piperidines and Cleft-Palate

To compare the clinical efficacies and safety of sevoflurane and propofol versus remifentanil and propofol anesthesia for children with cleft lip and palate repair surgery.. Upon the approval of hospital ethical committee,a total of 60 pediatric patients undergoing cleft lip and palate repair surgery were recruited from two hospitals between April 2011 and December 2012. All patients were randomly divided into 2 groups (n = 30 each). Group S:sevoflurane and propofol anesthesia; and group R: propofol and remifentanil anesthesia.Heart rate (HR), mean arterial pressure (MAP) and pulse oxygen saturation (SpO2) were recorded at the time before the induction (T0), after 2 min of induction (T1), the beginning of surgery (T2) and the end of surgery (T3).Intubating satisfaction, time to extubation,incidence of emergence agitation, postoperative nausea and vomiting, and the complications of the airway were recorded.. Satisfactory intubation rate was 90% in group S, versus 83% in group R. And there was no significantly difference between the two group. There were no significantly difference between the two group with MAP and HR.Compared with T0, There were significantly difference with MAP and HR at T1, T2 in group R (P < 0.05). The incidence of emergence agitation was significantly higher in group S (7 cases) than that in group R (2 cases).there were no records of nausea, vomiting and laryngospasm.. Under an adequate depth anesthesia, these two anesthesia techniques are safe for cleft lip and palate repair surgery, emergence agitation was high in sevoflurane anesthesia, propofol and remifentanil anesthesia provides lower heart rate.

Topics: Anesthesia; Child, Preschool; Cleft Lip; Cleft Palate; Female; Humans; Infant; Male; Methyl Ethers; Piperidines; Propofol; Remifentanil; Sevoflurane

Propofol-remifentanil anesthesia is widely used in adults but few studies are available in infants. We aimed at comparing the hemodynamic effects of propofol-remifentanil vs sevoflurane-fentanyl anesthesia. In addition, we sought to investigate recovery and whether remifentanil induced acute opioid tolerance.. In total, 39 infants 4-6 months old were prospectively enrolled and randomized to receive either a combination of remifentanil and propofol (n = 17) or a sevoflurane-fentanyl anesthesia (n = 22) for surgical repair of cleft lip and palate. In both groups, sevoflurane was used for induction of anesthesia and fentanyl was administered before tracheal extubation. Mean arterial blood pressure and heart rate were recorded every 5 min after induction. We also recorded time from termination of surgery to tracheal extubation, postoperative behavior and the need for analgesia for the first 24 h after surgery. Postoperative observations were blinded.. In the remifentanil-propofol group, the mean arterial blood pressure was higher [58 (51-65) vs 51 (45-55), P = 0.02] and the mean heart rate was lower [111 (108-113) vs 128 (122-143), P < 0.0001]. There were no differences in recovery time or behavior after surgery. In the remifentanil group, a median fentanyl dose of 4 microg x kg(-1) was required to insure a smooth recovery, but there was no difference in morphine consumption during the first 24 h after surgery.. A high-dose remifentanil-propofol infusion was associated with a higher blood pressure and lower heart rate than sevoflurane-fentanyl anesthesia in infants. Postoperative morphine consumption, recovery time and quality were similar.

Topics: Anesthesia Recovery Period; Anesthetics, Combined; Anesthetics, Inhalation; Anesthetics, Intravenous; Blood Pressure; Cleft Lip; Cleft Palate; Dose-Response Relationship, Drug; Female; Heart Rate; Humans; Infant; Intubation, Intratracheal; Male; Methyl Ethers; Mouth Abnormalities; Piperidines; Propofol; Prospective Studies; Remifentanil; Sevoflurane; Time Factors

