Determination of the optimal dose of ephedrine in the treatment of arterial hypotension due to general anesthesia in neonates and infants below 6 months old: the ephedrine study protocol for a randomized, open-label, controlled, dose escalation trial.

BACKGROUND: Arterial hypotension induced by general anesthesia is commonly identified as a risk factor of morbidity, especially neurological, after cardiac or noncardiac surgery in adults and children. Intraoperative hypotension is observed with sevoflurane anesthesia in children, in particular in neonates, infants younger than 6 months, and preterm babies. Ephedrine is commonly used to treat intraoperative hypotension. It is an attractive therapeutic, due to its dual action on receptors alpha and beta and its possible peripheral intravenous infusion. There are few data in the literature on the use of ephedrine in the context of pediatric anesthesia. The actual recommended dose of ephedrine (0.1 to 0.2 mg/Kg) frequently leads to a therapeutic failure in neonates and infants up to 6 months of age. The use of higher doses would probably lead to a better correction of hypotension in this population. The objective of our project is to determine the optimal dose of ephedrine for the treatment of hypotension after induction of general anesthesia with sevoflurane, in neonates and infants up to 6 months of age. METHODS: The ephedrine study is a prospective, randomized, open-label, controlled, dose-escalation trial. The dose escalation consists of 6 successive cohorts of 20 subjects. The doses studied are 0.6, 0.8, 1, 1.2, and 1.4 mg/kg. The dose chosen as the reference is 0.1 mg/kg, the actual recommended dose. Neonates and infants younger than 6 months, males and females, including preterm babies who undergo a surgery with general anesthesia inducted with sevoflurane were eligible. Parents of the subject were informed. Then, the subjects were randomized if presenting a decrease in mean blood pressure superior to 20% of their initial mean blood pressure (before induction of anesthesia), despite a vascular filling with sodium chloride 0.9%. The primary outcome is the success of the therapy defined as an mBP superior to 80% of the baseline mBP (prior to anesthesia) within 10 min post ephedrine administration. The subjects were followed-up for 3 days postanesthesia. DISCUSSION: This study is the first randomized, controlled trial intending to determine the optimal dose of ephedrine to treat hypotension in neonates and infants below 6 months old. TRIAL REGISTRATION: ClinicalTrials.gov NCT02384876 . Registered on March 2015.

Contribution of blood detection of insulin-like growth factor binding protein-1 for the diagnosis of amniotic-fluid embolism: a retrospective multicentre cohort study.

OBJECTIVE: To assess the contribution of maternal blood detection of IGFBP-1 for the diagnosis of amniotic-fluid embolism in clinical daily practice. DESIGN: A retrospective multicentre cohort study. SETTING: Three tertiary care obstetric units in France. SAMPLE: Data of 86 women for whom amniotic-fluid embolism had been suspected and maternal serum detection of IGFBP-1 had been performed between 2011 and 2019 were analysed. METHODS: The criteria defined by the United Kingdom Obstetric Surveillance System (UKOSS) were used for the retrospective diagnosis of amniotic-fluid embolism. The more structured definition proposed by the Society for Maternal-Fetal Medicine and the Amniotic Fluid Embolism Foundation (SMFM) was also used as secondary endpoint. MAIN OUTCOME MEASURES: Agreements between biological and clinical assessments were tested. The performance of blood detection of IGFBP-1 for the diagnosis of amniotic-fluid embolism according to the UKOSS criteria, and to the SMFM definition, was also assessed. RESULTS: There was only slight agreement between clinical and laboratory diagnosis of amniotic-fluid embolism (Cohen's Kappa coefficient: 0.04). Blood detection of IGFBP-1 had a sensitivity of 16%, a specificity of 88%, a positive and a negative likelihood ratio of 1.3 and 0.95, respectively, and a positive and a negative predictive value of 58 and 50%, respectively, for the diagnosis of amniotic-fluid embolism based on the UKOSS criteria. The use of the more structured SMFM definition of amniotic-fluid embolism did not substantially change the results. CONCLUSION: These results question the usefulness of blood detection of IGFBP-1 for the early diagnosis of amniotic-fluid embolism in daily clinical practice. TWEETABLE ABSTRACT: This retrospective multicentre study questions the contribution of IGFBP-1 detection for the diagnosis of AFE.

