Pharmacokinetics of propofol in severely obese surgical patients.

BACKGROUND: Existing PK models of propofol include sparse data from very obese patients. The aim of this study was to develop a PK model based on standardised surgical conditions and spanning from normal-weight up to, and including, a high number of very obese patients. METHODS: Adult patients scheduled for laparoscopic cholecystectomy or bariatric surgery were studied. Anaesthesia was induced with propofol 2 mg/kg adjusted body weight over 2 min followed by 6 mg/kg/h adjusted body weight over 30 min. For the remainder of the operation anaesthesia was maintained with sevoflurane. Remifentanil was dosed according to clinical need. Eight arterial samples were drawn in a randomised block sampling regimen over a span of 24 h. Time-concentration data were analysed by population PK modelling using non-linear mixed-effects modelling. RESULTS: Four hundred and seventy four serum propofol concentrations were collected from 69 patients aged 19-60 years with a BMI 21.6-67.3 kg/m2 . Twenty one patients had a BMI above 50 kg/m2 . A 3-compartment PK model was produced wherein three different body weight descriptors and sex were included as covariates in the final model. Total body weight was found to be a covariate for clearance and Q3; lean body weight for V1, V2 and Q2; predicted normal weight for V3 and sex for V1. The fixed allometric exponent of 0.75 applied to all clearance parameters improved the performance of the model. Accuracy and precision were 1.4% and 21.7% respectively in post-hoc performance evaluation. CONCLUSION: We have developed a new PK model of propofol that is suitable for all adult weight classes. Specifically, it is based on data from an unprecedented number of individuals with very high BMI.

Patient characteristics associated with posttraumatic stress symptoms in intensive care unit survivors during a one-year follow-up: A multicenter study.

BACKGROUND: Intensive care unit (ICU) patients are at risk of suffering from posttraumatic stress symptoms (PTSS) after ICU survival. OBJECTIVES: To describe the prevalence of high levels of PTSS the first year after ICU admission. Further, to identify specific combinations of patient characteristics (latent classes based on pre-ICU data, demographics, and clinical characteristics), and to investigate possible associations among these classes and PTSS at 3, 6, and 12 months after ICU admission. METHODS: Self-reported PTSS were measured with Impact of Event Scale-Revised (IES-R). PTSS and possible predictive factors (pre-ICU data, demographics, and clinical characteristics) were analyzed using descriptive statistics, latent class analysis, and linear mixed model for repeated measures. RESULTS: High PTSS levels (IES-R ≥ 33) were reported by 14.9 % (95 % confidence interval [CI] [10.0; 21.1]), 16.7 % (95 % CI [11.5; 23.1]), and 18.4 % (95 % CI [12.9; 25.0]) of patients (sample 1, n = 174) at 3, 6, and 12 months, respectively. Three latent classes were identified (sample 2, n = 417). PTSS were significantly associated with class 2 (male with longer hospital stay) at 6 months and class 3 (age≥70, lower level of education, higher Simplified Acute Physiology Score, being mechanically ventilated) at all three measurement times. CONCLUSIONS: The prevalence of high levels of PTSS is the greatest 12 months after ICU admission. Health professionals can use this information to be aware of specific groups of ICU patients reporting PTSS during the first year and follow up on these.

Pain management after open colorectal surgery: An update of the systematic review and procedure-specific postoperative pain management (PROSPECT) recommendations.

