POStoperative INTELLiVENT-adaptive support VEntilation in cardiac surgery patients (POSITiVE) II-study protocol of a randomized clinical trial.

BACKGROUND: One single-center randomized clinical trial showed that INTELLiVENT-adaptive support ventilation (ASV) is superior to conventional ventilation with respect to the quality of ventilation in post-cardiac surgery patients. Other studies showed that this automated ventilation mode reduces the number of manual interventions at the ventilator in various types of critically ill patients. In this multicenter study in patients post-cardiac surgery, we test the hypothesis that INTELLiVENT-ASV is superior to conventional ventilation with respect to the quality of ventilation. METHODS: "POStoperative INTELLiVENT-adaptive support VEntilation in cardiac surgery patients II (POSITiVE II)" is an international, multicenter, two-group randomized clinical superiority trial. In total, 328 cardiac surgery patients will be randomized. Investigators screen patients aged > 18 years of age, scheduled for elective cardiac surgery, and expected to receive postoperative ventilation in the ICU for longer than 2 h. Patients either receive automated ventilation by means of INTELLiVENT-ASV or ventilation that is not automated by means of a conventional ventilation mode. The primary endpoint is quality of ventilation, defined as the proportion of postoperative ventilation time characterized by exposure to predefined optimal, acceptable, and critical (injurious) ventilatory parameters in the first two postoperative hours. One major secondary endpoint is ICU team staff workload, captured by the ventilator software collecting manual settings on alarms. Patient-centered endpoints include duration of postoperative ventilation and length of stay in ICU. DISCUSSION: POSITiVE II is the first international, multicenter, randomized clinical trial designed to confirm that POStoperative INTELLiVENT-ASV is superior to non-automated conventional ventilation and secondary to determine if this closed-loop ventilation mode reduces ICU team staff workload. The results of POSITiVE II will support intensive care teams in their choices regarding the use of automated ventilation in postoperative care of uncomplicated cardiac surgery patients. TRIAL REGISTRATION: Clinicaltrials.gov NCT06178510 . Registered on December 4, 2023.

Anesthetic management for cesarean section in two parturient with ascending aortic aneurysm: a case-based discussion.

BACKGROUND: The anesthetic management of parturients with ascending aortic aneurysm for cesarean section can be particularly challenging, primarily because of increased risk for aortic dissection or aneurysm rupture. CASE PRESENTATION: We present some aspects of the anesthetic management of two parturients with ascending aortic aneurysm for cesarean sections; amongst, the use of remifentanil with its effects on patient and newborn. We emphasize the importance of a cardio-obstetric team in the context of preoperative planning of such patients. Also, we reviewed some literature on the anesthetic management with its effect on peri-operative hemodynamic stability. CONCLUSION: Maintaining hemodynamic stability is paramount in the prevention of the rupture or dissection of ascending aortic aneurysm during labor of parturient.

Effect of machine learning-guided haemodynamic optimization on postoperative free flap perfusion in reconstructive maxillofacial surgery: A study protocol.

AIMS: Intraoperative hypotension and liberal fluid haemodynamic therapy are associated with postoperative medical and surgical complications in maxillofacial free flap surgery. The novel haemodynamic parameter hypotension prediction index (HPI) has shown good performance in predicting hypotension by analysing arterial pressure waveform in various types of surgery. HPI-based haemodynamic protocols were able to reduce the duration and depth of hypotension. We will try to determine whether haemodynamic therapy based on HPI can improve postoperative flap perfusion and tissue oxygenation by improving intraoperative mean arterial pressure and reducing fluid infusion. METHODS: We present here a study protocol for a single centre, randomized, controlled trial (n = 42) in maxillofacial patients undergoing free flap surgery. Patients will be randomized into an intervention or a control group. In the intervention, group haemodynamic optimization will be guided by machine learning algorithm and functional haemodynamic parameters presented by the HemoSphere platform (Edwards Lifesciences, Irvine, CA, USA), most importantly, HPI. Tissue oxygen saturation of the free flap will be monitored noninvasively by near-infrared spectroscopy during the first 24 h postoperatively. The primary outcome will be the average value of tissue oxygen saturation in the first 24 h postoperatively.

