Complicating Objectification in the Medical Encounter: Embodied Experiences in the ICU during COVID-19.

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.

Intravenous MELAtonin for prevention of Postoperative Agitation and Emergence Delirium in children (MELA-PAED): A protocol and statistical analysis plan for a randomized clinical trial.

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.

Intensive care nurses' experiences of caring for isolated COVID-positive patients during first wave of COVID-19.

Background: COVID-19 has fundamentally changed all fields of health care. Intensive care nurses have been at the forefront of the pandemic facing the massive impact of the disease, both professionally and personally. This study investigated nurses' experiences of caring for isolated COVID-19 positive patients in the intensive care department during the first wave of the COVID-19 pandemic. The study investigated how isolation affected the nurses themselves, how they related with their patients, and how isolation affected patient care in general. Methods: The study was performed at a 20-bed university hospital intensive care department in Copenhagen, Denmark. COVID-19 positive patients were isolated or cohort isolated. A dedicated nurse cared for each isolated patient and wore full personal protective equipment. The study is based on in-depth phenomenological interviews with intensive care nurses conducted in summer 2020. The interviews were structured according to the principles of "Phenomenologically Grounded Qualitative Research." The data included observations from within the isolated patient rooms. Findings: Six intensive care nurses participated in the study. The analysis documented following themes consistently reported by all nurses: (1) a general sense of uncanniness, (2) intense feelings of confinement and co-isolation, and (3) heightened senses of bodily objectification, including how nurses' experienced their patients and also themselves. Conclusion: This is the first Scandinavian phenomenological study to focus on mapping the experiences of intensive care nurses during the extreme circumstances of the first wave of the COVID-19 pandemic. Further studies may explore long-term effects, such as psychiatric morbidity or psychological functioning in these individuals.

Remimazolam for sedation: A protocol for a systematic review with meta-analysis, trial sequential analysis, and GRADE approach.

BACKGROUND: Procedural sedation aims to facilitate a successful diagnostic or therapeutic procedure. The pharmacokinetic properties and pharmacodynamic effects need to be taken into consideration when choosing the ideal sedative. Midazolam and propofol are frequently employed. However, they are associated with respiratory depression with increasing dosage. Also, midazolam has a potentially unpredictable pharmacodynamic response and propofol may cause hypotension and injection site pain. Remimazolam may provide a superior alternative due to its rapid pharmacodynamic profile and insignificant circulatory effects. METHODS: This protocol employs the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. The review aims to assess the beneficial and harmful clinical effects of remimazolam versus placebo or other sedatives in adult patients requiring sedation in relation to a diagnostic or therapeutic procedure, or due to other circumstances. Three primary outcomes are identified: Sedation success rate, respiratory complications, and hemodynamic complications. Six secondary outcomes are identified: among these are quality of recovery and serious adverse events. All randomized trials are included. The search strategy includes six major biomedical databases. Literature screening and data extraction will be performed independently by two authors. Risk of systemic error will be assessed with Risk of Bias 2 Tool. Risk of random error will be assessed with trial sequential analysis. Heterogeneity will be evaluated by appropriate statistical tests. The certainty of the evidence will be judged using Grading of Recommendations Assessment, Development, and Evaluation. Meta-analysis will be carried out with Rstudio. A "Summary of Findings" table will be presented with our primary and secondary outcome results. DISCUSSION: The systematic review with up-to-date methodology outlined in this protocol investigates the clinical effects of remimazolam in relation to procedural sedation. The results may guide clinicians in the clinical use of remimazolam.

Experiences of isolation in patients in the intensive care unit during the COVID-19 pandemic.

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.

The use of melatonin in Danish intensive care departments-A nationwide observational study.

