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Effectiveness of alimemazine in controlling retching after Nissen fundoplication.

BACKGROUND: Retching, an early component of the emetic reflex, is a common and distressing symptom in children after Nissen fundoplication. Alimemazine (trimeprazine, Vallergan; Castlemead, Herts, UK) is a phenothiazine derivative histamine(1) antagonist, which anecdotally relieves the retching symptoms. MATERIAL AND METHODS: A prospective, double-blind, randomized, crossover, placebo-controlled study of 15 neurologically impaired children with retching after Nissen fundoplication over a period of 1 year (December 2002-December 2003). Patients were randomly allocated to receive 1 week each of alimemazine and placebo with crossover. A diary was maintained of retching episodes 1 week before, during, and 1 week after the trial. Dosage of alimemazine used was 0.25 mg/kg 3 times a day (maximum, 2.5 mg per dose). Statistical analysis was done using a paired Student's t test, where P value of less than .05 was considered significant. Results are presented as mean +/- SD. RESULTS: Twelve parents completed the diaries (9 open, 3 laparoscopic Nissen fundoplication). Median age of the child was 36 months (8-180 months), median duration of retching was 4.5 months (1-52 months), and mean number of retching episodes per week was 60 +/- 29.40. Mean number of retching episodes with alimemazine was 10.42 +/- 9.48 vs 47.67 +/- 27.79 with a placebo (P < .0001). No adverse effects were reported in those cases that completed the study. CONCLUSION: At low dose, alimemazine (Vallergan) is a safe and effective drug in the management of retching after Nissen fundoplication.

Antipruritics↗

Acute fatal poisoning with cyamemazine.

A case of fatal poisoning with cyamemazine is presented. The cyamemazine was identified in post-mortem blood using a specific gas chromatographic/mass spectrometry method. The autopsy blood concentration of cyamemazine was 1800 ng/ml. Chronic use of cyamemazine was demonstrated by the presence of the drug in hair. Two other drugs were also detected (bromazepam and trimeprazine). We think that this current blood concentration (1800 ng/ml) is a fatal blood concentration because of the negativity of the other parameters, but careful interpretation of analytical findings are important, the possibility that this death was a consequence of the toxicity of combined drugs could not be excluded. Not many therapeutics and toxic levels were previously reported in overdosage cases in which cyamemazine was involved. We consider that this concentration is only of guidance value for a fatal cyamemazine poisoning.

Anti-Anxiety Agents↗

Modification of radiation response of E. coli B/r cells by phenothiazines.

Promethazine and trimeprazine sensitized anoxic E. coli B/r cells to 60Co gamma-rays, but both drugs showed a radioprotective effect under euoxic conditions. Their radiosensitizing effect was found to be due to the reaction of radiolytically induced hydroxyl radicals with the sensitizers. The radioprotective effect of these drugs is attributed to changes in the membrane structure conducive with chemical repair of the damaged sites in the gel region of the cellular membrane by intracellular sulphydryl compounds. Pre-irradiation depletion of sulphydryls from E. coli B/r by treatment with N-ethyl maleimide abolished the radio-protective effect of these drugs under euoxic conditions.

Escherichia coli↗

Effects of calmodulin antagonists on radiation-induced lipid peroxidation in microsomes.

Rat liver microsomes were irradiated with gamma-rays at a dose rate of 1.31 Gys-1. The extent of lipid peroxidation, measured in terms of malondialdehyde (MDA) formed, increased with radiation dose. The presence of calmodulin antagonists during irradiation decreased lipid peroxidation. The order of their protective efficiency was: chlorpromazine (CPZ) greater than promethazine (PMZ) greater than trimeprazine (TMZ). Their protective effect was diminished in the presence of ferrous (Fe2+) ions and was restored on addition of EDTA. However, calmodulin antagonists considerably inhibited radiation-induced lipid peroxidation in the presence of ferric (Fe3+) ions. Calmodulin antagonists also decreased the cytochrome P-450 content of microsomes. These results are discussed with respect to their applicability to radiotherapy. A possible mechanism for the inhibition of radiation-induced lipid peroxidation is suggested.

Animals↗

A double-blind drug trial of treatment in young children with waking problems.

A double-blind trial using trimeprazine tartrate was carried out in 22 children with severe waking problems. On parental verbal reports sleep was significantly improved on the drug compared with the original baseline and the placebo, but diaries kept by the parents showed that this improvement was clinically only moderate, with many wakeful nights still occurring. Taking the drug produced no permanent effect on sleep patterns and a follow-up of 14 children 6 months later showed persisting sleep problems in the majority.

