Increasing Rate of Fatal Streptococcus pyogenes Bacteriemia-A Challenge for Prompt Diagnosis and Appropriate Therapy in Real Praxis.

Streptococcus pyogenes, group A streptococci (GAS) bacteriaemia, is a life-threatening infection with high mortality, requiring fast diagnosis together with the use of appropriate antibiotic therapy as soon as possible. Our study analysed data from 93 patients with GAS bacteraemia at the General University Hospital in Prague between January 2006 and March 2024. In the years 2016-2019 there was an increase in GAS bacteraemia. Mortality in the period 2006-2019 was 21.9%; in the period 2020-2024, the mortality increased to 41.4%, p = 0.08. At the same time, in the post-2020 period, the time from hospital admission to death was reduced from 9.5 days to 3 days. A significant predictor of worse outcome in this period was high levels of procalcitonin, >35.1 µg/L (100% sensitivity and 82.35% specificity), and lactate, >5 mmol/L (90.91% sensitivity and 91.67% specificity). Myoglobin was a significant predictor in both compared periods, the AUC was 0.771, p = 0.044, and the AUC was an even 0.889, p ≤ 0.001, respectively. All isolates of S. pyogenes were susceptible to penicillin, and resistance to clindamycin was 20.3% from 2006-2019 and 10.3% in 2020-2024. Appropriate therapy was initiated in 89.1%. and 96.6%, respectively. We hypothesise that the increase in mortality after 2020 might be due to a decrease in the immune status of the population.

Effect of intra-arrest transport, extracorporeal cardiopulmonary resuscitation and immediate invasive assessment in refractory out-of-hospital cardiac arrest: a long-term follow-up of the Prague OHCA trial.

BACKGROUND: Randomized data evaluating the impact of the extracorporeal cardiopulmonary resuscitation (ECPR) approach on long-term clinical outcomes in patients with refractory out-of-hospital cardiac arrest (OHCA) are lacking. The objective of this follow-up study was to assess the long-term clinical outcomes of the ECPR-based versus CCPR approach. METHODS: The Prague OHCA trial was a single-center, randomized, open-label trial. Patients with witnessed refractory OHCA of presumed cardiac origin, without return of spontaneous circulation, were randomized during ongoing resuscitation on scene to conventional CPR (CCPR) or an ECPR-based approach (intra-arrest transport, ECPR if ROSC is not achieved prehospital and immediate invasive assessment). RESULTS: From March 2013 to October 2020, 264 patients were randomized during ongoing resuscitation on scene, and 256 patients were enrolled. Long-term follow-up was performed 5.3 (interquartile range 3.8-7.2) years after initial randomization and was completed in 255 of 256 patients (99.6%). In total, 34/123 (27.6%) patients in the ECPR-based group and 26/132 (19.7%) in the CCPR group were alive (log-rank P = 0.01). There were no significant differences between the treatment groups in the neurological outcome, survival after hospital discharge, risk of hospitalization, major cardiovascular events and quality of life. Of long-term survivors, 1/34 (2.9%) in the ECPR-based arm and 1/26 (3.8%) in the CCPR arm had poor neurological outcome (both patients had a cerebral performance category score of 3). CONCLUSIONS: Among patients with refractory OHCA, the ECPR-based approach significantly improved long-term survival. There were no differences in the neurological outcome, major cardiovascular events and quality of life between the groups, but the trial was possibly underpowered to detect a clinically relevant difference in these outcomes. Trial registration ClinicalTrials.gov Identifier: NCT01511666, Registered 19 January 2012.

Prognostic Impact of Serial Imaging in Severe Acute Respiratory Distress Syndrome on the Extracorporeal Membrane Oxygenation.

