Characteristics of delirium and its association with sedation and in-hospital mortality in patients with COVID-19 on veno-venous extracorporeal membrane oxygenation.

Background: Veno-venous extracorporeal membrane oxygenation (VV-ECMO) has been used in patients with COVID-19 acute respiratory distress syndrome (ARDS). We aim to assess the characteristics of delirium and describe its association with sedation and in-hospital mortality. Methods: We retrospectively reviewed adult patients on VV-ECMO for severe COVID-19 ARDS in the Johns Hopkins Hospital ECMO registry in 2020-2021. Delirium was assessed by the Confusion Assessment Method for the ICU (CAM-ICU) when patients scored-3 or above on the Richmond Agitation-Sedation Scale (RASS). Primary outcomes were delirium prevalence and duration in the proportion of days on VV-ECMO. Results: Of 47 patients (median age = 51), 6 were in a persistent coma and 40 of the remaining 41 patients (98%) had ICU delirium. Delirium in the survivors (n = 21) and non-survivors (n = 26) was first detected at a similar time point (VV-ECMO day 9.5(5,14) vs. 8.5(5,21), p = 0.56) with similar total delirium days on VV-ECMO (9.5[3.3, 16.8] vs. 9.0[4.3, 28.3] days, p = 0.43). Non-survivors had numerically lower RASS scores on VV-ECMO days (-3.72[-4.42, -2.96] vs. -3.10[-3.91, -2.21], p = 0.06) and significantly prolonged delirium-unassessable days on VV-ECMO with a RASS of -4/-5 (23.0[16.3, 38.3] vs. 17.0(6,23), p = 0.03), and total VV-ECMO days (44.5[20.5, 74.3] vs. 27.0[21, 38], p = 0.04). The proportion of delirium-present days correlated with RASS (r = 0.64, p < 0.001), the proportions of days on VV-ECMO with a neuromuscular blocker (r = -0.59, p = 0.001), and with delirium-unassessable exams (r = -0.69, p < 0.001) but not with overall ECMO duration (r = 0.01, p = 0.96). The average daily dosage of delirium-related medications on ECMO days did not differ significantly. On an exploratory multivariable logistic regression, the proportion of delirium days was not associated with mortality. Conclusion: Longer duration of delirium was associated with lighter sedation and shorter paralysis, but it did not discern in-hospital mortality. Future studies should evaluate analgosedation and paralytic strategies to optimize delirium, sedation level, and outcomes.

Risk factors for nosocomial infections in COVID-19 ICU population

Introduction: The aim of this study is to identify the factors associated with an increased risk of developing nosocomial infections (NI) in COVID-19 patients admitted with pulmonary involvement in the ICU. NI in COVID-19 ICU population are an important cause of morbidity and mortality worldwide and its prompt identification might lead to its prevention and better outcomes. Method(s): This is a retrospective observational study of patients admitted with COVID-19 pneumonia in the ICU of a tertiary center in Portugal, between March 2020 and December 2021. We considered NI as any infection acquired > 48 h post ICU admission. Clinical, analytical and baseline patient data were evaluated. Logistic regression analysis was performed to correlate patient related variables with the development of NI. Result(s): A total of 338 patients were enrolled, from which 167 (47.9%) presented with NI. Baseline characteristics are described in Table 1. In the logistic regression analysis, older age (OR 1.13;95% CI 1.03-1.25;p = 0.013), coronary artery disease (CAD) (OR 28.7;95% CI 1.92-429;p = 0.02), obesity (OR 3.14;95% CI 0.86-11.42;p = 0.008), chronic liver disease (CLD) (OR 104.33;95% CI 1,.04-1008.49;p = 0.04), use of dexamethasone (OR 21.89;95% CI 3.04-157.85;p = 0.002) and days in RASS < 3 (OR 1.4;95% CI 1.05-1.86;p = 0.02) were associated with an increased risk of developing NI in the ICU. Surprisingly, SOFA at admission, days of invasive mechanical ventilation, days of sedation and PaO2/ FiO2 ratio at admission, although statistically significantly different between groups, did not correlate with the risk of infection. Conclusion(s): We identified prolonged deep sedation, corticosteroid use, and patient characteristics (CAD, obesity, CLD, older age) as independent risk factors for NI development in COVID-19 critically ill patients. It is also noteworthy to point out for the presence of confounding variables, including the excessive workload in the ICU during this period, leading to an increase in NI numbers.

Anesthetic management of toxic epidermal necrolysis: a report of two cases

Toxic epidermal necrolysis (TEN), is an acute, life-threatening emergent disease involving the skin and mucous membranes with serious systemic complications. It is characterized by widespread epidermal sloughing. Drugs are the most common triggers of TEN, but infection, vaccination, radiation therapy and malignant neoplasms can all induce it in susceptible patients. We report two cases in whom a hair dye and a COVID-19 vaccine (BioNTech, Pfizer) were believed to be the causative agents. These patients have to undergo repeated debridements of the necrotic tissue. In this manuscript the anesthetic management of TEN patients is discussed. Detailed preoperative evaluation, aggressive fluid and electrolyte replacement, avoidance of hypothermia during debridement, minimizing anesthetic agents and limiting traumatic procedures are key points in the management.Copyright © 2023 Faculty of Anaesthesia, Pain and Intensive Care, AFMS. All rights reserved.

