COMPARISON OF DIAZEPAM AND FLUNITRAZEPAM FOR SEDATION DURING LOCAL ANAESTHESIA FOR BRONCHOSCOPY

Transcription

1 Br.J. Anaesth. (1978), 5, 281 COMPARISON OF DIAZEPAM AND FLUNITRAZEPAM FOR SEDATION DURING LOCAL ANAESTHESIA FOR BRONCHOSCOPY K. KORTTILA, L. SAARNIVAARA, J. TARKKANEN, J.-J. HIMBERG AND M. HYTONEN SUMMARY Diazepam and flunitrazepam were compared as amnesic and sedative adjuncts to local anaesthesia for diagnostic bronchoscopy in 92 patients. After local anaesthesia of the pharynx, larynx and trachea with lignocaine, atropine plus diazepam or flunitrazepam was injected i.v. The co-operation of the patients and the technical circumstances under which the bronchoscopy was performed were good in each group. None of the treatments significantly modified arterial pressure or heart rate. Two hours after the injection, flunitrazepam.1 mg kg" 1 more frequently caused amnesia for pictures shown to the patients during the first 15 min after injection (failure to recall 2-75%, and for bronchoscopy 67%), than did diazepam.125 mg kg" 1 (failure to recall -67%; bronchoscopy 38%). Double doses of the drugs caused amnesic actions similar to those of flunitrazepam.1 mg kg" 1. When failure to recall was assessed on the following day, 29% and 5% of the patients remembered bronchoscopy after flunitrazepam.1 and.2 mg kg- 1 respectively; after diazepam.125 and.25 mg kg" 1 the corresponding percentages was 59% and % (P<.5 v. flunitrazepam). The ability to stand and walk on a straight line was similar after the smaller doses of both drugs, but after the larger doses recovery was slower after flunitrazepam. Psychomotor performance was still distinctly impaired 2 h after the injection of the larger doses. Bronchoscopy under local anaesthesia is often a disagreeable and frightening examination. In Finland bronchoscopy is usually performed as an outpatient procedure. If the patient is slightly sedated, the procedure is easier and more acceptable to the patient. Diazepam has been recommended for such sedation (Editorial, 1976). It induces amnesia without affecting the level of consciousness or causing any major depression of the cardiopulmonary system (Duncan and Barr, 1973; Trieger, 1973; Gregg, Ryan and Levin, 197). Flunitrazepam has similar properties (Stovner, Endresen and Osterud, 1973) and Dundee and colleagues (1976) suggest diazepam and flunitrazepam to be similar as i.v. sedative and anaesthetic induction agents. However, in a potency ratio of 1 : 1, the amnesic action of small doses of flunitrazepam is more effective than that of diazepam (Korttila and Linnoila, 1975, 1976). We have compared i.v. diazepam and flunitrazepam as amnesic and sedative adjuncts to local anaesthesia for diagnostic bronchoscopy. K. KORTTILA, M.D., Department of Anaesthesia, Helsinki University Central Hospital, Haartmaninkatu, SF-29 Helsinki 29, Finland. J.-J. HIMBERG, M.D., M.SC, Department of Pharmacology, University of Helsinki, Helsinki, Finland. L. SAARNIVAARA, M.D.; J. TARKKANEN, M.D.; M. HYTONEN; Otolaryngological Hospital, University of Helsinki, Helsinki, Finland. Correspondence to K. K. PATIENTS, MATERIALS AND METHODS Patients and sedation Ninety-two patients undergoing diagnostic bronchoscopy were studied. Patients over the age of 6 yr and those under the age of 5 yr were always given the smaller and larger doses, respectively. The patients between 5 and 6 years of age were allocated randomly to one of four groups (table I). Thus, the groups receiving the smaller doses were comparable with regard to age, weight and height, as were the groups given the larger doses. Any patient who had taken psychotropic or other drugs known to interact with benzodiazepines or who could not perform the recovery tests before the drugs were administered was excluded. Informed consent was obtained from each patient. Lignocaine (Lidocain, Orion, Helsinki) 17-2 mg was sprayed on the pharynx (2 ml, 1% solution), larynx and trachea (5-6 ml, 3% solution) immediately before injection of the drugs. Atropine (Atropin, Orion, Helsinki).1 mg kg" 1 was injected i.v. 5 min before the sedative. Diazepam (Valium, Roche, Basel).125 mg kg" 1 or.25 mg kg" 1 was injected into a cubital vein at a rate of 5 mg min" 1. Flunitrazepam (Ro 5-2, Roche, Basel).1 mg kg" 1 or.2 mg kg" 1 was given at a rate of.5 mg min" 1. The patient, the bronchoscopist and the investigator were unaware of the identity of the drug being used.

