Trends in Incidence and Outcomes of Cardiac Arrest Occurring in Swedish ICUs.

OBJECTIVE: To determine temporal trends in the incidence of cardiac arrest occurring in the ICU (ICU-CA) and its associated long-term mortality. DESIGN: Retrospective observational study. SETTING: Swedish ICUs, between 2011 and 2017. PATIENTS: Adult patients (≥18 yr old) recorded in the Swedish Intensive Care Registry (SIR). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: ICU-CA was defined as a first episode of cardiopulmonary resuscitation and/or defibrillation following an ICU admission, as recorded in SIR or the Swedish Cardiopulmonary Resuscitation Registry. Annual adjusted ICU-CA incidence trend (all admissions) was estimated using propensity score-weighted analysis. Six-month mortality trends (first admissions) were assessed using multivariable mixed-effects logistic regression. Analyses were adjusted for pre-admission characteristics (sex, age, socioeconomic status, comorbidities, medications, and healthcare utilization), illness severity on ICU admission, and admitting unit. We included 231,427 adult ICU admissions. Crude ICU-CA incidence was 16.1 per 1,000 admissions, with no significant annual trend in the propensity score-weighted analysis. Among 186,530 first admissions, crude 6-month mortality in ICU-CA patients was 74.7% (95% CI, 70.1-78.9) in 2011 and 68.8% (95% CI, 64.4-73.0) in 2017. When controlling for multiple potential confounders, the adjusted 6-month mortality odds of ICU-CA patients decreased by 6% per year (95% CI, 2-10). Patients admitted after out-of-hospital or in-hospital cardiac arrest had the highest ICU-CA incidence (136.1/1,000) and subsequent 6-month mortality (76.0% [95% CI, 73.6-78.4]). CONCLUSIONS: In our nationwide Swedish cohort, the adjusted incidence of ICU-CA remained unchanged between 2011 and 2017. More than two-thirds of patients with ICU-CA did not survive to 6 months following admission, but a slight improvement appears to have occurred over time.

Comparison of preoxygenation using a tight facemask, humidified high-flow nasal oxygen and a standard nasal cannula - a volunteer, randomised, crossover study.

BACKGROUND: Preoxygenation before anaesthesia induction is routinely performed via a tight-fitting facemask or humidified high-flow nasal oxygen. We hypothesised that effective preoxygenation, assessed by end-tidal oxygen (EtO 2 ) levels, can also be performed via a standard nasal cannula. OBJECTIVE: This study compared the efficacy of preoxygenation between a traditional facemask, humidified high-flow nasal oxygen and a standard nasal cannula. DESIGN: A volunteer, randomised, crossover study. SETTING: Karolinska University Hospital, Stockholm. The study was conducted between 2 May and 31 May 2023. PARTICIPANTS: Twenty cardiopulmonary healthy volunteers aged 25-65 years with a BMI <30. INTERVENTIONS: Preoxygenation using a traditional facemask, humidified high-flow nasal oxygen and standard nasal cannula. Volunteers were preoxygenated with all three methods, at various flow rates (10-50 l min -1 ), with open and closed mouths and during vital capacity manoeuvres. MAIN OUTCOME MEASURES: The study's primary outcome compared the efficacy after 3 min of preoxygenation, assessed by EtO 2 levels, between the three methods and various flow rates of preoxygenation. RESULTS: Three methods generated higher EtO 2 levels than others: (i) facemask preoxygenation using normal breathing, (ii) humidified high-flow nasal oxygen, closed-mouth breathing, at 50 l min -1 and (iii) standard nasal cannula, closed-mouth breathing, at 50 l min -1 , and expressed as means (SD): 90% (3), 90% (6) and 88% (5), respectively. Preoxygenation efficacy was greater via the bi-nasal cannulae using closed vs. open mouth breathing as well as with 3 min of normal breathing vs. eight vital capacity breaths. Preoxygenation with a facemask and humidified high-flow nasal oxygen was more comfortable than a standard nasal cannula. CONCLUSION: The efficacy of preoxygenation using a standard nasal cannula at high flow rates is no different to clinically used methods today. The standard nasal cannula provides less comfort but is highly effective and could be an option when alternative methods are unavailable. TRIAL REGISTRATION: Clinicaltrials.gov, NCT05839665.

