Volume status of a patient is difficult to assess clinically. Methods to measure plasma volume as well as changes in plasma volume in connection with fluid therapy are therefore valuable for research purposes and could potentially be used bedside to guide fluid therapy in individual patients. The objective of the present study was to evaluate hematocrit as a marker of changes in plasma volume and an anthropometric formula to estimate absolute plasma volume against the reference method, plasma volume measurements using radiolabeled albumin. A total of 64 postoperative patients received 10 mL/kg of albumin. The plasma volumes were measured with the reference method (radiolabeled albumin) at baseline, after 30 and 180 min. Plasma volumes were compared with plasma volumes derived from either the baseline measurements and subsequent changes in hematocrit (calibrated method) or from an anthropometric formula and subsequent hematocrit changes (anthropometric method). Bland-Altman plots were used to test agreements between methods. The mean difference in plasma volume between the anthropometric and the reference method at baseline was -0.1 mL/kg (95% CI -2.1 to 1.8) with lower and upper LOA of -18.0 and 17.0 mL/kg. The agreement remained essentially unchanged after fluid therapy (mean difference -0.1 mL/kg (95% CI -1.8 to 1.5) with LOAs of -18.0 and 17.0 mL/kg). The mean difference between the calibrated and reference methods was -0.1 mL/kg (95% CI -0.9 to 0.7) with LOAs of -9.4 and 9.2 mL/kg. The anthropometric formula yields low precision in predicting plasma volumes in postsurgical patients. Changes in hematocrit during fluid therapy cannot replace the reference method to assess changes in plasma volume in the individual patient because of the imprecision. EDITORIAL COMMENT: Clinical appreciation of plasma volume is relevant for assessing treatment where intravenous fluid resuscitation is involved. This analysis, using a reference method for plasma volume assessment, and comparing to simpler methods to estimate the same, demonstrates that there are important limitations with some simpler and readily acceptable methods to perform this estimation.

OBJECTIVES:This is a protocol for a Cochrane review (intervention). The objectives are as follows: The primary objective of this review is to evaluate the benefits and harms of a subanaesthetic dosage of ketamine/esketamine as an adjunct to perioperative analgesia versus standard analgesia or placebo for reducing postoperative pain in participants undergoing gynaecological surgical procedures. A secondary objective is to assess whether these outcomes differ by type of surgery, background condition, type of drug used (ketamine or esketamine), dosage, and presence of preoperative chronic pain or preoperative long-term or recurrent opioid use.

BACKGROUND:Halogenated anaesthetic agents are potent greenhouse gases, but little is known about the trajectory of their use and their greenhouse gas impact on a global level. The primary aim of this study was to estimate the global greenhouse gas impact of halogenated anaesthetic agents over the preceding 10 years. METHODS:We obtained global medical sales data for sevoflurane, desflurane, isoflurane, halothane, and methoxyflurane from the IQVIA MIDAS database between 2014 and 2023. We calculated their annual greenhouse gas impact, expressed as carbon dioxide equivalents (CO2e), using global warming potential factors for a 100-year period. The effect of using only sevoflurane, the clinically relevant alternative with the lowest impact, was estimated by calculating the volume of sevoflurane that was needed to replace the other agents for a standard anaesthesia using a simulation software (Gas Man). FINDINGS:The 91 countries in the dataset represented 97·8%, 90·5%, and 66·2% of the population in high-income, upper-middle-income, and low-income or lower-middle-income countries, respectively, and covered 80·0% of the global population in 2023. The greenhouse gas impact of halogenated anaesthetic agents decreased by 27% from 2754 kilotons of CO2e (ktonCO2e) in 2014 to 2005 ktonCO2e in 2023. During the study period, the greenhouse gas impact from desflurane in high-income countries decreased by 52% from 2180 to 1053 ktonCO2e, increased in upper-middle-income countries by 151% from 125 to 313 ktonCO2e, and increased in low-income and lower-middle-income countries by 2281% from 2 to 42 ktonCO2e. By replacing desflurane, isoflurane, and halothane with sevoflurane, the global impact from halogenated anaesthetic agents in 2023 could theoretically have been decreased by 73%. INTERPRETATION:The global greenhouse gas impact from halogenated anaesthetic agents is falling due to lower use of desflurane in high-income countries. Efforts to reverse the increased use of desflurane in middle-income countries are needed. Replacing desflurane and isoflurane with sevoflurane constitutes an opportunity to markedly reduce the greenhouse gas impact from halogenated anaesthetic agents. FUNDING:The Thelma Zoega Foundation, The Anna and Edwin Berger Foundation, Region Skåne, and a Swedish Government grant for clinical research within the Swedish National Health Service (ALF).

