Showing papers in "Acta Anaesthesiologica Scandinavica in 1965"

A Comparison of the Hydrochloride and Carbon Dioxide Salts of Lidocaine and Prilocaine in Epidural Analgesia

Abstract: SUMMARY Lumbar epidural blockade has been used in a series of 659 patients to compare the analgesic properties of lidocaine and prilocaine. Solutions of both compounds were compared as hydrochloride salts in 2% and 3% concentration with and without adrenaline 1:200,000. Solutions of base, made soluble by equilibration with carbon dioxide at a pC02 of 700 mm Hg were also compared in concentrations of 1.75% for lidocaine and 1.71% for prilocaine. Comparisons were based on measurements of latency, spread of analgesia, intensity of motor blockade and duration of analgesia. The quality of blockade in all the test solutions was increased by the addition of 1:200,000 adrenaline. Prilocaine has a slow latency compared with lidocaine, but in plain solution its duration is longer than that of lidocaine. The 3% hydrochloride solutions have no practical advantage over die 2% solutions for epidural blockade. Analgesia resulting from the C02-base solutions is superior in every respect to the blockade produced by equivalent concentrations of the hydrochloride salts.

Anaesthesia and premedication as factors in postoperative vomiting.

Abstract: SUMMARY Patients having a standard operative procedure in constant surroundings formed the population for a study of some factors influencing postoperative vomiting and nausea. With constant premedication thiopentone and halothane were followed by significantly fewer symptoms than propanidid or cyclopropane. With a constant form of anaesthesia the incidence of emetic sequelae was greater with pethidine 50 mg plus atropine 0.6 mg than with atropine alone, while morphine 10 mg resulted in even more symptoms than pethidine. Where there was a high “control” incidence of sequelae, such as with propanidid or cyclopropane after morphine premedication, the use of halothane reduced the frequency during the first hours after operation, but had little effect with less emetic combinations. Chloroform caused more postoperative vomiting than halothane, and there was some evidence to suggest that induction with thiopentone reduced symptoms. ZUSAMMENFASSUNG Patienten, bei denen unter den gleichen ausseren Bedingungen operative Standardeingriffe durchgefuhrt wurden, stellten das Vergleichskrankengut einer Studie dar, bei der der Einfluss verschiedener Faktoren auf postoperatives Erbrechen und Brechreiz festgestellt werden sollte. Bei konstanter Praemedika-tion waren Thiopenton und Halothan von signifikant geringeren Symptomen gefolgt als Propanidid und Cyclopropan. Bei gleichbleibender Art der Narkose war das Auftreten von Brechreiz oder Erbrechen nach 50 mg Pethidin und 0.6 mg Atropin starker als nach Atropin allein, wahrend sich nach 10 mg Morphin sogar mehr Symptome als nach Pethidin zeigten. In den Gruppen, bei denen es zu einem hohen “Kontroll-Prozentsatz” von Folgererscheinungen kam, wie z.B. mit Propanidid und Cyclopropan nach Morphin-Praemedikation, verminderte die Verwendung von Halothan die Haufigkeit wahrend der ersten Stunden nach der Operation, hatte jedoch wenig Wirkung bei den weniger zum Erbrechen reizenden Kombinationen. Chloroform hatte mehr operatives Erbrechen zur Folge als Halothan und manche Anzeichen deuteten darauf hin, dass Einleitung mit Thiopentone die Symptome verminderte.

Bilateral ulnar nerve blocks for the evaluation of local anaesthetic agents.