Chronic dysglycemia and risk of SARS-CoV-2 associated respiratory failure in hospitalized patients.

BACKGROUND: Diabetes is common among patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-induced respiratory failure. We aimed to investigate the relationship between different stages of chronic dysglycemia and development of respiratory failure in hospitalized SARS-CoV-2 positive patients. METHODS: In this retrospective observational study, we included 385 hospitalized SARS-CoV-2 positive patients at Karolinska University Hospital, Sweden with an HbA1c test obtained within 3 months before admission. Based on HbA1c level and previous diabetes history, we classified patients into the following dysglycemia categories: prediabetes, unknown diabetes, controlled diabetes, or uncontrolled diabetes. We used multivariable logistic regression analysis adjusted for age, sex, and body mass index, to assess the association between dysglycemia categories and development of SARS-CoV-2-induced respiratory failure. RESULTS: Of the 385 study patients, 88 (22.9%) had prediabetes, 68 (17.7%) had unknown diabetes, 36 (9.4%) had controlled diabetes, and 83 (21.6%) had uncontrolled diabetes. Overall, 299 (77.7%) patients were admitted with or developed SARS-CoV-2-induced respiratory failure during hospitalization. In multivariable logistic regression analysis compared with no chronic dysglycemia, prediabetes (OR 14.41, 95% CI 5.27-39.43), unknown diabetes (OR 15.86, 95% CI 4.55-55.36), and uncontrolled diabetes (OR 17.61, 95% CI 5.77-53.74) was independently associated with increased risk of SARS-CoV-2-induced respiratory failure. CONCLUSION: In our cohort of hospitalized SARS-CoV-2 positive patients with available HbA1c data, prediabetes, undiagnosed diabetes, and poorly controlled diabetes were associated with a markedly increased risk of SARS-CoV-2-associated respiratory failure.

Neuroinflammatory markers associate with cognitive decline after major surgery: Findings of an explorative study.

OBJECTIVE: Long-term cognitive decline is an adverse outcome after major surgery associated with increased risk for mortality and morbidity. We studied the cerebrospinal fluid (CSF) and serum biochemical inflammatory response to a standardized orthopedic surgical procedure and the possible association with long-term changes in cognitive function. We hypothesized that the CSF inflammatory response pattern after surgery would differ in patients having long-term cognitive decline defined as a composite cognitive z score of ≥1.0 compared to patients without long-term cognitive decline at 3 months postsurgery. METHODS: Serum and CSF biomarkers of inflammation and blood-brain barrier (BBB) integrity were measured preoperatively and up to 48 hours postoperatively, and cognitive function was assessed preoperatively and at 2 to 5 days and 3 months postoperatively. RESULTS: Surgery was associated with a pronounced increase in inflammatory biomarkers in both CSF and blood throughout the 48-hour study period. A principal component (PC) analysis was performed on 52 inflammatory biomarkers. The 2 first PC (PC1 and PC2) construct outcome variables on CSF biomarkers were significantly associated with long-term cognitive decline at 3 months, but none of the PC construct serum variables showed a significant association with long-term cognitive decline at 3 months. Patients both with and patients without long-term cognitive decline showed early transient increases of the astroglial biomarkers S-100B and glial fibrillary acidic protein in CSF, and in BBB permeability (CSF/serum albumin ratio). INTERPRETATION: Surgery rapidly triggers a temporal neuroinflammatory response closely associated with long-term cognitive outcome postsurgery. The findings of this explorative study require validation in a larger surgical patient cohort. Ann Neurol 2020;87:370-382.

Emergency Airway Management in Patients with COVID-19: A Prospective International Multicenter Cohort Study.

