Targeting striatal metabotropic glutamate receptor type 5 in Parkinson's disease: bridging molecular studies and clinical trials.

Metabotropic glutamate (mGlu) receptors are G protein-coupled receptors expressed primarily on neurons and glial cells modulating the effects of glutamatergic neurotransmission. The pharmacological manipulation of these receptors has been postulated to be valuable in the management of some neurological disorders. Accordingly, the targeting of mGlu5 receptors as a therapeutic approach for Parkinson's disease (PD) has been proposed, especially to manage the adverse symptoms associated to chronic treatment with classical PD drugs. Thus, the specific pharmacological blocking of mGlu5 receptors constitutes one of the most attractive non-dopaminergic-based strategies for PD management in general and for the L-DOPA-induced dyskinesia (LID) in particular. Overall, we provide here an update of the current state of the art of these mGlu5 receptor-based approaches that are under clinical study as agents devoted to alleviate PD symptoms.

Obstacles and solutions for spontaneous reporting of adverse drug reactions in the hospital.

AIM: To describe the opinions of hospital physicians concerning problems regarding the spontaneous reporting of adverse drug reactions (ADRs) and ways to solve them. METHODS: A qualitative study was carried out. Fifteen focus groups were conducted among physicians working in a tertiary teaching hospital. A total of 208 physicians from different medical specialities participated. The focus group discussions were recorded by three different observers and the transcripts of each session were analysed for issues and themes emerging from the text. RESULTS: Four types of obstacles to spontaneous reporting were considered particularly important: (i) problems with the ADR(S) diagnosis; (ii) problems with the usual workload and lack of time; (iii) problems related to the organization and activities of the pharmacovigilance system; (iv) and problems related to potential conflicts. The potential solutions suggested for improving spontaneous reporting were to define the kind of ADR(S) which should be reported, to facilitate an easy contact and quick access to the hospital pharmacovigilance system, to facilitate information and support for reporting and feedback of pharmacovigilance activities. CONCLUSIONS: The perception of the different obstacles by the hospital physicians is an important factor in determining the causes of the underreporting of ADRs and addressing these obstacles could lead to an improvement in spontaneous reporting. A closer relationship between the doctors and the pharmacovigilance centre is suggested as a means of solving these problems. More information is needed to improve the spontaneous reporting of ADR(S) in specialized healthcare.

Medical speciality and pattern of medicines prescription.

OBJECTIVE: To describe the prescribing patterns and their quality in relation to the prescriber's medical specialty in a defined population. METHODS: The study was done on a random sample of all primary care medical prescriptions made through the social security system during 1 year in Andorra, a small European country. Number and type of prescribed medicines, prescribers' medical speciality and patients' age and gender were recorded. Medical specialties considered were General Practice, Paediatrics, Cardiology, Pneumology, Gynaecology, Ophthalmology and Other. A set of various quality indicators [World Health Organisation (WHO)/International Network for Rational Use of Drugs (INRUD) indicators and others] was used. RESULTS: The number of medicines prescribed per encounter varied depending on the prescriber's medical specialty and patient's age. Cardiologists and pneumologists tended to prescribe more medicines than other medical specialties. Patients older than 65 years received more prescriptions than younger adults, mostly at the expense of cardiovascular drugs. The contribution of the various groups and subgroups of medicines and the scores of various prescribing indicators showed wide variability across the medical specialties. CONCLUSION: Prescribing patterns and indicators of prescription quality show wide variability depending on the prescriber's medical specialty. This has important implications for priority setting in information, continuous education and research.

[Use of levofloxacin in the hospital]. / Utilización hospitalaria de levofloxacino.

