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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). 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. No patient is currently included in the study. 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. 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.

Primary percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction has traditionally been supported by unfractionated heparin, which has never been directly compared with a new anticoagulant using consistent anticoagulation and similar antiplatelet strategies in both groups. We compared traditional heparin treatment with intravenous enoxaparin in primary PCI. In a randomised open-label trial, patients presenting with ST-elevation myocardial infarction were randomly assigned (1:1) to receive an intravenous bolus of 0·5 mg/kg of enoxaparin or unfractionated heparin before primary PCI. Wherever possible, medical teams travelling in mobile intensive care units (ambulances) selected, randomly assigned (using an interactive voice response system at the central randomisation centre), and treated patients. Patients who had received any anticoagulant before randomisation were excluded. Patients and caregivers were not masked to treatment allocation. The primary endpoint was 30-day incidence of death, complication of myocardial infarction, procedure failure, or major bleeding. The main secondary endpoint was the composite of death, recurrent acute coronary syndrome, or urgent revascularisation. Analysis was by intention to treat. This trial is registered at ClinicalTrials.gov, number NCT00718471. 910 patients were assigned to treatment with enoxaparin (n=450) or unfractionated heparin (n=460). The primary endpoint occurred in 126 (28%) patients after anticoagulation with enoxaparin versus 155 (34%) patients on unfractionated heparin (relative risk [RR] 0·83, 95% CI 0·68–1·01, p=0·06). The incidence of death (enoxaparin, 17 [4%] vs heparin, 29 [6%] patients; p=0·08), complication of myocardial infarction (20 [4%] vs 29 [6%]; p=0·21), procedure failure (100 [26%] vs 109 [28%]; p=0·61), and major bleeding (20 [5%] vs 22 [5%]; p=0·79) did not differ between groups. Enoxaparin resulted in a significantly reduced rate of the main secondary endpoint (30 [7%] vs 52 [11%] patients; RR 0·59, 95% CI 0·38–0·91, p=0·015). Death, complication of myocardial infarction, or major bleeding (46 [10%] vs 69 [15%] patients; p=0·03), death or complication of myocardial infarction (35 [8%] vs 57 [12%]; p=0·02), and death, recurrent myocardial infarction, or urgent revascularisation (23 [5%] vs 39 [8%]; p=0·04) were all reduced with enoxaparin. Intravenous enoxaparin compared with unfractionated heparin significantly reduced clinical ischaemic outcomes without differences in bleeding and procedural success. Therefore, enoxaparin provided an improvement in net clinical benefit in patients undergoing primary PCI. Direction de la Recherche Clinique, Assistance Publique-Hôpitaux de Paris; Sanofi-Aventis.

Background Despite differences in time of sepsis recognition, recent studies support that early initiation of norepinephrine in patients with septic shock (SS) improves outcome without an increase in adverse effects. This study aims to investigate the relationship between 30-day mortality in patients with SS and prehospital norepinephrine infusion in order to reach a mean blood pressure (MAP) > 65 mmHg at the end of the prehospital stage. Methods From April 06th, 2016 to December 31th, 2020, patients with SS requiring prehospital Mobile Intensive Care Unit intervention (MICU) were retrospectively analysed. To consider cofounders, the propensity score method was used to assess the relationship between prehospital norepinephrine administration in order to reach a MAP > 65 mmHg at the end of the prehospital stage and 30-day mortality. Results Four hundred and seventy-eight patients were retrospectively analysed, among which 309 patients (65%) were male. The mean age was 69 ± 15 years. Pulmonary, digestive, and urinary infections were suspected among 44%, 24% and 17% patients, respectively. One third of patients (n = 143) received prehospital norepinephrine administration with a median dose of 1.0 [0.5–2.0] mg h −1 , among which 84 (69%) were alive and 38 (31%) were deceased on day 30 after hospital-admission. 30-day overall mortality was 30%. Cox regression analysis after the propensity score showed a significant association between prehospital norepinephrine administration and 30-day mortality, with an adjusted hazard ratio of 0.42 [0.25–0.70], p < 10 –3 . Multivariate logistic regression of IPTW retrieved a significant decrease of 30-day mortality among the prehospital norepinephrine group: ORa = 0.75 [0.70–0.79], p < 10 –3 . Conclusion In this study, we report that prehospital norepinephrine infusion in order to reach a MAP > 65 mmHg at the end of the prehospital stage is associated with a decrease in 30-day mortality in patients with SS cared for by a MICU in the prehospital setting. Further prospective studies are needed to confirm that very early norepinephrine infusion decreases septic shock mortality.

