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BACKGROUND: Among ICU patients with COVID-19, it is largely unknown how the overall outcome and resource use have changed with time, different genetic variants, and vaccination status. METHODS: For all Danish ICU patients with COVID-19 from March 10, 2020 to March 31, 2022, we manually retrieved data on demographics, comorbidities, vaccination status, use of life support, length of stay, and vital status from medical records. We compared patients based on the period of admittance and vaccination status and described changes in epidemiology related to the Omicron variant. RESULTS: Among all 2167 ICU patients with COVID-19, 327 were admitted during the first (March 10-19, 2020), 1053 during the second (May 20, 2020 to June 30, 2021) and 787 during the third wave (July 1, 2021 to March 31, 2022). We observed changes over the three waves in age (median 72 vs. 68 vs. 65 years), use of invasive mechanical ventilation (81% vs. 58% vs. 51%), renal replacement therapy (26% vs. 13% vs. 12%), extracorporeal membrane oxygenation (7% vs. 3% vs. 2%), duration of invasive mechanical ventilation (median 13 vs. 13 vs. 9 days) and ICU length of stay (median 13 vs. 10 vs. 7 days). Despite these changes, 90-day mortality remained constant (36% vs. 35% vs. 33%). Vaccination rates among ICU patients were 42% as compared to 80% in society. Unvaccinated versus vaccinated patients were younger (median 57 vs. 73 years), had less comorbidity (50% vs. 78%), and had lower 90-day mortality (29% vs. 51%). Patient characteristics changed significantly after the Omicron variant became dominant including a decrease in the use of COVID-specific pharmacological agents from 95% to 69%. CONCLUSIONS: In Danish ICUs, the use of life support declined, while mortality seemed unchanged throughout the three waves of COVID-19. Vaccination rates were lower among ICU patients than in society, but the selected group of vaccinated patients admitted to the ICU still had very severe disease courses. When the Omicron variant became dominant a lower fraction of SARS-CoV-2 positive patients received COVID treatment indicating other causes for ICU admission.
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COVID-19 , Humanos , COVID-19/terapia , Cuidados Críticos , Dinamarca/epidemiologia , SARS-CoV-2 , IdosoRESUMO
BACKGROUND: Intensive care unit (ICU) patients with Coronavirus disease 2019 (COVID-19) have an increased risk of thromboembolic complications. We describe the occurrence of thromboembolic and bleeding events in all ICU patients with COVID-19 in Denmark during the first and second waves of the pandemic. METHODS: This was a sub-study of the Danish Intensive Care Covid database, in which all patients with SARS-CoV-2 admitted to Danish ICUs from 10th March 2020 to 30th June 2021 were included. We registered coagulation variables at admission, and all thromboembolic and bleeding events, and the use of heparins during ICU stay. Variables associated with thrombosis and bleeding and any association with 90-day mortality were estimated using Cox regression analyses. RESULTS: We included 1369 patients in this sub-study; 158 (12%, 95% confidence interval 10-13) had a thromboembolic event in ICU and 309 (23%, 20-25) had a bleeding event, among whom 81 patients (6%, 4.8-7.3) had major bleeding. We found that mechanical ventilation and increased D-dimer were associated with thrombosis and mechanical ventilation, low platelet count and presence of haematological malignancy were associated with bleeding. Most patients (76%) received increased doses of thromboprophylaxis during their ICU stay. Thromboembolic events were not associated with mortality in adjusted analysis (hazard ratio 1.35 [0.91-2.01, p = .14], whereas bleeding events were 1.55 [1.18-2.05, p = .002]). CONCLUSIONS: Both thromboembolic and bleeding events frequently occurred in ICU patients with COVID-19. Based on these data, it is not apparent that increased doses of thromboprophylaxis were beneficial.