BACKGROUND: Open colectomy is still performed around the world and associated with significant postoperative pain. OBJECTIVES: Unpublished recommendations based on a systematic review were proposed by the PROcedure SPECific postoperative pain managemenT (PROSPECT) group in 2016. We aimed to update these recommendations by evaluating the available literature and develop recommendations for optimal pain management after open colectomy according to the PROSPECT methodology. DESIGN AND DATA SOURCES: A systematic review using the PROSPECT methodology was undertaken. Randomised controlled trials and systematic reviews published in the English language from 2016 to 2022 assessing postoperative pain after open colectomy using analgesic, anaesthetic or surgical interventions were identified. The primary outcome included postoperative pain scores. RESULTS: The previous 2016 review included data from 93 studies. Out of 842 additional eligible studies identified, 13 new studies were finally retrieved for analysis. Intra-operative and postoperative interventions that improved postoperative pain were paracetamol, epidural analgesia. When epidural is not feasible, intravenous lidocaine or bilateral TAP block or postoperative continuous pre-peritoneal infusion are recommended. Intra-operative and postoperative Cyclo-oxygenase (COX)-2 specific-inhibitors or non-steroidal anti-inflammatory drugs (NSAIDs) are recommended for colonic surgery. CONCLUSIONS: The analgesic regimen for open colectomy should include intra-operative paracetamol and COX-2 specific inhibitors or NSAIDs (restricted to colonic surgery), epidural and continued postoperatively with opioids used as rescue analgesics. If epidural is not feasible, bilateral TAP block or IV lidocaine are recommended. Safety issues should be highlighted: local anaesthetics should not be administered by two different routes at the same time. Because of the risk of toxicity, careful dosing and monitoring are necessary.

The 2024 revision of the Norwegian standard for the safe practice of anaesthesia.

The Norwegian standard for the safe practice of anaesthesia was first published in 1991, and revised in 1994, 1998, 2005, 2010 and 2016 respectively. The 1998 version was published in English for the first time in Acta Anaesthesiologica Scandinavica in 2002. It must be noted that this is a national standard, reflecting the specific opportunities and challenges in a Norwegian setting, which may be different from other countries in some respects. A feature of the Norwegian healthcare system is the availability, on a national basis, of specifically highly trained and qualified nurse anaesthetists. Another feature is the geography, with parts of the population living in remote areas. These may be served by small, local emergency hospitals. Emergency transport of patients to larger hospitals is not always achievable when weather conditions are rough. These features and challenges were considered important when designing a balanced and consensus-based national standard for the safe practice of anaesthesia, across Norwegian clinical settings. In this article, we present the 2024 revision of the document. This article presents a direct translation of the complete document from the Norwegian original.

Cardiac output estimation using ballistocardiography: a feasibility study in healthy subjects.

There is no reliable automated non-invasive solution for monitoring circulation and guiding treatment in prehospital emergency medicine. Cardiac output (CO) monitoring might provide a solution, but CO monitors are not feasible/practical in the prehospital setting. Non-invasive ballistocardiography (BCG) measures heart contractility and tracks CO changes. This study analyzed the feasibility of estimating CO using morphological features extracted from BCG signals. In 20 healthy subjects ECG, carotid/abdominal BCG, and invasive arterial blood pressure based CO were recorded. BCG signals were adaptively processed to isolate the circulatory component from carotid (CCc) and abdominal (CCa) BCG. Then, 66 features were computed on a beat-to-beat basis to characterize amplitude/duration/area/length of the fluctuation in CCc and CCa. Subjects' data were split into development set (75%) to select the best feature subset with which to build a machine learning model to estimate CO and validation set (25%) to evaluate model's performance. The model showed a mean absolute error, percentage error and 95% limits of agreement of 0.83 L/min, 30.2% and - 2.18-1.89 L/min respectively in the validation set. BCG showed potential to reliably estimate/track CO. This method is a promising first step towards an automated, non-invasive and reliable CO estimator that may be tested in prehospital emergencies.

Wireless patient monitoring and Efficacy Safety Score in postoperative treatment at the ward: evaluation of time consumption and usability.