BACKGROUND: Tracheal intubation for patients with COVID-19 is required for invasive mechanical ventilation. The authors sought to describe practice for emergency intubation, estimate success rates and complications, and determine variation in practice and outcomes between high-income and low- and middle-income countries. The authors hypothesized that successful emergency airway management in patients with COVID-19 is associated with geographical and procedural factors. METHODS: The authors performed a prospective observational cohort study between March 23, 2020, and October 24, 2020, which included 4,476 episodes of emergency tracheal intubation performed by 1,722 clinicians from 607 institutions across 32 countries in patients with suspected or confirmed COVID-19 requiring mechanical ventilation. The authors investigated associations between intubation and operator characteristics, and the primary outcome of first-attempt success. RESULTS: Successful first-attempt tracheal intubation was achieved in 4,017/4,476 (89.7%) episodes, while 23 of 4,476 (0.5%) episodes required four or more attempts. Ten emergency surgical airways were reported-an approximate incidence of 1 in 450 (10 of 4,476). Failed intubation (defined as emergency surgical airway, four or more attempts, or a supraglottic airway as the final device) occurred in approximately 1 of 120 episodes (36 of 4,476). Successful first attempt was more likely during rapid sequence induction versus non-rapid sequence induction (adjusted odds ratio, 1.89 [95% CI, 1.49 to 2.39]; P < 0.001), when operators used powered air-purifying respirators versus nonpowered respirators (adjusted odds ratio, 1.60 [95% CI, 1.16 to 2.20]; P = 0.006), and when performed by operators with more COVID-19 intubations recorded (adjusted odds ratio, 1.03 for each additional previous intubation [95% CI, 1.01 to 1.06]; P = 0.015). Intubations performed in low- or middle-income countries were less likely to be successful at first attempt than in high-income countries (adjusted odds ratio, 0.57 [95% CI, 0.41 to 0.79]; P = 0.001). CONCLUSIONS: The authors report rates of failed tracheal intubation and emergency surgical airway in patients with COVID-19 requiring emergency airway management, and identified factors associated with increased success. Risks of tracheal intubation failure and success should be considered when managing COVID-19.

Awake prone positioning in patients with hypoxemic respiratory failure due to COVID-19: the PROFLO multicenter randomized clinical trial.

BACKGROUND: The effect of awake prone positioning on intubation rates is not established. The aim of this trial was to investigate if a protocol for awake prone positioning reduces the rate of endotracheal intubation compared with standard care among patients with moderate to severe hypoxemic respiratory failure due to COVID-19. METHODS: We conducted a multicenter randomized clinical trial. Adult patients with confirmed COVID-19, high-flow nasal oxygen or noninvasive ventilation for respiratory support and a PaO2/FiO2 ratio ≤ 20 kPa were randomly assigned to a protocol targeting 16 h prone positioning per day or standard care. The primary endpoint was intubation within 30 days. Secondary endpoints included duration of awake prone positioning, 30-day mortality, ventilator-free days, hospital and intensive care unit length of stay, use of noninvasive ventilation, organ support and adverse events. The trial was terminated early due to futility. RESULTS: Of 141 patients assessed for eligibility, 75 were randomized of whom 39 were allocated to the control group and 36 to the prone group. Within 30 days after enrollment, 13 patients (33%) were intubated in the control group versus 12 patients (33%) in the prone group (HR 1.01 (95% CI 0.46-2.21), P = 0.99). Median prone duration was 3.4 h [IQR 1.8-8.4] in the control group compared with 9.0 h per day [IQR 4.4-10.6] in the prone group (P = 0.014). Nine patients (23%) in the control group had pressure sores compared with two patients (6%) in the prone group (difference - 18% (95% CI - 2 to - 33%); P = 0.032). There were no other differences in secondary outcomes between groups. CONCLUSIONS: The implemented protocol for awake prone positioning increased duration of prone positioning, but did not reduce the rate of intubation in patients with hypoxemic respiratory failure due to COVID-19 compared to standard care. TRIAL REGISTRATION: ISRCTN54917435. Registered 15 June 2020 ( https://doi.org/10.1186/ISRCTN54917435 ).

Identification of Sleep Medicine and Anesthesia Core Topics for Anesthesia Residency: A Modified Delphi Technique Survey.

