Assessing SOFA score trajectories in sepsis using machine learning: A pragmatic approach to improve the accuracy of mortality prediction.

INTRODUCTION: An increasing amount of longitudinal health data is available on critically ill septic patients in the age of digital medicine, including daily sequential organ failure assessment (SOFA) score measurements. Thus, the assessment in sepsis focuses increasingly on the evaluation of the individual disease's trajectory. Machine learning (ML) algorithms may provide a promising approach here to improve the evaluation of daily SOFA score dynamics. We tested whether ML algorithms can outperform the conventional ΔSOFA score regarding the accuracy of 30-day mortality prediction. METHODS: We used the multicentric SepsisDataNet.NRW study cohort that prospectively enrolled 252 sepsis patients between 03/2018 and 09/2019 for training ML algorithms, i.e. support vector machine (SVM) with polynomial kernel and artificial neural network (aNN). We used the Amsterdam UMC database covering 1,790 sepsis patients for external and independent validation. RESULTS: Both SVM (AUC 0.84; 95% CI: 0.71-0.96) and aNN (AUC 0.82; 95% CI: 0.69-0.95) assessing the SOFA scores of the first seven days led to a more accurate prognosis of 30-day mortality compared to the ΔSOFA score between day 1 and 7 (AUC 0.73; 95% CI: 0.65-0.80; p = 0.02 and p = 0.05, respectively). These differences were even more prominent the shorter the time interval considered. Using the SOFA scores of day 1 to 3 SVM (AUC 0.82; 95% CI: 0.68 0.95) and aNN (AUC 0.80; 95% CI: 0.660.93) led to a more accurate prognosis of 30-day mortality compared to the ΔSOFA score (AUC 0.66; 95% CI: 0.58-0.74; p < 0.01 and p < 0.01, respectively). Strikingly, all these findings could be confirmed in the independent external validation cohort. CONCLUSIONS: The ML-based algorithms using daily SOFA scores markedly improved the accuracy of mortality compared to the conventional ΔSOFA score. Therefore, this approach could provide a promising and automated approach to assess the individual disease trajectory in sepsis. These findings reflect the potential of incorporating ML algorithms as robust and generalizable support tools on intensive care units.

The Aquaporin 3 Polymorphism (rs17553719) Is Associated with Sepsis Survival and Correlated with IL-33 Secretion.

Sepsis is a common life-threatening disease caused by dysregulated immune response and metabolic acidosis which lead to organ failure. An abnormal expression of aquaporins plays an important role in organ failure. Additionally, genetic variants in aquaporins impact on the outcome in sepsis. Thus, we investigated the polymorphism (rs17553719) and expression of aquaporin-3 (AQP3) and correlated these measurements with the survival of sepsis patients. Accordingly, we collected blood samples on several days (plus clinical data) from 265 sepsis patients who stayed in different ICUs in Germany. Serum plasma, DNA, and RNA were then separated to detect the promotor genotypes of AQP3 mRNA expression of AQP3 and several cytokines. The results showed that the homozygote CC genotype exhibited a significant decrease in 30-day survival (38.9%) compared to the CT (66.15%) and TT genotypes (76.3%) (p = 0.003). Moreover, AQP3 mRNA expression was significantly higher and nearly doubled in the CC compared to the CT (p = 0.0044) and TT genotypes (p = 0.018) on the day of study inclusion. This was accompanied by an increased IL-33 concentration in the CC genotype (day 0: p = 0.0026 and day 3: p = 0.008). In summary, the C allele of the AQP3 polymorphism (rs17553719) shows an association with increased AQP3 expression and IL-33 concentration accompanied by decreased survival in patients with sepsis.

AQP3 and AQP9-Contrary Players in Sepsis?

