Prevalence and Risk Factors for Chronic Postsurgical Pain After Thoracic Surgery: A Prospective Cohort Study.

OBJECTIVE: Thoracic surgery is associated with one of the highest rates of chronic postsurgical pain (CPSP) among all surgical subtypes. Chronic postsurgical pain carries significant medical, psychological, and economic consequences, and further interventions are needed to prevent its development. This study aimed to determine the prevalence, characteristics, and risk factors associated with CPSP after thoracic surgery. DESIGN: A prospective cohort study. SETTING: Single-center tertiary care hospital. PARTICIPANTS: This study included 285 adult patients who underwent thoracic surgery at Toronto General Hospital in Toronto, Canada, between 2012 and 2020. MEASUREMENTS AND MAIN RESULTS: Demographic, psychological, and clinical data were collected perioperatively, and follow-up evaluations were administered at 3, 6, and 12 months after surgery to assess CPSP. Chronic postsurgical pain was reported in 32.4%, 25.4%, and 18.2% of patients at 3, 6, and 12 months postoperatively, respectively. Average CPSP pain intensity was rated to be 3.37 (SD 1.82) at 3 months. Features of neuropathic pain were present in 48.7% of patients with CPSP at 3 months and 71% at 1 year. Multivariate logistic regression models indicated that independent predictors for CPSP at 3 months were scores on the Hospital Anxiety and Depression Scale (adjusted odds ratio [aOR] of 1.07, 95% CI of 1.02 to 1.14, p = 0.012) and acute postoperative pain (aOR of 2.75, 95% CI of 1.19 to 6.36, p = 0.018). INTERVENTIONS: None. CONCLUSIONS: Approximately 1 in 3 patients will continue to have pain at 3 months after surgery, with a large proportion reporting neuropathic features. Risk factors for pain at 3 months may include preoperative anxiety and depression and acute postoperative pain.

Electroencephalography-Guided Anesthesia and Delirium in Older Adults After Cardiac Surgery: The ENGAGES-Canada Randomized Clinical Trial.

Importance: Intraoperative electroencephalogram (EEG) waveform suppression, suggesting excessive general anesthesia, has been associated with postoperative delirium. Objective: To assess whether EEG-guided anesthesia decreases the incidence of delirium after cardiac surgery. Design, Setting, and Participants: Randomized, parallel-group clinical trial of 1140 adults 60 years or older undergoing cardiac surgery at 4 Canadian hospitals. Recruitment was from December 2016 to February 2022, with follow-up until February 2023. Interventions: Patients were randomized in a 1:1 ratio (stratified by hospital) to receive EEG-guided anesthesia (n = 567) or usual care (n = 573). Patients and those assessing outcomes were blinded to group assignment. Main Outcomes and Measures: The primary outcome was delirium during postoperative days 1 through 5. Intraoperative measures included anesthetic concentration and EEG suppression time. Secondary outcomes included intensive care and hospital length of stay. Serious adverse events included intraoperative awareness, medical complications, and 30-day mortality. Results: Of 1140 randomized patients (median [IQR] age, 70 [65-75] years; 282 [24.7%] women), 1131 (99.2%) were assessed for the primary outcome. Delirium during postoperative days 1 to 5 occurred in 102 of 562 patients (18.15%) in the EEG-guided group and 103 of 569 patients (18.10%) in the usual care group (difference, 0.05% [95% CI, -4.57% to 4.67%]). In the EEG-guided group compared with the usual care group, the median volatile anesthetic minimum alveolar concentration was 0.14 (95% CI, 0.15 to 0.13) lower (0.66 vs 0.80) and there was a 7.7-minute (95% CI, 10.6 to 4.7) decrease in the median total time spent with EEG suppression (4.0 vs 11.7 min). There were no significant differences between groups in median length of intensive care unit (difference, 0 days [95% CI, -0.31 to 0.31]) or hospital stay (difference, 0 days [95% CI, -0.94 to 0.94]). No patients reported intraoperative awareness. Medical complications occurred in 64 of 567 patients (11.3%) in the EEG-guided group and 73 of 573 (12.7%) in the usual care group. Thirty-day mortality occurred in 8 of 567 patients (1.4%) in the EEG-guided group and 13 of 573 (2.3%) in the usual care group. Conclusions and Relevance: Among older adults undergoing cardiac surgery, EEG-guided anesthetic administration to minimize EEG suppression, compared with usual care, did not decrease the incidence of postoperative delirium. This finding does not support EEG-guided anesthesia for this indication. Trial Registration: ClinicalTrials.gov Identifier: NCT02692300.