PURPOSE:Assess if cystatin C-derived measures of kidney function are associated with mortality in septic- and non-septic intensive care unit (ICU) patients. METHODS:Data from adult patients staying >24 h in four ICUs in Sweden from November 2015-December 2018 included. Outcomes were mortality and need for renal replacement therapy (RRT) due to acute kidney injury. Associations between cystatin C-estimated glomerular filtration rate (eGFRcys) and shrunken pore syndrome (SPS) and outcomes were assessed with Cox-regression in unadjusted and analyses adjusted for sex, age, illness severity, chronic kidney disease and creatinine. SPS was defined as a ratio between eGFRcys and eGFRcreatinine <0.6. RESULTS:In total, 4455 patients were included in the analysis, of which 32 % had sepsis. SPS was present in 7.4 % of the cohort, and 90-day mortality was 30.8 %. In sepsis- and non-sepsis patients, SPS and eGFRcys were associated with 90-day-, 1-year mortality and RRT in unadjusted analyses. In an adjusted analysis, SPS was associated with 1-year mortality in sepsis patients (hazard ratio [HR] 1.4, 95 % CI 1.1-1.9, p = 0.021), and eGFRcys was associated with RRT in both sepsis and non-sepsis patients (HR 3.1, 95 % CI 1.6-6.0, p < 0.001, eGFRcys <20 vs ≥60 ml/min/1.73m2). No other associations between eGFRcys, SPS and mortality were detected in adjusted analyses. CONCLUSION:Our finding that SPS is more robustly associated with mortality in sepsis patients than in non-sepsis patients suggests that the association between SPS and mortality may depend on underlying pathophysiology. A cystatin C-based estimate of GFR is independently associated with RRT in sepsis and non-sepsis.

In septic shock, administration of large fluid volumes is associated with poor outcomes. Recent evidence shows that non-resuscitation fluids are the major modifiable source of fluids for patients with septic shock in intensive care units (ICUs). This clinical trial is designed to test the hypothesis that restrictive administration of non-resuscitation fluids improves outcomes compared to usual care. Adult patients admitted to ICUs with septic shock will be randomly assigned within 12 h of admission to receive protocolized restrictive administration of non-resuscitation fluids or usual care. The primary outcome is all-cause mortality at 90 days. Secondary outcomes are complications during ICU stay up to 90 days (defined as any acute kidney injury or cerebral, coronary, intestinal, or limb ischemia), mechanical ventilation free days within 90 days, and for survivors cognitive function (by the Montreal Cognitive Assessment [MOCA-BLIND]) and Health-Related Quality of Life (by the EQ Visual Analogue Scale [EQ-VAS]), both at 6 months. In addition, the climate impact of the interventions will be assessed. To detect an absolute reduction in mortality of 7.5%, with an alpha of 5% and a power of 90%, we aim to include 1850 patients. The trial is approved by the Swedish Ethical Review Authority. Results of primary and secondary clinical outcomes and the environmental outcome will be submitted for publication in a peer-reviewed journal. Trial Registration: NCT06140147.