BACKGROUND: The impact of serial imaging on the outcome of ICU patients has not been studied specifically in patients with high illness severity. METHODS: The authors sought a relationship between the numbers of antero-posterior supine chest X-rays (CXR), computed tomography (CT) examinations, and outcome in a cohort of 292 patients with severe COVID-19 ARDS collected over 24 months in a high-volume ECMO center with established ultrasound and echocardiographic diagnostics. Of the patients, 172 (59%) were obese or morbidly obese, and 119 (41%) were treated with ECMO. RESULTS: The median number of CXRs was eight per 14 days of the length of stay in the ICU. The CXR rate was not related to ICU survival (p = 0.37). Patients required CT scanning in 26.5% of cases, with no relationship to the outcome except for the better ICU survival of the ECMO patients without a need for a CT scan (p = 0.01). The odds ratio for survival associated with ordering a CT scan in an ECMO patient was 0.48, p = 0.01. The calculated savings for not routinely requesting a whole-body CT scan in every patient were 98.685 EUR/24 months. CONCLUSIONS: Serial imaging does not impact the survival rates of patients with severe ARDS. Extracorporeal membrane oxygenation patients who did not need CT scanning had significantly better ICU outcomes.

Serum lactate in refractory out-of-hospital cardiac arrest: Post-hoc analysis of the Prague OHCA study.

BACKGROUND: The severity of tissue hypoxia is routinely assessed by serum lactate. We aimed to determine whether early lactate levels predict outcomes in refractory out-of-hospital cardiac arrest (OHCA) treated by conventional and extracorporeal cardiopulmonary resuscitation (ECPR). METHODS: This study is a post-hoc analysis of a randomized Prague OHCA study (NCT01511666) assessing serum lactate levels in refractory OHCA treated by ECPR (the ECPR group) or conventional resuscitation with prehospital achieved return of spontaneous circulation (the ROSC group). Lactate concentrations measured on admission and every 4 hours (h) during the first 24 h were used to determine their relationship with the neurological outcome (the best Cerebral Performance Category score within 180 days post-cardiac arrest). RESULTS: In the ECPR group (92 patients, median age 58.5 years, 83% male) 26% attained a favorable neurological outcome. In the ROSC group (82 patients, median age 55 years, 83% male) 59% achieved a favorable neurological outcome. In ECPR patients lactate concentrations could discriminate favorable outcome patients, but not consistently in the ROSC group. On admission, serum lactate >14.0 mmol/L for ECPR (specificity 87.5%, sensitivity 54.4%) and >10.8 mmol/L for the ROSC group (specificity 83%, sensitivity 41.2%) predicted an unfavorable outcome. CONCLUSION: In refractory OHCA serum lactate concentrations measured anytime during the first 24 h after admission to the hospital were found to correlate with the outcome in patients treated by ECPR but not in patients with prehospital ROSC. A single lactate measurement is not enough for a reliable outcome prediction and cannot be used alone to guide treatment.

Intraarrest transport, extracorporeal cardiopulmonary resuscitation, and early invasive management in refractory out-of-hospital cardiac arrest: an individual patient data pooled analysis of two randomised trials.

Background: Refractory out-of-hospital cardiac arrest (OHCA) treated with standard advanced cardiac life support (ACLS) has poor outcomes. Transport to hospital followed by in-hospital extracorporeal cardiopulmonary resuscitation (ECPR) initiation may improve outcomes. We performed a pooled individual patient data analysis of two randomised controlled trials evaluating ECPR based approach in OHCA. Methods: The individual patient data from two published randomised controlled trials (RCTs) were pooled: ARREST (enrolled Aug 2019-June 2020; NCT03880565) and PRAGUE-OHCA (enrolled March 1, 2013-Oct 25, 2020; NCT01511666). Both trials enrolled patients with refractory OHCA and compared: intra-arrest transport with in-hospital ECPR initiation (invasive approach) versus continued standard ACLS. The primary outcome was 180-day survival with favourable neurological outcome (defined as Cerebral Performance Category 1-2). Secondary outcomes included: cumulative survival at 180 days, 30-day favourable neurological survival, and 30-day cardiac recovery. Risk of bias in each trial was assessed by two independent reviewers using the Cochrane risk-of-bias tool. Heterogeneity was assessed via Forest plots. Findings: The two RCTs included 286 patients. Of those randomised to the invasive (n = 147) and standard (n = 139) groups, respectively: the median age was 57 (IQR 47-65) and 58 years (IQR 48-66), and the median duration of resuscitation was 58 (IQR 43-69) and 49 (IQR 33-71) minutes (p = 0.17). In a modified intention to treat analysis, 45 (32.4%) in the invasive and 29 (19.7%) patients in the standard arm survived to 180 days with a favourable neurological outcome [absolute difference (AD), 95% CI: 12.7%, 2.6-22.7%, p = 0.015]. Forty-seven (33.8%) and 33 (22.4%) patients survived to 180 days [HR 0.59 (0.43-0.81); log rank test p = 0.0009]. At 30 days, 44 (31.7%) and 24 (16.3%) patients had favourable neurological outcome (AD 15.4%, 5.6-25.1%, p = 0.003), 60 (43.2%), and 46 (31.3%) patients had cardiac recovery (AD: 11.9%, 0.7-23%, p = 0.05), in the invasive and standard arms, respectively. The effect was larger in patients presenting with shockable rhythms (AD 18.8%, 7.6-29.4; p = 0.01; HR 2.26 [1.23-4.15]; p = 0.009) and prolonged CPR (>45 min; HR 3.99 (1.54-10.35); p = 0.005). Interpretation: In patients with refractory OHCA, the invasive approach significantly improved 30- and 180-day neurologically favourable survival. Funding: None.