Effects of epidurally administered dexmedetomidine and dexamethasone on postoperative pain, analgesic requirements, inflammation, and oxidative stress in thoracic surgery.

The aim of this study was to compare the effects of dexmedetomidine and dexamethasone as adjuvants to preoperative epidural administration of local anesthetic (ropivacaine) in thoracic surgery on the postoperative level of pain, use of analgesics, inflammation, and oxidative stress. The study enrolled 42 patients who underwent elective thoracic surgery in a one-year period at the University Hospital Dubrava (Zagreb, Croatia). Based on a computer-generated randomization list the patients were assigned to the dexmedetomidine (n = 18) or dexamethasone (n = 24) group. Postoperatively, patients of dexmedetomidine group reported lower pain (VAS value 1 h post surgery, 3.4 ± 2.7 vs. 5.4 ± 1.8, dexmedetomidine vs. dexamethasone, p < 0.01) and had lower anal-gesic requirements in comparison with dexamethasone group. Thus, dexmedetomidine in comparison with dexamethasone was more efficient in lowering pain and analgesia requirements 24 h after the surgery. On the contrary, dexamethasone had better anti-inflammatory properties (CRP level 24 h post surgery, 131.9 ± 90.7 vs. 26.0 ± 55.2 mg L-1, dexmedetomidine vs. dexamethasone, p < 0.01). Both dexmedetomidine and dexamethasone exhibited antioxidant effects, however, their antioxidant properties should be further explored. The results of this study improve current knowledge of pain control in thoracic surgery.

Inflammatory Biomarkers Affecting Survival Prognosis in Patients Receiving Veno-Venous ECMO for Severe COVID-19 Pneumonia.

Severe COVID-19 pneumonia in which mechanical ventilation is unable to achieve adequate gas exchange can be treated with veno-venous ECMO, eliminating the need for aggressive mechanical ventilation which might promote ventilator-induced lung injury and increase mortality. In this retrospective observational study, 18 critically ill COVID-19 patients who were treated using V-V ECMO during an 11-month period in a tertiary COVID-19 hospital were analyzed. Biomarkers of inflammation and clinical features were compared between survivors and non-survivors. Survival rates were compared between patients receiving ECMO and propensity matched mechanically ventilated controls. There were 7 survivors and 11 non-survivors. The survivors were significantly younger, with a higher proportion of females, higher serum procalcitonin at ICU admission, and before initiation of ECMO they had significantly lower Murray scores, PaCO2, WBC counts, serum ferritin levels, and higher glomerular filtration rates. No significant difference in mortality was found between patients treated with ECMO compared to patients treated using conventional lung protective ventilation. Hypercapnia, leukocytosis, reduced glomerular filtration rate, and increased serum ferritin levels prior to initiation of V-V ECMO in patients with severe COVID-19 pneumonia may be early warning signs of reduced chance of survival. Further multicentric studies are needed to confirm these findings.

The Effect of Intravenous Lidocaine, Ketamine, and Lidocaine-Ketamine Combination in Colorectal Cancer Surgery: A Randomized Controlled Trial.

