Diagnostic Accuracy of Procalcitonin for Early Aspiration Pneumonia in Critically Ill Patients with Coma: A Prospective Study.

BACKGROUND: Early diagnostic orientation for differentiating pneumonia from pneumonitis at the early stage after aspiration would be valuable to avoid unnecessary antibiotic therapy. We assessed the accuracy of procalcitonin (PCT) in diagnosing aspiration pneumonia (AP) in intensive care unit (ICU) patients requiring mechanical ventilation after out-of-hospital coma. METHODS: Prospective observational 2-year cohort study in a medical-surgical ICU. PCT, C-reactive protein (CRP) and white blood cell count (WBC) were measured at admission (H0) and 6 h (H), H12, H24, H48, H96, and H120 after inclusion. Lower respiratory tract microbiological investigations performed routinely in patients with aspiration syndrome were the reference standard for diagnosing AP. Performance of PCT, CRP, and WBC up to H48 in diagnosing AP was compared based on the areas under the ROC curves (AUC) and likelihood ratios (LR+ and LR-) computed for the best cutoff values. RESULTS: Of 103 patients with coma, 45 (44%) had AP. Repeated PCT assays demonstrated a significant increase in patients with AP versus without AP from H0 to H120. Among the three biomarkers, PCT showed the earliest change. ROC-AUC values were poor for all three biomarkers. Best ROC-AUC values for diagnosing AP were for CRP at H24 [0.73 (95%CI 0.61-0.84)] and PCT at H48 [0.73 (95%CI 0.61-0.84)]. LR+ was best for PCT at H24 (3.5) and LR- for CRP and WBC at H24 (0.4 and 0.4, respectively). CONCLUSIONS: Early and repeated assays of PCT, CRP, and WBC demonstrated significant increases in all three biomarkers in patients with versus without AP. All three biomarkers had poor diagnostic performance for ruling out AP. Whereas PCT had the fastest kinetics, PCT assays within 48 h after ICU admission do not help to diagnose AP in ICU patients with coma.

Obstructive acute renal failure by severe gastric distension after binge.

Binge eating occurs in patients with eating disorders and can result in metabolic complications, leading to gastric rupture or necrosis. However, organ failure as acute renal failure is rarely observed. We report the case of an overeating episode resulting in massive gastric dilatation and acute renal failure with abdominal pressure and bilateral ureteral obstruction. The outcome was favorable with gastric aspiration and fasting.

Severe pain management in the emergency department: patient pathway as a new factor associated with IV morphine prescription.

Background: Across the world, 25-29% of the population suffer from pain. Pain is the most frequent reason for an emergency department (ED) visit. This symptom is involved in approximately 70% of all ED visits. The effective management of acute pain with adequate analgesia remains a challenge, especially for severe pain. Intravenous (IV) morphine protocols are currently indicated. These protocols are based on patient-reported scores, most often after an immediate evaluation of pain intensity at triage. However, they are not systematically prescribed. This aspect could be explained by the fact that physicians individualize opioid pain management for each patient and each care pathway to determine the best benefit-risk balance. Few data are available regarding bedside organizational factors involved in this phenomenon. Objective: This study aimed to analyze the organizational factors associated with no IV morphine prescription in a standardized context of opioid management in a tertiary-care ED. Methods: A 3-month prospective study with a case-control design was conducted in a French university hospital ED. This study focused on factors associated with protocol avoidance despite a visual analog scale (VAS) ≥60 or a numeric rating scale (NRS) ≥6 at triage. Pain components, physician characteristics, patient epidemiologic characteristics, and care pathways were considered. Qualitative variables (percentages) were compared using Fisher's exact test or the chi-squared tests. Student's t-test was used to compare continuous variables. The results were expressed as means with their standard deviation (SD). Factors associated with morphine avoidance were identified by logistic regression. Results: A total of 204 patients were included in this study. A total of 46 cases (IV morphine) and 158 controls (IV morphine avoidance) were compared (3:1 ratio). Pain patterns and patient's epidemiologic characteristics were not associated with an IV morphine prescription. Regarding NRS intervals, the results suggest a practice disconnected from the patient's initial self-report. IV morphine avoidance was significantly associated with care pathways. A significant difference between the IV morphine group and the IV morphine avoidance group was observed for "self-referral" [adjusted odds ratio (aOR): 5.11, 95% CIs: 2.32-12.18, p < 0.0001] and patients' trajectories (Fisher's exact test; p < 0.0001), suggesting IV morphine avoidance in ambulatory pathways. In addition, "junior physician grade" was associated with IV morphine avoidance (aOR: 2.35, 95% CIs: 1.09-5.25, p = 0.03), but physician gender was not. Conclusion: This bedside case-control study highlights that IV morphine avoidance in the ED could be associated with ambulatory pathways. It confirms the decreased choice of "NRS-only" IV morphine protocols for all patients, including non-trauma patterns. Modern pain education should propose new tools for pain evaluation that integrate the heterogeneity of ED pathways.