Pulmonary embolism-related refractory out-of-hospital cardiac arrest and extracorporeal cardiopulmonary resuscitation: Prague OHCA study post hoc analysis.

AIMS: Refractory out-of-hospital cardiac arrest (r-OHCA) in patients with pulmonary embolism (PE) is associated with poor outcomes. The role of extracorporeal cardiopulmonary resuscitation (ECPR) in this patient group is uncertain. This study aims to analyse clinical course, outcomes, and the effect of an invasive procedure, including ECPR, in a randomized population. METHODS AND RESULTS: A post hoc analysis of a randomized controlled trial (Prague OHCA study) was conducted to evaluate the effect of ECPR vs. a standard approach in r-OHCA. A subgroup of patients with PE-related r-OHCA was identified, and procedural and outcome characteristics, including favourable neurological survival, organ donation, and complications, were compared to patients without PE. Pulmonary embolism was identified as a cause of r-OHCA in 24 of 256 (9.4%) enrolled patients. Patients with PE were more likely to be women [12/24 (50%) vs. 32/232 (13.8%); P < 0.001] and presented more frequently with an initial non-shockable rhythm [23/24 (95.8%) vs. 77/232 (33.2%); P < 0.001], as well as more severe acidosis at admission [median pH (interquartile range); 6.83 (6.75-6.88) vs. 6.98 (6.82-7.14); P < 0.001]. Their favourable 180-day neurological survival was significantly lower [2/24 (8.3%) vs. 66/232 (28.4%); P = 0.049], but the proportion of accepted organ donors was higher (16.7 vs. 4.7%, P = 0.04). CONCLUSION: Refractory out-of-hospital cardiac arrest due to PE has a different presentation and inferior outcomes compared to other causes but may represent an important source of organ donations. The ECPR method did not improve patient outcomes.

Decentralized EHRs in the Semantic Web for Better Health Data Management.

Electronic Health Record (EHR) systems currently in use are not designed for widely interoperable longitudinal health data. Therefore, EHR data cannot be properly shared, managed and analyzed. In this article, we propose two approaches to making EHR data more comprehensive and FAIR (Findable, Accessible, Interoperable, and Reusable) and thus more useful for diagnosis and clinical research. Firstly, the data modeling based on the LinkML framework makes the data interoperability more realistic in diverse environments with various experts involved. We show the first results of how diverse health data can be integrated based on an easy-to-understand data model and without loss of available clinical knowledge. Secondly, decentralizing EHRs contributes to the higher availability of comprehensive and consistent EHR data. We propose a technology stack for decentralized EHRs and the reasons behind this proposal. Moreover, the two proposed approaches empower patients because their EHR data can become more available, understandable, and usable for them, and they can share their data according to their needs and preferences. Finally, we explore how the users of the proposed solution could be involved in the process of its validation and adoption.

Information System for Integration of Genetic Information and Clinical Knowledge.