Abstract: SUMMARY Bilateral ulnar-nerve blocks were performed with a double-blind technique on volunteers for the evaluation of the blocking effect of 1% mepivacaine, 1% mepivacaine with epinephrine 1:200,000, 0.25% LAC-43 (l-butyl-DL-2-piperidincarbon-2,6-dimethylanilide hydrochloride) with epinephrine 1:200,000, and 0.25% tetracaine with epinephrine 1:200,000. 1 It was found that bilateral ulnar-nerve blocks in this series gave the same results in different tests as in previous studies. 2 It was found that the duration of action of LAC-43 was 2-3 times that of mepivacaine with epinephrine, tetracaine with epinephrine and mepivacaine without epinephrine, i.e., LAC-43 blocks lasted for about 8 hours. The effect of mepivacaine with epinephrine was about 75% longer than that of mepivacaine without epinephrine. 3 The regression time, i.e. in this study the time from reappearance of pain perception to complete recovery of pain sensation, seems to be a quality characteristic of the action of a local anaesthetic solution. ZUSAMMENFASSUNG In einem Doppelblindversuch an Freiwilligen wurden zur Beurteilung der blockierenden Wirkung von 1% Mepivacain, 1% Mepivacain mit Adrenalin 1:200.000, 0,25% LAC-43 (l-Butyl-DL-2-piperidincarbon-2, 6-dimethylanilidhydrochlorid) mit Adrenalin 1:200.000 und 0,25% Tetracain mit Adrenalin 1:200.000 doppelseitige Blockadendes N. ulnaris ausgefuhrt. Folgende Ergebnisse wurden gewonnen: 1 Doppelseitige Blockaden des N. ulnaris gaben in dieser Untersuchungsreihe die selben Resultate wie bei fruheren Priifungen. 2 Die Wirkungsdauer von LAC-43 liegt 2-3 mal hoher als die von Mepivacain mit Adrenalin, Tetracain mit Adrenalin und Mepivacain ohne Adrenalin, das heisst, LAC-43-Blockaden halten ungefahr 8 Stunden an. Mepivacain mit Adrenalin ubertrifft Mepivacain ohne Adrenalinzusatz um ca. 75%. 3 Die Regressionszeit (darunter wird in dieser Untersuchung die Zeit vom Wiederauftreten erster Schmerzperception bis zur volligen Restitution der Schmerzempfindung verstanden) scheint ein qualitatives Testmerkmal der Wirkung eines Lokalanaesthetikums darzustellen.

Bilateral ulnar nerve blocks for the evaluation of local anaesthetic agents. ii. tests with new longer-acting agent, lac-43, and with tetracaine.

Abstract: Bilateral ulnar‐nerve blocks were performed with a double‐blind technique on volunteers for the evaluation of the blocking effect of 1% mepivacaine, 1% mepivacaine with epinephrine 1:200,000, 0.25% LAC‐43 (l‐butyl‐DL‐2‐piperidincarbon‐2,6‐dimethylanilide hydrochloride) with epinephrine 1:200,000, and 0.25% tetracaine with epinephrine 1:200,000.

Biochemical effects of aromatic amines. ii. cyanosis, methaemoglobinaemia and heinz-body formation induced by a local anaesthetic agent (prilocaine).

Abstract: SUMMARY The methaemoglobinaemia and cyanosis induced by 300, 600, 900, 1,200, and 1,600 mg of prilocaine, N-(2-propylaminopropionyl)-2-toluidine hydrochloride with epinephrine (1:250,000) in 67 patients and by 1,200 mg of the drug in nine healthy volunteers were investigated. There were great individual variations in the methaemoglobin response to a given dose of the drug. The peak values were reached six hours after administration of prilocaine, and the methaemoglobinaemia had disappeared after 24 hours in most cases. The time course and the intensity of the cyanosis was related to the time course andthe magnitude of the methaemoglobinaemia. 500 mg of lignocaine, diethyl-2,6-acetoxylidine with epinephrine (1:250,000) did not induce methaemoglobin formation or cyanosis. No clinical signs of deficient oxygen transport could be detected. No changes in the values of serum bilirubin, haptoglobin, creatinine, or transaminase (GPT) attributable to prilocaine were found. A slight increase in Heinz bodies was recorded. The mediaemoglobinaemia was readily prevented and reversed by metfiylene blue. The methaemoglobinaemia is probably induced by a metabolite of prilocaine. ZUSAMMENFASSUNG Die Methaemoglobinamie und Zyanose, die durch Zufuhr von 300, 600, 900, 1200 und 1600 mg Prilocain, N-(2-propylaminopropionyl)-2-toluidine Hydrochloride mit Epinephrin (1:250.000) bei 67 Patienten und durch die Zufuhr von 1200 mg des Mittels bei 9 gesunden Freiwilligen zustande kam, wurde untersucht. Es zeigten sich grosse individuelle Abweichungen im Auftreten von Methaemoglobinamie nach gleichen Dosen des Mittels. Die hochsten Werte wurden 6 Stunden nach der Gabe von Prilocain erreicht, in den meisten Fallen verschwand die Methaemoglobinamie nach 24 Stunden. Der zeidiche Verlauf und die Intensitat der Zyanose stand im Verhaltnis zum zeitlichen Verlauf und Ausmass der Methaemoglobinamie. 500 mg Lignocain, diethyl-2, 6-acetoxylidine mit Epinephrin (1:250.000) fuhrte nicht zur Bildung von Methaemoglobinamie oder Zyanose. Klinisch konnten keine Zeichen von gestorten Sauerstofftransport entdeckt werden. Desgleichen fanden sich keine Veranerungen in den Werten von Serum-Bilirubin, Haptoglobin, Kreatinin oder Transaminase, die dem Prilocain zugeschrieben werden konnten. Die Heinz-Korper wurden etwas vermehrt verzeichnet. Die Methaemoglobinamie konnte jederzeit durch Methylenblau verhutet bzw. zum Verschwinden gebracht werden. Wahrscheinlich ist ein Metabolit des Prilocains fur die Entstehung der Methaemoglobinamie verantwortlich.