2 282 BRITISH JOURNAL OF ANAESTHESIA (ing kg- 1, i.v.) TABLE I. Characteristics of the test groups No. of patients Age (yr) * ** 6±11 9 ±13 (mean ± SD) Weight (kg) Height (cm) ± 9 * P<.1 v. diazepam.25 mg kg- 1 ; ** P<.25 v. flunitrazepam.2 mg kg" 1 Clinical observations, assessment of amnesia and subjective assessments The systolic and diastolic arterial pressures were measured by auscultation and the heart rate was counted at the wrist after 5 min of rest in a horizontal position, after spraying with lignocaine, before bronchoscopy, after bronchoscopy was complete, and 15 and min after injection of the benzodiazepine. The subjects were shown a bank note, a picture of the President of Finland and a stamp as a memory test in a manner similar to the method of Dundee and Pandit (1972). The first figure was shown just after the injection of diazepam or flunitrazepam, the second after the bronchoscope was removed and the third 15 min after the injection of the drugs. Two hours after injection of the sedative the patient was asked which figures he or she could remember. Recollection of the i.v. injection, the insertion of the bronchoscope and the removal of the scope was sought also. The bronchoscopist (J. T.) rated both the efficiency of the anaesthesia and the co-operation of the patient (ease of bronchoscopy) on a visual analog scale (1 mm long) between poor ( mm) and good (1 mm). The patient gave an opinion of the pleasantness of the procedure in the same manner. Assessment of recovery Initial recovery was determined by Romberg's test and by the patients' ability to walk on a straight line (Korttila, 1976a). Assessments were made when the patient arrived in the operating theatre and, 6 and 12 min after the injection of the sedative. A visualization test (James, 1969) was performed: the subject must trace each of 1 intermixed lines from their origin on the left side of the paper to their termination on the right without the aid of a tracing finger. The score is the number of correct tracings in a 3-min period. The aiming test (James, 1969) consists of a piece of paper (2 cm x cm) with 15 rows of 2 open circles (diameter 2 mm). The subject must place a dot inside each of as many circles as possible in 3 min. The dot must not touch the edge of the circle, and the score is based on the number of correct responses. Questionnaire When leaving the operating theatre, the patients were given a sealed envelope, which they were asked to open the next day, and which contained a questionnaire concerning the bronchoscopy (table II). TABLE II. Questionnaire 1. I clearly remember: (a) local anaesthesia of the respiratory tract (b) the insertion of the needle into my vein and the injection of the sedative (c) the performance of the bronchoscopy 2. I would like a possible future bronchoscopy to be done in the same way 3. The next time I would insist on a general anaesthesia for the bronchoscopy. After the bronchoscopy I was requested to (a) stand still (b) walk on a line (c) mark spots inside circles on a paper 5. Yesterday afternoon after the sedation (a) I felt normal (b) I noticed the following to be unusual (specify, please) Drug concentrations in serum Venous blood was sampled from a cubital vein 2 h after the injection of diazepam or flunitrazepam. Sera were stored at C until the concentrations of serum diazepam and flunitrazepam were assayed after extraction by electron-capture gas-liquid chromatography according to a modification of the method of de Silva and others (1976). Data analysis Statistical treatment of the data was carried out according to the non-parametric Chi-square test and according to Student's t test for independent means.