Postoperative behavioral disorders are common in children, but the occurrence in infants is not yet clear. In the present study we focus on postoperative sleep disturbances, which we hypothesized would be more common after sevoflurane anesthesia than propofol-remifentanil anesthesia.. In total, 39 infants 4-6-mo-old were prospectively enrolled and randomized to receive either a combination of propofol and remifentanil (n = 17) or sevoflurane and fentanyl anesthesia (n = 22) for surgical repair of cleft lip-gum-palate. Postoperative observations were blinded. The parents kept a sleep diary for 2 wk before admission and 2 wk after returning home. The diary included information about how many times the infant awoke during the night and was difficult to comfort and the longest duration of continuous sleep during the night.. Longest continuous sleep was significantly longer in the sevoflurane group (median 7.2 h) compared with the propofol-remifentanil group (median 5.1 h, P < 0.05). No other significant difference was found between groups. Sleep pattern was impaired after surgery in both groups compared with that before surgery (P < 0.01), but it was considered by the parents to be back to normal after a median of 10 days, with no significant difference between groups.. Postoperative sleep disturbances occur in infants after both propofol-remifentanil and sevoflurane anesthesia. Sevoflurane seems to be associated with less impairment of postoperative sleep than propofol-remifentanil in the first weeks after repair of cleft lip and palate in infants.

Topics: Anesthetics, Combined; Anesthetics, Inhalation; Anesthetics, Intravenous; Cleft Lip; Cleft Palate; Follow-Up Studies; Humans; Infant; Methyl Ethers; Piperidines; Postoperative Period; Propofol; Prospective Studies; Remifentanil; Reproducibility of Results; Severity of Illness Index; Sevoflurane; Single-Blind Method; Sleep; Sleep Wake Disorders; Surveys and Questionnaires; Time Factors

The residual depressant effect of opioid is a major concern in infants scheduled for cleft palate repair. Remifentanil is associated with a fast and predictable recovery, independent of age.. About 40 infants in the 2-12 month age range were prospectively enrolled in this open study, to receive either remifentanil (infusion starting at 0.25 microg x kg(-1) x min(-1)) or sufentanil as part of a balanced anaesthesia regimen. Isoflurane was maintained at an endtidal concentration of 1.2% in oxygen and nitrous oxide and the opioid dosing was titrated to autonomic responses. Postoperative pain relief was provided by morphine infusion. Morphine administration started intraoperatively in the remifentanil group.. Consistent haemodynamic stability was achieved throughout surgery in both groups. Infants of the remifentanil group required, on average, lower concentrations of isoflurane than children of the sufentanil group (1.2 +/- 0.2% vs 1.7 +/- 0.3%, P < 0.001). The median time from last suture to tracheal extubation was 12.5 min (5-25 min) in the remifentanil group and 15.0 min (10-30 min) in the sufentanil group. There was no evidence of hyperalgesia or enhanced morphine consumption in the remifentanil group compared with the sufentanil group. Postoperative pain scores were even lower in the remifentanil group, compared with the sufentanil group, soon after arrival in the postanaesthesia care unit.. Remifentanil-based anaesthesia appeared well suited for primary cleft palate repair in young infants.

Topics: Analgesics, Opioid; Anesthetics, Inhalation; Blood Pressure; Cleft Palate; Female; Heart Rate; Humans; Infant; Isoflurane; Male; Morphine; Pain, Postoperative; Piperidines; Prospective Studies; Remifentanil; Sufentanil; Time Factors; Treatment Outcome

Topics: Acetaminophen; Analgesia; Analgesics, Non-Narcotic; Analgesics, Opioid; Child; Cleft Lip; Cleft Palate; Data Collection; Humans; Ireland; Pain, Postoperative; Piperidines; Remifentanil; United Kingdom

Casopitant is a potent and selective NK-1 receptor antagonist that has shown clinical efficacy in the prevention of chemotherapy-induced and postoperative-induced nausea and vomiting.. In an embryo-fetal development study, pregnant mice were given vehicle (sterile water) or doses of 30, 100, or 300 mg/kg/day casopitant on Gestation Day (GD) 6 to 15. Fetuses were evaluated for external, visceral, and skeletal abnormalities on GD 18. In a follow-on study to investigate casopitant-induced hormonal changes during the developmental period for palate formation, pregnant mice were given vehicle (sterile water) or 300 mg/kg/day casopitant once daily on GD 6 to 13. Blood was collected on GD 13 at various time-points for measurement of plasma adrenocorticotropic hormone and corticosterone (CRT) concentrations.. There was no evidence of developmental toxicity in mice at 30 or 100 mg/kg/day but 9% of fetuses at 300 mg/kg/day had cleft palate. Mice are sensitive to glucocorticoid-induced cleft palates, and NK-1 antagonists are known to modulate the hypothalamic-pituitary-adrenal axis leading to increases in corticosterone. On GD 13, mean plasma adrenocorticotropic hormone levels at 300 mg/kg/day were elevated by approximately twofold from vehicle-treated levels at 1 hr post-dose and mean plasma CRT levels were elevated by 3, 5, and 10-fold at 0.5, 1, and 2 hr post-dose, respectively.. The increased level of CRT was in the range previously shown in the literature to cause cleft palates in mice and was likely the underlying mechanism behind casopitant-induced cleft palate in mice.