The role of routine cardiac investigations before hyperbaric oxygen treatment.

Cardiac complications are a rare but potentially serious consequence of hyperbaric oxygen treatment (HBOT), resulting from increased blood pressure and decreased heart rate and cardiac output associated with treatment. These physiologic changes are generally well-tolerated by patients without preexisting cardiac conditions, although those with known or undetected cardiac disease may be more vulnerable to treatment complications. Currently, there are no universally accepted guidelines for pre-HBOT cardiac screening to identify these patients at heightened risk, leading to variability in practice patterns. In the absence of HBOT-specific evidence, screening protocols might be adapted from the diving medicine community; however, given the important differences in physiological stressors, these may not be entirely applicable to patients undergoing HBOT. Traditional cardiac investigations such as electro- and echo-cardiograms are limited in their ability to detect relevant risk modifying states in the pre-HBOT patient, stymieing their cost-effectiveness as routine tests. In the absence of strong evidence to support routine cardiac investigation, we argue that a comprehensive history and physical exam - tailored to identify high-risk patients based on clinical parameters - may serve as a more practical screening tool. While certain unique patient groups such as those undergoing dialysis or with implanted cardiac devices may warrant specialised assessment, thorough evaluation may be sufficient to identify many patients unlikely to benefit from cardiac investigation in the pre-HBOT setting. A clinical decision-making tool based on suggested low-risk and high-risk features is offered to guide the use of targeted cardiac investigation prior to HBOT.

Choice of anesthesia technique is associated with earlier hospital discharge and reduced costs after transcatheter transfemoral aortic valve implantation.

Background: Transcatheter aortic valve implantation (TAVI) has become a viable alternative to palliation in patients with severe aortic stenosis. We compared general anesthesia to conscious sedation for TAVI procedures with respect to post operative morbidity, hospital length of stay, and financial burden. Methods: We conducted a retrospective review of prospectively collected data in patients undergoing transfemoral TAVI procedures from 2012 to 2017. Patients were matched based on age and sex and classed into either general anesthesia or conscious sedation groups respectively. Conscious sedation was provided with a dexmedetomidine infusion, and patients in general anesthesia group received a standard induction, tracheal intubation, and maintenance with sevoflurane. The hospital case costs were compared between the two groups before and after adjustment for inflation. Results: We matched 124 pairs for a total of 248 patients. Both groups were similar with respect to demographic data, past medical history, medications, and intraoperative characteristics. There was no difference in postoperative morbidity and mortality between the two groups. The median hospital length of stay was 5 [interquartile range (IQR): 3, 10] and 7 (IQR: 4, 12) days, P=0.01, and after adjustment for inflation, the total hospital case costs were $48,984 (IQR: $44,802, $61,438) Canadian (CAD) vs. $55,333 (IQR: $46,832, $68,702) CAD, P=0.01, in the conscious sedation and general anesthesia groups, respectively. Conclusions: Advancements in TAVI technologies, conscious sedation and a collaborative, multidisciplinary team approach reduces overall length of hospital stay and procedure costs.

Impact of goal-directed hemodynamic therapy on perioperative outcomes in head and neck free flap surgery: A before-and-after pilot study.