To evaluate objective time consumption and how nurses perceived introducing wireless patient monitoring (WPM) and a validated score on patient quality and safety, the Efficacy Safety Score (ESS), at a mixed surgery ward. After fulfilling a randomised controlled trial combining the ESS and WPM, we addressed time consumption and conducted a questionnaire survey among nurses who participated in the study. The questionnaire appraised the nurses' evaluation of introducing these tools for postoperative management. Of 28 invited nurses, 24 responded to the questionnaire, and 92% reported the ESS and WPM-systems to increase patient safety and quality of care. 67% felt the intervention took extra time, but objective workload measurements revealed reduced time to 1/3 using ESS and WPM compared to standard manual assessment. Improved confidence when using the systems was reported by 83% and improved working situation by 75%. In a test situation to measure time consumption, the ESS and pre-attached WPM-systems require less time than the conventional standard of care, and may allow for more frequent clinical monitoring at the post-surgical ward. The combination of the ESS and the WPM systems was perceived as positive by participating nurses and further clinical development and research is warranted.

Prevalence of and predictive factors associated with high levels of post-traumatic stress symptoms 3 months after intensive care unit admission: A prospective study.

BACKGROUND: Post-traumatic stress symptoms (PTSS) following intensive care unit (ICU) treatment may increase morbidity and mortality. Therefore, it is important to identify patients at risk of suffering from such symptoms. OBJECTIVES: The objective of this study was to describe the prevalence and identify possible predictive factors associated with high levels of PTSS 3 months after ICU admission. METHODS: A multicentre, observational study was carried out in six ICUs in Norway. Patients aged ≥18 years were included. The Impact of Event Scale-Revised measured PTSS 3 months after ICU admission. The impacts of pre-ICU measures; demographic and clinical measures; and daily measures of pain, agitation, and delirium were analysed using univariate and multivariate logistic regression models. RESULTS: In total, of the 273 patients included, the prevalence rate of high levels of PTSS was 19.8% (n = 54) 3 months after ICU admission (95% confidence interval [CI]: [15.2, 25.0]). Female gender, age, pre-ICU unemployment, a minimum of one episode of agitation or delirium, and pre-ICU level of functioning in daily living were all significantly associated with high levels of PTSS in univariate logistic analyses. In the multivariate logistic regression, two models were analysed. In model 1, episodes of agitation during ICU stay (odds ratio [OR] = 4.73; 95% CI: [1.17, 19.0]), pre-ICU unemployment (OR = 3.33; 95% CI: [1.26, 8.81]), and pre-ICU level of functioning in daily living (OR = 0.78; 95% CI: [0.63, 0.96]) (implying lower level) increased the odds of reporting high levels of PTSS. In model 2, pre-ICU unemployment (OR = 2.70; 95% CI: [1.05, 6.93]) and pre-ICU level of functioning in daily living (OR = 0.77; 95% CI: [0.62, 0.95]) (implying lower level) increased the odds of reporting high levels of PTSS. CONCLUSIONS: Healthcare personnel are suggested to be aware of ICU patients' pre-ICU employment status, pre-ICU functioning in daily living, and agitation during ICU stay to identify those at risk of PTSS after discharge.

Maternal hypothermia during elective caesarean delivery: A prospective observational study.

BACKGROUND: Patients undergoing caesarean delivery are at risk of developing unintended perioperative hypothermia, defined as a core temperature <36.0°C. Most previous studies of core temperature in caesarean delivery patients have not been conducted with accurate measurements for the complete perioperative period. Therefore, we conducted a prospective observational study to identify the incidence and duration of pre- and post-operative maternal hypothermia with a high accuracy continuous temperature monitoring system. METHODS: Women ≥18 years old presenting for elective caesarean delivery under spinal anaesthesia were invited to participate in the study. The primary outcomes were the incidence and duration of perioperative maternal hypothermia (<36.0°C). Maternal core temperatures were measured with the non-invasive zero-heat-flux thermometer (Bair Hugger Temperature Monitoring System, 3M) throughout the perioperative course. RESULTS: A total of 40 participants were recruited to the study. The incidence of perioperative hypothermia was 32.5%, with a duration of 77 ± 40 min (mean ± standard deviation). The hypothermic patients had similar core temperature as the normothermic patients at baseline preoperatively, but significantly lower temperature at operating room arrival and during the remaining study period. Forty percent of all patients reported thermal discomfort and felt cold on admission to post anaesthesia care unit, whereas 33% had shivering. Neither thermal discomfort nor shivering were associated with hypothermia. CONCLUSION: In the present study almost a third of the women undergoing elective caesarean delivery developed perioperative hypothermia with a core temperature <36.0°C. The mean duration of maternal hypothermia was 77 min, lasting well into the postoperative period for many patients. These data should remind healthcare professionals of the importance of measuring core temperature in all phases of the perioperative setting and to consider optimal warming measures to avoid and treat hypothermia.

