Distinct clinical phenotypes in paediatric cancer patients with sepsis are associated with different outcomes:an international multicentre retrospective study

Background: Identifying phenotypes in sepsis patients may enable precision medicine approaches. However, the generalisability of these phenotypes to specific patient populations is unclear. Given that paediatric cancer patients with sepsis have different host response and pathogen profiles and higher mortality rates when compared to non-cancer patients, we determined whether unique, reproducible, and clinically-relevant sepsis phenotypes exist in this specific patient population. Methods: We studied patients with underlying malignancies admitted with sepsis to one of 25 paediatric intensive care units (PICUs) participating in two large, multi-centre, observational cohorts from the European SCOTER study (n = 383 patients; study period between January 1, 2018 and January 1, 2020) and the U.S. Novel Data-Driven Sepsis Phenotypes in Children study (n = 1898 patients; study period between January 1, 2012 and January 1, 2018). We independently used latent class analysis (LCA) in both cohorts to identify phenotypes using demographic, clinical, and laboratory data from the first 24 h of PICU admission. We then tested the association of the phenotypes with clinical outcomes in both cohorts. Findings: LCA identified two distinct phenotypes that were comparable across both cohorts. Phenotype 1 was characterised by lower serum bicarbonate and albumin, markedly increased lactate and hepatic, renal, and coagulation abnormalities when compared to phenotype 2. Patients with phenotype 1 had a higher 90-day mortality (European cohort 29.2% versus 13.4%, U.S. cohort 27.3% versus 11.4%, p &lt; 0.001) and received more vasopressor and renal replacement therapy than patients with phenotype 2. After adjusting for severity of organ dysfunction, haematological cancer, prior stem cell transplantation and age, phenotype 1 was associated with an adjusted OR of death at 90-day of 1.9 (1.04–3.34) in the European cohort and 1.6 (1.2–2.2) in the U.S. cohort. Interpretation: We identified two clinically-relevant sepsis phenotypes in paediatric cancer patients that are reproducible across two international, multicentre cohorts with prognostic implications. These results may guide further research regarding therapeutic approaches for these specific phenotypes. Funding: Part of this study is funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development.</p

Distinct clinical phenotypes in paediatric cancer patients with sepsis are associated with different outcomes:an international multicentre retrospective study

Background: Identifying phenotypes in sepsis patients may enable precision medicine approaches. However, the generalisability of these phenotypes to specific patient populations is unclear. Given that paediatric cancer patients with sepsis have different host response and pathogen profiles and higher mortality rates when compared to non-cancer patients, we determined whether unique, reproducible, and clinically-relevant sepsis phenotypes exist in this specific patient population. Methods: We studied patients with underlying malignancies admitted with sepsis to one of 25 paediatric intensive care units (PICUs) participating in two large, multi-centre, observational cohorts from the European SCOTER study (n = 383 patients; study period between January 1, 2018 and January 1, 2020) and the U.S. Novel Data-Driven Sepsis Phenotypes in Children study (n = 1898 patients; study period between January 1, 2012 and January 1, 2018). We independently used latent class analysis (LCA) in both cohorts to identify phenotypes using demographic, clinical, and laboratory data from the first 24 h of PICU admission. We then tested the association of the phenotypes with clinical outcomes in both cohorts. Findings: LCA identified two distinct phenotypes that were comparable across both cohorts. Phenotype 1 was characterised by lower serum bicarbonate and albumin, markedly increased lactate and hepatic, renal, and coagulation abnormalities when compared to phenotype 2. Patients with phenotype 1 had a higher 90-day mortality (European cohort 29.2% versus 13.4%, U.S. cohort 27.3% versus 11.4%, p &lt; 0.001) and received more vasopressor and renal replacement therapy than patients with phenotype 2. After adjusting for severity of organ dysfunction, haematological cancer, prior stem cell transplantation and age, phenotype 1 was associated with an adjusted OR of death at 90-day of 1.9 (1.04–3.34) in the European cohort and 1.6 (1.2–2.2) in the U.S. cohort. Interpretation: We identified two clinically-relevant sepsis phenotypes in paediatric cancer patients that are reproducible across two international, multicentre cohorts with prognostic implications. These results may guide further research regarding therapeutic approaches for these specific phenotypes. Funding: Part of this study is funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development.</p

