative opioid use included: female gender, underweight and obesity, pre-operative comorbidities, acute surgery, ICU-time > 1 day, and post-operative complications. Strongest predictor of chronic post-operative opioid use was post-discharge use of opioid within one month after surgery (odds ratio 3.3, 95% CI: 2.8-4.0). Conclusion New chronic post-operative opioid use after open cardiac surgery is common. Focus on post-discharge opioid use may help clinicians to reduce rates of new chronic opioid users.

A novel digital clock drawing test as a screening tool for perioperative neurocognitive disorders: A feasibility study

Abstract: Background We developed a digital clock drawing test (dCDT), an adaptation of the original pen and paper clock test, that may be advantageous over previous dCDTs in the perioperative environment. We trialed our dCDT on a tablet device in the preoperative period to determine the feasibility of administration in this setting. To assess the clinical utility of this test, we examined the relationship between the performance on the test and compared derived digital clock measures with the 4 A's Test (4AT), a delirium and cognition screening tool. Methods We recruited a sample of 102 adults aged 65 years and over presenting for elective surgery in a single tertiary hospital. Participants completed the 4AT, followed by both command and copy clock conditions of the dCDT. We recorded time-based clock-drawing metrics, alongside clock replications scored using the Montreal Cognitive Assessment (MoCA) clock scoring criteria. Results The dCDT had an acceptance rate of 99%. After controlling for demographic variables and prior tablet use, regression analyses showed higher 4AT scores were associated with greater dCDT time (seconds) for both command (β = 8.2, P = .020) and copy clocks (β = 12, P = .005) and lower MoCA-based clock scores in both command (OR = 0.19, P = .001) and copy conditions (OR = 0.14, P = .012). Conclusion The digital clock drawing test is feasible to administer and is highly acceptable to older adults in a preoperative setting. We demonstrated a significant association between both the dCDT time and clock score metrics, with the established 4AT. Our results provide convergent validity of the dCDT in the preoperative setting.

Interpreting the results of clinical trials, embracing uncertainty: A Bayesian approach.

Abstract: Most clinical trials use null hypothesis significance testing with frequentist statistical inference to report P values and confidence intervals for effect estimates. This method leads to a dichotomisation of results as 'significant' or 'non-significant'. A more nuanced interpretation may often be considered and in particular when the majority of the confidence interval for the effect estimate suggests benefit or harm. In contrast to the frequentist dichotomised approach based on a P value, the application of Bayesian statistics allocates credibility to a continuous spectrum of possibilities and for this reason a Bayesian approach to inference is often warranted as it will incorporate uncertainty when updating our current belief with information from a new trial. The use of Bayesian statistics is introduced in this paper for a hypothetical sepsis trial with worked examples in the R language for Statistical Computing environment and the open-source statistical software JASP. It is hoped that this general introduction to Bayesian inference stimulates some interest and confidence among clinicians to consider applying these methods to the interpretation of new evidence for interventions relevant to anaesthesia and intensive care medicine.

Evaluation of the factors related to difficult ultrasound-guided radial artery catheterization in small children: A prospective observational study.

Abstract: BACKGROUND Although ultrasound guidance has significantly improved the success rate of radial artery catheterization, the failure rate in children is still high. For the further improvement of success rate, we prospectively evaluated the factors that make ultrasound-guided radial artery catheterization difficult in children under two years old. METHODS From October 2018 to September 2019, patients who required radial artery catheterization for surgery were enrolled. After collecting the anatomical characteristics of the radial artery using ultrasound at the puncture site, ultrasound-guided radial artery catheterization was performed by one experienced anaesthesiologist. The primary outcome was to identify the factors related to the first attempt failure. The factors associated with the total duration of the procedure until success were also evaluated. RESULTS A total of 183 children were included in the analysis. A radial artery cross-sectional area of ≤1 mm2 (odds ratio [OR] = 5.26; 95% confidence interval [CI], 2.48-11.18; P < .0001) and the presence of an anomalous radial artery branch (OR = 3.37; 95% CI, 1.43-7.95; P = .005) were independent predictors of first-attempt failure during ultrasound-guided radial artery catheterization. The total procedure time was also negatively associated with the small cross-sectional area (P < .001). CONCLUSIONS A cross-sectional area of ≤ 1 mm2 and the presence of an anomalous branch of radial artery significantly increased the difficulty of ultrasound-guided radial artery catheterization in children under two years old. In patients of these ages, pre-procedural ultrasound scanning to find an optimal site for catheterization may increase the first-attempt success rate although further studies are needed to verify our results. TRIAL REGISTRATION Clinical Research Information Service (https://crits.nih.go.kr, October 6, 2018 [KCT0003239]; Principle investigator: Jong-Hwan Lee).