Pentobarbital for Sedation of Adults Receiving Extracorporeal Membrane Oxygenation for Covid-19

INTRODUCTION: Sedation for ventilated patients with COVID-19 is challenging given the severity and duration of the disease. Complicating this is the introduction of extracorporeal membrane oxygenation (ECMO) for patients with refractory respiratory failure. An ECMO circuit can meaningfully alter drug pharmacokinetics by sequestering drug, increasing the volume of distribution, and altering clearance. Many common sedatives are known to be significantly impacted, thus altering standard dosing. In circumstances warranting deep sedation, such as ARDS, clinicians need a wide array of sedatives and analgesics available when managing patients receiving ECMO support. To our knowledge, no studies have assessed the use of pentobarbital as a sedative in adult patients receiving ECMO support for severe ARDS. We aimed to characterize the use of pentobarbital infusions as part of a multi-modal sedation regimen in adult patients with COVID-19 who were receiving ECMO. METHOD(S): Adults with COVID-19 who were receiving both pentobarbital and VV-ECMO support between March 2020 and December 2021 were included. The primary outcome was change in the dose of concomitant sedatives at 24- and 48-hours post-initiation of pentobarbital. Secondary outcomes included depth of sedation, ventilator synchrony, mean arterial pressure (MAP), and vasopressor doses in norepinephrine equivalents. Additionally, we assessed for adverse drug reactions (ADRs) which included hypotension and transaminitis. RESULT(S): Five patients were included. All patients were initiated on a pentobarbital infusion for the indication of ventilator dyssynchrony. Patients received pentobarbital at an initial rate of 1 mg/kg/hr and infusion rates ranged between 0.5 - 2 mg/kg/hr. Following pentobarbital initiation, all patients became synchronous with the ventilator and doses of continuous sedative infusions decreased. Additionally, the total number and daily dose of rescue sedative medications decreased following pentobarbital initiation. ADRs were common and included hypotension (60%) and transaminitis (20%). CONCLUSION(S): A pentobarbital infusion can be used as part of a multimodal sedation regimen for patients requiring high doses of sedatives to achieve ventilator synchrony.

Evaluation of Sedative and Analgesic Practices and Outcomes in Mechanically Ventilated Patients

INTRODUCTION: Sedative and analgesic agents are used for patient comfort during mechanical ventilation (MV) but can cause deleterious effects such as prolonged MV and delirium. Maintaining light sedation and performing daily awakening trials (DATs) can reduce untoward effects. We assessed the relationship between sedative and analgesic dose and 28-day MV-free survival in medical ICU (MICU), surgical ICU (SICU), and cardiac (CICU) patients, hypothesizing that higher doses would be associated with lower 28-day MV-free survival. METHOD(S): In this single-center retrospective study, MICU, SICU, and CICU patients admitted to a tertiary care hospital from 1/1/21-6/30/21 and on MV admitted for 1-7 days were randomly selected if their goal Sedation Agitation Scale (SAS) score was 3-4. Baseline demographics and clinical characteristics were collected. The primary outcome was correlation between average sedative or analgesic dose and 28-day MV-free survival. Secondary outcomes included time at goal SAS score, DAT completion, and deep sedation (SAS < 3) within 48 hours of intubation. The primary outcome was evaluated using linear regression;secondary outcomes were assessed with descriptive statistics. RESULT(S): 411 subjects, including 99 MICU, 54 SICU, and 27 CICU patients, were evaluated. 53% were male and the median age and weight were 66.5 years (IQR, 56-77) and 84 kg (IQR 70-100), respectively. 8% of MICU patients but no SICU or CICU patients had Covid-19. A history of chronic opioid use was most common in MICU and SICU patients (19% and 17%, respectively) and CICU patients most often had a history of chronic kidney disease (33%). Doses of dexmedetomidine, propofol, midazolam, and fentanyl demonstrated poor correlation with 28-day MV-free survival among all patients, with R-squared values of 0.002, 0.06, 0.01, and 0.1, respectively. The association of sedative dose was strongest for midazolam in MICU patients, with each 1mg/hr increase corresponding to a 0.6 day reduction in 28- day MV-free survival. SAS scores were 3-4 70% of the time, SATs were completed in 73% of appropriate cases, and 57% of patients were deeply sedated within 48 hours of intubation. CONCLUSION(S): In this regression analysis, sedative and analgesic doses were not associated with 28-day MV-free survival in a mixed critically ill population.

Efficacy of high-flow nasal oxygenation compared with laryngeal mask airway in children undergoing ambulatory oral surgery under deep sedation: A randomized controlled non-inferiority trial.

Background: High-flow nasal oxygenation (HFNO) has been suggested as an alternative oxygenation method during procedural sedation. This randomized, non-inferiority trial evaluated the safety and efficacy of HFNO compared with laryngeal mask airway (LMA) in pediatric ambulatory oral surgery under deep sedation. Methods: In total, 120 children aged 2-7 years (weight: 10-30 kg) were equally assigned into two groups, namely, HFNO with propofol total intravenous anesthesia infusion (HFNO-IV) or LMA with propofol total intravenous anesthesia infusion (LMA-IV). The primary objective was to monitor carbon dioxide (CO2) accumulation during perioperative surgery. Secondary objectives included monitoring transcutaneous oxygen saturation, grade exposure to the surgical field, perioperative adverse events, or other events. The predefined non-inferiority margin was 7 mmHg. During the COVID-19 pandemic, a novel WeChat applet was implemented to gather follow-up data after discharge. Results: Non-inferiority could be declared for HFNO relative to LMA (mean difference in transcutaneous CO2 (TcCO2) = -1.4 mmHg, 95% CI: -2.9, 0.1 mmHg; P > 0.05). The pre-surgical TcCO2 of the HFNO-IV group (45.4 ± 4.5 mmHg) was similar to that of the LMA-IV group (44.0 ± 3.5 mmHg), within the clinically acceptable normal range. All the children maintained SpO2 levels of >97%. The surgical field exposure score of the HFNO group was significantly better than that of the LMA group. There was no significant difference between the two groups regarding risk or adverse events. Conclusion: HFNO was not inferior to LMA for maintaining oxygenation and ventilation in patients undergoing pediatric ambulatory oral surgery under deep sedation under strict isolation from the oral cavity to the upper airway.