This paper deals with a developed information system called a Personal Genetic Card (PGC). The system aims to integrate the known clinical knowledge (interpretations and recommendations) linked to genetic information with the analysis results of a patient. Genetic information has an increasing influence on the clinical decision of physicians as well as other medical and health services. All these services need to connect the genetic profile with the phenotypes such as drug metabolization, drug toxicity, drug dosing, or intolerance of some substances. It still applies that the best way to represent data of medical records is a structured form of record. Many approaches can be used to define the structure (syntax) of the record and the content (semantics) of the record and to exchange data in forms of various standards and terminologies. Moreover, the genetic analysis field has its terminology databases for representing genetic information (e.g. HGNC, NCBI). The next step is to connect the genetic analysis results with c clinical knowledge (interpretation, recommendation). This step is crucial because the genetic analysis results have clinical benefits if we can assign them to some valid clinical knowledge. And the best final result is when we can make a better recommendation based on the genetic results and clinical knowledge. Genetic knowledge databases (e.g. PharmGKB, SNPedia, ClinVar) contain many interpretations and even recommendations for genetic analysis results based on different purposes. This situation is appropriate for developing the PGC system that takes inspiration from case-based reasoning in purpose to allow integration of the assumptions and knowledge about phenotypes and the real genetic analysis results in the structured form.

Initial rhythm and survival in refractory out-of-hospital cardiac arrest. Post-hoc analysis of the Prague OHCA randomized trial.

BACKGROUND: The prognosis of refractory out-of-hospital cardiac arrest (OHCA) is generally poor. A recent Prague OHCA study has demonstrated that an invasive approach (including extracorporeal cardiopulmonary resuscitation, ECPR) is a feasible and effective treatment strategy in refractory OHCA. Here we present a post-hoc analysis of the role of initial rhythm on patient outcomes. METHODS: The study enrolled patients who had a witnessed OHCA of presumed cardiac cause without early recovery of spontaneous circulation. The initial rhythm was classified as either a shockable or a non-shockable rhythm. The primary outcome was a composite of 180 day-survival with Cerebral Performance in Category 1 or 2. RESULTS: 256 (median age 58y, 17% females) patients were enrolled. The median (IQR) duration of resuscitation was 52 (33-68) minutes. 156 (61%) and 100 (39%) of patients manifested a shockable and non-shockable rhythm, respectively. The primary outcome was achieved in 63 (40%) patients with a shockable rhythm and in 5 (5%) patients with a non-shockable rhythm (p < 0.001). When patients were analyzed separately based on whether the treatment was invasive (n = 124) or standard (n = 132), the difference in the primary endpoint between shockable and non-shockable initial rhythms remained significant (35/72 (49%) vs 4/52 (8%) in the invasive arm and 28/84 (33%) vs 1/48 (2%) in the standard arm; p < 0.001). CONCLUSION: An initial shockable rhythm and treatment with an invasive approach is associated with a reasonable neurologically favorable survival for 180 days despite refractory OHCA. Non-shockable initial rhythms bear a poor prognosis in refractory OHCA even when ECPR is readily available.

Extracorporeal versus conventional cardiopulmonary resuscitation for refractory out-of-hospital cardiac arrest: a secondary analysis of the Prague OHCA trial.

BACKGROUND: Survival rates in refractory out-of-hospital cardiac arrest (OHCA) remain low with conventional advanced cardiac life support (ACLS). Extracorporeal life support (ECLS) implantation during ongoing resuscitation, a method called extracorporeal cardiopulmonary resuscitation (ECPR), may increase survival. This study examined whether ECPR is associated with improved outcomes. METHODS: Prague OHCA trial enrolled adults with a witnessed refractory OHCA of presumed cardiac origin. In this secondary analysis, the effect of ECPR on 180-day survival using Kaplan-Meier estimates and Cox proportional hazard model was examined. RESULTS: Among 256 patients (median age 58 years, 83% male) with median duration of resuscitation 52.5 min (36.5-68), 83 (32%) patients achieved prehospital ROSC during ongoing conventional ACLS prehospitally, 81 (32%) patients did not achieve prehospital ROSC with prolonged conventional ACLS, and 92 (36%) patients did not achieve prehospital ROSC and received ECPR. The overall 180-day survival was 51/83 (61.5%) in patients with prehospital ROSC, 1/81 (1.2%) in patients without prehospital ROSC treated with conventional ACLS and 22/92 (23.9%) in patients without prehospital ROSC treated with ECPR (log-rank p < 0.001). After adjustment for covariates (age, sex, initial rhythm, prehospital ROSC status, time of emergency medical service arrival, resuscitation time, place of cardiac arrest, percutaneous coronary intervention status), ECPR was associated with a lower risk of 180-day death (HR 0.21, 95% CI 0.14-0.31; P < 0.001). CONCLUSIONS: In this secondary analysis of the randomized refractory OHCA trial, ECPR was associated with improved 180-day survival in patients without prehospital ROSC. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01511666, Registered 19 January 2012.