BACKGROUND: Colorectal resections are associated with a pronounced inflammatory response, severe postoperative pain, and postoperative ileus. The aim of this study was to evaluate the main effects of lidocaine and ketamine, and their interaction in colorectal cancer (CRC) patients after open surgery. The interaction could be additive if the effect of 2 drugs given in combination equals the sum of their individual effects, or multiplicative if their combined effect exceeds the sum of their individual effects. We hypothesized that the combination of lidocaine and ketamine might reduce the inflammatory response additively or synergistically. METHODS: Eighty-two patients undergoing elective open colorectal resection were randomized to receive either lidocaine or placebo and either ketamine or placebo in a 2 × 2 factorial design. After induction of general anesthesia, all subjects received an intravenous bolus (lidocaine 1.5 mg/kg and/or ketamine 0.5 mg/kg and/or a matched saline volume) followed by a continuous infusion (lidocaine 2 mg·kg-1·h-1 and/or ketamine 0.2 mg·kg-1·h-1 and/or a matched saline volume) until the end of surgery. Primary outcomes were serum levels of white blood cell (WBC) count, interleukins (IL-6, IL-8), and C-reactive protein (CRP) measured at 2 time points: 12 and 36 hours after surgery. Secondary outcomes included intraoperative opioid consumption; visual analog scale (VAS) pain scores at 2, 4, 12, 24, 36, and 48 hours postoperatively; cumulative analgesic consumption within 48 hours after surgery; and time to first bowel movement. We assessed the main effects of each of lidocaine and ketamine and their interaction on the primary outcomes using linear regression analyses. A Bonferroni-adjusted significance level was set at .05/8 = .00625 for primary analyses. RESULTS: No statistically significant differences were observed with either lidocaine or ketamine intervention in any of the measured inflammatory markers. No multiplicative interaction between the 2 treatments was confirmed at 12 or 36 hours after surgery: WBC count, P = .870 and P = .393, respectively; IL-6, P = .892 and P = .343, respectively; IL-8, P = .999 and P = .996, respectively; and CRP, P = .014 and P = .445, respectively. With regard to inflammatory parameters, no evidence of additive interactions was found. Lidocaine and ketamine, either together or alone, significantly reduced intraoperative opioid consumption versus placebo, and, except for lidocaine alone, improved pain scores. Neither intervention significantly influenced gut motility. CONCLUSIONS: Our study results do not support the use of an intraoperative combination of lidocaine and ketamine in patients undergoing open surgery for CRC.

Healthcare-Associated Bloodstream Infections Due to Multidrug-Resistant Acinetobacter baumannii in COVID-19 Intensive Care Unit: A Single-Center Retrospective Study.

Healthcare-associated infections are an emerging cause of morbidity and mortality in COVID-19 intensive care units (ICUs) worldwide, especially those caused by multidrug-resistant (MDR) pathogens. The objectives of this study were to assess the incidence of bloodstream infections (BSIs) among critically ill COVID-19 patients and to analyze the characteristics of healthcare-associated BSIs due to MDR Acinetobacter baumannii in an COVID-19 ICU. A single-center retrospective study was conducted at a tertiary hospital during a 5-month period. The detection of carbapenemase genes was performed by PCR and genetic relatedness by pulsed-field gel electrophoresis (PFGE) and multilocus-sequence typing. A total of 193 episodes were registered in 176 COVID-19 ICU patients, with an incidence of 25/1000 patient-days at risk. A. baumannii was the most common etiological agent (40.3%), with a resistance to carbapenems of 100%. The blaOXA-23 gene was detected in ST2 isolates while the blaOXA-24 was ST636-specific. PFGE revealed a homogeneous genetic background of the isolates. The clonal spread of OXA-23-positive A. baumannii is responsible for the high prevalence of MDR A. baumannii BSIs in our COVID-19 ICU. Further surveillance of resistance trends and mechanisms is needed along with changes in behavior to improve the implementation of infection control and the rational use of antibiotics.

Hypotension prediction index guided versus conventional goal directed therapy to reduce intraoperative hypotension during thoracic surgery: a randomized trial.