Sepsis involves an immunological systemic response to a microbial pathogenic insult, leading to a cascade of interconnected biochemical, cellular, and organ-organ interaction networks. Potential drug targets can depict aquaporins, as they are involved in immunological processes. In immune cells, AQP3 and AQP9 are of special interest. In this study, we tested the hypothesis that these aquaporins are expressed in the blood cells of septic patients and impact sepsis survival. Clinical data, routine laboratory parameters, and blood samples from septic patients were analyzed on day 1 and day 8 after sepsis diagnosis. AQP expression and cytokine serum concentrations were measured. AQP3 mRNA expression increased over the duration of sepsis and was correlated with lymphocyte count. High AQP3 expression was associated with increased survival. In contrast, AQP9 expression was not altered during sepsis and was correlated with neutrophil count, and low levels of AQP9 were associated with increased survival. Furthermore, AQP9 expression was an independent risk factor for sepsis lethality. In conclusion, AQP3 and AQP9 may play contrary roles in the pathophysiology of sepsis, and these results suggest that AQP9 may be a novel drug target in sepsis and, concurrently, a valuable biomarker of the disease.

Anesthesia for Morbidly Obese Patients.

BACKGROUND: The prevalence of morbid obesity (BMI >35 kg/m2) has risen steadily in recent decades. With the corresponding rise in the number of bariatric operations, anesthesiologists deal with this patient group more commonly than before, particularly in specialized centers. METHODS: This review is based on publications retrieved by a selective search in PubMed, including current guidelines and recommendations issued by specialist societies, as well as expert opinion. RESULTS: In the anesthesiological care of morbidly obese patients, a preoperative assessment and risk stratification are just as important as the thoughtful selection of the anesthesia technique, the drugs used and their dosage, and perioperative management. A thorough understanding of the pathophysiological changes and comorbidities of morbid obesity and the associated risks is essential. The risk of pulmonary complications such as respiratory failure, hypoxia, and apnea is markedly higher in morbidly obese patients, especially those with obstructive sleep apnea. Short-acting, less lipophilic anesthetic drugs are particularly useful, as is multimodal pain therapy for the avoidance of high opiate doses. The indication for intensified postoperative monitoring depends on the patient's preexisting illnesses, the type of anesthesia, and the type of surgical procedure. Regional anesthetic techniques should be used if possible. CONCLUSION: The perioperative care of morbidly obese patients presents special challenges. The anesthesiologist must be aware of potential comorbidities, specific risks, and pathophysiological changes in order to provide adequate care to this patient group.

A case of recurring perioperative circulatory arrest: mind the autonomic nervous system.

We report the case of an elderly woman who developed recurring episodes of unexplained cardiocirculatory arrest. The index event appeared during surgery to fix a fracture of the ankle and consisted of bradypnea, hypotension and asystole, coherent with a Bezold-Jarisch-like cardioprotective reflex. Classical signs of acute myocardial infarction were absent. Yet, occlusion of the right coronary artery (RCA) was observed and successfully revascularized, whereupon circulatory arrests vanished. We discuss several differential diagnoses. Unexplainable circulatory failure, with sinus bradycardia and arterial hypotension, despite lack of ECG signs of ischemia or significant troponin levels, suggest the action of cardioprotective reflexes of the autonomic nervous system. Coronary artery disease is a common source. Attention to cardioprotective reflexes should be taken in the case of unexplained cardiac arrest without overt reasons. We recommend performing coronary angiography to exclude significant coronary stenosis.

A New Approach in Airway Management for Tracheal Resection and Anastomosis: A Single-Center Prospective Study.