Effect of Intra-arrest Transport, Extracorporeal Cardiopulmonary Resuscitation, and Immediate Invasive Assessment and Treatment on Functional Neurologic Outcome in Refractory Out-of-Hospital Cardiac Arrest: A Randomized Clinical Trial.

Importance: Out-of-hospital cardiac arrest (OHCA) has poor outcome. Whether intra-arrest transport, extracorporeal cardiopulmonary resuscitation (ECPR), and immediate invasive assessment and treatment (invasive strategy) is beneficial in this setting remains uncertain. Objective: To determine whether an early invasive approach in adults with refractory OHCA improves neurologically favorable survival. Design, Setting, and Participants: Single-center, randomized clinical trial in Prague, Czech Republic, of adults with a witnessed OHCA of presumed cardiac origin without return of spontaneous circulation. A total of 256 participants, of a planned sample size of 285, were enrolled between March 2013 and October 2020. Patients were observed until death or day 180 (last patient follow-up ended on March 30, 2021). Interventions: In the invasive strategy group (n = 124), mechanical compression was initiated, followed by intra-arrest transport to a cardiac center for ECPR and immediate invasive assessment and treatment. Regular advanced cardiac life support was continued on-site in the standard strategy group (n = 132). Main Outcomes and Measures: The primary outcome was survival with a good neurologic outcome (defined as Cerebral Performance Category [CPC] 1-2) at 180 days after randomization. Secondary outcomes included neurologic recovery at 30 days (defined as CPC 1-2 at any time within the first 30 days) and cardiac recovery at 30 days (defined as no need for pharmacological or mechanical cardiac support for at least 24 hours). Results: The trial was stopped at the recommendation of the data and safety monitoring board when prespecified criteria for futility were met. Among 256 patients (median age, 58 years; 44 [17%] women), 256 (100%) completed the trial. In the main analysis, 39 patients (31.5%) in the invasive strategy group and 29 (22.0%) in the standard strategy group survived to 180 days with good neurologic outcome (odds ratio [OR], 1.63 [95% CI, 0.93 to 2.85]; difference, 9.5% [95% CI, -1.3% to 20.1%]; P = .09). At 30 days, neurologic recovery had occurred in 38 patients (30.6%) in the invasive strategy group and in 24 (18.2%) in the standard strategy group (OR, 1.99 [95% CI, 1.11 to 3.57]; difference, 12.4% [95% CI, 1.9% to 22.7%]; P = .02), and cardiac recovery had occurred in 54 (43.5%) and 45 (34.1%) patients, respectively (OR, 1.49 [95% CI, 0.91 to 2.47]; difference, 9.4% [95% CI, -2.5% to 21%]; P = .12). Bleeding occurred more frequently in the invasive strategy vs standard strategy group (31% vs 15%, respectively). Conclusions and Relevance: Among patients with refractory out-of-hospital cardiac arrest, the bundle of early intra-arrest transport, ECPR, and invasive assessment and treatment did not significantly improve survival with neurologically favorable outcome at 180 days compared with standard resuscitation. However, the trial was possibly underpowered to detect a clinically relevant difference. Trial Registration: ClinicalTrials.gov Identifier: NCT01511666.

Towards Personalized Medication.

The paper describes some aspects of precision medicine and shows the importance of pharmacokinetics and pharmacodynamics for the therapeutic drug monitoring and model-informed precision dosing. A key element in the design of the pharmacokinetics and pharmacodynamics (PKPD) models is relevant literature search that represents an essential step in the procurement and validation of a new drug. Available search engine resources do not offer specific functionalities that are required for efficient and relevant search in reliable literature sources. We present a prototype of such an intelligent search engine and show its results on real project data.

Maternal body mass index and external cephalic version success rate - are they related?

