Anders Perner

• PhD
• Professor (Full) at Rigshospitalet

Background Adult intensive care unit (ICU) patients receive many interventions, but few are supported by high‐certainty evidence. Randomised clinical trials (RCTs) are essential for trustworthy comparisons of intervention effects, but conventional RCTs are costly, cumbersome, inflexible, and often turn out inconclusive. Adaptive platform trials may...

Background Venous thromboembolism (VTE) is a frequent complication in critically ill patients, who often have multiple risk factors. Pharmacological thromboprophylaxis is widely applied to lower this risk, but guidelines lack dosing recommendations. Objective This survey aims to assess current thromboprophylaxis preferences and willingness to part...

Background Advanced adaptive randomised clinical trials are increasingly used. Compared to their conventional counterparts, their flexibility may make them more efficient, increase the probability of obtaining conclusive results without larger samples than necessary, and increase the probability that individual participants are allocated to more pr...

Objectives Randomized clinical trials informing clinical practice (e.g., like large, pragmatic, and late-phase trials) should ideally mostly use harmonized outcomes that are important to patients, family members, clinicians, and researchers. Core outcome sets for specific subsets of ICU patients exist, for example, respiratory failure, delirium, an...

Background Intravenous albumin is used for resuscitation and substitution but is not supported by high‐certainty evidence. As clinical practice likely varies, we aimed to describe the issuing of albumin solutions across Danish public hospitals. Methods We assessed issuing of intravenous albumin solutions (5% and 20%) to all Danish public hospitals...

Aim To describe the use of invasive mechanical ventilation core strategies, adjuvant treatments and the occurrence of barotrauma and prolonged ventilation in ICU patients with COVID‐19 in Denmark, retrospectively. Methods All ICUs admitting COVID‐19 patients in Denmark from 10 March 2020 to 2 April 2021 were invited to participate. All patients wi...

Background Clinical practice guidelines recommend use of buffered crystalloid solutions in critically ill patients but do not distinguish between solutions based on different buffering anions, that is, acetate‐ versus lactate‐buffered solutions. We therefore surveyed relevant physicians about their preferences and attitudes toward each solution. M...

Glycemic control poses a challenge in intensive care unit (ICU) patients and dysglycemia is associated with poor outcomes. Continuous glucose monitoring (CGM) has been successfully implemented in the type 1 diabetes out-patient setting and renewed interest has been directed into the transition of CGM into the ICU. This scoping review aimed to provi...

Background Feeding intolerance is common in critically ill patients and can lead to malnutrition. Prokinetic agents may be used to enhance the uptake of nutrition. However, the evidence on the effectiveness and safety of prokinetic agents is sparse, and there is a lack of data on their use in intensive care units (ICU). Methods We will conduct an...

Background: Serious adverse events (SAEs) are common in intensive care unit (ICU) patients. Reporting of SAEs in randomised clinical trials (RCTs) varies why underreporting is likely. We aim to describe the reporting of SAEs from 2020 onwards and to illustrate the recent reporting of SAEs published in major medical journals. Methods: We will con...

The aim of this study was to evaluate one-year outcomes of lower versus higher oxygenation targets in intensive care unit (ICU) patients with coronavirus disease 2019 (COVID-19) and severe hypoxaemia. We conducted pre-planned analyses of one-year mortality and health-related quality of life (HRQoL) in the Handling Oxygenation Targets in COVID-19 tr...

Importance Soluble thrombomodulin is a marker of endotheliopathy, and iloprost may improve endothelial function. In patients with septic shock, high plasma levels of soluble thrombomodulin (>10 ng/mL) have been associated with worse organ dysfunction and mortality. Objective To assess the effects of treatment with iloprost vs placebo on the severi...

Background Bacterial meningitis can cause a life-threatening increase in intracranial pressure (ICP). ICP-targeted treatment including an ICP monitoring device and external ventricular drainage (EVD) may improve outcomes but is also associated with the risk of complications. The frequency of use and complications related to ICP monitoring devices a...