BACKGROUND: Melatonin is widely employed as a hypnotic in various patient groups. In intensive care patients, melatonin seems to be increasingly used due to potential clinical effects and a favourable safety profile. OBJECTIVES: We aimed to investigate the extend of usage and clinical practice of melatonin therapy in intensive care departments in Denmark. DESIGN: Data from regional hospital pharmacies and the Danish Intensive Care Database were used to estimate defined daily dose and defined daily dose per 1000 ICU admission days. Also, related expenses in the period 2015-2019. Finally, a questionnaire describing the clinical practice of melatonin therapy was provided to all Danish intensive care departments. PRINCIPAL OBSERVATIONS: The usage of melatonin in intensive care departments in Denmark increased from 21,300 DDD (200.0 DDD per 1000 ICU admission days) in 2015 to 52,170 DDD (560.7 DDD per 1000 ICU admission days) in 2019. A total of 32 ICU departments participated in the study (97% of all Danish ICU departments). All included ICU departments employed melatonin as a hypnotic. Nineteen percent of included departments administered melatonin to all admitted patients, whereas 25% of departments rarely administered melatonin. Magistral melatonin 3-mg tablets was the most employed drug dose/formulation. Increased doses of melatonin were administered in selected patients. Melatonin was considered safe by prescribing clinicians. CONCLUSIONS: Melatonin is widely and increasingly used in Danish intensive care departments. The more than doubled usage of melatonin in the study period advocates for further studies employing validated outcomes of sleep and other patient-relevant outcomes. EDITORIAL COMMENT: This study documents that melatonin is frequently used as a hypnotic in Danish intensive care units during recent years despite a shortage of reliable evidence to support a recommendation to treat with melatonin in this context. These results support a need for conducting clinical trials to determine whether or not there is a beneficial effect of melatonin treatment in critically ill patients.

Methodology and applicability of the human contact burn injury model: A systematic review.

The contact burn injury model is an experimental contact thermode-based physiological pain model primarily applied in research of drug efficacy in humans. The employment of the contact burn injury model across studies has been inconsistent regarding essential methodological variables, challenging the validity of the model. This systematic review analyzes methodologies, outcomes, and research applications of the contact burn injury model. Based on these results, we propose an improved contact burn injury testing paradigm. A literature search was conducted (15-JUL-2020) using PubMed, EMBASE, Web of Science, and Google Scholar. Sixty-four studies were included. The contact burn injury model induced consistent levels of primary and secondary hyperalgesia. However, the analyses revealed variations in the methodology of the contact burn injury heating paradigm and the post-burn application of test stimuli. The contact burn injury model had limited testing sensitivity in demonstrating analgesic efficacy. There was a weak correlation between experimental and clinical pain intensity variables. The data analysis was limited by the methodological heterogenicity of the different studies and a high risk of bias across the studies. In conclusion, although the contact burn injury model provides robust hyperalgesia, it has limited efficacy in testing analgesic drug response. Recommendations for future use of the model are being provided, but further research is needed to improve the sensitivity of the contact burn injury method. The protocol for this review has been published in PROSPERO (ID: CRD42019133734).

Characteristics, interventions, and longer term outcomes of COVID-19 ICU patients in Denmark-A nationwide, observational study.

BACKGROUND: Most data on intensive care unit (ICU) patients with COVID-19 originate in selected populations from stressed healthcare systems with shorter term follow-up. We present characteristics, interventions and longer term outcomes of the entire, unselected cohort of all ICU patients with COVID-19 in Denmark where the ICU capacity was not exceeded. METHODS: We identified all patients with SARS-CoV-2 admitted to any Danish ICU from 10 March to 19 May 2020 and registered demographics, chronic comorbidities, use of organ support, length of stay, and vital status from patient files. Risk factors for death were analyzed using adjusted Cox regression analysis. RESULTS: There were 323 ICU patients with confirmed COVID-19. Median age was 68 years, 74% were men, 50% had hypertension, 21% diabetes, and 20% chronic pulmonary disease; 29% had no chronic comorbidity. Invasive mechanical ventilation was used in 82%, vasopressors in 83%, renal replacement therapy in 26%, and extra corporeal membrane oxygenation in 8%. ICU stay was median 13 days (IQR 6-22) and hospital stay 19 days (11-30). Median follow-up was 79 days. At end of follow-up, 118 had died (37%), 15 (4%) were still in hospital hereof 4 in ICU as of 16 June 2020. Risk factors for mortality included male gender, age, chronic pulmonary disease, active cancer, and number of co-morbidities. CONCLUSIONS: In this nationwide, population-based cohort of ICU patients with COVID-19, longer term survival was high despite high age and substantial use of organ support. Male gender, age, and chronic co-morbidities, in particular chronic pulmonary disease, were associated with increased risk of death.