BACKGROUND: Sleep disorders affect up to 25% of the general population and are associated with increased risk of adverse perioperative events. The key sleep medicine topics that are most important for the practice of anesthesiology have not been well-defined. The objective of this study was to determine the high-priority sleep medicine topics that should be included in the education of anesthesia residents based on the insight of experts in the fields of anesthesia and sleep medicine. METHODS: We conducted a prospective cross-sectional survey of experts in the fields of sleep medicine and anesthesia based on the Delphi technique to establish consensus on the sleep medicine topics that should be incorporated into anesthesia residency curricula. Consensus for inclusion of a topic was defined as >80% of all experts selecting "agree" or "strongly agree" on a 5-point Likert scale. Responses to the survey questions were analyzed with descriptive statistical methods and presented as percentages or weighted mean values with standard deviations (SD) for Likert scale data. RESULTS: The topics that were found to have 100% agreement among experts were the influence of opioids and anesthetics on control of breathing and upper airway obstruction; potential interactions of wake-promoting/hypnotic medications with anesthetic agents; effects of sleep and anesthesia on upper airway patency; and anesthetic management of sleep apnea. Less than 80% agreement was found for topics on the anesthetic implications of other sleep disorders and future pathways in sleep medicine and anesthesia. CONCLUSIONS: We identify key topics of sleep medicine that can be included in the future design of anesthesia residency training curricula.

Biomarkers for oxidative stress and organ injury during Transnasal Humidified Rapid-Insufflation Ventilatory Exchange compared to mechanical ventilation in adults undergoing microlaryngoscopy: A randomised controlled study.

BACKGROUND: Apnoeic oxygenation using Transnasal Humidified Rapid-Insufflation Ventilatory Exchange (THRIVE) during general anaesthesia prolongs the safe apnoeic period. However, there is a gap of knowledge how THRIVE-induced hyperoxia and hypercapnia impact vital organs. The primary aim of this randomised controlled trial was to characterise oxidative stress and, secondary, vital organ function biomarkers during THRIVE compared to mechanical ventilation (MV). METHODS: Thirty adult patients, American Society of Anesthesiologists (ASA) 1-2, undergoing short laryngeal surgery under general anaesthesia were randomised to THRIVE, FI O2 1.0, 70 L min-1 during apnoea or MV. Blood biomarkers for oxidative stress, malondialdehyde and TAC and vital organ function were collected (A) preoperatively, (B) at procedure completion and (C) at PACU discharge. RESULTS: Mean apnoea time was 17.9 (4.8) min and intubation to end-of-surgery time was 28.1 (12.8) min in the THRIVE and MV group, respectively. Malondialdehyde increased from 11.2 (3.1) to 12.7 (3.1) µM (P = .02) and from 9.5 (2.2) to 11.6 (2.6) µM (P = .003) (A to C) in the THRIVE and MV group, respectively. S100B increased from 0.05 (0.02) to 0.06 (0.02) µg L-1 (P = .005) (A to C) in the THRIVE group. No increase in TAC, CRP, leukocyte count, troponin-T, NTproBNP, creatinine, eGFRcrea or NSE was demonstrated during THRIVE. CONCLUSION: While THRIVE and MV was associated with increased oxidative stress, we found no change in cardiac, inflammation or kidney biomarkers during THRIVE. Further evaluation of stress and inflammatory response and cerebral and cardiac function during THRIVE is needed.

The impact of damage-associated molecular patterns on the neurotransmitter release and gene expression in the ex vivo rat carotid body.