Background: Free flap reconstruction for head and neck cancer is associated with a high risk of perioperative complications. One of the modifiable risk factors associated with perioperative morbidity is intraoperative hypotension (IOH). The main aim of this pilot study is to determine if the intraoperative use of goal-directed hemodynamic therapy (GDHT) is associated with a reduction in the number of IOH events in this population. Methods: A before-and-after study design. The patients who had intraoperative GDHT were compared to patients from a previous period before the implementation of GDHT. The primary outcome was the number of IOH episodes defined as five or more successive minutes with a mean arterial pressure <65 mmHg. The secondary outcomes included major postoperative morbidity and 30-day mortality. Results: A total of 414 patients were included. These were divided into two groups. The control group (n = 346; January 1, 2018, to December 31, 2019), and the monitored group (n = 68; January 1, 2020, to May 1, 2021). The median intraoperative administered fluid volume was similar between the control and monitored groups (2250 interquartile range [IQR] [1607-3050] vs. 2210 IQR [1700-2807] mL). The monitored group was found to have an increased use of norepinephrine and dobutamine (respectively, 1.2% vs. 5.9% and 2.4% vs. 30.9%; p < 0.05). When adjusting for confounders (comorbidities, estimated blood loss, and duration of anesthesia) the incidence rate ratio (95% confidence interval) of number of IOH events was 0.94 (0.86-1.03), p = 0.24. The rate of postoperative flap and medical complications did not differ between the two groups. Conclusions: Even though the use of vasopressors/inotropes was higher in the monitored group, the number of IOH episodes and postoperative morbidity and mortality were similar between the two groups. Further change in hemodynamic management will require the use of specific blood pressure targets in the GDHT fluid algorithm.

Safety of hyperbaric oxygen therapy in patients with heart failure: A retrospective cohort study.

BACKGROUND: Hyperbaric oxygen therapy (HBOT) has several hemodynamic effects including increases in afterload (due to vasoconstriction) and decreases in cardiac output. This, along with rare reports of pulmonary edema during emergency treatment, has led providers to consider HBOT relatively contraindicated in patients with reduced left ventricular ejection fraction (LVEF). However, there is limited evidence regarding the safety of elective HBOT in patients with heart failure (HF), and no existing reports of complications among patients with HF and preserved LVEF. We aimed to retrospectively review patients with preexisting diagnoses of HF who underwent elective HBOT, to analyze HBOT-related acute HF complications. METHODS: Research Ethics Board approvals were received to retrospectively review patient charts. Patients with a history of HF with either preserved ejection fraction (HFpEF), mid-range ejection fraction (HFmEF), or reduced ejection fraction (HFrEF) who underwent elective HBOT at two Hyperbaric Centers (Toronto General Hospital, Rouge Valley Hyperbaric Medical Centre) between June 2018 and December 2020 were reviewed. RESULTS: Twenty-three patients with a history of HF underwent HBOT, completing an average of 39 (range 6-62) consecutive sessions at 2.0 atmospheres absolute (ATA) (n = 11) or at 2.4 ATA (n = 12); only two patients received fewer than 10 sessions. Thirteen patients had HFpEF (mean LVEF 55 ± 7%), and seven patients had HFrEF (mean LVEF 35 ± 8%) as well as concomitantly decreased right ventricle function (n = 5), moderate/severe tricuspid regurgitation (n = 3), or pulmonary hypertension (n = 5). The remaining three patients had HFmEF (mean LVEF 44 ± 4%). All but one patient was receiving fluid balance therapy either with loop diuretics or dialysis. Twenty-one patients completed HBOT without complications. We observed symptoms consistent with HBOT-related HF exacerbation in two patients. One patient with HFrEF (LVEF 24%) developed dyspnea attributed to pulmonary edema after the fourth treatment, and later admitted to voluntarily holding his diuretics before the session. He was managed with increased oral diuretics as an outpatient, and ultimately completed a course of 33 HBOT sessions uneventfully. Another patient with HFpEF (LVEF 64%) developed dyspnea and desaturation after six sessions, requiring hospital admission. Acute coronary ischemia and pulmonary embolism were ruled out, and an elevated BNP and normal LVEF on echocardiogram confirmed a diagnosis of pulmonary edema in the context of HFpEF. Symptoms subsided after diuretic treatment and the patient was discharged home in stable condition, but elected not to resume HBOT. CONCLUSIONS: Patients with HF, including HFpEF, may develop HF symptoms during HBOT and warrant ongoing surveillance. However, these patients can receive HBOT safely after optimization of HF therapy and fluid restriction.

Adjunctive hyperbaric oxygen therapy for spinal cord ischemia after complex aortic repair.

