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Opioid dependence in 15 patients after a work injury.

OBJECTIVE: To document aspects of the management of 15 patients with workers' compensation injuries which led to opioid dependence and suggest preventive strategies. METHOD: Details of general practitioner and deputising service visits for a 38-week period, 1 May 1991 - 22 January 1992, were obtained from WorkCover case files and general practitioners' patient records, and claims for reimbursement for afterhours home visits (Item 97) were obtained from the Health Insurance Commission (HIC) for the years 1991, 1992 and 1993. RESULTS: Fourteen of the patients had a lumbosacral injury. A total of 2489 deputising service visits were provided on 3227 days (0.77/day). A statistically significant 20% higher visit rate occurred on Sundays and public holidays compared with the rate for the rest of the week. Deputising service practitioners provided 4.7 times as many services as general practitioners. In 1299 visits to 12 of these patients, parenteral drugs administered included 108 385 mg pethidine, 2680 mg morphine, and 20 400 mg promethazine. All 15 patients were independently assessed as having features indicating opioid dependence. In only one patient was there evidence of opioid dependence before injury. An alternative management plan not requiring deputising service visits was instituted early in 1992. The number of claims from the HIC for afterhours visits to these 15 patients rose from 125 in 1991 to 630 in 1992, while 409 were provided in 1993. CONCLUSION: Appropriate strategies, such as restricting the ability of deputising services to bill directly for the services they provide, and a sharing of information between the HIC and other statutory authorities, should prevent a similar occurrence in the future.

Adult↗

The prescribing pattern of hospital doctors.

OBJECTIVE: There has been no local data on the prescribing habits of doctors over the last 25 years. This is a retrospective study done to examine the outpatient prescribing pattern of doctors at Alexandra Hospital over a one month period in 1995. METHOD: Six-thousand five-hundred and three scripts were analysed. A total of 16,642 items were prescribed. The distribution of prescription scripts by departments included Accident & Emergency 39.0%; Medical 23.5%; Orthopaedics 10.3%; Surgery 18.5%; Paediatrics 4.4%, and Geriatrics 4.3%. The overall mean number of drugs prescribed was 2.6 (median = 2, mode = 2, range = 14). RESULTS: Analysis of the overall results by age groups showed the following means for "total number of drugs prescribed": (> 0 to 20 years) = 2.23, (> 20 to 40 years) = 2.42, (> 40 to 60 years) = 2.61 and (> 60 years) = 3.18. Analysis of variance showed highly significant results between the means of each age-group. Post-hoc analysis revealed that the oldest age group (> 60 years) accounted for most of this significant result. The top 10 drugs used by the hospital were (in descending order): NSAIDs, antacids, analgesics (other than NSAID), antibiotics, topical medications, anti-diarrhoeal agents, anti-histamines, vitamins, anti-emetics and promethazine cough syrup. There was a high usage of NSAID-antacid combination. Similarly, amoxycillin was often given with cloxacillin. There was an underuse of anti-depressants. There were very few (0.15%) illegible prescriptions. Only one prescription had an adverse combination of drugs. CONCLUSION: This is the first local study of prescribing pattern of a hospital. While this data may vary from hospital to hospital, depending on the patient mix, it does provide some useful baseline data which hitherto never existed. Our findings suggested that the elderly do receive more medications.

Adolescent↗

An in vitro study on the metabolism and possible drug interactions of rokitamycin, a macrolide antibiotic, using human liver microsomes.

