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Purpose: Sedative premedication in children may negatively impact their cardiorespiratory status during the perioperative course, and no clear consensus exists on the optimal premedication treatment for pediatric patients. The objective was to compare the perioperative cardiorespiratory responses to sedation using three different sedative premedication regimens in preschool children scheduled for surgery with total intravenous anesthesia. Design: A single-center randomized controlled trial. Methods: This is a planned secondary analysis of a study conducted at a 200-bed tertiary referral hospital. Ninety children participated in the study. They were aged 2–6 years and scheduled for ear, nose, and throat surgery with propofol/remifentanil anesthesia. Participants were randomly assigned to receive oral midazolam 0.5 mg/kg-1 (MID), oral clonidine 4 mcg/kg–1 (CLO), or intranasal dexmedetomidine 2 mcg/kg-1 (DEX). The main outcome measures were the sedation level, based on the Ramsay Sedation Scale (RSS), and cardiorespiratory status, monitored during the perioperative period. Findings: The final cohort had 83 children (MID, n=27; CLO, n=26; DEX, n=30), with similar intergroup patient characteristics. RSS scores were lower in the MID group than in the CLO and DEX groups before induction and within 30 min postsurgery (P

Patients admitted to intensive care after cardiac arrest are at risk of circulatory shock and early mortality due to cardiovascular failure. The aim of this study was to evaluate the ability of the veno-arterial pCO(2) difference ( increment pCO(2); central venous CO2 - arterial CO2) and lactate to predict early mortality in postcardiac arrest patients. This was a pre-planned prospective observational sub-study of the target temperature management 2 trial. The sub-study patients were included at five Swedish sites. Repeated measurements of increment pCO(2) and lactate were conducted at 4, 8, 12, 16, 24, 48, and 72 h after randomization. We assessed the association between each marker and 96-h mortality and their prognostic value for 96-h mortality. One hundred sixty-three patients were included in the analysis. Mortality at 96 h was 17%. During the initial 24 h, there was no difference in increment pCO(2) levels between 96-h survivors and non-survivors. increment pCO(2) measured at 4 h was associated with an increased risk of death within 96 h (adjusted odds ratio: 1.15; 95% confidence interval [CI]: 1.02-1.29; p = .018). Lactate levels were associated with poor outcome over multiple measurements. The area under the receiving operating curve to predict death within 96 h was 0.59 (95% CI: 0.48-0.74) and 0.82 (95% CI: 0.72-0.92) for increment pCO(2) and lactate, respectively. Our results do not support the use of increment pCO(2) to identify patients with early mortality in the postresuscitation phase. In contrast, non-survivors demonstrated higher lactate levels in the initial phase and lactate identified patients with early mortality with moderate accuracy.

While fluid resuscitation is fundamental in the treatment of sepsis-induced tissue hypo-perfusion, a sustained positive fluid balance is associated with excess mortality. Hyaluronan, an endogenous glycosaminoglycan with high affinity to water, has not been tested previously as adjuvant to fluid resuscitation in sepsis. In a prospective, parallel-grouped, blinded model of porcine peritonitis-sepsis, we randomized animals to intervention with adjuvant hyaluronan (add-on to standard therapy) (n=8) or 0.9% saline (n=8). After the onset of hemodynamic instability the animals received an initial bolus of 0.1 % hyaluronan 1 mg/kg/10 min or placebo (0.9% saline) followed by a continuous infusion of 0.1% hyaluronan (1 mg/kg/h) or saline during the experiment. We hypothesized that the administration of hyaluronan would reduce the volume of fluid administered (aiming at stroke volume variation

Purpose: This study intended to determine, and non-invasively evaluate, sternal intraosseous oxygen saturation (SsO2) and study its variation during provoked hypoxia or hypovolaemia. Furthermore, the relation between SsO2 and arterial (SaO2) or mixed venous oxygen saturation (SvO2) was investigated. Methods: Sixteen anaesthetised male pigs underwent exsanguination to a mean arterial pressure of 50 mmHg. After resuscitation and stabilisation, hypoxia was induced with hypoxic gas mixtures (air/N2). Repeated blood samples from sternal intraosseous cannulation were compared to arterial and pulmonary artery blood samples. Reflection spectrophotometry measurements by a non-invasive sternal probe were performed continuously. Results: At baseline SaO2 was 97.0% (IQR 0.2), SsO2 73.2% (IQR 19.6) and SvO2 52.3% (IQR 12.4). During hypovolaemia, SsO2 and SvO2 decreased to 58.9% (IQR 16.9) and 38.1% (IQR 12.5), respectively, p 2 remained unaltered (p = 0.44). During hypoxia all saturations decreased; SaO2 71.5% (IQR 5.2), SsO2 39.0% (IQR 6.9) and SvO2 22.6% (IQR 11.4) (p 2 relate well with changes in SvO2 during hypovolaemia or hypoxia. Further studies on the feasibility of using non-invasive measurement of changes in SsO2 to estimate changes in SvO2 are warranted.

Myocardial injury is now an acknowledged complication in patients undergoing noncardiac surgery. Heterogeneity in the definitions of myocardial injury contributes to difficulty in evaluating the value of cardiac troponins (cTns) measurement in perioperative care. Pre-, post-, and peri-operatively increased cTns are encompassed by the umbrella term myocardial injury and are likely to reflect different pathophysiological mechanisms. Increased cTns are independently associated with cardiovascular and non-cardiovascular complications, poor short-term and long-term cardiovascular outcomes, and increased mortality. Preoperative measurement of cTns aids preoperative risk stratification beyond the Revised Cardiac Risk Index. Systematic measurement detects acute perioperative increases and allows early identification of acute myocardial injury. Common definitions and standards for reporting are a prerequisite for designing impactful future trials and perioperative management strategies. Funding Agencies|Swedish Research Council, Sweden [2019-02833]; Linkoping University-Region Ostergotland, ALF, Sweden [687681, 792291]

Ventilator associated pneumonia (VAP) caused by P. aeruginosa is a cause of morbidity and mortality in critically ill patients. The spread of pathogens with anti-microbial resistance mandates the investigation of novel therapies. Specific polyclonal anti- P. aeruginosa IgY-antibodies ( Pa-IgY) might be effective for VAP caused by P. aeruginosa. The objective of this study was to investigate if intravenous Pa-IgY decreases the lower airway concentration of P. aeruginosa in VAP. We used a double blind randomized placebo controlled porcine model of VAP caused by P. aeruginosa. Eighteen pigs were randomized to either receive intravenous Pa-IgY or placebo. Repeated registration of physiological parameters and sampling was performed for 27 h. Concentration of P. aeruginosa in BAL-cultures was similar in both groups with 104.97 ± 102.09 CFU/mL in the intervention group vs 104.37 ± 102.62 CFU/mL in the control group at the end of the experiment. The intervention group had higher heart rate, cardiac index, oxygen delivery and arterial oxygen tension/fraction of inspired oxygen-ratio, but lower plasma lactate and blood hemoglobin levels than the control group. In summary, in an anesthetized and mechanically ventilated porcine model of VAP, Pa-IgY at the dose used did not decrease concentrations of P. aeruginosa in the lower airways.

Background The primary aim was to determine to what extent continuously monitored neurointensive care unit (neuro-ICU) targets predict cerebral blood flow (CBF) and delivery of oxygen (CDO2) after aneurysmal subarachnoid hemorrhage. The secondary aim was to determine whether CBF and CDO2 were associated with clinical outcome. Methods In this observational study, patients with aneurysmal subarachnoid hemorrhage treated at the neuro-ICU in Uppsala, Sweden, from 2012 to 2020 with at least one xenon-enhanced computed tomography (Xe-CT) obtained within the first 14 days post ictus were included. CBF was measured with the Xe-CT and CDO2 was calculated based on CBF and arterial oxygen content. Regional cerebral hypoperfusion was defined as CBF 2 was defined as CDO2 2/100 g/min. Neuro-ICU variables including intracranial pressure (ICP), pressure reactivity index, cerebral perfusion pressure (CPP), optimal CPP, and body temperature were assessed in association with the Xe-CT. The acute phase was divided into early phase (day 1–3) and vasospasm phase (day 4–14). Results Of 148 patients, 27 had underwent a Xe-CT only in the early phase, 74 only in the vasospasm phase, and 47 patients in both phases. The patients exhibited cerebral hypoperfusion and poor CDO2 for medians of 15% and 30%, respectively, of the cortical brain areas in each patient. In multiple regressions, higher body temperature was associated with higher CBF and CDO2 in the early phase. In a similar regression for the vasospasm phase, younger age and longer pulse transit time (lower peripheral resistance) correlated with higher CBF and CDO2, whereas lower hematocrit only correlated with higher CBF but not with CDO2. ICP, CPP, and pressure reactivity index exhibited no independent association with CBF and CDO2. R2 of these regressions were below 0.3. Lower CBF and CDO2 in the early phase correlated with poor outcome, but this only held true for CDO2 in multiple regressions. Conclusions Systemic and cerebral physiological variables exhibited a modest association with CBF and CDO2. Still, cerebral hypoperfusion and low CDO2 were common and low CDO2 was associated with poor outcome. Xe-CT imaging could be useful to help detect secondary brain injury not evident by high ICP and low CPP.