3 DIAZEPAM AND FLUNITRAZEPAM SEDATION FOR BRONCHOSCOPY 283 TABLE III. Amnesia for bronchoscopy and pictures 2 h afterwards (% of total) Failure of recall of picture Amnesia for scope (mg kg- 1 ) Shown after injection of sedative Shown after scope removal Shown 15 min after injection Insertion Removal n = 2) («= 23) (n = ) RESULTS The principal differences recorded between diazepam and flunitrazepam were that flunitrazepam.1 mg kg -1 induced more efficient and longer-lasting amnesia than diazepam.125 mg kg- 1, and that recovery was slower after the larger dose of flunitrazepam (.2 mg kg- 1 ) than after that of diazepam.25 mg kg" 1..1 mg kg- 1. Failure to recall the picture 15 min Cardiovascular effects and the performance of broncho-aftescopy the amnesic action of flunitrazepam seemed to last the administration of the drugs indicated that After each treatment both systolic and diastolic longer than that of diazepam. arterial pressure remained almost unaltered during bronchoscopy and were slightly reduced (always less Subjective assessments than 15 mm Hg systolic and 5 mm Hg diastolic) The efficiency of the local anaesthesia and the cooperation of the patients and the acceptability to the afterwards. The heart rate increased by an average of 1 beat min" 1 after each treatment. The mean time patients were similar in each experimental group ( ± SD) to perform the bronchoscopy varied according (table IV). The bronchoscopist rated the effect of to the treatment as follows: Diazepam.125 mg kg- 1 Flunitrazepam.1 mg kg" 1 Diazepam.25 mg kg" 1 Flunitrazepam.2 mg kg" ±3.3 min 5.2 ±2.1 min 3.6 ±2.1 min min Amnesia Flunitrazepam.1 mg kg- 1 induced amnesia for the pictures (2-75%) and for the insertion and removal of the bronchoscope (67%) more frequently than did diazepam.125 mg kg" 1 (failure to recall: pictures 25-67%, bronchoscopy 38-2%) (table III). Two hours after the injection the amnesic actions of the larger doses of the drugs were similar and did not differ significantly from that of flunitrazepam the local anaesthetic between (mean + SD) for flunitrazepam.2 mg kg- 1 and for diazepam.125 mg kg- 1. Co-operation of the patients in the four groups during the bronchoscopy varied between and 69 ±32. The patients of the TABLE IV. Efficiency of local anaesthesia and co-operation during bronchoscopy ( = poor, 1 = good) acceptability of procedure determined after 2 h ( = unpleasant, 1 = pleasant) (mean±sd) (mg kg- 1 ) Efficiency of local anaesthesia Co-operation of patients Acceptability to patients (» = 2) (n = 23) (n = ) ±38 69 ±32 56±2 62±3 5 ±26 55±19 59 ±1 57 ±15 23

4 28 BRITISH JOURNAL OF ANAESTHESIA TABLE V. Percentage of patients who could not stand steady or walk on line, 6 and 12 min after injection of diazepam or flunitrazepam Unable to stand steady after Unable to walk on line after (mg kg" 1 ) min 6 min 12 min min 6 min 12 min (n = 23) (n = ) » = 6.79; P<.1 v. diazepam.25 mg kg- 1. four groups used the same method to rate the pleasantness of sedation, the results ranging between 5 ±26 and 59 ±1. Recovery The patients' ability to stand steady and walk on a line after sedation is shown in table V. These functions were similar with the smaller doses of both drugs, but after the larger doses they recovered more slowly after flunitrazepam than after diazepam. One hour after the injection of diazepam.25 mg kg- 1 and flunitrazepam.2 mg kg- 1, % and % of the patients respectively could not stand steady. Two hours after sedation, each subject who received diazepam.25 mg kg" 1 