Lower vs Higher Oxygenation Target and Days Alive Without Life Support in COVID-19: The HOT-COVID Randomized Clinical Trial.

Importance: Supplemental oxygen is ubiquitously used in patients with COVID-19 and severe hypoxemia, but a lower dose may be beneficial. Objective: To assess the effects of targeting a Pao2 of 60 mm Hg vs 90 mm Hg in patients with COVID-19 and severe hypoxemia in the intensive care unit (ICU). Design, Setting, and Participants: Multicenter randomized clinical trial including 726 adults with COVID-19 receiving at least 10 L/min of oxygen or mechanical ventilation in 11 ICUs in Europe from August 2020 to March 2023. The trial was prematurely stopped prior to outcome assessment due to slow enrollment. End of 90-day follow-up was June 1, 2023. Interventions: Patients were randomized 1:1 to a Pao2 of 60 mm Hg (lower oxygenation group; n = 365) or 90 mm Hg (higher oxygenation group; n = 361) for up to 90 days in the ICU. Main Outcomes and Measures: The primary outcome was the number of days alive without life support (mechanical ventilation, circulatory support, or kidney replacement therapy) at 90 days. Secondary outcomes included mortality, proportion of patients with serious adverse events, and number of days alive and out of hospital, all at 90 days. Results: Of 726 randomized patients, primary outcome data were available for 697 (351 in the lower oxygenation group and 346 in the higher oxygenation group). Median age was 66 years, and 495 patients (68%) were male. At 90 days, the median number of days alive without life support was 80.0 days (IQR, 9.0-89.0 days) in the lower oxygenation group and 72.0 days (IQR, 2.0-88.0 days) in the higher oxygenation group (P = .009 by van Elteren test; supplemental bootstrapped adjusted mean difference, 5.8 days [95% CI, 0.2-11.5 days]; P = .04). Mortality at 90 days was 30.2% in the lower oxygenation group and 34.7% in the higher oxygenation group (risk ratio, 0.86 [98.6% CI, 0.66-1.13]; P = .18). There were no statistically significant differences in proportion of patients with serious adverse events or in number of days alive and out of hospital. Conclusion and Relevance: In adult ICU patients with COVID-19 and severe hypoxemia, targeting a Pao2 of 60 mm Hg resulted in more days alive without life support in 90 days than targeting a Pao2 of 90 mm Hg. Trial Registration: ClinicalTrials.gov Identifier: NCT04425031.

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.

Anesthesiologists' skills in emergency cricothyroidotomy mandate a brush-up training after 3 months-A randomized controlled trial.

BACKGROUND: In the Difficult Airway Society's 2015 "cannot intubate, cannot oxygenate" guideline, the emergency cricothyroidotomy is the final option when managing an unanticipated difficult airway. How often training for maintenance of this skill is required for anesthesiologists remains unknown. We aimed to assess if specialist-trained anesthesiologists' skills improved from a brush-up intervention and if skills were retained after 3 months. METHODS: In this multicenter, randomized, controlled trial, participants were randomized to either a simulation-based brush-up or no brush-up. Both groups performed a mannequin-based technical skills emergency cricothyroidotomy test twice and were assessed by a blinded rater using a structured assessment tool that included time, positioning, palpation, appropriate employment of instruments, and stepwise progression. After 3 months of non-training, participants completed identical tests of retention. RESULTS: A total of 54 anesthesiologists were included from three hospitals in the Region of Southern Denmark. Thirty-seven percent of the participants had received skills training in emergency cricothyroidotomy in the prior 12 months. The intervention group (N = 27) performed better in the initial tests, with a mean time of 51.5 s (SD = 10.82), a total score per minute of 15.9 points (SD = 4.91), and 93% passing both initial tests compared to the control group (N = 27) with a mean time of 76.8 s (SD = 35.82), a total score per minute of 6.6 (SD = 4.68) and only 15% passing both initial tests. The intervention group managed to retain overall performance in retention tests in terms of performance time (48.9 s, p = .26), total score per minute (13.6 points, p = .094), and passing the tests (75%, p = .059). CONCLUSION: Exposure to simulation-based brush-up training in emergency cricothyroidotomy improved anesthesiologists' technical performance and was overall retained after 3 months. Some loss of skill concerning specific items was observed, highlighting the need for regular training in emergency cricothyroidotomy. Simulation-based training should be prioritized to improve and maintain technical skills in infrequent high-stakes procedures.

"Gives peace of mind" - Relatives' perspectives of end-of-life conversations.