BACKGROUND: Approximately 25% of ambulatory surgery patients experience post-discharge nausea and vomiting (PDNV). We aimed to investigate whether palonosetron, a long-acting anti-emetic, decreases the incidence of PDNV in high-risk patients. METHODS: In this prospective, randomised, double-blind, placebo-controlled trial, 170 male and female patients undergoing ambulatory surgery under general anaesthesia, with a high predicted risk for PDNV, were randomised to receive either palonosetron 75 μg i.v. (n=84) or normal saline (n=86) before discharge. During the first 3 postoperative days (PODs), we measured outcomes using a patient questionanaire. The primary outcome was the incidence of a complete response (no nausea, vomiting, or use of rescue medication) until POD 2. Secondary outcomes included the incidence of PDNV each day until POD 3. RESULTS: The incidence of a complete response until POD 2 was 48% (n=32) in the palonosetron group and 36% (n=25) in the placebo group (odds ratio 1.69 [95% confidence interval: 0.85-3.37]; P=0.131). No significant difference in the incidence of PDNV was observed between the two groups on the day of surgery (47% vs 56%; P=0.31). Significant differences in the incidence of PDNV were found on POD 1 (18% vs 34%; P=0.033) and POD 2 (9% vs 27%; P=0.007). No differences were observed on POD 3 (15% vs 13%; P=0.700). CONCLUSIONS: Compared with placebo, palonosetron did not reduce the overall incidence of PDNV up to POD 2. The lower incidence of PDNV on POD 1 and POD 2 in the palonosetron group requires further investigation.

PurposeThis study describes preparedness of emergency physicians and general practitioners following chemical, radiological and nuclear incidents.Design/methodology/approachFive emergency physicians and six general practitioners were interviewed individually, and data was analysed using qualitative content analysis.FindingsThe study results showed that physicians' preparedness for chemical, radiological and nuclear incidents is linked to one main category: to be an expert and to seek expertise and two categories: preparations before receiving CRN patients, and physical examination and treatment of CRN patients with subcategories.Research limitations/implicationsThe results have implications for further research on the complexity of generalist vs specialist competence and knowledge when responding to chemical, radiological and nuclear incidents.Originality/valueThis study provides insights regarding chemical, radiological and nuclear preparedness among physicians at emergency departments and primary healthcare centres.

Background: Anesthesia preinduction anxiety in children can according to some studies lead to long-term anxiety and negative behavioral changes (NBC), while other studies have not found this effect. This secondary analysis from a recent premedication trial comparing clonidine and midazolam aimed to test the relation between preoperative anxiety assessed with modified Yale Preoperative Anxiety Scale (mYPAS) and postoperative NBCs assessed with Post Hospital Behavior Questionnaire (PHBQ), regardless of premedication type. Methods: This is a planned secondary analysis from a published premedication comparison trial in an outpatient surgery cohort, children aged 2–7 years. Participant and preoperative factors, particularly preoperative anxiety as mYPAS scores, were assessed for association with development of postoperative NBCs. Results: Fifty-four of the 115 participants had high preinduction anxiety (mYPAS >30), and 19 of 115 developed >3 postoperative NBCs 1 week after surgery. There was no association between preinduction anxiety level as mYPAS scores and the development of postoperative NBCs at 1 week after surgery (10 of 19 had both, p =.62) nor after 4- or 26-weeks post-surgery. Only lower age was associated with development of NBCs postoperatively. Conclusions: Based on the findings from this cohort, high preinduction anxiety does not appear to be associated with NBCs postoperatively in children premedicated with clonidine or midazolam.

Introduction Acute pain is a frequent symptom among patients in the pre-hospital setting, and opioids are the most widely used class of drugs for the relief of pain in these patients. However, the evidence base for opioid use in this setting appears to be weak. The aim of this systematic review was to explore the efficacy and safety of opioid analgesics in the pre-hospital setting and to assess potential alternative therapies. Methods The PubMed, EMBASE, Cochrane Library, Centre for Reviews and Dissemination, Scopus, and Epistemonikos databases were searched for studies investigating adult patients with acute pain prior to their arrival at hospital. Outcomes on efficacy and safety were assessed. Risk of bias for each included study was assessed according to the Cochrane approach, and confidence in the evidence was assessed using the GRADE method. Results A total of 3453 papers were screened, of which the full text of 125 was assessed. Twelve studies were ultimately included in this systematic review. Meta-analysis was not undertaken due to substantial clinical heterogeneity among the included studies. Several studies had high risk of bias resulting in low or very low quality of evidence for most of the outcomes. No pre-hospital studies compared opioids with placebo, and no studies assessed the risk of opioid administration for subgroups of frail patients. The competency level of the attending healthcare provider did not seem to affect the efficacy or safety of opioids in two observational studies of very low quality. Intranasal opioids had a similar effect and safety profile as intravenous opioids. Moderate quality evidence supported a similar efficacy and safety of synthetic opioid compared to morphine. Conclusions Available evidence for pre-hospital opioid administration to relieve acute pain is scarce and the overall quality of evidence is low. Intravenous administration of synthetic, fast-acting opioids may be as effective and safe as intravenous administration of morphine. More controlled studies are needed on alternative routes for opioid administration and pre-hospital pain management for potentially more frail patient subgroups. Funding Agencies|Scandinavian Society of Anaesthesia and Intensive care medicine (SSAI)

Background: Systems for smartphone dispatch of lay responders to perform cardio-pulmonary resuscitation (CPR) and bring automated external defibrillators to out-of-hospital cardiac arrests (OHCAs) are advocated by recent international guidelines and emerging worldwide. Objectives: This study aimed to investigate the emotional responses, posttraumatic stress reactions and levels of wellbeing among smartphonealerted lay responders dispatched to suspected OHCAs. Methods: Lay responders were stratified by level of exposure: unexposed (Exp-0), tried to reach (Exp-1), and reached the suspected OHCA (Exp2). Participants rated their emotional responses online, at 90 minutes and at 4-6 weeks after an incident. Level of emotional response was measured in two dimensions of core affect: "alertness" - from deactivation to activation, and "pleasantness" - from unpleasant to pleasant. At 4-6 weeks, WHO wellbeing index and level of posttraumatic stress (PTSD) were also rated. Results: Altogether, 915 (28%) unexposed and 1471 (64%) exposed responders completed the survey. Alertness was elevated in the exposed groups: Exp-0: 6.7 vs. Exp-1: 7.3 and Exp-2: 7.5, (p < 0.001) and pleasantness was highest in the unexposed group: 6.5, vs. Exp-1: 6.3, and Exp-2: 6.1, (p < 0.001). Mean scores for PTSD at follow-up was below clinical cut-off, Exp-0: 9.9, Exp-1: 8.9 and Exp-2: 8.8 (p = 0.065). Wellbeing index showed no differences, Exp-0: 78.0, Exp-1: 78.5 and Exp-2: 79.9 (p = 0.596). Conclusion: Smartphone dispatched lay responders rated the experience as high-energy and mainly positive. No harm to the lay responders was seen. The exposed groups had low posttraumatic stress scores and high-level general wellbeing at follow-up.

This article represents the response to the inquiries adopted by Dr. Raghuraman M Sethuraman, M.D., regarding our recently published study which compared the erector spinae plane block (ESPB) versus paravertebral block (PVB) regarding postoperative analgesic consumption following breast surgeries (Elewa et al, BMC Anesthesiol 22: 1-9, 2022). We would like to introduce our appreciation and gratitude to the author for his interest in our work, despite being inaccurate in some of his comments.

Background While frailty is a known predictor of adverse outcomes in older patients, its effect in younger populations is unknown. This prospective observational study was conducted in a tertiary-level mixed ICU to assess the impact of frailty on long-term survival in intensive care patients of different ages. Methods Data on premorbid frailty (Clinical Frailty Score; CFS), severity of illness (the Simplified Acute Physiology Score, third version; SAPS3), limitations of care and outcome were collected in 817 adult ICU patients. Hazard ratios (HR) for death within 180 days after ICU admission were calculated. Unadjusted and adjusted analyses were used to evaluate the association of frailty with outcome in different age groups. Results Patients were classified into predefined age groups (18–49 years (n = 241), 50–64 (n = 188), 65–79 (n = 311) and 80 years or older (n = 77)). The proportion of frail (CFS ≥ 5) patients was 41% (n = 333) in the overall population and increased with each age strata (n = 46 (19%) vs. n = 67 (36%) vs. n = 174 (56%) vs. n = 46 (60%), P P P P P = 0.02). The effect remained significant after adjustment for SAPS3, comorbidity and limitations of treatment only in patients aged 50–64 (2.1 (1.1–3.1), P Conclusions Premorbid frailty is common in ICU patients of all ages and was found in 55% of patients aged under 64 years. Frailty was independently associated with mortality only among middle-aged patients, where the risk of death was increased twofold. Our study supports the use of frailty assessment in identifying younger ICU patients at a higher risk of death.