could stand steady and walk on a straight line, whereas 33% of those receiving flunitrazepam.2 mg kg" 1 could not. In respect of the visualization and aiming tests, there were no differences between the smaller doses or between the larger doses of the sedatives (table VI). Questionnaire In each group the acceptability of both sedation and the procedure were confirmed (table VII). Fewer than 15% would have preferred general anaesthesia. On the day after flunitrazepam.1 mg kg- 1 and.2 mg kg- 1 only 29% and 5% respectively remembered the performance of bronchoscopy, whereas after diazepam.125 mg kg" 1 and.25 mg kg" 1 the corresponding recall percentages were 58% and % respectively. Drug concentrations in serum {table VIII) There was a dose-related residuum of diazepam and flunitrazepam 2 h after injection. DISCUSSION Results with healthy volunteers (Korttila and Linnoila, 1975,1976) indicate that flunitrazepam may have a better amnesic action in small doses than comparable doses of diazepam. Our aim was to find comparable doses of diazepam and flunitrazepam in respect of side and residual effects and to compare their amnesic action. We used a 1: 12.5 potency ratio; previous results indicate that with a ratio of 1: 1 flunitrazepam is associated with a longer recovery period (Korttila and Linnoila, 1975,1976). TABLE VI. Recovery {visualization and aiming tests). Mean±SD before sedation and change ± SD 2 h afterwards Visualization test, number correct Aiming test, number correct (mg kg- 1 ) Before sedation Change 2 h after sedation Before sedation Change 2h after sedation ± ± ± ± ± ± ±

5 DIAZEPAM AND FLUNITRAZEPAM SEDATION FOR BRONCHOSCOPY 285 Remembered local anaesthesia insertion of needle bronchoscopy Would like next bronchoscopy performed similarly Remembered standing walking on line marking spots Following afternoon normal unusually tired sore throat miscellaneous TABLE VII. Answers to the questionnaire (numbers are %) Diazepam.125 mg kg" Flunitrazepam.1 mg kg" * Diazepam.25 mg kg Flunitrazepam.2 mg kg" 1 1 5** * X 2 = 5.31,P<.5a.diazepam.125 mg kg- 1 ; ** x a = 6.,P<.5v.diazepam.25 mg kg" TABLE VIII. Concentration of diazepam or flunitrazepam in serum {mean ± SEM) 2 h after injection Diazepam No. of Concentration (mgkg -1 ) patients (ngrnl" 1 ) Flunitrazepam ± ±.8 58±11 In Finland the testing of recovery after sedation is important since examinations like bronchoscopy are mostly undertaken as outpatient procedures. Our tests, however, do not indicate "street-fitness" or psychomotor recovery (Korttila, 1976a, b, 1978). Romberg's test and walking on a straight line are indices of the skills that are affected most and longest after sedation with both diazepam and flunitrazepam (Korttila and Linnoila, 1975, 1976). Both tests are easy to perform and there is no training effect (Kortilla, 1976a). The visualization test and the aiming test proved to be sensitive measures of mental functions after cyclopropane anaesthesia (James, 1969). Subjects who are untrained show improvement in performance when the tests are repeated. However, we used the tests to reveal differences between diazepam and flunitrazepam. Effects of diazepam and flunitrazepam We found previously that flunitrazepam.1 mg kg -1 caused amnesia more frequently than did i.v. diazepam.15 mg kg- 1 (Korttila and Linnoila, 1976). Dundee and others (1976) found an equal degree of amnesia after both drugs administered i.v. in a 1 : 1 potency ratio 1 h after injection, but that amnesic action lasted longer after