Excessive Sedation as a Risk Factor for Delirium: A Comparison between Two Cohorts of ARDS Critically Ill Patients with and without COVID-19.

Excessive sedation is associated with poor outcome in critically ill acute respiratory distress syndrome (ARDS) patients. Whether this prognostic effect varies among ARDS patients with and without COVID-19 has yet to be determined. We compared the prognostic value of excessive sedation­in terms of delirium, length of stay in intensive care unit (ICU-LOS) and ICU mortality­between COVID-19 and non-COVID-19 critically ill ARDS patients. This was a second analysis of prospectively collected data in four European academic centers pertaining to 101 adult critically ill ARDS patients with and without COVID-19 disease. Depth of sedation (DOS) and delirium were monitored through processed electroencephalogram (EEG) and the Confusion Assessment Method for ICU (CAM-ICU). Our main exposure was excessive sedation and how it relates to the presence of delirium, ICU-LOS and ICU mortality. The criterion for excessive sedation was met in 73 (72.3%) patients; of these, 15 (82.2%) and 58 (69.1%) were in non-COVID-19 and COVID-19 ARDS groups, respectively. The criteria of delirium were met in 44 patients (60.3%). Moreover, excessive sedation was present in 38 (86.4%) patients with delirium (p < 0.001). ICU death was ascertained in 41 out of 101 (41.0%) patients; of these, 37 (90.2%) had excessive sedation (p < 0.001). The distribution of ICU-LOS among excessive-sedated and non-sedated patients was 22 (16−27) vs. 14 (10.5−19.5) days (p < 0.001), respectively. In a multivariable framework, excessive sedation was independently associated with the development of delirium (p = 0.001), increased ICU mortality (p = 0.009) and longer ICU-LOS (p = 0.000), but only in COVID-19 ARDS patients. Independent of age and gender, excessive sedation might represent a risk factor for delirium in COVID-19 ARDS patients. Similarly, excessive sedation shows to be an independent predictor of ICU-LOS and ICU mortality. The use of continuous EEG-based depth of sedation (DOS) monitoring and delirium assessment in critically ill COVID-19 patients is warranted.

DIFFUSE ALVEOLAR HEMORRHAGE SECONDARY TO IMMUNE THROMBOCYTOPENIA FOLLOWING SARS-COV-2 VACCINATION: A CASE REPORT

SESSION TITLE: COVID-Related Critical Care Cases SESSION TYPE: Case Reports PRESENTED ON: 10/19/2022 11:15 am - 12:15 pm INTRODUCTION: We present a case of diffuse alveolar hemorrhage (DAH) secondary to Immune Thrombocytopenia (ITP) temporally related to SARS-CoV-2 (CoV) vaccine. CASE PRESENTATION: An 80-year-old female presented with dyspnea, hemoptysis, diffuse petechiae, and ecchymosis;no focal neurological deficits or hepatosplenomegaly. She had no history of bleeding or autoimmune disorders;no recent respiratory or gastrointestinal infections;but received Moderna CoV vaccine 4 weeks prior to presentation. Chest X-ray (CXR) and CTA of chest demonstrated multifocal bilateral patchy airspace opacities. Initial platelet was 1 x 109/L with normal morphology of platelet and WBC, and no schistocytes. Coagulation panel, LDH, haptoglobin, and bilirubin were all normal. CoV NAAT was negative. Dexamethasone and IVIG for high suspicion of ITP was initiated. Supportive care including platelet transfusion and oxygen via nasal cannula was maintained. Platelets were severely consumed in spite of treatment with platelets undetectable at nadir and rapid decrease of hemoglobin, approximately 6 g/dL, within 24 hours of admission. IgM and IgG plasma platelet autoantibodies returned positive, confirming ITP diagnosis. Additional workup was unremarkable for infections, rheumatologic disorders, and malignancy. Respiratory state rapidly declined with worsening hemoptysis and significant increase of bilateral airspace opacities on repeat CXR, indicative of DAH. Lung protective mechanical ventilation protocol was initiated on day 2 with medically induced deep sedation and paralysis to minimize hemorrhage exacerbation. Rituximab, romiplostim, and nebulized tranexamic acid were added for severe and refractory ITP, which eventually slowed platelet consumption, reduced pulmonary hemorrhage, and stabilized hemoglobin. Platelets recovered above 30 x 109/L on day 9, and subsequent bronchoscopy showed persistent blood on bronchoalveolar lavage. She was successfully extubated after prolonged 14-day intubation. Platelet normalized before discharge. DISCUSSION: Incidence of ITP related to CoV vaccine is approximately 0.8-0.9 case per million vaccinated. Most cases present with superficial bleeding and respond to first-line agents with rapid recovery. GI bleeding and intracranial hemorrhage, but not DAH, have been reported in several cases, requiring third-line agents to promote platelets recovery and achieve hemostasis. We report a case of DAH secondary to ITP following CoV vaccine. Temporal relationship and severe presentation are consistent with other reports of ITP with life-threatening internal bleeding probably secondary to CoV vaccine. CONCLUSIONS: When DAH is suspected, rapid escalation of treatment to include third-line agents is desired. If intubated, lung protective ventilation with paralysis is preferred to minimize further lung injury due to DAH. Reference #1: Lee EJ, Cines DB, Gernsheimer T, et al. Thrombocytopenia following Pfizer and Moderna SARS-CoV-2 vaccination. Am J Hematol. 2021;96(5):534-537. doi:10.1002/ajh.26132 doi:10.1016/J.VACCINE.2021.04.054 Reference #2: Welsh KJ, Baumblatt J, Chege W, Goud R, Nair N. Thrombocytopenia including immune thrombocytopenia after receipt of mRNA COVID-19 vaccines reported to the Vaccine Adverse Event Reporting System (VAERS). Vaccine. 2021;39(25):3329-3332. Reference #3: Tarawneh O, Tarawneh H. Immune thrombocytopenia in a 22-year-old post Covid-19 vaccine. Am J Hematol. 2021;96(5):E133-E134. doi:10.1002/ajh.26106 DISCLOSURES: No relevant relationships by Timothy Barreiro No relevant relationships by Tiewei Cheng No relevant relationships by Zeina El Amil No relevant relationships by Jin Huang No relevant relationships by Sanaullah Khalid