Background Adequate training and preparation of medical first responders (MFRs) are essential for an optimal performance in highly demanding situations like disasters (e.g., mass accidents, natural catastrophes). The training needs to be as effective as possible, because precise and effective behavior of MFRs under stress is central for ensuring patients’ survival and recovery. This systematic review offers an overview of scientifically evaluated training methods used to prepare MFRs for disasters. It identifies different effectiveness indicators and provides an additional analysis of how and to what extent the innovative training technologies virtual (VR) and mixed reality (MR) are included in disaster training research. Methods The systematic review was conducted according to the PRISMA guidelines and focused specifically on (quasi-)experimental studies published between January 2010 and September 2021. The literature search was conducted via Web of Science and PubMed and led to the inclusion of 55 articles. Results The search identified several types of training, including traditional (e.g., lectures, real-life scenario training) and technology-based training (e.g., computer-based learning, educational videos). Most trainings consisted of more than one method. The effectiveness of the trainings was mainly assessed through pre-post comparisons of knowledge tests or self-reported measures although some studies also used behavioral performance measures (e.g., triage accuracy). While all methods demonstrated effectiveness, the literature indicates that technology-based methods often lead to similar or greater training outcomes than traditional trainings. Currently, few studies systematically evaluated immersive VR and MR training. Conclusion To determine the success of a training, proper and scientifically sound evaluation is necessary. Of the effectiveness indicators found, performance assessments in simulated scenarios are closest to the target behavior during real disasters. For valid yet inexpensive evaluations, objectively assessible performance measures, such as accuracy, time, and order of actions could be used. However, performance assessments have not been applied often. Furthermore, we found that technology-based training methods represent a promising approach to train many MFRs repeatedly and efficiently. These technologies offer great potential to supplement or partially replace traditional training. Further research is needed on those methods that have been underrepresented, especially serious gaming, immersive VR, and MR.

Purpose To provide consensus, and a list of experts’ recommendations regarding the basic skills for head-to-toe ultrasonography in the intensive care setting. Methods The Executive Committee of the European Society of Intensive Care (ESICM) commissioned the project and supervised the methodology and structure of the consensus. We selected an international panel of 19 expert clinicians–researchers in intensive care unit (ICU) with expertise in critical care ultrasonography (US), plus a non-voting methodologist. The panel was divided into five subgroups (brain, lung, heart, abdomen and vascular ultrasound) which identified the domains and generated a list of questions to be addressed by the panel. A Delphi process based on an iterative approach was used to obtain the final consensus statements. Statements were classified as a strong recommendation (84% of agreement), weak recommendation (74% of agreement), and no recommendation (less than 74%), in favor or against. Results This consensus produced a total of 74 statements (7 for brain, 20 for lung, 20 for heart, 20 for abdomen, 7 for vascular Ultrasound). We obtained strong agreement in favor for 49 statements (66.2%), 8 weak in favor (10.8%), 3 weak against (4.1%), and no consensus in 14 cases (19.9%). In most cases when consensus was not obtained, it was felt that the skills were considered as too advanced. A research agenda and discussion on training programs were implemented from the results of the consensus. Conclusions This consensus provides guidance for the basic use of critical care US and paves the way for the development of training and research projects. Supplementary Information The online version contains supplementary material available at 10.1007/s00134-021-06486-z.

Background The physiological response and the potentially beneficial effects of positive end-expiratory pressure (PEEP) for lung protection and optimization of ventilation during spontaneous breathing in patients with acute respiratory distress syndrome (ARDS) are not fully understood. The aim of the study was to compare the effect of different PEEP levels on tidal volume distribution and on the ventilation of dependent lung region during neurally adjusted ventilatory assist (NAVA). Methods ARDS-like lung injury was induced by using saline lavage in 10 anesthetized and spontaneously breathing farm-bred pigs. The animals were ventilated in NAVA modality and tidal volume distribution as well as dependent lung ventilation were assessed using electric impedance tomography during the application of PEEP levels from 0 to 15 cmH20, in steps of 3 cmH20. Tidal volume distribution and dependent fraction of ventilation were analysed using Wilcoxon signed rank test. Furthermore, airway, esophageal and transpulmonary pressure, as well as airway flow and delivered volume, were continuously measured during the assisted spontaneous breathing. Results Increasing PEEP improved oxygenation and re-distributed tidal volume. Specifically, ventilation distribution changed from a predominant non-dependent to a more even distribution between non-dependent and dependent areas of the lung. Dependent fraction of ventilation reached 47 ± 9% at PEEP 9 cmH20. Further increasing PEEP led to a predominant dependent ventilation. Conclusion During assisted spontaneous breathing in this model of induced ARDS, PEEP modifies the distribution of ventilation and can achieve a homogenizing effect on its spatial arrangement. The study indicates that PEEP is an important factor during assisted spontaneous breathing and that EIT can be of valuable interest when titrating PEEP level during spontaneous breathing, by indicating the most homogeneous distribution of gas volumes throughout the PEEP spectrum.

Approximately 7% of patients undergoing non-cardiac surgery with general anesthesia develop postoperative acute kidney injury (AKI). It is well-known that general anesthesia may have an impact on renal function and water bal-ance regulation, but the mechanisms and potential differences between anesthetics are not yet completely clear. Recently published large animal studies have demonstrated that volatile (gas) anesthesia stimulates the renal sym-pathetic nervous system more than intravenous propofol anesthesia, resulting in decreased water and sodium excretion and reduced renal perfusion and oxygenation. Whether this is the case also in humans remains to be clar-ified. Increased renal sympathetic nerve activity may impair renal excretory function and oxygenation and induce structural injury in ischemic AKI models and could therefore be a contributing factor to AKI in the perioperative set-ting. This review summarizes anesthetic agents' effects on the renal sympathetic nervous system that may be important in the pathogenesis of perioperative AKI.

Funding Information: The study was funded by the SciLifeLab/Knut and Alice Wallenberg national COVID-19 research program (M.H.: KAW 2020.0182, KAW 2020.0241), the Swedish Heart-Lung Foundation (M.H.: 20210089, 20190639, 20190637), the Swedish Research Council (R.F.: 2014-02569, 2014-07606), The Swedish Kidney Foundation (R.F.: F2020-0054), and The Swedish Society of Medicine (M.H. SLS-938101). Funding bodies had no role in the design of the study, data collection, interpretation, or in the writing of the manuscript. Publisher Copyright: © 2022 by the authors. A selective decrease in the renal filtration of larger molecules is attributed to the shrinkage of glomerular pores, a condition termed Shrunken Pore Syndrome (SPS). SPS is associated with poor long-term prognosis. We studied SPS as a risk marker in a cohort of patients with COVID-19 treated in an intensive care unit. SPS was defined as a ratio < 0.7 when the estimated glomerular filtration rate (eGFR), determined by cystatin C, calculated by the Cystatin C Caucasian-Asian-Pediatric-Adult equation (CAPA), was divided by the eGFR determined by creatinine, calculated by the revised Lund–Malmö creatinine equation (LMR). Clinical data were prospectively collected. In total, SPS was present in 86 (24%) of 352 patients with COVID-19 on ICU admission. Patients with SPS had a higher BMI, Simplified Physiology Score (SAPS3), and had diabetes and/or hypertension more frequently than patients without SPS. Ninety-nine patients in the total cohort were women, 50 of whom had SPS. In dexamethasone-naïve patients, C-reactive protein (CRP), TNF-alpha, and interleukin-6 did not differ between SPS and non-SPS patients. Demographic factors (gender, BMI) and illness severity (SAPS3) were independent predictors of SPS. Age and dexamethasone treatment did not affect the frequency of SPS after adjustments for age, sex, BMI, and acute severity. SPS is frequent in severely ill COVID-19 patients. Female gender was associated with a higher proportion of SPS. Demographic factors and illness severity were independent predictors of SPS. publishersversion published

Fluid administration is a cornerstone of treatment of critically ill patients. The aim of this review is to reappraise the pathophysiology of fluid therapy, considering the mechanisms related to the interplay of flow and pressure variables, the systemic response to the shock syndrome, the effects of different types of fluids administered and the concept of preload dependency responsiveness. In this context, the relationship between preload, stroke volume (SV) and fluid administration is that the volume infused has to be large enough to increase the driving pressure for venous return, and that the resulting increase in end-diastolic volume produces an increase in SV only if both ventricles are operating on the steep part of the curve. As a consequence, fluids should be given as drugs and, accordingly, the dose and the rate of administration impact on the final outcome. Titrating fluid therapy in terms of overall volume infused but also considering the type of fluid used is a key component of fluid resuscitation. A single, reliable, and feasible physiological or biochemical parameter to define the balance between the changes in SV and oxygen delivery (i.e., coupling “macro” and “micro” circulation) is still not available, making the diagnosis of acute circulatory dysfunction primarily clinical.