PURPOSE: Intraoperative hypotension is linked to increased incidence of perioperative adverse events such as myocardial and cerebrovascular infarction and acute kidney injury. Hypotension prediction index (HPI) is a novel machine learning guided algorithm which can predict hypotensive events using high fidelity analysis of pulse-wave contour. Goal of this trial is to determine whether use of HPI can reduce the number and duration of hypotensive events in patients undergoing major thoracic procedures. METHODS: Thirty four patients undergoing esophageal or lung resection were randomized into 2 groups -"machine learning algorithm" (AcumenIQ) and "conventional pulse contour analysis" (Flotrac). Analyzed variables were occurrence, severity and duration of hypotensive events (defined as a period of at least one minute of MAP below 65 mmHg), hemodynamic parameters at 9 different timepoints interesting from a hemodynamics viewpoint and laboratory (serum lactate levels, arterial blood gas) and clinical outcomes (duration of mechanical ventilation, ICU and hospital stay, occurrence of adverse events and in-hospital and 28-day mortality). RESULTS: Patients in the AcumenIQ group had significantly lower area below the hypotensive threshold (AUT, 2 vs 16.7 mmHg x minutes) and time-weighted AUT (TWA, 0.01 vs 0.08 mmHg). Also, there were less patients with hypotensive events and cumulative duration of hypotension in the AcumenIQ group. No significant difference between groups was found in terms of laboratory and clinical outcomes. CONCLUSIONS: Hemodynamic optimization guided by machine learning algorithm leads to a significant decrease in number and duration of hypotensive events compared to traditional goal directed therapy using pulse-contour analysis hemodynamic monitoring in patients undergoing major thoracic procedures. Further, larger studies are needed to determine true clinical utility of HPI guided hemodynamic monitoring. TRIAL REGISTRATION: Date of first registration: 14/11/2022 Registration number: 04729481-3a96-4763-a9d5-23fc45fb722d.

OPIOID FREE GENERAL ANESTHESIA IN CLINICAL PRACTICE - A REVIEW ARTICLE.

Currently, enhanced recovery after surgery (ERAS) protocols are multimodal perioperative care pathways with the goal to achieve early patient recovery after surgery with minimal postoperative complications. According to studies, opioid free general anesthesia has many perioperative benefits and should be part of the ERAS protocols in specific surgical and patient indications. Opioid free general anesthesia is a multimodal balanced technique that is based on the concept that opioids are not used preoperatively or intraoperatively until the patient has aroused. The basic concept of opioid free general anesthesia is intravenous administration of several nonopioid drugs that operate at different pharmacological sites blocking surgical stress and sympathetic activation response. Moreover, current studies have shown that opioid free anesthesia is a technique which satisfactorily controls postoperative pain as the fifth vital sign, and has minimal side effects and better patient recovery with the same surgical conditions as general multimodal balanced anesthesia. However, further research is needed.

Distribution of Pathogens and Predictive Values of Biomarkers of Inflammatory Response at ICU Admission on Outcomes of Critically Ill COVID-19 Patients with Bacterial Superinfections-Observations from National COVID-19 Hospital in Croatia.

BACKGROUND: Superinfections contribute to mortality and length of stay in critically ill COVID-19 patients. The aim of this study was to determine the incidence and pathogen distribution of bacterial and fungal superinfections of the lower respiratory tract (LRTI), urinary tract (UTI) and bloodstream (BSI) and to determine the predictive value of biomarkers of inflammatory response on their ICU survival rates. METHODS: A retrospective observational study that included critically ill COVID-19 patients treated during an 11-month period in a Croatian national COVID-19 hospital was performed. Clinical and diagnostic data were analyzed according to the origin of superinfection, and multivariate regression analysis was performed to determine the predictive values of biomarkers of inflammation on their survival rates. RESULTS: 55.3% critically ill COVID-19 patients developed bacterial or fungal superinfections, and LRTI were most common, followed by BSI and UTI. Multidrug-resistant pathogens were the most common causes of LRTI and BSI, while Enterococcus faecalis was the most common pathogen causing UTI. Serum ferritin and neutrophil count were associated with decreased chances of survival in patients with LRTI, and patients with multidrug-resistant isolates had significantly higher mortality rates, coupled with longer ICU stays. CONCLUSION: The incidence of superinfections in critically ill COVID-19 patients was 55.3%, and multidrug-resistant pathogens were dominant. Elevated ferritin levels and neutrophilia at ICU admission were associated with increased ICU mortality in patients with positive LRTI.

Short-term outcomes of patients with chronic liver disease hospitalised with COVID-19.