Child, Preschool↗

Mechanism of action of antipruritic drugs.

Astemizole and terfenadine, two potent non-sedative H1 antihistamines, had no effect on itch measured objectively as nocturnal scratching and subjectively on a 10 cm line. Trimeprazine, however, a more sedative but less potent H1 antihistamine, was antipruritic, as was nitrazepam, a sedative benzodiazepine. We concluded (a) that antipruritic drugs act centrally by a property related to sedation; (b) H1 receptor antagonists have a peripheral antipruritic action only when itch is due to histamine release, as in the wealing disorders. Thus the new nonsedative H1 antihistamines have no place in the treatment of itch from other causes.

Adolescent↗

The effect of premedication on the incidence of postoperative vomiting in children after E.N.T. surgery.

The influence of premedication and intraoperative narcotic administration on the incidence of vomiting after E.N.T. surgery was studied over a six-month period in 596 children. A high incidence of vomiting was found after intramuscular papaveretum and hyoscine and after oral diazepam. Oral trimeprazine tartrate was associated with a low incidence of vomiting and was found to have an anti-emetic effect when an opiate analgesic was administered after induction of anaesthesia.

Adolescent↗

Sedation in children scanned with high-field magnetic resonance; the experience at the Hospital for Sick Children, Great Ormond Street.

Patient movement is the most common cause of image degradation when performing magnetic resonance scans in children. This is a particular problem scanning at high field, as noise levels of up to 90 dB may be reached. Movement can be reduced by adequate sedation. We present the results of two sedation protocols when scanning with a 1.5T Magnetom scanner. Optimal scan quality can be achieved in up to 85% of scans using Pethco combined with triclofos in children aged 1 month-2 years, and trimeprazine combined with papaveretum in children over 2 years. When heavy sedation is used, patient selection must be cautious, and there is a minimum acceptable level of monitoring including close physical observation, electrocardiographic and apnoea monitoring.

Child↗

Treatment of itching; a preliminary report on results with a new oral antipruritic.

A new antipruritic, trimeprazine, was used in the treatment of itching associated with a variety of dermatologic disorders in 215 patients.Good to excellent relief of itching was experienced by 71 per cent of the patients, fair relief by 15 per cent and poor relief by 14 per cent.Side effects included mild and transient drowsiness or dizziness that cleared spontaneously; six cases of drowsiness that necessitated discontinuance of the drug; three cases of drowsiness that was controlled by reduction of the dosage; and one case of generalized eruption that cleared upon discontinuance of the drug.

Antipruritics↗

Behavioural changes in children following minor surgery--is premedication beneficial?

One hundred and twenty-three male children, aged one to ten years, were studied to determine the influence of premedication on changes in patterns of behaviour following hospitalization for repair of inguinal hernias. Four comparable groups were selected for premedication regimen: (1) A control group without premedication; (2) oral trimeprazine tartrate 2 mg/kg, methadone 0.1 mg/kg and droperidol 0.15 mg/kg; (3) oral midazolam 0.45 mg/kg; (4) intramuscular midazolam 0.15 mg/kg. Standard inhalational anesthesia was used and caudal blocks employed for analgesia. The parents returned a questionnaire at two weeks. Changes in behaviour were reported in 78% of the children and overall, premedication showed little benefit. However, midazolam premedication was associated with a significantly lower incidence of night-time crying and awakening, compared with no premedication. Only for night-time crying and day-time toilet training did age below five years prove to be a significant contributing factor.

Anxiety, Separation↗

Midazolam and amnesia in pediatric premedication.

One hundred and twenty-eight children aged three to ten years, were studied to determine the effect of premedication on amnesia for the preanesthetic period. Four comparable groups were used: A control group, no premedication; oral trimeprazine tartrate 2 mg/kg, methadone 0.1 mg/kg plus droperidol 0.15 mg/kg (T.M.D.); oral midazolam 0.45 mg/kg; intramuscular midazolam 0.15 mg/kg. Amnesia was tested for four pictorial facts, and for induction of anesthesia. For pictorial facts, both routes of midazolam administration gave a sixty percent incidence of amnesia compared with sixteen percent in the control group (p less than 0.001). The T.M.D. premedication provided a forty-three percent incidence, also better than the control group (p less than 0.05). Induction was remembered by fifty percent of the midazolam children compared with sixty-six percent of the T.M.D. group (p greater than 0.05) and eight-one percent of the control group (p less than 0.05). The potential advantages of amnesia in pediatric premedication are discussed.