OBJECTIVE: Spinal cord ischemia (SCI) with paraplegia or paraparesis is a devastating complication of complex aortic repair (CAR). Treatment includes cerebrospinal fluid drainage, maintenance of hemoglobin concentration (>10 g/L), and elevating mean arterial blood pressure. Animal and human case series have reported improvements in SCI outcomes with hyperbaric oxygen therapy (HBOT). We reviewed our center's experience with HBOT as a rescue treatment for spinal cord ischemia post-CAR in addition to standard treatment. METHODS: A retrospective review of the University Health Network's Hyperbaric Medicine Unit treatment database identified HBOT sessions for patients with SCI post-CAR between January 2013 and June 2021. Mean estimates of overall motor function scores were determined for postoperative, pre-HBOT, post-HBOT (within 4 hours of the final HBOT session), and at the final assessment (last available in-hospital evaluation) using a linear mixed model. A subgroup analysis compared the mean estimates of overall motor function scores between improvement and non-improvement groups at given timepoints. Improvement of motor function was defined as either a ≥2 point increase in overall muscle function score in patients with paraparesis or an upward change in motor deficit categorization (para/monoplegia, paraparesis, and no deficit). Subgroup analysis was performed by stratifying by improvement or non-improvement of motor function from pre-HBOT to final evaluation. RESULTS: Thirty patients were treated for SCI. Pre-HBOT, the motor deficit categorization was 10 paraplegia, three monoplegia, 16 paraparesis, and one unable to assess. At the final assessment, 14 patients demonstrated variable degrees of motor function improvement; eight patients demonstrated full motor function recovery. Seven of the 10 patients with paraplegia remained paraplegic despite HBOT. The estimated mean of overall muscle function score for pre-HBOT was 16.6 ± 2.9 (95% confidence interval [CI], 10.9-22.3) and for final assessment was 23.4 ± 2.9 (95% CI, 17.7-29.1). The estimated mean difference between pre-HBOT and final assessment overall muscle function score was 6.7 ± 3.1 (95% CI, 0.6-16.1). The estimated mean difference of the overall muscle function score between pre-HBOT and final assessment for the improved group was 16.6 ± 3.5 (95% CI, 7.5-25.7) vs -4.9 ± 4.2 (95% CI, -16.0 to 6.2) for the non-improved group. CONCLUSIONS: HBOT, in addition to standard treatment, may potentially improve recovery in spinal cord function following SCI post-CAR. However, the potential benefits of HBOT are not equally distributed among subgroups.

Benzodiazepine-Free Cardiac Anesthesia for Reduction of Postoperative Delirium (B-Free): A Protocol for a Multi-centre Randomized Cluster Crossover Trial.

Delirium is common after cardiac surgery and is associated with adverse outcomes. Administration of benzodiazepines before and after cardiac surgery is associated with delirium; guidelines recommend minimizing their use. Benzodiazepine administration during cardiac surgery remains common because of its recognized benefits. The Benzodiazepine-Free Cardiac Anesthesia for Reduction of Postoperative Delirium (B-Free) trial is a randomized cluster crossover trial evaluating whether an institutional policy of restricting intraoperative benzodiazepine administration (ie, ≥ 90% of patients do not receive benzodiazepines during cardiac surgery), as compared with a policy of liberal intraoperative benzodiazepine administration (ie, ≥ 90% of patients receive ≥ 0.03 mg/kg midazolam equivalent), reduces delirium. Hospitals performing ≥ 250 cardiac surgeries a year are included if their cardiac anesthesia group agrees to apply both benzodiazepine policies per their randomization, and patients are assessed for postoperative delirium every 12 hours in routine clinical care. Hospitals apply the restricted or liberal benzodiazepine policy during 12 to 18 crossover periods of 4 weeks each. Randomization for all periods takes place in advance of site startup; sites are notified of their allocated policy during the last week of each crossover period. Policies are applied to all patients undergoing cardiac surgery during the trial period. The primary outcome is the incidence of delirium at up to 72 hours after surgery. The B-Free trial will enroll ≥ 18,000 patients undergoing cardiac surgery at 20 hospitals across North America. Delirium is common after cardiac surgery, and benzodiazepines are associated with the occurrence of delirium. The B-Free trial will determine whether an institutional policy restricting the administration of benzodiazepines during cardiac surgery reduces the incidence of delirium after cardiac surgery. Clinicaltrials.gov registration number: NCT03928236 (First registered April 26, 2019).