NEW FINDINGS: What is the central question of this study? Are carotid bodies (CBs) modulated by the damage-associated molecular patterns (DAMPs) and humoral factors of aseptic tissue injury? What are the main findings and their importance? DAMPs (HMGB1, S100 A8/A9) and blood plasma from rats subjected to tibia surgery, a model of aseptic injury, stimulate the release of neurotransmitters (ATP, dopamine) and TNF-α from ex vivo rat CBs. All-thiol HMGB1 mediates upregulation of immune-related biological pathways. These data suggest regulation of CB function by endogenous mediators of innate immunity. ABSTRACT: The glomus cells of carotid bodies (CBs) are the primary sensors of arterial partial O2 and CO2 tensions and moreover serve as multimodal receptors responding also to other stimuli, such as pathogen-associated molecular patterns (PAMPs) produced by acute infection. Modulation of CB function by excessive amounts of these immunomodulators is suggested to be associated with a detrimental hyperinflammatory state. We have hypothesized that yet another class of immunomodulators, endogenous danger-associated molecular patterns (DAMPs), released upon aseptic tissue injury and recognized by the same pathogen recognition receptors as PAMPs, might modulate the CB activity in a fashion similar to PAMPs. We have tested this hypothesis by exposing rat CBs to various DAMPs, such as HMGB1 (all-thiol and disulfide forms) and S100 A8/A9 in a series of ex vivo experiments that demonstrated the release of dopamine and ATP, neurotransmitters known to mediate CB homeostatic responses. We observed a similar response after incubating CBs with conditioned blood plasma obtained from the rats subjected to tibia surgery, a model of aseptic injury. In addition, we have investigated global gene expression in the rat CB using an RNA sequencing approach. Differential gene expression analysis showed all-thiol HMGB1-driven upregulation of a number of prominent pro-inflammatory markers including Il1α and Il1ß. Interestingly, conditioned plasma had a more profound effect on the CB transcriptome resulting in inhibition rather than activation of the immune-related pathways. These data are the first to suggest potential modulation of CB function by endogenous mediators of innate immunity.

The immune response of the human brain to abdominal surgery.

OBJECTIVE: Surgery launches a systemic inflammatory reaction that reaches the brain and associates with immune activation and cognitive decline. Although preclinical studies have in part described this systemic-to-brain signaling pathway, we lack information on how these changes appear in humans. This study examines the short- and long-term impact of abdominal surgery on the human brain immune system by positron emission tomography (PET) in relation to blood immune reactivity, plasma inflammatory biomarkers, and cognitive function. METHODS: Eight males undergoing prostatectomy under general anesthesia were included. Prior to surgery (baseline), at postoperative days 3 to 4, and after 3 months, patients were examined using [11 C]PBR28 brain PET imaging to assess brain immune cell activation. Concurrently, systemic inflammatory biomarkers, ex vivo blood tests on immunoreactivity to lipopolysaccharide (LPS) stimulation, and cognitive function were assessed. RESULTS: Patients showed a global downregulation of gray matter [11 C]PBR28 binding of 26 ± 26% (mean ± standard deviation) at 3 to 4 days postoperatively compared to baseline (p = 0.023), recovering or even increasing after 3 months. LPS-induced release of the proinflammatory marker tumor necrosis factor-α in blood displayed a reduction (41 ± 39%) on the 3rd to 4th postoperative day, corresponding to changes in [11 C]PBR28 distribution volume. Change in Stroop Color-Word Test performance between postoperative days 3 to 4 and 3 months correlated to change in [11 C]PBR28 binding (p = 0.027). INTERPRETATION: This study translates preclinical data on changes in the brain immune system after surgery to humans, and suggests an interplay between the human brain and the inflammatory response of the peripheral innate immune system. These findings may be related to postsurgical impairments of cognitive function. Ann Neurol 2017;81:572-582.

Can STOP-Bang and Pulse Oximetry Detect and Exclude Obstructive Sleep Apnea?

BACKGROUND: Obstructive sleep apnea (OSA) is related to postoperative complications and is a common disorder. Most patients with sleep apnea are, however, undiagnosed, and there is a need for simple screening tools. We aimed to investigate whether STOP-Bang and oxygen desaturation index can identify subjects with OSA. METHODS: In this prospective, observational multicenter trial, 449 adult patients referred to a sleep clinic for evaluation of OSA were investigated with ambulatory polygraphy, including pulse oximetry and the STOP-Bang questionnaire in 4 Swedish centers. The STOP-Bang score is the sum of 8 positive answers to Snoring, Tiredness, Observed apnea, high blood Pressure, Body mass index >35 kg/m, Age >50 years, Neck circumference >40 cm, and male Gender. RESULTS: The optimal STOP-Bang cutoff score was 6 for moderate and severe sleep apnea, defined as apnea-hypopnea index (AHI) ≥15, and the sensitivity and specificity for this score were 63% (95% CI, 0.55-0.70) and 69% (95% CI, 0.64-0.75), respectively. A STOP-Bang score of <2 had a probability of 95% (95% CI, 0.92-0.98) to exclude an AHI >15 and a STOP-Bang score of ≥6 had a specificity of 91% (95% CI, 0.87-0.94) for an AHI >15. The items contributing most to the STOP-Bang were the Bang items. There was a positive correlation between AHI versus STOP-Bang and between AHI versus oxygen desaturation index, Spearman ρ 0.50 (95% CI, 0.43-0.58) and 0.96 (95% CI, 0.94-0.97), respectively. CONCLUSIONS: STOP-Bang and pulse oximetry can be used to screen for sleep apnea. A STOP-Bang score of <2 almost excludes moderate and severe OSA, whereas nearly all the patients with a STOP-Bang score ≥6 have OSA. We suggest the addition of nightly pulse oximetry in patients with a STOP-Bang score of 2-5 when there is a need for screening for sleep apnea (ie, before surgery).