BACKGROUND: Patients with chronic liver disease (CLD) might have an aggravated course after acquisition of coronavirus disease 2019 (COVID-19). AIMS: To analyse the outcomes of patients with CLD who were hospitalised due to COVID-19. METHODS: The medical records of 4014 patients hospitalised because of COVID-19 in a regional referral hospital over a 12-month period were analysed. Patients with CLD were identified based on discharge diagnoses according to the International Classification of Diseases-10th Revision. Patients were followed for 30 days from admission and their outcomes (intensive care unit (ICU) admission, mechanical ventilation (MV) or death) were analysed. RESULTS: Of the 4014 patients, 110 (2.7%) had CLD and 49 (1.2%) had cirrhosis. The median age of CLD patients was 67.5 years, 79 (71.8%) were males, 224 (23.5%) were obese, 56 (50.9%) reported alcohol abuse, 24 (21.8%) had non-alcoholic fatty liver disease, 11 (10%) had viral hepatitis and 98 (89.1%) had pneumonia. The median length of hospitalisation was 12 days; 32 (29.1%) patients required ICU admission and 23 (20.9%) patients required MV, while 43 (39.1%) died. In univariate analysis, patients with cirrhosis (45% vs 73%, hazard ratio (HR) = 2.95; P < 0.001), but not those with non-cirrhotic CLD (74% vs 73%; P > 0.05), experienced worse 30-day survival when compared with age, sex and COVID-19 duration-matched cohorts. In a logistic regression analysis conducted on the overall and matched cohorts, liver cirrhosis, but not CLD, predicted inferior survival independently of age, comorbidities and severity of COVID-19, with a fourfold higher adjusted risk of 30-day mortality. CONCLUSION: Cirrhosis is independently associated with higher 30-day mortality of hospitalised patients with COVID-19.

Epidemiological characteristics, baseline clinical features, and outcomes of critically ill patients treated in a coronavirus disease 2019 tertiary center in continental Croatia.

AIM: To describe epidemiological characteristics and baseline clinical features, laboratory findings at intensive care unit (ICU) admission, and survival rates of critically ill coronavirus disease 2019 (COVID-19) patients treated at a tertiary institution specialized for COVID-19 patients. METHODS: This retrospective study recruited 692 patients (67.1% men). Baseline demographic data, major comorbidities, anthropometric measurements, clinical features, and laboratory findings at admission were compared between survivors and non-survivors. RESULTS: The median age was 72 (64-78) years. The median body mass index was 29.1 kg/m2. The most relevant comorbidities were diabetes mellitus (32.6%), arterial hypertension (71.2%), congestive heart failure (19.1%), chronic kidney disease (12.6%), and hematological disorders (10.3%). The median number of comorbidities was 3 and median Charlson Comorbidity Index (CCI) was 5. A total of 61.8% patients received high-flow nasal oxygen therapy (HFNO) and 80.5% received mechanical ventilation (MV). Median duration of HFNO was 3, and that of MV was 7 days. ICU mortality rate was 72.7%. Survivors had significantly lower age, number of comorbidities, CCI, sequential organ failure assessment score, serum ferritin, C-reactive protein, D-dimer, and procalcitonin, interleukin-6, lactate, white blood cell, and neutrophil counts. They also had higher lymphocyte counts, PaO2/FiO2 ratio, and glomerular filtration rate at admission. Length of ICU stay was 9 days. The median survival was 11 days for mechanically ventilated patients, and 24 days for patients who were not mechanically ventilated. CONCLUSION: The parameters that differentiate survivors from non-survivors are in agreement with published data. Further multivariate analyses are warranted to identify individual mortality risk factors.

Clinical and laboratory predictors at ICU admission affecting course of illness and mortality rates in a tertiary COVID-19 center.