Topics: Adrenocorticotropic Hormone; Animals; Cesarean Section; Cleft Palate; Corticosterone; Feeding Behavior; Female; Fetal Development; Mice; Neurokinin-1 Receptor Antagonists; Piperazines; Piperidines; Pregnancy; Receptors, Neurokinin-1; Weight Gain

Stickler's syndrome is an autosomal multisystem disorder accompanying characteristic midface hypoplasia, retromicrognathia, and cleft palate. Mandibular hypoplasia causes difficulties in mask ventilation and endotracheal intubation, especially in infants. A 7-month-old girl diagnosed as Stickler's syndrome was scheduled for the laparoscopic inguinal hernia repair. However, during the direct laryngoscopy for endotracheal intubation, neither the vocal cords nor the epiglottis were visualized. At fifth intubation attempts, the part of the vocal cords was barely visualized, and the tracheal intubation was finaly successful. Anesthesia was maintained with sevoflurane and remifentanil. The patient had an uneventful recovery and was discharged on the second postoperative day without any complications. Sevoflurane and remifentanil allow faster recovery from anesthesia and both have been recommended for patients with difficult tracheal intubation in a patient such as with Stickler's syndrome.

Topics: Anesthesia; Cleft Palate; Face; Female; Hernia, Inguinal; Humans; Infant; Intubation, Intratracheal; Laparoscopy; Laryngoscopy; Methyl Ethers; Mouth Abnormalities; Piperidines; Remifentanil; Sevoflurane; Syndrome

To compare the clinical effects and safety of propofol and remifentanil anaesthesia with sevoflurane and remifentanil anaesthesia for cleft lip and palate repair surgery in children.. Forty children undergoing elective cleft lip and palate repair surgery were randomly divided into two groups, 20 in each group. Group PR: Propofol and remifentanil anaesthesia; and group S: Sevoflurane and remifentanil anaesthesia. Heart rate (HR), mean arterial pressure (MAP), pulse oxygen saturation (SPO2), and end tidal carbon dioxide (ETCO2) were observed, and recorded at the time before the induction (T0), after 15 min of induction (T1), after 30 min of induction (T2), and after 1 min of extubation (T3). The time to extubation, incidence of restlessness, postoperative nausea and vomiting, and the complication of the airway were recorded.. There were no significantly differences between the two groups with respect to sex, age, weight, category of operation, and the time of operation. In group PR, after the period of induction, two children used atropine for bradycardia. One was 3-years-old, and the other was 8-years-old. The HR of former was lower than 100 beats per minute, and the latter was lower than 70 beats per minute. The average of HR in group PR was increased after 1 min of extubation compared with that before induction (P<0.05). In group S, the average of HR was increased in 30 min after induction and 1 min after extubation (P<0.05), and HR kept in faster range compared with that in group PR (P<0.05) at the 15 min and 30 min after induction. During the operation, SPO2 and ETCO2 of both groups consistently maintained in normal range. The time to extubation was comparable in two groups. The incidence of agitation after surgery was significantly higher in group S (8 cases) than that in group PR (2 cases). There were no records of nausea, vomiting, asphyxia, and laryngospasm.. Propofol and remifentanil anaesthesia was more significantly inhibited the HR of children. The emergence agitation has higher incidence in sevoflurane anaesthesia. Both methods can attain extubation requirement quickly.