OBJECTIVES: The evaluation of the use of laryngeal mask airways (LMA) as an alternative form of airway management for surgical tracheal reconstruction. DESIGN: A prospective case series. SETTING: At a single German university hospital. PARTICIPANTS: Ten patients. INTERVENTIONS: The use of LMA for airway management in surgical reconstruction of the trachea. MEASUREMENTS AND MAIN RESULTS: Ten patients with tracheal stenosis of 50% to 90% were enrolled prospectively during the study period. The airway management consisted of the insertion of an LMA. During resection and reconstruction, high-frequency jet ventilation was used. Several arterial blood gas analyses (ABG) were performed before, during, and after the tracheal resection and reconstruction. All values were presented as median and interquartile ranges or as absolute and relative values, and no emergency change to cross-field intubation was necessary. The lowest PaO2 was 93 mmHg in 1 patient after 20 minutes of jet ventilation, whereas PaO2 increased after the induction phase and remained stable in 9 patients. There were no intraoperative complications related to anesthetic management apart from transient hypercarbia during and after jet ventilation. Preoperative and postoperative ABG were comparable. One patient required immediate postoperative ventilatory support. Two patients developed postoperative pneumonia, leading to their admission to the intensive care unit. One patient was operated with a palliative approach due to massive dyspnea and died in the next postoperative course. CONCLUSIONS: The use of LMA is an alternative option in airway management for tracheal reconstruction, even in patients with significant tracheal stenosis. Potential advantages compared to tracheal intubation are unimpaired access to the operative field and the lack of stress on the fresh anastomosis.

[Anaesthetic Management of Non-intubated Video-assisted Thoracic Surgery]. / Anästhesie bei nicht intubierter videoassistierter Thoraxchirurgie (NiVATS).

Non-intubated thoracic surgery is currently gaining popularity. In select patients and in experienced centres, non-intubated approaches may enable patients to safely undergo thoracic surgical procedures, who would otherwise be considered at high risk from general anaesthesia. While non-intubated techniques have been widely adopted for minor surgical procedures, its role in major thoracic surgery is a topic of controversial debate.This article discusses disadvantages of intubated anaesthetic approaches and advantages of non-intubated thoracic surgery as well as the anaesthetic management. This includes surgical and anaesthetic criteria for patient selection, suitable regional anaesthetic techniques, concepts for sedation and maintenance of airway patency as well as the management of perioperative complications.Non-intubated thoracic surgery has the potential to reduce postoperative morbidity and hospital length of stay. Successful non-intubated management depends on a standardised and well-trained interdisciplinary approach, especially regarding patient selection and perioperative complications.

Dental Strain on Maxillary Incisors During Tracheal Intubation With Double-Lumen Tubes and Different Laryngoscopy Techniques - A Blinded Mannequin Study.

OBJECTIVES: To quantify dental forces during double-lumen tube intubations with different laryngoscopy techniques. DESIGN: Experimental biomechanical mannequin study. SETTING: Two German university hospitals. PARTICIPANTS: One hundred four anesthesiologists with varying levels of experience. INTERVENTIONS: Participants performed a sequence of intubations on a mannequin equipped with hidden forces sensors in the maxillary incisors. Different laryngoscopy techniques were evaluated under normal and difficult airway conditions. Direct laryngoscopy was compared with different videolaryngoscopy techniques: the C-MAC with a Macintosh blade, the GlideScope, and the KingVision with hyperangulated blades. MEASUREMENTS AND MAIN RESULTS: A total of 624 intubations were evaluated. In normal airway conditions, the median (interquartile range [range]) peak forces were significantly lower when the GlideScope (15.7 (11.3-22.0 [2.1-110.5]) N) was used compared with direct laryngoscopy (21.0 (14.1-28.5[4.7-168.6]) N) (p = 0.007). In difficult airways, resulting forces were reduced using hyperangulated videolaryngoscopes (GlideScope: -13.7 N [p < 0.001]; KingVision: -11.9 N [p < 0.001]) compared with direct laryngoscopy, respectively. The time to intubation was prolonged with the use of the KingVision (25.5 (17.1-41.9[9.2-275.0])s [p < 0.001]) in comparison to direct laryngoscopy (20.8 (15.9-27.4[8.7-198.6]) s). The C-MAC demonstrated the shortest time to intubation. CONCLUSIONS: Although hyperangulated videolaryngoscopes improve dental strain, clinicians also should consider the time to intubation, which is shortest with nonhyperangulated videoblades, when choosing a laryngoscopy technique on an individual patient basis.

The impact of the COVID-19 pandemic on non-COVID induced sepsis survival.