Levofloxacin is a new, recently commercialized fluoroquinolone. We aimed to assess the use of levofloxacin after its inclusion in the hospital drug guide. In a prospective observational study, patients treated with levofloxacin in a university hospital were selected from July 2000 to June 2001. Using a structured questionnaire, data were recorded on patients' demographic characteristics and comorbidities, indications for levofloxacin use and previous use of other antibiotics. In addition, the adherence to the instructions for use as recommended by the antibiotic subcommittee of the hospital, and the use of other alternative antibiotics were analyzed. Ninety-seven patients were treated [mean age 67 years; range 17-93; 64 men], of whom 83 (85.6%) had comorbidity and 51 (52.6%) a possible allergy to the betalactam antibiotics. The treatment began after the use of other antibiotics in 47 (48.5%) patients. The main clinical indications were pneumonia (54; 55.7%) and acute exacerbation of chronic bronchitis (25; 25.8%). The use of other antibiotics was possible in 56 (57.7%) patients, and levofloxacin was only used according to the recommended indications in 41 (42.3%). Levofloxacin is mainly used in the treatment of patients with respiratory infections, those who are allergic to the betalactam antibiotics and those previously treated with other antibiotics; however, in many cases, the use of other antibiotics may still be possible. As part of the antibiotic policy, it is necessary to define the indications of use for new antibiotics introduced in the hospital and surveillance studies need to be developed.

Utilización hospitalaria de levofloxacino / Use of levofloxacin in the hospital

El objetivo del estudio fue evaluar el uso de levofloxacino después de su inclusión en la guía hospitalaria de medicamentos. Fue un estudio observacional prospectivo (julio 2000-junio 2001) en el cual se seleccionaron los pacientes tratados con levofloxacino en un hospital universitario. Mediante un cuestionario estructurado se recogieron datos sobre las características demográficas y comorbilidad de los pacientes, indicaciones de uso y uso previo de otros antibióticos. Además, se analizó la adecuación a las indicaciones de uso recomendadas por la subcomisión de antibióticos del hospital y el uso de otros antibióticos alternativos. Se trataron 97 pacientes (edad mediana 67 años, rango 17-93; 64 hombres), de los cuales 83 (85,6 por ciento) tenían comorbilidad y 51 (52,6 por ciento) una posible alergia a los betalactámicos. Se inició el tratamiento después del uso de otros antibióticos en 47 (48,5 por ciento) pacientes. Las principales indicaciones clínicas fueron neumonía (54; 55,7 por ciento) y sobreinfecciones respiratorias (25; 25,8 por ciento). En 56 (57,7 por ciento) pacientes era posible el uso de otros antibióticos alternativos y sólo en 41 (42,3 por ciento) se utilizó según las indicaciones recomendadas. Levofloxacino se utiliza sobre todo en el tratamiento de pacientes con infecciones respiratorias, alérgicos a los betalactámicos y tratados previamente con otros antibióticos, aunque en muchos casos todavía sea posible el uso de otros antibióticos. Dentro de la política de antibióticos es necesario definir las indicaciones para los nuevos antibióticos introducidos en el hospital y el desarrollo de estudios de seguimiento después de su inclusión (AU)

Beta-adrenergic blocking agents in heart failure: benefits of vasodilating and non-vasodilating agents according to patients' characteristics: a meta-analysis of clinical trials.

BACKGROUND: In patients with heart failure, beta-adrenergic blocking agents reduce overall and cardiovascular mortality. This meta-analysis aimed at clarifying their effect on sudden death, the magnitude of their benefit according to the cause of heart failure, and whether there is any difference between vasodilating and nonvasodilating agents. METHODS: Randomized, clinical trials were included if they evaluated a beta-adrenergic blocking agent without intrinsic sympathomimetic activity, included a control group receiving placebo or standard treatment, evaluated mortality on an intention-to-treat basis, and lasted at least 8 weeks. RESULTS: Twenty-one trials with 5,849 patients (3,130 receiving beta-blockers) were included. Median length of treatment was 6 months. Most patients had mild or moderate heart failure and were treated with angiotensin-converting enzyme inhibitors, diuretics, and digitalis. The beta-blockers significantly reduced overall mortality, cardiovascular mortality, and mortality due to pump failure and sudden death by 34% to 39%. The decrease in overall mortality in patients with ischemic heart disease (IHD) (30%) was no different from that among patients with non-IHD (26%) (P = .08). The reduction in overall mortality was greater with vasodilating than with nonvasodilating agents (45% vs 27%; P = .007), particularly in patients without IHD (62%), compared with those with IHD (22%; P =.03). CONCLUSIONS: In patients with heart failure, beta-blockers reduce total and cardiovascular mortality at the expense of a decrease in mortality due to pump failure and sudden death. The magnitude of the benefit is similar in patients with IHD and in those with non-IHD. Vasodilating beta-blockers have a greater effect on overall mortality than nonvasodilating agents, particularly in patients with non-IHD.

