The chain of survival and rehabilitation for sepsis: concepts and proposals for healthcare trajectory optimization.

This article describes the structures and processes involved in healthcare delivery for sepsis, from the prehospital setting until rehabilitation. Quality improvement initiatives in sepsis may reduce both morbidity and mortality. Positive outcomes are more likely when the following steps are optimized: early recognition, severity assessment, prehospital emergency medical system activation when available, early therapy (antimicrobials and hemodynamic optimization), early orientation to an adequate facility (emergency room, operating theater or intensive care unit), in-hospital organ failure resuscitation associated with source control, and finally a comprehensive rehabilitation program. Such a trajectory of care dedicated to sepsis amounts to a chain of survival and rehabilitation for sepsis. Implementation of this chain of survival and rehabilitation for sepsis requires full interconnection between each link. To date, despite regular international recommendations updates, the adherence to sepsis guidelines remains low leading to a considerable burden of the disease. Developing and optimizing such an integrated network could significantly reduce sepsis related mortality and morbidity.

Glycaemic Effects of a 156-km Ultra-trail Race in Athletes: An Observational Field Study.

BACKGROUND: Ultra-trail running races pose appreciable physiological challenges, particularly for glucose metabolism. Previous studies that yielded divergent results only measured glycaemia at isolated times. OBJECTIVES: We aimed to explore the impact of an ultra-endurance race on continuously measured glycaemia and to understand potential physiological mechanisms, as well as the consequences for performance and behavioural alertness. METHODS: Fifty-five athletes (78% men, 43.7 ± 9.6 years) ran a 156-km ultra-trail race (six 26-km laps, total elevation 6000 m). Participants wore a masked continuous glucose monitoring sensor from the day before the race until 10 days post-race. Blood was taken at rest, during refuelling stops after each lap, and after 24-h recovery. Running intensity (% heart rate reserve), performance (lap times), psychological stress, and behavioural alertness were explored. Linear mixed models and logistic regressions were carried out. RESULTS: No higher risk of hypo- or hyperglycaemia was observed during the exercise phases of the race (i.e. excluding stops for scientific measurements and refuelling) compared with resting values. Laps comprising a greater proportion of time spent at maximal aerobic intensity were nevertheless associated with more time > 180 mg/dL (P = 0.021). A major risk of hyperglycaemia appeared during the 48-h post-race period compared with pre-race (P < 0.05), with 31.9% of the participants spending time with values > 180 mg/dL during recovery versus 5.5% during resting. Changes in circulating insulin, cortisol, and free fatty acids followed profiles comparable with those usually observed during traditional aerobic exercise. However, creatine phosphokinase, and to a lesser extent lactate dehydrogenase, increased exponentially during the race (P < 0.001) and remained high at 24-h post-race (P < 0.001; respectively 43.6 and 1.8 times higher vs. resting). Glycaemic metrics did not influence physical performance or behavioural alertness. CONCLUSION: Ultra-endurance athletes were exposed to hyperglycaemia during the 48-h post-race period, possibly linked to muscle damage and inflammation. Strategies to mitigate muscle damage or subsequent inflammation before or after ultra-trail races could limit recovery hyperglycaemia and hence its related adverse health consequences. TRIAL REGISTRATION NUMBER: NCT05538442 2022-09-21 retrospectively registered.

RELATIONSHIP BETWEEN SHOCK INDEX, MODIFIED SHOCK INDEX, AND AGE SHOCK INDEX AND 28-DAY MORTALITY AMONG PATIENTS WITH PREHOSPITAL SEPTIC SHOCK.

BACKGROUND: A relative hypovolemia occurs during septic shock (SS); the early phase is clinically reflected by tachycardia and low blood pressure. In the prehospital setting, simple objective tools to assess hypovolemia severity are needed to optimize triaging. OBJECTIVE: The aim of this study was to evaluate the relationship between shock index (SI), diastolic SI (DSI), modified SI (MSI), and age SI (ASI) and 28-day mortality of patients with SS initially cared for in a prehospital setting of a mobile intensive care unit (MICU). METHODS: From April 6, 2016 through December 31, 2021, 530 patients with SS cared for at a prehospital MICU were analyzed retrospectively. Initial SI, MSI, DSI, and ASI values, that is, first measurement after MICU arrival to the scene were calculated. A propensity score analysis with inverse probability of treatment weighting (IPTW) method was used to assess the relationship between SI, DSI, MSI, and ASI and 28-day mortality. RESULTS: SS resulted mainly from pulmonary, digestive, and urinary infections in 44%, 25%, and 17% of patients. The 28-day overall mortality was 31%. IPTW propensity score analysis indicated a significant relationship between 28-day mortality and SI (adjusted odds ratio [aOR] 1.13; 95% CI 1.01-1.26; p = 0.04), DSI (aOR 1.16; 95% CI 1.06-1.34; p = 0.03), MSI (aOR 1.03; 95% CI 1.01-1.17; p = 0.03), and ASI (aOR 3.62; 95% CI 2.63-5.38; p < 10-6). CONCLUSIONS: SI, DSI, MSI, and ASI were significantly associated with 28-day mortality among patients with SS cared for at a prehospital MICU. Further studies are needed to confirm the usefulness of SI and SI derivates for prehospital SS optimal triaging.