Sedation with Dexmedetomidine or Propofol Impairs Hypoxic Control of Breathing in Healthy Male Volunteers: A Nonblinded, Randomized Crossover Study.

BACKGROUND: In contrast to general anesthetics such as propofol, dexmedetomidine when used for sedation has been put forward as a drug with minimal effects on respiration. To obtain a more comprehensive understanding of the regulation of breathing during sedation with dexmedetomidine, the authors compared ventilatory responses to hypoxia and hypercapnia during sedation with dexmedetomidine and propofol. METHODS: Eleven healthy male volunteers entered this randomized crossover study. Sedation was administered as an intravenous bolus followed by an infusion and monitored by Observer's Assessment of Alertness/Sedation (OAA/S) scale, Richmond Agitation Sedation Scale, and Bispectral Index Score. Hypoxic and hypercapnic ventilatory responses were measured at rest, during sedation (OAA/S 2 to 4), and after recovery. Drug exposure was verified with concentration analysis in plasma. RESULTS: Ten subjects completed the study. The OAA/S at the sedation goal was 3 (3 to 4) (median [minimum to maximum]) for both drugs. Bispectral Index Score was 82 ± 8 and 75 ± 3, and the drug concentrations in plasma at the sedation target were 0.66 ± 0.14 and 1.26 ± 0.36 µg/ml for dexmedetomidine and propofol, respectively. Compared with baseline, sedation reduced hypoxic ventilation to 59 and 53% and the hypercapnic ventilation to 82 and 86% for dexmedetomidine and propofol, respectively. In addition, some volunteers displayed upper airway obstruction and episodes of apnea during sedation. CONCLUSIONS: Dexmedetomidine-induced sedation reduces ventilatory responses to hypoxia and hypercapnia to a similar extent as sedation with propofol. This finding implies that sedation with dexmedetomidine interacts with both peripheral and central control of breathing.

Lung impedance changes during awake prone positioning in COVID-19. A non-randomized cross-over study.

BACKGROUND: The effects of awake prone positioning (APP) on respiratory mechanics in patients with COVID-19 are not well characterized. The aim of this study was to investigate changes of global and regional lung volumes during APP compared with the supine position using electrical lung impedance tomography (EIT) in patients with hypoxemic respiratory failure due to COVID-19. MATERIALS AND METHODS: This exploratory non-randomized cross-over study was conducted at two university hospitals in Sweden between January and May 2021. Patients admitted to the intensive care unit with confirmed COVID-19, an arterial cannula in place, a PaO2/FiO2 ratio <26.6 kPa (<200 mmHg) and high-flow nasal oxygen or non-invasive ventilation were eligible for inclusion. EIT-data were recorded at supine baseline, at 30 and 60 minutes after APP-initiation, and 30 minutes after supine repositioning. The primary outcomes were changes in global and regional tidal impedance variation (TIV), center of ventilation (CoV), global and regional delta end-expiratory lung-impedance (dEELI) and global inhomogeneity (GI) index at the end of APP compared with supine baseline. Data were reported as median (IQR). RESULTS: All patients (n = 10) were male and age was 64 (47-73) years. There were no changes in global or regional TIV, CoV or GI-index during the intervention. dEELI increased from supine reference value 0 to 1.51 (0.32-3.62) 60 minutes after APP (median difference 1.51 (95% CI 0.19-5.16), p = 0.04) and returned to near baseline values after supine repositioning. Seven patients (70%) showed an increase >0.20 in dEELI during APP. The other EIT-variables did not change during APP compared with baseline. CONCLUSION: Awake prone positioning was associated with a transient lung recruiting effect without changes in ventilation distribution measured with EIT in patients with hypoxemic respiratory failure due to COVID-19.