Clinical chemistry of prilocaine and clinical evaluation of methaemoglobinaemia induced by this agent.

Abstract: Methaemoglobin is normally continuously formed in circulating erythrocytes, but reducing substances furnished by the normal erythrocyte metabolism convert this methaemoglobin to haemoglobin. Thus the concentration of methaemoglobin normally does not exceed about 1 yo of the total haemoglobin concentration. Higher levels of methaemoglobin may occur if the rate of oxidation of haemoglobin is increased or the rate of reduction of spontaneously formed methaemoglobin is decreased. Drugs or metabolites of drugs are often responsible and Heinz bodies may also be present in the erythrocytes.

Muscle pains after suxamethonium.

Abstract: SUMMARY Muscle pains after intermittent administration of suxamethonium are a common complication in modern anaesthetia. They can be prevented to a certain extent through postoperative immobilization of the patient. However, it is important to mobilize the patients as early as possible, particularly in the elderly age groups. In these cases, it is therefore of the greatest importance to prevent postoperative muscle pains, which can be of considerable intensity. We have tried a method in which increasing doses of tubocurarine were given before administration of suxamethonium. At a dosage of 3 mg tubocurarine the patients were kept free from pain, but more suxamethonium was necessary for relaxation. We have found no untoward effects of this method. ZUSAMMENFASSUNG Muskelschmerzen nach intermittierender Verabreichung von Suxamethonium sind eine haufige Komplikation der modernen Anaesthesie. Sie konnen bis zu einem gewissen Grad durch postoperative Immobilisierung der Patienten verhiitet werden. Es ist jedoch wichtig, die Patienen so rasch wie moglich zu mobilisieren, besonders im hoheren Alter. In diesen Fallen ist es daher von grosster Bedeutung, postoperativen Muskelschmerzen vorzubeugen, die von betrachtlicher Intensitat sein konnen. Wir haben eine Methode, bei der an-steigende Dosen von Tubocurarin vor der Verabreichung von Suxamethonium gegeben wurden, ausprobiert. Bei einer Dosierung von 3 mg Tubocurarin konnten die Patienten schmerzfrei gehalten werden, jedoch war fur die Er-schlaffung mehr Suxamethonium erforderlich. Wir haben bei dieser Methode keine unerwunschten Wirkungen gefunden.

Clinical evaluation of Citanest in peridural anesthesia.

Abstract: Citanest, a new local anesthetic belonging to the same chemical group as lidocaine, was synthesized by LOFGREN and TEGNBR (1960). The first clinical experiments in man were done by ERIKSON (1961), who found that the drug had anesthetic properties comparable to those of lidocaine, with longer duration of action and less toxicity. CRAWFORD (1964) later published a clinical evaluation of this agent comparing its action in the peridural space with that of lidocaine and mepivacaine. This paper is concerned with the results we have obtained in 230 peridural anesthesias done with 3 yo Citanest without epinephrine.

Differences in Tolerance to Intravenous Xylocaine® and Citanest®

Abstract: SUMMARY In a study of the tolerance to intravenous injections of two equipotent local anesthetics, Xylocaine and Citanest, in man, marked differences in subjective and objective symptoms have been recorded. No significant circulatory response was recorded and the EEG was also without significant change. A statement is made that Citanest is twice as well tolerated as Xylocaine in intravenous injection and the justification of this statement is discussed.

The cost of the quiet lung: fluctuations in pa o2 when the carlens tube is used in pulmonary surgery.