This in vitro study was designed to identify the enzyme(s) involved in the two major metabolic pathways of rokitamycin [formations of leucomycin A7 (LMA7) from rokitamycin and of leucomycin V (LMV) from LMA7] and to assess possible drug interactions using human liver microsomes. Formation of LMA7 or LMV was NADPH-independent. Anti-rat NADPH cytochrome P-450 (CYP) reductase serum, specific inhibitors, or substrates of CYP isoforms showed no effects on the formation of LMA7 or LMV. The mean Vmax and Vmax/Km for the formation of LMA7 from rokitamycin were much greater (P <.01) than those for the formation of LMV from LMA7. Two esterase inhibitors, bis-nitro-phenylphosphate and physostigmine (100 microM), inhibited the formation of LMA7 or LMV by more than 85%, whereas no appreciable inhibition occurred by several substrates of carboxylesterase (EC 3.1.1.1). Except the moderate inhibition produced by promethazine and terfenadine, theophylline, mequitazine, chlorpheniramine, and diphenhydramine showed little or no inhibition for the formation of LMA7 or LMV. Rokitamycin, LMA7, LMV, erythromycin, and clarithromycin (up to 500 microM) had no appreciable inhibition for CYP1A2-, 2C9-, and 2D6-mediated catalytic reactions. However, rokitamycin, LMA7, erythromycin, and clarithromycin inhibited the CYP3A4-catalyzed triazolam alpha-hydroxylation with IC50 (Ki) values of 5.8 (2.0), 40, 33 (20), and 56 (43) microM, respectively. It is concluded that the formations of LMA7 from rokitamycin and of LMV from LMA7 are catalyzed mainly by human esterase enzyme [possibly cholinesterase (EC3.1.1.8)]. However, whether rokitamycin would inhibit the CYP3A-mediated drug metabolism in vivo requires further investigations in patients.

Anti-Bacterial Agents↗

Pharmaceutical use by U.S. astronauts on space shuttle missions.

We evaluated in-flight use of medications from astronaut debriefings after 79 U.S. Space Shuttle missions. From the 219 records obtained (each representing one person-flight), 94% included some medication being taken during flight; of that number, 47% were for space motion sickness, 45% for sleep disturbances, and smaller percentages for headache, backache, and sinus congestion. Drugs were taken most often orally, followed in decreasing order of frequency by intranasal, intramuscular, and rectal routes. Drugs for space motion sickness were taken mostly during the first 2 d of flight, drugs for pain during the first 4 d, and drugs for sleeplessness and sinus congestion were taken consistently for 9 flight days. About 85% of all doses had no reported side effects, and most of the side effects that were reported happened during the first mission day. About 80% of the drug-dose events were perceived effective by the recipients; most of the reports of ineffectiveness occurred during the first mission day. Promethazine, the only drug given by three different routes (orally, intramuscularly, and rectally), was most effective and had minimal side effects when taken intramuscularly. This information, although useful, should be expanded to include objective measures of effectiveness so that therapeutic efficacy can be assessed during flight.

Astronauts↗

The prescribing pattern of outpatient polyclinic doctors.

OBJECTIVE: This study aims to analyse the prescribing pattern of doctors working in a government outpatient polyclinic in Singapore. DESIGN: Retrospective study of 1 week of prescription scripts in 1996. MAIN OUTCOME MEASURES: Number, types and duration of drugs prescribed; combination of drugs; age distribution; bad handwriting. RESULTS: Two thousand six hundred and seventy-nine scripts were analysed. The age of patients ranged from 1 to 93 years with a mean of 43.8 years. There were 44.0% males and 56.0% females. The overall mean of 'total number of drugs prescribed' was 2.8 items. The means of 'number of drug items prescribed for more than 1 week' by age-group were: < 20 years = 0.2, 20 to < 40 years = 0.5, 40 to < 60 years = 1.3 and > 60 years = 2.4. One way analysis of variance showed significant difference between the means of each age-group. Post hoc analysis revealed that the oldest age group accounted for most of this significant result. The top 10 drugs prescribed in descending order were: antihistamines, paracetamol, throat medications (eg. lozenges, gargles, etc), nifedipine, beta-blockers, antacids, mist benadryl expectorant, Procodin cough syrup (containing codeine and promethazine), amoxycillin and vitamin B. Nifedipine and beta-blockers were the most commonly prescribed anti-hypertensives. Non-steroidal anti-inflammatory drugs were usually prescribed with antacids. One hundred and twenty (4.5%) scripts were illegible. CONCLUSION: This study provides a baseline data for monitoring future prescribing trends. There may be a need to re-evaluate the appropriateness of nifedipine as the first line anti-hypertensive drug and the usefulness of NSAID-antacid and amoxycillin-cloxacillin combinations. The prevalence of illegible handwriting was high.

Adolescent↗

[Non-oral routes of administration of psychotropic agents].