Preventing hypothermia in pediatric neurosurgery in Africa-A randomized controlled non-inferiority trial of insulation versus active warming.

PURPOSE: The objective of this study was to compare the efficacy of a low-cost heat-preserving method in preventing intraoperative hypothermia with that of forced-air warming in a resource-limited setting. METHODS: In this randomized controlled non-inferiority trial, we recruited children younger than 12 years scheduled for cranial neurosurgery in a large East-African hospital. Patients were block-randomized by age to intraoperative warming measures using Hibler's method (intervention) or warm air (comparator). Hibler's group patients were circumferentially wrapped in transparent plastic sheeting (providing a vapor-trap) over a layer of cotton blankets, then laid on an insulating foam mattress. Warm air group patients were treated with forced-air convection via an underlying Snuggle Warm™ Pediatric Full Body mattress. Allocated warming measures were initiated in the operating theatre and discontinued upon anesthesia emergence. Perioperative temperatures were measured using noninvasive forehead probes (SpotOn™). The primary outcome was incidence of hypothermia (core temperature < 36.0° for longer than 5 min). Our null hypothesis was that Hibler's method is inferior in efficacy to the warm air method by a margin exceeding 20%. Among secondary outcomes were duration of hypothermia as proportion of surgical duration, incidence of postoperative shivering and rescue measure requirements. RESULTS: We analyzed data for 77 participants (Hibler's = 38; warm air = 39). There was no significant difference between the Hibler's and warm air arms of the study in the primary outcome of incidence of hypothermia (59.0% vs. 60.5% respectively; OR 1.07; 95% CI 0.43-2.65; p = .890). However, the risk difference (1.55%; 95% CI -0.20 to -0.24) exceeded the 0.2 margin and non-inferiority could not be declared. There was considerable need for rescue measures in both groups (71.1 0% vs. 69.2%; OR 1.09; 95% CI 0.41-2.90; p = .861). There was no statistically significant difference between groups for any prespecified secondary outcome. CONCLUSION: Although perioperative core temperatures were not significantly different, we could not declare an inexpensive heat-preserving method non-inferior to warm air convection in preventing intraoperative hypothermia in children undergoing anesthesia for cranial neurosurgery in a resource-limited setting. The extensive need for rescue measures may have masked important differences. TRIAL REGISTRATION: US National Institutes of Health Clinicaltrials.gov database (ID no. NCT02975817).

Prevalence of psychological distress in nurses, physicians and leaders working in intensive care units during the COVID-19 pandemic: a national one-year follow-up study.