Background The average treatment effect (ATE) reported by most randomised clinical trials provides estimates of treatment effects for the theoretical, non‐existent average patient. However, ATE may not accurately reflect the outcomes for all subsets of the trial population; some individuals may benefit from the intervention, while others experience...

Introduction Use of albumin is suggested for some patients with shock, but preferences for its use may vary among intensive care unit (ICU) physicians. Methods We conducted an international online survey of ICU physicians with 20 questions about their use of albumin and their opinion towards a randomised trial among adults with shock comparing the...

Introduction Hyperglycaemia is common in intensive care unit (ICU) patients. Glycaemic monitoring and effective glycaemic control with insulin are crucial in the ICU to improve patient outcomes. However, glycaemic control and insulin use vary between ICU patients and hypo‐ and hyperglycaemia occurs. Therefore, we aim to provide contemporary data on...

Background: The goal of this systematic review was to examine the efficacy and safety of proton-pump inhibitors for stress ulcer prophylaxis in critically ill patients. Methods: We included randomized trials comparing proton-pump inhibitors versus placebo or no prophylaxis in critically ill adults, performed meta-analyses, and assessed certainty...

Background Enteral nutrition may affect risks of gastrointestinal bleeding, pneumonia and mortality in critically ill patients and may also modify the effects of pharmacological stress ulcer prophylaxis. We undertook post hoc analyses of the stress ulcer prophylaxis in the intensive care unit trial to assess for any associations and interactions be...

Background Platelet transfusions are frequently used in the intensive care unit (ICU), but current practices including used product types, volumes, doses and effects are unknown. Study design and methods Sub‐study of the inception cohort study ‘Thrombocytopenia and Platelet Transfusions in the ICU (PLOT‐ICU)’, including acutely admitted, adult ICU...

Purpose Randomised clinical trials should ideally use harmonised outcomes that are important to patients and to facilitate meta-analyses and ensuring generalisability. Core outcome sets for specific subsets of ICU patients exist, e.g., respiratory failure, delirium, and COVID-19, but not for ICU patients in general. Accordingly, we aimed to develop...

Purpose To identify key components and variations in family-centered care practices. Methods A cross-sectional study, conducted across ESICM members. Participating ICUs completed a questionnaire covering general ICU characteristics, visitation policies, team-family interactions, and end-of-life decision-making. The primary outcome, self-rated fami...

Background Piperacillin/tazobactam may be associated with less favourable outcomes than carbapenems in patients with severe bacterial infections, but the certainty of evidence is low. Methods The Empirical Meropenem versus Piperacillin/Tazobactam for Adult Patients with Sepsis (EMPRESS) trial is an investigator‐initiated, international, parallel‐g...

Background The optimal amount and timing of protein intake in critically ill patients are unknown. REPLENISH (Replacing Protein via Enteral Nutrition in a Stepwise Approach in Critically Ill Patients) trial evaluates whether supplemental enteral protein added to standard enteral nutrition to achieve a high amount of enteral protein given from ICU d...

Background Oxygen supplementation is ubiquitous in intensive care unit (ICU) patients with chronic obstructive pulmonary disease (COPD) and acute hypoxaemia, but the optimal oxygenation target has not been established. Methods This was a pre-planned subgroup analysis of the Handling Oxygenation Targets in the ICU (HOT-ICU) trial, which allocated p...

The aim of this study was to examine the effects of intravenous (IV) fluid restriction on time to resolution of hyperlactatemia in septic shock. Hyperlactatemia in sepsis is associated with worse outcome. Sepsis guidelines suggest targeting lactate clearance to guide fluid therapy despite the complexity of hyperlactatemia and the potential harm of...

Background Proton pump inhibitors (PPIs) are the most commonly prescribed drugs for preventing upper gastrointestinal bleeding in critically ill patients. However, concerns have arisen about the possible harms of using PPIs, including potentially increased risk of pneumonia, Clostridioides difficile infection, and more seriously, an increased risk...

