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Anxiolytic premedication reduces preoperative anxiety and pain during oocyte retrieval. A randomized double-blinded placebo-controlled trial.

BACKGROUND: The role of anxiolytic premedication remains unclear and significant postoperative side-effects may result from routine use. METHODS: In this double-blinded study, 100 infertile patients were randomized on the day of ultrasound-guided oocyte retrieval (TUGOR) by a computer-generated randomization list in sealed envelopes to receive either (i) 50 mg pethidine and 25 mg promethazine (premedication group) or (ii) normal saline (placebo group) i.m. 30 min prior to TUGOR. Anxiety level, pain levels and severity of postoperative side-effects were recorded. RESULTS: No differences were seen in demographic data, TUGOR duration, number of follicles punctured and clinical outcome. Preoperative anxiety level was significantly higher than the basal anxiety level in the placebo group only. The vaginal and abdominal pain levels during TUGOR and 4 h after TUGOR were significantly higher in the placebo group than the premedication group. Significantly more patients complained of drowsiness after TUGOR in the premedication group than the placebo group and other side-effects were comparable in both groups. CONCLUSION: Routine use of anxiolytic premedication prevented an increase of preoperative anxiety level, reduced pain levels during oocyte retrieval but was associated with a higher percentage of moderate/severe drowsiness in the postoperative period.

Adult↗

Inhibitory effects of antihistamines and antiserotonins on the bone marrow reactions produced by Escherichia coli endotoxin in mice.

The bone marrow reactions (that is, decrease of nucleated cell counts and increase of red blood cell counts) of mouse bone were observed 1 hr after injection of endotoxin and peaked after 18 hr. These reactions were significantly inhibited when diphenhydramine, promethazine (antihistamines), chlorpromazine (antiserotonin), or cyproheptadine (antihistamine and antiserotonin) was given 30 min before endotoxin. Such bone marrow reactions were also induced with histamine or serotonin and peaked 1 hr after administration. The histamine-induced changes were inhibited by prior treatment with diphenhydramine. These reactions were also produced by injection of a small amount of both histamine and serotonin, whereas no change was found when mice were given a single injection of a larger dose of histamine or serotonin. These results indicate that histamine and serotonin released in mice at the initial stage after endotoxin synergistically trigger the bone marrow reactions, which then continue in the presence of further mediators. Antihistamines and antiserotonins are considered to hinder the whole process of reactions produced by endotoxin.

Animals↗

Site-to-site variability of drug concentrations in skeletal muscle.

The homogeneity of drug concentrations in skeletal muscle was assessed in eight fatal overdoses. Ten to 30 random samples were taken from leg muscle weighing 1,650 to 7,985 g. For cases involving paracetamol the mean muscle-to-blood ratio ranged from 0.1 to 1.1 (n = 4) for amitriptyline 1.1 to 3.6 (n = 3), and for dothiepin 0.8 to 2.1 (n = 2). The coefficient of variance was large for all drugs, ranging from 10.5 (carbamazepine) to 50 (thioridazine). Skeletal muscle is not homogeneous with respect to drug concentrations in fatal overdose cases. Of 16 instances of drug detection in blood 2 (nortriptyline and promethazine) were not detected in muscle. Muscle-to-blood drug ratios varied significantly among cases, possibly influenced by survival time after drug ingestion. Quantitative interpretations of muscle drug levels present significant difficulties. However, skeletal muscle can be used for qualitative corroboration of blood analyses and is a suitable specimen for drug detection where none other is available.

Acetaminophen↗

Carboplatin-related idiosyncrasy.

Side effects of cisplatin and carboplatin include nausea, vomiting, peripheral neuropathy, nephrotoxicity, hearing loss, bone marrow depression, and rarely Lhermitte's sign and allergic reactions. A unique case of idiosyncrasy related to carboplatin administration was observed in a young woman treated for ovarian cancer. Symptoms and signs included skin rash, shortness of breath, and redness of face and upper trunk, without drop in blood pressure or change in heart rate, and were resolved within a short time following administration of hydrocortisone and promethazine.

Adenocarcinoma↗

Influence of topical anesthesia on the sedation of pediatric emergency department patients with lacerations.