Background Optimal oxygen targets in patients resuscitated after cardiac arrest are uncertain. The primary aim of this study was to describe the values of partial pressure of oxygen values (PaO2) and the episodes of hypoxemia and hyperoxemia occurring within the first 72 h of mechanical ventilation in out of hospital cardiac arrest (OHCA) patients. The secondary aim was to evaluate the association of PaO2 with patients’ outcome. Methods Preplanned secondary analysis of the targeted hypothermia versus targeted normothermia after OHCA (TTM2) trial. Arterial blood gases values were collected from randomization every 4 h for the first 32 h, and then, every 8 h until day 3. Hypoxemia was defined as PaO2 2 > 300 mmHg. Mortality and poor neurological outcome (defined according to modified Rankin scale) were collected at 6 months. Results 1418 patients were included in the analysis. The mean age was 64 ± 14 years, and 292 patients (20.6%) were female. 24.9% of patients had at least one episode of hypoxemia, and 7.6% of patients had at least one episode of severe hyperoxemia. Both hypoxemia and hyperoxemia were independently associated with 6-month mortality, but not with poor neurological outcome. The best cutoff point associated with 6-month mortality for hypoxemia was 69 mmHg (Risk Ratio, RR = 1.009, 95% CI 0.93–1.09), and for hyperoxemia was 195 mmHg (RR = 1.006, 95% CI 0.95–1.06). The time exposure, i.e., the area under the curve (PaO2-AUC), for hyperoxemia was significantly associated with mortality (p = 0.003). Conclusions In OHCA patients, both hypoxemia and hyperoxemia are associated with 6-months mortality, with an effect mediated by the timing exposure to high values of oxygen. Precise titration of oxygen levels should be considered in this group of patients. Trial registration: clinicaltrials.gov NCT02908308, Registered September 20, 2016.

Background: Head computed tomography (CT) is a guideline recommended method to predict functional outcome after cardiac arrest (CA), but standardized criteria for evaluation are lacking. To date, no prospective trial has systematically validated methods for diagnosing hypoxic-ischaemic encephalopathy (HIE) on CT after CA. We present a protocol for validation of pre-specified radiological criteria for assessment of HIE on CT for neuroprognostication after CA. Methods/design: This is a prospective observational international multicentre substudy of the Targeted Hypothermia versus Targeted Normother-mia after out-of-hospital cardiac arrest (TTM2) trial. Patients still unconscious 48 hours post-arrest at 13 participating hospitals were routinely exam-ined with CT. Original images will be evaluated by examiners blinded to clinical data using a standardized protocol. Qualitative assessment will include evaluation of absence/presence of "severe HIE". Radiodensities will be quantified in pre-specified regions of interest for calculation of grey-white matter ratios (GWR) at the basal ganglia level. Functional outcome will be dichotomized into good (modified Rankin Scale 0-3) and poor (modified Rankin Scale 4-6) at six months post-arrest. Prognostic accuracies for good and poor outcome will be presented as sensitivities and speci-ficities with 95% confidence intervals (using pre-specified cut-offs for quantitative analysis), descriptive statistics (Area Under the Receiver Operating Characteristics Curve), inter-and intra-rater reliabilities according to STARD guidelines. Conclusions: The results from this prospective trial will validate a standardized approach to radiological evaluations of HIE on CT for prediction of functional outcome in comatose CA patients. The TTM2 trial and the TTM2 CT substudy are registered at ClinicalTrials.gov NCT02908308 and NCT03913065.

Aims and objectives: The aims of this study were to compare the anesthetic effect of a lidocaine/prilocaine (L/P) topical anesthetic with placebo on pain from needle sticks and to compare the anesthetic effect of the L/P topical anesthetic with an infiltrative anesthetic on pain from orthodontic miniscrew placement. Materials and methods: Pain elimination was analyzed from two interventions: (a) needle stick and (b) miniscrew insertion. When assessing pain from needle stick, one side of the mandible received 2.5% lidocaine/2.5% prilocaine topical anesthetic, and the other side received placebo. When evaluating pain from miniscrew placement, one side of the mandible received L/P topical anesthetic and the other side received infiltrative anesthetic. The findings were recorded on a Visual Analogue Scale after needle stick and after miniscrew placement. Subjective assessment was analyzed by a questionnaire. Results: The L/P topical anesthetic significantly eliminated the pain from needle stick (Mann–Whitney test of medians, 29.0 vs 0.0, respectively, p

Objective: Diagnosis of ventriculostomy related infections (VRI) in the neuro-intensive care unit remains chal-lenging and current biomarkers lack adequate precision. The aim of this study was to explore the potential of Heparin-binding protein (HBP) in cerebrospinal fluid (CSF) as a diagnostic biomarker of VRI. Methods: All patients treated with an external ventricular drain (EVD) between January 2009 and March 2010 at Skane university hospital in Lund, Sweden, were consecutively included. CSF samples obtained during routine care were analyzed for HBP. VRI was defined as a positive bacterial microbiology test result on a CSF sample with an erythrocyte-corrected leukocyte count of > 50 x 106/l. HBP levels at VRI diagnosis was compared to peak HBP levels in non-VRI controls. Results: In total, 394 CSF samples from 103 patients were analyzed for HBP. Seven patients (6.8%) fulfilled VRI criteria. Levels of HBP were significantly higher in VRI subjects (31.7 ng/mL [IQR 26.9-40.7 ng/mL]) compared to non-VRI controls (7.7 ng/mL [IQR 4.1-24.5 ng/mL]) (p = 0.024). The AUC of the receiver operating char-acteristic (ROC) curve was 0.76 (95% confidence interval [CI], 0.62-0.90). Among non-VRI patients, HBP was highest in patients with acute bacterial meningitis. Patients with subarachnoid hemorrhage displayed higher HBP levels than those with traumatic brain injury or shunt dysfunction. Conclusions: HBP levels were higher in VRI subjects and varied between patients and different diagnoses. To validate the clinical usefulness and added value of HBP as a biomarker for VRI, the results need to be confirmed in larger studies with head-to-head comparisons to current biomarkers.

OBJECTIVES: This study examined whether sociodemographic factors, including distance to hospital, were associated with differences in the diagnostic interval and the treatment interval for colorectal cancer in northern Sweden. METHODS: Data were retrieved from the Swedish cancer register on patients (n = 446) diagnosed in three northern regions during 2017-2018, then linked to data from Statistics Sweden and medical records. Also, Google maps was used to map the distance between patients' place of residence and nearest hospital. The different time intervals were analysed using Mann-Whitney U-test and Cox regression. RESULTS: Differences in time to diagnosis were found between groups for income and distance to hospital, favouring those with higher income and shorter distance. The unadjusted regression analysis showed higher income to be associated with more rapid diagnosis (HR 1.004, CI 1.001-1.007). This association remained in the fully adjusted model for income (HR 1.004, CI 1.000-1.008), but not for distance. No differences between sociodemographic groups were found in the treatment interval. CONCLUSION: Higher income and shorter distance to hospital were in the unadjusted models associated with shorter time to diagnosis for patients with CRC in northern Sweden. The association remained for income when adjusting for other variables even though the difference was small.

Background We aimed to optimize prediction of long-term all-cause mortality of intensive care unit (ICU) patients, using quantitative register-based comorbidity information assessed from hospital discharge diagnoses prior to intensive care treatment. Material and methods Adult ICU admissions during 2006 to 2012 in the Swedish intensive care register were followed for at least 4 years. The performance of quantitative comorbidity measures based on the 5-year history of number of hospital admissions, length of stay, and time since latest admission in 36 comorbidity categories was compared in time-to-event analyses with the Charlson comorbidity index (CCI) and the Simplified Acute Physiology Score (SAPS3). Results During a 7-year period, there were 230,056 ICU admissions and 62,225 deaths among 188,965 unique individuals. The time interval from the most recent hospital stays and total length of stay within each comorbidity category optimized mortality prediction and provided clear separation of risk categories also within strata of age and CCI, with hazard ratios (HRs) comparing lowest to highest quartile ranging from 1.17 (95% CI: 0.52–2.64) to 6.41 (95% CI: 5.19–7.92). Risk separation was also observed within SAPS deciles with HR ranging from 1.07 (95% CI: 0.83–1.38) to 3.58 (95% CI: 2.12–6.03). Conclusion Baseline comorbidity measures that included the time interval from the most recent hospital stay in 36 different comorbidity categories substantially improved long-term mortality prediction after ICU admission compared to the Charlson index and the SAPS score. Trial registration ClinicalTrials.gov ID NCT04109001, date of registration 2019-09-26 retrospectively.

Introduction: Intrapartum-related events account for nearly 700,000 neonatal deaths globally yearly. Endotracheal intubation is a cornerstone in preventing many of these deaths, but it is a difficult skill to acquire. Previous studies have described intubation performances in high-income coun-tries, but data from low-and middle-income countries are lacking. We aimed to assess the performance of delivery room intubation in a lower middle -income country.Methods: This prospective observational study was conducted at the Phu San Hanoi Hospital, Vietnam, from September 2020 to January 2021. Video cameras were positioned above the resuscitation tables and data were extracted using adopted software (NeoTapAS). All neonates requiring positive pressure ventilation were included. Our main variables of interest were time to first intubation attempt, first intubation attempt duration, and successful first intubation attempt.Results: 18,107 neonates were born during the five months. Of these, 75 (0.4%) received positive pressure ventilation, and 36 (0.2%) required endotracheal intubation of whom 24 were captured on video. The median time to the first intubation attempt was 252 seconds (range 91-771 sec-onds), the median first attempt duration was 49 seconds (range 10-105 seconds), and the first attempt success rate was 75%.Conclusion: Incidences of positive pressure ventilation and endotracheal intubation were low in comparison to global estimates. Three out of four intubations were successful at the first attempt and the procedural duration was often longer than recommended. Future studies should focus on how to achieve and maintain intubation skills and could include considering alternative devices for airway management at birth.