Systemic perturbation of cytokine and chemokine networks in Erdheim-Chester disease: a single-center series of 37 patients.

Immunopathogenesis of Erdheim-Chester disease (ECD), a rare non-Langerhans cell histiocytosis, is poorly known. In previous studies, various cytokines were detected in ECD lesions, presumably orchestrating lesional histiocyte recruitment. Because ECD lesions are frequently associated with systemic symptoms, we postulated that underlying global immune perturbations might also be revealed. We quantitatively analyzed 23 cytokines in serum samples obtained from a large single-center cohort of 37 patients with ECD, and studied the impact of treatment on cytokine production. IL-6, IL-12, interferon-α (IFN-α), and monocyte chemotactic protein-1 (MCP-1) levels were significantly higher in untreated patients than in controls, whereas interferon-γ (IFN-γ) inducible protein 10, IL-12, MCP-1, and IL-1 receptor antagonist were found significantly increased in IFN-α-treated patients. A biomathematical approach was used to rationalize multiparameter data, to generate new hypotheses, and identify global control pathways. Interestingly, cytokine profiles proved to be particularly stable at the individual level, and an "ECD signature" further distinguished patients from controls, based on their production of IFN-α, IL-12, MCP-1, IL-4, and IL-7. Altogether, our data underline the systemic immune Th-1-oriented perturbation associated with this condition and provide clues for the choice of more focused therapeutic agents in this rare disease with noncodified therapeutic management.

Periodontal pathogens of the interdental microbiota in a 3 months pregnant population with an intact periodontium.

Steroid hormones and the oral microbiota of pregnant women both appear as cumulative risk factors for gingivitis. This cross-sectional study, using real-time PCR, investigated the composition and diversity of the microbiota in interdental spaces of 3 months pregnant women with intact periodontium according the 2018 EFP/AAP classification. Bacteria identified were belonged to the red (Porphyromonas gingivalis Treponema denticola, and Tanerella forsythia), orange (Fusobacterium nucleatum, Prevotella intermedia, Campylobacter rectus, and Parvimonas micra), and green (Eikenella corrodens and A. actinomycetencomitans) Socransky complexes. Approximatively 109.11 bacteria were counted per interdental space in pregnant women. Bacteria from the red complex represented 33.80% versus 62.81% for the orange group versus 3.39% for the green group of the total number spread over the 3 groups. Dietary habits and physical activity did not have a significant impact on interdental microbiota, although a decrease in the median amount of 9 periodontopathogens was observed when fruit and vegetable consumption increased. Pregnant women who brushed their teeth at least twice a day had lower counts of total bacteria and 9 periodontal pathogens than those who brushed less. In 3 months pregnant women at high risk of periodontal disease (>30% bleeding sites), the dendogram revealed 2 clusters of the 9 periodontopathogens. This provides further support for the "key pathogen" hypothesis, among which Porphyromonas gingivalis plays a key role, indicating that specific bacteria in limited quantities can influence the host immune system and convert the microbiota from symbiotic to dysbiotic to induce inflammatory disorder. As a result, this study reported that 3 months pregnant women with healthy periodontium had high levels of interdental bleeding and a dysbiotic microbiota with periodontal pathogens of the Socransky orange and red complexes. These subjects were therefore potentially at increased risk of developing periodontal disease and, consequently, an adverse pregnancy outcome. So, preventive oral prophylaxis measures, in particular individual interdental prophylaxis, should be implemented as soon as pregnancy is established.

Relevance of early management by proton-pump inhibitor in acute upper gastro-intestinal tract disorder: A scoping review.