Background Variation in usual practice in fluid trials assessing lower versus higher volumes may affect overall comparisons. To address this, we will evaluate the effects of heterogeneity in treatment intensity in the Conservative versus Liberal Approach to Fluid Therapy of Septic Shock in Intensive Care trial. This will reflect the effects of diff...

Objective: To describe the change in admission rate and demographic profile of patients admitted to ICUs throughout Denmark before and during first wave of the SARS-CoV-2 pandemic. Methods: A register-based national observational study of all patients admitted to ICU from December 2019 until April 2020, comparing ICU admission before and after lock...

It is unclear how sceptical priors impact adaptive trials. We assessed the influence of priors expressing a spectrum of scepticism on the performance of several Bayesian, multi‐stage, adaptive clinical trial designs using binary outcomes under different clinical scenarios. Simulations were conducted using fixed stopping rules and stopping rules cal...

Background Critically ill patients in intensive care units (ICU) are frequently administered broad‐spectrum antibiotics (e.g., carbapenems or piperacillin/tazobactam) for suspected or confirmed infections. This retrospective cohort study aimed to describe the use of carbapenems and piperacillin/tazobactam in two international, prospectively collect...

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 Pa o 2 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 randomi...

Background The Handling Oxygenation Targets in the Intensive Care Unit (HOT‐ICU) trial was a multicentre, randomised, parallel‐group trial of a lower oxygenation target (arterial partial pressure of oxygen [PaO 2 ] = 8 kPa) versus a higher oxygenation target (PaO 2 = 12 kPa) in adult ICU patients with acute hypoxaemic respiratory failure; the Handl...

We assessed long-term outcomes in acutely admitted adult patients with delirium treated in intensive care unit (ICU) with haloperidol versus placebo. We conducted pre-planned analyses of 1-year outcomes in the Agents Intervening against Delirium in the ICU (AID-ICU) trial, including mortality and health-related quality of life (HRQoL) assessed by E...

Introduction Platelet transfusions are frequently used in intensive care unit (ICU) patients, but contemporary epidemiological data are sparse. We aim to present contemporary international data on the use of platelet transfusions in adult ICU patients with thrombocytopenia. Methods This is a protocol and statistical analysis plan for a post hoc su...

Background Albumin administration is suggested in patients with sepsis and septic shock who have received large volumes of crystalloids. Given lack of firm evidence, clinical practice variation may exist. To address this, we investigated if patient characteristics or trial site were associated with albumin use in septic shock. Methods We conducted...

Randomiserede kliniske forsøg er det mest pålidelige studiedesign til vurdering af effekten af interventioner. Den metodologiske kvalitet i randomiserede kliniske forsøg varierer. De vaesentligste punkter for kritisk vurdering af randomiserede kliniske forsøg gennemgås. Du går stuegang hos en 67-årig mand, som har svaer pneumoni og har udviklet sep...

The randomised clinical trial is the most reliable study design to compare the effects of different interventions, however, the methodological quality of randomised clinical trials varies. In this review, the central considerations for critically appraising a randomised clinical trial are described along with an example, terminological references,...

Background The optimal dose of dexamethasone for severe/critical COVID‐19 is uncertain. We compared higher versus standard doses of dexamethasone in adults with COVID‐19 and hypoxia. Methods We searched PubMed and trial registers until 23 June 2023 for randomised clinical trials comparing higher (>6 mg) versus standard doses (6 mg) of dexamethason...

Background The CLASSIC trial assessed the effects of restrictive versus standard intravenous (IV) fluid therapy in adult intensive care unit (ICU) patients with septic shock. This pre‐planned study provides a probabilistic interpretation and evaluates heterogeneity in treatment effects (HTE). Methods We analysed mortality, serious adverse events (...

Background Response time for emergency medical service units is a key performance indicator. Studies have shown reduced response time association with improved outcome for specific critical conditions. To achieve short response time, emergency vehicles utilize lights and sirens, and crews are allowed to be non‐compliant with traffic rules, posing a...