Administration, Oral↗

Oral midazolam in paediatric premedication.

In a premedication study involving 135 children, aged 1-10 years, four regimens were investigated: (i) no premedication; (ii) oral trimeprazine tartrate 2 mg/kg, methadone 0.1 mg/kg, droperidol 0.15 mg/kg (TMD); (iii) intramuscular midazolam (Dormicum; Roche) 0.15 mg/kg; and (iv) oral midazolam 0.45 mg/kg. All premedications were given 60 minutes before a standard halothane anaesthetic. No impairment of cardiovascular stability occurred but after premedication the mean oxygen saturation decreased by 1.6% and 1.1%, respectively, in the intramuscular midazolam and TMD groups. Overall, children under 5 years of age behaved less satisfactorily in the holding room and at induction, than those over 5 years (P less than 0.01). Midazolam, intramuscularly and orally, produced more satisfactory behaviour than the other two regimens (P less than 0.05) and, combined with a 70% more rapid recovery than the TMD regimen (P less than 0.05), suggests that oral midazolam is a more effective paediatric premedication agent than placebo or TMD.

Administration, Oral↗

Midazolam premedication in paediatric anaesthesia.

To investigate the efficacy of midazolam (Dormicum; Roche) as a paediatric premedication, 150 children, aged 6 months-5 years, were divided into three groups. All three groups spent time with the anaesthetist to allow rapport to be established. Group A received midazolam premedication, group B received oral trimeprazine, droperidol and methadone (TDM) and group C received no sedative medication. Midazolam gave the best behaviour patterns in the holding room. Behaviour at induction was the same in all three groups. The recovery times were similar in the midazolam and unsedated groups, but in the TDM group recovery was significantly delayed. Temperatures remained stable in the unsedated and midazolam groups, but decreased in the TDM group. It is concluded that midazolam is a satisfactory paediatric premedication agent.

Anesthesia Recovery Period↗

Comparative effects of selected phenothiazine tranquilizers and antihistaminics on bacterial cells and possible interactions with antibiotics.

Evaluation of the antibacterial effect of phenothiazine antihistaminics (trimeprazine, promethazine, and fonazine) and phenothiazine tranquilizers (promazine, chlorpromazine, triflupromazine, and propiomazine) on Staphylococcus aureus showed that tranquilizers were more active [minimum inhibitory concentration (MIC) 0.5-1.6 micrograms/mL] than antihistaminics (MIC greater than 1.6 micrograms/mL). The antibacterial activity was found to correlate with both the rate of adsorption of these drugs on the bacterial cells and the surface tension of their solutions. Phenothiazine tranquilizers caused rapid and extensive leakage of potassium ions from bacterial cells, while phenothiazine antihistaminics produced relatively slower leakage of these ions. A study of the effect of the phenothiazines on the antibacterial activity of some antibiotics showed that all phenothiazines produced a synergistic effect with erythromycin and an antagonistic effect with tobramycin. Variable effects were observed with chloramphenicol, and no effect was observed with penicillin. Results were explained on the basis of structural characteristics of the phenothiazines.

Adsorption↗

Thermodynamics of partitioning and efflux of phenothiazines from liposomes.

The partitioning of nine phenothiazines between dimyristoylphosphatidylcholine (DMPC) liposomes and 0.9% wt/vol saline at pH 6 has been studied both below and above the phase transition temperature (Tc) of the phospholipid. Higher partitioning was observed above Tc. Both the entropy and enthalpy of partitioning were positive below and above Tc, and a linear relationship between the entropy and enthalpy has been derived. In general, the partitioning and transport of alkylaminophenothiazines in DMPC liposomes over the temperature range of 5 to 40 degrees C is entropically controlled. The entropies and enthalpies of partitioning of various groups in the phenothiazine structure have been calculated. No relationship was found between particle size of the DMPC liposomes and the equilibrium partition coefficient at 25 degrees C. However, the particle size of liposomes did increase with increasing acyl chain length of the phospholipid. Using differential scanning calorimetry, the enthalpy and entropy of transition of the DMPC liposomes in the absence and presence of phenothiazines has been calculated. The temperature dependence of the first-order rate constant of trimeprazine tartrate transport in DMPC liposomes was investigated and was found to be maximum at the Tc of the phospholipid.

Dimyristoylphosphatidylcholine↗

Arterial oxygen desaturation during peripheral venous cannulation in children.