Clinical pharmacist's views on the role of alpha-2-agonists in practice and research for the management of agitation, sedation and delirium (ASD)

Introduction: Patients in the intensive care (ICU) commonly receive analgesics and sedatives to facilitate mechanical ventilation. Recommendations suggest patients are kept as lightly sedated as feasible. Studies report an inconsistent association between deep sedation, prolonged ventilation and ICU stay.1 Opinions around patients 'wakefulness' include discomfort and the potential increased prevalence of psychological morbidity.2 Alpha-2-agonists (clonidine and dexmedetomidine) are agents used in ASD management and reported to produce lighter sedation. The aim of this project was to explore ICU pharmacist's perspective on ASD practice over UK. Objectives: • Explore ICU pharmacist's views on: ASD practices, sedation research priority, importance of A2B clinical trial and the impact of Covid19. • Determine the prevalence of clonidine and dexmedetomidine prescribing. Methods: An online survey was devised on SurveyMonkey. The survey was designed in 2 sections: -1. Respondents provided responses based on a 'point prevalence' of clonidine and dexmedetomidine prescriptions, on day of completion. 2. Their local ICU sedation practice, their views on priority of sedation research, the A2B study and whether they believed ASD was more challenging during the Covid19 pandemic. The online survey was distributed via the UK Clinical Pharmacy Association Critical Care Group (UKCPA CCG), the NIHR Critical Care National Speciality Group (NSG), the UK Critical Care Research Group and Twitter. The survey remained active for 12 weeks from 30.3.2021 with reminders sent for completion every fortnight. Results: There were 121 respondents, all but 1 were ICU pharmacists. There are approximately 243 ICU pharmacist posts in the UK, this represents a response rate of approximately 50%. 37 (30%) of respondent reported clonidine (but not dexmedetomidine) was prescribed in their ICU;7 (6%) described dexmedetomidine only;and 76 (63%) reported both. In describing ASD during Covid-19 pandemic, 107 (88%) respondents reported it had become more challenging. 83 (69%) of respondents stated that clonidine usage increased during the pandemic (27 (22%) no change). 46 (39%) stated that dexmedetomidine usage increased during the pandemic (50 (42%) no change). Among the respondents 98 (81%) 'strongly agreed', and 20 (17%) 'agreed' that research involving ASD is a priority. A2B is set to compare clinical and cost effectiveness of propofol, clonidine, and dexmedetomidine as primary sedative for ICU patients. 49 (40%) of respondents reported participating in A2B. 65 (54%) respondents felt that A2B was a 'very important', and 63 (52%) said it was an 'important' research question. Conclusion: This survey reported widespread use of alpha-2-agonists in ASD practice. Almost two-thirds of ICUs report using both agents. Clonidine use is the most prevalent. Given the paucity of high quality clinical effectiveness and safety data for this drug, clinical trials which assess clinical effectiveness, including ASD are a priority. Respondents endorsed that ASD research is a priority, with ASD management much more challenging during the Covid19 pandemic. Limitations include that the design was a brief online survey;although had a high pharmacist response it did not incorporate the views of other members of the ICU team.