The prehospital NEW score to assess septic shock in-hospital, 30-day and 90-day mortality.

BACKGROUND: The early identification of sepsis presenting a high risk of deterioration is a daily challenge to optimise patient pathway. This is all the most crucial in the prehospital setting to optimize triage and admission into the appropriate unit: emergency department (ED) or intensive care unit (ICU). We report the association between the prehospital National Early Warning Score 2 (NEWS-2) and in-hospital, 30 and 90-day mortality of SS patients cared for in the pre-hospital setting by a mobile ICU (MICU). METHODS: Septic shock (SS) patients cared for by a MICU between 2016, April 6th and 2021 December 31st were included in this retrospective cohort study. The NEWS-2 is based on 6 physiological variables (blood pressure, heart rate, respiratory rate, temperature, oxygen saturation prior oxygen supplementation, and level of consciousness) and ranges from 0 to 20. The Inverse Probability Treatment Weighting (IPTW) propensity method was applied to assess the association with in-hospital, 30 and 90-day mortality. A NEWS-2 ≥ 7 threshold was chosen for increased clinical deterioration risk definition and usefulness in clinical practice based on previous reports. RESULTS: Data from 530 SS patients requiring MICU intervention in the pre-hospital setting were analysed. The mean age was 69 ± 15 years and presumed origin of sepsis was pulmonary (43%), digestive (25%) or urinary (17%) infection. In-hospital mortality rate was 33%, 30 and 90-day mortality were respectively 31% and 35%. A prehospital NEWS-2 ≥ 7 is associated with an increase in-hospital, 30 and 90-day mortality with respective RRa = 2.34 [1.39-3.95], 2.08 [1.33-3.25] and 2.22 [1.38-3.59]. Calibration statistic values for in-hospital mortality, 30-day and 90-day mortality were 0.54; 0.55 and 0.53 respectively. CONCLUSION: A prehospital NEWS-2 ≥ 7 is associated with an increase in in-hospital, 30 and 90-day mortality of septic shock patients cared for by a MICU in the prehospital setting. Prospective studies are needed to confirm the usefulness of NEWS-2 to improve the prehospital triage and orientation to the adequate facility of sepsis.

Influence of antibiotic therapy with hemodynamic optimization on 30-day mortality among septic shock patients cared for in the prehospital setting.

BACKGROUND: In order to reduce septic shock mortality, international guidelines recommend early treatment implementation, antibiotic therapy (ABT) and hemodynamic optimisation, within 1-h. This retrospective multicentric study aims to investigate the relationship between prehospital ABT delivered within 1st hour and mean blood pressure (MAP) ≥ 65 mmHg at the end of the prehospital stage, and 30-day mortality among patients with septic shock. METHODS: From May 2016 to December 2021, patients with septic shock requiring pre-hospital Mobile Intensive Care Unit intervention (MICU) were retrospectively analysed. To assess the relationship between 30-day mortality and prehospital ABT delivered within 1st hour and/or MAP ≥ 65 mmHg at the end of the prehospital stage, Inverse Probability Treatment Weighting (IPTW) propensity score method was performed. RESULTS: Among the 530 patients included, 341 were male gender (64%) with a mean age of 69 ± 15 years. One-hundred and thirty-two patients (25%) patients received prehospital ABT, among which 98 patients (74%) were treated with 3rd generation cephalosporin. Suspected pulmonary, urinary and digestive infections were the cause of sepsis in respectively 43%, 25% and 17%. The 30-day overall mortality was 31%. A significant association was observed between 30-day mortality rate and (i) ABT administration within the first hour: RRa = 0.14 [0.04-0.55], (ii) ABT administration within the first hour associated with a MAP ≥ 65 mmHg: RRa = 0.08 [0.02-0.37] and (iii) ABT administration within the first hour in the prehospital setting associated with a MAP < 65 mmHg at the end of the prehospital stage: RRa = 0.75 [0.45-0.85]. Patients who received prehospital ABT after the first hour have also a 30-day mortality rate decrease: RRa = 0.87 [0.57-0.99], whereas patients who did not received ABT had an increased 30-day mortality rate: RRa = 2.36 [1.89-2.95]. CONCLUSION: In this study, we showed that pre-hospital ABT within the first hour and MAP≥65 mmHg at the end of prehospital stage are both associated with 30-day mortality decrease among patients suffering from septic shock cared for by a MICU. Further prospective studies are needed to confirm these preliminary results.

