Background. Sequestration of vancomycin in ST® filters used in continuous renal therapy is a pending question. Direct vancomycin-ST® interaction was assessed using the in vitro NeckEpur® technology. Method. ST150® filter and Prismaflex dialyzer, Baxter-Gambro, were used. Two modes were assessed in duplicate: (i) continuous diafiltration (CDF): 4 L/h, (ii) continuous dialysis (CD): 2.5 L/h post-filtration. Results. The mean initial vancomycin concentration in the central compartment (CC) was 51.4 +/− 5.0 mg/L. The mean percentage eliminated from the CC over 6 h was 91 +/− 4%. The mean clearances from the CC by CDF and CD were 2.8 and 1.9 L/h, respectively. The mean clearances assessed using cumulative effluents were 4.4 and 2.2 L/h, respectively. The mean percentages of the initial dose eliminated in the effluents from the CC by CDF and CD were 114 and 108% with no detectable sequestration of vancomycin in both modes of elimination. Discussion. Significant sequestration adds a clearance to that provided by CDF and CD. The study provides multiple evidence from the CC, the filter, and the effluents of the lack of an increase in total clearance in comparison with the flow rates without significant sequestration in the ST® filter comparing cumulative effluents to the initial dose in the CC. Conclusions. There is no evidence ST® filters directly sequestrate vancomycin.

Objective Septic shock results in a decreased blood pressure (BP) leading to organ failure. The haemodynamic resuscitation aims at restoring the BP to allow efficient tissue perfusion. The aim of the present study was to evaluate the association between the mean BP (MBP) reached after haemodynamic resuscitation in patients with septic shock cared for in the prehospital setting by a mobile intensive care unit (MICU) and mortality at 28 days after intensive care unit (ICU) admission. Methods Patients with septic shock managed by a mobile intensive care unit (MICU) and admitted in the ICU were retrospectively analysed. The association between mortality and MBP after prehospital resuscitation was studied. Results A total of 85 patients with septic shock were included in the study. The origin of sepsis was mainly pulmonary (64%). Mortality reached 35%. Haemodynamic resuscitation was performed using crystalloids (98%) with a mean infused volume indexed on a body weight of 16±11 mL kg−1 in the prehospital setting. No patient received catecholamine or antibiotic prior to hospital admission. Final prehospital MBP was 64±8 mm Hg in the overall population and 66±8 mm Hg versus 62±8 mm Hg in alive and deceased patients, respectively (p=0.02). After adjustment, final prehospital MBP [odds ratio adjusted (ORa) (95% confidence interval (CI)]=0.89 (0.80–0.99), MBP <65 mmHg [ORa (95% CI)=14.3 (3.35–77.7)] and MBP >65 mmHg [ORa (95% CI)=0.06 (0.01–0.25)] were associated with mortality. Conclusion Persistent low MBP after prehospital initial resuscitation measures in patients with septic shock managed in the prehospital setting is associated with increased mortality. Further studies are needed to evaluate the impact of prehospital haemodynamic management in septic shock to further optimise prehospital care and improve outcome.

Introduction: In continuous renal replacement therapy, conduction and convection are controlled allowing prescribing dosage regimen improving survival. In contrast, adsorption is an uncontrolled property altering drug disposition. Whether adsorption depends on flowrates is unknown. We hypothesized an in vitro model may provide information in conditions mimicking continuous renal replacement therapy in humans. Methods: ST150(R)-AN69 filter and Prismaflex dialyzer, Baxter-Gambro were used. Simulated blood flowrate was set at 200 mL/min. The flowrates in the filtration (continuous filtration), dialysis (continuous dialysis), and diafiltration (continuous diafiltration) were 1500, 2500, and 4000 mL/h, respectively. Routes of elimination were assessed using NeckEpur(R) analysis. Results: The percentages of the total amount eliminated by continuous filtration, continuous dialysis, and continuous diafiltration were 82%, 86%, and 94%, respectively. Elimination by effluents and adsorption accounted for 42% +/- 7% and 58% +/- 5%, 57% +/- 7% and 43% +/- 6%, and 84% +/- 6% and 16% +/- 6% of amikacin elimination, respectively. There was a linear regression between flowrates and amikacin clearance: Y = 0.6 X +/- 1.7 (R-2 = 0.9782). Conversely, there was a linear inverse correlation between the magnitude of amikacin adsorption and flowrate: Y = -16.9 X +/- 84.1 (R-2 = 0.9976). Conclusion: Low flowrates resulted in predominant elimination by adsorption, accounting for 58% of the elimination of amikacin from the central compartment in the continuous filtration mode at 1500 mL/h of flowrate. Thereafter, the greater the flowrate, the lower the adsorption of amikacin in a linear manner. Flowrate is a major determinant of adsorption of amikacin. There was an about 17% decrease in the rate of adsorption per increase in the flowrate of 1 L/min.