Different combined outcome‐data lags (follow‐up durations plus data‐collection lags) may affect the performance of adaptive clinical trial designs. We assessed the influence of different outcome‐data lags (0–105 days) on the performance of various multi‐stage, adaptive trial designs (2/4 arms, with/without a common control, fixed/response‐adaptive...

Thrombocytopenia (platelet count < 150 × 109/L) is common in intensive care unit (ICU) patients and is likely associated with worse outcomes. In this study we present international contemporary data on thrombocytopenia in ICU patients. We conducted a prospective cohort study in adult ICU patients in 52 ICUs across 10 countries. We assessed frequenc...

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 co...

Background In the COVID-STEROID 2 trial there was suggestion of heterogeneity of treatment effects (HTE) between patients enrolled from Europe vs. India on the primary outcome. Whether there was HTE for the remaining patient-centred outcomes is unclear. Methods In this post hoc analysis of the COVID-STEROID 2 trial, which compared 12 mg vs. 6 mg d...

Background When caring for mechanically ventilated adults with acute hypoxaemic respiratory failure (AHRF), clinicians are faced with an uncertain choice between ventilator modes allowing for spontaneous breaths or ventilation fully controlled by the ventilator. The preferences of clinicians managing such patients, and what motivates their choice o...

Background: This is an updated review concerning 'Higher versus lower fractions of inspired oxygen or targets of arterial oxygenation for adults admitted to the intensive care unit'. Supplementary oxygen is provided to most patients in intensive care units (ICUs) to prevent global and organ hypoxia (inadequate oxygen levels). Oxygen has been admin...

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 t...

Background Acute respiratory failure (ARF) is the leading cause of intensive care unit (ICU) admission in patients with Acute Myeloid Leukemia (AML) and data on prognostic factors affecting short-term outcome are needed. Methods This is a post-hoc analysis of a multicenter, international prospective cohort study on immunocompromised patients with...

Background: Health-related quality of life (HRQoL) is a patient-centred outcome increasingly used as a secondary outcome in critical care research. It may cover several important dimensions of clinical status in intensive care unit (ICU) patients that arguably elude other more easily quantified outcomes such as mortality. Poor associations with ha...

Background: Randomised clinical trials in critical care are prone to inconclusiveness due, in part, to undue optimism about effect sizes and suboptimal accounting for heterogeneous treatment effects. Although causal evidence from rich real-world critical care can help overcome these challenges by informing predictive enrichment, no overview exists...

Background Haloperidol is frequently used in critically ill patients with delirium, but evidence for its effects has been sparse and inconclusive. By including recent trials, we updated a systematic review assessing effects of haloperidol on mortality and serious adverse events in critically ill patients with delirium. Methods This is an updated s...

Background: Protein intake is recommended in critically ill patients to mitigate the negative effects of critical illness-induced catabolism and muscle wasting. However, the optimal dose of enteral protein remains unknown. We hypothesize that supplemental enteral protein (1.2 g/kg/day) added to standard enteral nutrition formula to achieve high am...

PurposeTo assess long-term outcomes of restrictive versus standard intravenous (IV) fluid therapy in adult intensive care unit (ICU) patients with septic shock included in the European Conservative versus Liberal Approach to Fluid Therapy in Septic Shock in Intensive Care (CLASSIC) trial.Methods We conducted the pre-planned analyses of mortality, h...

The aim of these guidelines is to update the 2017 clinical practice guideline (CPG) of the European Society of Intensive Care Medicine (ESICM). The scope of this CPG is limited to adult patients and to non-pharmacological respiratory support strategies across different aspects of acute respiratory distress syndrome (ARDS), including ARDS due to cor...

Background Days alive without life support (DAWOLS) and similar outcomes that seek to summarise mortality and non-mortality experiences are increasingly used in critical care research. The use of these outcomes is challenged by different definitions and non-normal outcome distributions that complicate statistical analysis decisions. Methods We scr...