For patients not able to take oral medication, a psychotropic agent may be selected not only according to its therapeutic and side effects but also to the optional alternative routes of administration. Partly because of the various options of routes of administration haloperidol is the first choice 'classic' antipsychotic medication. As to 'atypical' antipsychotics, the preparation of an ill-tasting clozapine liquid is possible. Lorazepam, clorazepate and diazepam injections (oil in water emulsion) or diazepam per rectiole are non-oral anxiolytics of first choice. Clomipramine and amitriptyline are the only parenteral antidepressants available in the Netherlands. Lithium tablets without controlled release may be administered as a suspension via a catheter. Carbamazepine or valproate may serve as a parenteral alternative for lithium. In case of extrapyramidal side effects of antipsychotics, biperiden or promethazine may be administered parenterally.

Formularies as Topic↗

Enhanced antibacterial effect of erythromycin in the presence of 3,5-dibenzoyl-1,4-dihydropyridines.

Fifteen 3,5-dibenzoyl-1,4-dihydropyridines (BzDHP, GB1-GB15) (nifedipine (NP) analogs) were tested on three different E. coli strains. The compounds had relatively high MIC values on these strains. In combination with erythromycin (Er), compounds (G1,3,4,6,7,10,12) reduced MIC values of Er. When the BzDHPs were tested on E. coli Gy-1/Apsen.Erres strain isolated from a clinical specimen, the reduction of MIC values were similar to the previous strains, but not identical. In the polyresistant clinically isolated E. coli Gy-2/Apres.Erres strain, the MIC values of Er were slightly reduced in the presence of GB1-GB7. Compound GB12 was the most effective in enhancing the activity of Er, and was selected for plasmid elimination studies. However, GB12 itself had no antiplasmid effect and did not alter the promethazine induced plasmid elimination.

Anti-Bacterial Agents↗

[A systematic screening and identification method for 29 central nervous system drugs in body fluid by high performance capillary electrophoresis].

A systematic screening method has been developed for the detection of 29 central nervous system (CNS) drugs in human plasma, urine and gastric juice by high performance capillary electrophoresis (HPCE). The first step is sample preparation. The patient's or normal human plasma (0.5 ml) spiked with CNS drugs was extracted with 2 x 4 ml dichloromethane, while 2 ml of patient's or spiked urine was extracted with 2 x 6 ml chloroform. The combined extract from plasma or urine was evaporated to dryness in a rotation evaporator at 35 degrees C. The residue was dissolved in 100 microliters methanol and subsequently 400 microliters of redistilled water was added. The patient gastric juice (3 ml) was centrifuged at 2,000 r.min-1 for 5 min. The supernatant was filtered through 0.45 micron microporous membrane for injection onto capillary columns. The second step was to perform CZE separation in acidic buffer composed of 30 mmol.L-1(NH4)3PO4(pH 2.50) and 10% acetonitrile (condition A). Most of the benzodiazepines (diazepam, nitrazepam, chlordiazepoxide, flurazepam, extazolam, alprazolam) and methaqualone were baseline separated and detected at 5-13 min, while thiodiphenylamines showed group peaks at 3-5 min and barbiturates migrate with electroosmotic fluid (EOF) together. The third step is to separate the drugs in basic buffer constituted of 70 mmol.L-1 Na2HPO4(pH 8.60) and 30% acetonitrile (condition B). The thiodiphenylamines and some other basic drugs could be well separated, which include thihexyphenidyl, imipramine, amitriptyline, diphenhydramine, chlorpromazine, doxepin, chlorprothixene, promethazine and flurazepam, while the rest of the CNS drugs did not interfere with the separation. The last step was to separate the drugs by micellar electrokinetic chromatography (MEKC) in such a buffer as 70 mmol.L-1 SDS plus 15 mmol.L-1 Na2HPO4 (pH 7.55) and 5% methanol (condition C). Barbiturates (barbital, phenobarbital, methylphenobarbital, amobarbital, thiopental, pentobarbital, secobarbital) and some hydrophobic drugs (glutethimide, alprazolam, clonazepam, carbamazepine, trifluoperazine, oxazepam) could be well separated. These drugs might be identified by both the relative migration time (rtm = tdrug/tEOF) and the ratios of peak heights (rh) monitored at different wavelength, since the ratios are characteristic of the spectrum of a drug. This method has been used in several real clinical samples of intoxication. For example, perphenazine and doxepin were detected in the gastric juice and phenobarbital in blood and gastric juice of an intoxicated patient.