About 4.4% of the global emissions of greenhouse gases can be ascribed to healthcare. Intensive care is among the most resource intensive specialties and the purpose of this study was to quantify the total climate impact of a Swedish intensive care unit (ICU) and identify modifiable elements that can lower the intensive care unit’s climate impact. A process-based life cycle assessment was conducted to estimate the climate impact per inpatient day in Sweden using the ReCiPe2016 impact assessment method. The analysis included single-use items; reusable instruments and textiles; pharmaceuticals and fluids; medical gases; and energy consumption for electronics equipment, lighting, and heating, ventilation, and air conditioning (HVAC). Input data were collected in 2022 at a mixed surgical and medical ICU in Sweden. Swedish low-climate-impact energy mix were used in the primary analysis. Results are reported as the global warming potential of carbon dioxide equivalents for 100 years (CO 2 eq). The median climate impact of one inpatient day was 30 kg CO 2 eq (95%-reference interval: [27–31]). Approximately 63% (19 kg CO 2 eq [18-20] could be attributed to single-use items, 19% (5.5 kg CO 2 eq [4.3–7.9]) was attributed to the unit’s energy consumption, pharmaceuticals and fluids contributed 7% (1.9 kg CO 2 eq [1.7–2.2]), and 5% (1.5 kg CO 2 eq [1.2–1.9]) was attributed to medical gases. A sensitivity analysis, using a high-climate-impact energy mix increased the total climate impact to 126.5 kg CO 2 eq (103–154). In countries with low-climate-impact energy mixes, such as Sweden, the opportunity to reduce the climate impact of intensive case lies primarily in the reduced use of single-use items. For countries that depend on high-climate-impact energy mixes, the foremost opportunity to reduce the climate impact of intensive care is to transition to renewable energy.

Introduction To increase the sustainability of healthcare, clinical trials must assess the environmental impact of interventions alongside clinical outcomes. This should be guided by Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) and Consolidated Standards of Reporting Trials (CONSORT) extensions, which will be developed by The Implementing Climate and Environmental Outcomes in Trials Group. The objective of the scoping review is to describe the existing methods for reporting and measuring environmental outcomes in randomised trials. The results will be used to inform the future development of the SPIRIT and CONSORT extensions on environmental outcomes (SPIRIT-ICE and CONSORT-ICE).Methods and analysis This protocol outlines the methodology for a scoping review, which will be conducted in two distinct sections: (1) identifying any existing guidelines, reviews or methodological studies describing environmental impacts of interventions and (2) identifying how environmental outcomes are reported in randomised trial protocols and trial results. A search specialist will search major medical databases, reference lists of trial publications and clinical trial registries to identify relevant publications. Data from the included studies will be extracted independently by two review authors. Based on the results, a preliminary list of items for the SPIRIT and CONSORT extensions will be developed.Ethics and dissemination This study does not include any human participants, and ethics approval is not required according to the Declaration of Helsinki. The findings from the scoping review will be published in international peer-reviewed journals, and the findings will be used to inform the design of a Delphi survey of relevant stakeholders.Open science Registered with Open Science 28 of February 2025.

INTRODUCTION:The WHO has declared climate change the defining public health challenge of the 21st century. Incorporating climate and environmental outcomes in randomised trials is essential for enhancing healthcare treatments' sustainability and safeguarding global health. To implement such outcomes, it is necessary to establish a framework for unbiased and transparent planning and reporting. We aim to develop extensions to the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT 2025) and Consolidated Standards of Reporting Trials (CONSORT 2025) statements by introducing guidelines for reporting climate and environmental outcomes. METHODS AND ANALYSIS:This is a protocol for SPIRIT and CONSORT extensions on reporting climate and environmental outcomes in randomised trials termed SPIRIT-Implementing Climate and Environmental (ICE) and CONSORT-ICE. The development of the extensions will consist of five phases: phase 1-project launch, phase 2-review of the literature, phase 3-Delphi survey, phase 4-consensus meeting and phase 5-dissemination and implementation. The phases are expected to overlap. The SPIRIT-ICE and CONSORT-ICE extensions will be developed in parallel. The extensions will guide researchers on how and what to report when assessing climate and environmental outcomes. ETHICS AND DISSEMINATION:The protocol was submitted to the Danish Research Ethics Committees, Denmark in June 2025. Ethics approval is expected in September 2025. The SPIRIT and CONSORT extensions will be published in international peer-reviewed journals.