CONTEXT:In the prehospital setting, early identification of septic shock (SS) with high risk of poor outcome is a daily issue. There is a need for a simple tool aiming to early assess outcome in order to decide delivery unit (emergency department (ED) or intensive care unit (ICU)). In France, prehospital emergencies are managed by the Service d'Aide Médicale d'Urgence (SAMU). The SAMU physician decides the destination ward either to the ICU or to the ED after on scene severity assessment. We report the association between The Prehospital Shock Precautions on Triage (PSPoT) score, and in-hospital mortality of SS patients initially cared for in the prehospital setting by a mobile ICU (MICU). METHODS:SS patients cared for by MICU were prospectively included between February 2017 and July 2019. The PSPoT score was established by adding shock index>1 and criterion based on past medical history: age >65 years and at least 1 previous comorbidity (chronic cardiac failure, chronic renal failure, chronic obstructive pulmonary disease, previous or actual history of cancer, institutionalization, hospitalisation within previous 3 months. A threshold of ≥2, was arbitrarily chosen for clinical relevance and usefulness in clinical practice. RESULTS:One-hundred and sixty-nine with a median age of 72 [20-93] years were analysed. SS origin was mainly pulmonary (54%), abdominal (19%) and urinary (15%). The median PSPoT score was 2 [1-2]. PSPoT score and PSPoT score ≥ 2 were associated with in-hospital mortality: OR = 1.24 [0.77-2.05] and OR = 2.19 [1.09-4.59] respectively. CONCLUSION:We report an association between PSPoT score, and in-hospital mortality of SS patients cared for by a MICU. A PSPoT score ≥ 2 early identifies poorer outcome.

Objective: The objective of this study was to assess the association of early pupil evaluation with death occurrence on Day 28 in patients with refractory out-of-hospital cardiac arrest (ROHCA) admitted to the intensive care unit (ICU) and treated by extra-corporeal cardiopulmonary resuscitation (eCPR). Methods: The pupil size (miosis, intermediary or mydriasis) and bilateral pupillary light reactivity (present or absent) were monitored in sedated and paralysed patients treated by eCPR. Mortality was assessed on Day 28. Results: A total of 46 consecutive patients with ROHCA were included in the study. Thirty (65%) patients died on Day 28. Twenty-seven (90%) patients had pupils non-reactive to light, and 18 (60%) had mydriasis at the ICU admission. Using logistic regression, including age, gender, no flow, low-flow, size and pupil reactivity to light, only the pupillary reactivity to light remained associated with death on Day 213 (Odds ratio=0.12, 95%CI= [0.0 1-0.96]). Conclusion: Pupils not reacting to light at the ICU admission were associated with mortality on Day 213 in patients with ROHCA. Pupillary light reactivity is a simple and easy tool that can be used to early detect a poor outcome in patients with ROHCA treated by eCPR.

To specify whether an association exists between pre-hospital body temperature collected by the emergency medical services (EMS) call centre, and intensive care unit (ICU) admission of patients with septic shock. An observational study based on data collected by the EMS of Paris. All septic shocks were included. Among, the 140 calls concerning septic shock, 22 patients (16%) were admitted to ICU. The mean core temperature was 37.4±1.6°C for ICU and 38.6±1.1°C (p<4.10^-5) for non-ICU patients. Using propensity score analysis, the relative risk for ICU admission of patients with pre-hospital fever or hypothermia was 0.31 and 2 respectively. The study highlights the potential usefulness of early temperature measurement in septic shock patients to allow early proper orientation.