Abstract: SUMMARY Fluctuations in arterial Po2 occur during anaesthesia when pronounced hyperventilation or intermittent deep breaths are not part of the ventilation pattern. The decrease in Pao2 is mostly dependent on variable shunts. The extent of the shunting has been measured when a Carlens tube is used in pulmonary surgery, and when one lung is permitted to collapse during the dissection. The conclusions reached are as follows: 1 The widely used technique when a Carlens tube is in place to let one lung collapse for some length of time may jeopardize the cerebral tissue oxygenation. 2 If collapse of die lung subjected to operation is desirable, attempts to dissect and occlude the pulmonary artery should be made early. This protects the patient from extremely low PaO2 values. 3 When collapse of a lung is necessary from a surgical point of view, the anaestiietic mixture should contain the highest possible percentage of oxygen. ZUSAMMENFASSUNG Wenn im Ventilationsmuster ausgepragte Hyperventilation oder intermittierende tiefe Atemzuge fehlen, kommt es zu Schwankungen des arteriellen Sauerstoffdrucks wahrend der Narkose. Das Absinken des PaO2 hangt im wesentlichen von den variablen Kurzschlussen ab. Das Ausmass der Kurzschlusse wurde in Fallen gemessen, bei denen wahrend eines lungenchirurgischen Eingriffes ein Carlens-Tubus verwendet wurde und eine Lune wahrend der Praparation kollabierte. Dabei kam man zu den nachfolgenden Schlussfolgerungen: 1 Bei der weitverbreiteten Technik der Verwendung eines Carlens-Tubus zum Kollaps einer Lunge uber langere Zeit, kann die Sauerstoffversorgung der Hirngewebe gefahrdet sein. 2 Wenn der Kollaps der zu operierenden Lunge erwunscht erscheint, sollte versucht werden, die Pulmonalarterie so fruh wie moglich zu praparieren und zu unterbinden. Dieses Vorgehen schutzt den Patienten vor extrem niedrigen SauerstofFdruckwerten. 3 Wenn vom chirurgischen Standpunkt der Kollaps einer Lunge unbedingt erforderlich ist, dann muss die Narkosegasmischung zumindest den hochstmoglichen Prozentsatz an Sauerstoff enthalten.

2. Effects of Propanidid on Respiration: Changes of Respiratory Rate and Volume After Propanidid

Abstract: HOWELLS : Propanidid exerts a biphasic action on ventilation characterised by hyperventilation followed by ventilatory depression. A study by Dr. E. HARNIK (1965)' of a hundred patients was made in order to relate the extent of ventilatory stimulation with that of depression in each case and also to quantify the influence of sedative premedicants on the respiratory effects. The patients were selected at random with regard to sex and age and were divided into four premedicant groups: (1) atropine alone, (2) pethidine and atropine, (3) papaveretum and hyoscine, and (4) chlorpromazine and promethazine. In all cases, a 10 mg/kg dose of propanidid was used and the lengths of hyperventilation and apnoea were timed. Apnoea was chosen as the index of respiratory depression because it was easy to observe and presented definitive evidence of depression. Results : At the 5 yo level of significance there is no difference in the extent of either hyperpnoea or apnoea among the four premedicant groups. Also, it may be shown that there is a tendency for the duration of apnoea to be shorter when the preceding hyperpnoea is lower, which is surprising. The conclusion of this study is that propanidid is unpredictable in its effect on duration of hyperventilation and apnoea, and that sedative premedications do not appear to modify either components of the biphasic respiratory effect. Furthermore, it would appear that a lowered pCO,, presumably brought about by the hyperpnoeic phase, is by no means solely responsible for the depressant phase that may follow. Periodic respiration has been noticed occasionally after single doses and is not infrequently witnessed during propanidid infusions, which were used for anaesthesia of longer duration.

Electrical seizure activity produced by Xylocaine and Citanest.

Abstract: By implanting electrodes in the hippocampus and amygdala in the brains of cats, WACMAN and DE JONC (1964) have demonstrated the occurrence of electrical seizure activity after the intravenous administration of Xylocaine. They have shown that high arterial pC0, lowers the seizure threshold to Xylocaine. Utilizing their technique of electrode implantation on dogs, we have attempted to compare seizure thresholds for two local anesthetic agents, Xylocaine and Citanest, at varying levels of respiratory acidosis. To minimize cumulative effects of repeated drug injections, our injections were made into the common carotid artery instead of being given intravenously.

Studies of the Metabolism of Citanest C14

Abstract: SUMMARY Citanest C14 has been shown to be degraded by liver and kidney slices. In vivo experiments demonstrate that metabolites are excreted in the urine and decarboxylation with excretion of C1402 has been demonstrated in the rat. Further studies are needed to establish all the pathways for metabolism of Citanest.

Axillary brachial plexus anaesthesia in children with Citanest.

