Lars Peter Holst Andersen

Background: The inflammatory response to whole‐body ischemia, as seen in comatose survivors after out‐of‐hospital cardiac arrest (OHCA), is associated with increased morbidity and mortality. Early high‐dose dexamethasone may dampen the inflammatory response, which may diminish secondary brain damage and other organ injury and decrease mortality. The aim is to evaluate the effect of high‐dose dexamethasone in post‐resuscitation care. Methods: The Danish Out‐of‐Hospital Cardiac Arrest (DANOHCA) trial is an investigator‐initiated, multicenter, randomized, controlled trial evaluating four post‐resuscitation interventions in adult patients resuscitated after OHCA including blinded early administration of high‐dose dexamethasone compared with placebo (isotonic saline). Adult OHCA patients with presumed cardiac etiology and sustained return of spontaneous circulation will be randomized 1:1 to receive 20 mg of dexamethasone or placebo immediately after inclusion in the trial and repeated the following two mornings for a total of three doses. The primary outcome is all‐cause mortality within 90 days using a log‐binomial regression analysis to estimate the relative risk of death from any cause between randomization and Day 90. Enrollment began in June 2023, with the aim to include 1000 patients at five sites in 3–4 years. The trial is registered at clinicaltrials.gov (identifier: NCT05895838) and euclinicaltrials.eu (2024‐515997‐28‐00). Perspectives: It is of paramount importance to optimize post‐resuscitation care through large‐scale randomized trials. Global ischemia–reperfusion–induced inflammatory response with resulting organ failures represents a possible target for interventions after OHCA. This part of the DANOHCA trial will provide new evidence on the impact of high‐dose dexamethasone in survivors of OHCA. Trial Registration: Clinical Trials Information System (CTIS): 2024‐515997‐28‐00

Background: Delirium is a frequent complication in comatose Out‐of‐Hospital Cardiac Arrest (OHCA) survivors requiring postresuscitation intensive care and is associated with higher mortality and longer hospitalization. Despite this, there is no established pharmacologic strategy for delirium prevention in OHCA survivors. This trial aims to evaluate if prophylactic use of olanzapine in comatose OHCA patients can reduce delirium incidence, thereby leading to a shorter duration of hospitalization. Methods: The Danish Out‐of‐Hospital Cardiac Arrest (DANOCHA) trial is an investigator‐initiated, multicenter, randomized, controlled trial evaluating four postresuscitation interventions in adult patients resuscitated after OHCA including administration of prophylactic olanzapine compared with placebo. Comatose adult patients with OHCA of presumed cardiac cause and sustained return of spontaneous circulation (> 20 min) will be randomized 1:1 to receive either 10 mg of olanzapine or placebo immediately after inclusion in the trial and the two following evenings for a total of three doses. The primary outcome is days alive and out of the hospital within 30 days after admission. Analysis of primary outcome will be analyzed using the Wilcoxon rank‐sum test. Results will be presented as medians with interquartile ranges and 95% confidence intervals for the median difference. Inclusion began in June 2023, and the study aims to include 1000 patients from five sites over an estimated time period of 3–4 years. The trial is registered at clinicaltrials.gov (identifier: NCT05895838) and euclinicaltrials.eu (2024‐515997‐28‐00). Perspectives: Optimizing postresuscitation care through large‐scale randomized trials is essential for improving outcomes of OHCA survivors. The findings from this part of the DANOHCA trial will provide evidence regarding the effects of prophylactic olanzapine in comatose OHCA survivors. Trial Registration: EudraCT no 2016‐003265‐26; EU CTIS no 2024‐515997‐28‐00; ClinicalTrials.gov identifier NCT05895838