flunitrazepam. Thornton and Martin (1976) found that flunitrazepam 1 mg induced anterograde amnesia during the 1 min following its injection and thought that flunitrazepam may be capable of alleviating the anxiety of dental outpatients. In the present study the amnesic action of flunitrazepam.1 mg kg- 1 was superior to that of diazepam.125 mg kg- 1. In the larger doses, the amnesic action of the drugs was similar and indicates differences in the dose-response. The observation that failure to recall bronchoscopy was more frequent on the following day than 2 h after the procedure suggests that studies on the amnesic effects of drugs should include questioning over longer than a few hours after administration. Recent studies (Ghoneim, Mewaldt and Thatcher, 1975; Korttila and Linnoila, 1975) indicate that psychomotor skills are impaired for at least 6 h after diazepam.15 mg kg- 1 and 8h after diazepam.3 mg kg" 1 given i.v. E.e.g. sleep patterns have been demonstrated at 18 h and an impairment on behavioural tests at 12 h after the oral intake of

6 286 BRITISH JOURNAL OF ANAESTHESIA flunitrazepam 1 or 2 mg (Bond and Lader, 1975). After flunitrazepam.1 mg kg" 1 i.v. eye-hand coordination was impaired slightly for as long as 6 h after the injection, and after.2 mg kg" 1 the impairment was still significant at the last observation period 1 h after the injection (Korttila and Linnoila, 1976). The results of the present study agree with previous findings that recovery after small doses of diazepam and flunitrazepam is similar, but, when the dose is increased, flunitrazepam has more prolonged residual effects. When small doses of diazepam and flunitrazepam are used to supplement local anaesthesia for bronchoscopy, the procedure is accepted and seldom recalled by patients. Recovery is not prolonged and the procedure can be performed on outpatients without general anaesthesia. Flunitrazepam may be useful in other procedures where amnesia is needed. Drug concentrations in blood Klotz and others (1975) have demonstrated a fourto five-fold increase in the half-life of diazepam as a function of age. This would appear to be true of flunitrazepam also. In a previous study (Korttila and Linnoila, 1976) of flunitrazepam.1 mg kg" 1 i.v. in young subjects, the mean serum concentration of flunitrazepam 2 h after administration was 5.5 ± SEM.7 ng ml" 1, whereas in this study (average age 58 yr) it was ng ml" 1 (mean ± SEM). ACKNOWLEDGEMENT Flunitrazepam was kindly provided by F. Hoffmann-La Roche & Co. Ltd, Basle, Switzerland. REFERENCES Bond, A. J., and Lader, M. H. (1975). Residual effects of flunitrazepam. Br.J. Clin. Pharmacol., 2, 13. Duncan, A. W., and Barr, A. M. (1973). Diazepam premedication and awareness during general anaesthesia for bronchoscopy and laryngoscopy. Br. J. Anaesth., 5, 115. Dundee, J. W., George, K. A., Vandarajan, C. R., Clarke, R. S. J., and Nair, S. K. G. (1976). Anaesthesia and amnesia with flunitrazepam. Br. J. Anaesth., 8, 266. Pandit, S. K. (1972). Anterograde amnesic effects of pethidine, hyoscine and diazepam in adults. Br. J. Pharmacol.,, 1. Editorial (1976). Sedation for minor procedures. Drug Ther. Bull., 1, 19. Ghoneim, M. M., Mewaldt, S. P., and Thatcher, J. W. (1975). The effect of diazepam and fentanyl on mental, psychomotor and electroencephalographic functions and their rate of recovery. Psychopharmacologia,, 61. Gregg, J. M., Ryan, E., and Levin, K. H. (197). The amnesic actions of diazepam. J. Oral Surg., 32, 651. James, F. M. (1969). The effects of cyclopropane