Extracorporeal Cardiopulmonary Resuscitation—A Chance for Survival after Sudden Cardiac Arrest

Extracorporeal membrane oxygenation (ECMO) is an increasingly popular method for the treatment of patients with life-threatening conditions. The case we have described is characterized by the effectiveness of therapy despite resuscitation lasting more than one hour. A 3.5-year-old girl with a negative medical history was admitted to the Department of Cardiology due to ectopic atrial tachycardia. It was decided to perform electrical cardioversion under intravenous anaesthesia. During the induction of anaesthesia, cardiac arrest with pulseless electrical activity (PEA) occurred. Despite resuscitation, a permanent hemodynamically effective heart rhythm was not achieved. Due to prolonged resuscitation (over one hour) and persistent PEA, it was decided to use veno-arterial extracorporeal membrane oxygenation. After three days of intensive ECMO therapy, hemodynamic stabilization was achieved. The time of implementing ECMO therapy and assessment of the initial clinical status of the patient should be emphasized

Efficacy of tranexamic acid supplemented with local infiltration analgesia in reducing blood loss in patients undergoing unicompartmental knee arthroplasty

Abstract This study aimed to investigate the efficacy of tranexamic acid supplemented with local infiltration analgesia in reducing blood loss in patients undergoing unicompartmental knee arthroplasty (UKA). This retrospective study was conducted on 176 individuals with a mean age of 64.27 (standard deviation [SD], 7.16) years undergoing unicompartmental cemented knee arthroplasty. The patients were divided into three groups according to patient blood management: I, patients without additional bleeding protocol (control group); II, patients intravenously administered tranexamic acid (TXA) (TXA group); and III, patients with exact TXA protocol combined with intraoperative local infiltration analgesia (LIA) (TXA + LIA group). Blood loss was measured as a substitute for blood loss by the maximal haemoglobin (Hb) drop compared with the preoperative Hb level. The mean Hb drops for the control, TXA, and TXA + LIA groups were 2.24 (16.0%), 2.14 (15.4%), and 1.81 (12.6%) g/dl, respectively. The mean hospitalisation days for patients in the control, TXA, and TXA + LIA groups were 5.91 (SD 1.24), 5.16 (SD 0.95), and 4.51 (SD 0.71) days, respectively. The combination of TXA with LIA reduces perioperative blood loss for patients after UKA

Limiting futile therapy as part of end-of-life care in intensive care units

The debate about medical futility often involves intensive care units where life-support procedures are routinely applied. Futile therapy is part of end-of-life therapy. In the discussion about medical futility it is important to distinguish the effect of therapy from the benefit for the patient. The goal of treatment is not to maintain the function of an organ, body part or physiological activity, but to maintain health as a whole. Prolonging ineffective treatment violates the standard of good medical practice. In 2014, the first Polish guidelines on limiting futile therapy in patients treated in intensive care units were published. This document presents the official position of intensive care experts consulted by medical societies of other medical disciplines. Limitation of futile therapy by withdrawing from already used treatments or withholding new therapies does not mean that the role of medical personnel has ended. Intensive care turns into palliative care. The list of comorbidities showing a statistically significant correlation with medical futility has been refined. These include heart failure (NYHA III/IV), neoplastic disease and disseminated neoplastic process, and failure of two or more organs. The published survey results are devastating; 66-89% of intensive care nurses have provided futile treatment in their careers. Intensivists estimated that, on average, 20% of patients in intensive care units receive futile therapy. There is a need to disseminate standards and procedures related to end-of-life care in Polish intensive care units

COVID-19 in Pediatric Intensive Care Units in Poland, PAPITCO-19 Study (Polish Analysis of PICU Trends during COVID-19)