OBJECTIVE: To report and compare psychological distress as symptoms of anxiety, depression and post-traumatic stress among intensive care units' (ICU) nurses, physicians and leaders at 12 months after the baseline survey (spring 2020), during the COVID-19 pandemic in Norway. Furthermore, to analyse which baseline demographic and COVID ICU-related factors have a significant impact on psychological distress at 12 months. DESIGN: Prospective, longitudinal, observational cohort study. SETTING: Nationwide, 27 of 28 hospitals with COVID ICUs in Norway. PARTICIPANTS: Nurses, physicians and their leaders. At 12 month follow-up 287 (59.3%) of 484 baseline participants responded. PRIMARY AND SECONDARY OUTCOME MEASURES: Symptoms of anxiety and depression using the Hopkins Symptoms Checklist-10 (HSCL-10). Symptoms of post-traumatic stress using the post-traumatic stress disease checklist for the Diagnostic and Statistical Manual of Mental Disorders 5 (PCL-5).Demographics (included previous symptoms of anxiety and depression) and COVID ICU-related factors (professional preparations, emotional experience and support) impacting distress at 12 months. RESULTS: Psychological distress, defined as caseness on either or both HSCL-10 and PCL-5, did not change significantly and was present for 13.6% of the participants at baseline and 13.2% at 12 month follow-up. Nurses reported significantly higher levels of psychological distress than physicians and leaders. Adjusted for demographics and the COVID ICU-related factors at baseline, previous symptoms of depression and fear of infection were significantly associated with higher levels of anxiety and depression at 12 months. Previous symptoms of depression, fear of infection and feeling of loneliness was significantly associated with more symptoms of post-traumatic stress. CONCLUSION: One year into the COVID-19 pandemic 13.2% of the ICUs professionals reported psychological distress, more frequently among the nurses. Fear of infection, loneliness and previous symptoms of depression reported at baseline were associated with higher levels of distress. Protective equipment and peer support are recommended to mitigate distress. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov. Identifier: NCT04372056.

Cerebrospinal fluid quinolinic acid is strongly associated with delirium and mortality in hip-fracture patients.

BACKGROUNDThe kynurenine pathway (KP) has been identified as a potential mediator linking acute illness to cognitive dysfunction by generating neuroactive metabolites in response to inflammation. Delirium (acute confusion) is a common complication of acute illness and is associated with increased risk of dementia and mortality. However, the molecular mechanisms underlying delirium, particularly in relation to the KP, remain elusive.METHODSWe undertook a multicenter observational study with 586 hospitalized patients (248 with delirium) and investigated associations between delirium and KP metabolites measured in cerebrospinal fluid (CSF) and serum by targeted metabolomics. We also explored associations between KP metabolites and markers of neuronal damage and 1-year mortality.RESULTSIn delirium, we found concentrations of the neurotoxic metabolite quinolinic acid in CSF (CSF-QA) (OR 2.26 [1.78, 2.87], P < 0.001) to be increased and also found increases in several other KP metabolites in serum and CSF. In addition, CSF-QA was associated with the neuronal damage marker neurofilament light chain (NfL) (ß 0.43, P < 0.001) and was a strong predictor of 1-year mortality (HR 4.35 [2.93, 6.45] for CSF-QA ≥ 100 nmol/L, P < 0.001). The associations between CSF-QA and delirium, neuronal damage, and mortality remained highly significant following adjustment for confounders and multiple comparisons.CONCLUSIONOur data identified how systemic inflammation, neurotoxicity, and delirium are strongly linked via the KP and should inform future delirium prevention and treatment clinical trials that target enzymes of the KP.FUNDINGNorwegian Health Association and South-Eastern Norway Regional Health Authorities.

Spread of local anesthetics after erector spinae plane block: an MRI study in healthy volunteers.