Abstract: SUMMARY In 114 children 1-15 years old, axillary block was induced with 1% Citanest plus, as a rule, epinephrine. For small children, however, a plain 1% solution was used, while some older children received 1.5% Citanest with epinephrine. In 93% of the cases satisfactory anaesthesia was obtained. No complications occurred. Citanest is an excellent local anaesthetic for axillary blocks in children.

Methemoglobin in man Following the use of Prilogaine

Abstract: SUMMARY We have demonstrated in clinical practice that (1) a dose-response relationship exists between the dose of prilocaine and the incidence of methe-moglobin, (2) the methemoglobin is probably related to a metabolite of prilocaine and not to the agent itself, (3) dosages of prilocaine in excess of 16 mg/kg are necessary to produce methemoglobin levels capable of producing symptoms of hypoxia; however, the dosages exceeding 20 mg/kg in this study did not, on these occasions, produce such symptoms of hypoxia, and (4) that dose of 0.5 to 1.0 mg/kg methylene blue can effectively revert methemoglobin levels to normal.

Drop size in disposable sets for intravenous infusion.

Abstract: UMMARY Determination of the number of drops per ml delivered by 125 different infusion sets (equally distributed on five current makes) revealed a range from 14 to 21 drops/ml. If 20 drops/ml are used as the basis for calculating the amount of fluid administered to a patient—a measure frequently used in clinical practice—an overdosage of up to 40% may be administered by the tested infusion sets. The experiments showed that variations in the drip rate (from about 10 to about 110 drops/min.) cause alterations in drop size of up to 10%. A microscopic study of the drop formation in the drip chambers revealed that die smaller the difference between the external and internal diameters of the tips, the more accurate are the infusion sets. However, some infusion sets are accurate in spite of a marked difference in these diameters, but this difference involves a latent possibility of jumps in drop size. These jumps are due to variation in the moistening of the tips by the fluids used or to irregularities in the finer structures of the tips. It is suggested that the drip-tube delivery of the individual makes, in terms of number of drops of distilled water per ml, should be stated on the packing of each set of infusion equipment. It is pointed out that it would be a great improvement if the drip-tube delivery of the infusion sets were included in the international standard requirements for infusion equipment. ZUZAMMENFASSUNG UND SCHLUSSFOLGERUNG Die Bestimmung der Tropfenzahl pro ml bei 125 verschiedenen Infusions-geraten (5 verschiedene Erzeugnisse gleichmassig verteilt) zeigte eine Streuung von 14-21 Tropfen pro ml. Wenn man also, der haufig geubten klinischen Praxis folgend, 20 Tropfen pro ml als Basis fur die Berechnung der den Patienten zugefuhrten Flussigkeitsmenge benutzt, konnte es zu einer Uberdosierung bis zu 40% kommen, wenn man sich der getesteten Infusionsgerate bedient. Die Untersuchungen zeigten auch, dass Variationen der Tropfgeschwindigkeit (zwischen 10 und etwa 110 Tropfen pro Min.) eine Anderung der Tropfengrosse bis zu 10% zur Folge ha ben. Eine mikroskopische Untersuchung der Tropfenbildung in den Tropfkammern ergab, dass die Infusionsgerate umso genauer sind, je geringer der Unterschied zwischen asserem und innerem Durchmesser der Tropfduse (“tips”) ist. Manche Infusionsgerate sind jedoch trotz eines deutlichen Unterschiedes dieser Durchmesser genau, aber dieser Unterschied tragt die latente Moglichkeit starker Anderungen der Tropfengrosse in sich. Diese sind durch Unterschiede in der Befeuchtung der Tropfdusen durch die verwendeten Flussigkeiten oder durch Unregelmassigkeiten in der Feinstruktur dieser Dusen bedingt. Es wird vorgeschlagen, dass von den Erzeugungsfirmen auf jedem Infusionsgerat die Zahl der auf einen ml kommenden Tropfen von destilliertem Wasser angegeben wird. Es wird betont, dass eine internationale Standardisierung der von den Infusionsgeraten zu liefernden Tropfenzahl ein grosser Vorteil ware.

Methemoglobin formation by a local anesthetic and some related compounds.