BACKGROUND: Proton-pump inhibitors (PPI) are frequently used in the emergency and general practice settings in several clinical presentations linked to acute upper gastro-intestinal tract disorders as abdominal or chest pain without recommendations. OBJECTIVE: The aim of this scoping review was to assess pain reduction, diagnostic performance, and safety in the first 24 h-management in primary care or emergency medicine. METHODS: Search was realized by 2 independent reviewers in PubMed, Embase, and Web of Science following PRISMA-ScR guidelines. Only original articles or systematic reviews in English were included. Studies about chronic and/or bleeding conditions, therapeutic cocktails and studies without pain evaluation were excluded. Two methodologies were used for bias estimation. RESULTS: From 4442 titles, 79 full-text articles were assessed, and 9 were included. There is no strong evidence supporting the use of PPI as a first line analgesic or diagnostic test in acute syndromes linked to acute upper gastro-intestinal tract disorder. A small effect in pain reduction was retrieved in patients with low pain scores. A poor additional value in patients with gastric reflux, and a low specificity compared to other diagnostic tests were observed. A short-term PPI administration appears to be safe with low risk of serious allergic reactions, and poor adverse effects (moderate evidence). CONCLUSION: Although PPIs may contribute to the multimodal analgesia in acute settings, with few and/or minor side effects, no recommendation can be drawn for their use as a primary analgesic. Data regarding the relevance of the PPI test are much less clear, no data regarding care pathways are available.

Supporting health education policies: translation, cross-cultural adaptation and validation of a health literacy instrument, in French.

Background: Oral health is a fundamental human right and is inseparable and indivisible from overall health and well-being. Oral Health Literacy (OHL) has been proved to be fundamental to promoting oral health and reducing oral health inequalities. To our knowledge, no OHL instrument to evaluate OHL level is currently validated in French language despite the fact it is the fifth most widely spoken languages on the planet. The Oral health literacy Instrument (OHLI) appears to be the most interesting OHL instrument to adapt into French because it is already available in English, Spanish, Russian, Malaysian, and it contains both reading comprehension and numeracy sections. Its psychometric properties have been rated as adequate. Objective: The aim of this study was to translate and adapt cross-culturally the OHLI into French, to evaluate its psychometric properties and to compare its results to oral health knowledge. Method: This study followed and applied well-established processes of translation, cross-cultural adaptation and validation, based on the recommendations of the World Health Organization guidelines and on the Consensus-Based Standards for the Selection of Health Measurement Instruments (COSMIN) study design checklist for patient-reported outcomes. Two psychometric assessments were planned, the comparison of OHLI-F scores according to education level and frequency of dental visits, and the test-retest reliability of the OHLI-F. Results: A total of 284 participants answered the OHLI-F. The OHLI-F scores were significantly different between participants with different levels of education and frequency of dental visits (p < 0.001). Participants with an education level lower than the baccalaureate, and those who never visit the dentist or only in case of pain, had significantly lower OHLI-F scores. Internal consistency was excellent (Cronbach's alpha = 0.881-0.914). Test-retest reliability was very high (intraclass correlation = 0.985 to 0.996). Conclusion: The OHLI-F has demonstrated adequate psychometric properties and can therefore be used to measure oral health literacy in French-speaking populations.

Morphine consumption is not modified in patients with severe pain and classified by the DN4 score as neuropathic.

Neuropathic pain has been poorly investigated in the emergency department, although it is known to be less sensitive to opioids than other forms of pain. We tested the hypothesis that morphine requirements are increased in patients having severe pain classified as neuropathic using the DN4 score. We included adult patients with acute severe pain (visual analog scale ≥ 70), assessed using the DN4 score, and treated with intravenous morphine titration (bolus of 2 or 3 mg [body weight >60 kg] with 5-minute intervals between each bolus). Pain relief was defined as a visual analog scale 30 or less. Patients were divided into 2 groups: control group (DN4 score <4) and neuropathic pain group (DN4 score ≥ 4). The main outcome was the total dose of morphine administered. Data are mean ± SD or median (interquartile range). Among the 239 patients included (mean age, 43+14 years), 35 patients (15%) had a DN4 score 4 or more. The main characteristics of the 2 groups were comparable. There were no significant differences between the 2 groups in morphine dose (0.16+0.09 vs 0.17+0.11 mg/kg, P=.32), number of boluses administered (3.5 [3-5] vs 3 [3-6], P=.97), proportion of patients with pain relief (75 vs 83%, P=.39), or morphine-related adverse effects (11% vs 3%, P=.14). In conclusion, morphine consumption was not significantly modified in patients having severe pain classified as neuropathic using the DN4 score as compared with a control group, suggesting that specific detection of neuropathic pain may not be useful in the emergency department.