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COVID-19 , Trombose , Tromboembolia Venosa , Humanos , COVID-19/complicações , SARS-CoV-2 , Anticoagulantes/efeitos adversos , Tromboembolia Venosa/epidemiologia , Cuidados Críticos , Hemorragia , Unidades de Terapia IntensivaRESUMO
BACKGROUND: ICU admission due to COVID-19 may result in cognitive and physical impairment. We investigated the long-term cognitive and physical status of Danish ICU patients with COVID-19. METHODS: We included all patients with COVID-19 admitted to Danish ICUs between March 10 and May 19, 2020. Patients were the contacted prospectively at 6 and 12 months for follow-up. Our primary outcomes were cognitive function and frailty at 6 and 12 months after ICU admission, estimated by the Mini Montreal Cognitive Assessment, and the Clinical Frailty Scale. Secondary outcomes were 6- and 12-month mortality, health-related quality of life (HRQoL) assessed by EQ-5D-5L, functional status (Barthel activities of daily living and Lawton-Brody instrumental activities of daily living), and fatigue (Fatigue Assessment Scale). The study had no information on pre-ICU admission status for the participants. RESULTS: A total of 326 patients were included. The 6- and 12-month mortality was 37% and 38%, respectively. Among the 204 six-month survivors, 105 (51%) participated in the 6-month follow-up; among the 202 twelve-month survivors, 95 (47%) participated in the 12-month follow-up. At 6 months, cognitive scores indicated impairment for 26% (95% confidence interval [CI], 11.4-12.4) and at 12 months for 17% (95% CI, 12.0-12.8) of participants. Frailty was indicated in 20% (95% CI, 3.4-3.9) at 6 months, and for 18% (95% CI, 3.3-3.8) at 12 months. Fatigue was reported by 52% at 6 months, and by 47% at 12 months. For HRQoL, moderate, severe, or extreme health problems were reported by 28% at 6 months, and by 25% at 12 months. CONCLUSION: Long-term cognitive, functional impairment was found in up to one in four of patients surviving intensive care for COVID-19. Fatigue was present in nearly half the survivors at both 6 and 12 months. However, pre-ICU admission status of the patients was unknown.
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COVID-19 , Fragilidade , Atividades Cotidianas/psicologia , COVID-19/terapia , Cognição , Dinamarca/epidemiologia , Fadiga/epidemiologia , Fragilidade/epidemiologia , Estado Funcional , Humanos , Unidades de Terapia Intensiva , Estudos Prospectivos , Qualidade de VidaRESUMO
BACKGROUND: Characteristics and care of intensive care unit (ICU) patients with COVID-19 may have changed during the pandemic, but longitudinal data assessing this are limited. We compared patients with COVID-19 admitted to Danish ICUs in the first wave with those admitted later. METHODS: Among all Danish ICU patients with COVID-19, we compared demographics, chronic comorbidities, use of organ support, length of stay and vital status of those admitted 10 March to 19 May 2020 (first wave) versus 20 May 2020 to 30 June 2021. We analysed risk factors for death by adjusted logistic regression analysis. RESULTS: Among all hospitalised patients with COVID-19, a lower proportion was admitted to ICU after the first wave (13% vs. 8%). Among all 1374 ICU patients with COVID-19, 326 were admitted during the first wave. There were no major differences in patient's characteristics or mortality between the two periods, but use of invasive mechanical ventilation (81% vs. 58% of patients), renal replacement therapy (26% vs. 13%) and ECMO (8% vs. 3%) and median length of stay in ICU (13 vs. 10 days) and in hospital (20 vs. 17 days) were all significantly lower after the first wave. Risk factors for death were higher age, larger burden of comorbidities (heart failure, pulmonary disease and kidney disease) and active cancer, but not admission during or after the first wave. CONCLUSIONS: After the first wave of COVID-19 in Denmark, a lower proportion of hospitalised patients with COVID-19 were admitted to ICU. Among ICU patients, use of organ support was lower and length of stay was reduced, but mortality rates remained at a relatively high level.
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COVID-19 , COVID-19/terapia , Dinamarca/epidemiologia , Mortalidade Hospitalar , Humanos , Unidades de Terapia Intensiva , Pandemias , Estudos Retrospectivos , SARS-CoV-2RESUMO
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.