Local anesthetic infiltration of wounds causes pain which distresses children. A painless topical anesthetic solution containing tetracaine, adrenaline, and cocaine (TAC) may reduce this distress. We hypothesized that the use of TAC for anesthesia may reduce the utilization of sedation for laceration repair. We performed a retrospective review of all pediatric emergency department (PED) patients receiving parenteral meperidine, promethazine, and chlorpromazine (DPT) during the period after TAC became routinely available. For comparison, data from a recent retrospective study of DPT (preTAC) use in the same PED were used. There was a reduction in the percent of total PED patients receiving DPT, from 1.7% preTAC to 1.2% during the TAC period (P less than 0.05). During the TAC period, there were no significant changes in patient volume or case-mix indicators. Of the major indications for DPT, there was no significant change in the percent receiving DPT for fractures, abscesses, burns, foreign body removal, or head injuries. However, there was a significant reduction in the percent of patients with lacerations receiving DPT during the experimental period, from 12% to 7.6% (P less than 0.05). There were no significant differences in laceration frequency (119/mo and 116/mo), length (2.7 and 2.7 cm), location (85% and 93% total for face and digits), or complexity (64% and 63%) for preTAC and TAC periods, respectively. We conclude that TAC used for local anesthesia may reduce the need for sedation in PED patients with lacerations that require suturing.

Administration, Topical↗

Conscious sedation of the pediatric patient for suturing: a survey.

No single drug or combination of drugs was used routinely in pediatric emergency departments to sedate children for suturing. A meperidine-promethazine-chlorpromazine "cocktail" was chosen most frequently. Many physicians were dissatisfied with the method they selected, however, leading some to experiment with newer medications such as fentanyl. The American Academy of Pediatrics (AAP) guidelines for the elective use of conscious sedation, specifically, those regarding monitoring during sedation and discharge post sedation, were not adhered to uniformly. Further study of conscious sedation in children is needed.

Child↗

The value of end-tidal CO2 monitoring when comparing three methods of conscious sedation for children undergoing painful procedures in the emergency department.

BACKGROUND: Many studies have evaluated conscious sedation regimens commonly used in pediatric patients. Recent advances in capnography equipment now enable physicians to assess respiratory parameters, specifically end-tidal CO2 (et-CO2), more accurately in spontaneously breathing sedated children than was possible in the earlier studies. This study was designed to: 1) compare the safety and efficacy of intravenous fentanyl, intravenous fentanyl combined with midazolam, and intramuscular meperidine-promethazine-chlorpromazine (MPC) compound when used for painful emergency department (ED) procedures: and 2) to determine whether the addition of et-CO2 monitoring enabled earlier identification of respiratory depression in this population. METHODS: Forty-two children requiring analgesia and sedation for painful ED procedures were randomly assigned to receive either fentanyl, fentanyl-midazolam, or MPC compound. Vital signs, oxygen saturation, and et-CO2 were monitored continuously. Pain, anxiety, and sedation scores were recorded every five minutes. RESULTS: Respiratory depression (O2 saturation < or = 90% for over the minute or any et-CO2 > or = 50) occurred in 20% of fentanyl, 23% of fentanyl-midazolam, and 11% of MPC patients (P = NS). Of those patients manifesting respiratory depression, 6/8 were detected by increased et-CO2 only. MPC patients required significantly longer periods of time to meet discharge criteria than fentanyl and fentanyl-midazolam patients (P < 0.05). No differences were noted in peak pain, anxiety, or sedation scores. CONCLUSIONS: Fentanyl, fentanyl-midazolam, and MPC produced a high incidence of subclinical respiratory depression. End-tidal CO2 monitoring provided an earlier indication of respiratory depression than pulse oximetry and respiratory rate alone. MPC administration resulted in a significantly delayed discharge from the ED.

Capnography↗

Analgesia for the reduction of fractures in children: a comparison of nitrous oxide with intramuscular sedation.

A prospective, randomized study was undertaken to compare the effectiveness of nitrous oxide with intramuscular sedation (meperidine and promethazine) in providing analgesia and amnesia during the reduction and treatment of children's fractures in an outpatient clinic setting. Fifteen patients received a 50:50 mixture of nitrous oxide and oxygen, and 15 received intramuscular injection. The two groups were similar in regard to gender distribution, age, and fracture types. Pain response was recorded using the Children's Hospital of Eastern Ontario (Canada) Pain Scale (CHEOPS) at the time of fracture reduction and 30 min postreduction. At the first follow-up visit a questionnaire regarding the patient's memory and subjective experience of the fracture reduction was answered. Data between the two groups were compared using the Mann-Whitney test. The CHEOPS scores, and the memory and subjective experience of the fracture reduction were similar between the two groups. Time in the outpatient department averaged 83 min for the intramuscular group and 30 min for the nitrous oxide group (p < 0.01). All of the nitrous oxide patients stated they would use nitrous oxide again, whereas only eight of 15 intramuscular patients stated they would try intramuscular sedation again. Nitrous oxide is as effective as intramuscular sedation in providing analgesia and amnesia in the treatment of children's fractures while having a more rapid onset and a shorter recovery period with greater patient acceptance.