DNase use in the daily care of cystic fibrosis: who benefits from it and to what extent? Results of a cohort study of 199 patients in 13 centres. DNase National Study Group.

UNLABELLED: Short-term clinical trials with DNase have shown minor to moderate benefits in cystic fibrosis patients. This study was performed to analyse the effectiveness of DNase use in daily practice and to obtain information on its effects in the long term and at different disease stages. Patients being treated in 13 specialised units were included if they started DNase treatment before June 1996. Baseline data before DNase use and data during the DNase treatment period were recorded. Of the 199 patients included in the study 166 continued on DNase treatment while the data were being collected. The mean age (95% CI) was 14.5 (13.7; 15,2) years; 103 (51.8%) patients were female. The mean maximum change in forced expiratory volume in 1 s (FEV(1)) was observed during the first month of treatment [11.1% (6.1; 16.1)]. By the end of the first and the second year of treatment mean changes in FEV(1) were 3.3% (-1.1; 7. 6) and 5.1% (-0.7; 10.9) respectively; at the end of the same periods 34% of patients had improved their baseline FEV(1) by 10% or more but in around 50% of patients the level fell below the baseline. A large inter-individual variability in changes in pulmonary function after the start of DNase treatment was documented. In addition, the medium-term response to treatment was correlated with early response during the first 3 months. No consistent changes in exacerbation pattern were found during the first year of treatment. CONCLUSIONS: The benefits of DNase use in daily practice are limited but apparently can be maintained in the medium term in some patients. A large inter-individual variability in response to DNase treatment has been documented and the benefits are doubtful in around 50% of patients. This observation points to the need to set up a withdrawal trial in these patients, using as an eligibility criterion the early response observed during the first 3 months of treatment.

Management of postoperative pain in abdominal surgery in Spain. A multicentre drug utilization study.

AIMS: Postoperative pain is common in hospital-admitted patients. Its management is determined by different therapeutic traditions and by the attitudes of health professionals in each hospital. The aim of this study was to describe the patterns of prescription and administration of analgesic drugs used for postoperative pain after abdominal surgery in Spanish hospitals, to know the prevalence and the severity of postoperative pain, and to determine the extent of variability in the management of postoperative pain among the participating centres. METHODS: The study was a multicentre descriptive cross-sectional drug utilization study in 12 Spanish hospitals. The subjects were an unselected sample of consecutive patients undergoing abdominal surgery, admitted between October 1994 and January 1995. For each patient, information about the surgical procedure and the use of analgesics was prospectively collected. The severity of postoperative pain was assessed during the first day after surgery by means of a six-category (none, mild, moderate, severe, very severe, and unbearable) rating scale and a visual analogue scale (VAS). RESULTS: Nine hundred and ninety-three patients (547 men) were included. The most common surgical procedures were inguinal hernia repair (315, 32%), cholecystectomy (268, 27%), appendectomy (140, 14%), bowel resection (137, 14%), and gastric surgery (58, 6%). Fifty-nine percent of patients (587) received nonopioid analgesics only, 9% (89) received opioid analgesics only, and 27% (263) received both opioid and nonopioid analgesics. The most frequently administered drugs were metamizole (667 patients) and pethidine (213 patients). Although in the majority of medical orders the administration of analgesics was scheduled at regular time intervals, the majority of actual doses were given 'as-needed'. The average administered daily doses of all analgesics were lower than those prescribed. Thirty-eight percent (371/967) of patients rated their maximum pain on the first day as severe to unbearable. Wide interhospital variability was recorded in the surgical procedures which had been performed, in the analgesics used, and also in the pain scores referred by patients. The percentage of patients in each centre who suffered severe to unbearable pain varied from 22 to 67%. CONCLUSIONS: In Spain many patients still suffer severe pain after abdominal surgery, and this seems to be due to an inadequate use of analgesics. Wide interhospital variability in the management of postoperative pain and in its prevalence was also recorded.