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COVID-19/terapia , Cuidados Críticos , Idoso , COVID-19/mortalidade , Estudos de Coortes , Comorbidade , Revisão Concomitante , Demografia , Dinamarca , Feminino , Mortalidade Hospitalar , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Resultado do Tratamento , Sinais VitaisRESUMO
Importance: A daily dose with 6 mg of dexamethasone is recommended for up to 10 days in patients with severe and critical COVID-19, but a higher dose may benefit those with more severe disease. Objective: To assess the effects of 12 mg/d vs 6 mg/d of dexamethasone in patients with COVID-19 and severe hypoxemia. Design, Setting, and Participants: A multicenter, randomized clinical trial was conducted between August 2020 and May 2021 at 26 hospitals in Europe and India and included 1000 adults with confirmed COVID-19 requiring at least 10 L/min of oxygen or mechanical ventilation. End of 90-day follow-up was on August 19, 2021. Interventions: Patients were randomized 1:1 to 12 mg/d of intravenous dexamethasone (n = 503) or 6 mg/d of intravenous dexamethasone (n = 497) for up to 10 days. Main Outcomes and Measures: The primary outcome was the number of days alive without life support (invasive mechanical ventilation, circulatory support, or kidney replacement therapy) at 28 days and was adjusted for stratification variables. Of the 8 prespecified secondary outcomes, 5 are included in this analysis (the number of days alive without life support at 90 days, the number of days alive out of the hospital at 90 days, mortality at 28 days and at 90 days, and ≥1 serious adverse reactions at 28 days). Results: Of the 1000 randomized patients, 982 were included (median age, 65 [IQR, 55-73] years; 305 [31%] women) and primary outcome data were available for 971 (491 in the 12 mg of dexamethasone group and 480 in the 6 mg of dexamethasone group). The median number of days alive without life support was 22.0 days (IQR, 6.0-28.0 days) in the 12 mg of dexamethasone group and 20.5 days (IQR, 4.0-28.0 days) in the 6 mg of dexamethasone group (adjusted mean difference, 1.3 days [95% CI, 0-2.6 days]; P = .07). Mortality at 28 days was 27.1% in the 12 mg of dexamethasone group vs 32.3% in the 6 mg of dexamethasone group (adjusted relative risk, 0.86 [99% CI, 0.68-1.08]). Mortality at 90 days was 32.0% in the 12 mg of dexamethasone group vs 37.7% in the 6 mg of dexamethasone group (adjusted relative risk, 0.87 [99% CI, 0.70-1.07]). Serious adverse reactions, including septic shock and invasive fungal infections, occurred in 11.3% in the 12 mg of dexamethasone group vs 13.4% in the 6 mg of dexamethasone group (adjusted relative risk, 0.83 [99% CI, 0.54-1.29]). Conclusions and Relevance: Among patients with COVID-19 and severe hypoxemia, 12 mg/d of dexamethasone compared with 6 mg/d of dexamethasone did not result in statistically significantly more days alive without life support at 28 days. However, the trial may have been underpowered to identify a significant difference. Trial Registration: ClinicalTrials.gov Identifier: NCT04509973 and ctri.nic.in Identifier: CTRI/2020/10/028731.
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Tratamento Farmacológico da COVID-19 , Dexametasona/administração & dosagem , Glucocorticoides/administração & dosagem , Cuidados para Prolongar a Vida , Idoso , COVID-19/complicações , COVID-19/mortalidade , Dexametasona/efeitos adversos , Relação Dose-Resposta a Droga , Feminino , Glucocorticoides/efeitos adversos , Humanos , Hipóxia/etiologia , Hipóxia/terapia , Masculino , Pessoa de Meia-Idade , Micoses/etiologia , Respiração Artificial , Choque Séptico/etiologia , Método Simples-CegoRESUMO
BACKGROUND: Rhabdomyolysis-induced acute kidney injury (AKI) is a common and serious condition. We aimed to summarise the available evidence on this topic and provide recommendations according to current standards for trustworthy guidelines. METHODS: This guideline was developed using Grading of Recommendations Assessment, Development, and Evaluation (GRADE). The following preventive interventions were assessed: (a) fluids, (b) diuretics, (c) alkalinisation, (d) antioxidants, and (e) renal replacement therapy. Exclusively patient-important outcomes were assessed. RESULTS: We suggest using early rather than late fluid resuscitation (weak recommendation, very low quality of evidence). We suggest using crystalloids rather than colloids (weak recommendation, low quality of evidence). We suggest against routine use of loop diuretics as compared to none (weak recommendation, very low quality of evidence). We suggest against use of mannitol as compared to none (weak recommendation, very low quality of evidence). We suggest against routine use of any diuretic as compared to none (weak recommendation, very low quality of evidence). We suggest against routine use of alkalinisation with sodium bicarbonate as compared to none (weak recommendation, low quality of evidence). We suggest against the routine use of any alkalinisation as compared to none (weak recommendation, low quality of evidence). We suggest against routine use of renal replacement therapy as compared to none (weak recommendation, low quality of evidence). For the remaining PICO questions, no recommendations were issued. CONCLUSION: The quantity and quality of evidence supporting preventive interventions for rhabdomyolysis-induced AKI is low/very low. We were able to issue eight weak recommendations and no strong recommendations.