L'état confusionnel est fréquent après une chirurgie cardiaque et il est associé à des complications. L'administration de benzodiazépines avant et après une chirurgie cardiaque est associée à l'état confusionnel; dans les lignes directrices, on recommande de réduire leur utilisation au minimum. L'administration de benzodiazépines pendant une chirurgie cardiaque demeure fréquente, en raison des leurs bienfaits reconnus. L'essai B-Free (Benzodiazepine-Free Cardiac Anesthesia for Reduction of Postoperative Delirium ou l'anesthésie sans benzodiazépine en contexte de chirurgie cardiaque pour la réduction de l'état confusionnel postopératoire) est un essai à répartition aléatoire par grappes et avec permutation, visant à évaluer si une politique institutionnelle de restriction de l'administration peropératoire de benzodiazépines (c.-à-d. que ≥ 90 % des patients ne reçoivent pas de benzodiazépines durant une chirurgie cardiaque) réduit l'état confusionnel, comparativement à une politique d'administration peropératoire libérale de benzodiazépines (c.-à-d. que ≥ 90 % des patients reçoivent ≥ 0,03 mg/kg d'équivalent du midazolam). Des hôpitaux effectuant au moins 250 chirurgies cardiaques par année sont inclus dans l'essai si leurs équipes d'anesthésie cardiaque acceptent d'appliquer les deux politiques relatives aux benzodiazépines en vertu de la répartition aléatoire et si les patients sont évalués toutes les 12 heures, en ce qui a trait à l'état confusionnel postopératoire, dans le cadre des soins cliniques habituels. Les hôpitaux mettent en œuvre la politique d'administration restreinte ou libérale de benzodiazépines durant 12 à 18 périodes de permutation de 4 semaines chacune. La répartition aléatoire de l'ensemble des périodes a lieu avant le début de l'essai à l'hôpital; les établissements sont avisés de la politique qui leur est attribuée au cours de la dernière semaine de chaque période de permutation. Les politiques sont appliquées à tous les patients qui subissent une chirurgie cardiaque durant la période de l'essai. Le critère d'évaluation principal est l'incidence de l'état confusionnel dans les 72 heures suivant l'intervention chirurgicale. L'étude B-Free inclura au moins 18 000 patients qui subiront une chirurgie cardiaque dans 20 hôpitaux en l'Amérique du Nord. L'état confusionnel est fréquent après une chirurgie cardiaque, et les benzodiazépines sont associées à la survenue de l'état confusionnel. L'essai B-Free permettra de déterminer si une politique institutionnelle de restriction de l'administration de benzodiazépines durant une chirurgie cardiaque réduit l'incidence de l'état confusionnel après une telle chirurgie.Clinicaltrials.gov registration number: NCT03928236 (First registered April 26, 2019).

Pulmonary function following hyperbaric oxygen therapy: A longitudinal observational study.

