Jérôme Dimet

Impact of not measuring residual gastric volume in mechanically ventilated patients receiving early enteral feeding: a prospective before-after study.

BACKGROUND Monitoring of residual gastric volume (RGV) to prevent aspiration is standard practice in mechanically ventilated patients receiving early enteral nutrition (EN). No data are available to support a correlation between RGV and adverse event rates. We evaluated whether not measuring RGV affected EN delivery, vomiting, or risk of nosocomial pneumonia. METHODS Two hundred and five eligible patients with nasogastric feeding within 48 hours after intubation were included in a 7-day prospective before-after study. Continuous 24-hour nutrition was started at 25 mL/h then increased by 25 mL/h every 6 hours, to 85 mL/h. In both groups, intolerance was treated with erythromycin (250 mg IV/6 h) and a delivery rate decrease to the previously well-tolerated rate. RGV monitoring was used during the first study period (n = 102), but not during the subsequent intervention period (n = 103). Intolerance was defined as RGV >250 mL/6 h or vomiting in the standard-practice group and as vomiting in the intervention group. RESULTS Groups were similar for baseline characteristics. Median daily volume of enteral feeding was higher in the intervention group (1489; interquartile range [IQR], 1349-1647) than in the controls (1381; IQR, 1151-1591; P = .002). Intolerance occurred in 47 (46.1%) controls and 27 (26.2%) intervention patients (P = .004). The vomiting rate did not differ between controls and intervention group patients (24.5% vs 26.2%, respectively; P = .34), and neither was a difference found for ventilator-associated pneumonia (19.6% vs 18.4%; P = .86). CONCLUSION Early EN without RGV monitoring in mechanically ventilated patients improves the delivery of enteral feeding and may not increase vomiting or ventilator-associated pneumonia.

Maternal-Fetal Transfer and Amniotic Fluid Accumulation of Nucleoside Analogue Reverse Transcriptase Inhibitors in Human Immunodeficiency Virus-Infected Pregnant Women

ABSTRACT This study was performed to investigate placental transfer of nucleoside analogue reverse transcriptase inhibitors (NRTIs) and their concentrations in amniotic fluid when given to human immunodeficiency virus (HIV)-infected pregnant women. A total of 100 HIV type 1-infected mothers receiving antiretroviral therapy, including one or more NRTIs, for clinical indications at the time of delivery were enrolled. Maternal blood samples and amniotic fluid were obtained during delivery or cesarean section, and paired cord blood samples were obtained by venipuncture immediately after delivery. Drug concentrations were measured by using high-performance liquid chromatography. A significant relationship between concentrations in maternal and cord plasma samples was found for zidovudine, lamivudine, stavudine, and didanosine. The ratio between the concentrations in cord and maternal plasma samples (R) was high for zidovudine (R = 1.22), its glucuronide metabolite (3′-azido-3′-deoxythymidine-β-d-glucuronide) (R = 1.01), stavudine (R = 1.32), lamivudine (R = 0.93), and abacavir (R = 1.03) and was low for didanosine (R = 0.38). The ratio between the concentrations in amniotic fluid and cord plasma samples was high for zidovudine (R = 2.24), its glucuronide metabolite (R = 2.83), stavudine (R = 4.87), and lamivudine (R = 3.99) and was lower for didanosine (R = 1.14). These findings indicate that most NRTIs cross the placenta by simple diffusion and are concentrated in the amniotic fluid, probably through fetal urinary excretion. The efficacy or toxicity of NRTIs may vary according to placental transfer.

Before-after study of a standardized ICU protocol for early enteral feeding in patients turned in the prone position.

BACKGROUNDS & AIMS To evaluate an intervention for improving the delivery of early enteral nutrition (EN) in patients receiving mechanical ventilation with prone positioning (PP). METHODS Eligible patients receiving EN and mechanical ventilation in PP were included within 48h after intubation in a before-after study. Patients were semi-recumbent when supine. Intolerance to EN was defined as residual gastric volume greater than 250ml/6h or vomiting. In the before group (n=34), the EN rate was increased by 500ml every 24h up to 2000ml/24h; patients were flat when prone and received erythromycin (250mgIV/6h) to treat intolerance. In the intervention group (n=38), the EN rate was increased by 25ml/h every 6h to 85ml/h, 25 degrees head elevation was used in PP, and prophylactic erythromycin was started at the first turn. RESULTS Compared to the before group, larger feeding volumes were delivered in the intervention group (median volume per day with PP, 774ml [IQR 513-925] vs. 1170ml [IQR 736-1417]; P<0.001) without increases in residual gastric volume, vomiting, or ventilator-associated pneumonia. CONCLUSION An intervention including PP with 25 degrees elevation, an increased acceleration to target rate of EN, and erythromycin improved EN delivery.