Background Targeted temperature management at 33 °C (TTM33) has been employed in effort to mitigate brain injury in unconscious survivors of out-of-hospital cardiac arrest (OHCA). Current guidelines recommend prevention of fever, not excluding TTM33. The main objective of this study was to investigate if TTM33 is associated with mortality in patients with vasopressor support on admission after OHCA. Methods We performed a post hoc analysis of patients included in the TTM-2 trial, an international, multicenter trial, investigating outcomes in unconscious adult OHCA patients randomized to TTM33 versus normothermia. Patients were grouped according to level of circulatory support on admission: (1) no-vasopressor support, mean arterial blood pressure (MAP) ≥ 70 mmHg; (2) moderate-vasopressor support MAP 0.25 µg/kg/min. Hazard ratios with TTM33 were calculated for all-cause 180-day mortality in these groups. Results The TTM-2 trial enrolled 1900 patients. Data on primary outcome were available for 1850 patients, with 662, 896, and 292 patients in the, no-, moderate-, or high-vasopressor support groups, respectively. Hazard ratio for 180-day mortality was 1.04 [98.3% CI 0.78–1.39] in the no-, 1.22 [98.3% CI 0.97–1.53] in the moderate-, and 0.97 [98.3% CI 0.68–1.38] in the high-vasopressor support groups with regard to TTM33. Results were consistent in an imputed, adjusted sensitivity analysis. Conclusions In this exploratory analysis, temperature control at 33 °C after OHCA, compared to normothermia, was not associated with higher incidence of death in patients stratified according to vasopressor support on admission. Trial registration Clinical trials identifier NCT02908308, registered September 20, 2016.

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Background Previous studies have found an increase in cardiac troponins (cTns) and echocardiographic abnormalities in patients with COVID-19 and reported their association with poor clinical outcomes. Whether acute injury occurs during the course of critical care and if it is associated with cardiac function is unknown. The purpose of this study was to document the incidence of acute myocardial injury (AMInj) and echocardiographically defined left ventricular (LV) and right ventricular (RV) systolic dysfunction in consecutive patients admitted to an intensive care unit (ICU) for COVID-19. The relationship between AMInj and echocardiographic abnormalities during the first 14 days of ICU admission was studied. Finally, the association between echocardiographic findings, AMInj and clinical outcome was evaluated. Methods Seventy-four consecutive patients (≥18 years) admitted to the ICU at Linköping University Hospital between 19 Mar 2020 and 31 Dec 2020 for COVID-19 were included. High-sensitivity troponin-T (hsTnT) was measured daily for up to 14 days. Transthoracic echocardiography was conducted within 72 h of ICU admission. Acute myocardial injury was defined as an increased hsTnT > 14ng/l and a > 20% absolute change with or without ischaemic symptoms. LV and RV systolic dysfunction was defined as at least 2 abnormal indicators of systolic function specified by consensus guidelines. Results Increased hsTnT was observed in 59% of patients at ICU admission, and 82% developed AMInj with peak levels at 8 (3–13) days after ICU admission. AMInj was not statistically significantly associated with 30-day mortality but was associated with an increased duration of invasive mechanical ventilation (10 (3–13) vs. 5 days (0–9), p=0.001) as well as ICU length of stay (LOS) (19.5 (11–28) vs. 7 days (5–13), p=0.015). After adjustment for SAPS-3 and admission SOFA score, the effect of AMInj was significant only for the duration of mechanical ventilation (p=0.030). The incidence of LV and RV dysfunction was 28% and 22%, respectively. Only indices of LV and RV longitudinal contractility (mitral and tricuspid annular plane systolic excursion) were associated with AMInj. Echocardiographic parameters were not associated with clinical outcome. Conclusions Myocardial injury is common in critically ill patients with COVID-19, with AMInj developing in more than 80% after ICU admission. In contrast, LV and RV dysfunction occurred in approximately one-quarter of patients. AMInj was associated with an increased need for mechanical ventilation and ICU LOS but neither AMInj nor ventricular dysfunction was significantly associated with mortality.

Introduction Low socioeconomic status has been associated with worse outcome after cardiac arrest. This study aims to investigate if patients´ income influences the probability to receive early coronary angiography in out-of-hospital cardiac arrest (OHCA) patients. Methods In this nationwide retrospective observational study, 3906 OHCA patients admitted alive and registered in the Swedish Registry for Cardiopulmonary Resuscitation were included. Individual data on income and educational level, prehospital parameters, coronary angiography results and comorbidity were linked from SWEDEHEART and other national registers. Results Patients were divided into quarters depending on their income level. In the unadjusted model there was a strong correlation between income level and rate of early coronary angiography where 35.5% of patients in the highest income quarters received early angiography compared to 15.4% in the lowest income quarters. When adjusting for educational level, sex, age, comorbidity and hospital type, there were still higher chance of receiving early coronary angiography with increasing income, OR 1.31 (CI 1.01–1.68) and 1.67 (CI 1.29–2.16) for the two highest income quarters respectively compared to the lowest income quarter. When adding potential mediators to the model (first recorded ECG rhythm by the EMS, location, response time, bystander cardiopulmonary resuscitation and if the arrest was witnessed) no difference in early angiography related to income level where found. The main mediator was first recorded ECG rhythm. Conclusion Income level is associated with the probability to undergo early coronary angiography in OHCA patients. This association seems to be mediated by the initial ECG rhythm.

Introduction Lung protective ventilation can decrease post-operative pulmonary complications. The aim of this study was to evaluate a capnodynamic method estimating effective lung volume (ELV) as a proxy for end-expiratory lung volume in response to PEEP changes in patients, healthy subjects and a porcine model. Methods Agreement and trending ability for ELV in anaesthetized patients and agreement in awake subjects were evaluated using nitrogen multiple breath wash-out/in and plethysmography as a reference respectively. Agreement and trending ability were evaluated in pigs during PEEP elevations with inert gas wash-out as reference. Results In anaesthetized patients bias (95% limits of agreement [LoA]) and percentage error (PE) at PEEP 0 cm H2O were 133 mL (-1049 to 1315) and 71%, at PEEP 5 cm H2O 161 mL (-1291 to 1613 mL) and 66%. In healthy subjects: 21 mL (-755 to 796 mL) and 26%. In porcines, at PEEP 5-20 cm H2O bias decreased from 223 mL to 136 mL LoA (34-412) to (-30 to 902) and PE 29%-49%. Trending abilities in anaesthetized patients and porcines were 100% concordant. Conclusion The ELV-method showed low bias but high PE in anaesthetized patients. Agreement was good in awake subjects. In porcines, agreement was good at lower PEEP levels. Concordance related to PEEP changes reached 100% in all settings. This method may become a useful trending tool for monitoring lung function during mechanical ventilation, if findings are confirmed in other clinical contexts.

The Revised (or "Extended") Starling principle is based on highly controlled laboratory-based frog and rodent experiments and remains a hypothesis awaiting clinical validation. A key point is that the endothelial glycocalyx layer moves the oncotic gradient from being between the plasma and the interstitium to between the plasma and a virtually protein-free space between the glycocalyx and the endothelial cell membrane, which dramatically changes the prerequisites for fluid absorption from tissue to plasma. However, many experimental and clinical observations in humans agree poorly with the new microcirculatory proposals. The most troubling aspect of the explanation regarding the role of the glycocalyx in the Revised Starling principle is the effective reabsorption of fluid by skeletal muscle when the capillary filtration pressure is acutely reduced. Other issues include the plasma volume effects of hypertonic saline, iso-oncotic and hyper-oncotic albumin, fluid distribution during cardio-pulmonary bypass, and the virtually identical capillary leakage of plasma and albumin despite marked inflammation found in our fluid therapy studies. The Revised Starling principle deals mainly with steady-state conditions, but the circulatory system is highly dynamic. Second to second vasomotion is always operational and must be considered to understand what we observe in humans.