The Incidence of peri-intubation cardiac arrest (PICA) has been rarely assessed in the out-of-hospital setting. The objectives of this study were to assess the incidence and factors associated with PICA (cardiac arrest occurring within 15 min of intubation) in an out-of-hospital emergency setting, wherein emergency physicians perform standardized airway management using a rapid sequence intubation technique in adult patients. This was a secondary analysis of the “Succinylcholine versus Rocuronium for out-of-hospital emergency intubation” (CURASMUR) trial, which compared the first attempt intubation success rate between succinylcholine and rocuronium in adult patients requiring emergency tracheal intubation for any vital distress except cardiac arrest. Enrollment occurred from January 2014 to August 2016 in 17 French out-of-hospital emergency medical units. All operators were emergency physicians. The PICA incidence was recorded and multivariable logistic regression analysis was used to identify the factors associated with its occurrence. A total of 1226 patients were included with a mean age of 55.9 ± 19 years. PICA was recorded in 35 (2.8%) patients. Multivariable analysis indicated that the occurrence of PICA was independently associated with a body mass index (BMI) > 30 kg m2 [adjusted odds ratio (aOR) 4.85; 95% confidence interval (CI) 1.82–12.90, p = 0.02], oxygen saturation (SpO2) before intubation < 90% (aOR 3.4; 95% CI 1.50–7.60, p = 0.003), difficult intubation (defined by an Intubation Difficulty Score [IDS] > 5, [aOR 3.59; 95% CI 1.82–8.08, p = 0.02], the use of rocuronium instead of succinylcholine (aOR 2.47; 95% CI 1.08–5.64, p = 0.03), post intubation hypoxaemia (aOR 2.70; 95% CI 1.05–6.95, p = 0.04), post-intubation hypotension (aOR 4.07; 95% CI 1.62–10.22, p = 0.003), and pulmonary aspiration(aOR 4.78; 95% CI 1.48–15.36, p = 0.009). Early PICA occurred in approximately 3% of cases in the out-of-hospital setting. We identified several independent risk factors for PICA, including obesity, hypoxaemia before intubation and difficult intubation.

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.

In the prehospital setting, early identification of septic shock (SS) at risk of poor outcome is mainly based on clinical vital signs alteration evaluation. The Charlson Comorbidity Index (CCI) is an in-hospital tool used for burden of co-morbidity assessment. We report the relationship between the modified prehospital CCI, and 30-day mortality of SS patients initially cared for in the prehospital setting by a mobile ICU (MICU). SS patients defined according to the 2016 sepsis-3 conference cared for by MICU between February 2017 and December 2021 were retrospectively analysed. The modified prehospital CCI calculation was based on the available comorbid conditions collected in the prehospital setting. A threshold of ≥5, was chosen according to previous results. Five-hundred and twenty-nine patients were included among which 154 suffering from septic shock were analysed. Presumed origin of septic shock was mainly pulmonary (36%), digestive (33%) and urinary (16%). 30 day-mortality reached 33%. Logistic regression after propensity score matching found a significant association between the 30-day mortality in the modified prehospital CCI ≥ 5: aOR = 1.12 [1.07–1.31], p = 0.041. Among septic shock patients initially cared for by a MICU in the prehospital setting, a significant association between 30-day mortality. A modified prehospital CCI of at least 6 appears to be useful for early identification of septic shock patients with poorer outcome.

Purpose Respiratory dysfunction is one of the most frequent symptoms observed during sepsis reflecting hypoxemia and/or acidosis that may be assessed by the ROX index (ratio of oxygen saturation by pulse oximetry/fraction of inspired oxygen to respiratory rate). This study aimed to describe the relationship between the prehospital ROX index and 30-day mortality rate among septic shock patients cared for in the prehospital setting by a mobile intensive care unit (MICU). Methods From May 2016 to December 2021, 530 septic shock patients cared for by a prehospital MICU were retrospectively analysed. Initial ROX index value was calculated at the first contact with MICU. A Cox regression analysis after propensity score matching was performed to assess the relationship between 30-day mortality rate and a ROX index ≤ 10. Results Pulmonary, digestive and urinary sepsis were suspected among 43%, 25% and 17% patients, respectively. The 30-day overall mortality reached 31%. Cox regression analysis showed a significant association between 30-day mortality and a ROX index ≤ 10: adjusted hazard ratio of 1.54 [1.08–2.31], p  < 0.05. Conclusions During the prehospital stage of septic shock patients cared for by a MICU, ROX index is significantly associated with 30-day mortality. A prehospital ROX ≤ 10 value is associated with a 1.5-fold 30-day mortality rate increase. Prospective studies are needed to confirm the ability of prehospital ROX to predict sepsis outcome since the prehospital setting.