A discrepant presentation of bacteremia in the emergency department linked to a Fusobacterium nucleatum infection: a case report.

BACKGROUND: Fusobacterium nucleatum is an anaerobic bacterium mainly responsible for acute or chronic infection of the ear, nose, and throat, potentially bacteremic with a risk of extraoral metastatic infection. Bacteremia occurs mainly in the elderly or in immunodeficient individuals, with high mortality. F. nucleatum is not the first cause of tonsillar infection in emergency departments, which are more often the consequence of a viral or streptococcal infection, but it is a risk factor for severe bacterial infection, especially in a viral pandemic context. CASE PRESENTATION: A 25-year-old European woman with no history presented to the emergency department with fever (38.9 °C), pharyngeal symptoms, intermittent headaches, and alteration of general condition. On examination, she presented odynophagia associated with moderate tonsillar hypertrophy, her neck was painful but flexible. A rapid diagnostic test for beta-hemolytic group streptococcus was negative. First biological analyses revealed an inflammatory syndrome with C-reactive protein of 76 mg/L. Procalcitonin was measured secondarily, and was 2.16 µg/L. Faced with discordant clinical and biological findings, a lumbar puncture was performed, which came back negative. At hour eight, hypotension was observed but corrected after filling with physiological serum. The patient was hospitalized for monitoring, based on a hypothesis of severe viral presentation. At hour 24, pyrexia confirmed this hypothesis. A spontaneous but transient improvement and no new hemodynamic event led to early discharge. At day three, she was rehospitalized for increased and continuous headaches, without hemodynamic severity. A broad-spectrum probabilistic antibiotic therapy of ceftriaxone and metronidazole was started due to first blood cultures positive for anaerobic Gram-negative bacilli, while waiting for identification of the pathogen. Three days later, F. nucleatum was identified. According to the microbiological results, antibiotic therapy was adapted with amoxicillin and clavulanic acid, and no further complications were observed during clinical or complementary examinations. The final diagnosis was a F. nucleatum oropharyngeal infection complicated by bacteremia, without metastatic spread. CONCLUSION: The etiologies of tonsillar infection are not limited to benign viruses or bacteria. These should not be overlooked in emergency medicine, especially when the clinical presentation is discrepant. A combination of early bacterial investigations as blood culture and close clinical monitoring is the only safe way to detect bacteremia, especially in immunocompetent patients.

Pharmacokinetic modeling of morphine and its glucuronides: Comparison of nebulization versus intravenous route in healthy volunteers.

Intravenous (i.v.) morphine is a safe, robust, and recommended treatment for severe pain using the titration principle. Despite its high efficacy, it is impacted by organizational constraints related to venous access. Nebulized (NEB) morphine may represent an alternative for titration but pharmacokinetic (PK) properties of short nebulization using routine devices need evaluation. Twenty-seven healthy volunteers were included to receive NEB or i.v. morphine administration using increasing amounts according to Dixon's reference method. Plasma morphine, morphine-3-glucuronide (M3G), and morphine-6-glucuronide (M6G) were quantified. PK modeling and simulations were performed using Monolix. Dixon's method exhibited a significantly higher morphine dose regimen in the NEB group versus the i.v. group (6.2 [5.3-7.1] vs. 3.0 [2.0-4.0] mg, p < 0.001). Morphine, M3G, and M6G dose-normalized exposure were significantly lower in the NEB group versus the i.v. group: morphine (19 [13-23] vs. 1044 [702-1266] µg min/L, p < 0.001), M3G (245 [162-287] vs. 3752 [2487-5165] µg min/L, p < 0.001) and M6G (28 [21-43] vs. 466 [370-723] µg min/L, p < 0.001). The model that best fitted the data consisted in a transit compartment for morphine absorption, three compartments for morphine distribution followed by multiple transit compartments (8.2 and 57.5-min transit time for M3G and M6G, respectively) and a first order elimination for M3G and M6G. Morphine bioavailability in the NEB group was 3.5% using the i.v. group as reference. Administration route and sex significantly influenced morphine and metabolite PKs. This work aimed to evaluate the PKs of NEB morphine compared with the i.v. route. Despite a bioavailability to improve, NEB morphine administration using a routine device is suitable to plan morphine titration.