Background Clinical research has shown that therapeutic hypothermia after neonatal hypoxic-ischemic injury improves survival without disability. There is no consensus regarding pain relief or sedation during therapeutic hypothermia in newborns; however, therapeutic hypothermia seems to be associated with pain and stress, and adequate analgesia and sedation are central to maximize the effect of therapeutic hypothermia. Pain needs to be adequately managed in all patients, especially the newborn infant due to the potential short- and long-term negative effects of inadequately treated pain in this population. Methods We will perform a systematic review of pharmacological and non-pharmacological interventions for the management of pain and sedation in newborn infants undergoing therapeutic hypothermia for hypoxic-ischemic encephalopathy. We will include randomized, quasi-randomized controlled trials and observational studies. The use of pharmacological or non-pharmacological interventions will be compared to other pharmacological and or non-pharmacological interventions or no intervention/placebo. The primary outcomes for this review will be analgesia and sedation assessed with validated pain scales, circulatory instability, mortality to discharge, and moderate-to-severe neurodevelopmental disability. We will search the following databases: CINAHL, ClinicalTrials.gov, Cochrane Library, Embase, PubMed, Scopus, and Web of Science. Two independent researchers will screen the records for inclusion, extract data using a data extraction form, and assess the risk of bias in the included trials. Discussion The result of this review will summarize the knowledge regarding the management of pain and sedation in infants treated with therapeutic hypothermia and potentially provide clinicians with guidance on the effective and safe methods. Systematic review registration PROSPERO CRD42020205755

Background Hyperchloremic metabolic acidosis that develops during the treatment of diabetic ketoacidosis is usually attributed to the chloride content of resuscitation fluids. We explored an alternative explanation, namely that fluid-induced plasma volume expansion alters the absolute differences in the concentrations of sodium and chloride (the Na–Cl gap) enough to affect the acid–base balance. We analyzed data from a prospective single-center cohort study of 14 patients treated for diabetic ketoacidosis. All patients received 1 L of 0.9% saline over 30 min on two consecutive days. Blood gases were sampled before and after the infusions. Results The initial plasma volume was estimated to be 25 ± 13% (mean ± SD) below normal on admission to the intensive care unit. At that time, most patients had an increased actual Na–Cl gap, which counteracts acidosis. However, the correction of the plasma volume deficit revealed that these patients would have had a decreased Na–Cl gap upon admission if they had been normovolemic at that time; the estimated “virtual Na–Cl gap” of 29 ± 5 mmol/L was significantly lower than the uncorrected value, which was 39 ± 5 mmol/L (P . Conclusions The hyperchloremic acidosis commonly seen in diabetic ketoacidosis may not be primarily caused by the chloride content of resuscitation fluids but, rather, by the restoration of plasma volume, which reveals the hidden metabolic acidosis caused by a decreased Na–Cl gap. Trial registration Clinical Trials Identifier NCT02172092, registered June 24, 2014, https://www.clinicaltrials.gov/NCT02172092

Objectives: To investigate postoperative morbidity and mortality after paediatric adenoidectomy. Methods: This was a retrospective national population-based cohort study of data from the Swedish National Patient Register (NPR) and The Swedish Cause of Death Register (CDR). All patients aged 0-18 years who underwent adenoidectomy from 2007 to 2017 (without concomitant tonsil surgery) were included in this study. To evaluate postoperative morbidity and mortality, all diagnostic and surgical codes registered in the NPR for health care contacts within 30 days of surgery were analysed. The patients retrieved from the NPR were matched with the CDR to identify any deaths occurring within 30 days of the surgery. Results: A total of 51 746 adenoidectomies were included in this study. No deaths related to adenoidectomy were identified. All types of haemorrhagic complications were rare. Only 0.1% of the surgeries resulted in an outpatient contact due to postoperative haemorrhage and only 0.1% of the adenoidectomies resulted in a readmission due to haemorrhage. The rarest haemorrhagic complication was RTT (return to theatre), with only 4 events (0.01%). Postoperative haemorrhage was most frequent on the first day after surgery. Other complications were rare as well, requiring a total of 922 (2.6%) outpatient visits and 75 (0.2%) readmissions in the adenoidectomy group, with postoperative infection being the most commonly reported. Conclusions: Overall, adenoidectomy should be considered a safe surgical procedure associated with few postoperative complications. No deaths related to adenoidectomy were found. Severe complications, such as late postoperative haemorrhage after adenoidectomy, were rare, and haemorrhage resulting in RTT was even rarer. The highest rate of postoperative haemorrhage was observed the first day after surgery, and most haemorrhagic complications occurred within a week. Comparisons with studies on tonsil surgery show that adenoidectomy is associated with substantially lower postoperative morbidity. Funding Agencies|Futurum, Academy for Health and Care, Region Jonkopings lan

IntroductionMost patients with idiopathic normal pressure hydrocephalus (iNPH) improve gait after surgery. However, knowledge on physical capacity and activity after shunt surgery is limited. One of the aims of this study was to evaluate the effect of shunt surgery in patients with iNPH on short-distance walking, functional exercise capacity, functional strength, and variables of activity and sleep, 3 and 6 months postoperatively. Another aim was to evaluate the effect of a physical exercise program. Additionally, we studied how changes in short-distance walking were correlated with functional exercise capacity and voluntary walking.MethodsIn total, 127 patients were consecutively included and randomized to the exercise group (n = 62) or the control group (n = 65). Participants in the exercise group underwent the supervision of a 12-week exercise program. All patients were assessed before surgery, at 3 and 6 months postoperatively with the 10-m walk test (10MWT), the 6-min walk test (6MWT), 30-s chair stand test (30sCST), and with the actigraphic recordings of activity variables measured for a total of 24 h/day for at least 3 days.ResultsAll patients improved at 3 months postoperatively in the 10MWT (p < 0.001), 6MWT (p < 0.001), and 30sCST (p < 0.001). These results were maintained after 6 months. Actigraphic recordings for voluntary walking (steps per minute) were improved and nighttime sleep (%) increased after 6 months (p = 0.01, p = 0.04). There were no significant differences between the exercise group and the control group, except for the postoperative change in the proportion of daytime sleep after 3 months, which was slightly more reduced compared to baseline in the exercise group (p = 0.04). Changes after 3 months in the 10MWT and 6MWT were moderately correlated (ρ= −0.49, p = 0.01) whereas the correlation between the 10MWT and voluntary walking was weak (ρ = −0.34, p = 0.01).ConclusionShunt surgery improved short-distance walking, functional exercise capacity, functional strength, and voluntary walking. An exercise program did not affect these outcomes. Short-distance walking was weakly correlated with voluntary walking, indicating improved physical capacity does not directly translate to increased physical activity. Further research should address how interventions should be tailored to promote physical activity after shunt surgery.Trial Registrationclinicaltrials.gov, Id: NCT02659111.

Background The ratio of partial pressure of arterial oxygen to inspired oxygen fraction (PaO2/FIO2) during invasive mechanical ventilation (MV) is used as criteria to grade the severity of respiratory failure in acute respiratory distress syndrome (ARDS). During the SARS-CoV2 pandemic, the use of PaO2/FIO2 ratio has been increasingly used in non-invasive respiratory support such as high-flow nasal cannula (HFNC) and non-invasive ventilation (NIV). The grading of hypoxemia in non-invasively ventilated patients is uncertain. The main hypothesis, investigated in this study, was that the PaO2/FIO2 ratio does not change when switching between MV, NIV and HFNC. Methods We investigated respiratory function in critically ill patients with COVID-19 included in a single-center prospective observational study of patients admitted to the intensive care unit (ICU) at Uppsala University Hospital in Sweden. In a steady state condition, the PaO2/FIO2 ratio was recorded before and after any change between two of the studied respiratory support techniques (i.e., HFNC, NIV and MV). Results A total of 148 patients were included in the present analysis. We find that any change in respiratory support from or to HFNC caused a significant change in PaO2/FIO2 ratio. Changes in respiratory support between NIV and MV did not show consistent change in PaO2/FIO2 ratio. In patients classified as mild to moderate ARDS during MV, the change from HFNC to MV showed a variable increase in PaO2/FIO2 ratio ranging between 52 and 140 mmHg (median of 127 mmHg). This made prediction of ARDS severity during MV from the apparent ARDS grade during HFNC impossible. Conclusions HFNC is associated with lower PaO2/FIO2 ratio than either NIV or MV in the same patient, while NIV and MV provided similar PaO2/FIO2 and thus ARDS grade by Berlin definition. The large variation of PaO2/FIO2 ratio indicates that great caution should be used when estimating ARDS grade as a measure of pulmonary damage during HFNC.

Background High frequency jet ventilation (HFJV) can be used to minimise sub-diaphragmal organ displacements. Treated patients are in a supine position, under general anaesthesia and fully muscle relaxed. These are factors that are known to contribute to the formation of atelectasis. The HFJV-catheter is inserted freely inside the endotracheal tube and the system is therefore open to atmospheric pressure. Aim The aim of this study was to assess the formation of atelectasis over time during HFJV in patients undergoing liver tumour ablation under general anaesthesia. Method In this observational study twenty-five patients were studied. Repeated computed tomography (CT) scans were taken at the start of HFJV and every 15 minutes thereafter up until 45 minutes. From the CT images, four lung compartments were defined: hyperinflated, normoinflated, poorly inflated and atelectatic areas. The extension of each lung compartment was expressed as a percentage of the total lung area. Result Atelectasis at 30 minutes, 7.9% (SD 3.5, p = 0.002) and at 45 minutes 8,1% (SD 5.2, p = 0.024), was significantly higher compared to baseline 5.6% (SD 2.5). The amount of normoinflated lung volumes were unchanged over the period studied. Only a few minor perioperative respiratory adverse events were noted. Conclusion Atelectasis during HFJV in stereotactic liver tumour ablation increased over the first 45 minutes but tended to stabilise with no impact on normoinflated lung volume. Using HFJV during stereotactic liver ablation is safe regarding formation of atelectasis.