Infrared thermography to assess dermatomal levels of labor epidural analgesia with 1 mg/mL ropivacaine plus 0.5 µg/mL sufentanil: a prospective cohort study.

BACKGROUND: Assessment of the effectiveness of obstetric epidural analgesia may be difficult and techniques for objective assessment of epidural spread of local anesthetic would be useful. In this prospective cohort study we assessed whether obstetric epidural analgesia from a low concentration of ropivacaine led to significant change in cutaneous temperature, related to sympathetic block detected by infrared thermography, at dermatomes C4, T4, T10, L2 and L5. METHODS: Women in spontaneous labor who requested epidural analgesia were consecutively recruited. Epidural analgesia was induced with a bolus of 10-15 mL of ropivacaine 1 mg/mL and sufentanil 0.5 µg/mL, followed by continuous epidural infusion. Skin temperature was measured using thermography before and 20 min after the epidural bolus. The verbal pain score using a numeric rating scale was recorded before and 60 min after the epidural bolus. The upper sensory block to cold sensation was tested 30 and 60 min after the bolus by a physician blinded to the skin temperature. Failed epidural analgesia was defined as verbal pain score >3 at 60 min. RESULTS: Fifty-three parturients were included and analyzed. We found a significant increase in skin temperatures measured at T4, T10, L2 and L5 dermatomes, but not at C4, and a significant difference in the change in skin temperature at T10 between failed (n=3) and successful (n=50) epidural analgesia. CONCLUSIONS: These results suggest that infrared thermography might be useful for the early diagnosis of successful obstetric epidural analgesia.

Reliability of gastric suctioning compared with ultrasound assessment of residual gastric volume: a prospective multicentre cohort study.

We aimed to compare the reliability of aspiration via a nasogastric tube with ultrasound for assessment of residual gastric volume. Sixty-one adult patients who were mechanically ventilated and received continuous enteral feeding through a nasogastric tube for > 48 h were included. A first qualitative and quantitative ultrasound examination of the gastric antrum was followed by gastric suctioning, performed by an operator blinded to the result of the ultrasound examination. A second ultrasound examination was performed thereafter, followed by re-injection of the aspirated gastric contents (≤ 250 ml) into the stomach. A third ultrasound assessment was then immediately performed. If the suctioned volume was ≥ 250 ml, 250 mg erythromycin was infused over 30 min. A fourth ultrasound was performed 90 min after the third. Sixty (98%) patients had a qualitatively assessed full stomach at first ultrasound examination vs. 52 (85%) after gastric suctioning (p = 0.016). The calculated gastric volume significantly decreased after gastric suctioning, without a significant decrease in the number of patients with volume ≥ 250 ml. Four of the nine patients with calculated gastric volume ≥ 250 ml had vomiting within the last 24 h (p = 0.013). The antral cross-sectional area significantly decreased between the third and the fourth ultrasound examination (p = 0.015). Erythromycin infusion did not make a significant difference to gastric volume (n = 10). Our results demonstrate that gastric suctioning is not a reliable tool for monitoring residual gastric volume. Gastric ultrasound is a feasible and promising tool for gastric volume monitoring in clinical practice.

Effect of body position on qualitative and quantitative ultrasound assessment of gastric fluid contents.

We assessed the impact of raising the upper section of the bed, and patient positioning, on ultrasound assessment of gastric fluid contents. We performed ultrasound examinations in 25 subjects lying on their back, left and right sides at bed angles of 0°, 30°, 45° and 90°; this was carried out while the subjects were fasted, and repeated 10 min after drinking ≥ 50 ml water. After drinking, gastric contents were detected more frequently in the 45° semirecumbent position compared with the supine and 30° positions. The diagnostic performance of the Perlas qualitative grading scale to detect gastric fluid volume > 1.5 ml.kg-1 was improved at 45°, compared with 0° and 30° angles. The use of a composite ultrasound grading scale at a 45° angle was associated with the best performance, with a sensitivity and specificity of 82%. Antral cross-sectional area was significantly increased when measured in the right lateral position, but there was no effect of raising the bed. In conclusion, raising the upper section of the bed significantly affected qualitative assessment of gastric fluid contents. Further studies are required to determine the most appropriate composite ultrasound grading scale and bed angle for fast and reliable qualitative ultrasound detection of fluid volumes > 1.5 ml.kg-1 .