Anticachectic efficacy of megestrol acetate at different doses and versus placebo in patients with neoplastic cachexia.

Anorexia and cachexia are present in the majority of patients with advanced-stage cancer. Several agents have been tested for their ability to reverse weight loss in these patients. Megestrol acetate has been demonstrated to improve appetite and weight, independent of tumor response, when used in the treatment of metastatic breast cancer. Several trials have studied the ability of megestrol acetate to stimulate weight gain in patients with non-hormone-sensitive tumors. One hundred fifty patients with a weight lost of more than 5% in the 3 previous months were randomized between double-blind megestrol acetate 160 mg daily (LMA), megestrol acetate 480 mg daily (HMA), or placebo (P). Weight, mid-arm circumference, triceps skinfold thickness (TST), performance status (Karnofsky index), and a quality-of-life status by seven linear analogic self-assessment scales were assessed before the start of treatment and at 4, 8, and 12 weeks thereafter. One hundred seven patients were assessable at 4 weeks, 79 at 8 weeks, and 64 at 12 weeks. Sixty-eight percent of patients treated with HMA increased their weights during their permanence on study, versus 37% and 38% of patients treated with P or LMA (p < 0.03). The mean weight gain after 12 weeks of treatment with HMA was 5.41 kg. A significant increase on TST was observed in the HMA group versus the LMA and P groups. There was no gain in performance status or quality of life in any group of treatment. The toxicity registered was mild. There were no thromboembolic events. This trial supports the efficacy of megestrol acetate at 480 mg/day in the treatment of cancer-related cachexia and anorexia, with mild toxicity. However, performance status and quality of life were not influenced by this treatment.

Trends of prescribing patterns for the secondary prevention of myocardial infarction over a 13-year period.

OBJECTIVE: The efficacy of beta-adrenergic blocking agents and acetylsalicylic acid in the secondary prevention of myocardial infarction has been well recognized since the beginning of the 1980s. In a previous paper, however, we reported a lower than expected use of these drugs during the period 1982 1988. In 1989 the results of this survey were presented and discussed with the prescribing physicians. In the present paper we describe the prescription patterns for the same indication and in the same centre over the following 6 years (1989-1994). We also describe the use of angiotensin-converting enzyme (ACE) inhibitors, for which efficacy in certain subgroups has been recently shown. METHODS: Random samples of patients discharged from our hospital between 1989 and 1994 with a diagnosis of acute myocardial infarction with Q-wave were studied. Information about diagnoses, other clinical variables and treatments prescribed at discharge was obtained from the hospital discharge forms. The results were compared with those obtained in the previous study. RESULTS: We studied 514 patients (80% men) with a median age of 59 years (range 31-89). The proportions of patients prescribed beta-adrenergic blocking agents and acetylsalicylic acid increased from 34% and 28%, respectively, in 1986-1988, to 62% and 75% in 1989 1991. In 1994 they had reached a steady state (63% and 71%). In addition, a continued decrease in the use of calcium channel blockers was noted, from 36% in 1986-1988 to 17% in 1994. The increase in the prescription of beta-adrenergic blocking agents was especially remarkable in the subgroups for which a larger underuse was recorded in the previous study, such as the elderly. The proportion of patients prescribed an ACE inhibitor increased from 14% in 1989-1991 to 23% in 1994. In a multivariate analysis the prescription of ACE inhibitors was associated with female gender, hypertension during admission, heart failure during admission, and previous myocardial infarction. A substantial increase in the prescription of beta-adrenergic blocking agents and acetylsalicylic acid and a decrease in the prescription of calcium channel blockers was recorded between 1982 and 1994. The prescription rate of beta-adrenergic blocking agents has increased substantially in certain subgroups where underuse had been previously recorded. Most of the changes occurred in 1989-1991, and reached a steady state in 1994. In 1994 an increase in the prescription of ACE inhibitors was also recorded.