Background Central venous access is essential for the administration of chemotherapy and frequent blood sampling in patients with cancer. The subcutaneous venous port is commonly used for this purpose. Subcutaneous venous port implantation is a minor surgical procedure; however, it can provoke pain and anxiety in these vulnerable patients. The aim of this study was, before a full-scale RCT, to determine the feasibility of patient-controlled sedation with propofol and alfentanil as an adjunct to local anaesthesia during SVP implantation. Methods We prospectively studied 40 patients scheduled for SVP implantation between 14 April 2021 and 15 October 2021 at a 500-bed secondary level hospital in Sweden. Anaesthesiologists performed subcutaneous venous port implantation with patient-controlled sedation using propofol and alfentanil. We determined pain perception (primary outcome), patient satisfaction, sedation score, and key safety measures. Results Of the 40 patients with cancer, 80% reported a pain score ≤3 on an 11-point numeric rating scale during subcutaneous venous port implantation. Overall satisfaction with pain management and operating conditions was graded as 10 of 10 on the numeric rating scale. Four patients (10%) had bradypnoea (

Background The transcapillary leakage of albumin is increased by inflammation and major surgery, but whether exogenous albumin also disappears faster is unclear. Methods An intravenous infusion of 3 mL/kg of 20% albumin was given over 30 min to 70 subjects consisting of 15 healthy volunteers, 15 post-burn patients, 15 patients who underwent surgery with minor bleeding, 10 who underwent surgery with major bleeding (mean, 1.1 L) and 15 postoperative patients. Blood Hb and plasma albumin were measured on 15 occasions over 5 h. The rate of albumin disappearance from the plasma was quantitated with population kinetic methodology and reported as the half-life (T1/2). Results No differences were observed for T1/2 between volunteers, post-burn patients, patients who underwent surgery with minor bleeding and postoperative patients. The T1/2 averaged 16.2 h, which corresponds to 3.8% of the amount infused per h. Two groups showed plasma concentrations of C-reactive protein of approximately 60 mg/L and still had a similarly long T1/2 for albumin. By contrast, patients undergoing surgery associated with major hemorrhage had a shorter T1/2, corresponding to 15% of the infused albumin per h. In addition, our analyses show that the T1/2 differ greatly depending on whether the calculations consider plasma volume changes and blood losses. Conclusion The disappearance rate of the albumin in 20% preparations was low in volunteers, in patients with moderately severe inflammation, and in postoperative patients.

Background: With the emergence of Brain Computer Interfaces (BCI), clinicians have been facing a new group of patients with severe acquired brain injury who are unable to show any behavioral sign of consciousness but respond to active neuroimaging or electrophysiological paradigms. However, even though well documented, there is still no consensus regarding the nomenclature for this clinical entity. Objectives: This systematic review aims to 1) identify the terms used to indicate the presence of this entity through the years, and 2) promote an informed discussion regarding the rationale for these names and the best candidates to name this fascinating disorder. Methods: The Disorders of Consciousness Special Interest Group (DoC SIG) of the International Brain Injury Association (IBIA) launched a search on Pubmed and Google scholar following PRISMA guidelines to collect peer-reviewed articles and reviews on human adults (>18 years) published in English between 2006 and 2021. Results: The search launched in January 2021 identified 4,089 potentially relevant titles. After screening, 1,126 abstracts were found relevant. Finally, 161 manuscripts were included in our analyses. Only 58% of the manuscripts used a specific name to discuss this clinical entity, among which 32% used several names interchangeably throughout the text. We found 25 different names given to this entity. The five following names were the ones the most frequently used: covert awareness, cognitive motor dissociation, functional locked-in, non-behavioral MCS (MCS*) and higher-order cortex motor dissociation. Conclusion: Since 2006, there has been no agreement regarding the taxonomy to use for unresponsive patients who are able to respond to active neuroimaging or electrophysiological paradigms. Developing a standard taxonomy is an important goal for future research studies and clinical translation. We recommend a Delphi study in order to build such a consensus., Fil: Schnakers, Caroline. Casa Colina Hospital and Centers for Healthcare. Research Institute; Estados Unidos, Fil: Bauer, Chase. Western University of Health Sciences. College of Osteopathic Medicine; Estados Unidos, Fil: Formisano, Rita. IRCCS Santa Lucia Foundation; Italia, Fil: Noé, Enrique. Fundación Hospitales Vithas. Vithas Neuro Rehab Human Brain; España, Fil: Llorens, Roberto. Fundación Hospitales Vithas. Vithas Neuro Rehab Human Brain; España, Fil: Llorens, Roberto. Universitat Politècnica de València. Instituto de Investigación e Innovación en Bioingeniería. Neurorehabilitation and Brain Research Group; España, Fil: Lejeune, Nicolas. University of Liège. Coma Science Group. GIGA-Consciousness; Bélgica, Fil: Lejeune, Nicolas. Ottignies-Louvain-la-Neuve. Centre Hospitalier Neurologique William Lennox; Bélgica, Fil: Farisco, Michele. Uppsala University. Centre for Research Ethics and Bioethics,; Suecia, Fil: Farisco, Michele. Biology and Molecular Genetics Research Institute. Science and Society Unit, Biogem; Italia, Fil: Teixeira, Liliana. Polytechnic of Leiria. School of Health Sciences. Center for Innovative Care and Health Technology; Portugal, Fil: Morrissey, Ann-Marie. University of Limerick. Health Research Institute. Ageing Research Centre; Irlanda, Fil: De Marco, Sabrina. Universidad Católica de Córdoba. Clínica Universitaria Reina Fabiola; Argentina, Fil: Veeramuthu, Vigneswaran. Subang Jaya Medical Center; Malasia, Fil: Ilina, Kseniya. Research Center of Neurology; Rusia, Fil: Ilina, Kseniya. Lomonosov Moscow State University. Faculty of Fundamental Medicine; Rusia, Fil: Edlow, Brian L. Harvard Medical School. Massachusetts General Hospital; Estados Unidos, Fil: Gosseries, Olivia. University of Liège. Coma Science Group; Bélgica, Fil: Gosseries, Olivia. University Hospital of Liege. Centre du Cerveau; Bélgica, Fil: Zandalasini, Matteo. Azienda USL di Piacenza. Dipartimento di Medicina Riabilitativa. Neuroriabilitazione e Medicina Riabilitativa Intensiva. Unità Spinale; Italia, Fil: De Bellis, Francesco. IRCCS Fondazione Don Carlo Gnocchi; Italia, Fil: Thibaut, Aurore. University of Liège. Coma Science Group. GIGA-Consciousness; Bélgica, Fil: Thibaut, Aurore. University Hospital of Liege. Centre du Cerveau; Bélgica, Fil: Estraneo, Anna. IRCCS Fondazione Don Carlo Gnocchi; Italia, Fil: Estraneo, Anna. SM della Pietà General Hospital. Neurology Unit; Italia

BackgroundThe Nephrocheck® test is a single-use cartridge designed to measure the concentrations of two novel cell-cycle arrest biomarkers of acute kidney injury, namely tissue inhibitor of metalloproteinase 2 (TIMP-2) and insulin-like growth factor binding protein 7 (IGFBP7). Correlations of serum creatine values and TIMP-2 and IGFBP7 with and without correction for urine dilution have not been previously undertaken in patients undergoing major abdominal surgery. We hypothesized that the Nephrocheck® values would be significantly different with and without correction for urine dilution in patients with elevated creatinine values post major abdominal surgery.MethodsWe performed a post hoc analysis of serum and urine specimens sampled preoperatively and postoperatively in 72 patients undergoing major abdominal surgery. Thirty samples were measured from patients with the greatest decrease and the greatest increase in postoperative serum creatinine values. Urine was analyzed with the Nephrocheck to predict the risk of acute kidney injury (AKIRisk™). We then examined the relationship between serum creatinine and the urinary excretion of TIMP-2 and IGFBP7 as measured by the Nephrocheck test. The AKIRisk between the groups with and without correction for urine dilution was assessed.ResultsThe median perioperative change in serum creatinine in the two groups was −19% and +57%, respectively. The uncorrected median baseline AKIRisk decreased from 0.70 (25th−75th percentiles, 0.09–1.98) to 0.35 (0.19–0.57) (mg/L)2 in the first group and rose from 0.57 (0.22–1.53) to 0.85 (0.67–2.20) (mg/L)2 in the second group. However, when corrected for the squared urine dilution, the AKIRisk™ in patients with postoperative increases in serum creatinine was not indicative of kidney injury; the corrected AKIRisk was 8.0 (3.2–11.7) μg2/mmol2 before surgery vs.6.9 (5.3–11.0) μg2/mmol2 after the surgery (P = 0.69).ConclusionIn the setting of major abdominal surgery, after correction of TIMP-2 and IGFBP7 for urine dilution, the Nephrocheck AKIRisk scores were significantly different from the uncorrected values. These finding imply that the AKIRisk index is a function of urine flow in addition to an increased release of the biomarkers.