Abstract: SUMMARY Citanest (L 67, α-n-propylamino-2-methylpropionanilide) and some related compounds were studied for methemoglobin formation in vitro and in vivo. In vitro, Citanest did not induce met-Hb formation in red cell suspension. Under the same conditions a related compound, o-toluidine, in a dose of 40 mg/dl, did produce met-Hb. Intramuscular injection of Citanest and o-toluidine in cats induced met-Hb in the circulating blood. Lidocaine and a related compound, 2,6-xylidine, did not produce met-Hb in the cat on intramuscular injection. In clinical experiments on 50 patients who received Citanest (200-1,600 mg) by epidural injection, met-Hb, exceeding 10% of the total hemoglobin, was observed in a few cases. The met-Hb concentration increased roughly parallel with the dose of Citanest administered. The only complication encountered was slight cyanosis in one case, whose met-Hb concentration was 2.79 g/dl. In most cases maximum met-Hb concentration was attained three to five hours after administration of Citanest, and met-Hb disappeared within 24 hours after the injection. On the basis of these results, it is suggested that the safe upper limit of Citanest for a single injection is 10 mg/kg body weight.

Effects of Epinephrine in Solutions of Local Anaesthetic Agents

Abstract: Carefully standardized test procedures are necessary to obtain true information on the blocking effect of local anaesthetic agents, as has been stressed by BONICA (1957). Stimulated by his article we tried several blocks possibly suited for testing local anaesthetic agents. We found that bilateral ulnar nerve blocks in double blind studies were ideal for testing local anaesthetic agents. A thin needle was used and exactly 1 ml of the test solution was injected into the nerve. In the preliminary study we obtained what seemed to be reliable data on onset time, duration of action (Table 1) and also of the penetration power or the frequency of successful blocks (Fig. 1). In this study a simple pinch test was used to evaluate analgesia. This test has also been compared to some objective methods by L.THULIN and B. LOFSTROM (Fig. 2). The relative differences between the blocked and unblocked side in skin temperature, in sympatho-galvanic response to a stimulus, and in muscle power were compared with a pinch test. As can be seen from the figure the results of the pinch test were well in accordance with the more

Citanest (prilocaine) in spinal analgesia.

Abstract: SUMMARY A report of 339 cases of subarachnoid block is presented. Citanest was used in 106 cases. The advantages of this drug are discussed. A very small number with Citanest 1.9% compared with two other drugs (4.6% and 6.5%) required supplementary anaesthesia.

Neuromuscular Transmission in vivo and the Actions of Decamethonium: a Micro-Electrode Study

Abstract: SUMMARY The lateral segmental tail muscles of the rat has been used successfully for micro-electrode studies of neuromuscular transmission and the effects of decamethonium in vivo. The values obtained for the resting membrane potential of single muscle fibres and of miniature end-plate potential amplitude and frequency were similar to those previously obtained in other rat muscles in vitro. Decamethonium given intravenously produced end-plate depolarization, desensitization of acetylcholine receptors and, at high frequencies of nerve stimulation, a presynaptic block of impulse transmission. ZUSAMMENFASSUNG Die lateralen segmentalen Schwanzmuskel der Ratte konnten erfolgreich fur Mikroelektrodenuntersuchungen der neuromuskularen Ubertragungen und der Wirkungen von Dekamethonium in vivo herangezogen werden. Die gefundenen Werte fur das Ruhemembranpotential der einzelnen Muskelfasern, ebenso wie die Miniatur-Endplattenpotentialamplitude und -frequenz waren ahnlich der bei fruheren Untersuchungen an anderen Rattenmuskeln in vitro erhaltenen. I.v. verabreichtes Dekamethonium fuhrte zu einer Depolarisation der Endplatte, einer Unempfindlichkeit der Azetylcholinrezeptoren und bei hoheren Frequenzen der Nervreizung zu einem prasynaptischen Block der Impulsubertragung.

Studies on the renal excretion of Citanest and Xylocaine.

Abstract: 1 In clearance studies on normal human subjects Xylocaine was found to have a lower clearance than Citanest. 2 The clearance value is dependent on the pH of the urine. The drugs are excreted by non‐ionic diffusion. 3 The clearances are not enhanced by augmented urine flow induced by mannitol as an osmotic diuretic. 4 During rapid infusion of mannitol general toxic cerebral symptoms appeared. The acid‐base balance could also explain these reactions as the dehydration with mannitol might give an intracellular acidosis.

Pre-operative spirometry in thoracic surgery.