Background: The aim of the present study is to describe the prevalence of NPS and conventional DOA in Paris and its suburbs over a six-year period using hair testing approach. Method: Hair was sampled in patients admitted to different departments of Paris hospitals between 2012 and 2017. Two high-risk populations were mainly considered: 1) drug-dependent and 2) acutely intoxicated patients. Segmental hair analysis was performed by validated LC-MS/MS method to screen for DOA and 83 NPS. Results: 480 patients (280 M/200 F, 15-70 years) were included. 141 patients tested positive for NPS (99 M/42 F; median age: 33). NPS prevalence was 29%, that of amphetamines, cocaine and opioids were 32%, 38.5% and 52%, respectively. 27 NPS were identified, 4-MEC and mephedrone (number of cases n = 24 each) were the most detected cathinones. JWH-122 (n = 1) was the only detected synthetic cannabinoid while ketamine (n = 104) was present in numerous NPS users (67%). 3-fluorofentanyl (n = 1), furanylfentanyl (n = 1), N-ethylpentylone (n = 2), pentedrone (n = 2), mexedrone (n = 1), methcathinone (n = 3), 6-APDB (n = 2), TFMPP (n = 2), 2-CE (n = 1), 3,4-MD-alpha PHP (n = 1) and dextromethorphan (n = 27) were identified for the first time in hair. Users were found to have more than one NPS in 53% of cases, mostly in combination with conventional DOA. The number of detected NPS rose from 5 in 2012 to 42 in 2017. A broad range of hair concentrations (0.001-318 ng/mg) was found, but the low median concentrations seem to show an occasional exposure more than chronic use. Conclusion: NPS screening should be assessed in routine clinical practice, especially in high-risk populations.

Objective: Mechanical ventilation can help improve the prognosis of septic shock. While adequate delivery of oxygen to the tissue is crucial, hyperoxemia may be deleterious. Invasive out-of-hospital ventilation is often promptly performed in life-threatening emergencies. We propose to determine whether the arterial oxygen pressure (PaO2) at the intensive care unit (ICU) admission is associated with mortality in patients with septic shock subjected to pre-hospital mechanical ventilation. Methods: We performed a monocentric retrospective observational study on 77 patients. PaO2 was measured at ICU admission. The primary outcome was mortality at day 28 (D28). Results: Forty-nine (64%) patients were included. The mean PaO2 at ICU admission was 153 +/- 77 and 202 +/- 82 mm Hg for alive and deceased patients respectively. Mortality concerned 18% of patients for PaO2 < 100, 25% for 100 < PaO2 < 150 and 57% for a PaO2 > 150mm Hg. PaO2 was significantly associated with mortality at D28 (p = 0.04). Using propensity score analysis including SOFA score, pre-hospital duration, lactate, and prehospital fluid volume expansion, association with mortality at D28 only remained for PaO2 > 150 mm Hg (p = 0.02, OR [CI95] = 1.59 [1.20-2.10]). Conclusions: In this study, we report a significant association between hyperoxemia at ICU admission and mortality in patients with septic shock subjected to pre-hospital invasive mechanical ventilation. The early adjustment of the PaO2 should be considered for these patients to avoid the toxic effects of hyperoxemia. However, blood gas analysis is hard to get in a pre-hospital setting. Consequently, alternative and feasible measures are needed, such as pulse oximetry, to improve the management of pre-hospital invasive ventilation. (C) 2018 Elsevier Inc. All rights reserved.

OBJECTIVE:The outcome of sepsis relies on the early diagnosis and implementation of appropriate treatments. For management of out-of-hospital patients with sepsis, prehospital emergency services, named Service d'Aide Médicale d'Urgence (SAMU) in France, dispatch to the scene an emergency mobile team (EMT) or a mobile intensive care unit (MICU) based on the patient's severity. Therefore, patients are admitted to the emergency department (ED) or to the intensive care unit (ICU). The impact of MICU intervention on patient's prognosis remains unclear. The aim of the present study was to describe the impact of MICU intervention on mortality on day 28 (D28) of patients with sepsis. METHODS:We performed a retrospective study on patients with sepsis managed by prehospital teams, MICU or EMT, before admission to the ED or ICU. The primary outcome was mortality on D28. RESULTS:The SAMU received 30,642 calls during the study period with 140 patients with suspected sepsis. The suspected origin of sepsis was mainly pulmonary for 78 (55%) patients. Thirteen (9%) patients died on D28, 12 in the ED and 1 in the ICU. Two patients were admitted to the hospital by a MICU. After adjusting for confounding factors, the relative risk of mortality on D28 for patients admitted to the hospital by a MICU was 0.40. CONCLUSION:We describe an association between MICU intervention and mortality on D28. MICU intervention for out-of-hospital patients with sepsis is associated with 60% reduced mortality on D28. Larger studies are needed to confirm the impact of the intervention of MICU on mortality of patients with sepsis.