Resolving postoperative neuroinflammation and cognitive decline.

OBJECTIVE: Cognitive decline accompanies acute illness and surgery, especially in the elderly. Surgery engages the innate immune system that launches a systemic inflammatory response that, if unchecked, can cause multiple organ dysfunction. We sought to understand the mechanisms whereby the brain is targeted by the inflammatory response and how this can be resolved. METHODS: C57BL/6J, Ccr2(RFP/+)Cx3cr1(GFP/+), Ikk(F/F) mice and LysM-Cre/Ikk(F/F) mice underwent stabilized tibial fracture operation under analgesia and general anesthesia. Separate cohorts of mice were tested for systemic and hippocampal inflammation, integrity of the blood-brain barrier (BBB), and cognition. The putative resolving effects of the cholinergic pathway on these postoperative responses were also studied. RESULTS: Peripheral surgery disrupts the BBB via release of tumor necrosis factor-alpha (TNFα), which facilitates the migration of macrophages into the hippocampus. Macrophage-specific deletion of Ikappa B kinase (IKK)ß, a central coordinator of TNFα signaling through activation of nuclear factor (NF) κB, prevents BBB disruption and macrophage infiltration in the hippocampus following surgery. Activation of the α7 subtype of nicotinic acetylcholine receptors, an endogenous inflammation-resolving pathway, prevents TNFα-induced NF-κB activation, macrophage migration into the hippocampus, and cognitive decline following surgery. INTERPRETATION: These data reveal the mechanisms for bidirectional communication between the brain and immune system following aseptic trauma. Pivotal molecular mechanisms can be targeted to prevent and/or resolve postoperative neuroinflammation and cognitive decline.

Characteristics and outcome of traumatic cardiac arrest at a level 1 trauma centre over 10 years in Sweden.

BACKGROUND: Historically, resuscitation in traumatic cardiac arrest (TCA) has been deemed futile. However, recent literature reports improved but varying survival. Current European guidelines emphasise the addressing of reversible aetiologies in TCA and propose that a resuscitative thoracotomy may be performed within 15 min from last sign of life. To improve clinician understanding of which patients benefit from resuscitative efforts we aimed to describe the characteristics and 30-day survival for traumatic cardiac arrest at a Swedish trauma centre with a particular focus on resuscitative thoracotomy. METHODS: Retrospective cohort study of adult patients (≥ 15 years) with TCA managed at Karolinska University Hospital Solna between 2011 and 2020. Trauma demographics, intra-arrest factors, lab values and procedures were compared between survivors and non-survivors. RESULTS: Among the 284 included patients the median age was 38 years, 82.2% were male and 60.5% were previously healthy. Blunt trauma was the dominant injury in 64.8% and median Injury Severity Score (ISS) was 38. For patients with a documented arrest rhythm, asystole was recorded in 39.2%, pulseless electric activity in 24.8% and a shockable rhythm in 6.8%. Thirty patients (10.6%) survived to 30 days with a Glasgow Outcome Scale score of 3 (n = 23) or 4 (n = 7). The most common causes of death were haemorrhagic shock (50.0%) and traumatic brain injury (25.5%). Survivors had a lower ISS (P < 0.001), more often had reactive pupils (P < 0.001) and a shockable rhythm (P = 0.04). In the subset of prehospital TCA, survivors less frequently received adrenaline (epinephrine) (P < 0.001) and in lower amounts (P = 0.02). Of patients that underwent resuscitative thoracotomy (n = 101), survivors (n = 12) had a shorter median time from last sign of life to thoracotomy (P = 0.03), however in four of these survivors the time exceeded 15 min. CONCLUSION: Survival after TCA is possible. Determining futility in TCA is difficult and this study demonstrates survivors outside of recent guidelines.