Relevance of cortisol and copeptin blood concentration changes in an experimental pain model.

The effect of pain and analgesics on stress biomarkers is not well studied. We evaluated the effect of acute pain and analgesics on serum cortisol and copeptin in an experimental pain model in healthy volunteers. Healthy volunteers presented at 8 a.m. for an experimental pain stimulation. Cortisol and copeptin levels were measured before, during and after electrophysiological stimulation, first before and then during opioid delivery. Difference in biomarker levels compared to baseline levels was calculated, and potential influencing factors were evaluated by linear regression analysis. Cortisol decreased by 13% during the 10 min of rest at baseline, but copeptin did not change significantly. Cortisol had a median decrease of -24% or -83 nmol/l (-44 to -124 nmol/l, p = 0.0002) during the electrophysiological stimulation training session, while the median difference for copeptin was -22% or -1.01 pmol/l (-2.35 to 0.08 pmol/l, p = 0.0003). After administration of opioids, cortisol did not decrease but increased by 3% (p = 0.043), indicating an increasing opioids effect on cortisol. This effect was not visible for copeptin (median change -0.003 pmol/l (-0.50 to 0.24), p = 0.45). In this experimental pain model performed in the morning, moderate pain did not have a relevant effect on cortisol or copeptin levels, whereas opioids led to a discrete peak of cortisol.Clinicaltrials.gov identifier: NCT01975753 (registered on November 5, 2013, before start of recruitment).

Knowledge, Attitudes and Practices Related to Medication, Antibiotics, and Vaccination among Public Service Population: National Survey Conducted in France.

Medication, antibiotics, and immunization are three major and cost-effective medical interventions but their use is balanced. Knowledge, attitudes and practices (KAP) are a cornerstone. This retrospective study aims at analyzing KAP related to these concerns among the public service population in order to establish the basis for the implementation of selective preventive actions. From a cross-sectional anonymous online questionnaire-based survey among the insurees of a French mutual organization (Union Prévention Santé pour la Fonction publique, UROPS), 33 questions related to medication, antibiotics and vaccination were extracted to evaluate KAP. New variables were constituted: levels of knowledge, antibiotic misuse, proactive behavior and vaccinophobia. Multiple correspondence analysis was performed to identify respondents' homogenous groups. In addition, bivariate statistical comparisons were provided and logistic regressions were carried out to identify determinants of these new variables. Public service population (workers and retired) were highly exposed to polymedication (8.7% vs. 24.4%, p < 0.0001), hypnotics overtake (24.3% vs. 18.4%, p < 0.0001), and misuse antibiotics (33.2% vs. 22.6%, p < 0.0001) despite good levels of knowledge. Proportions of vaccinophobia was low (0.8% vs. 1.7%, p < 0.0001). However, workers have different KAP than retired, without shared determinants in the 3 health domains studied. Respondents were proactive (85.8% vs. 81.6%, p < 0.0001), used multiple sources of trustworthy information and seems to be ready for the delegation of health tasks. Thus, preventive actions related to antibiotics and polymedication should be a priority in vaccination education for mutual organizations such as UROPS. Studying their insurees longitudinally could be interesting to highlight the impact of selective prevention on behaviors, through trusted health professionals (general practitioners, pharmacists…).

Bedside Evaluation of Early VAS/NRS Based Protocols for Intravenous Morphine in the Emergency Department: Reasons for Poor Follow-Up and Targeted Practices.

Intravenous (IV) morphine protocols based on patient-reported scores, immediately at triage, are recommended for severe pain in Emergency Departments. However, a low follow-up is observed. Scarce data are available regarding bedside organization and pain etiologies to explain this phenomenon. The objective was the real-time observation of motivations and operational barriers leading to morphine avoidance. In a single French hospital, 164 adults with severe pain at triage were included in a cross-sectional study of the prevalence of IV morphine titration; caregivers were interviewed by real-time questionnaires on "real" reasons for protocol avoidance or failure. IV morphine prevalence was 6.1%, prescription avoidance was mainly linked to "Pain reassessment" (61.0%) and/or "alternative treatment prioritization" (49.3%). To further evaluate the organizational impact on prescription decisions, a parallel assessment of "simulated" prescription conditions was simultaneously performed for 98/164 patients; there were 18 titration decisions (18.3%). Treatment prioritization was a decision driver in the same proportion, while non-eligibility for morphine was more frequently cited (40.6% p = 0.001), with higher concerns about pain etiologies. Anticipation of organizational constraints cannot be excluded. In conclusion, IV morphine prescription is rarely based on first pain scores. Triage assessment is used for screening by bedside physicians, who prefer targeted practices to automatic protocols.