Background: Mechanical ventilation can cause deleterious effects on the lung and thus alter patient's prognosis. The aim of this study was to describe the characteristics of prehospital mechanical ventilation in patients with septic shock requiring mechanical ventilation in the prehospital setting. Methods: Patients with septic shock subjected to pre-hospital intubation and mechanical ventilation by a mobile intensive care unit were consecutively included and retrospectively analysed. Septic shock was defined according to the international sepsis-3 consensus conference. Patient's characteristics, interventions, prehospital ventilatory parameters and outcome were retrieved from medical records. The association between the tidal volume indexed on ideal body weight (VTIBW) and mortality at day 28 was evaluated. Results: Fifty-nine patients were included. Septic shock was mainly associated with pulmonary (64%) infection. Mean pre-hospital VTIBW was 7 +/- 1 ml.kg(-1) in the overall population. Mortality reached 42%. The AUC of VTIBW was 0.83 [0.72-0.94]. Using logistic regression model including: age, prehospital mean blood pressure, volume infused in the prehospital setting, FiO(2) and length of stay in the intensive care unit, the association with mortality remained significant for VTIBW (OR adjusted [CI95] = 4.11 [1.89-10.98]), VTIBW >8 ml.kg(-1) (OR adjusted [CI95] = 8.29 [2.35-34.98]) and VTIBW <8 ml.kg(-1) (OR adjusted [CI95] = 0.12 [0.03-0.43]). Conclusion: In this retrospective study, we observed an association between mortality at day 28 and prehospital VTIBW in pre-hospital mechanically ventilated patients with septic shock. A VTIBW <8 ml.kg(-1) was associated with a decrease and a VTIBW >8 ml.kg(-1) with an increase in mortality. (C) 2019 Elsevier Inc. All rights reserved.

OBJECTIVE:Cardiac arrest (CA) resuscitation is associated with an 'ischaemia-reperfusion' syndrome characterised by lactic acidosis as assessed by lactate and base deficit (BD). Both biomarkers are usually measured in patients suffering from refractory CA (RCA) subjected to extracorporeal life support (ECLS) to evaluate tissue reperfusion. However, their prognostic value has never been compared. The aim of the present study was to compare the prognostic value of both biomarkers measured at 0 and 3 h after the initiation of ECLS in patients with RCA on mortality.METHODS:Patients who were admitted to the intensive care unit with RCA were consecutively included in the study.RESULTS:Sixty-six patients were included. Lactate correlated with BD (R2=0.44, p<0.001). An area under the curve of 0.72 (95% confidence interval (CI) 0.59-0.84) was found for lactate and of 0.60 (95% CI 0.46-0.73) for BD. Using multivariable logistic regression, lactate (odds ratio (OR) 1.22, 95% CI 1.03-1.48) remained associated with mortality on day 28, but not BD (OR 0.99, 95% CI 0.86-1.14).CONCLUSION:We report a difference in the prognostic value of lactate and BD on mortality. Three hours from the initiation of ECLS in patients with RCA, lactate should be preferred to BD to predict the efficiency of ECLS.