Central Nervous System Agents↗

Extractive-spectrophotometric determination of some 2- and 10-disubstituted phenothiazines with dipicrylamine.

Dipicrylamine reacts in neutral medium with some 2,10-disubstituted phenothiazines (promazine, chlorpromazine and promethazine hydrochlorides, trifluoperazine dihydrochloride, thioproperazine dimethanosulphonate) forming orange or brown ion-association compounds. The compounds are insoluble in water but quantitatively extracted into chloroform. These properties have been exploited for the determination of phenothiazines in pure solutions and pharmaceuticals.

Calibration↗

Interaction of protonated anticancer thiazines with water-insoluble phospholipids and antineoplastic agents.

A series of neuroleptic protonated phenothiazine derivatives (promethazine, promazine, triflupromazine, methotrimeprazine, propiomazine, trifluoperazine and fluphenazine), some with known anticancer properties, were complexed with water-insoluble antineoplastice agents such as 5-fluorouracil (5FU), methotrexate (MTX) and sulindac, as well as with components of biomembrane and synthetic phospholipids as possible models of cancer and microbial cells. In all cases water-soluble micellar inclusion adducts were formed exhibiting electron charge transfer complex behaviour, with the appearance of thazine free radicals. The thiazines sequestered the drugs and phospholipids in well-defined molar ratios (MR) parabolically-dependent on the dipole moments (mu) of the protonated phenothiazine derivatives. pH comparisons showed that the inclusion adducts followed a model in which the compounds were enveloped in the lipophilic interior of the thiazine aggregates, while the side-chains of the latter faced the aqueous environment. In the model experiment, interaction of the thiazines and the 5FU adducts with E. coli F' lac was additive to marginally synergistic, confirmed by the checkerboard technique. The parabolic dependence of the molar minimum inhibitory concentration of the thiazines and thiazine/5FU adducts on the thiazine dipole moments suggests that their primary loci of interaction are the cell wall or membrane phospholipid components. Thiazines, especially those with dipole moments centered on about 6 D, near which the lowest MR occurs, can act as effective carriers for insoluble or sparsely soluble drugs. Any new thiazine drug for use alone or as a carrier in anticancer therapy should be designed with this criterion in mind.

Antineoplastic Agents↗

Antiallergic anti-inflammatory effects of H1-antihistamines in humans.

Data from in vitro, in vivo, and ex vivo studies suggest that second-generation antihistamines have a number of antiallergic, anti-inflammatory properties that appear to be independent of their H1-blockade activity. First-generation antihistamines also have antiallergic, anti-inflammatory properties, as suggested by the studies with azatadine, chlorpheniramine, mepyramine, and promethazine; most other first-generation antihistamines have not been studied for these properties. In vitro studies have shown that H1-antihistamines reduce the release of proinflammatory mediators from mast cells and basophils, the chemotaxis and activation of inflammatory cells (especially eosinophils), and the expression of adhesion molecules induced by immunological and nonimmunological stimuli in epithelial cell lines. Nasal allergen challenge models have similarly demonstrated that H1-antihistamines inhibit mediator release from mast cells and basophils, and that they decrease inflammatory cell infiltration and the expression of adhesion molecules on epithelial cells. The results of published studies of the effects of H1-antihistamines on nasal allergic inflammation in humans have been summarized in this chapter. Recent investigations indicate that H1-antihistamines may modulate airway inflammation by downregulating the activity of airway epithelial cells, which have an important role in allergic airway inflammation. The modulation of adhesion molecules and of inflammatory cell infiltration by H1-antihistamines may be beneficial during long-term treatment in patients with allergic rhinitis. The rationale for this hypothesis is the persistence of inflammation on the nasal epithelial cells even when patients are symptom-free (16). All of the events affected by H1-antihistamines are important in the allergic inflammation cascade. The underlying mechanisms for such effects remain unclear, but are unrelated to H1-antagonist activity. Several studies have demonstrated that H1-antihistamines can form an ionic association with cell membranes and inhibit calcium ion influx into the mast cell or basophil plasma membrane, or inhibit Ca2+ release within the cells, and may therefore influence the signal transduction pathways. However, these effects appear to occur at concentrations higher than those achieved in therapeutic practice (126-128). It has recently been hypothesized that the anti-inflammatory activity of H1-antihistamines may be a consequence of their ability to influence the activation of genes responsible for the expression and synthesis of proinflammatory mediators (129). The contribution of the antiallergic effects of H1-receptor antagonists to their clinical efficacy is not fully understood. There have been no data suggesting that H1-antihistamines with well-documented antiallergic properties are superior to the others for which such properties have not been as extensively investigated. Additional studies are needed to elucidate the mechanisms(s) by which H1-antihistamines exert anti-inflammatory effects. This knowledge might lead to the development of novel therapies with more potent and specific anti-inflammatory effects.