Pharmacokinetics and Safety of Intravenous, Intravesical, Rectal, Transdermal, and Vaginal Melatonin in Healthy Female Volunteers: A Cross-Over Study.

INTRODUCTION: We aimed to investigate the pharmacokinetic properties and safety of melatonin administered by alternative routes of administration. METHODS: This study employed a cross-over design in healthy female volunteers. Twenty-five milligrams of melatonin was administered intravenously, intravesically, rectally, transdermally, and vaginally. Blood samples were collected at specified time points up to 24 h following intravenous, intravesical, rectal, and vaginal administration, and up to 48 h following transdermal administration. Plasma melatonin concentrations were determined by radioimmunoassay. Sedation was evaluated by a simple reaction-time test, and sleepiness was assessed by the Karolinska Sleepiness Scale. Adverse events were registered for each route of administration. RESULTS: Ten participants were included. We documented a mean (SD) time to maximal concentration of 51 (29) min for intravesical, 24 (20) min for rectal, 21 (8) h for transdermal, and 147 (56) min for vaginal administration. The mean (SD) elimination half-life was 47 (6) min for intravenous, 58 (7) min for intravesical, 60 (18) min for rectal, 14.6 (11.1) h for transdermal, and 129 (17) min for vaginal administration. The mean (SD) bioavailability was 3.6 (1.9)% for intravesical, 36.0 (28.6)% for rectal, 10.0 (5.7)% for transdermal, and 97.8 (31.7)% for vaginal administration. No significant changes in reaction times were observed following administration of melatonin by any of the administration routes. Increased tiredness was documented following transdermal administration only. No serious adverse effects were documented. CONCLUSION: Rectally and vaginally administered melatonin may serve as relevant alternatives to standard oral melatonin therapy. Transdermal delivery of melatonin displayed an extended absorption and can be applied if prolonged effects are intended. Intravesical administration displayed, as expected, a very limited bioavailability. Melatonin administered by these routes of administration was safe.

[Fatal outcome of coronavirus disease 2019 in a previously healthy 50-year-old man].

In this case report, a 50-year-old man who had no medical history, presented with multiple cardiac arrests following a week with progressing symptoms of pneumonia. After achieving return of spontaneous circulation he presented with respiratory failure with severe hypoxia, septic shock, and multiple organ failure. A chest X-ray showed signs of acute respiratory distress syndrome. Despite aggressive intensive care management, the patient died 7.5 hours after admission. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was later confirmed, and the presumed cause of death was SARS-CoV-2 pneumonia. In conclusion: coronavirus disease 2019 (COVID-19) can lead to a fatal outcome in younger healthy residents, who are not treated timely in case of severe symptoms like dyspnoea.

Assessment of Postoperative Analgesic Drug Efficacy: Method of Data Analysis Is Critical.