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 s...

Background: Intravenous (IV) albumin is suggested for patients with septic shock who have received large amounts of IV crystalloids; a conditional recommendation based on moderate certainty of evidence. Clinical variation in the administration of IV albumin in septic shock may exist according to patient characteristics and location. Methods: Thi...

Introduction Intravenous crystalloid fluid resuscitation forms a crucial part of the early intervention bundle for sepsis and septic shock, with the Surviving Sepsis Campaign guidelines recommending a 30 mL/kg fluid bolus within the first hour. Compliance with this suggested target varies in patients with comorbidities such as congestive heart fail...

Aim: To investigate the effects of lower versus higher oxygenation targets in adult intensive care unit (ICU) patients with hypoxaemic respiratory failure after cardiac arrest. Methods: Subgroup analysis of the international Handling Oxygenation Targets in the ICU (HOT-ICU) trial which randomised 2928 adults with acute hypoxaemia to targets of a...

Background: Intravenous (IV) fluids are recommended to adults with sepsis. However, the optimal strategy for IV fluid management in sepsis is unknown, and clinical equipoise exists. Research question: Do lower vs higher fluid volumes improve patient-important outcomes in adult patients with sepsis? Study design & methods: We updated a systemat...

The currently recommended dose of dexamethasone for patients with severe or critical COVID-19 is 6 mg per day (mg/d) regardless of patient features and variation. However, patients with severe or critical COVID-19 are heterogenous in many ways (e.g., age, weight, comorbidities, disease severity, and immune features). Thus, it is conceivable that a...

Background: Health-related quality of life (HRQoL) is frequently assessed in randomised clinical trials (RCTs) in the intensive care unit (ICU), but data are limited regarding the proportions of patients without responses or not surviving to HRQoL follow-up and the handling of this. We aimed to describe the extent and pattern of missing HRQoL data...

Objectives: To assess the incidence, risk factors, and outcomes of atrial fibrillation (AF) in the ICU and to describe current practice in the management of AF. Design: Multicenter, prospective, inception cohort study. Setting: Forty-four ICUs in 12 countries in four geographical regions. Subjects: Adult, acutely admitted ICU patients withou...

Background Abnormal serum levels of magnesium, phosphate, and zinc appear common in intensive care unit (ICU) patients, but the epidemiology, management, and associations with outcomes are less well described. We described these factors and estimated associations with outcomes in a large dataset of Danish ICU patients. Methods We included adults w...

PurposeThe AID–ICU trial was a randomised, blinded, placebo-controlled trial investigating effects of haloperidol versus placebo in acutely admitted, adult patients admitted in intensive care unit (ICU) with delirium. This pre-planned Bayesian analysis facilitates probabilistic interpretation of the AID–ICU trial results.Methods We used adjusted Ba...

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 b...

Purpose To assess long-term outcomes of restrictive versus standard intravenous (IV) fluid therapy in adult intensive care unit (ICU) patients with septic shock included in the European Conservative versus Liberal Approach to Fluid Therapy in Septic Shock in Intensive Care (CLASSIC trial). Methods We conducted the pre-planned analyses of mortality...

Background: Piperacillin/tazobactam or meropenem are often used to treat patients with severe bacterial infections. We aimed to compare the desirable and undesirable effects of empirical and/or definitive piperacillin/tazobactam versus carbapenems in patients with severe bacterial infections. Methods: We searched PubMed, Embase, CENTRAL, Epistem...

Background: Thromboembolism is more common in patients with critical COVID-19 than in other critically ill patients, and inflammation has been proposed as a possible mechanism. The aim of this study was to investigate if 12 mg vs. 6 mg dexamethasone daily reduced the composite outcome of death or thromboembolism in patients with critical COVID-19....

Background: Trials in critically ill patients increasingly focus on days alive without life support (DAWOLS) or days alive out of hospital (DAOOH) and health-related quality of life (HRQoL). DAWOLS and DAOOH convey more information than mortality and are simpler and faster to collect than HRQoL. However, whether these outcomes are associated with...