Anti-Allergic Agents↗

A case of homicide by lethal injection with lidocaine.

This report describes a homicide by overdosage with lidocaine. The decedent, a 32-year-old male hospitalized for a lengthy period with acute intermittent porphyria and chronic pancreatitis, suffered apparent asystole and seizure. Failed resuscitation preceded death. A forensic autopsy was conducted based upon suspicions of alleged patient mistreatment by one of the attending nurses. Toxicological analyses revealed the presence of lidocaine in blood, liver, kidney, brain, and heart at 22.2 mg/L and 43.6, 28.3, 23.1, and 13.1 mg/kg, respectively. Also present were diazepam, phenytoin, and promethazine. Both diazepam and phenytoin had been administered during resuscitation, but lidocaine had not. The cause of death was determined to be ventricular arrhythmia precipitated by lidocaine overdosage. The administered dose was calculated to have been approximately 1500 mg. The manner of death was determined to be homicide. The nurse was arrested and subsequently tried for murder by administering a lethal quantity of lidocaine.

Adult↗

[Anaphylaxia induced by etoposide--a case report].

A 32-year-old woman, gravida 4, para 2, visited Teikyo University Hospital with complaints of abnormal uterine bleeding and lower abdominal pain. Urine hCG level was 1,024 x 10(3) IU/l. MRI examination showed a vascular, rich solid mass 10 cm in diameter at the posterior region of the uterus. Under the clinical diagnosis of choriocarcinoma, she underwent total hysterectomy with right salpingooophorectomy. The ovarian choriocarcinoma was confirmed by pathologic examination. Additional chemotherapy was planned using the combined regimen of etoposide, methotrexate, actinomycin D, cyclophosphamide and oncovin. After 2 min of etoposide administration (100 mg/m2), the patient complained of acute dyspnea, which was caused by bronchospasms and cutaneous flushing. Etoposide infusion was immediately stopped, and anti-anaphylaxic treatment was done by administering hydroxyzine hydrochloride. Five min after the episode had occurred, the patient recovered. This episode was thought to have been induced by etoposide, but etoposide was a key agent for choriocarcinoma. Thus, we devised a modified chemotherapy using etoposide as follows. The regimen was hydrocortisone 100 mg i.v. q6 h and promethazine hydrochloride 50 mg i.m. q6 h for 24 h before infusion of etoposide. The etoposide concentration was diluted to 50%, and the drug administration rate reduced by half. With the modified regimen, the patient showed no anaphylaxic symptoms. The few reports on anaphylaxic reactions to chemotherapeutic agents induced by side effects must be taken into account when we use these drugs.

Adult↗

Antiplasmid activity: loss of bacterial resistance to antibiotics.

The antiplasmid activity of tricyclic compounds, e.g. phenothiazines, dibenzoazepines, dibenzocykloheptene derivatives and some stereoisomers, was shown on E. coli in vitro. Some ring-substituted phenothiazine and cannabis derivatives had only an antibacterial effect. Promethazine, a selected phenothiazine, cured antibiotic resistance and lactose fermentation of E.coli, tumour inducing ability of Agrobacterium tumefaciens and nodule formation of Rhizobium meliloti. Plasmids of different E.coli strains were eliminated with varying frequency. The antiplasmid activity of the compounds can be due to the increased membrane permeability. Inhibition of DNA gyrase and complex formation with the supercoiled form of plasmid DNA can lead to the cessation of plasmid replication in the bacterial cells. In addition, in vivo plasmid curing was demonstrated at a low frequency.