Objective: During cardiac arrest (CA) resuscitation, an 'ischaemia-reperfusion' syndrome occurs leading to multiorgan failure reflected by an increase in blood lactate. Blood lactate is a diagnosis and prognosis biomarker in extracorporeal life support (ECLS), but its kinetic appears more informative to assess a patient's outcome. The aim of the present study was to describe the prognostic value of blood lactate and lactate clearance (LC) 3 (H3) and 6 h (H6) after the initiation of ECLS in the treatment of refractory CA. Methods: Patients admitted to the intensive care unit for refractory CA were included. Lactate measurements were performed at the initiation of ECLS (H0) and at H3 and H6 upon the initiation of ECLS. LC was measured from 0 to 3 h (LC03), 0 to 6 h (LC06) and 3 to 6 h (LC36). The primary endpoint was in-hospital mortality within 28 days. Results: Sixty-six patients were enrolled in the study. Lactate levels were higher in deceased patients. Increased mortality was observed with increasing levels of lactate at H3 and H6 and with decreasing LC03. Using logistic regression, an association was observed between mortality and lactate at H3 with an odds ratio (OR) of 1.21 (95% confidence interval (CI) 1.05-1.42); LC03, OR of 0.93 (95% CI 0.87-0.99) and LC06, OR of 0.96 (95% CI 0.92-0.99). Conclusion: Blood lactate and LC within the first 3 h of ECLS in refractory CA are associated with mortality. LC is a more relevant parameter than blood lactate, taking into account both the production and elimination of lactate. We suggest to preferentially use LC to assess the patient's outcome.

ObjectiveExtracorporeal Life Support (ECLS) can help to improve the outcome of refractory cardiac arrest (CA). ECLS allows to maintain blood pressure and tissue perfusion until the cause of CA is treated. The aim of the present study was to describe the mean blood pressure (MBP) during the first 24 h of ECLS for out-of-hospital CA (OHCA).MethodsWe performed a retrospective analysis of consecutive refractory OHCA requiring ECLS admitted to the intensive care unit. MBP was examined after starting ECLS (H0) and every 6 h during the first 24 h (H6, H12, H18 and H24).ResultsForty patients were analysed. MBP significantly differs between survivors and non-survivors since 6 h: 77 vs 44 mm Hg (p=0.002), 51 vs 87 mm Hg at H12 (p=0.008), 57 vs 75 mm Hg at H18 (p=0.015) and 79 vs 53 mm Hg at H24 (p=0.004), whereas no difference was observed at H0: 69 vs 55 mm Hg (p=0.06). An MBP lower than 65 mm Hg since 6 h is associated with a poor outcome (sensitivity and specificity of death of 87% and 66% at H6, 80% and 75% at H12, 100% and 75% at H18 and 70% and 80% at H24, respectively).ConclusionDespite high levels of catecholamine, the inability to maintain MBP higher than 60 mm Hg after starting ECLS for OHCA is associated with a poor outcome.

OBJECTIVE:Assess whether elevated oxygen partial arterial pressure (PaO2) measured after the initiation of extra-corporeal cardiopulmonary resuscitation (eCPR), is associated with mortality in patients suffering from refractory out-of-hospital cardiac arrest (rOHCA).METHODS:Retrospective cohort study including rOHCA admitted to the ICU. Patients were divided into 3 groups, defined according to the PaO2 measured from arterial blood gas analysis 30 min after the initiation of eCPR. Hyperoxemia was defined as PaO2 ≥ 300 mmHg, hypoxemia as PaO2 ≤ 60 mmHg and normoxemia, as 60 < PaO2 < 300 mmHg. The main outcome was the mortality rate on day 28 after hospital admission.RESULTS:Sixty-six consecutive rOHCA, 77% male, with a mean age of 51 ± 14 years, were admitted to the ICU. rOHCA were mainly due to acute coronary syndrome (67%), hypertrophic cardiomyopathy (8%) and cardiotoxic overdose (8%). Mortality at day 28 reached 61%. In the overall population, the mean PaO2 was 227 ± 124 mmHg. An association between mortality and PaO2 was observed (OR = 1.01 [1.01-1.02]). The AUC for PaO2 after starting eCPR was 0.77 [0.65-0.89]. After adjustment for witnessed arrest, bystander's CPR, location, no-flow, low-flow, lactate and pH, age, and PaCO2, hyperoxemia had an ORa of 1.89 (CI95 [1.74-2.07]).CONCLUSION:We found an association between mortality and hyperoxemia in patients admitted to the ICU for rOHCA requiring eCPR. These data underline the potential toxicity of high dose of oxygen and suggest that controlled oxygen administration for these patients is crucial.