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Injúria Renal Aguda/prevenção & controle , Guias de Prática Clínica como Assunto , Rabdomiólise/complicações , Antioxidantes/uso terapêutico , Diuréticos/uso terapêutico , Hidratação , Humanos , Terapia de Substituição RenalRESUMO
BACKGROUND: Secondary peritonitis is a severe condition with a 20-32% reported mortality. The accepted treatment modalities are vacuum-assisted closure (VAC) or primary closure with relaparotomy on-demand (ROD). However, no randomised controlled trial has been completed to compare the two methods potential benefits and disadvantages. METHODS: This study will be a randomised controlled multicentre trial, including patients aged 18 years or older with purulent or faecal peritonitis confined to at least two of the four abdominal quadrants originating from the small intestine, colon, or rectum. Randomisation will be web-based to either primary closure with ROD or VAC in blocks of 2, 4, and 6. The primary endpoint is peritonitis-related complications within 30 or 90 days and one year after index operation. Secondary outcomes are comprehensive complication index (CCI) and mortality after 30 or 90 days and one year; quality of life assessment by (SF-36) after three and 12 months, the development of incisional hernia after 12 months assessed by clinical examination and CT-scanning and healthcare resource utilisation. With an estimated superiority of 15% in the primary outcome for VAC, 340 patients must be included. Hospitals in Denmark and Europe will be invited to participate. DISCUSSION: There is no robust evidence for choosing either open abdomen with VAC treatment or primary closure with relaparotomy on-demand in patients with secondary peritonitis. The present study has the potential to answer this important clinical question. TRIAL REGISTRATION: The study protocol has been registered at clinicaltrials.gov (NCT03932461). Protocol version 1.0, 9 January 2022.
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Laparotomia , Tratamento de Ferimentos com Pressão Negativa , Peritonite , Reoperação , Cavidade Abdominal/cirurgia , Humanos , Laparotomia/efeitos adversos , Estudos Multicêntricos como Assunto , Tratamento de Ferimentos com Pressão Negativa/efeitos adversos , Peritonite/cirurgia , Complicações Pós-Operatórias/epidemiologia , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Reoperação/efeitos adversosRESUMO
OBJECTIVES: Evaluate six commercial serological assays for detection of IgA, IgM or IgG SARS-CoV-2 antibodies in different disease severities. METHODS: Three lateral flow tests (LFTs) (Acro IgM/IgG, CTK IgM/IgG, Livzon IgM/IgG) and three ELISA assays (Euroimmun IgA and IgG, Wantai IgM) were included. Application was evaluated using samples from 57 patients with a positive SARS-CoV-2 reverse transcription polymerase chain reaction, stratified according to disease severity. Specificity was assessed using historical samples from 200 blood donors. RESULTS: While IgM LFTs failed to detect SARS-CoV-2 antibodies in 37-84% of non-hospitalised patients, the Wantai IgM ELISA detected antibodies in 79%. The Euroimmun IgG ELISA detected antibodies in 95% of non-hospitalised patients. IgA, IgM and IgG ELISA levels were initially low, increased over time, and correlated with disease severity. LFT sensitivity declined in samples taken >28 days after symptom onset/resolution. The Livzon IgG LFT had the highest specificity (98.5%), followed by the Euroimmun IgG ELISA (96.2%). The specificity for Euroimmun IgA ELISA improved (≥97.5%) using a custom cut-off value (4.0). CONCLUSIONS: The sensitive and semi-quantitative ELISA assays are most appropriate for serologic detection of SARS-CoV-2 infection in mild cases. Livzon LFT and Euroimmun ELISA had the highest specificity among the IgG assays, making them most suitable for seroprevalence studies.