Motor blockade after iliopsoas plane (IPB) and pericapsular nerve group (PENG) blocks: A little may go a long way.

Abstract: We read with interest the article by Nielson et al.1 describing the iliopsoas plane block (IPB), targeting the sensory hip articular branches of the femoral nerve without causing motor blockade. We applaud this group on the development2,3 of this clinically relevant technique. The authors also discuss the pericapsular nerve group (PENG) block as a reasonable alternative.1,4 In our clinical practice we have utilized PENG blocks extensively and have observed excellent analgesia for various hip surgeries. We have previously reported several cases of inadvertent motor blockade using the PENG block in patients undergoing total hip arthroplasty.5 Possible explanations of inadvertent motor blockade include technical issues, specifically injecting local anesthetic superficial to the iliopsoas plane or medial to the psoas tendon and performing the block postoperatively within disrupted tissue planes.3 Subsequent to this publication we have had additional cases of quadriceps motor weakness despite the PENG block being performed by experienced staff and taking precautions outlined by Girón-Arango et al.6 This has led to reduced usage of the PENG block in our institution. We suggest that randomized controlled clinical trials be performed to further assess the effectiveness and adverse effects of the PENG block.

Validation of the Hospital Frailty Risk Score in older surgical patients: A population-based retrospective cohort study

Abstract: BACKGROUND There is a need for standardized and cost-effective identification of frailty risk. The objective was to validate the Hospital Frailty Risk Score which utilizes International Classification Diagnoses in a cohort of older surgical patients, assess the score as an independent risk factor for adverse outcomes and compare discrimination properties of the frailty risk score with other risk stratification scores. METHODS Data were analysed from all patients ≥65 years undergoing primary surgical procedures from 2006-2018. Patients were categorized based on the frailty risk score. The primary outcomes were 30-day mortality and 180-day risk of readmission. RESULTS Of 16 793 patients evaluated, 7480 (45%), 7605 (45%) and 1708 (10%) had a low, intermediate and high risk of frailty. There was a higher incidence of 30-day mortality for individuals with intermediate (2.9%) and high (8.3%) compared with low (1.4%) risk of frailty (P < .001 for both comparisons). Similarly, the hazard of readmission within the first 180 days was higher for intermediate (HR 1.25; 95% CI: 1.16-1.34) and high (HR 1.84; 95% CI: 1.66-2.03) compared with low (HR 1.00, P < .001 for both comparisons) risk of frailty. The hazard of long-term mortality was higher for intermediate (HR 1.70; 95% CI: 1.61-1.80) and high (HR 4.16; 95% CI: 3.84-4.49) compared with low (HR 1.00, P < .001 for both comparisons) risk of frailty. Finally, long length of primary hospitalization occurred for 9.3%, 15.0% and 27.3% of individuals with low, intermediate and high frailty risk (P < .001 for all comparisons). A model including age and ASA classification had the best discrimination for 30-day mortality (AUC 0.862; 95% CI: 0.847-0.877). CONCLUSION Our findings suggest that the Hospital Frailty Risk Score might be used to screen older surgical patients for risk of frailty. While only slightly improving prediction of 30-day mortality using the ASA classification, the Hospital Frailty Risk Score can be used to independently classify older patients for the risk of important outcomes using pre-existing readily available electronic data.