Multiple criteria decision analysis approach to consider therapeutic innovations in the emergency department: The methoxyflurane organizational impact in acute trauma pain.

BACKGROUND: Acute trauma pain is poorly managed in the emergency department (ED). The reasons are partly organizational: ED crowding and rare trauma care pathways contribute to oligoanalgesia. Anticipating the organizational impact of an innovative care procedure might facilitate the decision-making process and help to optimize pain management. METHODS: We used a multiple criteria decision analysis (MCDA) approach to consider the organizational impact of methoxyflurane (self-administered) in the ED, introduced alone or supported by a trauma care pathway. A MCDA experiment was designed for this specific context, 8 experts in emergency trauma care pathways (leading physicians and pharmacists working in French urban tertiary hospitals) were recruited. The study involved four steps: (i) Selection of organizational criteria for evaluating the innovation's impact; (ii) assessment of the relative weight of each criterion; (iii) choice of appropriate scenarios for exploring the organizational impact of MEOX under various contexts; and (iv) software-assisted simulation based on pairwise comparisons of the scenarios. The final outcome measure was the expected overall organizational impact of methoxyflurane on a 0-to-100 scale (score >50: positive impact). RESULTS: Nine organizational criteria were selected. "Mean length of stay in the ED" was the most weighted. Methoxyflurane alone obtained 59 as a total score, with a putative positive impact for eight criteria, and a neutral effect on one. When a trauma care pathway was introduced concomitantly, the impact of methoxyflurane was greater overall (score: 75) and for each individual criterion. CONCLUSIONS: Our model highlighted the putative positive organizational impact of methoxyflurane in the ED-particularly when supported by a trauma care pathway-and the relevance of expert consensus in this particular pharmacoeconomic context. The MCDA approach could be extended to other research fields and healthcare challenges in emergency medicine.

Medico-economic study of pain in an emergency department: a targeted literature review.

Background: Pain management in emergency departments is a complex objective. The absence of a care pathway or a high level of activity complicates diagnostic or analgesic therapeutic strategies. Medical innovation can impact both individual practices and the functioning of an emergency department. Objective: We then wanted to understand how medico-economic studies on pain were carried out in an emergency department. Study design: We reviewed the literature of the last 20 years (between 1998 and 2018). Setting: Of 846 titles screened, a total of 268 abstracts qualified for further screening, and 578 titles were excluded. A total of 14 studies qualified for inclusion in the review. Studies on medico-economics in an emergency department are very diverse. None of the methods used are identical; the studies differ in their very nature (prospective, retrospective, cost-effectiveness, etc.) and the determination of emergency room costs differs according to the part of the world studied. In addition, organizational impact is rarely measured, although it is an essential dimension for choosing or not a medical innovation.

Nebulized versus intravenous morphine titration for the initial treatment of severe acute pain in the emergency department: study protocol for a multicenter, prospective randomized and controlled trial, CLIN-AEROMORPH.