Non-resuscitation fluids constitute the majority of fluid administered for septic shock patients in the intensive care unit (ICU). This multicentre, randomized, feasibility trial was conducted to test the hypothesis that a restrictive protocol targeting non-resuscitation fluids reduces the overall volume administered compared with usual care. Adults with septic shock in six Swedish ICUs were randomized within 12 h of ICU admission to receive either protocolized reduction of non-resuscitation fluids or usual care. The primary outcome was the total volume of fluid administered within three days of inclusion. Median (IQR) total volume of fluid in the first three days, was 6008 ml (interquartile range [IQR] 3960–8123) in the restrictive fluid group (n = 44), and 9765 ml (IQR 6804–12,401) in the control group (n = 48); corresponding to a Hodges–Lehmann median difference of 3560 ml [95 https://clinicaltrials.gov/ct2/show/NCT05249088

BACKGROUND:Reusing anaesthesia infusion-set components may reduce the climate impact from plastic waste and discarded medications. Infusion-set contents can be shielded from patient contact by single use of an infusion line fitted with dual antireflux valves, preventing retrograde entry of microorganisms, and eliminating the risk for patient-to-patient cross-contamination. However, infusion-set contamination from compromised aseptic handling could affect quality of care. INTERVENTIONS:To determine the prevalence of infusion-set bacterial contamination and compare the climate effects, we randomised operating rooms scheduled for total intravenous anaesthesia to handle procedures by infusion-set reuse or single-use. Both methods used dual single-use antireflux valves. OUTCOMES:The primary outcome was infusion-set bacterial contamination assessed by aerobic culture of infusion-set fluid collected after each procedure. The secondary outcome was CO 2 emissions (CO 2 -eq) estimated by life cycle assessment of component and medication use. To assess feasibility of detecting an inter-method difference in bacterial contamination, an interim analysis was planned after including at least 150 procedures per group. RESULTS:After allocating 54 operating rooms per method, 189 and 159 procedures of reuse and single use were included. Reuse permitted a median of three procedures per infusion set (range 1 to 8). Positive cultures occurred in two procedures per method [mean (95% CI)]; prevalence 1.15% (0.03 to 2.27); relative risk of reuse versus single use 0.84 (0.12 to 5.93), P  = 0.861. As prespecified, inclusion was stopped due to futility. The median (95% CI) per-procedure climate emissions were 0.43 (0.41 to 0.47) and 1.39 (1.37 to 1.40) kg CO 2 -eq for reuse and single-use respectively; difference -0.96 (-0.99 to -0.93), P  < 0.0005. The main sources for climate emissions were production of infusion-set components and waste handling. CONCLUSIONS:We conclude that the prevalence of bacterial contamination was low for both methods. A much larger study would be needed to detect an inter-method difference. Reuse of infusion-set components allowed significantly reduced intravenous anaesthesia climate emissions.

BACKGROUND Reusing anaesthesia infusion-set components may reduce the climate impact from plastic waste and discarded medications. Infusion-set contents can be shielded from patient contact by single use of an infusion line fitted with dual antireflux valves, preventing retrograde entry of microorganisms, and eliminating the risk for patient-to-patient cross-contamination. However, infusion-set contamination from compromised aseptic handling could affect quality of care. INTERVENTIONS To determine the prevalence of infusion-set bacterial contamination and compare the climate effects, we randomised operating rooms scheduled for total intravenous anaesthesia to handle procedures by infusion-set reuse or single-use. Both methods used dual single-use antireflux valves. OUTCOMES The primary outcome was infusion-set bacterial contamination assessed by aerobic culture of infusion-set fluid collected after each procedure. The secondary outcome was CO2 emissions (CO2-eq) estimated by life cycle assessment of component and medication use. To assess feasibility of detecting an inter-method difference in bacterial contamination, an interim analysis was planned after including at least 150 procedures per group. RESULTS After allocating 54 operating rooms per method, 189 and 159 procedures of reuse and single use were included. Reuse permitted a median of three procedures per infusion set (range 1 to 8). Positive cultures occurred in two procedures per method [mean (95% CI)]; prevalence 1.15% (0.03 to 2.27); relative risk of reuse versus single use 0.84 (0.12 to 5.93), P = 0.861. As prespecified, inclusion was stopped due to futility. The median (95% CI) per-procedure climate emissions were 0.43 (0.41 to 0.47) and 1.39 (1.37 to 1.40) kg CO2-eq for reuse and single-use respectively; difference -0.96 (-0.99 to -0.93), P < 0.0005. The main sources for climate emissions were production of infusion-set components and waste handling. CONCLUSIONS We conclude that the prevalence of bacterial contamination was low for both methods. A much larger study would be needed to detect an inter-method difference. Reuse of infusion-set components allowed significantly reduced intravenous anaesthesia climate emissions.