Romain Jouffroy, M.D.⁎ Anastasia Saade, M.D., Ph.D. Alexandre Muret, M.D. Pascal Philippe, M.D. Maud Michaloux, M.D. Pierre Carli, M.D., Ph.D. Benoit Vivien, M.D., Ph.D. Intensive Care Unit, Anesthesiology Department and SAMU of Paris, Hôpital Necker Enfants Malades, Assistance Publique Hôpitaux de Paris, Paris Descartes University, Paris, France ⁎Corresponding author at: Department of Anesthesia & Intensive Care Unit, SAMU, Hôpital Necker EnfantsMalades, University Paris Descartes, 149 rue de Sèvres, 75015 Paris, France. E-mail address: romain.jouffroy@aphp.fr (R. Jouffroy).

Background: Septic shock is associated with hypovolemia resulting in organs failure and poor prognosis. The first step in hemodynamic resuscitation relies on early fluid expansion. In this study, we describe qualitative and quantitative fluid resuscitation of septic shock initially managed in a pre-hospital setting by a mobile intensive care unit. Methods: Patients with septic shock who received pre-hospital medical care were retrospectively analysed. Qualitative and quantitative fluid resuscitation performed in the pre-hospital setting were analysed. Applying the "grey zone" concept, we define 3 categories of fluid expansion indexed on ideal body weight (IBW): >20ml/kg, 10-20ml/kg and < 10ml/kg.The relationship between the pre-specified categories and mortality at day 28 were analyzed. Results: Ninety-five patients were included. The origin of sepsis was mainly pulmonary (68%). Mortality reached 34%. Pre-hospital fluid expansion was performed using serum saline (98%) with a mean of 1158 +/- 559ml. An inversed linear relationship between pre-specified categories and mortality was observed. Using logistic regression model, significant association with mortality remained for fluid expansion indexed on IBW: p=0.02, ORa [CI95] = 0.93 [0.89-0.98]. For fluid expansion indexed on IBW < 10m1/kg, the OR [095] was 4.03 [1.78-9.41] (p=0.005) whereas for fluid expansion indexed on IBW > 20m1/kg, the OR [095] was 0.30 [0.13-0.66] (p=0.01). Discussion: Pre-hospital fluid resuscitation in septic shock is mainly performed using crystalloids with quantitative fluid expansion lower than recommended. Low pre-hospital fluid expansion was associated with increased mortality. Further prospective studies are needed to evaluate the impact of optimized early fluid expansion on mortality in the prehospital management of septic shock. (C) 2018 Elsevier Inc. All rights reserved.

Angiotensin II (AII) is a strong physiological vasopressor hormone. Sartans act as antagonists of AT1 receptors of AII, inducing a vasodilatation via an upregulation of AT2 receptors. In July 2017, in the New England Journal of Medicine, efficiency of AII to increase blood pressure and reduce conventional vasopressors's dose in severe vasodilatory shock refractory to high-dose vasopressors were observed.

Background: Epinephrine is recommended for the treatment of non-shockable out of hospital cardiac arrest (OHCA) to obtain return of spontaneous circulation (ROSC). Epinephrine efficiency and safety remain under debate. Objective: We propose to describe the association between the cumulative dose of epinephrine and the failure of ROSC during the first 30 min of advanced life support (ALS). Methodology: A retrospective observational cohort study using the Paris SAMU 75 registry including all non-traumatic OHCA. All OHCA receiving epinephrine during the first 30 min of ALS were enrolled. Cumulative epinephrine dose given during ALS to ROSC was retrieved from medical reports. Results: Among 1532 patients with OHCA, 776 (51%) had initial non-shockable rhythm. Fifty-four patients were excluded for missing data. The mean value of cumulative dose of epinephrine was 10 +/- 4 mg in patients who failed to achieve ROSC (ROSC-) and 4 +/- 3 mg (p = 0.04) for those who achieved ROSC. ROC curve analysis indicated a cut-off point of 7 mg total cumulative epinephrine associated with ROSC- (AUC = 0.89[0.86-0.92]). Using propensity score analysis including age, sex and no-flow duration, association with ROSC- only remained significant for epinephrine > 7 mg (p <= 10-3. OR [CI95] = 1.53 [1.42-1.65]). Conclusion: An association between total cumulative epinephrine dose administered during OHCA resuscitation and ROSC- was reported with a threshold of 7 mg, best identifying patients with refractory OHCA. We suggest using this threshold in this context to guide the termination of ALS and early decide on the implementation of extracorporeal life support or organ harvesting in the first 30 min of ALS. (C) 2018 Elsevier Inc. All rights reserved.