Incidence, characteristics, and predictive factors for medication errors in paediatric anaesthesia: a prospective incident monitoring study.

BACKGROUND: Medication errors are not uncommon in hospitalized patients. Paediatric patients may have increased risk for medication errors related to complexity of weight-based dosing calculations or problems with drug preparation and dilution. This study aimed to determine the incidence of medication errors in paediatric anaesthesia in a university paediatric hospital, and to identify their characteristics and potential predictive factors. METHODS: This prospective incident monitoring study was conducted between November 2015 and January 2016 in an exclusively paediatric surgical centre. Children <18 yr undergoing general anaesthesia were consecutively included. For each procedure, an incident form was completed by the attending anaesthetist on an anonymous and voluntary basis. RESULTS: Incident forms were completed in 1400 (73%) of the 1925 general anaesthetics performed during the study period with 37 reporting at least one medication error (2.6%). Drugs most commonly involved in medication errors were opioids and antibiotics. Incorrect dose was the most frequently reported type of error (n=27, 67.5%), with dilution error involved in 7/27 (26%) cases of incorrect dose. Duration of procedure >120 min was the only factor independently associated with medication error [adjusted odds ratio: 4 (95% confidence interval: 2-8); P=0.0001]. CONCLUSIONS: Medication errors are not uncommon in paediatric anaesthesia. Identification of the mechanisms related to medication errors might allow preventive measures that can be assessed in further studies.

Assessment of Neurological Toxicity of Hydroxyethyl Starch 130/0.4 Injected in the Intrathecal Space in Rats.

Objective: Epidural blood patch is the procedure of choice to relieve postdural puncture headache. Hydroxyethyl-starch (HES) has been proposed as a patch in some circumstances such as in the case of hematological disease due to the theoretical risk of neoplastic seeding to the central nervous system. Acute neurological HES toxicity has been excluded by a previous animal study, but the long-term neurological toxicity has not been evaluated. Methods: Rats were randomly assigned to one of three groups: no intrathecal injection, 20 µL of intrathecal saline, or a 20-µL intrathecal HES (6% hydroxyethyl starch 130/0.4) administered via a cervical puncture. Clinical daily rat activity was measured before and after dural puncture by actinometry. The rats were killed at day 28, and the spinal cord was surgically removed and stained with hematoxylin-phloxine-saffron for gross and microscopic examination. Results: Eleven rats underwent dural puncture without injection, 11 were injected with normal saline, and 12 received intrathecal HES. No clinical or actimetric changes (total distance traveled, number of direction changes, and number of rearings) were observed up to one month after injection. Nonspecific histopathological changes were equally observed in all groups. Conclusions: The results of the current study indicate that intrathecal injection of HES in rats does not induce any clinical or histopathological evidence of long-term neuronal toxicity. Further safety studies in animals are warranted before HES might be considered a safe alternative to the classic epidural blood patch.

The effect of pre-operative gastric ultrasound examination on the choice of general anaesthetic induction technique for non-elective paediatric surgery. A prospective cohort study.

Ultrasound examination of the gastric antrum is a non-invasive tool that allows reliable estimation of gastric contents. We performed this prospective cohort study in non-elective paediatric surgery to assess whether gastric ultrasound may help to determine the best anaesthetic induction technique, whether rapid sequence or routine. The primary outcome was the reduction of inappropriate induction technique. A pre-operative clinical assessment was performed by the attending anaesthetist who made a provisional plan for induction. Gastric ultrasound was performed in the semirecumbent and right lateral decubitus positions for a qualitative assessment of gastric contents, using a 0-2 grading scale. A final induction plan was made based on this assessment. Immediately after tracheal intubation, gastric contents were suctioned through a multi-orifice nasogastric tube; these were defined as above risk threshold for regurgitation and aspiration if there was clear fluid > 0.8 ml.kg-1 , and/or the presence of thick fluid and/or solid particles. Gastric ultrasound was feasible in 130 out of 143 (90%) of children, and led to a change in the planned induction technique in 67 patients: 30 from routine to rapid sequence, and 37 from rapid sequence to routine. An appropriate induction technique was therefore performed in 85% of children, vs. 49% planned after pre-operative clinical assessment alone (p < 0.00001). Our results suggest that gastric ultrasound is a useful guide to the general anaesthetic induction technique with respect to the risk of pulmonary aspiration, in comparison with pre-operative clinical assessment alone.