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Anticorpos Antivirais/sangue , Teste Sorológico para COVID-19/métodos , COVID-19/diagnóstico , Adulto , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Masculino , Pessoa de Meia-Idade , SARS-CoV-2 , Sensibilidade e EspecificidadeRESUMO
OBJECTIVE: Necrotizing fasciitis is a difficult diagnosis with a very high mortality. However, thermal imaging has the potential to identify increasing skin temperature and rapid progression. MATERIALS AND METHODS: We used repeat photographs taken with a thermal camera to visualize changes in skin temperature over time. RESULTS: An unstable male patient presented at the emergency department. Thermal imaging showed increased skin temperature of his left foot with a rapid increase and progression in extent within 1 hour. Necrotizing fasciitis was suspected and later confirmed. CONCLUSIONS: We believe thermal imaging could be an important adjunct for the diagnosis of suspected necrotizing fasciitis. LEARNING POINTS: Necrotizing fasciitis is a difficult diagnosis to make.Thermal imaging can visualize skin temperature and thus show increased temperature and extent.Rapid identification of necrotizing fasciitis is vital for patient survival.
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INTRODUCTION: The first year following graduation from medical school is challenging as learning from books changes to workplace-based learning. Analysis and reflection on experience may ease this transition. We used Significant Event Analysis (SEA) as a tool to explore what pre-registration house officers (PRHOs) consider successful and problematic events, and to identify what problem-solving strategies they employ. MATERIAL AND METHODS: A senior house officer systematically led the PRHO through the SEA of one successful and one problematic event following a night call. The PRHO wrote answers to questions about diagnosis, what happened, how he or she contributed and what knowledge-gaining activities the PRHO would prioritise before the next call. RESULTS: By using an inductive, thematic data analysis, we identified five problem-solving strategies: non-analytical reasoning, analytical reasoning, communication with patients, communication with colleagues and professional behaviour. On average, 1.5 strategies were used in the successful events and 1.2 strategies in the problematic events. Most PRHOs were unable to suggest activities other than reading textbooks. CONCLUSION: SEA was valuable for the identification of PRHOs' problem-solving strategies in a natural setting. PRHOs should be assisted in increasing their repertoire of strategies, and they should also be helped to "learn to learn" as they were largely unable to point to new learning strategies. FUNDING: not relevant. TRIAL REGISTRATION: not relevant.
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Aprendizagem , Médicos/psicologia , Resolução de Problemas , Comunicação , Feminino , Humanos , Internato e Residência , Relações Interprofissionais , Masculino , Relações Médico-Paciente , LeituraRESUMO
The peptide AM (adrenomedullin) is stimulated by hypoxia through HIF-1 (hypoxia-inducible factor-1). The majority of human CC-RCCs (clear cell renal cell carcinomas) display mutations in the tumour suppressor protein von Hippel-Lindau, which leads to constitutively elevated HIF-1. We hypothesized that AM is increased in CC-RCC tumours and that AM is a plasma biomarker for CC-RCC. Tumours and non-malignant kidney tissue were obtained from patients that underwent unilateral nephrectomy. Blood samples were drawn at the day of surgery, 3-6 days after surgery and 4-5 weeks after surgery. AM mRNA and peptide expression in tissue and AM plasma concentration were determined. HIF-1alpha was localized in tissue by immunohistochemistry. AM mRNA was elevated in CC-RCC compared with adjacent renal cortex (6-fold, n=18; P<0.02). There was no difference in AM mRNA between cortex and non-CC-RCC tissue (n=7). AM peptide concentration was elevated in CC-RCC tissue compared with adjacent cortex (4-fold, n=6; P<0.02), whereas there was no difference between cortex and non-CC-RCC tissue (n=5). HIF-1alpha immunoreactivity was detected in the majority of cell nuclei in 76% of CC-RCC, consistent with constitutive stabilization. In non-CC-RCC, HIF-1alpha staining was focal. Before surgery there was no difference in plasma AM concentration between tumour types. Nephrectomy increased plasma AM significantly after 3-6 days and a similar pre-surgery level was observed after 4-5 weeks in both groups of tumour patients. We conclude that elevated tissue AM is a distinguishing feature of CC-RCC compared with other kidney tumours. Plasma AM is not suited as a tumour marker for this disease.