BACKGROUND: Pain intensity ratings and opioid consumption (OC) are ubiquitous indicators of pain in postoperative trials of the efficacy of interventional procedures. Unfortunately, consensus on the appropriate statistical handling of these outcomes has not been reached. The aim of this article was, therefore, to reexamine original data obtained from a postoperative analgesic drug trial, applying a collection of standard statistical methods in analgesic outcome assessments. Furthermore, a modified integrated assessment method of these outcomes was evaluated. METHODS: Data from a randomized, double-blind, placebo-controlled study investigating the analgesic efficacy of a regional anesthetic block following a major elective surgical procedure were analyzed. The original data included measurements of pain intensity (visual analog scale [VAS]) at rest and during coughing (VAS0/2/4/6/12/18/24 h) and OC0-6/0-24 h administered by patient-controlled analgesia. The statistical analyses included comparisons of discrete pain intensity scores (VAS0/2/4/6/12/18/24 h), summary measures of pain intensity ratings (area under the curve [AUC]-VAS0-6/0-24 h; mean VAS0-6/0-24 h), and OC0-6/0-24 h. Finally, the analyses also included an integrated assessment of longitudinally measured pain intensity and opioid consumption (PIOC0-6/0-24 h). Also, estimation of effect size, generalized odds ratio of the individual analgesic outcome variables was performed. RESULTS: Sixty-one patients were included in the final data analysis. Discrete pain intensity ratings differed significantly between the treatment groups at specific postoperative time points, but appropriate correction for multiple comparisons eliminated some of these differences. AUC-VAS0-6 h differed significantly at rest and during coughing, while no difference was found for AUC-VAS0-24 h. In contrast, mean VAS0-6 h and VAS0-24 h differed significantly between treatment groups at rest and during coughing. OC0-6/0-24 h differed significantly between the treatment groups. Finally, also PIOC0-6/0-24 h differed significantly at rest and during coughing. CONCLUSIONS: Our analyses demonstrate that the applied statistical method may alter the statistical significance and estimates of effect size of analgesic outcome variables in postoperative pain trials. Our findings underline the importance of defining valid statistical methods for future analgesic drug trials. We propose an integrated assessment of longitudinally measured pain intensity and opioid consumption (PIOC). The method combines two interdependent analgesic outcomes, lowers the risk of mass significance, and provides more accurate representation of the dynamic nature of postoperative pain and analgesic drug efficacy.

Pharmacokinetics of Repeated Melatonin Drug Administrations Prior to and After Surgery.

BACKGROUND: Recent clinical studies have documented the analgesic, anti-inflammatory, antioxidative and anxiolytic effects of exogenous melatonin. The pharmacokinetic properties of melatonin have primarily been investigated in experimental studies. OBJECTIVE: The aim of this study was to estimate the pharmacokinetics of melatonin in patients undergoing surgery and general anesthesia. METHODS: The study was designed as a prospective, two-phase cohort study. Patients were candidates for subpectoral breast augmentation surgery, and surgical procedures were performed by a single surgeon. The perioperative treatment protocol was standardized between patients. During the study, each patient received two separate oral administrations of melatonin 10 mg. Melatonin was administered 60 min before surgery, and at 9:00 p.m. the evening after surgery. The pharmacokinetic variables absorption half-life (t ½ absorption), time to maximal plasma concentration (T max), maximal plasma concentration (C max), elimination half-life (t ½ elimination), and area under the melatonin plasma concentration-time curve from time zero to infinity (AUC ∞) were estimated for both study phases. RESULTS: Median (interquartile range) values of t ½ absorption and T max were significantly increased during the postoperative phase [10.8 (6.9-15.1) min; 90.0 (48.8-120.0) min] compared with perioperatively [9.5 (6.3-16.5) min; 30.0 (15.0-30.0) min] (p = 0.034; p = 0.002), respectively. C max values were significantly higher during surgery [5497.5 (2077.1-13,233.8) pg/ml] compared with postoperative values [2340.5 (1672.4-8871.4) pg/ml] (p = 0.005). Correspondingly, t ½ elimination was significantly extended during the postoperative phase [103.5 (57.8-237.8) min] compared with the perioperative phase [60.5 (47.8-83.6) min] (p = 0.015). AUC ∞ did not differ between the study phases (p > 0.05). CONCLUSIONS: These preliminary results indicate that postoperative melatonin dose should be augmented compared with preoperative administration if corresponding melatonin plasma levels are intended. Furthermore, postoperative administration times should be advanced compared with preoperative administration.