Background: Post‐cardiac arrest care for patients resuscitated from out‐of‐hospital cardiac arrest (OHCA) includes multiple pharmacological and physiological interventions, yet optimal strategies to reduce post‐cardiac arrest syndrome–related morbidity and mortality remain uncertain. The DANOHCA (Danish Out‐of‐Hospital Cardiac Arrest) trial evaluates four such interventions—high‐dose dexamethasone, prophylactic olanzapine, elevated backrest position, and early wakeup—in a factorial trial framework. This manuscript presents the complete statistical analysis plan for analyses common to all four DANOHCA interventions. Methods: DANOHCA is an investigator‐initiated, multicenter, randomized, 2 × 2 × 2 × 2 factorial clinical trial enrolling comatose adult OHCA patients with a presumed cardiac etiology who achieve sustained return of spontaneous circulation, with randomization within 180 min of return of spontaneous circulation. Participants are co‐randomized to Dexamethasone versus placebo, olanzapine versus placebo, backrest elevation at 35° versus 5°, and early (≤ 6 h) versus late (28–36 h) wakeup, with pharmacological interventions blinded and physiological interventions open‐label. This statistical analysis plan specifies the primary and secondary outcomes, covariate adjustment, handling of missing data, assessments of interactions between interventions, and assumption checks, with all primary analyses conducted according to the intention‐to‐treat principle. The analysis plan is finalized prior to completion of randomization. Results: The primary outcomes are 90‐day all‐cause mortality for the dexamethasone and backrest interventions, and days alive outside hospital within 30 days for the olanzapine and early wakeup interventions, with common secondary and tertiary endpoints including mortality at later time points, neurological function, health‐related quality of life, organ function, and safety outcomes. Mixed‐effects regression models, Cox regression, stratified nonparametric tests, and prespecified sensitivity analyses will be applied to minimize bias and quantify intervention effects, including their associated uncertainties. Conclusion: This predefined statistical analysis plan provides a detailed, transparent framework for the primary analyses and reporting of the DANOHCA trial. Trial Registration: Clinical Trials Information System (CTIS): 2024‐515997‐28‐00

Background: Melatonin may have several beneficial clinical effects in the perioperative setting. In children, it has been studied for preoperative anxiety, postoperative pain, and emergence delirium. Melatonin's pharmacokinetic profile is well‐known in adults, but data in young children are sparse. We aimed to investigate the pharmacokinetic parameters of an intravenous intraoperative bolus of melatonin in pediatric surgical patients. Methods: We enrolled 20 participants aged 1–6 years undergoing general anesthesia for elective surgery to receive an intravenous melatonin dose of 0.15 mg·kg ⁻¹ before end of surgery. A total of six blood samples were drawn from each participant at the following time points: baseline, 0, 15, 30, 60, and 90 min post‐injection. Plasma melatonin concentrations were determined with High‐Performance Liquid Chromatography with Fluorescence Detection (HPLC‐FLD). Pharmacokinetic parameters were estimated with non‐compartmental analysis. Clinical outcomes were recorded. Results: We included 98 samples in the pharmacokinetic analysis. We found a maximum plasma concentration ( C _max ) of 416 298 [IQR 322 230–508 006] pg·mL ⁻¹ and an elimination half‐life ( t _1/2 ) of 35.2 (SD 8.4) minutes. Clearance (CL) was 0.0183 (SD 0.0039) L·min ⁻¹ ·kg ⁻¹ and volume of distribution (V _d ) 0.92 (SD 0.27) L·kg ⁻¹ . There were no cases of emergence delirium, mean maximum pain (FLACC) score was 1.3 (SD 2.0), and time to awakening and discharge readiness averaged one and two hours, respectively. Adverse events could be attributed to routine postoperative symptoms. Conclusion: Administering intravenous melatonin in a dose of 0.15 mg·kg ⁻¹ in 1–6‐year‐olds yielded pharmacokinetic characteristics comparable to those reported in adults. The observed postoperative events were consistent with expected perioperative findings. These data support dose selection for trials investigating the perioperative use of melatonin in children. Trial Registration: CTIS: EU CT 2024‐517592‐20. Clinicaltrials.gov : NCT05541276 (registered 12/09‐2022)