OBJECTIVES: External cephalic version (ECV) is a useful method helping to reduce the incidence of planned caesarean deliveries for fetal malpresentation. There is an effort to look for the best predictors for a successful ECV, the effect of maternal weight is still unclear. The aim of our study is to determine maternal body mass index (BMI) in association with the ECV success rate and the risk of complications. MATERIAL AND METHODS: A retrospective observational cohort study in 981 women after the 36th week of gestation with a fetus in a breech presentation who had undergone an ECV attempt. We evaluated the success rate and complications of ECV in association with BMI categories according to the WHO classification of obesity. RESULTS: ECV was successful in 478 cases (48.7%). In the category of overweight patients (BMI > 25; n = 484), ECV was successful in 51% and unsuccessful in 49% (p = 0.28) of cases. In obese patients (BMI > 30; n = 187), ECV was successful in 44.8% and unsuccessful in 55.2% (p = 0.28) of cases. The effect of BMI on the success rate of ECV for the category of overweight and obesity was not proven by statistical analysis. Serious complications occurred in seven cases in similar numbers in all three subgroups according to BMI. CONCLUSIONS: BMI in the categories of overweight and obesity is not a factor influencing the success rate and risk of complications of ECV. These results can be helpful when consulting pregnant women the chance of successful ECV.

Representation and Interpretation of Genetic Analysis: A Strategy of Development for the Personal Genetics Card Information System.

In this paper, we describe a strategy for the development of a genetic analysis comprehensive representation. The primary intention is to ensure the available utilization of genetic analysis results in clinical practice. The system is called Personnel Genetic Card (PGC), and it is developed in cooperation of CIIRC CTU in Prague and the Mediware company. Nowadays, genetic information is more and more part of medicine and life quality services (e.g. nutritional consulting). Therefore, there is necessary to bind genetic information with the clinical phenotype, such as drug metabolism or intolerance to various substances. We proposed a structured form of the record, where we utilize the LOINC® standard to identify genetic test parameters, and several terminology databases for representing specific genetic information (e.g. HGNC, NCBI RefSeq, NCBI dbNSP, HGVS). Further, there are also several knowledge databases (PharmGKB, SNPedia, ClinVar) that collect interpretation for genetic analysis results. In the results of this paper, we describe our idea in the structure and process perspective. The structural perspective includes the representation of the analysis record and its binding with the interpretations. The process perspective describes roles and activities within the PGC system use.

The effect of transient fetal bradycardia and other heart rate changes during and after external cephalic version on perinatal outcomes.

OBJECTIVES: To evaluate the effect of transient fetal bradycardia and other heart rate changes during and after external cephalic version (ECV) on perinatal outcomes. To determine factors associated with a higher risk of occurrence of transient fetal bradycardia during and after ECV. STUDY DESIGN: Prospective study in 286 women after the 36th week of gestation with a fetus in breech presentation who have undergone an ECV attempt. The study analyses the incidence of transient fetal bradycardia during and immediately after ECV, the time interval to complete adjustment of fetal bradycardia, the factors associated with the occurrence of transient fetal bradycardia, cardiotocography (CTG) changes after ECV and perinatal outcomes. All the data were statistically analyzed. RESULTS: The ECV was successful in 51 % (146/286). Transient fetal bradycardia occurred during and after ECV in 81 cases (28.3 %). A successful version was a factor significantly associated with fetal bradycardia (54; 37.0 % versus 27; 19.3 %; p < 0.01). Clinically significant hypotension of the mother was accompanied by transient fetal bradycardia in 12 cases (4.2 %). After the successful ECV there was no significant difference in the percentage of vaginal deliveries between subgroups with and without transient fetal bradycardia (85.2 % versus 83.7 %; p = 1.00). Nor in occurrence of acute fetal distress during labor (18.5 % versus 15.6 %; p = 0.65). In cases of a successful ECV transient CTG changes after ECV had no effect on the incidence of acute fetal distress during labor (23.5 % versus 15.7 %; p = 0.49). CONCLUSIONS: Transient fetal bradycardia and other heart rate changes during and immediately after ECV was not associated with a higher incidence of acute fetal distress during labor and did not affect perinatal outcomes. Higher occurrence of transient bradycardia after ECV was associated only with successful ECV. Transient hypotension of the mother as one of the causes of transient fetal bradycardia during ECV should be considered.

Brain perfusion evaluated by regional tissue oxygenation as a possible quality indicator of ongoing cardiopulmonary resuscitation. An experimental porcine cardiac arrest study.