The past century has seen progress in healthcare unheard of in the history of humankind. This development has taken place concurrent with an increase in the global population from about 2 billion at the beginning of the 20th century to above 8 billion at present and was made possible by increasing the use of the earth's resources to such an extent that several so-called planetary boundaries have been overstepped.1 If the trajectory of resource utilisation is not altered we risk destabilising the planet with devastating consequences for the climate and the environment. This will be disastrous for the health of current and future generations through a multitude of interconnected effects on extreme weather events, food security, spread of infectious disease, and heat waves.2 Our axiomatic dependence on our planet was aptly described by the UN secretary Gutierrez when he said that ‘There is no human health without planetary health’. The fulfilment of the Paris agreement and sustainable development goals (SDGs) is therefore essential for the health of future generations, and it follows that we as healthcare providers have a vested interest in sustainability. Paradoxically, healthcare has a significant negative impact on planetary health. On a global scale healthcare contributes to about 5% of net global climate gas emissions; if healthcare was a country it would be the fifth largest greenhouse gas emitter.3 Peri-operative and intensive care are resource-intensive sectors of healthcare and, although incompletely quantified, their climate and environmental footprints are probably substantial.4,5 Consequently, increased sustainability in anaesthesia and intensive care must be a part of the transition to the net zero greenhouse gas emissions required to limit global warming to below the 1.5°C, as stipulated in the Paris Agreement. The need for a change in practice has been recognised for some time and several guidelines and position papers for environmentally sustainable practice have been published by professional societies, including the World Federation of Societies of Anaesthesiologists.6 The abolition of desflurane in many centres is inspiring and shows that we can change practice for environmental reasons. However, for anaesthesia and intensive care to become sustainable and contribute to reaching the goal of net zero greenhouse gas emissions other and more fundamental changes in the provision of care are required. While such changes must involve multiple stakeholders such as governments, international organisations, and the pharmaceutical and medical device industries, it is essential that anaesthetists and intensivists also rise to the challenge. As medical professionals and researchers we are uniquely positioned to identify areas in which we can improve sustainability while preserving quality of care against the backdrop of finite resources. The R's of sustainability (Refuse, Reduce, Recycle, Reuse, Rethink, Research) may serve as a framework for an agenda of change by which anaesthetists and intensivists can contribute. We can Refuse the provision of care which lacks a proven effect/value. Recent data suggest that interventions with limited effects are considerably overused, including the overly liberal use of the intensive care unit (ICU) and operative procedures.7,8 By targeting such interventions, we can achieve both financial and environmental gains. We can also Reduce the environmental impact of necessary and effective procedures in several ways. For example, we can engage in, and take a leading role in, green teams that critically examine procedures and processes on a local level. Such efforts could include relatively simple interventions such as promoting Recycling or Reuse and removing unnecessary items in prepacked kits for surgical procedures.9 Despite a growing body of evidence suggesting that disposable items have a higher environmental impact than reusable items, the use of disposable items is increasing. The underlying reasons are multifactorial and beyond the scope of this editorial. As experts in our field, we should engage in procurement and require that manufacturers provide environmental product declarations to enable informed decisions similar to that already required by law in the building industry in some European countries.10 As clinical experts become involved in procurement, we could also shape procurement specifications to encourage or mandate reusability which will in turn encourage reusable product development. Life cycle assessment (LCA) is a method to assess the environmental impact of a service or a product from the extraction of raw material to the destruction of the product. LCA is increasingly applied to medical products and could be used to inform public procurements. A valuable feature of an LCA is that it can also identify hotspots for environmental impact which can be targeted by interventions. LCA data are now available for several of the drugs and some of the procedures used in anaesthesia and intensive care, enabling us to incorporate environmental sustainability in practice guidelines.11 To incorporate environmental sustainability in practice guidelines we will have to Rethink how we assess the value of healthcare interventions. We should expand the definition of value of an intervention to include effects on patients and on the global population against a bottom line consisting of financial, environmental, and social costs or impacts using a so-called triple bottom line approach.12 The efficacy of many interventions and treatments in anaesthesia and intensive care, which may have considerable side-effects on the general population and on the environment as a whole, is based on low grade evidence. Such treatments include drugs like desflurane, which is about 70 times more potent as a greenhouse gas than sevoflurane for the same anaesthetic effect. Other examples include more complex interventions such as targeted temperature management after cardiac arrests, as well as different hygiene measures that are likely to drive resource consumption in the ICU or operating room.13 A triple bottom line approach could create a framework to assess such interventions. In situations where clinical efficacy is uncertain and a high environmental impact is certain, the intervention should be questioned. However, when an intervention is likely to be effective but has a large environmental footprint the situation becomes more challenging. For such situations, it may be helpful to quantify the environmental impact in a way which would facilitate assessment of the trade-off between clinical and environmental impacts. As suggested previously, such a quantification could be based on the available CO2 budget as defined in the Paris agreement, and could also include measures reflecting other planetary boundaries.12 We should add sustainability as ubiquitous component in our Research agenda. As mentioned above LCAs are increasingly used to assess the environmental impact of healthcare interventions, and are particularly important when marginal to no health gains are expected for patients. However, a recent review of LCA analyses in surgery and in anaesthesia identified methodological heterogeneity and a lack of detailed background data in databases as limitations in the research field.14 As researchers, we need to establish a consensus on the design, analysis, data sharing, and reporting of LCA studies similar to those of the Equator network for other study types in healthcare. In addition to increasing transparency, data sharing of the labour-intensive LCA studies could facilitate sensitivity analyses in which LCA models are adapted to local conditions as well as enable easy reuse of models in further research. Similarly, there is a need to develop methods to incorporate analysis of environmental effects of an intervention into both research ethics assessments and trial design, and to update current trial design guidelines to include an environmental analysis plan.15 Interestingly, the Sustainable Healthcare Coalition recently estimated that the climate footprint of clinical research corresponds to 5% of healthcare's global climate footprint, highlighting the need to consider sustainability of the trials themselves in trial design.16 Finally, we need to Rethink education in anaesthesia and intensive care and include education in sustainability in the training and in continuing medical education. This need is increasingly recognised, and sustainability was recently added to the curriculum of the Royal College of Anaesthetists. We encourage other national and international societies to follow this example. This will allow our specialty to take an active role in the transition to a sustainable healthcare system from the bottom up, for example by taking on leadership in green teams. The magnitude of the task ahead of us is daunting and can be paralysing. No one can do everything, but everyone can do something. The increasing number of publications in the field suggests a growing interest for change in our community, which is very encouraging. By embracing the interconnection between humans and planetary health, as first described by Alexander von Humboldt more than 200 years ago, there is reason to believe that we together can turn danger into opportunity for the benefit of global human health.