Arterial oxygen saturation (SpO2) was measured to determine oxygen desaturation during peripheral venous cannulation prior to induction of anaesthesia in 40 consecutive patients in each of the three age groups; Group I: 1-4 mo, Group II: 4-12 mo, Group III: 12-24 mo. Following premedication with oral trimeprazine tartarate 3 mg.kg-1, one to two hours before operation, baseline SpO2 was noted with child breathing room air. Continuous monitoring during peripheral venous cannulation was done and maximum decrease and duration of SpO2 < 90% was noted. Decreases in mean SpO2, 3.2 +/- 1.4 in Group I, 2.6 +/- 2.0 in Group II and 1.7 +/- 1.9 in Group III, were observed (P < 0.001). Desaturation > or = 4% was noted in 17 patients in Group I, ten patients in Group II and six patients in Group III. Two children, one each in Groups I and II, experienced SpO2 < 90% for 30 sec and 80 sec respectively. We conclude that clinically undiagnosed desaturation occurs during peripheral venous cannulation in healthy children. The authors suggest that continuous monitoring of SpO2 using pulse oximetry should be performed routinely during peripheral venous cannulation.

Anesthesia, General↗

The anaesthetic management of the child with Eisenmenger's syndrome.

There is little clinical data in the literature on the anaesthetic management of paediatric patients with Eisenmenger's syndrome undergoing non-cardiac surgery. This paper reviews our experiences with either such patients who underwent a total of 11 surgical procedures. Of the eight children, six had Down's syndrome and an atrio-ventricular septal defect, one had a ventricular septal defect and one an atrial septal defect. Nine of the eleven operations consisted of minor dental, plastic or ENT procedures, while one patient underwent two laparotomies. Premedication (trimeprazine/ meperidine combination or midazolam) was administered on three occasions. Induction of anaesthesia was achieved by either inhalation of halothane (2), or intravenously with thiopentone (6), ketamine (2) or propofol (1). Muscle relaxation and mechanical ventilation were employed only for both intra-abdominal procedures, otherwise patients were allowed to breathe spontaneously with, or without, manual assistance. Halothane (8), isoflurane (2) and enflurane (1) were all used for maintenance of anaesthesia. Non-invasive monitoring was applied intraoperatively for minor procedures, and arterial and central venous catheters inserted for the laparotomies. Postoperative analgesia for both these cases was provided by an epidural infusion of bupivacaine 0.125% and fentanyl 5 micrograms x ml(-1). A single im bolus of morphine was required following a dental clearance, otherwise pain relief for the rest of the cases was achieved by local anaesthetic infiltration and NSAIDS. With the exception of a single episode of bradycardia, induction, maintenance and recovery from anaesthesia were well tolerated in all cases. In conclusion, our experience suggests that despite theoretical risks, children with Eisenmenger's syndrome appear to tolerate a variety of anaesthetic techniques.

Anesthesia↗

Antihistamines in the treatment of dermatitis.

BACKGROUND: Atopic dermatitis (AD) is an inflammatory skin disorder that is exceedingly challenging to treat. A prominent feature of AD is chronic pruritus. Early evidence suggested that pruritus in AD was partially due to mast cell release of histamines. Conversely, recent studies do not validate the role of histamine in the pathogenesis of pruritus. Conventional management continues to include the wide use of antihistamines to treat the persistent itch, however, there is an urgent need for therapy which will reduce the severity of pruritus for these patients. OBJECTIVE: To review the evidence in the literature for the use of antihistamines in the treatment of atopic dermatitis. METHODS: A MEDLINE search (1966-2002) was performed to obtain studies examining the use of antihistamines in the treatment of atopic dermatitis. Search terms included: atopic dermatitis; eczema; antihistamines; azatadine; brompheniramine; cetirizine; chlorpheniramine; clemastine; cyclizine; cyproheptadine; desloratadine; diphenhydramine; fexofenadine; hydroxyzine; loratadine; meclizine; promethazine; trimeprazine. Further references were gathered from these publications. RESULTS: Historically, antihistamines have been used in the treatment of AD. However, this review shows that the evidence for its use is inconclusive. At present, several antihistamines continue to provide relief of pruritus by central sedation, and they can also be used therapeutically for concomitant allergic conditions associated with AD. More clinical trials examining the therapeutic efficacy of antihistamines, especially with the newer nonsedating antihistamines, are necessary to elucidate their role in the treatment of AD. CONCLUSION: Dermatologists require additional evidence regarding the efficacy of antihistamines and their mechanism of action in the treatment of AD to enhance patient care.

Dermatitis, Atopic↗