Is aspirin underused in myocardial infarction?

This article reviews the relevant published literature in order to assess whether aspirin (acetylsalicylic acid; ASA) is underused in myocardial infarction (MI), taking into account: (i) the evidence of efficacy and safety from clinical trials; (ii) authoritative recommendations about its use; and (iii) published drug-utilisation studies. The use of low-dosage aspirin in the acute phase of MI, and as secondary prevention, should be recommended to all patients who do not have contraindications to the drug. This is a solid evidence-based recommendation with potential benefits that are, at least, similar to those obtained with other standard treatments. As this treatment is well tolerated and inexpensive, it is also assumed that net savings can be achieved. No conventionally used prophylactic aspirin regimen seems to be free from the risk of serious gastrointestinal toxicity. This is especially important in primary prevention, in which the benefits are small; there is, as yet, no clear evidence that aspirin is indicated for routine use in patients at low risk of occlusive vascular events. We have identified 21 published drug-utilisation studies, and the potential underuse of aspirin in MI was not properly assessed in most of them. In these studies, fairly high aspirin prescription rates were usually documented. However, it seems clear that there is room for improvement, and that a significant proportion of patients who could have benefited from aspirin did not receive it or received less well-studied and more costly drugs. The prescription rates for other drugs with proven efficacy have been lower, and the potential underuse greater, than those documented for aspirin.

[Analgesics in the postoperative period of abdominal interventions. The Study Group on Postoperative Analgesia of the Spanish Society of Clinical Pharmacology]. / Analgésicos en el postoperatorio de intervenciones abdominales, y Grupo de Estudio sobre la Analgesia Postoperatoria de la Sociedad Española de Farmacología Clínica.

BACKGROUND: Analgesics can avoid postoperative pain. The aim of this study was to evaluate their prescription after abdominal surgery. PATIENTS AND METHODS: Prospective study including patients who had undergone abdominal surgery in two hospitals in Barcelona, in 1993. Prescription and administration of analgesic drugs, and pain severity during the first 48 hours of the postoperative period were evaluated. RESULTS: One hundred and sixty-four patients (83 men) were included. The most frequently prescribed drugs were metamizol (111; 68%), pethidine (83, 51%), and diclofenac (44; 27%). A high percentage of analgesic prescriptions on an "as needed" basis was recorded. Administered doses were lower than those recommended, and lower than those prescribed. Fifty-three percent of patients suffered significant pain during the first day. CONCLUSION: A too low proportion of analgesic drugs is prescribed in a predetermined schedule, in contrast to "as needed" prescription. Opiate derivatives are underused. All analgesic drugs are prescribed at inadequate dosage. This prescription pattern is associated with a high prevalence of postoperative pain.

[Utilization of thrombolytic drugs in Barcelona. Study Group on Secondary Prevention of Myocardial Infarction]. / Utilización de fármacos trombolíticos en Barcelona. Grupo de Estudio para la Prevención Secundaria del Infarto de Miocardio.

BACKGROUND: A number of clinical trials including more than 50,000 patients have shown the efficacy of thrombolytic therapy in reducing mortality associated with acute myocardial infarction (AMI). However, the results of some recently published drug utilization studies have shown that only one third of admitted patients with a diagnosis of AMI receive thrombolytic treatment. The aim of the present study was to quantify and characterize the use of thrombolytic drugs in three hospitals in Barcelona, Spain. PATIENTS AND METHODS: We collected retrospective information about some clinical variables and drug prescription of patients discharged with a diagnosis of AMI from three hospitals in Barcelona between January and June 1994. RESULTS: Three hundred and sixty-four patients (247 men, 68%) with a mean age of 68 years (SD 13) were included in the study. The median time from the beginning of clinical symptoms to hospital admission was 3 h (range 1 to 96). One hundred and two patients (28%) were prescribed thrombolytic drugs, and of these, 62%, received streptokinase. No one patient received any thrombolytic treatment before hospital admission. In a multivariate analysis the following variables were negatively associated with thrombolytic use: age over 75 years, more than three hours from the beginning of symptoms to hospital admission and an EKG with bundle-branch block, ST depression or normal. After excluding patients with limitations to thrombolytic use, 18% of all patients could be identified who did not receive any thrombolytic treatment they could have benefited from. CONCLUSIONS: Only one third of admitted patients with a diagnosis of AMI in the three study hospitals receive thrombolytic treatment. One fifth of the study population with AMI does not receive any thrombolytic therapy but could have benefited from it.