Background: Children suffering from COVID-19 constitute about 10% of the entire population infected with the virus. In most of them, we observe asymptomatic or mild courses; however, about 1% of affected children require a stay in a paediatric intensive care unit (PICU) due to the course of the disease becoming severely life-threatening. The risk of respiratory failure, as with adults, is associated with the coexistence of concomitant diseases. The aim of our study was to analyse patients admitted to PICUs due to the severe course of their SARS-CoV-2 infection. We studied epidemiological and laboratory parameters, as well as the endpoint (survival or death). Methods: A retrospective multi-centre study, the analysis covered all children with a confirmed diagnosis of SARS-CoV-2 virus infection who were admitted to PICUs in the period from November 2020 to August 2021. We studied epidemiological and laboratory parameters, as well as the endpoint (survival or death). Results: The study analysed 45 patients (0.075% of all children hospitalised in Poland due to COVID-19 at that time). Mortality calculated in the entire study group was 40% (n = 18). Statistically significant differences between the compared groups (survived and died) concerned the parameters of the respiratory system. Lung Injury Score and the Paediatric Sequential Organ Failure Assessment were used. A significant correlation between disease severity and the patient’s prognosis was shown by the liver function parameter AST (p = 0.028). During the analysis of patients requiring mechanical ventilation and assuming survival as the primary outcome, a significantly higher oxygen index on the first day of hospitalisation, lower pSOFA scores and lower AST levels (p: 0.007; 0.043; 0.020; 0.005; 0.039, respectively) were found. Conclusions: As with adults, children with comorbidities are most frequently at risk of severe SARS-CoV-2 infection. Increasing symptoms of respiratory failure, the need for mechanical ventilation and persistently high values of aspartate aminotransferase are indicators of poor prognosis

Incidence of severe critical events in paediatric anaesthesia (APRICOT): a prospective multicentre observational study in 261 hospitals in Europe

Background Little is known about the incidence of severe critical events in children undergoing general anaesthesia in Europe. We aimed to identify the incidence, nature, and outcome of severe critical events in children undergoing anaesthesia, and the associated potential risk factors. Methods The APRICOT study was a prospective observational multicentre cohort study of children from birth to 15 years of age undergoing elective or urgent anaesthesia for diagnostic or surgical procedures. Children were eligible for inclusion during a 2-week period determined prospectively by each centre. There were 261 participating centres across 33 European countries. The primary endpoint was the occurence of perioperative severe critical events requiring immediate intervention. A severe critical event was defined as the occurrence of respiratory, cardiac, allergic, or neurological complications requiring immediate intervention and that led (or could have led) to major disability or death. This study is registered with ClinicalTrials.gov, number NCT01878760. Findings Between April 1, 2014, and Jan 31, 2015, 31â127 anaesthetic procedures in 30â874 children with a mean age of 6·35 years (SD 4·50) were included. The incidence of perioperative severe critical events was 5·2% (95% CI 5·0â5·5) with an incidence of respiratory critical events of 3·1% (2·9â3·3). Cardiovascular instability occurred in 1·9% (1·7â2·1), with an immediate poor outcome in 5·4% (3·7â7·5) of these cases. The all-cause 30-day in-hospital mortality rate was 10 in 10â000. This was independent of type of anaesthesia. Age (relative risk 0·88, 95% CI 0·86â0·90; p<0·0001), medical history, and physical condition (1·60, 1·40â1·82; p<0·0001) were the major risk factors for a serious critical event. Multivariate analysis revealed evidence for the beneficial effect of years of experience of the most senior anaesthesia team member (0·99, 0·981â0·997; p<0·0048 for respiratory critical events, and 0·98, 0·97â0·99; p=0·0039 for cardiovascular critical events), rather than the type of health institution or providers. Interpretation This study highlights a relatively high rate of severe critical events during the anaesthesia management of children for surgical or diagnostic procedures in Europe, and a large variability in the practice of paediatric anaesthesia. These findings are substantial enough to warrant attention from national, regional, and specialist societies to target education of anaesthesiologists and their teams and implement strategies for quality improvement in paediatric anaesthesia. Funding European Society of Anaesthesiology