BACKGROUND: Survival rates of critically ill COVID-19 patients are affected by various clinical features and laboratory parameters at ICU admission. Some of these predictors are universal but others may be population specific. OBJECTIVE: To determine utility of baseline clinical and laboratory parameters in a multivariate regression model to predict outcomes in critically ill COVID-19 patients in a tertiary hospital in Croatia. METHODS: 692 critically ill COVID-19 patients treated during a 10-month period were included in this retrospective observational trial to assess the risk factors determining mortality rates. Various anthropometric features, comorbidities, laboratory parameters, clinical features and therapeutic interventions were included in the analysis. ICU mortality rates and length of ICU stay were primary endpoints analyzed in this study. RESULTS: After multivariate adjustment, only the SOFA score, PaO2/FiO2 and history of arterial hypertension had an effect on ICU mortality, as well as the need to initiate invasive mechanical ventilation. Increase in PaO2/FiO2 over the first 7 days was present in survivors, while reverse applied to SOFA. Length of ICU stay was 9 (4-14) days. Factors affecting survival times were admission from wards, congestive heart failure, invasive mechanical ventilation, bacterial superinfections, age > 75 years, SOFA score, and serum ferritin, CRP and IL-6 values at ICU admission. CONCLUSION: Elevated inflammatory biomarkers and SOFA score at ICU admission were detected as significant predictors of ICU mortality in this cohort, while initiation of invasive mechanical ventilation is the most relevant interventional mortality risk factor in critically ill COVID-19 patients.

Experiences and attitudes of medical professionals on treatment of end-of-life patients in intensive care units in the Republic of Croatia: a cross-sectional study.

BACKGROUND: Decisions about limitations of life sustaining treatments (LST) are made for end-of-life patients in intensive care units (ICUs). The aim of this research was to explore the professional and ethical attitudes and experiences of medical professionals on treatment of end-of-life patients in ICUs in the Republic of Croatia. METHODS: A cross-sectional study was conducted among physicians and nurses working in surgical, medical, neurological, and multidisciplinary ICUs in the total of 9 hospitals throughout Croatia using a questionnaire with closed and open type questions. Exploratory factor analysis was conducted to reduce data to a smaller set of summary variables. Mann-Whitney U test was used to analyse the differences between two groups and Kruskal-Wallis tests were used to analyse the differences between more than two groups. RESULTS: Less than third of participants (29.2%) stated they were included in the decision-making process, and physicians are much more included than nurses (p < 0.001). Sixty two percent of participants stated that the decision-making process took place between physicians. Eighteen percent of participants stated that 'do-not-attempt cardiopulmonary resuscitations' orders were frequently made in their ICUs. A decision to withdraw inotropes and antibiotics was frequently made as stated by 22.4% and 19.9% of participants, respectively. Withholding/withdrawing of LST were ethically acceptable to 64.2% of participants. Thirty seven percent of participants thought there was a significant difference between withholding and withdrawing LST from an ethical standpoint. Seventy-nine percent of participants stated that a verbal or written decision made by a capable patient should be respected. Physicians were more inclined to respect patient's wishes then nurses with high school education (p = 0.038). Nurses were more included in the decision-making process in neurological than in surgical, medical, or multidisciplinary ICUs (p < 0.001, p = 0.005, p = 0.023 respectively). Male participants in comparison to female (p = 0.002), and physicians in comparison to nurses with high school and college education (p < 0.001) displayed more liberal attitudes about LST limitation. CONCLUSIONS: DNACPR orders are not commonly made in Croatian ICUs, even though limitations of LST were found ethically acceptable by most of the participants. Attitudes of paternalistic and conservative nature were expected considering Croatia's geographical location in Southern Europe.

HIGH-FLOW NASAL CANNULA COMBINED WITH PRONE POSITIONING AS AN INTUBATION ALTERNATIVE IN COVID-19: A CASE REPORT AND REVIEW OF THE LITERATURE.

The use of high-flow nasal cannula (HFNC) in COVID-19 patients is a controversial topic due to the benefits and risks which may occur in patients and healthcare workers. The goal of this treatment modality is potential avoidance of invasive mechanical ventilation, but generation of aerosol and increased healthcare professional infection risk must be considered. We present a case of a SARS-CoV-2-positive 71-year-old male with acute hypoxemic respiratory failure, who was successfully treated with HFNC combined with prone positioning. Furthermore, we discuss recent literature concerning potential issues of HFNC treatment in COVID-19 patients.

Prevalence and Prognostic Impact of Deranged Liver Blood Tests in COVID-19: Experience from the Regional COVID-19 Center over the Cohort of 3812 Hospitalized Patients.