OBJECTIVES: Planning for end-of-life (EOL) and future treatment and care through advance care planning (ACP) is being increasingly implemented in different healthcare settings, and interest in ACP is growing. Several studies have emphasized the importance of relatives participating in conversations about wishes for EOL and being included in the process. Likewise, research has highlighted how relatives can be a valuable resource in an emergency setting. Although relatives have a significant role, few studies have investigated their perspectives of ACP and EOL conversations. This study explores relatives' experiences of the benefits and disadvantages of having conversations about wishes for EOL treatment. METHODS: Semi-structured telephone interviews were held with 29 relatives who had participated in a conversation about EOL wishes with a patient and physician 2 years prior in a variety of Danish healthcare settings. The relatives were interviewed between September 2020 and June 2022. Content analysis was performed on the qualitative data. RESULTS: The interviews revealed two themes: "gives peace of mind" and "enables more openness and common understanding of EOL." Relatives found that conversations about EOL could help assure that patients were heard and enhance their autonomy. These conversations relieved the relatives of responsibility by clarifying or confirming the patients' wishes, and they also made the relatives reflect on their own wishes for EOL. Moreover, they helped patients and relatives address other issues regarding EOL and made wishes more visible across settings. SIGNIFICANCE OF RESULTS: The results indicate that conducting conversations about wishes for EOL treatment and having relatives participate in those conversations were perceived as beneficial for both relatives and patients. Involving relatives in ACP should be prioritized by physicians and healthcare personnel when holding conversations about EOL.

Platform trials.

Platform trials focus on the perpetual testing of many interventions in a disease or a setting. These trials have lasting organizational, administrative, data, analytic, and operational frameworks making them highly efficient. The use of adaptation often increases the probabilities of allocating participants to better interventions and obtaining conclusive results. The COVID-19 pandemic showed the potential of platform trials as a fast and valid way to improved treatments. This review gives an overview of key concepts and elements using the Intensive Care Platform Trial (INCEPT) as an example.

Long-term outcomes in COVID-19 patients admitted to intensive care in Denmark: A nationwide observational study.

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.

Routine Versus On-Demand Blood Sampling in Critically Ill Patients: A Systematic Review.

OBJECTIVES: We aimed to provide an overview of the current evidence on routine versus on-demand blood sampling in critical care. We assessed the reported proportion of patients exposed to daily routine blood sampling, the tests performed, characteristics associated with more frequent blood sampling, and the reported benefits and harms of routine blood sampling compared with on-demand sampling. DATA SOURCES: We systematically searched the Cochrane Library, the Excerpta Medica Database, and the Medical Literature Analysis and Retrieval System Online for studies assessing routine versus on-demand blood testing in critically ill patients from inception to September 2022. STUDY SELECTION: Abstracts and full texts were assessed independently and in duplicate by two reviewers. STUDY EXTRACTION: Data were extracted independently and in duplicate by two reviewers using predefined extraction forms. DATA SYNTHESIS: Of 12,212 records screened, 298 full-text articles were assessed for eligibility. We included 70 studies; 50 nonrandomized interventional studies and 20 observational studies. Exposure to routine blood testing was 52-100% (very low certainty of evidence). Blood testing seemed to occur more frequently in medical intensive care settings with a median of 18 blood tests per patient day (interquartile range, 10-33) (very low certainty of evidence). Mixed biochemistry seemed to be the most frequently performed blood tests across all settings (five tests per patient day; interquartile range, 2-10) (very low certainty of evidence). Reductions in routine blood testing seemed to be associated with reduced transfusion rates and costs without apparent adverse patient outcomes (low certainty of evidence). CONCLUSIONS: In this systematic review, routine blood testing in critically ill patients was common and varied considerably. A reduction in routine blood testing appeared to be associated with reduced transfusion rates and costs without adverse effects, but the evidence was very uncertain.

Goal-directed fluid removal with furosemide versus placebo in intensive care patients with fluid overload: A randomised, blinded trial (GODIF trial-First version).