BACKGROUND: Intravenous morphine titration (IVMT) is the French gold standard for opioid treatment in the emergency department (ED). Nebulized morphine titration (NMT) may represent an alternative without venous access, but it has not been adequately studied in adults. We test the hypothesis that NMT is at least as effective as IVMT to initially manage severe acute pain in the ED. METHODS/DESIGN: We designed a multicenter (10 French EDs), single-blind, randomized and controlled trial. Adults between 18 and 75 years with visual analog scale (VAS) ≥ 70/100 or numeric rating scale (NRS) ≥ 7/10 will be enrolled. We will randomize 850 patients into two groups to compare two routes of MT as long as VAS >  30 or NRS >  3. In group A (425), patients will receive an initial NMT for 5-25 min associated with titration of an intravenously (IV) administered placebo of physiologic serum (PS). In group B (425), patients will receive IVMT plus nebulized PS placebo. NMT is defined as a minimum of 1 and a maximum of 3 5-min nebulized boluses of 10 mg or 15 mg (weight ≥ 60 kg), at 10-min fixed intervals. IVMT is defined as a minimum of 1 and a maximum of 6 boluses of 2 mg or 3 mg (weight ≥ 60 kg), at 5-min fixed intervals. Nebulized placebo titration will be performed every 10 min. IV titration of PS will be performed every 5 min. In both groups, after 25 min, if VAS > 30/100 or NRS > 3/10, routine IVMT will be continued until pain relief. Pain severity, vital signs, bronchospasm, and Ramsay score will be recorded every 5 min. The primary outcome is the rate of relief obtained 1 h from the start of drug administration. Complete pain relief in both groups will be compared with a non-inferiority design. Secondary outcomes are pain relief at 30 min (the end of NMT) and at 2 h and median pain relief. We will compare final doses, and study the feasibility and tolerance of NMT (protocol deviations, respiratory or hemodynamic depression, sedation, and minor vegetative side effects). Co-analgesia will be recorded. Discharge criteria from the ED and hospital are defined. DISCUSSION: This trial is the first multicenter randomized and controlled NMT protocol for severe pain in the ED using the titration concept. We propose an original approach of combined titration with an endpoint at 1 h and a non-inferiority design. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03257319 . Registered on 22 August 2017.

Is procalcitonin a marker of critical illness in heatstroke?

OBJECTIVE: To study the effect of non-exertional heatstroke on serum procalcitonin (PCT) levels. DESIGN: Cohort study. SETTING: The emergency and intensive care departments of two academic tertiary-care hospitals, Paris, France PATIENTS: A total of 53 patients with defined heatstroke attending the emergency department and/or the intensive care unit during the August 2003 heat wave in France. INTERVENTIONS: None. MEASUREMENTS: Serum PCT measurement using a sensitive assay and vital and routine biological variables on arrival of patients presenting with classic heatstroke. Thirty-day mortality was recorded. RESULTS: Among the 53 patients included, 14 (26%) were admitted to an intensive care unit (ICU). At 30 days, 24 patients (45%) had died. Median PCT value was 0.58 microg/l (95% confidence interval 0.16-1.61) and 31 (58%) patients had PCT above 0.2 microg/l (PCT+). Temperature above or equal to 40 degrees C was the only variable significantly associated with fatal outcome. Median PCT values were 1.4 microg/l (0.16-4.71) and 0.18 microg/l (0.12-1.61) in the group of deceased and surviving patients respectively (p = 0.22). All patients admitted in ICU had elevated PCT values. Patients PCT+ initially presented with a more pronounced systemic inflammatory response. Microbiologically or clinically documented infection was not more frequent in PCT+ group. CONCLUSION: High serum PCT levels can be observed in heatstroke without any concomitant documented bacterial infection. The PCT is not a valid mortality predictor in heatstroke but could be an indicator of the severity of illness. Heatstroke could represent a model of a "non-septic" pathway of PCT synthesis.

Intravenous morphine titration to treat severe pain in the ED.

PURPOSE: We assessed the safety of intravenous morphine titration in the emergency setting. METHODS: A total of 621 consecutive adult patients admitted in the ED with acute severe pain (visual analogue scale pain score > 70) were included. Intravenous morphine titration was administered as a bolus of 2 (body weight < or = 60 kg) or 3 mg (body weight > 60 kg) with 5-minute interval between each bolus. Pain relief was defined as a visual analogue pain score of 30 or lower. RESULTS: The dose of morphine administered was 0.16 +/- 0.10 mg/kg and the median number of boluses was 3. Pain relief was obtained in 512 (82%) patients. Morphine-induced adverse events occurred in 67 patients (11%) without severe adverse event. Titration was interrupted before pain relief had been obtained in 107 (17%) patients. In the remaining 514 patients, pain relief was obtained in 507 (99%) patients. Two variables were significantly associated with no pain relief: major protocol deviation (odds ratio, 17.3; 95% confidence interval, 10.0-30.1) and morphine-induced adverse effect (odds ratio, 13.0; 95% confidence interval, 6.7-25.3). CONCLUSION: Intravenous morphine titration is a safe and effective option for severe pain when used according to a strict protocol.