Potential benefit of Bayesian forecasting for therapeutic drug monitoring in neonates

Therapeutic drug monitoring in neonate has been hampered by invasiveness of blood samplings raising ethical problems. A methodologic approach has been developped in adults and in children that is still unsufficiently developped in neonates, the Bayesian forecasting of drug plasma concentration. This method is particularly attractive in neonates using a few blood samples from an individual patient and more informations from a prior patient sample representative of the population the individual patient belongs to. The present article aims at reviewing the different procedures and methods to minimize invasiveness during therapeutic drug monitoring in neonate and at reviewing the methods for improving the quality of different dose adjustments using a Bayesian approach.

The Readability of Information and Consent Forms in Clinical Research in France

Background Quantitative tools have been developed to evaluate the readability of written documents and have been used in several studies to evaluate information and consent forms. These studies all showed that such documents had a low level of readability. Our objective is to evaluate the readability of Information and Consent Forms (ICFs) used in clinical research. Methods and Findings Clinical research protocols were collected from four public clinical research centers in France. Readability was evaluated based on three criteria: the presence of an illustration, the length of the text and its Flesch score. Potential effects of protocol characteristics on the length and readability of the ICFs were determined. Medical and statutory parts of the ICF form were analyzed separately. The readability of these documents was compared with that of everyday contracts, press articles, literary extracts and political speeches. We included 209 protocols and the corresponding 275 ICFs. The median length was 1304 words. Their Flesch readability scores were low (median: 24), and only about half that of selected press articles. ICF s for industrially sponsored and randomized protocols were the longest and had the highest readability scores. More than half (52%) of the text in ICFs concerned medical information, and this information was statistically (p<0.05) more readable (Flesch: 28) than statutory information (Flesch: 21). Conclusion Regardless of the field of research, the ICFs for protocols included had poor readability scores. However, a prospective analysis of this test in French should be carried out before it is put into general use.

Neuromuscular blockade during therapeutic hypothermia after cardiac arrest: Observational study of neurological and infectious outcomes

INTRODUCTION Neuromuscular blockade (NMB) is widely used during therapeutic hypothermia (TH) after cardiac arrest but its effect on patient outcomes is unclear. We compared the effects of NMB on neurological outcomes and frequency of early-onset pneumonia in cardiac-arrest survivors managed with TH. METHODS We retrospectively studied consecutive adult cardiac-arrest survivors managed with TH in a tertiary-level intensive care unit between January 2008 and July 2013. Patients given continuous NMB for persistent shivering were compared to those managed without NMB. Cases of early-onset pneumonia and vital status at ICU discharge were recorded. To avoid bias due to between-group baseline differences, we adjusted the analysis on a propensity score. RESULTS Of 311 cardiac-arrest survivors, 144 received TH, including 117 with continuous NMB and 27 without NMBs. ICU mortality was lower with NMB (hazard ratio [HR], 0.54 [0.32; 0.89], p=0.016) but the difference was not significant after adjustment on the propensity score (HR, 0.70 [0.39; 1.25], p=0.22). The proportion of patients with good neurological outcomes was not significantly different (36% with and 22% without NMB, p=0.16). Early-onset pneumonia was more common with NMB (HR, 2.36 [1.24; 4.50], p=0.009) but the difference was not significant after adjustment on the propensity score (HR, 1.68 [0.90; 3.16], p=0.10). CONCLUSIONS Continuous intravenous NMB during TH after cardiac arrest has potential owns effects on ICU survival with a trend increase in the frequency of early-onset pneumonia. Randomised controlled trials are needed to define the role for NMB among treatments for TH-induced shivering.

Do parents understand the medical information provided in paediatric emergency departments? A prospective multicenter study.

Aim:  We evaluated the extent to which parents understood the medical information about hospitalization of their child in an emergency department and looked for characteristics likely to increase the risk of poor comprehension.