BACKGROUND: Erector spinae plane block (ESPB) is a truncal fascial block with a disputed mechanism and anatomical site of effect. This study aimed to perform a one-sided ESPB and use MRI to investigate the spread of the local anesthetic (LA) and the corresponding cutaneous loss of sensation to pinprick and cold. METHODS: Ten volunteers received a right-sided ESPB at the level of the seventh thoracic vertebra (Th7), consisting of 30 mL 2.5 mg/mL ropivacaine with 0.3 mL gadolinium. The primary outcome was the evaluation of the spread of LA on MRI 1-hour postblock. The secondary outcome was the loss of sensation to cold and pinprick 30-50 min after the block was performed. RESULTS: All volunteers had a spread of LA on MRI in the erector spinae muscles and to the intercostal space. 9/10 had spread to the paravertebral space and 8/10 had spread to the neural foramina. 4/10 volunteers had spread to the epidural space. One volunteer had extensive epidural spread as well as contralateral epidural and foraminal spread. Four volunteers had a loss of sensation both posterior and anterior to the midaxillary line, while six volunteers had a loss of sensation only on the posterior side. CONCLUSION: We found that LA consistently spreads to the intercostal space, the paravertebral space, and the neural foramina after an ESPB. Epidural spread was evident in four volunteers. Sensory testing 30-50 min after an ESPB shows highly variable results, and generally under-represents what could be expected from the visualized spread on MRI 60 min after block performance. TRIAL REGISTRATION NUMBER: NCT05012332.

Efficacy of a TAP block versus an anterior QLB for laparoscopic inguinal hernia repair: A randomised controlled trial.

BACKGROUND: Both the transversus abdominis plane (TAP) block and the anterior quadratus lumborum block (QLB) have been shown effective in reducing postoperative pain after laparoscopic inguinal hernia repair. Our hypothesis was that there is no difference in analgesic effect between the two blocks for this procedure. METHODS: In this prospective, double-blind, randomised controlled study, 60 adult patients undergoing laparoscopic inguinal hernia repair were equally randomly assigned to either a preoperative TAP block or an anterior QLB. The primary outcome was oral morphine equivalent (OME) consumption at 4 h postoperatively. Secondary outcomes were OME consumption at 24, 48 h and 7 days, pain scores at rest and when coughing, nausea, and level of sedation measured at 1, 2, 3, 24, and 48 h and 7 days postoperatively. RESULTS: Fifty-three patients completed the study. There was no significant difference in OME consumption at 4 h postoperatively, TAP group (10.3 ± 7.85 mg) (mean ± SD) versus the anterior QLB group (10.9 ± 10.85 mg) (p = .713). The pain scores were similar at rest and when coughing during the 7 day observation period, as were the level of sedation and incidence of nausea. There were no cases of serious side-effects or muscle weakness of the thigh on the same side as the block. CONCLUSION: There is no difference in OME consumption, pain, nausea or sedation between the TAP and the anterior QLB. Thus, the choice between the two blocks in a clinical setting of laparoscopic inguinal hernia repair should be based on other aspects, such as skills, practicalities, and potential risks.

Correction: Stafseth et al. Symptoms of Anxiety, Depression, and Post-Traumatic Stress Disorder in Health Care Personnel in Norwegian ICUs during the First Wave of the COVID-19 Pandemic, a Prospective, Observational Cross-Sectional Study. Int. J. Environ. Res. Public Health 2022, 19, 7010.

In the original publication [...].

Pain treatment and prophylaxis on pain.

PURPOSE OF REVIEW: Also in ambulatory surgery, there will usually be a need for analgesic medication to deal with postoperative pain. Even so, a significant proportion of ambulatory surgery patients have unacceptable postoperative pain, and there is a need for better education in how to provide proper prophylaxis and treatment. RECENT FINDINGS: Postoperative pain should be addressed both pre, intra- and postoperatively. The management should be with a multimodal nonopioid-based procedure specific guideline for the routine cases. In 10-20% of cases, there will be a need to adjust and supplement the basic guideline with extra analgesic measures. This may be because there are contraindications for a drug in the guideline, the procedure is more extensive than usual or the patient has extra risk factors for strong postoperative pain. Opioids should only be used when needed on top of multimodal nonopioid prophylaxis. Opioids should be with nondepot formulations, titrated to effect in the postoperative care unit and eventually continued only when needed for a few days at maximum. SUMMARY: Multimodal analgesia should start pre or per-operatively and include paracetamol, nonsteroidal anti-inflammatory drug (NSAID), dexamethasone (or alternative glucocorticoid) and local anaesthetic wound infiltration, unless contraindicated in the individual case. Paracetamol and NSAID should be continued postoperatively, supplemented with opioid on top as needed. Extra analgesia may be considered when appropriate and needed. First-line options include nerve blocks or interfascial plane blocks and i.v. lidocaine infusion. In addition, gabapentinnoids, dexmedetomidine, ketamine infusion and clonidine may be used, but adverse effects of sedation, dizziness and hypotension must be carefully considered in the ambulatory setting.