Bedside diaphragmatic ultrasound used to diagnose an unexpected cause of weaning difficulty in a patient with COVID-19 pneumonitis

Introduction: Diaphragm dysfunction has been described as being responsible for weaning failure with an incidence of 23-80%. It has also been associated with difficult weaning from mechanical ventilation, prolonged intensive care unit (ICU) stay and increased ICU and hospital mortality.1 This case report describes the use of bedside ultrasound to diagnose diaphragm dysfunction, assess the severity of dysfunction, refer to specialist care and monitor disease progression in patient with COVID-19 pneumonitis with difficulty weaning from mechanical ventilation. Main body: A 59 year-oldmale with no known past medical history was admitted to our ICU with respiratory failure due to COVID-19 pneumonitis. He had received continuous positive pressure ventilation with oxygen supplementation on the medical high dependency unit for 15 days prior to deteriorating and requiring invasive ventilation in ICU. In ICU, the patient was mandatory ventilated using lung protective ventilation strategies for 26 days before he was switched to pressure support ventilation for attempts to wean him from mechanical ventilation. During the initial phase of his ICU admission, he was severely hypoxaemic and required deep sedation as well as muscle relaxation for a total of 370 hours. Prone positioning was required on 4 occasions before he was stable in the supine position. Once attempts to liberate him from mechanical ventilation were being made, pressure support was gradually reduced along with PEEP and FiO2. Progress with this reduction in support was slow due to marked tachypnoea and a dyssynchronous respiratory pattern. It was also noted that he had poor air entry in his right base with corresponding right lower zone opacities on his chest x-ray. At this stage a bedside ultrasound was used to investigate the cause of weaning difficulty and consequently, the diagnosis of right diaphragmatic paralysis was made. This was a new finding, as his admission chest x-ray did not show a raised hemidiaphragm. This diagnosis led to an increased focus on physical rehabilitation and mobilisation with tolerance of his tachypnoea and respiratory pattern as we now appreciated this didn't represent ongoing underlying parenchymal lung disease. We also made a referral to the respiratory team in order to facilitate longer-term rehabilitation and follow up. The patient was successfully extubated after intense physical rehabilitation, post extubation he remained tachypnoeic and still required supplemental oxygen at the point of hospital discharge. A follow up diaphragm ultrasound 6 months after discharge did not show any improvement in the right diaphragmatic function, he remains dyspnoeic on exertion and still occasionally uses ambulatory supplemental oxygen. Conclusion: Ultrasound assessment revealed an unexpected cause of weaning difficulty in our patient that allowed us to individualise his weaning plan and rehabilitation. This case shows that bedside intensivist performed ultrasound can accurately evaluate diaphragmatic function in patients who are difficult to wean from mechanical ventilation. Brief description of ultrasound video: The diaphragm was scanned using low frequency curvilinear ultrasound probe. There is lack of diaphragmatic excursion and absent thickening of the right hemidiaphragm on subcostal and intercostal views. M-mode evaluation and 'sniff test' confirms diaphragmatic paralysis.

Factors associated with non-attendance at appointments in the gastroenterology endoscopy unit: a retrospective cohort study.

Background and Aims: Gastrointestinal (GI) endoscopy is a limited health resource because of a scarcity of qualified personnel and limited availability of equipment. Non-adherence to endoscopy appointments therefore wastes healthcare resources and may compromise the early detection and treatment of GI diseases. We aimed to identify factors affecting non-attendance at scheduled appointments for GI endoscopy and thus improve GI healthcare outcomes. Methods: This was a single-center retrospective cohort study performed at a tertiary hospital gastroenterology endoscopy unit, 12 months before and 12 months after the start of the COVID-19 pandemic. We used multiple logistic regression analysis to identify variables associated with non-attendance at scheduled appointments. Results: Overall, 5,938 appointments were analyzed, and the non-attendance rate was 18.3% (1,088). The non-attendance rate fell significantly during the pandemic (22.6% vs. 11.6%, p < 0.001). Multivariable regression analysis identified the absence of deep sedation (OR: 3.253, 95% CI [2.386-4.435]; p < 0.001), a referral from a physician other than a gastroenterologist (OR: 1.891, 95% CI [1.630-2.193]; p < 0.001), a longer lead time (OR: 1.006, 95% CI [1.004-1.008]; p < 0.001), and female gender (OR: 1.187, 95% CI [1.033-1.363]; p = 0.015) as associated with appointment non-attendance. Conclusions: Female patients, those undergoing endoscopic procedures without deep sedation, those referred by physicians other than gastroenterologists, and with longer lead time were less likely to adhere to appointments. Precautions should be directed at patients with one or more of these risk factors, and for those scheduled for screening procedures during the COVID-19 pandemic.

Erythema multiforme major requiring intensive care admission in conjunction with COVID-19 infection

A 13-year-old boy presented with oral pain and mucositis on a background of preceding sore throat, fever and malaise. His lips were swollen and ulcerated with tonsillar exudate visible. Reverse transcriptase polymerase chain reaction testing for SARS-CoV-2 was positive, and inflammatory markers were raised (C-reactive protein 77 mg L-1, erythrocyte sedimentation rate 31 mm h-1);additional virology (herpes simplex virus, cytomegalovirus, Epstein-Barr virus and HIV) was negative. Intravenous fluids, ceftriaxone, acyclovir and analgesia including morphine were commenced. He was unable to tolerate soluble oral steroid rinses. Over 24 h, his oral mucositis progressed with the additional development of conjunctival injection and nontargetoid, erythematous papules. A diagnosis of erythema multiforme (EM) major in conjunction with COVID-19 infection was made. His condition deteriorated with oral intubation required to maintain airway patency and deep sedation for pain control. During a 13-day paediatric intensive care admission he developed an extensive rash including ulceration of the external genitalia. There was marked ulceration of the trachea but fortunately tracheostomy was avoided. The patient has subsequently recovered well. A variety of cutaneous features, including EM, have been described in conjunction with COVID-19 infection. The incidence of distinct rashes varies between adults and children with EM uncommon in both groups but seemingly more frequent in paediatric patients (Bennardo L, Nistoc®o SP, Dastoli S et al. Erythema multiforme and COVID-19: what do we know? Medicina (Kaunas) 2021;57: 828). The relationship of EM to outcome from COVID-19 infection itself is yet to be fully established. As with other infections, EM in children with COVID-19 exhibits a range of clinical presentations. This case highlights the severe end of the disease spectrum and underlines the role of the multidisciplinary team in management.

