Blood levels of phosphatidylethanol in pregnant women reporting positive alcohol ingestion, measured by an improved LC-MS/MS analytical method.

OBJECTIVE: A reliable biomarker of low alcohol exposure during pregnancy is needed to clarify the controversy on the teratogenicity of low-to-moderate alcohol levels. METHODS: Blood samples were obtained from 13 pregnant women who self-reported alcohol ingestion between 2.5 and 20 drinks/week, and from 26 controls. Total lipids were extracted, and phosphatidylethanol (PEth) species 16:0/16:0, 16:0/18:1, and 16:0/18:1 were separated by high-performance liquid chromatography (HPLC) on a reverse-phase phenyl column. These PEth species were quantified by MS/MS using phosphatidylpropanol as internal standard, with electrospray ionization and MRM. RESULTS: PEth species were not detected in women who abstained from alcohol ingestion during pregnancy, whereas PEth-16:0/18:1 was > 5 nmol/L in those with positive alcohol ingestion. PEth species were detected for up to 4 weeks after cessation of exposure. CONCLUSIONS: PEth-16:0/18:1 was detected in pregnant women at 4-6 weeks after their last low-to-moderate alcohol ingestion, and therefore appears to be a reliable biomarker of prenatal alcohol exposure to study the teratogenicity of alcohol at these exposure levels.

Influence of time at which oxytocin is administered during labor on uterine activity and perinatal death in pigs.

Oxytocin is extensively used to induce or augment uterine contractions, especially to facilitate the third stage of labor in humans. Administration of oxytocin to parturient sows reduces duration of labor whereas mortality of the offspring may remain unchanged. This study aimed to evaluate whether time of administration of oxytocin during parturition may alter the uterine response and fetal outcomes. Two hundred parturient sows were randomly assigned to intramuscularly receive either saline solution (control group) or oxytocin 0.083 IU/kg immediately after the delivery of the 1st, 4th or 8th piglet (groups O-1, 0-4 and 0-8, respectively). Uterine effects and fetal outcomes were registered in all groups. The duration of labor was 20-40 min shorter (P < 0.0001) and time interval between babies was reduced by 3-5 min (P < 0.0001) in the three groups receiving oxytocin. The duration and intensity of contractions, meconium-stained piglets and intrapartum deaths decreased as time at which oxytocin administered during labor was increased. In group 0-8, we observed approximately 70% less meconium-stained piglets and intrapartum deaths than in the control group. In conclusion, oxytocin administered at early phases of parturition to sows may increase duration and intensity of uterine contractions as well as adverse fetal outcomes.

Influence of time at which oxytocin is administered during labor on uterine activity and perinatal death in pigs

Oxytocin is extensively used to induce or augment uterine contractions, especially to facilitate the third stage of labor in humans. Administration of oxytocin to parturient sows reduces duration of labor whereas mortality of the offspring may remain unchanged. This study aimed to evaluate whether time of administration of oxytocin during parturition may alter the uterine response and fetal outcomes. Two hundred parturient sows were randomly assigned to intramuscularly receive either saline solution (control group) or oxytocin 0.083 IU/kg immediately after the delivery of the 1st, 4th or 8th piglet (groups O-1, 0-4 and 0-8, respectively). Uterine effects and fetal outcomes were registered in all groups. The duration of labor was 20-40 min shorter (P < 0.0001) and time interval between babies was reduced by 3-5 min (P < 0.0001) in the three groups receiving oxytocin. The duration and intensity of contractions, meconium-stained piglets and intrapartum deaths decreased as time at which oxytocin administered during labor was increased. In group 0-8, we observed approximately 70 percent less meconium-stained piglets and intrapartum deaths than in the control group. In conclusion, oxytocin administered at early phases of parturition to sows may increase duration and intensity of uterine contractions as well as adverse fetal outcomes.

Use of proton pump inhibitors during pregnancy and breastfeeding.

QUESTION: A 36-year-old pregnant patient has symptoms of peptic disease. Treatment with diet and lifestyle modifications and also antacids has given her little relief. If she were not pregnant, I would prescribe a proton pump inhibitor (PPI) for her. She is now 4 weeks pregnant, and I need to determine whether PPIs are safe during pregnancy. ANSWER: Data currently available suggest that omeprazole is not teratogenic in humans. While information on other PPIs is limited, a systematic review of the evidence suggests that they are also not teratogenic.

Caudal block with 4 mg x kg-1 (1.6 ml x kg-1) of bupivacaine 0.25% in children undergoing surgical correction of congenital pyloric stenosis.