Symptoms of Anxiety, Depression, and Post-Traumatic Stress Disorder in Health Care Personnel in Norwegian ICUs during the First Wave of the COVID-19 Pandemic, a Prospective, Observational Cross-Sectional Study.

Background: The COVID-19 pandemic has induced demanding work situations in intensive care units (ICU). The objective of our study was to survey psychological reactions, the disturbance of social life, work effort, and support in ICU nurses, physicians, and leaders. Methods: From May to July 2020, this cross-sectional study included 484 ICU professionals from 27 hospitals throughout Norway. Symptoms of anxiety and depression were measured on Hopkins Symptom Checklist-10 (HSCL-10). Symptoms of post-traumatic stress disorder (PTSD) were measured on the PCL-5. Results: The study population were highly educated and experienced professionals, well prepared for working with COVID-ICU patients. However, 53% felt socially isolated and 67% reported a fear of infecting others. Probable cases of anxiety and depression were found in 12.5% of the registered nurses, 11.6% of the physicians, and 4.1% of the leaders. Younger age and <5 years previous work experiences were predictors for high HSCL-10 scores. Reported symptom-defined PTSD for nurses 7.1%; the leaders, 4.1%; and 2.3% of physicians. Conclusions: ICU health care professionals experienced talking with colleagues as the most helpful source of support. The COVID-ICU leaders reported a significantly higher mean score than physicians and nurses in terms of pushing themselves toward producing high work effort.

Alpha-2-adrenergic receptor agonists for the prevention of delirium and cognitive decline after open heart surgery (ALPHA2PREVENT): protocol for a multicentre randomised controlled trial.

INTRODUCTION: Postoperative delirium is common in older cardiac surgery patients and associated with negative short-term and long-term outcomes. The alpha-2-adrenergic receptor agonist dexmedetomidine shows promise as prophylaxis and treatment for delirium in intensive care units (ICU) and postoperative settings. Clonidine has similar pharmacological properties and can be administered both parenterally and orally. We aim to study whether repurposing of clonidine can represent a novel treatment option for delirium, and the possible effects of dexmedetomidine and clonidine on long-term cognitive trajectories, motor activity patterns and biomarkers of neuronal injury, and whether these effects are associated with frailty status. METHODS AND ANALYSIS: This five-centre, double-blind randomised controlled trial will include 900 cardiac surgery patients aged 70+ years. Participants will be randomised 1:1:1 to dexmedetomidine or clonidine or placebo. The study drug will be given as a continuous intravenous infusion from the start of cardiopulmonary bypass, at a rate of 0.4 µg/kg/hour. The infusion rate will be decreased to 0.2 µg/kg/hour postoperatively and be continued until discharge from the ICU or 24 hours postoperatively, whichever happens first.Primary end point is the 7-day cumulative incidence of postoperative delirium (Diagnostic and Statistical Manual of Mental Disorders, fifth edition). Secondary end points include the composite end point of coma, delirium or death, in addition to delirium severity and motor activity patterns, levels of circulating biomarkers of neuronal injury, cognitive function and frailty status 1 and 6 months after surgery. ETHICS AND DISSEMINATION: This trial is approved by the Regional Committee for Ethics in Medical Research in Norway (South-East Norway) and by the Norwegian Medicines Agency. Dissemination plans include publication in peer-reviewed medical journals and presentation at scientific meetings. TRIAL REGISTRATION NUMBER: NCT05029050.