Topics: Anesthesia; Child; Cleft Lip; Cleft Palate; Female; Humans; Male; Methyl Ethers; Piperidines; Propofol; Remifentanil; Sevoflurane

Topics: Abnormalities, Multiple; Adjuvants, Anesthesia; Anesthetics, Inhalation; Anesthetics, Intravenous; Atropine; Cleft Palate; Developmental Disabilities; Face; Female; Humans; Infant; Intellectual Disability; Intubation, Intratracheal; Methyl Ethers; Microcephaly; Midazolam; Muscle Hypotonia; Nitrous Oxide; Piperidines; Remifentanil; Sevoflurane; Syndrome

Cleft palate and minor front limb contractures were induced in calves by maternal ingestion of the piperidine alkaloid-containing lupines, Lupinus formosus and L. arbustus. Crooked calf disease, which includes an occasional cleft palate, is a congenital condition of widespread occurrence in cattle in the western U.S. and Canada. It is known to occur after maternal ingestion of certain species of Lupinus during specific gestational periods. Although many lupine species contain quinolizidine alkaloids including the teratogenic alkaloid anagyrine, L. formosus and L. arbustus produce piperidine alkaloids including the reported teratogen ammodendrine. In addition to ammodendrine, L. formosus contains both N-acetyl hystrine and N-methyl ammodendrine, whereas L. arbustus contains ammodendrine, trace amounts of N-methyl ammodendrine, and no N-acetyl hystrine. L. formosus and L. arbustus were fed to pregnant cows at equivalent ammodendrine doses during a 10-day period from days 40-50 of gestation. One calf from a cow fed L. formosus had a full cleft palate. Embryonic death and resorption of one fetus and minor front limb contractures (arthrogryposis) in another calf occurred with two cows fed L. arbustus. Alkaloid analysis of blood samples taken during the feeding period, and up to and including 48 hours after the last dose, demonstrated comparative plasma elimination times with N-methyl ammodendrine > ammodendrine > N-acetyl hystrine. The objectives of this experiment were to: 1) determine if N-acetyl hystrine is a potential teratogen; and 2) define the narrow cleft palate induction period in cows.

Topics: Alkaloids; Animal Feed; Animals; Arthrogryposis; California; Cattle; Cattle Diseases; Cleft Palate; Dihydropyridines; Female; Fetal Death; Gestational Age; Idaho; Piperidines; Plants, Toxic; Pregnancy; Prenatal Exposure Delayed Effects; Pyridines; Structure-Activity Relationship; Teratogens

A teratogenic compound cis-1-[4-(p-menthane 8-yloxy)phenyl]piperidine (YM9429) induces cleft palate selectively in rat fetuses. The effect of YM9429 on chondrogenic differentiation was investigated using mouse embryonic carcinoma ATDC5 cells that produce chondrocyte specific extracellular matrix upon insulin stimulation. YM9429 at concentrations that showed no growth-inhibitory effect on logarithmic proliferating cells suppressed insulin-mediated increases in Alcian blue staining and expression of type II collagen almost completely. Under the identical conditions, insulin-stimulated cell growth was only partially blocked by the compound. The early response genes such as c-fos and c-jun were induced by insulin even in the presence of YM9429. On the other hand, YM9429 inhibited accumulation of cAMP during the differentiation process. These results indicate that YM9429 selectively inhibits in vitro chondrogenic differentiation of ATDC5 cells.

Topics: Animals; Cartilage; Cell Differentiation; Cell Division; Cleft Palate; Gene Expression Regulation, Developmental; Genes, fos; Genes, jun; Insulin; Insulin Antagonists; Neoplastic Stem Cells; Piperidines; Rats; Receptor, Parathyroid Hormone, Type 1; Receptors, Parathyroid Hormone; Signal Transduction; Teratogens

The teratogenic potential of cis-1-[4-(p-menthane-8-yloxy)phenyl] [corrected] piperidine (YM9429) was evaluated using CD (SD) rats. YM9429 induced cleft palate and specific skeletal variations including accessory cervical and lumbar ribs or excessive formation of the 7th lumbar vertebra by oral treatment during the organogenetic periods. No visceral or external malformations were induced, and no embryo/fetal mortality or fetal growth retardation was observed. Maternal plasma biochemical examination revealed decreases of cholesterol and phospholipid levels during days 15-17 of pregnancy after the treatment. The results suggest that YM9429 is a potent and specific teratogen inducing cleft palate in CD rats, and the reduced maternal plasma levels of cholesterol and phospholipid during the period of palatine closure are related to the induction of cleft palate.