Vestibular disorders following BNT162b2 mRNA COVID-19 vaccination: A retrospective case series.

BACKGROUND: There are few publications regarding manifestations of vestibular disorders (VDs) following BNT162b2 mRNA COVID-19 vaccination. PURPOSE: We describe cases of VD potentially related to BNT162b2 vaccination and calculate its reporting rate, in order to enlarge knowledge about this adverse effect. METHODS: A retrospective analysis of cases of VD following BNT162b2 vaccination reported to the pharmacovigilance centre of Georges-Pompidou European Hospital (France), in 2021 was performed. In order to identify these cases from the pharmacovigilance database containing all our registered cases, we used the Standardised MedDRA Query (SMQ) 'vestibular disorders'. Then we analysed cases with vestibular symptoms, based on the association of typical manifestations. The reporting rate was calculated based on the number of VD cases and the number of vaccinated patients. RESULTS: Among 6608 cases reported to our centre related to COVID-19 vaccines during 2021, 34 VDs associated with BNT162b2 administration were included. They were mainly reported in females (79%), 62% occurred after the first dose and 32% were serious. Symptoms had completely resolved in 13 cases (38%). Vertigo was the most common symptom followed by balance disorders. Three patients received second dose without reappearance of VD. The final diagnosis was reported in 10 patients (six cases of vestibular neuritis, two cases of central VD, two cases of benign paroxysmal positional vertigo). The regional reporting rate was 26 [95% CI: 17-34] cases of VD per 1 million persons vaccinated. CONCLUSION: Although the relationship between vaccination and VD cannot be established, clinicians should be aware of this rare adverse effect.

Prehospital pulse pressure and mortality of septic shock patients cared for by a mobile intensive care unit.

BACKGROUND: Septic shock medical treatment relies on a bundle of care including antibiotic therapy and hemodynamic optimisation. Hemodynamic optimisation consists of fluid expansion and norepinephrine administration aiming to optimise cardiac output to reach a mean arterial pressure of 65mmHg. In the prehospital setting, direct cardiac output assessment is difficult because of the lack of invasive and non-invasive devices. This study aims to assess the relationship between 30-day mortality and (i) initial pulse pressure (iPP) as (ii) pulse pressure variation (dPP) during the prehospital stage among patients cared for SS by a prehospital mobile intensive care unit (MICU). METHODS: From May 09th, 2016 to December 02nd, 2021, septic shock patients requiring MICU intervention were retrospectively analysed. iPP was calculated as the difference between systolic blood pressure (SBP) and diastolic blood pressure (DBP) at the first contact between the patient and the MICU team prior to any treatment and, dPP as the difference between the final PP (the difference between SBP and DBP at the end of the prehospital stage) and iPP divided by prehospital duration. To consider cofounders, the propensity score method was used to assess the relationship between (i) iPP < 40mmHg, (ii) positive dPP and 30-day mortality. RESULTS: Among the 530 patients analysed, pulmonary, digestive, and urinary infections were suspected among 43%, 25% and 17% patients, respectively. The 30-day overall mortality rate reached 31%. Cox regression analysis showed an association between 30-day mortality and (i) iPP < 40mmHg; aHR of 1.61 [1.03-2.51], and (ii) a positive dPP; aHR of 0.56 [0.36-0.88]. CONCLUSION: The current study reports an association between 30-day mortality rate and iPP < 40mmHg and a positive dPP among septic shock patients cared for by a prehospital MICU. A negative dPP could be helpful to identify septic shock with higher risk of poor outcome despite prehospital hemodynamic optimization.

Trends in survival from out-of-hospital cardiac arrest with a shockable rhythm and its association with bystander resuscitation: a retrospective study.

OBJECTIVE: Over 300 000 cases of out-of-hospital cardiac arrests (OHCAs) occur each year in the USA and Europe. Despite decades of investment and research, survival remains disappointingly low. We report the trends in survival after a ventricular fibrillation/pulseless ventricular tachycardia OHCA, over a 13-year period, in a French urban region, and describe the simultaneous evolution of the rescue system. METHODS: We investigated four 18-month periods between 2005 and 2018. The first period was considered baseline and included patients from the randomised controlled trial 'DEFI 2005'. The three following periods were based on the Paris Sudden Death Expertise Center Registry (France). Inclusion criteria were non-traumatic cardiac arrests treated with at least one external electric shock with an automated external defibrillator from the basic life support team and resuscitated by a physician-staffed ALS team. Primary outcome was survival at hospital discharge with a good neurological outcome. RESULTS: Of 21 781 patients under consideration, 3476 (16%) met the inclusion criteria. Over all study periods, survival at hospital discharge increased from 12% in 2005 to 25% in 2018 (p<0.001), and return of spontaneous circulation at hospital admission increased from 43% to 58% (p=0.004).Lay-rescuer cardiopulmonary resuscitation (CPR) and telephone CPR (T-CPR) rates increased significantly, but public defibrillator use remained limited. CONCLUSION: In a two-tiered rescue system, survival from OHCA at hospital discharge doubled over a 13-year study period. Concomitantly, the system implemented an OHCA patient registry and increased T-CPR frequency, despite a consistently low rate of public defibrillator use.