Abstract Background Preload responsive postoperative patients with signs of inadequate organ perfusion are commonly assumed to be hypovolemic and therefore treated with fluids to increase preload. However, preload is influenced not only by blood volume, but also by venous vascular tone and the contribution of these factors to preload responsiveness in this setting is unknown. Based on this, the objective of this study was to investigate blood volume status in preload-responsive postoperative patients. Methods Data from a clinical trial including postoperative patients after major abdominal surgery were analyzed. Patients with signs of inadequate organ perfusion and with data from a passive leg raising test (PLR) were included. An increase in pulse pressure by ≥ 9% was used to identify patients likely to be preload responsive. Blood volume was calculated from plasma volume measured using radiolabelled albumin and hematocrit. Patients with a blood volume of at least 10% above or below estimated normal volume were considered hyper- and hypovolemic, respectively. Results A total of 63 patients were included in the study. Median (IQR) blood volume in the total was 57 (50–65) ml/kg, and change in pulse pressure after PLR was 14 (7–24)%. A total of 43 patients were preload responsive. Of these patients, 44% were hypovolemic, 28% euvolemic and 28% hypervolemic. Conclusions A large fraction of postoperative patients with signs of hypoperfusion that are likely to be preload responsive, are hypervolemic. In these patients, treatments other than fluid administration may be a more rational approach to increase cardiac output. Trial registration EudraCT 2013-004446-42