Topics: Abnormalities, Drug-Induced; Abnormalities, Multiple; Animals; Cholesterol; Cleft Palate; Female; Fetus; Lumbar Vertebrae; Phospholipids; Piperidines; Pregnancy; Rats; Rats, Sprague-Dawley; Ribs; Teratogens

Three piperidine alkaloid containing plants, Conium maculatum (poison-hemlock), Nicotiana glauca (tree tobacco) and Lupinus formosus (lunara lupine), induced multiple congenital contractures (MCC) and palatoschisis in goat kids when their dams were gavaged with the plant during gestation days 30-60. The skeletal abnormalities included fixed extension or flexure of the carpal, tarsal, and fetlock joints, scoliosis, lordosis, torticollis and rib cage abnormalities. Clinical signs of toxicity included those reported in sheep, cattle and pigs--ataxia, incoordination, muscular weakness, prostration and death. One quinolizidine alkaloid containing plant, Lupinus caudatus (tailcup lupine), on the other hand, which is also known to cause MCC in cows, caused only slight signs of toxicity in pregnant goats and no teratogenic effects in their offspring.

Topics: Abnormalities, Multiple; Alkaloids; Anabasine; Animals; Bone and Bones; Cleft Palate; Female; Goat Diseases; Goats; Nicotiana; Piperidines; Plant Extracts; Plant Poisoning; Plants, Toxic; Pregnancy; Pyridines; Teratogens

Fetal movement, observed by ultrasound imaging, was significantly reduced (P less than or equal to 0.001) in pregnant goats gavaged with Conium seed and Nicotiana glauca and temporarily reduced with fresh Conium plant. Conium seed and Nicotiana glauca induced cleft palate and multiple congenital contractures in 100% of the kids born to pregnant goats gavaged with these plants. Multiple congenital contractures included torticollis, scoliosis, lordosis, arthrogryposis, rib cage anomalies, over extension, and flexure and rigidity of the joints. However, in goats gavaged with fresh Conium plant, fetal movement was inhibited for only about 5 hours after each individual dosage and gradually returned to control levels 12 hours after dosing. Fetal malformations in this group were limited from modest to moderate contractures of the front limbs, which resolved by 8-10 weeks post partum. No cleft palates were induced. Fetal movement was not inhibited in goats fed Lupinus caudatus and no cleft palates or multiple congenital contractures were induced in their offspring. The duration of the reduction in fetal movement appears to be an important factor in the severity and permanence of the deformities, particularly with cleft palate, spinal column defects, and severe joint deviation and fixation.

Topics: Abnormalities, Drug-Induced; Abnormalities, Multiple; Administration, Oral; Alkaloids; Animals; Cleft Palate; Female; Fetal Movement; Goats; Maternal-Fetal Exchange; Piperidines; Pregnancy

Cleft palates were induced in newborn pigs of gilts fed Conium maculatum seed or plant during gestation days 30 through 45. Twelve of 23 newborn pigs born to 3 gilts given Utah-grown C maculatum seed and 9 of 12 newborn pigs born to a single gilt given the fresh Utah spring-growth C maculatum plant had cleft palates. The cleft palates ranged from a unilateral cleft, involving only 1 side of the palate, to a full bilateral cleft. Brachygnathia was also observed in some of these newborn pigs with cleft palate. Other malformations were not observed. Chemical analysis of seed and plant samples indicated that gamma-coniceine was the responsible teratogenic alkaloid. A daily dose of plant or seed that provided greater than or equal to 1.07 mg of gamma-coniceine/kg of body weight fed to gilts during the 30th through the 45th day of pregnancy resulted in teratogenic effects.

Topics: Alkaloids; Animals; Animals, Newborn; Chromatography, Gas; Cleft Palate; Female; Piperidines; Plant Poisoning; Plants, Toxic; Pregnancy; Pregnancy Complications; Pyridines; Seeds; Swine; Swine Diseases