INTRODUCTION: Relationship between regional tissue oxygenation (rSO2) and microcirculatory changes during cardiac arrest (CA) are still unclear. Therefore, we designed an experimental study to correlate rSO2, microcirculation and systemic hemodynamic parameters in a porcine model of CA. METHODS: Ventricular fibrillation was induced in 24 female pigs (50±3kg) and left for three minutes untreated followed by five minutes of mechanical CPR. Regional and peripheral saturations were assessed by near-infrared spectroscopy, sublingual microcirculation by Sidestream Dark Field technology and continuous hemodynamic parameters, including systemic blood pressure (MAP) and carotid blood flow (CF), during baseline, CA and CPR periods. The Wilcoxon Signed-Rank test, the Friedman test and the partial correlation method were used to compare these parameters. RESULTS: Brain and peripheral rSO2 showed a gradual decrease during CA and only an increase of brain rSO2 during mechanical CPR (34.5 to 42.5; p=0.0001), reflected by a rapid decrease of microcirculatory and hemodynamic parameters during CA and a slight increase during CPR. Peripheral rSO2 was not changed significantly during CPR (38 to 38.5; p=0.09). We only found a moderate correlation of cerebral/peripheral rSO2 to microcirculatory parameters (PVD: r=0.53/0.46; PPV: r=0.6/0.5 and MFI: r=0.64/0.52) and hemodynamic parameters (MAP: r=0.64/0.71 and CF: 0.71/0.67). CONCLUSIONS: Our experimental study confirmed that monitoring brain and peripheral rSO2 is an easy-to-use method, well reflecting the hemodynamics during CA. However, only brain rSO2 reflects the CPR efforts and might be used as a potential quality indicator for CPR.

Effect of Pulsatility on Microcirculation in Patients Treated with Extracorporeal Cardiopulmonary Resuscitation: A Pilot Study.

The effect of pulsatile blood flow on microcirculation during extracorporeal cardiopulmonary resuscitation (ECPR) is not elucidated; therefore, we designed an observational study comparing sublingual microcirculation in patients with refractory cardiac arrest (CA) with spontaneously pulsatile or low/nonpulsatile blood flow after treatment with ECPR. Microcirculation was assessed with Sidestream Dark Field technology in 12 patients with CA who were treated with ECPR and 12 healthy control subjects. Microcirculatory images were analyzed offline in a blinded fashion, and consensual parameters were determined for the vessels ≤20 µm. The patients' data, including actual hemodynamic parameters, were documented. Pulsatile blood flow was defined by a pulse pressure (PP) ≥ 15 mm Hg. Compared with the healthy volunteers, the patients who were treated with ECPR exhibited a significantly lower proportion of perfused capillaries (PPC); other microcirculatory parameters did not differ. The groups of patients with pulsatile (n = 7) versus low/nonpulsatile (n = 5) blood flow did not differ in regards to the collected data and hemodynamic variables (except for the PP and ejection fraction of the left ventricle) as well as microcirculatory parameters. In conclusion, microcirculation appeared to be effectively supported by ECPR in our group of patients with CA with the exception of the PPC. We found only nonsignificant contribution of spontaneous pulsatility to extracorporeal membrane oxygenation-generated microcirculatory blood flow.

Microcirculatory blood flow during cardiac arrest and cardiopulmonary resuscitation does not correlate with global hemodynamics: an experimental study.