Background: Survivors of out‐of‐hospital cardiac arrest (OHCA) who remain comatose after return of spontaneous circulation are routinely sedated and mechanically ventilated during early post‐resuscitation care. Although prolonged sedation has traditionally been considered necessary, contemporary normothermia‐based temperature control allows earlier wake‐up call. The optimal timing of an early wake‐up call remains unknown and may influence overall mortality, neurological recovery, duration of mechanical ventilation, and length of hospital stay. Methods: The Danish Out‐of‐Hospital Cardiac Arrest (DANOHCA) trial (clinicaltrials.gov identifier: NCT05895838; and euclinicaltrials.eu, identifier: 2024–515,997–28‐00) is an investigator‐initiated, multicenter, randomized clinical trial using a 2 × 2 × 2 × 2 factorial design evaluating four interventions in patients resuscitated from OHCA. The present protocol describes the comparison of an early versus late wake‐up call strategy. Adult patients (≥ 18 years) with presumed cardiac‐cause of OHCA, sustained return of spontaneous circulation, and persistent unconsciousness on intensive care unit admission are randomized 1:1 to early wake‐up call (≤ 6 h after randomization) or late wake‐up call (28–36 h after randomization). Wake‐up call includes interruption of sedation, assessment of neurology, and may be followed by extubation if predefined neurological and respiratory criteria are fulfilled. The primary endpoint is days alive and out of hospital within 30 days after randomization. Analyses will follow a modified intention‐to‐treat principle. Perspectives: Optimizing post‐resuscitation care remains a cornerstone in managing comatose cardiac arrest survivors and improving outcomes. We hypothesize that sedation for 28–36 h leads to more days alive outside of the hospital in 30 days compared to sedation for ≤ 6 h. Trial Registration: EudraCT number: 2016‐003265‐26; EU CTIS no 2024‐515997‐28‐00; ClinicalTrials.gov identifier: NCT05895838.

Purpose: Delirium is frequent and associated with increased health expenditures, unfavourable outcomes and increased mortality. Diagnosis currently relies on clinical scales and is often missed. However, blood-based biomarkers may represent a feasible tool to enhance risk stratification, early diagnosis, and monitoring. We aimed to identify blood-based biomarkers associated with delirium in adult intensive care unit patients, to provide a structured summary of the evidence, and to highlight gaps of knowledge to inform future research. Methods: A systematic literature search was performed in PubMed, EMBASE, The Cochrane Library , and Web of Science from inception to 3rd September 2025 with no date or language restrictions. Eligible studies were observational, assessing associations between blood-based biomarkers and delirium in critically ill adults admitted to an intensive care unit. The Newcastle–Ottawa Scale was applied to assess study quality. Data were qualitatively synthesized in a systematic narrative synthesis. Results: Out of 2130 records including duplicates, 61 studies were included, comprising 39,355 adult patients, of whom 16,762 were screened positive for delirium. Delirium definition, assessment tools and frequency, reported delirium outcomes, and timing of biomarker sampling varied. In total, 153 blood-based biomarkers were identified, 101 were significantly associated with delirium and 40 were associated with delirium across two studies or more. Study quality was generally poor and substantial study heterogeneity limited comparability. Conclusion: Current evidence does not support clinical use of any biomarker. Poor study quality, small sample sizes, and considerable methodological heterogeneity limit interpretation, generalizability, validation, and firm conclusions. Standardized methodology and international consensus are essential in future research.

Background: Surgery is often needed to provide disease control in patients with inflammatory bowel disease. Studies document increased postoperative pain and complicated perioperative courses. This study examines postoperative pain and opioid consumption in patients with inflammatory bowel disease undergoing laparoscopic subtotal colectomy. Furthermore, the impact of epidural anesthesia is investigated. Methods: This study encompassed an observational cohort of patients with inflammatory bowel disease undergoing subtotal colectomy in the period 1 January 2018 to 30 June 2023 at a university hospital in Denmark. Demographic and perioperative data, opioid consumption, pain scores, and procedural data of epidural anesthesia were retrieved from patient records. Data were stratified according to the use of epidural anesthesia. Results: The study included 153 patients. Overall, 45% of patients received epidural anesthesia. Opioid consumption in the postoperative care unit was 9.2 mg (3.3–15.8 mg) and 3.8 mg (0–15 mg) ( P = 0.04) in patients without and with epidural anesthesia, respectively. Correspondingly, opioid consumption during the first 24 h postoperatively was 23.3 mg (10–33 mg) and 6.8 mg (0–21.7 mg) ( P < 0.001). Numerical rating scale (NRS) pain in the postoperative care unit was 3.5 (2–4.6) and 2.7 (1.3–4.3) in patients without and with epidural anesthesia, respectively ( P = 0.1645). Thirty percent of patients treated with epidural anesthesia experienced ≥ 1 adverse event(s) related to epidural anesthesia. Conclusions: Our study demonstrates a relatively low consumption of opioids and low pain scores in the early postoperative period following laparoscopic subtotal colectomy regardless of the use of epidural anesthesia. Epidural anesthesia was associated with a substantial frequency of adverse events.