anesthesia without surgical operation on mental functions of normal man. Anesthesiology., 26. Klotz, U., Avant, G. R., Hoyumpa, A., Schenker, S., and Wilkinson, G. R. (1975). The effect of age and liver disease on the disposition and elimination of diazepam in adult man. J. Clin. Invest., 55, 37. Korttila, K. (1976a). Recovery after intravenous sedation. A comparison of clinical and paper and pencil tests used in assessing late effects of diazepam. Anaesthesia, 31, 72. (1976b). Minor outpatient anaesthesia and driving; in Modem Problems in Pharmacopsychiatria (ed. M. J. Manila), vol. 11, p. 91. Basle: Karger. (1978). Recovery and driving after brief anesthesia; in New Directions in Anesthesiology (ed. R. E. Johnstone). Medical Examination Publishing Company. (In press). Linnoila, M. (1975). Skills related to driving after intravenous sedation: dose-response relationship with diazepam. Br. J. Anaesth., 7, 57. (1976). Amnesic action and skills related to driving after intravenous flunitrazepam. Acta Anaesthesiol. Scand., 2, 16. de Silva, A. F., Bekersky, I., Puglisi, C. V., Brooks, M. A., and Weinfeld, R. E. (1976). Determination of 1,- benzodiazepines and diazepin-2-ones in blood by electron-capture gas-liquid chromatography. Anal. Chem., 8, 1. Stovner, J., Endresen, R., and Osterud, A. (1973). Intravenous anaesthesia with a new benzodiazepine Ro 5-2. Acta Anaesthesiol. Scand., 17, 163. Thornton, J. A., and Martin, V. C. (1976). Flunitrazepam in dental outpatients. Anaesthesia, 31, 297. Trieger, N. (1973). Intravenous sedation. Dent. Clin. N. Am., 17, 29. COMPARAISON DU DIAZEPAM ET DU FLUNITRAZEPAM EN TANT QUE SEDATIFS PENDANT UNE ANESTHESIE LOCALE POUR BRONCHOSCOPIE RESUME On a compare sur 92 malades les proprietes amnesiques et sedatives du diazepam et du flunitrazepam utilises conjointement avec une anesthesie locale pour une bronchoscopie de diagnostic. Apres anesthesie locale du pharynx, du larynx et de la trachee a l'aide de lignocaine, on a injecte par voie intraveineuse de l'atropine additionse de diazepam ou de flunitrazepam. La cooperation des malades et les conditions techniques dans lesquelles la bronchoscopie a ete effectuee etaient bonnes dans chaque groupe. Aucun des traitements n'a modifie d'une maniere significative la tension arterielle ou le poul. Deux heures apres l'injection, le flunitrazepam a raison de,1 mg kg" 1 a plus frequemment provoque une amnesie des images qui avaient ete montr6es aux malades au cours des 15 premieres min qui ont suivi l'injection (absence de souvenir 2-75%) et de la bronchoscopie (67%) que ce n'a ete le cas avec le diazepam a raison de,125 mg kg" 1 (souvenir des images -67% et de la bronchoscopie 38%). Des doses doublees de ces medicaments ont cause des actions amnesiques similaires a celles du flunitrazepam administre a,1 mg kg" 1. Lorsqu'on a evalu6, le lendemain, les absences de souvenir, 29% et 5% des malades se sont souvenus de la broncho-

7 DIAZEPAM AND FLUNITRAZEPAM SEDATION FOR BRONCHOSCOPY 287 scopie apres administration de flunitrazepam a raison de,1 et,2 mg kg" 1 respectivement; alors qu'apres le diazepam a raison de,125 et,25 mg kg" 1 les pourcentages correspondants etaient de 59% et % respectivement (P<,5 v. flunitrazepam). La capacite des malades a se tenir debout et a marcher en suivant une ligne droite a ete similaire apres les plus faibles doses des deux medicaments, mais apres les plus fortes doses, la recuperation a ete plus lente apres le flunitrazepam. Les performances psychomotrices des malades