Factors Influencing Anti-Xa Assays: A Multicenter Prospective Study in Critically Ill and Noncritically Ill Patients Receiving Unfractionated Heparin.

BACKGROUND: The presence of dextran sulfate (DS) in reagents and the type of blood collection tube (citrate/citrated-theophylline-adenosine-dipyridamole [CTAD]) can lead to discrepancies between unfractionated heparin (UFH) anti-Xa levels. OBJECTIVES: To evaluate the extent of the effect (1) of different reagents containing or not containing DS and (2) of the blood collection tubes, on UFH anti-Xa levels, in various clinical situations (NCT04700670). METHODS: We prospectively included patients from eight centers: group (G)1, cardiopulmonary bypass (CPB) after heparin neutralization (n = 39); G2, cardiothoracic intensive care unit (ICU) after CPB (n = 35); G3, medical ICU (n = 53); G4, other medical inpatients (n = 38). Blood was collected into citrated and CTAD tubes. Chromogenic anti-Xa assays were centrally performed, using seven reagent/analyzer combinations including two without DS. The association between anti-Xa levels and covariates was tested using a linear mixed-effects model. RESULTS: We analyzed 4,546 anti-Xa values from 165 patients. Median anti-Xa levels were systematically higher with reagents containing DS, whatever the patient group, with the greatest effect observed in G1 (0.32 vs. 0.05 IU/mL). Anti-Xa levels were slightly higher in CTAD than in citrate samples, irrespective of the assay. The model showed: (1) a significant dextran-patient group interaction (p < 0.0001), the effect of DS on anti-Xa levels varying from 30.9% in G4 to 296% in G1, and (2) a significant effect of CTAD, varying between patient groups (p = 0.0302). CONCLUSION: The variability of anti-Xa levels with a great overestimation of the values, using a reagent containing DS, can lead to different treatment decisions, especially after heparin neutralization by protamine. Clinical consequences of these differences remain to be demonstrated.

Evaluation of the effectiveness of potassium chloride in the management of out-of hospital cardiac arrest by refractory ventricular fibrillation: Study protocol of the POTACREH study.

PURPOSE: Out-of-hospital cardiac arrest (OHCA) has a poor prognosis, with an overall survival rate of about 5% at discharge. Shockable rhythm cardiac arrests (ventricular fibrillation (VF) and pulseless ventricular tachycardia (VT)) have a better prognosis. In case of shockable rhythm, treatment is based on defibrillation, and thereafter, in case of failure of 3 external electric shocks (EES), on direct intravenous administration of 300 mg amiodarone, or lidocaine when amiodarone is unavailable or inefficient. During surgical procedures under extracorporeal circulation, a high potassium cardioplegia solution is administered to interrupt cardiac activity and facilitate surgical procedure. By extension, direct intravenous administration of potassium chloride (KCl) has been shown to convert VF, resulting in return to a hemodynamically efficient organized heart rate within a few minutes. The aim of this study is to provide clinical evidence that direct intravenous injection of KCl, into a patient presenting with OHCA due to refractory VF although 3 EES, should interrupt this VF and then allow rapid restauration of an organized heart rhythm, and thus return of spontaneous circulation (ROSC). METHODS: A multicenter, prospective, single group, phase 2 study will be conducted on 81 patients presenting with refractory VF. After failure of 3 EES, each patient will receive direct intravenous injection of 20 mmol KCl instead of amiodarone. The primary outcome will be survival rate at hospital admission. Major secondary outcomes will include ROSC and time to ROSC in the prehospital setting, number of VF recidivism after KCl injection, survival rate at hospital discharge with a good neurologic prognostic, and survival rate 3 months after hospital discharge with a good neurologic prognostic. RESULTS: No patient is currently included in the study. DISCUSSION: Conventional guideline strategy based on antiarrhythmic drug administration, i.e. amiodarone or lidocaine, for OHCA due to shockable rhythm, has not yet demonstrated an increase in survival at hospital admission or at hospital discharge. This may be related to the major cardiodepressant effect of those drugs. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04316611. Registered on March 2020. AP-HP180577 / N° EUDRACT: 2019-002544-24. Funded by the French Health Ministry. https://clinicaltrials.gov/ct2/show/NCT04316611.