Background: Gastrointestinal motility is important for adequate uptake of fluids and nutrition but is often impaired in hospitalised patients. Prokinetic agents enhance gastrointestinal motility and are prescribed for many hospitalised patients. In this scoping review, we aimed to systematically describe the body of evidence on the use of prokinet...

Background The optimal amount and timing of protein intake in critically ill patients are unknown. REPLENISH (Replacing Protein via Enteral Nutrition in a Stepwise Approach in Critically Ill Patients) trial evaluates whether supplemental enteral protein added to standard enteral nutrition to achieve a high amount of enteral protein given from ICU d...

Background: Long-term cognitive impairment occurs in up to 60% of intensive care unit (ICU) survivors. Early use of functional and cognitive rehabilitation interventions while patients are still in ICU may reduce cognitive decline. We aim to describe the functional and cognitive interventions used during the ICU stay, the healthcare professionals...

Objectives: To assess any benefit or harm, we conducted a systematic review of randomised clinical trials allocating adults to dexmedetomidine versus placebo/no intervention for the prevention of delirium in intensive care units or postoperative care units. Data sources: We searched Medline, Embase, CENTRAL, and other databases. The last search...

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...

Background: Critically ill patients are at risk of gastrointestinal (GI) bleeding. Counter measures to minimise this risk include the use of pharmacological stress ulcer prophylaxis (SUP). The effect of enteral nutrition as SUP on GI bleeding event rates is unknown. There are conflicting data describing the effect of coadministration of enteral nu...

Background: Low serum levels of magnesium, phosphate, and zinc are observed in many intensive care unit (ICU) patients, but clinical equipoise exists regarding supplementation strategies. We aimed to assess the desirable and undesirable effects of supplementation with magnesium, phosphate, or zinc in adult ICU patients. Methods: We conducted a s...

Background: Patient and public involvement in randomised clinical trials has received increased focus, including in intensive care trials, but the frequency, method and extent is unknown. This meta-epidemiological study investigated patient and public involvement in contemporary, large ICU trials. Methods: We systematically searched PubMed for l...

Background Patients admitted to an intensive care unit (ICU) with active haematological malignancy and hypoxaemic respiratory failure have a high mortality. Oxygen supplementation is essential, but limited information exists on the optimum oxygenation targets in these patients. Methods This subgroup analysis was specified before completion of the...

Background: The COVID-STEROID 2 trial found high probability of benefit with dexamethasone 12 mg vs. 6 mg daily among patients with COVID-19 and severe hypoxemia. There was suggestion of heterogeneity of treatment effects (HTE)between patients enrolled from Europe vs. India on the primary outcome. Whether there was HTE by geographical region for th...

Background: Intravenous (IV) fluid therapy is a ubiquitous intervention in daily clinical practice. However, nationwide detailed hospital- and departmental-level information on IV fluid use is limited. Hence, we aimed to describe the current issuing of isotonic crystalloid solutions across Danish public hospitals. Methods: We conducted a nationw...

Background: Protein intake is recommended in critically ill patients to mitigate the negative effects of critical illness-induced catabolism and muscle wasting. However, the optimal dose of enteral protein remains unknown. We hypothesize that supplemental enteral protein (1.2 g/kg/day) added to standard enteral nutrition formula to achieve high amo...

Objective Adaptive features may increase flexibility and efficiency of clinical trials, and improve participants’ chances of being allocated to better interventions. Our objective is to provide thorough guidance on key methodological considerations for adaptive clinical trials. Study Design and Setting We provide an overview of key methodological...

Background: Haloperidol is frequently used to treat delirium in patients in the intensive care unit (ICU), but evidence of its effect is limited. Methods: In this multicenter, blinded, placebo-controlled trial, we randomly assigned adult patients with delirium who had been admitted to the ICU for an acute condition to receive intravenous haloper...