BACKGROUND: Salt and water accumulation leading to fluid overload is associated with increased mortality in intensive care unit (ICU) patients, but diuretics' effects on patient outcomes are uncertain. In this first version of the GODIF trial, we aimed to assess the effects of goal-directed fluid removal with furosemide versus placebo in adult ICU patients with fluid overload. METHODS: We conducted a multicentre, randomised, stratified, parallel-group, blinded, placebo-controlled trial in clinically stable, adult ICU patients with at least 5% fluid overload. Participants were randomised to furosemide versus placebo infusion aiming at achieving neutral cumulative fluid balance as soon as possible. The primary outcome was the number of days alive and out of the hospital at 90 days. RESULTS: The trial was terminated after the enrolment of 41 of 1000 participants because clinicians had difficulties using cumulative fluid balance as the only estimate of fluid status (32% of participants had their initially registered cumulative fluid balance adjusted and 29% experienced one or more protocol violations). The baseline cumulative fluid balance was 6956 ml in the furosemide group and 6036 ml in the placebo group; on day three, the cumulative fluid balances were 1927 ml and 5139 ml. The median number of days alive and out of hospital at day 90 was 50 days in the furosemide group versus 45 days in the placebo group (mean difference 1 day, 95% CI -19 to 21, p-value .94). CONCLUSIONS: The use of cumulative fluid balance as the only estimate of fluid status appeared too difficult to use in clinical practice. We were unable to provide precise estimates for any outcomes as only 4.1% of the planned sample size was randomised.

Presence of the partner in the operating room during emergency caesarean section: A scoping review.

BACKGROUND: Emergency caesarean sections are often very urgent, with limited time for informing and guiding parents. Is it preferable to leave the partner outside of the operating room, or let the partner accompany the mother? OBJECTIVE: This review aimed to provide an overview of the available evidence regarding the presence of the partner in the operating room during emergency caesarean sections. DESIGN: Scoping review. DATA SOURCES: A systematic literature search was performed in PubMed, Embase, Cinahl and the Cochrane Library. ELIGIBILITY CRITERIA: All published literature reporting on emergency caesarean sections in regional or general anaesthesia with the partner present in the operating room were eligible, no matter the design. RESULTS: Twenty-four titles, published between 1984 and 2020, were included; 15 contained original clinical findings and 9 were letters/debates. Quality of evidence was assessed using the Mixed Methods Appraisal Tool and found to be very low/low (17 studies), moderate (6) or good (1). Studies originated from Europe (16 studies), USA/Canada (4), South America (2), Asia (1) and Africa (1). Content data were thematically summarised and were overall either in favour or against having the partner present. Staff seemed reluctant to let partners be present for caesarean sections under general anaesthesia; mothers and partners preferred the partners' presence. Under regional anaesthesia, parents also wished for the partners' presence and described the caesarean section under regional anaesthesia as a predominantly positive experience. Most staff had a favourable attitude towards letting the partner be present for caesarean sections under regional anaesthesia. CONCLUSION: Limited evidence exists regarding the presence of the partner during emergency caesarean sections, but is of low quality. Most parents prefer having their partner present. Staff can be reluctant, especially when general anaesthesia is used.

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.

Changes over time in characteristics, resource use and outcomes among ICU patients with COVID-19-A nationwide, observational study in Denmark.

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.

Long-term cognitive and functional status in Danish ICU patients with COVID-19.

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.

Restriction of Intravenous Fluid in ICU Patients with Septic Shock.

BACKGROUND: Intravenous fluids are recommended for the treatment of patients who are in septic shock, but higher fluid volumes have been associated with harm in patients who are in the intensive care unit (ICU). METHODS: In this international, randomized trial, we assigned patients with septic shock in the ICU who had received at least 1 liter of intravenous fluid to receive restricted intravenous fluid or standard intravenous fluid therapy; patients were included if the onset of shock had been within 12 hours before screening. The primary outcome was death from any cause within 90 days after randomization. RESULTS: We enrolled 1554 patients; 770 were assigned to the restrictive-fluid group and 784 to the standard-fluid group. Primary outcome data were available for 1545 patients (99.4%). In the ICU, the restrictive-fluid group received a median of 1798 ml of intravenous fluid (interquartile range, 500 to 4366); the standard-fluid group received a median of 3811 ml (interquartile range, 1861 to 6762). At 90 days, death had occurred in 323 of 764 patients (42.3%) in the restrictive-fluid group, as compared with 329 of 781 patients (42.1%) in the standard-fluid group (adjusted absolute difference, 0.1 percentage points; 95% confidence interval [CI], -4.7 to 4.9; P = 0.96). In the ICU, serious adverse events occurred at least once in 221 of 751 patients (29.4%) in the restrictive-fluid group and in 238 of 772 patients (30.8%) in the standard-fluid group (adjusted absolute difference, -1.7 percentage points; 99% CI, -7.7 to 4.3). At 90 days after randomization, the numbers of days alive without life support and days alive and out of the hospital were similar in the two groups. CONCLUSIONS: Among adult patients with septic shock in the ICU, intravenous fluid restriction did not result in fewer deaths at 90 days than standard intravenous fluid therapy. (Funded by the Novo Nordisk Foundation and others; CLASSIC ClinicalTrials.gov number, NCT03668236.).