Background We have previously shown that iatrogenic dehydration is associated with a shift to organic osmolyte production in the general ICU population. The aim of the present investigation was to determine the validity of the physiological response to dehydration known as aestivation and its relevance for long-term disease outcome in COVID-19. Methods The study includes 374 COVID-19 patients from the Pronmed cohort admitted to the ICU at Uppsala University Hospital. Dehydration data was available for 165 of these patients and used for the primary analysis. Validation was performed in Biobanque Québécoise de la COVID-19 (BQC19) using 1052 patients with dehydration data. Dehydration was assessed through estimated osmolality (eOSM = 2Na + 2 K + glucose + urea), and correlated to important endpoints including death, invasive mechanical ventilation, acute kidney injury, and long COVID-19 symptom score grouped by physical or mental. Results Increasing eOSM was correlated with increasing role of organic osmolytes for eOSM, while the proportion of sodium and potassium of eOSM were inversely correlated to eOSM. Acute outcomes were associated with pronounced dehydration, and physical long-COVID was more strongly associated with dehydration than mental long-COVID after adjustment for age, sex, and disease severity. Metabolomic analysis showed enrichment of amino acids among metabolites that showed an aestivating pattern. Conclusions Dehydration during acute COVID-19 infection causes an aestivation response that is associated with protein degradation and physical long-COVID. Trial registration: The study was registered à priori (clinicaltrials.gov: NCT04316884 registered on 2020-03-13 and NCT04474249 registered on 2020-06-29). Graphical abstract

Introduction: The number of interhospital transports with intubated patients or where intubation readiness is required is increasing in Sweden and globally. Specialist nurses are often responsible for these transports, which involve numerous risks for critically ill patients. Aim: The aim of this study was to describe nurse anaesthetists’ and intensive care nurses’ strategies for safe interhospital transports with intubated patients or where intubation readiness is required. Method: A qualitative study was conducted using the critical incident technique. During March and April 2020, 12 semi-structured interviews were conducted with nurse anaesthetists and intensive care nurses. Data were analysed according to the critical incident technique, and a total of 197 critical incidents were identified. The analysis revealed five final strategies for safe interhospital transport. Results: Participants described the importance of ensuring clear and adequate information transfers between caregivers to obtain vital patient information that enables the nurse in charge to identify risks and problems in advance and create an action plan. Stabilising and optimising the patient's condition before departure and preparing drugs and equipment were other strategies described by the participants, as well as requesting assistance or support if questions or complications arose during transport. Conclusion: Transports with intubated patients or where intubation readiness is required are complex and require systematic patient-safety work to ensure that strategies for increasing patient safety and decreasing risks are visible to the nurses in charge, that they are applied, and that they are, indeed, effective. Validerad;2023;Nivå 2;2023-02-10 (joosat);Licens fulltext: CC BY License

Dexamethasone (Dex) has been shown to decrease mortality in severe coronavirus disease 2019 (COVID-19), but the mechanism is not fully elucidated. We aimed to investigate the physiological and immunological effects associated with Dex administration in patients admitted to intensive care with severe COVID-19. A total of 216 adult COVID-19 patients were included—102 (47%) received Dex, 6 mg/day for 10 days, and 114 (53%) did not. Standard laboratory parameters, plasma expression of cytokines, endothelial markers, immunoglobulin (Ig) IgA, IgM, and IgG against SARS-CoV-2 were analyzed post-admission to intensive care. Patients treated with Dex had higher blood glucose but lower blood lactate, plasma cortisol, IgA, IgM, IgG, D-dimer, cytokines, syndecan-1, and E-selectin and received less organ support than those who did not receive Dex (Without-Dex). There was an association between Dex treatment and IL-17A, macrophage inflammatory protein 1 alpha, syndecan-1 as well as E-selectin in predicting 30-day mortality. Among a subgroup of patients who received Dex early, within 14 days of COVID-19 debut, the adjusted mortality risk was 0.4 (95% CI 0.2–0.8), i.e., 40% compared with Without-Dex. Dex administration in a cohort of critically ill COVID-19 patients resulted in altered immunological and physiologic responses, some of which were associated with mortality.

Background Pain control following breast surgery is of utmost importance in order to reduce the chance of chronic pain development, and facilitate early rehabilitation. The erector spinae plane block (ESPB) is a recently developed regional anaesthesia procedure successfully used for different types of surgical procedures including thoracic and abdominal surgeries. Methods A double-blind, randomized, controlled trial was conducted on 90 patients who were scheduled for modified radical mastectomy (MRM). Patients were randomly categorized into groups I (women who underwent ESPB), II (women who underwent paravertebral block (PVB), and III (women who underwent general anaesthesia). Results The ESPB (4.9 ± 1.2 mg) and PVB (5.8 ± 1.3 mg) groups had significantly lower total morphine consumption than the control group had (16.4 ± 3.1 mg; p p = 0.076). Moreover, patients in the ESPB and PVB groups had a significantly longer time to first required anaesthesia than those in the control group (7.9 ± 1.2 versus 7.5 ± 0.9 versus 2 ± 1.2 h, respectively; p p Conclusion ESPB and PVB provide effective postoperative analgesia for women undergoing MRM. The ESPB appears to be as effective as the PVB. Trial registration The study was registered before the enrolment of the first patient at the Pan African Clinical Trial Registry (www.pactr.org) database. Identification number for the registry is (PACTR202008836682092).

Background: The contribution of endothelial injury in the pathogenesis of COVID-19-associated acute respiratory distress syndrome (ARDS) and resulting respiratory failure remains unclear. Plasma endostatin, an endogenous inhibitor of angiogenesis and endothelial dysfunction is upregulated during hypoxia, inflammation and progress of pulmonary disease. Aim: To investigate if plasma endostatin is associated to hypoxia, inflammation and 30-day mortality in patients with severe COVID-19 infection. Method: Samples for blood analysis and plasma endostatin quantification were collected from adult patients with ongoing COVID-19 (n = 109) on admission to intensive care unit (day 1). Demographic characteristics and 30-day mortality data were extracted from medical records. The ability of endostatin to predict mortality was analyzed using receiving operating characteristics and Kaplan–Meier analysis with a cutoff at 46.2 ng/ml was used to analyze the association to survival. Results: Plasma endostatin levels correlated with; PaO2/FiO2 (r = -0.3, p 46.2 ng/ml predicts mortality with a sensitivity of 92% and specificity of 71%. In patients with plasma endostatin >46.2 ng/ml probability of survival was lower (p = 0.02) in comparison to those with endostatin

Background: An inserted central venous catheter (CVC) is considered foreign material by the inert host defence systems and induce inflammation and thrombus formation. The objective of this study was to evaluate blood compatibility of six commonly used CVCs.Methods: Three coated and three uncoated CVC materials were tested in a modified Chandler loop model. Each catheter material circulated in blood from ten different healthy volunteers for 1 hour. Blood cell counts and measurements of the inert host defence systems were performed on blood samples from the loop.Results: All the tested catheters demonstrated impact on blood cells, contact coagulation, the complement system, or inflammatory markers, although the impact varied significantly.Conclusions: Of the catheters we evaluated, the most unfavourable blood compatibility profile was found for the polyurethane CVC coated with chlorohexidine and silver sulfadiazine. The greatest variation in blood compatibility between test runs was noted for the silicone dialysis catheter. Poor blood compatibility should be taken seriously but given the experimental design of the current study the clinical significance remains to be evaluated.

Background There is little evidence of which sepsis screening tool to use in the ambulance setting. The primary aim of the current study was to compare the performance of NEWS2 (National Early Warning score 2) and RETTS (Rapid Emergency Triage and Treatment System) with respect to identification of sepsis among ambulance patients with clinically suspected infection. The secondary aim was to compare the performance of the novel Predict Sepsis screening tools with that of NEWS2, RETTS and clinical judgment. Methods Prospective cohort study of 323 adult ambulance patients with clinically suspected infection, transported to hospitals in Stockholm, during 2017/2018. The sensitivity, specificity, and AUC (Area Under the receiver operating Curve) were calculated and compared by using McNemar´s test and DeLong’s test. Results The prevalence of sepsis in the current study population was 44.6% (144 of 323 patients). No significant difference in AUC was demonstrated between NEWS2 ≥ 5 and RETTS ≥ orange. NEWS2 ≥ 7 demonstrated a significantly greater AUC than RETTS red. The Predict Sepsis screening tools ≥ 2 demonstrated the highest sensitivity (range 0.87–0.91), along with RETTS ≥ orange (0.83), but the lowest specificity (range 0.39–0.49). The AUC of NEWS2 (0.73) and the Predict Sepsis screening tools (range 0.75–0.77) was similar. Conclusions The results indicate that NEWS2 could be the better alternative for sepsis identification in the ambulance, as compared to RETTS. The Predict Sepsis screening tools demonstrated a high sensitivity and AUCs similar to that of NEWS2. However, these results need to be interpreted with caution as the Predict Sepsis screening tools require external validation. Trial registration: ClinicalTrials.gov, NCT03249597. Registered 15 August 2017—Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT03249597.