A dual-center cohort study on the association between early deep sedation and clinical outcomes in mechanically ventilated patients during the COVID-19 pandemic: The COVID-SED study.

BACKGROUND: Mechanically ventilated patients have experienced greater periods of prolonged deep sedation during the coronavirus disease (COVID-19) pandemic. Multiple studies from the pre-COVID era demonstrate that early deep sedation is associated with worse outcome. Despite this, there is a lack of data on sedation depth and its impact on outcome for mechanically ventilated patients during the COVID-19 pandemic. We sought to characterize the emergency department (ED) and intensive care unit (ICU) sedation practices during the COVID-19 pandemic, and to determine if early deep sedation was associated with worse clinical outcomes. STUDY DESIGN AND METHODS: Dual-center, retrospective cohort study conducted over 6 months (March-August, 2020), involving consecutive, mechanically ventilated adults. All sedation-related data during the first 48 h were collected. Deep sedation was defined as Richmond Agitation-Sedation Scale of - 3 to - 5 or Riker Sedation-Agitation Scale of 1-3. To examine impact of early sedation depth on hospital mortality (primary outcome), we used a multivariable logistic regression model. Secondary outcomes included ventilator-, ICU-, and hospital-free days. RESULTS: 391 patients were studied, and 283 (72.4%) experienced early deep sedation. Deeply sedated patients received higher cumulative doses of fentanyl, propofol, midazolam, and ketamine when compared to light sedation. Deep sedation patients experienced fewer ventilator-, ICU-, and hospital-free days, and greater mortality (30.4% versus 11.1%) when compared to light sedation (p < 0.01 for all). After adjusting for confounders, early deep sedation remained significantly associated with higher mortality (adjusted OR 3.44; 95% CI 1.65-7.17; p < 0.01). These results were stable in the subgroup of patients with COVID-19. CONCLUSIONS: The management of sedation for mechanically ventilated patients in the ICU has changed during the COVID pandemic. Early deep sedation is common and independently associated with worse clinical outcomes. A protocol-driven approach to sedation, targeting light sedation as early as possible, should continue to remain the default approach.

Deep sedation with dexmedetomidine administered by electrophysiologists during COVID-19 pandemic compared with propofol administered by anesthesiologists for ablation of atrial fibrillation

Background: COVID-19 pandemic, limiting the availability of anesthesiologists, has impacted heavily on the organization of invasive cardiac procedures such as transcatheter atrial fibrillation (AF) ablation. Purpose: We compared the safety and efficacy of deep sedation with dexmedetomidine administered by electrophysiologists without anesthesiologist supervision, against the standard protocol performed with propofol. Methods: We retrospectively included all AF ablation procedures performed in 2020: 23 patients sedated with 1% propofol (2 ml bolus followed by infusion starting at 1 mg/Kg/h), 26 patients with dexmedetomidine (infusion starting at 0.7 mcg/Kg/h). Both groups additionally received 1 mcg/Kg of midazolam as a single bolus and 0.05 mg single boluses of fentanyl prior to ablation on each pair of pulmonary veins (PV). Primary outcomes were oxygen desaturation (< 90%) or need for assisted ventilation/intubation, bradycardia (heart rate < 45 bpm) and persistent hypotension (systolic blood pressure < 90 mmHg). Results: Baseline characteristics and hemodynamic variables did not differ between the two groups (all p > 0.05). In 8/23 (35%) patients propofol infusion velocity reduction was necessary to maintain the hemodynamic values, compared to 7/26 (27%) with dexmedetomidine. Inter-group comparison of hemodynamic variables during the procedure showed no statistically significant difference, despite a trend in favor of dexmedetomidine (3 respiratory depressions and 3 persistent hypotension episodes with propofol vs. 0 with dexmedetomidine;p = 0.057). Conclusion: Deep sedation with dexmedetomidine administered by electrophysiologists without anesthesiologist supervision is safe and effective for AF transcatheter ablation. A trend towards a lower incidence of hypotension and respiratory depression was noted when compared to propofol.

Inhaled Sedation for Invasively Ventilated COVID-19 Patients: A Systematic Review.

BACKGROUND: Volatile anesthetics were used as sedative agents in COVID-19 (Coronavirus Disease 2019) invasively ventilated patients for their potentially beneficial pharmacological effects and due to the temporary shortages of intravenous agents during the pandemic crisis. METHODS: Online databases (PubMed, EMBASE, The Cochrane Central Register of Controlled Trial) and the "clinicaltrials.gov" website were searched for studies reporting the use of isoflurane, sevoflurane or desflurane. RESULTS: We identified three manuscripts describing the beneficial effects of isoflurane on 41 COVID-19 patients with acute respiratory distress syndrome (ARDS) in Germany (n = 2) and in the USA (n = 1), in terms of reduction in the use of opioids and other sedatives. We also found a case report of two patients with transient nephrogenic diabetes insipidus, which started after 6 and 8 days of sevoflurane sedation. We identified two randomized controlled trials (RCTs; 92 patients overall), two observational studies (238 patients) on the use of volatile anesthetics in COVID-19 patients that were completed but not yet published, and one RCT interrupted for a low recruitment ratio (19 patients) and thus not published. We also identified five ongoing RCTs on the use of inhaled sedation in ARDS, which are also likely to be recruiting COVID-19 patients and which have currently enrolled a total of >1643 patients. CONCLUSION: Isoflurane was the most frequently used volatile agent in COVID-19 patients and allowed a reduction in the use of other sedative and analgesic drugs. Randomized evidence is building up and will be useful to confirm or challenge these findings.