Oxygenation targets in ICU patients with COVID-19: A post hoc subgroup analysis of the HOT-ICU trial.

BACKGROUND: Supplemental oxygen is the key intervention for severe and critical COVID-19 patients. With the unstable supplies of oxygen in many countries, it is important to define the lowest safe dosage. METHODS: In spring 2020, 110 COVID-19 patients were enrolled as part of the Handling Oxygenation Targets in the ICU trial (HOT-ICU). Patients were allocated within 12 h of ICU admission. Oxygen therapy was titrated to a partial pressure of arterial oxygen (PaO2 ) of 8 kPa (lower oxygenation group) or a PaO2 of 12 kPa (higher oxygenation group) during ICU stay up to 90 days. We report key outcomes at 90 days for the subgroup of COVID-19 patients. RESULTS: At 90 days, 22 of 54 patients (40.7%) in the lower oxygenation group and 23 of 55 patients (41.8%) in the higher oxygenation group had died (adjusted risk ratio: 0.87; 95% confidence interval, 0.58-1.32). The percentage of days alive without life support was significantly higher in the lower oxygenation group (p = 0.03). The numbers of severe ischemic events were low with no difference between the two groups. Proning and inhaled vasodilators were used more frequently, and the positive end-expiratory pressure was higher in the higher oxygenation group. Tests for interactions with the results of the remaining HOT-ICU population were insignificant. CONCLUSIONS: Targeting a PaO2 of 8 kPa may be beneficial in ICU patients with COVID-19. These results come with uncertainty due to the low number of patients in this unplanned subgroup analysis, and insignificant tests for interaction with the main HOT-ICU trial. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov number, NCT03174002. Date of registration: June 2, 2017.

Long-term cognitive and pulmonary functions following a lower versus a higher oxygenation target in the HOT-ICU trial: protocol and statistical analysis plan.

BACKGROUND: Although supplemental oxygen can be lifesaving, liberal oxygen administration causing hyperoxaemia may be harmful. The targets for oxygenation in patients with acute hypoxaemic respiratory failure acutely admitted to the intensive care unit (ICU) are strongly debated, and consensus on which targets to recommend has not been reached. The Handling Oxygenation Targets in the ICU (HOT-ICU) trial is a multicentre, randomised, parallel-group trial of a lower oxygenation target (arterial partial pressure of oxygen [PaO2 ] = 8 kPa) versus a higher oxygenation target (PaO2  = 12 kPa) in adult ICU patients with acute hypoxaemic respiratory failure. In this study, we aim to evaluate the effects of these targets on long-term cognitive and pulmonary function in Danish patients, enrolled in the HOT-ICU trial and surviving to 1-year follow-up. We hypothesise that a lower oxygenation target throughout the ICU stay may result in cognitive impairment, whereas a higher oxygenation target may result in impaired pulmonary function. METHODS: All patients enrolled in the HOT-ICU trial at Danish sites and surviving to 1 year after randomisation are eligible to participate. The last patient is expected to be included by November 2021. A Repeatable Battery for the Assessment of Neuropsychological Status and a body plethysmography, including diffusion capacity for carbon monoxide, both pre-planned secondary long-term outcomes of the HOT-ICU trial, will be obtained. CONCLUSION: This study will provide important information on the long-term effects of a lower versus a higher oxygenation target on cognitive and pulmonary function in adult ICU patients with acute hypoxaemic respiratory failure.

Facilitators and Barriers for Initiating Conversations About End of Life.

Background: Conducting a conversation about wishes for treatment at end of life (EOL) has been shown to improve EOL care for patients and relatives. Still, only a minority of physicians conduct the conversation, which might lead to unwanted interventions and treatments. Objectives: The purpose of this survey was to examine which factors facilitate and hinder physicians across a wide range of health care facilities to initiate the conversation about wishes for treatment at EOL. Design: A questionnaire survey based on a Delphi-developed questionnaire. Setting/Subjects: The questionnaire was sent to both hospital physicians and general practitioners (GPs) in a Danish region. Results: More than 3000 physicians were invited to participate in the survey. Of these, 782 responded, 622 working at a hospital department, and 160 from general practice clinics. Results showed that senior physicians, GPs, and physicians working in a medical department feel best equipped to conduct the conversation. Moreover, senior physicians pointed to their experience as physicians as being of great importance for conducting the conversation, whereas junior physicians found training in conducting the conversation as an important factor. Conclusion: Our study indicates that different factors depending on the health care setting and the seniority of the physician facilitate or hinder physicians from conducting the conversation about wishes for treatment at EOL. Being aware of these differences and making a concerted effort depending on setting and seniority might help implement and conduct the conversation.