[Profile of self-medication in Brazil]. / Perfil da automedicação no Brasil.

INTRODUCTION: The data presented are part of a World Health Organization (WHO) multicenter study of self-medication in Latin America. Brazilian sites included: Belo Horizonte, Fortaleza, the city of S. Paulo and outlying locations. The objective was to characterize self-medication practices by analyzing drugs sought by consumers in pharmacies without a physician's prescription. MATERIAL AND METHOD: Drugs were classified according to the Anatomic Therapeutic Classification codes, and analyzed with respect to 1) intrinsic value; 2) recognition as an essential drug (by either WHO or Brazil); 3) number of active ingredients; and 4) requirement for prescription. RESULTS: Five thousand, three hundred and thirty-two (5,332) different drugs, with 785 distinct active ingredients were sought. Of these, 49.5% were fixed dose combinations, 53.0% were of little intrinsic value, 44.1% required a physician's prescription, 71.0% were not essential drugs, and 40.0% of requests were based on prior prescriptions from the physician. The drugs most requested were analgesics (17.3%), nasal descongestants (7.0%), antirheumatic anti-inflammatory drugs (5.6%), and systemic anti-infective drugs (5.6%). CONCLUSIONS: Self-medication in Brazil reflects the needs and habits of the population. It is strongly influenced by physician's-prescribing habits and by the inadequate selectivity of the Brazilian pharmaceutical market.

From clinical trials to clinical practice: oral anticoagulation among patients with non-rheumatic, atrial fibrillation.

OBJECTIVES: The aim of the present study was to evaluate the impact of the results of clinical trials on the prophylactic treatment of non-rheumatic atrial fibrillation with oral anticoagulants. METHODS: Retrospectively, we studied a random sample of 375 patients discharged from our hospital with a diagnosis of non-rheumatic atrial fibrillation between 1991 and 1993. Information about diagnoses, other clinical variables and treatments prescribed at discharge was obtained from the hospital medical records. RESULTS: During the whole study period, 14% of patients were prescribed an oral anticoagulant agent and 17% were prescribed acetylsalicylic acid. A non-significant increase in the proportion of patients prescribed oral anticoagulant drugs, from 9% to 17%, was observed. Multivariate analysis showed that a history of stroke (OR = 5.96) and younger age were significantly associated with the prescription of oral anticoagulants. ASA prescription was strongly associated with a history of concomitant vascular disease (OR = 5.8), but not with other risk factors for stroke. Sixty-five percent of patients had one or more risk factors for stroke, did not present any contraindications to anticoagulant agents, but nevertheless were not prescribed one of these drugs. CONCLUSIONS: Anticoagulant agents and acetylsalicylic acid were largely underprescribed to patients with non-rheumatic atrial fibrillation, and oral anticoagulants were not prescribed according to the individual patients' risk of stroke.

[Electromyographic characteristics of postanesthetic tremor]. / Características electromiográficas del temblor postanestésico.

Postanesthetic tremor is a frequent complication during recovery from surgery. Its etiopathogenesis is poorly understood and its electromyographic characteristics have scarcely been studies. We report the electromyographic characteristics of three normothermic patients with postanesthetic tremor. Electromyography revealed tremor to be consistent with that recorded for patients with exacerbated physiological tremor. None of the three patients had electromyographic signs typical of hypothermic patients with tremor. We conclude that the electromyographic signs of postanesthetic tremor should be studied further and consider it noteworthy that the recordings we made could be attributable to high levels of circulating catecholamines, leading to exacerbation of physiologic tremor manifested in the form of postanesthetic shivering.