Adolescent↗

Attempts to attenuate the cardiostimulatory effects of ketamine.

In an attempt to attenuate the cardiostimulatory effects of ketamine, a number of drugs were given individually, or in combination, to fit adults undergoing body surface operations, either before or aftera ketamine induction of 1 mg kg-1 followed by an infusion of 1 mg ml-1. Of these, practolol, phentolamine, practolol-phentolamine, phentolamine-practolol, promethazine, hexamethonium, procainamide and verapamil were unacceptable. Labetalol, in doses of 0.5 mg kg-1 and 1.0 mg kg-1, proved to be the most promising drug and is worthy of further study.

Adult↗

Reduction of postoperative vomiting in high-risk patients.

Twenty-eight patients who had a history of severe postoperative vomiting were divided into two groups. The first group received various anaesthetic drugs and the second group received a pethidine promethazine premedication and thiopentone, alcuronium, fentanyl and droperidol. There was a significant reduction in postoperative vomiting as assessed by vomiting score in both groups of patients, with the second group having a greater reduction in vomiting score than the control group. Nine of the patients in the second group have received the same anaesthetic uneventfully on a subsequent occasion. We propose that reassurance and the anaesthetic technique described can significantly reduce the incidence of postoperative vomiting in a high risk group.

Anesthesia, General↗

Fluid deprivation before operation. The effect of a small drink.

The effect of oral fluids before operation, followed by intramuscular morphine, on gastric volume and pH was examined in 150 elective surgical patients, ASA physical status 1 and 2, who were randomly assigned to one of the three groups of 50 each. Group 1 (control) continued their overnight fast; patients in Groups 2 and 3 received 150 ml water 2 hours before the scheduled time of surgery. Patients in Group 3 received intramuscular morphine 0.15 mg/kg and promethazine 0.5 mg/kg one hour before operation. The residual gastric volume was obtained by suction and its volume and pH measured immediately after induction of anaesthesia. Statistically significant (p less than 0.05) decrease in residual gastric volume was observed in Groups 2 and 3 as compared to Group 1. However, the difference between these two groups was not statistically significant. There was no statistically significant difference in pH among the three groups. Overnight fluid fasting is not justified in elective surgical patients. Morphine can be safely given one hour before surgery in patients who have received water (150 ml) 2 hours before operation.

Adolescent↗

Lytic cocktail in children. Rectal versus intramuscular administration.

The efficacy of the lytic cocktail (1 ml contains pethidine 28 mg, promethazine 7 mg, chlorpromazine 7 mg) administered intramuscularly or rectally as premedication was studied in 51 children aged 1-12 years who had minor elective otological surgery. One group received 0.05 ml/kg intramuscularly (maximum dose 2.0 ml) and the other 0.07 ml/kg per rectum (maximum dose 2.8 ml). Most were satisfactorily sedated before operation, but after operation the rectally premedicated children were less sedated, which was in agreement with lower plasma pethidine concentrations in this group. The rectal dose should be increased if prolonged postoperative sedation is desireable.

Administration, Rectal↗

Inappropriate drug prescribing in older adults: the updated 2002 Beers criteria--a population-based cohort study.

BACKGROUND: In 1997, Beers and colleagues developed explicit criteria for potentially inappropriate drug prescribing in ambulatory older adults aged 65 years and over. Several studies have been performed to estimate the prevalence of inappropriate drug prescribing based on these criteria. In 2002, the criteria were updated. AIMS: To examine the extent and trend of inappropriate drug prescribing to ambulatory older adults in the Netherlands between 1997 and 2001, according to the 1997 and the updated Beers criteria. METHODS: Data were retrieved from the Integrated Primary Care Information (IPCI) project, a general practice research database with data from computer-based patient records of a group of 150 general practitioners in the Netherlands. All subjects aged 65 and over were included. Prescriptions were classified as inappropriate if they fulfilled the Beers criteria of prescriptions that generally should be avoided in older adults because of a high risk of adverse effects, while also considering dose and comorbidity. RESULTS: Between 1997 and 2001, the 1-year risk of receiving at least one inappropriate drug prescription for older adults ranged between 16.8% (95% CI: 16.3-17.3%) and 18.5% (18.3-18.7%) according to the 1997 criteria and between 19.1% (18.6-19.6%) and 20.0% (19.5-20.5%) according to the updated Beers criteria. According to the updated criteria, the most frequently prescribed inappropriate drugs were nitrofurantoin, long-acting benzodiazepines, amitriptyline, promethazine and cimetidine. Temazepam and zolpidem were mostly prescribed in supratherapeutic dose. Conventional NSAIDs in persons with a history of gastric/duodenal ulcer were the most frequently prescribed contra-indicated drugs. CONCLUSIONS: Prescribing potentially inappropriate prescriptions to ambulatory older people in the Netherlands is substantial. Compared with other studies using the 1997 Beers criteria, inappropriate prescribing to the elderly is lower than in the USA but similar to Finland. Despite a restrictive medication policy and a growing attention for medication surveillance in Europe, inappropriate drug prescribing is still a substantial problem.