Association of sedation level and 28-day mortality: a COVID-19 cohort multicentre study sub analysis

Introduction: COVID-19 started in Wuhan (China) in December 2019 [1]. World pandemic was declared by the WHO in March 2020 [2]. Since then, millions of patients have been infected worldwide. Our group published in March 2021 a multicentre study analysing the prevalence and risk factors for delirium in critically ill patients with COVID-19 infection [3]. In this sub analysis of the main study, the primary outcome was the association of sedation level since ICU admission with 28-day mortality in patients admitted to ICU due to COVID-19. Methods: The exposure tested against mortality was excessive sedation (in the coma range) defined as 'Did patients have a documented sedation score in the coma range at any point this day? RASS = - 4 or - 5;SAS = 2 or 1;MAAS = 0 or 1;Ramsay 5 or 6'. Data from 2017 patients was available for analysis, collected after patients' admission to ICU. Other covariates analyzed were baseline patient characteristics, medical history and treatment applied in the ICU. Logistic regression was used in all analyses and results presented as odd ratios (OR) with 95% confidence intervals. Results: Deep sedation (RASS = - 4 or - 5, SAS = 2 or 1, MAAS = 0 or 1, Ramsay 5 or 6) was positively and significantly associated to mortality within 28 days since ICU admission. P value was 0.012 and the OR was 2.00 with a 95% confidence interval of 1.16-3.45. Conclusions: As shown by this sub analysis, deep sedation increases mortality rates in critically ill COVID 19 patients. We should try to decrease sedation levels to avoid RASS of - 4 and - 5 to favor patients' outcomes admitted to the ICU.

Acute food refusal in 12 year old with anorexia nervosa requiring sedation and mechanical ventilation for enteral feedings

Case Report Anorexia Nervosa is a mental health disorder with significant morbidity and mortality. Acute food refusal is one of the indications for admission. We present a patient who went to extreme lengths to restrict food intake, requiring intensive care sedation and ventilation to enable enteral feedings. 12 year old male, was admitted with symptoms of anorexia nervosa and BMI of 12.0, (<1%ile) with baseline BMI of 16 (25%ile), K of 3.3 and glucose of 54. He was treated with supervised eating on an inpatient pediatric floor with no need for enteral feeding. Psychiatry consultation confirmed the diagnosis of anorexia nervosa and recommended the addition of Olanzapine to his Sertraline. He was discharged pending placement in an eating disorder center after 21 days of hospitalization with discharge BMI of 14. He was followed as an outpatient by his pediatrician, dietician and counselor but unfortunately, he required readmission 11 days after discharge due to acute food refusal, with BMI that had dropped to 13.1. Patient was readmitted and started on nasogastric (NG) feeds but he became severely agitated, pulling NG out multiple times and continued to lose weight with BMI dropping to 12. Sedation was attempted to facilitate maintenance of NG feedings, with Benadryl, Haldol and Ativan, but was ineffective at levels deemed safe without compromising his airway and breathing. Due to severe malnourishment and unsuccessful NG feeds he was transferred to PICU for sedation, endotracheal intubation and continuous nasoduodenal (ND) tube feedings on two separate occasions while inpatient. He was able to wean from the ventilator but once awake he found ways to manipulate delivery of his calories, even finding scissors and cutting the ND tube. The patient ultimately agreed to eat in order to avoid replacement of the feeding tube. He was finally transferred to an eating disorder facility, with a BMI of 13.9 and persistent anorexia thinking with restriction of eating anything but pizza. Patient completed three months of an inpatient program and had significant improvement in BMI to 19.3 (70%ile). He was subsequently discharged for continued outpatient follow-up and since discharge from the eating disorder center, his BMI has shown steady improvement in outpatient follow-up. He shows no signs of food refusal and is doing well with Family Based Therapy. This case highlights several unique characteristics in management of eating disorder patients. The age and being male along with extreme food refusal and resistance to enteral feeding that led to the requirement of deep sedation are quite unusual and not well described in the medical literature. The severity of his illness was a significant barrier to inpatient placement. In addition, despite a nationwide attempt to find an inpatient facility for him, which took several weeks, we identified shortages in eating disorder beds that have been exacerbated by the COVID-19 pandemic.