BACKGROUND: Since 1970, bupivacaine 0.25% in a dose of 4 mg x kg-1 (1.6 ml x kg-1) has been used at the Hospital Infantil de México for caudal block in children undergoing surgical correction of congenital pyloric stenosis (CPS). Although this dose is considered unsafe, in our experience, it has been associated with a high success rate and a low incidence of adverse events. This experience has not been previously documented. METHODS: A retrospective cohort of patients undergoing surgical correction of CPS was studied. Nineteen patients received general anaesthesia while 223 received caudal block. The latter were then grouped according to the sedation technique. The rate of successful caudal blocks and complications were considered the major outcomes of the study, whereas the postsurgical fasting period and hospital stay were considered secondary outcomes. RESULTS: The rate of success of caudal block was 96%. Anaesthetic complications related to bupivacaine were present in 1.3%. Mortality occurred in the postoperatory period in one septic patient who also was suffering from gastroschisis that required general anaesthesia. Postoperatory fasting period and hospital stay tended to be higher with general anaesthesia than caudal block. However, of the 19 patients receiving general anaesthesia, five suffered serious comorbidity and nine were failed caudal blocks. CONCLUSIONS: Caudal block with bupivacaine 0.25% (4 mg x kg-1) was associated with a low rate of anaesthetic complications. Further prospective studies to clarify the risks and benefits are required.

Population pharmacodynamic modeling without plasma concentrations of rocuronium in children.

Using the pharmacodynamic model without plasma concentrations described by Bragg et al, an individual approach resulted in highly variable parameters for rocuronium. Using a population approach of the model, the time course of the effect of an IV bolus dose of 400, 600, and 800 microg/kg of rocuronium was studied. Response was measured by accelerometry (TOF-Guard) in 45 low-risk surgical children, ages 2 to 14 years, who were receiving general anesthesia with isoflurane. Using a Bayesian approach and the software P-PHARM, response (the first twitch of the TOF) was modeled. The apparent rate constant of elimination, the rate constant for equilibrium between plasma and the effect compartment, the sigmoidicity factor of the relationship between drug concentration in the effect compartment and the effect, and the infusion rate that produces 50% of the effect at steady state were obtained. Population and individual post hoc parameters were similar among groups and variability was reduced.

Effect of mivacurium 200 and 250 &mgr;g/kg in infants during isoflurane anesthesia: a randomized controlled trial [ISRCTN07742712].

BACKGROUND: Infants usually respond differently to a neuromuscular relaxant compared to children or adults. Isoflurane is commonly used as an anesthetic gas in infants. In an RCT design, we investigated whether a dose of mivacurium 250 &mgr;g/kg results in faster onset of action than 200 &mgr;g/kg in infants under isoflurane anesthesia. Spontaneous recovery times and cardiovascular response were also evaluated. METHODS: Twenty-four low surgical risk children, aged 6-24 months, undergoing an elective surgery and requiring tracheal intubation were selected. After anesthetic induction, patients randomly received an iv bolus dose of mivacurium 200 or 250 &mgr;g/kg. After maximal relaxation, the patient was intubated. Isoflurane was administered to maintain anesthetic level during the surgical procedure. Neuromuscular function was monitored by accelerometry (TOF-Guard) at the adductor pollicies. The first twitch (T) of the TOF and the T4/T1 were measured. The time-course of heart rate and systolic and diastolic blood pressure were analysed by transforming them into their respective areas under the curve. RESULTS: Mivacurium 250 &mgr;g/kg produced a maximal T block faster than 200 &mgr;g/kg, i.e. 2.4 +/- 1.1 vs. 3.5 +/- 1.4 min (p < 0.05). Spontaneous recovery times were similar in both groups. Heart rate was similar between doses while systolic and diastolic blood pressures were lower with the higher dose (p < 0.05). Flushing was observed in two cases, one in each group. CONCLUSIONS: The maximal effect of mivacurium 250 &mgr;g/kg, in infants under isoflurane anesthesia, was present one minute faster than 200 &mgr;g/kg. However, it produced a significant cardiovascular response.

Rocuronium administration in children during isoflurane anesthesia: neuromuscular effects

Brockground. The time-course of the effect of rocuronium during isoflurane anesthesia in children rarely evaluated. Forty-five children, aged 2-14 years, ASA 1, undergoing elective surgery and receiving isoflurane anesthesia, were studied. Methods. Patients randomly received a dose of 400, 600, or 800 µg/kg of rocuronium. The first response to control height (T1:TO) was fitted to time in order to obtain times to onset of action (TOA) including time to 90 (b10) and 99.9 percent (B100) of relaxation and to spontaneous reconver of 10 (T10), 25 (t25), 50 (t75), and 90 percent (T90) of neuromuscular function (NMF). Each time was compared among group. Linear regression analysis between the TOA or the times to spontaneous recovery of NMF (TSRNMF) and age or weight were also performed. Results. The TOA were similar among the three groups while TSRNF in children receiving 600 or 800 µg/kg were longer (p< 0.05) than children receiving 400 µg/kg. The T10 and T25 were related to age (p= 0.05), whereas T10, T50, T75, and T90 were related to weight (p< 0.01). These relationships were stringer in males than females. Conclusions. Maximal relaxation was reached in all children receiving 600 or 800 µg/kg of rocuronium. The TSRNMF were mainly related to the weight of the children, and gender affected each relationship. Widely variable response were observed with all three doses