BACKGROUND: The COVID-19 pandemic has taken a toll on health care systems worldwide, which has led to increased mortality of different diseases like myocardial infarction. This is most likely due to three factors. First, an increased workload per nurse ratio, a factor associated with mortality. Second, patients presenting with COVID-19-like symptoms are isolated, which also decreases survival in cases of emergency. And third, patients hesitate to see a doctor or present themselves at a hospital. To assess if this is also true for sepsis patients, we asked whether non-COVID-19 sepsis patients had an increased 30-day mortality during the COVID-19 pandemic. METHODS: This is a post hoc analysis of the SepsisDataNet.NRW study, a multicentric, prospective study that includes septic patients fulfilling the SEPSIS-3 criteria. Within this study, we compared the 30-day mortality and disease severity of patients recruited pre-pandemic (recruited from March 2018 until February 2020) with non-COVID-19 septic patients recruited during the pandemic (recruited from March 2020 till December 2020). RESULTS: Comparing septic patients recruited before the pandemic to those recruited during the pandemic, we found an increased raw 30-day mortality in sepsis-patients recruited during the pandemic (33% vs. 52%, p = 0.004). We also found a significant difference in the severity of disease at recruitment (SOFA score pre-pandemic: 8 (5 - 11) vs. pandemic: 10 (8 - 13); p < 0.001). When adjusted for this, the 30-day mortality rates were not significantly different between the two groups (52% vs. 52% pre-pandemic and pandemic, p = 0.798). CONCLUSIONS: This led us to believe that the higher mortality of non-COVID19 sepsis patients during the pandemic might be attributed to a more severe septic disease at the time of recruitment. We note that patients may experience a delayed admission, as indicated by elevated SOFA scores. This could explain the higher mortality during the pandemic and we found no evidence for a diminished quality of care for critically ill sepsis patients in German intensive care units.

Anesthesia for tracheal and carinal resection and reconstruction.

PURPOSE OF REVIEW: The aim of this review is to provide an overview of current anesthetic management of tracheal and carinal resection and reconstruction. RECENT FINDINGS: In addition to the traditional anesthetic approach using conventional tracheal intubation after induction of general anesthesia and cross-field intubation or jet-ventilation once the airway has been surgically opened, there is a trend toward less invasive anesthetic procedures. Regional anesthetic techniques and approaches focusing on the maintenance of spontaneous respiration have emerged. Especially for cervical tracheal stenosis, laryngeal mask airways appear to be an advantageous alternative to tracheal intubation.Extracorporeal support can ensure adequate gas exchange and/or perfusion during complex resections and reconstructions without interference of airway devices with the operative field. It also serves as an effective rescue technique in case other approaches fail. SUMMARY: The spectrum of available anesthetic techniques for major airway surgery is immense. To find the safest approach for the individual patient, comprehensive interdisciplinary planning is essential. The location and anatomic consistency of the stenosis, comorbidities, the functional status of respiratory system, as well as the planned reconstructive technique need to be considered. Until more data is available, however, a reliable evidence-based comparison of different approaches is not possible.

Current practice of thoracic anaesthesia in Europe - a survey by the European Society of Anaesthesiology Part I - airway management and regional anaesthesia techniques.

BACKGROUND: The scientific working group for "Anaesthesia in thoracic surgery" of the German Society of Anaesthesiology and Intensive Care Medicine (DGAI) has performed an online survey to assess the current standards of care and structural properties of anaesthesia workstations in thoracic surgery. METHODS: All members of the European Society of Anaesthesiology (ESA) were invited to participate in the study. RESULTS: Thoracic anaesthesia was most commonly performed by specialists/board-certified anaesthetists and/or senior/attending physicians. Across Europe, the double lumen tube (DLT) was most commonly chosen as the primary device for lung separation (461/ 97.3%). Bronchial blockers were chosen less frequently (9/ 1.9%). Throughout Europe, bronchoscopy was not consistently used to confirm correct double lumen tube positioning. Respondents from Eastern Europe (32/ 57.1%) frequently stated that there were not enough bronchoscopes available for every intrathoracic operation. A specific algorithm for difficult airway management in thoracic anaesthesia was available to only 18.6% (n = 88) of the respondents. Thoracic epidural analgesia (TEA) is the most commonly used form of regional analgesia for thoracic surgery in Europe. Ultrasonography was widely available 93,8% (n = 412) throughout Europe and was predominantly used for central line placement and lung diagnostics. CONCLUSIONS: While certain "gold standards "are widely met, there are also aspects of care requiring substantial improvement in thoracic anaesthesia throughout Europe. Our data suggest that algorithms and standard operating procedures for difficult airway management in thoracic anaesthesia need to be established. A European recommendation for the basic requirements of an anaesthesia workstation for thoracic anaesthesia is expedient and desirable, to improve structural quality and patient safety.