Illness and injury are often accompanied by experiences of bodily objectification. Medical treatments intended to restore the structure or function of the body may amplify these experiences of objectification by recasting the patient’s body as a biomedical object—something to be examined, measured, and manipulated. In this article, we contribute to the phenomenology of embodiment in illness and medicine by reexamining the results of a qualitative study of the experiences of nurses and patients isolated in an intensive care unit during the first wave of COVID-19. Drawing upon the phenomenological concept of embodiment—as developed in the work of Edmund Husserl, Maurice Merleau-Ponty, Jean-Paul Sartre, and Emmanuel Levinas—we reconsider how bodily objectification manifests in complex clinical encounters. We show that, in these settings, objectification is not simply the unilateral act of a clinician objectifying a patient. Rather, both clinicians and patients reported a variety of objectifying experiences influenced by their interactions, the immediate context of the intensive care milieu, and the broader atmosphere of a global pandemic. In light of these findings, we argue that bodily objectification in illness and medicine can often be more complicated than typically presented in the phenomenological literature.

Background Emergence agitation and delirium in children remain a common clinical challenge in the post-anesthetic care unit. Preoperative oral melatonin has been suggested as an effective preventive drug with a favorable safety profile. The oral bioavailability of melatonin, however, is low. Therefore, the MELA-PAED trial aims to investigate the efficacy and safety of intraoperative intravenous melatonin for the prevention of emergence agitation in pediatric surgical patients.Methods MELA-PAED is a randomized, double-blind, parallel two-arm, multi-center, superiority trial comparing intravenous melatonin with placebo. Four hundred participants aged 1-6 years will be randomized 1:1 to either the intervention or placebo. The intervention consists of intravenous melatonin 0.15 mg/kg administered approximately 30 min before the end of surgery. Participants will be monitored in the post-anesthetic care unit (PACU), and the Post Hospitalization Behavior Questionnaire for Ambulatory Surgery (PHBQ-AS) will be performed on days 1, 7, and 14 after the intervention. Serious Adverse Events (SAE) will be assessed up to 30 days after the intervention.Results The primary outcome is the incidence of emergence agitation, assessed dichotomously as any Watcha score >2 during the participant's stay in the post-anesthetic care unit. Secondary outcomes are opioid consumption in the post-anesthetic care unit and adverse events. Exploratory outcomes include SAEs, postoperative pain, postoperative nausea and vomiting, and time to awakening, to first oral intake, and to discharge readiness.Conclusion The MELA-PAED trial investigates the efficacy of intravenous intraoperative melatonin for the prevention of emergence agitation in pediatric surgical patients. Results may provide further knowledge concerning the use of melatonin in pediatric perioperative care.

Background: During the COVID‐19 pandemic, patients in the intensive care unit have been subjected to strict isolation precautions, and potentially long and complicated patient courses. The aim of the study is to provide an investigation of the experiences of isolation in COVID‐19‐positive patients in the ICU during the first phase of the COVID‐19 pandemic in Denmark.Methods: The study was performed in a 20‐bed ICU at a university hospital in Copenhagen, Denmark. The study is based on a phenomenological framework, Phenomenologically Grounded Qualitative Research. This approach provides insights into the tacit, pre‐reflective and embodied dimensions of the specific experience under investigation. Methods included a combination of in‐depth structured interviews with ICU patients 6–12 months after ICU discharge, and observations from inside the isolated patient rooms. The descriptions of experiences gathered through the interviews were subjected to systematic thematic analysis.Results: Twenty‐nine patients were admitted to the ICU in the period 10 March and 19 May 2020. A total of six patients was included in the study. Themes consistently reported across all patients included (1) being objectified to degrees that implied self‐alienation; (2) feeling a sense of being in captivity; (3) being in an experiential state of surrealism, and finally (4) experiencing extreme loneliness and intercorporeal deprivation.Conclusion: This study provided further insights into the liminal patient experiences of being isolated in the ICU due to COVID‐19. Robust themes of experience were achieved through an in‐depth phenomenological approach. Although, similarities in experiences compared to other patient groups exist, the precarious situation constituted by COVID‐19 lead to significant intensifications across multiple parameters.