Aged↗

Influence of "lytic cocktail" on blood flow and oxygen consumption in the rat brain.

The influence of a sedative dose of "lytic cocktail" (chlorpromazine, promethazine and pethidine) on cerebral blood flow (CBF) and oxygen consumjtion (CMRO2) was tested in artificially ventilated rats, maintained on either 70% N2 or 70% N2O. When given alone, the lytic cocktail had no significant effect on CBF or CMRO2. However, in the presence of nitrous oxide there was a 25% reduction in blood flow and oxygen consumption.

Animals↗

Preanaesthetic medication with rectal diazepam in children.

With the purpose of avoiding injections to children, the quality of rectal premedication with a solution of diazepam (Apozepam) was investigated in a double-blind study. Compared with a lytic cocktail (containing pethidine, promethazine and chlorpromazine), adequate preanaesthetic sedation was obtained with rectally administered diazepam in a dose of 0.75 mg kg-1. However, following rectal diazepam, the majority of the children were very restless during recovery, but the combination of diazepam premedications and a small dose of lytic cocktail given i.m. during anaesthesia secured a smooth recovery in practically all children. The proportion of cases classified as "unsatisfactory' was higher in children below the age of 5 years than in the older children.

Child↗

Rectal diazepam compared to intramuscular pethidine/promethazine/chlorpromazine with regard to gastric contents in paediatric anaesthesia.

Sixty children, aged 1-12 years, were investigated with regard to gastric pH and volume before general anaesthesia. Thirty children (group D) received diazepam 0.75 mg/kg b.w. rectally 1 h before anaesthesia. Thirty children (group L) received a "lytic cocktail" (pethidine 28 mg, promethazine 7 mg, chlorpromazine 7 mg per ml) 0.05 ml/kg b.w. intramuscularly 1 h before anaesthesia. The pH values were significantly higher and the amount of gastric juice was significantly lower in group L compared to group D. The number of children in group L with gastric juice volume exceeding 0.4 ml/kg and the number of children with pH less than 2.5 was significantly smaller compared to group D. The number of children with both gastric pH less than 2.5 and gastric juice volume greater than 0.4 ml/kg was significantly smaller in the group receiving "lytic cocktail" intramuscularly compared to the group receiving diazepam rectally. Bile-stained gastric contents was not related to the gastric pH.

Child↗

Central effects produced by injection of 48/80 into the cerebral ventricles of mice.

Injections of 20 to 30 mug. of 48/80 into the cerebral ventricular spaces of mice produced a condition of motor excitement termed "delirium ambulatorium." This condition was aggravated by previous intraperitoneal injection of tranquillizers, atropine, and promethazine, not affected by previous injection of mepyramine and abolished by a previous injection of pentobarbitone. When an intraperitoneal injection of strychnine was followed by an intraventricular injection of 48/80, the strychnine convulsions became more violent, but the pattern of delirium ambulatorium was not produced.

Animals↗

Antagonism of apomorphine-induced pecking in pigeons.

Central nervous system stimulants, tranquillizers and other central nervous system depressants, antiemetics, antihistamine drugs and autonomic blocking agents were examined for their ability to prevent the pecking response in pigeons induced by apomorphine (250 mug/kg intramuscularly). Reduction in the proportion of positive responses or significant increase in the latent period of pecking were taken as the criterion of effectiveness. Protection was afforded by caffeine, lysergic acid diethylamide, morphine, rauwolscine, triflupromazine and yohimbine. In addition, a significant increase in latent period was produced by artane, pentobarbitone, benactyzine, 2-bromolysergic acid diethylamide, cyclizine, diphenhydramine, ergotoxine, hyoscine, promethazine, 5-(2-chloroethyl)-4-methylthiazole and trimethobenzamide. Most of these drugs influenced the pecking and emetic responses to apomorphine in an identical manner. It is possible that identical receptors may be concerned with apomorphine pecking (in pigeons) and emesis (in other species).

Animals↗