Validation of specific questionnaires to assess nausea and vomiting of pregnancy in a French population

To validate the modified Pregnancy‐Unique Quantification of Emesis and Nausea (PUQE) score and the Health‐Related Quality of Life for Nausea and Vomiting of Pregnancy (NVP‐QOL) score in a French population.

Efficacy of maternal and biological parameters at the time of diagnosis of gestational diabetes mellitus in predicting neonatal morbidity

OBJECTIVE Gestational diabetes mellitus (GDM) is independently associated with an increased risk of maternal-fetal complications. Improved glycemic control allows reducing perinatal morbidity and mortality and, specifically, the risk of macrosomia and shoulder dystocia which are the most common complications associated with GDM. Nonetheless, a need for early antenatal predictor of neonatal morbidity in women suffering from GDM is required. The objective of the study was to evaluate the efficacy of different maternal, biological, and antenatal parameters at the time of diagnosis of GDM or perinatal variables as predictors of neonatal morbidity. STUDY DESIGN This was a prospective observational study recruited all pregnant women with diagnosis of GDM at first- or second-trimester in a tertiary care hospital from July 2014 to October 2015. Different antenatal parameters (maternal weight, weight gain during pregnancy, history of GDM, history of macrosomia, serum fructosamine, HbA1c) were obtained at the time of diagnosis of GDM. Mode of delivery was also analyzed. Neonatal morbidity was defined by at least one of the following criteria: preterm birth <37 weeks, macrosomia, shoulder dystocia, respiratory distress syndrome, 5-min Apgar score <7, pH < 7.10 and admission to the NICU (neonatal intensive care unit) for 24 h. Univariate and logistic regression analyses were performed to determine independent antenatal predictors of neonatal morbidity. RESULTS Two hundred pregnant women with diagnosis of GDM were included. The mean gestational age at the time of diagnosis of GDM was 22 ± 6 weeks. Insulin was required in 72/200 (36%) women for glycemic control during pregnancy. Neonatal morbidity occurred in 21% (n = 42). In the univariate analysis, neonatal morbidity was associated with nulliparity (50% compared to 32%, p = 0.03), induction of labor (36% compared to 27%, p = 0.03) and cesarean section (36% compared to 12%, p < 0.01). Multivariable logistic regression analysis found a significant association between nulliparity and neonatal morbidity (adjusted odds ratio [OR] 2.3, 95% confidence interval [CI] 1.1-4.7). Cesarean delivery was also significantly associated with neonatal morbidity (aOR 7.6, 95% CI 2.9-20). CONCLUSION This suggests that nulliparity was an efficient antenatal predictor of neonatal morbidity at the time of diagnosis of GDM. Cesarean section was also associated with neonatal morbidity in women with GDM.

Under sevoflurane anaesthesia, a reduced dose of neostigmine can antagonize a shallow neuromuscular block: A double-blind, randomised study

BACKGROUND It has been demonstrated that small doses of neostigmine (10-30μg.kg(-1)) effectively antagonize atracurium blocks at a train-of-four (TOF) ratio of 0.4 under propofol anaesthesia. The results might not be valid with halogenated agents, which potentiate neuromuscular blockades. The goal of this study was to determine the dose of neostigmine required to antagonize a block corresponding to a TOF ratio of 0.4, a level at which fade is not visually detected. METHODS Sixty patients were included and anaesthesia was induced with propofol, remifentanil and cisatracurium, and maintained with sevoflurane and remifentanil. Patients were randomized to receive neostigmine at 40, 20, 10μg.kg(-1) or placebo with atropine (20, 10, 5 or 0μg.kg(-1), respectively) as soon as the TOF ratio reached 0.4. Elapsed times to 0.9 and 1.0 TOF ratios were measured. RESULTS The median times elapsed from 0.4 to 0.9 and 1.0 TOF ratios in the placebo group were 19 (10.5-36) min and 26 (20-50) min, respectively, and significantly shorter (I=0.002) with any dose of neostigmine than without. Times for complete recovery after 40 and 20μg.kg(-1) neostigmine were similar [5.5 (4-11) min and 7.8 (3.5-11) min, respectively] but significantly shorter than after 10μg.kg(-1) neostigmine [17min (7-55); I=0.001]. CONCLUSION Under sevoflurane anaesthesia, in absence of tactile or visual TOF fade, which corresponds to a TOF ratio≥0.4, 20μg.kg(-1) neostigmine is as effective as 40μg.kg(-1) in antagonizing shallow cisatracurium block.