Abstract: SUMMARY All thoracic surgery cases in this clinic during the period from 1954 to 1961, comprising 1332 operations, were analyzed with regard to operative mortality and need for special respiratory care. The results were related to pre-operative spirometry findings. The total death rate was 4.5%. It was highest in the pneumonectomy group (12%) and decreased roughly with decreasing extent of lung surgery. However, after removal of 6-8 segments the death rate was as low as 1/45, which was not markedly higher than after removal of 3-5 segments. The mortality and frequency of respiratory complications were lowest in the group with normal ventilatory capacity. In the pneumonectomy group, patients with “obstructive ventilatory impairment” had a higher death rate and required special respiratory care more frequently than those with “restrictive ventilatory impairment.” ZUSAMMENFASSUNG Alle thoraxchirurgischen Falle unserer Klinik aus dem Zeitraum von 1954 bis 1962, insgesamt 1332 Operationen, wurden in Hinblick auf die operative Mortalitat und die Notwendigkeit einer besonderen respiratorischen Obsorge analysiert. Die Resultate wurden zu den praoperativen Spirometriebefunden in Beziehung gesetzt. Die Gesamtsterberate war 4,5%. Sie war am hochsten in der Gruppe der Pneumonektomien (12%) und wird etwa in dem Mass geringer in dem die Ausdehnung des operativen Eingriffes abnimmt. Allerdings war die Mortality nach Entfernung von 6-8 Segmenten mit 1:45 auch nicht deutlich hoher als nach Resektion von 3-5 Segmenten. Mortalitat und Haufigkeit respiratorischer Komplikationen waren am geringsten in der Gruppe mit normaler Atemkapazitat. In der Pneumonek-tomie-Gruppe zeigten die Patienten mit “obstruktiven Atemstorungen” eine hohere Sterberate und benotigten haufiger eine respiratorische Spezialpflege als jene mit “restriktiven Atemstorungen”.

General Pharmacology of Propanidid

Abstract: Propanidid is chemically 3-methoxy-4-(N,N-diethylcarbamoyl-methoxy)phenylacetic acid-n-propylester (Fig. 3). I t is available for clinical use in the form,of 5 yo and 2.5% solution of the active substance. I t is an aqueous solution containing sodium chloride and 20 or 12 yo of the solubilizing agent Cremophor EL@. Propanidid is a colourless or faintly yellowish oil, insoluble in water, with B. P.o., 210-212\" C. After intravenous administration it produces in various animal species anaesthesia of short duration. The smallest dose which induces full anaesthesia in animals is about 20 mg/kg. Its toxicity values are shown in Table 111. Propanidid is rapidly broken down in the body by esterases to J-methoxy4-(N,N-diethylcarbamoylmethoxy)-phenylacetic acid (PUTTER ( 1965)8, WIRTH and HOFFMEISTER ( 1965) Q, as seen in Fig. 3. Investigations by DUHM et al. ( 19655) with 14C-labelled propanidid (radioactive tracer on the carboxyl group of the ester component) have shown that a low degree of further splitting to 4-(carboxy-methoxy)-phenylacetic acid takes place. After intravenous injection of the labelled propanidid into rats, the maximal concentrations of activity were present 2 minutes after injection. Activity was greatest in the kidneys, somewhat less in the liver and the blood, and least in the brain. The rate of elimination corresponded to the half-life of the substance and its metabolites of about 20 minutes. Less than 10% of the adminis-

Anaesthesia for the respiratory cripple.