Hyperbaric oxygen therapy (HBOT) is known to be associated with pulmonary oxygen toxicity. However, the effect of modern HBOT protocols on pulmonary function is not completely understood. The present study evaluates pulmonary function test changes in patients undergoing serial HBOT. We prospectively collected data on patients undergoing HBOT from 2016-2021 at a tertiary referral center (protocol registration NCT05088772). Patients underwent pulmonary function testing with a bedside spirometer/pneumotachometer prior to HBOT and after every 20 treatments. HBOT was performed using 100% oxygen at a pressure of 2.0-2.4 atmospheres absolute (203-243 kPa) for 90 minutes, five times per week. Patients' charts were retrospectively reviewed for demographics, comorbidities, medications, HBOT specifications, treatment complications, and spirometry performance. Primary outcomes were defined as change in percent predicted forced expiratory volume in one second (FEV1), forced vital capacity (FVC), and forced mid-expiratory flow (FEF25-75), after 20, 40, and 60 HBOT sessions. Data was analyzed with descriptive statistics and mixed-model linear regression. A total of 86 patients were enrolled with baseline testing, and the analysis included data for 81 patients after 20 treatments, 52 after 40 treatments, and 12 after 60 treatments. There were no significant differences in pulmonary function tests after 20, 40, or 60 HBOT sessions. Similarly, a subgroup analysis stratifying the cohort based on pre-existing respiratory disease, smoking history, and the applied treatment pressure did not identify any significant changes in pulmonary function tests during HBOT. There were no significant longitudinal changes in FEV1, FVC, or FEF25-75 after serial HBOT sessions in patients regardless of pre-existing respiratory disease. Our results suggest that the theoretical risk of pulmonary oxygen toxicity following HBOT is unsubstantiated with modern treatment protocols, and that pulmonary function is preserved even in patients with pre-existing asthma, chronic obstructive lung disease, and interstitial lung disease.

Prevalence and Risk Factors for Chronic Postsurgical Pain after Cardiac Surgery: A Single-center Prospective Cohort Study.

BACKGROUND: Chronic postsurgical pain is a common complication of surgery. The role of psychologic risk factors like depression and anxiety is substantially understudied in cardiac surgery. This study sought to identify perioperative factors associated with chronic pain at 3, 6, and 12 months after cardiac surgery. The authors hypothesize that baseline psychologic vulnerabilities have a negative influence on chronic postsurgical pain. METHODS: The authors prospectively collected demographic, psychologic, and perioperative factors in a cohort of 1,059 patients undergoing cardiac surgery at the Toronto General Hospital between 2012 and 2020. Patients were followed and completed chronic pain questionnaires at 3, 6, and 12 months after surgery. RESULTS: The study included 767 patients who completed at least one follow-up questionnaire. The incidence of postsurgical pain (more than 0 out of 10) at 3, 6, and 12 months after surgery was 191 of 663 (29%), 118 of 625 (19%), and 89 of 605 (15%), respectively. Notably, among patients reporting any pain, the incidence of pain compatible with a neuropathic phenotype increased from 56 of 166 (34%) at 3 months to 38 of 97 (39%) at 6 months and 43 of 67 (64%) at 12 months. Factors associated with postsurgical pain scores at 3 months include female sex, pre-existing chronic pain, previous cardiac surgery, preoperative depression, baseline pain catastrophizing scores, and moderate-to-severe acute pain (4 or more out of 10) within 5 postoperative days. CONCLUSIONS: Nearly one in three patients undergoing cardiac surgery reported pain at 3 months of follow-up, with approximately 15% reporting persistent pain at 1 yr. Female sex, pre-existing chronic pain, and baseline depression were associated with postsurgical pain scores across all three time periods.

The role of routine pulmonary imaging before hyperbaric oxygen treatment.

Respiratory injury during or following hyperbaric oxygen treatment (HBOT) is rare, but associated pressure changes can cause iatrogenic pulmonary barotrauma with potentially severe sequelae such as pneumothoraces. Pulmonary blebs, bullae, and other emphysematous airspace abnormalities increase the risk of respiratory complications and are prevalent in otherwise healthy adults. HBOT providers may elect to use chest X-ray routinely as a pre-treatment screening tool to identify these anomalies, particularly if a history of preceding pulmonary disease is identified, but this approach has a low sensitivity and frequently provides false negative results. Computed tomography scans offer greater sensitivity for airspace lesions, but given the high prevalence of incidental and insignificant pulmonary findings among healthy individuals, would lead to a high false positive rate because most lesions are unlikely to pose a hazard during HBOT. Post-mortem and imaging studies of airspace lesion prevalence show that a significant proportion of patients who undergo HBOT likely have pulmonary abnormalities such as blebs and bullae. Nevertheless, pulmonary barotrauma is rare, and occurs mainly in those with known underlying lung pathology. Consequently, routinely using chest X-ray or computed tomography scans as screening tools prior to HBOT for low-risk patients without a pertinent medical history or lack of clinical symptoms of cardiorespiratory disease is of low value. This review outlines published cases of patients experiencing pulmonary barotrauma while undergoing pressurised treatment/testing in a hyperbaric chamber and analyses the relationship between barotrauma and pulmonary findings on imaging prior to or following exposure. A checklist and clinical decision-making tool based on suggested low-risk and high-risk features are offered to guide the use of targeted baseline thoracic imaging prior to HBOT.