Background International guidelines recommend early a bundle of care to reduce sepsis mortality. Among bundle of care, antibiotic therapy is all the additionally effective when early initiated, especially for the sicker patients, i.e., those with septic shock, for whom it should be started within the first hour. This study aims to examine the impact of prehospital antibiotics administration on 30-day mortality in patients with septic shock, as defined by Sepsis-2, cared for by a prehospital mobile intensive care unit (MICU). Methods We performed a nationwide observational cohort study in France using data from May 2016 to December 2021 including septic shock patients admitted to ICU after receiving prehospital care from a MICU. An emulate retrospective randomized controlled trial using a weighted Cox proportional hazards model was conducted to compare the efficacy of prehospital antibiotic administration versus no prehospital antibiotic administration on 30-day mortality. A secondary analysis assessed the association between prehospital antibiotic administration and 30-day mortality according to presumed septic shock origin. Results Among the 530 patients analyzed, 341 (64%) were males and the mean age was 70  ±  15 years. The 30-day mortality was 31%. The presumed origins of sepsis in the prehospital setting were primarily pulmonary, digestive, and urinary, with respective percentages of 43%, 25%, and 17%, respectively. One-hundred and thirty-two patients (25%) received prehospital antibiotic therapy, a 3rd generation cephalosporin for 98 patients (18%). The inverse probability of treatment weighting analysis emulating the target trial revealed that prehospital antibiotic administration was associated with a lower risk of 30-day mortality compared with no prehospital antibiotic administration: RR = 0.64, 95%CI [0.41–0.97]. The weighted logistic regression model showed a significant association between 30-day mortality and prehospital antibiotic administration for pulmonary origin: RRa = 0.80 [0.86–0.93], urinary origin: RRa = 0.89 [0.80–0.98], and unknown origin: RRa = 0.94 [0.86–0.99]. Conclusion The prehospital antibiotics administration is associated with a reduced risk of 30-day mortality among patients suffering from septic shock cared for by a prehospital MICU. The prehospital antibiotic treatment effect differs according to septic shock origin. However, prospective studies are necessary to validate these preliminary findings and to assess the supplementary effects of the bundle of care components.

Background Septic shock may occur in the prehospital setting requiring a prehospital mobile intensive care unit (MICU) intervention. The prehospital MICU is equipped to deliver antibiotics and hemodynamic optimization on scene in order to implement effective treatment measures within the initial hour. The study objective is to assess the relationship between the duration of prehospital care and 30‐day mortality among patients with septic shock who received MICU prehospital antibiotic and norepinephrine administration. Methods From 2016, May, to 2021, March, patients with septic shock managed by a prehospital MICU of nine French hospital centers were retrospectively analyzed. Multivariate logistic regression and propensity score analysis with the inverse probability weighting (IPTW) method were used to assess the association between prehospital care duration and 30‐day mortality. Results Five‐hundred and thirty patients were analyzed among which 341 (64%) were males, and the mean age was 70 ± 15 years old. The 3 main presumed sepsis origins were pulmonary, digestive, and urinary for 43%, 25%, and 17% of the patients, respectively. One‐hundred and thirty‐two patients (25%) received prehospital antibiotic and 155 (29%) norepinephrine administration with a median dose of 1.0 [0.5–2.0] mg.h−1 within the first prehospital hour. The 30‐day mortality was 31%. The mean prehospital care duration was 71 ± 34 min. Multivariate logistic regression analysis revealed an association between prehospital care duration and 30‐day mortality rate: adjusted odds ratio (aOR) = 1.01 [1.00–1.02], p = 0.017. Multivariate logistic regression adjusted on the same potential confounders reported an association between prehospital care duration < 60 min and 30‐day mortality: aOR = 0.64 [0.41–0.99], p = 0.044. Log binomial regression weighted with the IPTW revealed an association between prehospital care duration < 60 min and 30‐day mortality: aOR = 0.56 [0.46–0.67], p < 10−3. Conclusion The present study reports the association between prehospital care duration and 30‐day mortality among septic shock patients who received MICU prehospital antibiotic and norepinephrine administration.

Guidelines on sepsis management recommend early recognition, diagnosis and treatment, especially early antibiotic therapy (ABT) administration in order to reduce septic shock (SS) mortality. However, the adequacy of probabilistic prehospital ABT remains unknown. From May 2016 to March 2021, all consecutive patients with SS cared for by a prehospital mICU intervention were retrospectively analyzed. Among 386 patients retrospectively analyzed, 119 (33%) received probabilistic prehospital ABT, among which 74% received a 3rd generation cephalosporin: 31% cefotaxime and 42% ceftriaxone. No patient had a serious adverse effect related to ABT administration. Overall mortality rate on day-30 was 29%. Among the 119 patients with prehospital ABT, bacteriological identification was obtained for 81 (68%) patients with adequate prehospital ABT for 65 patients (80%) of which 10 (15%) deceased on day-30. Conversely, among the 16 (20%) patients with inadequate prehospital ABT, 9 patients (56%) were deceased on day-30. Prehospital adequate ABT was significantly different between alive and deceased patients on day-30 (p = 4.10−3). After propensity score matching, a significant association between adequate prehospital ABT administration and day-30 mortality was observed (aOR = 0.09 [0.01–0.47]). Inverse probability treatment weighting with multivariable logistic regression reported a day-30 mortality decrease in the adequate prehospital ABT group: aOR = 0.70 [0.53–0.93]. Among SS cared for by a mICU, probabilistic prehospital ABT is adequate most of the time and associated with a day-30 mortality decrease. Further prospective studies are needed to confirm these results and the weight of prehospital ABT in the prehospital bundle of care for SS.