BACKGROUND: Derangement of liver blood tests (LBT) is frequent in patients with Coronavirus disease 2019 (COVID-19). We aimed to evaluate (a) the prevalence of deranged LBT as well as their association with (b) clinical severity at admission and (c) 30-day outcomes among the hospitalized patients with COVID-19. METHODS: Consecutive patients with COVID-19 hospitalized in the regional referral center over the 12-month period were included. Clinical severity of COVID-19 at hospital admission and 30-day outcomes (need for intensive care, mechanical ventilation, or death) were analyzed. RESULTS: Derangement of LBT occurred in 2854/3812 (74.9%) of patients, most frequently due to elevation of AST (61.6%), GGT (46.1%) and ALT (33.4%). Elevated AST, ALT, GGT and low albumin were associated with more severe disease at admission. However, in multivariate Cox regression analysis, when adjusted for age, sex, obesity and presence of chronic liver disease, only AST remained associated with the risk of dying (HR 1.5081 and 2.1315, for elevations 1-3 × ULN and >3 × ULN, respectively) independently of comorbidity burden and COVID-19 severity at admission. Patients with more severe liver injury more frequently experienced defined adverse outcomes. CONCLUSIONS: Deranged LBTs are common among patients hospitalized with COVID-19 and might be used as predictors of adverse clinical outcomes.

Effects of Environmental Factors on Severity and Mortality of COVID-19.

Background: Most respiratory viruses show pronounced seasonality, but for SARS-CoV-2, this still needs to be documented. Methods: We examined the disease progression of COVID-19 in 6,914 patients admitted to hospitals in Europe and China. In addition, we evaluated progress of disease symptoms in 37,187 individuals reporting symptoms into the COVID Symptom Study application. Findings: Meta-analysis of the mortality risk in seven European hospitals estimated odds ratios per 1-day increase in the admission date to be 0.981 (0.973-0.988, p < 0.001) and per increase in ambient temperature of 1°C to be 0.854 (0.773-0.944, p = 0.007). Statistically significant decreases of comparable magnitude in median hospital stay, probability of transfer to the intensive care unit, and need for mechanical ventilation were also observed in most, but not all hospitals. The analysis of individually reported symptoms of 37,187 individuals in the UK also showed the decrease in symptom duration and disease severity with time. Interpretation: Severity of COVID-19 in Europe decreased significantly between March and May and the seasonality of COVID-19 is the most likely explanation.

Influence of different PEEP levels on electrical impedance tomography findings in patients under general anesthesia ventilated in the lateral decubitus position.

To determine the effect of various PEEP levels on electrical impedance tomography (EIT) measured differences in regional ventilation, hemodynamics, lung mechanics and parameters of alveolar gas exchange. Thirty three patients scheduled for elective urologic surgery in general anesthesia in lateral decubitus position were randomized into three groups-PEEP 0, 5 and 10 mbar. EIT recording, arterial blood gas analysis and hemodynamic parameters were captured at three timepoints-before induction (T0), 5 min after lateral positioning (T1) and 90 min after positioning (T2). Dynamic compliance (Cdyn) was measured at T1 and T2. Offline EIT data analysis was performed to calculate EIT derived parameters of ventilation distribution. Patients ventilated with PEEP of 10 mbar had a significantly lower A-a (alveolo arterial) gradient over measurements and symmetrical distribution of ventilation measured by EIT. There was no significant difference in Cdyn, center of ventilation indices and inhomogeneity index between groups. There was no difference of mean arterial pressure, cardiac index and heart rate between groups. Patients with 5 mbar of PEEP had higher stroke volume index compared to 0 and 10 mbar at baseline and over measurements. Nondependent/dependent TV ratio as well as global inhomogeneity index were correlated with A-a gradient. Dynamic compliance showed no correlation to A-a gradient. In our study, a PEEP level of 10 mbar improved alveolar gas exchange without compromising hemodynamic stability in patients mechanically ventilated in the lateral decubitus position. EIT measured parameters may be used to determine optimal ventilation parameters in these patients with inhomogeneous lung mechanics. Further studies are needed in patients with various lung pathologies.