Antidepressive Agents, Tricyclic↗

The potentiation of narcotic analgesics with phenothiazines.

Potentiation of narcotic analgesics with phenothiazines have been used for preoperative and postoperative analgesia for a number of years by the podiatric community. The agents most frequently cited in studies are the combination of meperidine with either the phenothiazines chlorpromazine, trimeprazine, or promethazine. Due to the fact that the double-blind clinical studies of pain are mainly subjective, and difficult to quantify, the usefulness of phenothiazines for the sole purpose of potentiation of analgesia is questionable, especially in view of the many side effects of this group of drugs.

Analgesics, Opioid↗

The discriminative stimulus effects of clozapine in pigeons: involvement of 5-hydroxytryptamine1C and 5-hydroxytryptamine2 receptors.

Pigeons were trained to discriminate i.m. injections of the atypical antipsychotic clozapine (1.0 mg/kg) from saline in a two-key operant procedure. In substitution tests, compounds that shared antagonistic action at 5-hydroxytryptamine (5-HT)1C and 5-HT2 receptors produced discriminative stimulus effects similar to clozapine: cyproheptadine, metergoline, mianserin, pizotifen and fluperlapine. 5-HT antagonists selective for 5-HT2 vs. 5-HT1C receptors (e.g., ketanserin, pirenperone, risperidone and methiothepin) failed to produce substantial clozapine-appropriate responding. Other serotonergic compounds failed to produce substantial clozapine-appropriate responding: the 5-HT3 antagonist, ondansetron; the 5-HT1A agonists, (+-)-8-hydroxy-2-(di-n-propylamino)tetralin and BMY 14802; the 5-HT1A/1B agonist, RU24969; the 5-HT1A partial agonist, NAN190; the 5-HT1C/2 antagonist, mesulergine; the 5-HT1 agonist, I-5-hydroxytryptophane; and the 5-HT1C/2 agonist, quipazine. Other reference compounds such as the typical antipsychotics, chlorpromazine and thioridazine; the selective dopamine D-2 antagonists, droperidol and sulpiride; the dopamine D-1 antagonist, SCH 23390; the antimuscarinics, atropine and scopolamine; the antihistamines, pyrilamine and diphenhydramine; the alpha-1 antagonist, prazosin; and the antidepressants, imipramine and chloromipramine also failed to produce clozapine-appropriate responding. Promethazine, cinanserin and amitriptyline produced only partial generalization to the clozapine cue. The results suggest that blockade of both 5-HT2 and/or 5-HT1C receptors is important in the pharmacological mediation of the discriminative stimulus effects of clozapine. Blockade of 5-HT2 receptors appears not to be sufficient to produce clozapine-like discriminative stimulus effects. The precise role of 5-HT1C receptors in the clozapine discriminative stimulus is unclear due to the lack of compounds selective for this receptor.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

AANA journal course. Update for nurse anesthetists. Neuroleptic malignant syndrome.

Neuroleptic malignant syndrome (NMS) is a potentially fatal condition composed of hyperthermia, extrapyramidal symptoms, autonomic nervous system disturbances, and altered levels of consciousness. Although uncertainty exists about its cause, most studies suggest it is the result of dopaminergic deficiency in the central nervous system, most commonly caused by neuroleptic medications. Excessive dopaminergic blockade occurs most commonly in psychiatric patients receiving neuroleptic medications, but many antiemetic medications used in anesthesia also have been implicated. Promethazine (Phenergan), prochlorperazine (Compazine), droperidol (Inapsine), and metoclopramide (Reglan) are most problematic. Reversal of dopaminergic blockade in the central nervous system is believed to be the treatment of choice for an acute episode of NMS. Once identified, withdrawal of causative medications, administration of dantrolene or dopamine agonists (bromocriptine and amantadine), and supportive measures will result in a 90% to 94% survival rate from the acute episode. Anesthetists must be aware of the pathophysiology, diagnosis, and treatment of this syndrome. Avoidance of neuroleptic medications, prompt diagnosis, and appropriate treatment will make the difference between success and failure when treating a patient during the acute phase of NMS.