ObjectivesTo assess the effects of interventions authorised by the European Medicines Agency (EMA) or the US Food and Drug Administration (FDA) for prevention of COVID-19 progression to severe disease in outpatients. SettingOutpatient treatment. ParticipantsParticipants with a diagnosis of COVID-19 and the associated SARS-CoV-2 virus irrespective of age, sex and comorbidities. InterventionsDrug interventions authorised by EMA or FDA. Primary outcome measuresPrimary outcomes were all-cause mortality and serious adverse events. ResultsWe included 17 clinical trials randomising 16 257 participants to 8 different interventions authorised by EMA or FDA. 15/17 of the included trials (88.2%) were assessed at high risk of bias. Only molnupiravir and ritonavir-boosted nirmatrelvir seemed to improve both our primary outcomes. Meta-analyses showed that molnupiravir reduced the risk of death (relative risk (RR) 0.11, 95% CI 0.02 to 0.64; p=0.0145, 2 trials; very low certainty of evidence) and serious adverse events (RR 0.63, 95% CI 0.47 to 0.84; p=0.0018, 5 trials; very low certainty of evidence). Fisher's exact test showed that ritonavir-boosted nirmatrelvir reduced the risk of death (p=0.0002, 1 trial; very low certainty of evidence) and serious adverse events (p<0.0001, 1 trial; very low certainty of evidence) in 1 trial including 2246 patients, while another trial including 1140 patients reported 0 deaths in both groups. ConclusionsThe certainty of the evidence was very low, but, from the results of this study, molnupiravir showed the most consistent benefit and ranked highest among the approved interventions for prevention of COVID-19 progression to severe disease in outpatients. The lack of certain evidence should be considered when treating patients with COVID-19 for prevention of disease progression. PROSPERO registration numberCRD42020178787.

Introduction Administration of large volumes of fluids is associated with poor outcome in septic shock. Recent data suggest that non-resuscitation fluids are the major source of fluids in the intensive care unit (ICU) patients suffering from septic shock. The present trial is designed to test the hypothesis that a protocol targeting this source of fluids can reduce fluid administration compared with usual care. Methods and analysis The design will be a multicentre, randomised, feasibility trial. Adult patients admitted to ICUs with septic shock will be randomised within 12 hours of admission to receive non-resuscitation fluids either according to a restrictive protocol or to receive usual care. The healthcare providers involved in the care of participants will not be blinded. The participants, outcome assessors at the 6-month follow-up and statisticians will be blinded. Primary outcome will be litres of fluids administered within 3 days of randomisation. Secondary outcomes will be proportion of randomised participants with outcome data on all-cause mortality; days alive and free of mechanical ventilation within 90 days of inclusion; any acute kidney injury and ischaemic events in the ICU (cerebral, cardiac, intestinal or limb ischaemia); proportion of surviving randomised patients who were assessed by European Quality of Life 5-Dimensions 5-Level questionnaire and Montreal Cognitive Assessment; proportion of all eligible patients who were randomised and proportion of participants experiencing at least one protocol violation. Ethics and dissemination Ethics approval has been obtained in Sweden. Results of the primary and secondary outcomes will be submitted for publication in a peer-reviewed journal. Trial registration number NCT05249088 .

Purpose: To assess the association between cystatin C-derived estimates of kidney function and mortality and acute kidney injury (AKI) in sepsis.Materials and methods: Post-hoc analysis of sepsis patients in the FINNAKI-cohort (n = 802). Primary outcome was 90-day mortality. We measured plasma cystatin C and creatinine at intensive care unit (ICU) admission and estimated glomerular filtration rates (eGFRcys, eGFRcrea) and shrunken pore syndrome (SPS; defined as eGFRcys/eGFRcrea ratio < 0.7). Associations were assessed using Cox-or logistic regression.Results: Increased cystatin C and decreased eGFRcyswere associated with mortality in unadjusted analyses and in analyses adjusted for illness severity and creatinine. Hazard ratios (HRs) in unadjusted analyses were 3.30 (95% CI; 2.12-5.13, p < 0.001) and 3.26 (95% CI; 2.12-5.02, p < 0.001) respectively. SPS was associated with mortality in an unadjusted-(HR 1.78, 95% CI; 1.33-2.37, p < 0.001) and in an adjusted analysis (HR 1.54, 95% CI; 1.07-2.22, p = 0.021). All cystatin C-derived measures were associated with mortality also after adjustment for AKI devel-opment. Cystatin C was associated with AKI in unadjusted analyses but not in analyses adjusted for creatinine.Conclusion: Cystatin C and derived measures of kidney function at ICU admission are associated with an increased 90-day mortality. Increased AKI incidence does not fully explain this association.(c) 2022 The Authors. Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http:// creativecommons.org/licenses/by-nc-nd/4.0/).