Improving Pediatric Drug Safety in Prehospital Emergency Care-10 Years on.

OBJECTIVES: The Pediatric Emergency Ruler (PaedER) is a height-based drug dose recommendation tool that was reported to reduce life-threatening medication errors by 90%. The PaedER was introduced into the Cologne Emergency Medical Service (EMS) in 2008 along with educational measures, publications, and lectures for pediatric drug safety. We reviewed the impact of these continuously ongoing measures on medication errors after 10 years. METHODS: The PaedER was introduced and distributed to all 14 emergency ambulances and 2 helicopters staffed with emergency physicians in the city of Cologne in November 2008. Electronic records and medical protocols of the Cologne EMS over two 20-month periods from March 2007 to October 2008 and March 2018 to October 2019 data sets were retrieved. The administered doses of either intravenous, intraosseous, intranasal, or buccal fentanyl, midazolam, ketamine, or epinephrine were recorded. Primary outcome measure was the rate of severe drug dosing errors with a deviation from the recommended dose of greater than 300%. RESULTS: A total of 59 and 443 drug administrations were analyzed for 2007/08 and 2018/19, respectively. The overall rate of drug dosing errors decreased from 22.0% to 9.9% (P = 0.014; relative risk reduction, 55%). Four of 5 severe dosing errors for epinephrine were avoided (P < 0.021; relative risk reduction, 78%). Documentation of patient's weight increased from 3.2% in 2007/08 to 30.5% in 2018/19 (P < 0.001). CONCLUSIONS: The distribution of the PaedER combined by educational measures significantly reduced the rates of life-threatening medication errors in a large EMS. Those results should motivate further initiatives on pediatric drug safety in prehospital emergency care.

Machine learning identifies ICU outcome predictors in a multicenter COVID-19 cohort.

BACKGROUND: Intensive Care Resources are heavily utilized during the COVID-19 pandemic. However, risk stratification and prediction of SARS-CoV-2 patient clinical outcomes upon ICU admission remain inadequate. This study aimed to develop a machine learning model, based on retrospective & prospective clinical data, to stratify patient risk and predict ICU survival and outcomes. METHODS: A Germany-wide electronic registry was established to pseudonymously collect admission, therapeutic and discharge information of SARS-CoV-2 ICU patients retrospectively and prospectively. Machine learning approaches were evaluated for the accuracy and interpretability of predictions. The Explainable Boosting Machine approach was selected as the most suitable method. Individual, non-linear shape functions for predictive parameters and parameter interactions are reported. RESULTS: 1039 patients were included in the Explainable Boosting Machine model, 596 patients retrospectively collected, and 443 patients prospectively collected. The model for prediction of general ICU outcome was shown to be more reliable to predict "survival". Age, inflammatory and thrombotic activity, and severity of ARDS at ICU admission were shown to be predictive of ICU survival. Patients' age, pulmonary dysfunction and transfer from an external institution were predictors for ECMO therapy. The interaction of patient age with D-dimer levels on admission and creatinine levels with SOFA score without GCS were predictors for renal replacement therapy. CONCLUSIONS: Using Explainable Boosting Machine analysis, we confirmed and weighed previously reported and identified novel predictors for outcome in critically ill COVID-19 patients. Using this strategy, predictive modeling of COVID-19 ICU patient outcomes can be performed overcoming the limitations of linear regression models. Trial registration "ClinicalTrials" (clinicaltrials.gov) under NCT04455451.