[Maternal deaths due to anesthesia complications. Results from the French confidential enquiry into maternal deaths, 2010-2012]. / Mortalité maternelle liée à l'anesthésie-réanimation. Résultats de l'ENCMM, France 2010­2012.

Over the period 2010-2012, maternal mortality linked to anesthesia accounted for 2% of maternal deaths, with no significant change since 2007-2009. Of the 7 maternal deaths analyzed by the expert committee, anesthetic complications were in 5 cases the main cause of death: 4 attributed to direct causes related to anesthetic procedures during childbirth and 1 to indirect cause in connection with an ENT complication during pregnancy. The anesthetic causes of maternal mortality were for the 2010-2012 period: cardiac arrest under spinal anesthesia during caesarean section, local anesthetic intoxication with unsuccessful resuscitation after cardiac arrest without intralipid administration, acute respiratory distress syndrome in the postpartum period after pulmonary aspiration during caesarean section, cardiac arrest during caesarean section under general anesthesia in a context of non-Hodgkin lymphoma with mediastinal syndrome, unsuccessful endotracheal intubation in a context of cellulitis of the oral cavity floor. In two other cases, anesthetic complications were identified as associated causes of death, the primary cause being intracerebral hemorrhage stroke and pulmonary hypertension. In most of the cases analyzed over the period 2010-2012, anesthesia and resuscitation have been involved in the occurrence of maternal deaths, mainly through strategic errors in the management of patients with severe pathology before delivery, as well as through insufficient cardiac resuscitation duration after cardiac arrest.

[Maternal deaths due to cardiovascular disease. Results from the French confidential enquiry into maternal deaths, 2010-2012]. / Mortalité maternelle par pathologies cardiovasculaires. Résultats de l'enquête nationale française confidentielle sur la mortalité maternelle, 2010­2012.

Between 2010 and 2012, 29 maternal deaths were caused by cardiovascular disease, i.e. an overall maternal mortality ratio of 1.2 per 100,000 live births. Deaths occurred in pre-existing heart disease (n=19), peripartum cardiomyopathy (n=5), or arterial rupture (n=5). Care was considered non-optimal in three of five patients with congenital heart disease and due to delayed management by specialized teams. Pregnant patients with heart disease should be considered to be at high risk of mortality or severe cardiovascular complications and therefore reoriented as soon as possible to a perinatal center with the expertise of these pathologies. A delay in the management related to incorrect diagnosis was reported in three patients with peripartum cardiomyopathy. Peripartum cardiomyopathy should be considered in patients with severe left ventricular failure on cardiac ultrasound and particularly in women without pre-existing cardiac disease. A diagnosis of myocardial infarction was never suspected despite suggestive clinical and paraclinical criteria. A suggestive symptomatology of myocardial infarction reported in any pregnant woman and during the immediate postpartum period, and regardless of cardiovascular risk factors, should be promptly investigated and managed.

Effect of gum chewing on gastric volume and emptying: a prospective randomized crossover study.

BACKGROUND: Current fasting guidelines allow oral intake of water up to 2 h before induction of anaesthesia. We assessed whether gum chewing affects gastric emptying of 250 ml water and residual gastric fluid volume measured 2 h after ingestion of water. METHODS: This prospective randomized observer-blind crossover trial was performed on 20 healthy volunteers who attended two separate study sessions: Control and Chewing gum (chlorophyll flavour, with 2.1 g carbohydrate). Each session started with an ultrasound measurement of the antral area, followed by drinking 250 ml water. Then, volunteers either chewed a sugared gum for 45 min (Chewing gum) or did not (Control). Serial measurements of the antral area were performed during 120 min, and the half-time to gastric emptying (t½), total gastric emptying time, and gastric fluid volume before ingestion of water and 120 min later were calculated. RESULTS: Gastric emptying of water was not different between sessions; the mean (sdsd) t½ was 23 (10) min in the Control session and 21 (7) min in the Chewing gum session (P=0.52). There was no significant difference between sessions in gastric fluid volumes measured before ingestion of water and 120 min later. CONCLUSIONS: Chewing gum does not affect gastric emptying of water and does not change gastric fluid volume measured 2 h after ingestion of water. CLINICAL TRIAL REGISTRATION: NCT02673307.