Abstract: SUMMARY It is frequently held that patients with severe respiratory disability should not be subjected to anaesthesia involving the use of relaxant drugs and positive pressure ventilation since it may be found impossible to provide adequate pulmonary ventilation after the relaxant has been given, or it may prove difficult to re-start spontaneous ventilation if the blood carbon dioxide tension has been reduced during anaesthesia. This paper describes a simple investigation into this problem based on data obtained from 12 ‘respiratory cripples.’ All had a maximum breathing capacity of less than 40 litres/min., and eight showed pre-operative respiratory acidosis. Premedication was with promethazine and atropine. Anaesthesia was induced with a small dose of thiopentone; muscular relaxation was produced by a large dose of tubocurarine, endotracheal intubation effected without the use of topical analgesics, and anaesthesia maintained with a mixture of nitrous oxide and oxygen, without die use of depressant drugs or volatile agents. A deliberate attempt was made to produce passive pulmonary hyperventilation by manual pressure on the reservoir bag, and in every case it was found possible to reduce the blood carbon dioxide tension to below the level found pre-operatively and usually to below 40 mm Hg. In no case was it found difficult to ventilate the patient's lungs, and there was no evidence of progressive hyper-inflation. At the end of the operation, atropine and neostigmine were administered; it was found that after stimulation of the pharynx and trachea spontaneous respiration appeared with the endotracheal tube still in situ and the patient still unconscious when the blood carbon dioxide tension was still lower than it had been pre-operatively. After extubation, which was accompanied by some breath-holding and coughing, a regular pattern was soon re-established at a blood carbon dioxide tension strikingly similar to that which had been found before anaesthesia. It is suggested that these results would not have been obtained had depressant drugs or volatile anaesthetic agents been used, and that the application of topical analgesic solutions to the larynx may likewise cause difficulty in re-starting spontaneous respiration. The use of full muscular relaxation would also seem to be of importance in preventing progressive hyperinflation and difficulty in maintaining adequate ventilation. ZUSAMMENFASSUNG Vielfach wird die Ansicht vertreten, dass bei Patienten mit schweren respiratorischen Storungen die Anaesthesie ohne Relaxans und ohne positive Druckbeatmung durchgefuhrt werden solle; einmal konne es schwierig sein, eine ausreichende Ventilation der Lungen nach Verabreichung des Relaxans zu erzielen, zum anderen konne die Wiederkehr der Spontanatmung schwierig zu erreichen sein, wenn die Kohlensaurespannung wahrend der Narkose verringert wurde. Diese Arbeit beschreibt eine einfache Untersuchung dieser Frage an Hand der Ergebnisse an 12 “respiratorischen Kriippeln” (Atemgrenzwert unter 40 1/min, in 8 Fallen praeoperative respiratorische Acidose). Die Praemedikation bestand aus Promethazin und Atropin; Narkoseeinleitung mit einer kleinen Dosis Thiopental, Relaxation mit einer hohen Dosis Tubocurarin, Intubation ohne Lokalanaesthesie; weitere Narkosefuhrung mit N2O-O2 ohne Zusatz anderer Inhalationsanaesthetika oder depressiv wirksamer Medikamente. Es wurde passive, manuelle Hyperventilation angestrebt; stets gelang es, die Kohlensaurespannung des Blutes unter praeoperative Werte zu senken, meist sogar unter 40 mm Hg. Ventilationsschwierigkeiten oder Zeichen allmahlicher Uberblahung traten nicht auf. Zu Operationsende Gabe von Atropin und Neostigmin. Bei Stimulation von Pharynx und Trachea trat-am bewussdosen Patienten bei noch liegender Tube-wieder Spontanatmung auf, obwohl der Kohlensauredruck noch unter den praeoperativen Werten lag. Nach Extubation (meist unter Husten und Atemanhalten) kam es bald zu einer regelmassigen Spontanatmung bei Werten der Kohlensaurespannung, die fast genau den praeoperativen Befunden entsprachen. Die Autoren sind der Ansicht, dass bei Gebrauch von Analgetika und Inhalationsanaesthetika diese Ergebnisse nicht zu erzielen gewesen waren, Gleiches gilt hinsichtlich ordicher Betaubung des Larynx. Fur die Verhutung allmahlicher uberblahung und von Schwierigkeiten der Beatmung scheint die komplette Relaxierung von grosser Bedeutung.

Antiarrhythmic and neuromuscular effects of qx‐572 in man

Abstract: SUMMARY Twenty-six patients in whom cardiac arrhythmias developed during anesthesia and operation were successfully treated with QX-572. This agent did not usually produce hypotension, but tachycardia was observed. Although QX-572 itself showed no neuromuscular blocking activity, it increased the neuromuscular blocking action of succinylcholine and d-tubocurare. There were no signs of central-nervous-system stimulation in the unanesthetized patients who received QX-572. It is concluded that QX-572 has a significant antiarrhythmic activity in man, and that further clinical trials are indicated. ZUSAMMENFASSUNG 26 Patienten, bei denen Herzarrhythmie wahrend der Narkose und Operation auftraten, wurden erfolgreich mit QX-572 behandelt. Dieses Mittel fuhrte normalerweise nicht zu Blutdruckabfall, doch wurde Tachycardie beobachtet. Obwohl QX-572 selbst keine neuromuskular blockierende Eigenschaft besitzt, verstarkt es die neuromuskular blockierende Wirkung von Succinylcholin und d-Tubocurarin. Bei nicht narkotisierten Patienten, die QX-572 erhielten, traten keine Zeichen zentral nervoser Stimulation auf. Es kann somit der Schluss gezogen werden, dass QX-572 eine signifikant antiarrhydimische Wirkung beim Menschen besitzt und dass weitere klinische Versuche indiziert scheinen.