Antipsychotic Agents↗

[Intraoperative awareness in balanced anesthesia. A literature review based on a randomized double blind study using fentanyl, pentazocine and ketamine].

Since the first case report by Winter-bottom [106], the problem of intraoperative awareness or recall has received increasing attention from patients, anaesthesiologists and, more recently, even law courts [4, 20, 21, 78]. Our own interest in awareness derives from a study with the opiate agonist tramadol as a supplement to balanced anaesthesia, which revealed an unexpectedly high incidence of about 65% of patients who could recall intraoperative music [55]. It was the aim of the present randomized double-blind study to evaluate, under identical experimental conditions, what the incidence would be with other analgesic supplements to balanced anaesthesia (fentanyl, pentazocine and ketamine). Because few reports on this subject are available in the German literature, it was felt that the result should be discussed within a comprehensive review. PATIENTS AND METHODS. A total of 60 patients (ASA I-II, age 27-66 years, weight 48-93 kg) undergoing elective gynaecological surgery of at least 90 min duration were each randomly assigned to one of three study groups (F, fentanyl; P, pentazocine; K, ketamine). Premedication was performed with diazepam 10 mg p.o. the evening before surgery and pethidine 1 mg/kg i.m.+promethazine 1.5 mg/kg i.m.+atropine 0.5 mg i.m. 60 min before anaesthesia. Induction was performed with alcuronium (2 + 8 mg), methohexital (1.5 mg/kg) and a bolus dose of the analgesic supplement (F, 5 micrograms/kg; P or K, 2 mg/kg), followed by continuous infusion (F, 2 micrograms kg-1 h-1, P or K 0.8 mg kg-1 h-1). Endotracheal intubation was performed with succinylcholine (1 mg/kg). Patients were ventilated to normocarbia using a Takaoka respirator (4 breaths/min, tidal volume 1600 ml, N2O/O2 75:25). If insufficient anaesthesia was suggested by increases in blood pressure or heart rate to more than 20% of preinduction values, excessive sweating or lacrimation, enflurane (0.5-2 vol.%) was added for short periods of time. At the end of surgery, patients were ventilated with 100% O2, and the neuromuscular block antagonized using atropine 0.5 mg and neostigmine 1 mg. Without prior announcement, tape-recorded music (Mantovani, 3 min followed by 3 min silence) was played to all patients via earphones throughout the time period between intubation and the end of nitrous oxide administration. Vegetative parameters, cumulative and relative enflurane application times and retrospective judgement of quality of anaesthesia by the anaesthesiologist were documented. Post-operative recovery and pain were monitored using verbal rating scales. Patients were interviewed immediately after extubation and on the day after surgery to determine the incidence of dreams and recollection of music. Patients were classified as amnestic if they could not recall the music, even with prompting, and partially amnestic if they remembered the music but were unable to define the time when they had heard it. No amnesia was assumed if patients recalled the intraoperative music spontaneously. Groups were statistically compared by means of analysis of variance, Mann-Wilcoxon rank sum test and chi-square test. RESULTS. Mean duration of anaesthesia was 129-134 min in the subgroups. The total analgesic supplement dose was F 614 +/- 129 micrograms, P 238 +/- 38 mg, and K 230 +/- 50 mg (mean +/- SD). Enflurane substitution was necessary in 45 patients, regardless of the type of analgesic supplement. Mean cumulative enflurane application time was 26-28% in the treatment groups, corresponding to about 20% of anaesthesia duration. The most important reasons for enflurane substitution were increases in blood pressure (mostly in groups F and P) or heart rate (K). Recovery was fastest with F, followed by P, and slowest with K. Retrospective judgement of the quality of anaesthesia by the anaesthesiologist did not differ significantly between the treatment groups. Most (93%) of the patients were satisfied with their anaesthesia; 2 patients each who received P and K were dis

Adult↗