Physicians' attitudes and perceptions of neuromuscular blocker infusions in ARDS

INTRODUCTION: With the COVID pandemic, and recently updated practice guidelines for neuromuscular infusion (NMBI) use during ARDS, the practices/perceptions of ICU physicians regarding NMBI use during ARDS may not be evidence-based. METHODS: We developed, tested, and electronicallyadministered a questionnaire (9 questions/70 subquestions) to medical and surgical ICU fellow and attending physicians at 3 geographically-diverse U.S. health systems (U Arizona, U Chicago, Mass General Brigham). The IRB-approved questionnaire focused on adults with moderate-severe ARDS (PaO2:FiO2 < 150) with critical hypoxemia where dyssynchrony causes were addressed and PEEP optimized. Weekly reminders were sent twice. RESULTS: Respondents [173/342(50.5%)] primarily worked as an attending 117(75%) in a medical ICU 94(60%) for 12±8 weeks/year. COVID+ ARDS patients were twice as likely to receive a NMBI (56±37 vs. 28±19%;p< 0.01). Respondents somewhat/strongly agreed a NMBI: should be reserved until after a trial of deep sedation 142 (82%) or proning 59 (34%), be dose-titrated based on trainof- four monitoring 107(62%);and effectively reduced dyssynchrony 149(86%), plateau pressure 106(62%) and barotrauma 102(60%). Few respondents [23(18%)] somewhat/strongly agreed a NMBI should be initiated at ARDS onset 20(12%) or administered at a fixed-dose 12(7%). Only 2/14 potential NMBI risks were frequently reported to be of high/very high concern: prolonged muscle weakness during steroids 135(79%) and paralysis awareness due to inadequate sedation 114(67%). Only absence of dyssynchrony 146(87%) was frequently reported to be a very/extremely important NMBI titration target. Train-of-four 78(46%) and BIS 39(23%) monitoring and plateau pressure 67(40%) or PaO2:FiO2 64(38%) evaluation were deemed less important. Absence of dysschrony 93(56%) and use ≥48 hours 87(53%) were preferred NMBI stopping criteria. For COVID+ patients, few felt reduced self-extubation and COVID aerosolization during reintubation 16(9%) or reduced ventilator adjustments 7(5%) were very/extremely important reasons for NMBI use. CONCLUSIONS: Most physicians agree NMBI infusions in ARDS should be reserved until after trials of deep sedation. Paralysis awareness and prolonged muscle weakness are the greatest NMBI use concerns. Unique considerations in COVID+ ARDS patients exist.

P.0811 Factors and outcomes associated with delirium in critically ill COVID-19 patients

Introduction: Evidence demonstrates that 25-33% of hospitalized patients with COVID-19 develop delirium [1,2], with rates up to 65% in critically ill patients [3]. Several potential reasons, including the use of deep sedation and invasive mechanical ventilation (IMV), as well as the restrictions to limit infection transmission, such as prohibition of family visits and minimal contact with health staff were identified [4]. Although factors and outcomes associated with delirium are well documented, limited data are available regarding severe COVID-19 patients. Aims: This study aims to estimate the rates of delirium in critically ill COVID-19 patients and to analyze factors that may be associated with its development, as well as to examine long-term outcomes. Methods: From March to May 2020 (in COVID-19 first wave), all adult patients (≥18y.o.) admitted due to COVID-19, in the Intensive Care Medicine Department (ICMD) of a University Hospital (CHUSJ), in Porto, Portugal, were assessed, unless they had a ICMD length of stay (LoS) ≤24h, terminal illness or major sensory loss or inability to communicate at the time of follow-up. Participants were evaluated during a scheduled telephone follow-up appointment with a comprehensive protocol, including: Six-item Cognitive Impairment Test (6CIT) (cognitive impairment);Patient Health Questionnaire (PHQ-9) (symptoms of depression);General Anxiety Disorder (GAD-7) (symptoms of anxiety);and EuroQol five-dimension five-level questionnaire (EQ-5D-5L) (health-related quality of life-HRQoL), which includes EQ-Visual Analogue Scale (EQ-VAS) (global health status patient perception). Data on acute illness severity, sedative/analgesic drugs use, respiratory support and major complications (including delirium, nosocomial infections and difficulty weaning from mechanical ventilation) during ICMD stay, were obtained from hospital electronic records review. Patients with and without delirium were compared, using Mann-Whitney test for continuous variables, and Chi-square or Fisher tests for paired categorical variables (significance level of 0.05). This study is part of an ongoing larger multidisciplinary research project (MAPA-Mental Health in Critically ill patients with COVID-19). Results: The sample included 59 patients (median age=65 years;66.1% male). Delirium was registered in almost half of the sample (49.2%). Patients with delirium were significantly older (median=72 vs. 62;p=0.010) and presented more nosocomial infections (82.8% vs 53.3%;p=0.032) particularly ventilator-associated pneumonia (75.9% vs. 33.3%;p=0.003). Also, they were significantly more likely to be deeply sedated (89.7% vs 60%;p=0.021), more often required IMV (89.7% vs 60%;p=0.021). Moreover, those with delirium stayed longer in the hospital (median=67 vs 37 days;p=0.014). Concerning HRQoL, assessed at follow-up appointment, patients who have developed delirium reported more problems in self-care (48.3% vs 10%;p=0.003) and in everyday activities (79.3% vs 53.3%;p=0.035) after hospital discharge. Nevertheless, no statistically significant differences were found for cognitive impairment, symptoms of anxiety and depression. Conclusions: Delirium was common in this critically ill COVID-19 sample, namely in older patients, who have been deeply sedated, invasively ventilated or had major ICU complications. It was associated with longer hospital stay and worse HRQoL. Recognizing potential associated factors will allow the identification of high-risk patients that should be targeted for early screening with preventive interventions to minimize the adverse outcomes associated to delirium in critical COVID-19 patients. No conflict of interest