[Target Temperature Control in Patients with Burns]. / Zieltemperaturkontrolle beim Patienten mit Verbrennungen.

Severe burns lead to a persistent hypermetabolic response of the organism with significantly increased resting energy turnover, multi-organ dysfunction, muscle breakdown and increased risk of infection. Elevated core and skin temperatures are characteristic. A further increase in the metabolic rate can be triggered by heat losses, for which these patients are particularly predisposed due to high heat dissipation via evaporation of moisture and impairment of the thermoregulatory and insulating properties of the burnt skin. This is especially true in all treatment situations with exposure to large, uncovered skin surfaces, such as primary care, dressing changes in the intensive care unit and surgery with extensive sterile operating field. It has been shown that hypothermia is associated with numerous risks for the burn patient. Consistent heat management with measurement of the core body temperature and application of external and internal heat protection measures is recommended. Traditionally, an increase in room temperature is used here. However, this effective measure is limited by the resilience of the intensive care practitioners and the surgeons. To avoid perioperative hypothermia, strict surgical planning with limitation of the duration of surgery and close intraoperative communication about the risk of hypothermia are of particular importance.The differentiation between accepted temperature increase and infectious fever is often only possible by the inclusion of further examination findings. The criterion for sepsis is a temperature above 39 °C or below 36.5 °C.

Most patient conditions do not a priori debilitate the sensitivity of thoracic ultrasound in thoracic surgery-a prospective comparative study.

BACKGROUND: The few existing studies on the accuracy of lung ultrasound in the detection of a postoperative pneumothorax after thoracic surgery differ in the sonographic technique and the inclusion criteria. Several conditions are considered unfavourable in the sonographic examination of the lung. We aim to test these conditions for their impact on the diagnostic accuracy of lung ultrasound. METHODS: We compared lung ultrasound and chest roentgenograms for the detection of a pneumothorax after lung-resecting surgery in two prospective trials (register ID DRKS00014557 and DRKS00020216). The ultrasound examiners and radiologists were blinded towards the corresponding findings. We performed posthoc subgroup analyses to determine the influence of various patient or surgery related conditions on the sensitivity and specificity of ultrasound in the detection of pneumothorax. RESULTS: We performed 340 examinations in 208 patients. The covariates were age, gender, body mass index, smoking status, severity of chronic obstructive pulmonary disease, previous ipsilateral operation or irradiation, thoracotomy, postoperative skin emphysema, indwelling chest tube and X-ray in supine position. In univariate analysis, an indwelling chest-tube was associated with a higher sensitivity (58%, p = 0.04), and a postoperative subcutaneous emphysema with a lower specificity (73% vs. 88%, p = 0.02). None of the other subgroups differed in sensitivity or specificity from the total population . CONCLUSIONS: Most of the patient- or surgery related conditions usually considered unfavourable for lung ultrasound did not impair the sensitivity or specificity of lung ultrasound. Further studies should not excluce patients with these conditions, but test the accuracy under routine conditions. TRIAL REGISTRATION: DRKS, DRKS00014557, registered 06/09/2018, https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00014557 and DRKS00020216, registered 03/12/2019, https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00020216.

Hypopharyngeal Perforation Mimicking Esophageal Atresia: A Case Report of an Extremely Low Birth Weight Infant Emphasizing the Need for Preoperative Endoscopy.

We report a case of an extremely low birth weight premature infant born at 27 weeks of gestation, transferred to our tertiary pediatric referral center for surgical repair of an esophageal atresia. Endoscopic evaluation before the start of surgery revealed a hypopharyngeal perforation, resulting in the false impression of esophageal atresia. If no tracheoesophageal fistula is found during tracheoscopy, esophagoscopy should be done before surgical intervention as the inability to pass a nasogastric tube into the stomach is not sufficiently reliable for a correct diagnosis of esophageal atresia.