Whole blood gene expression signature in patients with obstructive sleep apnea and effect of continuous positive airway pressure treatment.

The molecular mechanisms of obstructive sleep apnea (OSA), in particular the gene expression patterns in whole blood of patients with OSA, can shed more light on the underlying pathophysiology of OSA and suggest potential biomarkers. In the current study, we have enrolled thirty patients with untreated moderate-severe OSA together with 20 BMI, age, and sex-matched controls and 15 normal-weight controls. RNA-sequencing of whole blood and home sleep apnea testing were performed in the untreated state and after three and twelve months of continuous positive airway pressure (CPAP) treatment. Analysis of the whole blood transcriptome of the patients with OSA revealed a unique pattern of differential expression with a significant number of downregulated immune-related genes including many heavy and light chain immunoglobulins and interferon-inducible genes. This was confirmed by the gene ontology analysis demonstrating enrichment with the biological processes associated with various immune functions. Expression of these genes was recovered after three months of CPAP treatment. After 12 months of CPAP treatment, the overall gene expression profile returns to the initial, untreated level. In addition, we have confirmed the importance of choosing BMI-matched controls as a reference group as opposed to normal-weight healthy individuals based on the significantly different gene expression signatures between these two groups.

Positive Expiratory Pressure Therapy on Oxygen Saturation and Ventilation After Abdominal Surgery: A Randomized Controlled Trial.

Objective: To evaluate the immediate effects of positive expiratory pressure therapy on oxygen saturation and ventilation after abdominal surgery. Background: Positive expiratory pressure therapy to treat postoperative hypoxia is widespread, despite a lack of evidence of effect. Methods: This randomized, sham-controlled, crossover trial investigated adults 1-2 days after abdominal surgery at Umeå University Hospital, Sweden. The intervention was positive expiratory pressure of 10-15 cm H2O. The control was a sham device. The investigations were ended with deep-breathing maneuvers. Outcomes were the gradient of changes in peripheral oxygen saturation and transcutaneous carbon-dioxide partial pressure (PtcCO2). Results: Eighty patients were included and randomized and 76 patients were analyzed. Oxygen saturation increased from a baseline mean of 92% to 95%, P < 0.001, during positive expiratory pressure breathing, while PtcCO2 decreased from a mean of 36 to 33 mm Hg, P < 0.001. This was followed by apnea, oxygen desaturations to a mean of 89%, P < 0.001, and increased PtcCO2 before returning to baseline values. The changes in oxygen saturation and PtcCO2 did not differ from sham breathing or deep-breathing maneuvers. Conclusions: Positive expiratory pressure breathing after abdominal surgery improves oxygen saturation during the maneuver because of hyperventilation, but it is followed by apnea, hypoventilation, and oxygen desaturation. The effect is not different from the expiration to a sham device or hyperventilation. It is time to stop positive expiratory pressure therapy after abdominal surgery, as there is no evidence of effect in previous trials, apart from the adverse effects reported here.

COVID-19 pathophysiology may be driven by an imbalance in the renin-angiotensin-aldosterone system.

SARS-CoV-2 uses ACE2, an inhibitor of the Renin-Angiotensin-Aldosterone System (RAAS), for cellular entry. Studies indicate that RAAS imbalance worsens the prognosis in COVID-19. We present a consecutive retrospective COVID-19 cohort with findings of frequent pulmonary thromboembolism (17%), high pulmonary artery pressure (60%) and lung MRI perfusion disturbances. We demonstrate, in swine, that infusing angiotensin II or blocking ACE2 induces increased pulmonary artery pressure, reduces blood oxygenation, increases coagulation, disturbs lung perfusion, induces diffuse alveolar damage, and acute tubular necrosis compared to control animals. We further demonstrate that this imbalanced state can be ameliorated by infusion of an angiotensin receptor blocker and low-molecular-weight heparin. In this work, we show that a pathophysiological state in swine induced by RAAS imbalance shares several features with the clinical COVID-19 presentation. Therefore, we propose that severe COVID-19 could partially be driven by a RAAS imbalance.