A randomized, double-blind, placebo-controlled trial comparing pethidine to metamizol for treatment of post-anaesthetic shivering.

1. Shivering is frequent during the post-anaesthetic recovery period, and there is no clear consensus about the best strategy for its treatment. We tested the efficacy of two commonly used analgesic drugs, pethidine and metamizol. 2. A randomized, double-blind, placebo-controlled clinical trial was performed, including 104 adult patients who presented with post-anaesthetic shivering during the recovery from general anaesthesia. They were randomized to receive placebo (n = 32), metamizol 25 mg kg-1 (n = 37), or pethidine 0.4 mg kg-1 (n = 35). The response to treatment was assessed 5, 15 and 45 min after drug administration, and the main outcome variable was complete suppression of shivering. 3. The efficacy at 5, 15 and 45 min was as follows: placebo 6%, 16% and 37%; metamizol 13.5%, 32% and 76%, and pethidine 89%, 91% and 89%. With both active drugs the efficacy at all three time intervals was significantly higher than that with placebo (P < 0.05). The differences (at 5 and 15, but not at 45 min) between pethidine and metamizol were statistically significant (P < 0.05). Both drugs were well tolerated. 4. The persistence of shivering at 45 min in two thirds of placebo-treated patients indicates that drug treatment is worthwhile; metamizol produces a better postanaesthetic shivering response than placebo, especially 15 and 45 min after drug administration; the efficacy of pethidine was the highest and the response to it appeared more quickly; however, at 45 min it was similar to that observed with metamizol. 5. Both metamizol and pethidine suppress postanaesthetic shivering, but the latter induces a quicker and more reliable response.

Intravenous amiodarone in treatment of recent-onset atrial fibrillation: results of a randomized, controlled study.

OBJECTIVES: This study was designed to determine the efficacy of intravenous amiodarone in the management of recent-onset atrial fibrillation. BACKGROUND: The optimal approach for acute atrial fibrillation has not been established. Amiodarone is a unique antiarrhythmic agent with activity in both supraventricular and ventricular tachyarrhythmias, but its value for the restoration of sinus rhythm in patients with recent-onset atrial fibrillation has not been demonstrated. METHODS: Sample size was calculated to detect a 25% increase in reversion rate with amiodarone with a statistical power of 80%. One hundred consecutive patients with recent-onset (<1 week) atrial fibrillation and not taking antiarrhythmic agents were randomized to receive either intravenous amiodarone, 5 mg/kg body weight in 30 min followed by 1,200 mg over 24 h, or an identical amount of saline. Both groups received intravenous digoxin, 0.5 mg initially, followed by 0.25 mg at 2 h and 0.25 mg every 6 h thereafter, to complete 24 h while the ventricular rate was >100 beats/min. Amiodarone and digoxin blood levels were determined. Both groups were homogeneous regarding underlying heart disease, time from onset to treatment, initial ventricular rate and left atrial size. RESULTS: By the end of the 24-h treatment period, 34 patients (68%, 95% confidence interval [CI] 53% to 80%) in the amiodarone group and 30 (60%, 95% CI 45% to 74%) in the control group had returned to sinus rhythm (p = 0.532). Mean times (+/-SD) of conversion were 328 +/- 335 and 332 +/- 359 min, respectively (p =0.957). Among patients who did not convert to sinus rhythm, treatment with amiodarone was associated with a slower ventricular rate (82 +/- 15 beats/min in the amiodarone group vs. 91 +/- 23 beats/min in the control group, p = 0.022). After restoration of sinus rhythm, atrial fibrillation recurred during a 15-day follow-up period in 4 (12%) of 34 patients (95% CI 3% to 27%) in the amiodarone group and in 3 (10%) of 30 (95% CI 2% to 26%) in the control group (p = 0.861). CONCLUSIONS: Intravenous amiodarone, at the doses used in this study, produces a modest but not significant benefit in converting acute atrial fibrillation to sinus rhythm.