BACKGROUND: Current research highlights the role of microcirculatory disorders in post-cardiac arrest patients. Affected microcirculation shows not only dissociation from systemic hemodynamics but also strong connection to outcome of these patients. However, only few studies evaluated microcirculation directly during cardiac arrest (CA) and cardiopulmonary resuscitation (CPR). The aim of our experimental study in a porcine model was to describe sublingual microcirculatory changes during CA and CPR using recent videomicroscopic technology and provide a comparison to parameters of global hemodynamics. METHODS: Cardiac arrest was induced in 18 female pigs (50 ± 3 kg). After 3 min without treatment, 5 min of mechanical CPR followed. Continuous hemodynamic monitoring including systemic blood pressure and carotid blood flow was performed and blood lactate was measured at the end of baseline and CPR. Sublingual microcirculation was assessed by the Sidestream Dark Field (SDF) technology during baseline, CA and CPR. Following microcirculatory parameters were assessed off-line separately for capillaries (≤20 µm) and other vessels: total and perfused vessel density (TVD, PVD), proportion of perfused vessels (PPV), microvascular flow index (MFI) and heterogeneity index (HI). RESULTS: In comparison to baseline the CA small vessel microcirculation was only partially preserved: TVD 15.64 (13.59-18.48) significantly decreased to 12.51 (10.57-13.98) mm/mm(2), PVD 15.57 (13.56-17.80) to 5.53 (4.17-6.60) mm/mm(2), PPV 99.64 (98.05-100.00) to 38.97 (27.60-46.29) %, MFI 3.00 (3.00-3.08) to 1.29 (1.08-1.58) and HI increased from 0.08 (0.00-0.23) to 1.5 (0.71-2.00), p = 0.0003 for TVD and <0.0001 for others, respectively. Microcirculation during ongoing CPR in small vessels reached 59-85 % of the baseline values: TVD 13.33 (12.11-15.11) mm/mm(2), PVD 9.34 (7.34-11.52) mm/mm(2), PPV 72.34 (54.31-87.87) %, MFI 2.04 (1.58-2.42), HI 0.65 (0.41-1.07). The correlation between microcirculation and global hemodynamic parameters as well as to lactate was only weak to moderate (i.e. Spearman's ρ 0.02-0.51) and after adjustment for multiple correlations it was non-significant. CONCLUSIONS: Sublingual microcirculatory parameters did not correlate with global hemodynamic parameters during simulated porcine model of CA and CPR. SDF imaging provides additional information about tissue perfusion in the course of CPR.

Agreement on intrapartum cardiotocogram recordings between expert obstetricians.

RATIONALE, AIMS AND OBJECTIVES: To evaluate obstetricians' inter- and intra-observer agreement on intrapartum cardiotocogram (CTG) recordings and to examine obstetricians' evaluations with respect to umbilical artery pH and base deficit. METHODS: Nine experienced obstetricians annotated 634 intrapartum CTG recordings. The evaluation of each recording was divided into four steps: evaluation of two 30-minute windows in the first stage of labour, evaluation of one window in the second stage of labour and labour outcome prediction. The complete set of evaluations used for this experiment is available online. The inter- and intra-observer agreement was evaluated using proportion of agreement and kappa coefficient. Clinicians' sensitivity and specificity was computed with respect to umbilical artery pH, base deficit and to Apgar score at the fifth minute. RESULTS: The overall proportion of agreement between clinicians reached 48% with 95% confidence intervals (CI) (CI: 47-50). Regarding the different classes, proportion of agreement ranged from 57% (CI: 54-60) for normal to 41% (CI: 36-46) for pathological class. The sensitivity of clinicians' majority vote to objective outcome was 39% (CI: 16-63) for the umbilical artery base deficit and 27% (CI: 16-42) for pH. The specificity was 89% (CI: 86-92) for both types of objective outcome. CONCLUSIONS: The reported inter-/intra-observer variability is large and this holds irrespective of clinicians' experience or work place. The results support the need of modernized guidelines for CTG evaluation and/or objectivization and repeatability by introduction of a computerized approach that could standardize the process of CTG evaluation within the delivery ward.

Analysis of obstetricians' decision making on CTG recordings.

Interpretation of cardiotocogram (CTG) is a difficult task since its evaluation is complicated by a great inter- and intra-individual variability. Previous studies have predominantly analyzed clinicians' agreement on CTG evaluation based on quantitative measures (e.g. kappa coefficient) that do not offer any insight into clinical decision making. In this paper we aim to examine the agreement on evaluation in detail and provide data-driven analysis of clinical evaluation. For this study, nine obstetricians provided clinical evaluation of 634 CTG recordings (each ca. 60min long). We studied the agreement on evaluation and its dependence on the increasing number of clinicians involved in the final decision. We showed that despite of large number of clinicians the agreement on CTG evaluations is difficult to reach. The main reason is inherent inter- and intra-observer variability of CTG evaluation. Latent class model provides better and more natural way to aggregate the CTG evaluation than the majority voting especially for larger number of clinicians. Significant improvement was reached in particular for the pathological evaluation - giving a new insight into the process of CTG evaluation. Further, the analysis of latent class model revealed that clinicians unconsciously use four classes when evaluating CTG recordings, despite the fact that the clinical evaluation was based on FIGO guidelines where three classes are defined.