Effect of 12 mg vs 6 mg of Dexamethasone on the Number of Days Alive Without Life Support in Adults With COVID-19 and Severe Hypoxemia: The COVID STEROID 2 Randomized Trial.

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.

Lower or Higher Oxygenation Targets for Acute Hypoxemic Respiratory Failure.

BACKGROUND: Patients with acute hypoxemic respiratory failure in the intensive care unit (ICU) are treated with supplemental oxygen, but the benefits and harms of different oxygenation targets are unclear. We hypothesized that using a lower target for partial pressure of arterial oxygen (Pao2) would result in lower mortality than using a higher target. METHODS: In this multicenter trial, we randomly assigned 2928 adult patients who had recently been admitted to the ICU (≤12 hours before randomization) and who were receiving at least 10 liters of oxygen per minute in an open system or had a fraction of inspired oxygen of at least 0.50 in a closed system to receive oxygen therapy targeting a Pao2 of either 60 mm Hg (lower-oxygenation group) or 90 mm Hg (higher-oxygenation group) for a maximum of 90 days. The primary outcome was death within 90 days. RESULTS: At 90 days, 618 of 1441 patients (42.9%) in the lower-oxygenation group and 613 of 1447 patients (42.4%) in the higher-oxygenation group had died (adjusted risk ratio, 1.02; 95% confidence interval, 0.94 to 1.11; P = 0.64). At 90 days, there was no significant between-group difference in the percentage of days that patients were alive without life support or in the percentage of days they were alive after hospital discharge. The percentages of patients who had new episodes of shock, myocardial ischemia, ischemic stroke, or intestinal ischemia were similar in the two groups (P = 0.24). CONCLUSIONS: Among adult patients with acute hypoxemic respiratory failure in the ICU, a lower oxygenation target did not result in lower mortality than a higher target at 90 days. (Funded by the Innovation Fund Denmark and others; HOT-ICU ClinicalTrials.gov number, NCT03174002.).

Post-Hypoxic Myoclonus Status following Out-of-Hospital Cardiac Arrest-Does It still Predict a Poor Outcome? A Retrospective Study.

In patients with out-of-hospital cardiac arrest (OHCA), the initial prehospital treatment and transfer of patients directly to intervention clinics-bypassing smaller hospitals-have improved outcomes in recent years. Despite the improved treatment strategies, some patients develop myoclonic status following OHCA, and this phenomenon is usually considered an indicator of poor outcome. With this study, we wanted to challenge this perception. The regional prehospital database in Odense in the Region of Southern Denmark was searched for patients with OHCA from the period of 2011-2016. All 900 patients presenting with a diagnosis of OHCA were included in the study. Patients surviving to the hospital and presenting with myoclonic status were followed for up to one year. Only 2 out of 38 patients with myoclonic status and status epilepticus verified by an EEG survived more than one year. Eleven out of 36 patients with myoclonic status but without status epilepticus survived for more than one year. We found no evidence that myoclonic status is an unmistakable sign of poor outcome when not associated with EEG-verified status epilepticus. The conclusion for clinicians involved in post-resuscitation care is that myoclonic status is uncomfortable to witness but does not necessarily indicate that further treatment is futile.

Long-term patient-important outcomes after septic shock: A protocol for 1-year follow-up of the CLASSIC trial.

BACKGROUND: In patients with septic shock, mortality is high, and survivors experience long-term physical, mental and social impairments. The ongoing Conservative vs Liberal Approach to fluid therapy of Septic Shock in Intensive Care (CLASSIC) trial assesses the benefits and harms of a restrictive vs standard-care intravenous (IV) fluid therapy. The hypothesis is that IV fluid restriction improves patient-important long-term outcomes. AIM: To assess the predefined patient-important long-term outcomes in patients randomised into the CLASSIC trial. METHODS: In this pre-planned follow-up study of the CLASSIC trial, we will assess all-cause mortality, health-related quality of life (HRQoL) and cognitive function 1 year after randomisation in the two intervention groups. The 1-year mortality will be collected from electronic patient records or central national registries in most participating countries. We will contact survivors and assess EuroQol 5-Dimension, -5-Level (EQ-5D-5L) and EuroQol-Visual Analogue Scale and Montreal Cognitive Assessment 5-minute protocol score. We will analyse mortality by logistic regression and use general linear models to assess HRQoL and cognitive function. DISCUSSION: With this pre-planned follow-up study of the CLASSIC trial, we will provide patient-important data on long-term survival, HRQoL and cognitive function of restrictive vs standard-care IV fluid therapy in patients with septic shock.