etaient toujours nettement alterees 2h apres l'injection des plus fortes doses. VERGLEICH ZWISCHEN DIAZEPAM UND FLUNITRAZEPAM ALS SEDATIVA BEI LOKALANASTHESIE WAHREND EINER BRONCHOSKOPIE ZUSAMMENFASSUNG Diazepam und Flunitrazepam wurden als Sedativzusatze bei Lokalanasthesie fur diagnostische Bronchoskopie bei 92 Patienten miteinander verglichen. Nach Lokalanasthesie fur Pharynx, Larynx und Trachea mit Lignocain, wurde Atropin plus Diazepam oder Flunitrazepam intravenos verabreicht. Die Mithilfe der Patienten und die technischen Umstande, unter denen die Bronchoskopien vorgenommen wurden in alien Gruppen vorteilhaft. Keine dieser Behandlungen fuhrte zu einer wesentlichen Veranderung von arteriellem Druck und Herztatigkeit. Zwei Stunden nach der Injektion wurde durch,1 mg/kg Flunitrazepam haufiger eine Amnesie im Bezug auf Bilder hervorgerufen, die den Patienten wahrend der ersten 15 min nach der Injektion gezeigt worden waren (2-75% konnten sich nicht daran erinnern) und im Bezug auf die Bronchoskopie (67%); bei Verabreichung von,125 mg/kg Diazepam diese Werte nur -67%, bezw. 38%. Doppelte Dosen dieser Drogen bewirkten ahnliche Amnesiewirkungen wie die Dosis von,1 mg/kg Flunitrazepam. Wenn der Gedachtnisverlust am folgenden Tag bewertet wurde zeigte sich, dass nach,1, bezw. nach,2 mg/kg Flunitrazepam 29%, bezw. 5% der Patienten sich an die Bronchoskopie erinnern konnten, wahrend nach,125, bezw. nach,25 mg/kg Diazepam die entsprechenden Prozentsatze bei 59%, bezw. bei % lagen (P<,5 v. Flunitrazepam). Die Fahigkeit zu stehen und einer geraden Linie entlang zu gehen war bei den kleineren Dosen beider Drogen ahnlich, bei grosseren Dosen jedoch war die Erholung nach Flunitrazepam langsamer. Die psychomotorische Leistung war 2 Stunden nach Injektion der grosseren Dosen immer noch deutiich beeintrachtigt. COMPARACION ENTRE DIAZEPAM Y FLUNITRAZEPAM PARA PROPOSITOS DE SEDACION DURANTE ANESTESIA LOCAL PARA BRONCOSCOPIA SUMARIO Se compararon diazepam y flunitrazepam como adiciones amnesicas y sedativas a la anestesia local para broncoscopias de diagnosis en 92 pacientes. Despues de la anestesia de la farinje, larinje y traquea con lignocaina, se inyecto atropina mas diazepam o flunitrazepam intravenosamente. La cooperation de los pacientes y las circunstancias tecnicas bajo las cuales se llevaron a cabo las broncoscopias en cada grupo fueron buenas. Ninguno de los tratamientos modifico significativamente la presion arterial ni la frecuencia del corazon. Dos horas despues de la inyeccion, el flunitrazepam,1 mg kg" 1 causo amnesia mas frecuentemente en el caso de ilustraciones mostradas a los pacientes durante los primeros 15 min despues de la inyeccion (una falta de evocacion de 2-75%) y para broncoscopia un 67%, que el diazepam,125 mg kg" 1 (evocacion -67%; broncoscopia 38%). Una doble dosis de las drogas caus6 acciones amnesicas semejantes a aquellas de flunitrazepam,1 mg kg" 1. Cuando se evaluo la falta de evocacion al dia siguiente, un 29% y un 5% de los pacientes recordaron la broncoscopia despues de recibir flunitrazepam,1 y,2 mg kg" 1 respectivamente; despues del diazepam,125 y,25 mg kg" 1 los porcentajes correspondientes fueron de 59% y % (P<,5 v. flunitrazepam). La habilidad de levantarse y caminar en linea recta resulto semejante despues de las dosis pequefias de ambas drogas, pero despues de las dosis mayores la recuperation resulto mas lenta despues del flunitrazepam. La funcion psicomotora estaba aun claramente impedida despues de 2 h de haberse inyectado las dosis mayores.