Efficacy and safety of hyperbaric oxygen treatment in SARS-COV-2 (COVID-19) pneumonia: a systematic review.

INTRODUCTION: The need for intubation and mechanical ventilation among COVID-19 patients is associated with high mortality rates and places a substantial burden on the healthcare system. There is a strong pathophysiological rationale suggesting that hyperbaric oxygen treatment (HBOT), a low-risk and non-invasive treatment, may be beneficial for COVID-19 patients. This systematic review aimed to explore the potential effectiveness and safety of HBOT for treating patients with COVID-19. METHODS: Medline, Embase, Scopus, and Google Scholar were searched from December 2019 to February 2021, without language restrictions. The grey literature was searched via an internet search engine and targeted website and database searches. Reference lists of included studies were searched. Independent reviewers assessed studies for eligibility and extracted data, with disagreements resolved by consensus or a third reviewer. Risk of bias was assessed using the Newcastle Ottawa Scale. Data were summarised descriptively. RESULTS: Six publications (one cohort study, five case reports/series) met the inclusion criteria with a total of 37 hypoxaemic COVID-19 patients treated with HBOT. Of these 37 patients, the need for intubation and mechanical ventilation and in-hospital survival were assessed for 26 patients across three studies. Of these 26 patients, intubation and mechanical ventilation were not required for 24, and 23 patients survived. No serious adverse events of HBOT in COVID-19 patients were reported. No randomised trials have been published. CONCLUSIONS: Limited and weak evidence from non-randomised studies including one propensity-matched cohort study suggests HBOT is safe and may be a promising intervention to optimise treatment and outcomes in hypoxaemic COVID-19 patients. Randomised controlled studies are urgently needed.

Cognitive Outcomes after DEXmedetomidine sedation in cardiac surgery: CODEX randomised controlled trial protocol.

INTRODUCTION: Older patients undergoing cardiac surgery carry the highest risk for developing major postoperative neurocognitive disorder (postoperative NCD or P-NCD) with up to 25% incidence 3 months after surgery. P-NCD is associated with significant morbidity, mortality, loss of independence, premature retirement and increased healthcare costs. This multicentre randomised trial is investigating the efficacy of postoperative dexmedetomidine sedation in reducing the incidence of major P-NCD after cardiac surgery compared with standard protocols. CODEX will be the largest interventional trial with major P-NCD as the primary outcome. METHODS AND ANALYSIS: CODEX is recruiting patients ≥60 years old, undergoing elective cardiac surgery and without pre-existing major cognitive dysfunction or dementia. Eligible participants are randomised to receive postoperative dexmedetomidine or standard institutional sedation protocols in the intensive care unit. Baseline preoperative cognitive function is assessed with the computer-based Cogstate Brief Battery. The primary outcome, major P-NCD, 3 months after surgery is defined as a decrease in cognitive function ≥1.96 SD below age-matched, non-operative controls. Secondary outcomes include delirium, major P-NCD at 6/12 months, depressive symptoms, mild P-NCD and quality of surgical recovery at 3/6/12 months. The specific diagnostic criteria used in this protocol are consistent with the recommendations for clinical assessment and management of NCD from the Nomenclature Consensus Working Group on perioperative cognitive changes. Intention-to-treat analysis will compare major P-NCD at 3 months between study groups. ETHICS AND DISSEMINATION: CODEX was approved by Sunnybrook Health Sciences Centre Research Ethics Board (REB) (Project ID 1743). This will be the first multicentre, randomised controlled trial to assess the efficacy of a pharmacological intervention to reduce the incidence of major P-NCD after cardiac surgery in patients ≥60 years old. Dissemination of the study results will include briefings of key findings and interpretation, conference presentations and peer-reviewed publications. TRIAL REGISTRATION NUMBER: NCT04289142.