Introduction Climate change is one of the 21st century’s biggest public health issues and health care contributes up to 10% of the emissions of greenhouse gases in developed countries. About 15 million laparoscopic procedures are performed annually worldwide and single-use medical equipment is increasingly used during these procedures. Little is known about costs and environmental footprint of this change in practice. Methods We employed Life Cycle Assessment method to evaluate and compare the environmental impacts of single-use, reusable, and mixed trocar systems used for laparoscopic cholecystectomies at three hospitals in southern Sweden. The environmental impacts were calculated using the IMPACT 2002+ method and a functional unit of 500 procedures. Monte Carlo simulations were used to estimate differences between trocar systems. Data are presented as medians and 2.5th to 97.5th percentiles. Financial costs were calculated using Life Cycle Costing. Results The single-use system had a 182% higher impact on resources than the reusable system [difference: 5160 MJ primary (4400–5770)]. The single-use system had a 379% higher impact on climate change than the reusable system [difference: 446 kg CO2eq (413–483)]. The single-use system had an 83% higher impact than the reusable system on ecosystem quality [difference: 79 PDF*m2*yr (24–112)] and a 240% higher impact on human health [difference: 2.4x10-4 DALY/person/yr (2.2x10-4-2.6x10-4)]. The mixed and single-use systems had a similar environmental impact. Differences between single-use and reusable trocars with regard to resource use and ecosystem quality were found to be sensitive to lower filling of machines in the sterilization process. For ecosystem quality the difference between the two were further sensitive to a 50% decrease in number of reuses, and to using a fossil fuel intensive electricity mix. Differences regarding effects on climate change and human health were robust in the sensitivity analyses. The reusable and mixed trocar systems were approximately half as expensive as the single-use systems (17360 € and 18560 € versus 37600 €, respectively). Conclusion In the Swedish healthcare system the reusable trocar system offers a robust opportunity to reduce both the environmental impact and financial costs for laparoscopic surgery.

Background: Limited data are available on the incidence of mechanical complications after ultrasound-guided central venous catheterisation. We aimed to determine the incidence of mechanical complications in hospitals where real-time ultrasound guidance is clinical practice for central venous access and to identify variables associated with mechanical complications. Methods: All central venous catheter insertions in patients >= 16 yr at four emergency care hospitals in Sweden from March 2, 2019 to December 31, 2020 were eligible for inclusion. Every insertion was monitored for complete documentation and occurrence of mechanical complications within 24 h after catheterisation. Multivariable logistic regression analyses were used to determine associations between predefined variables and mechanical complications. Results: In total, 12 667 catheter insertions in 8586 patients were included. The incidence (95% confidence interval [CI]) of mechanical complications was 7.7% (7.3e8.2%), of which 0.4% (0.3e0.5%) were major complications. The multivariable analyses showed that patient BMI <20 kgm(-2) (odds ratio 2.69 [95% CI: 1.17e5.62]), male operator gender (3.33 [1.60e7.38]), limited operator experience (3.11 [1.64e5.77]), and increasing number of skin punctures (2.18 [1.59e2.88]) were associated with major mechanical complication. Subclavian vein catheterisation was associated with pneumothorax (5.91 [2.13e17.26]). Conclusions: The incidence of major mechanical complications is low in hospitals where real-time ultrasound guidance is the standard of care for central venous access. Several variables independently associated with mechanical complications can be used for risk stratification before catheterisation procedures, which might further reduce complication rates. Clinical trial registration: NCT03782324.