Ronald L. Katz

RO 21-3981 for intravenous surgical premedication and induction of anesthesia.

RO 21-3981, a new water soluble benzodiazepine, was studied in 21 patients both as an intravenous premedicant and to induce anesthesia. The premedicant dose of 5 mg produced lack of recall and marked sedation within 1 to 2 minutes after injection and persisted for at least 32 minutes. Subsequent induction of anesthesia required an additional 5 to 25 mg of RO 21-3981. However, anesthesia was not induced in 1 patient with 25 mg and was accomplished only with inhalation anesthesia. Loss of lid reflex was unreliable as a sign of induction for patients in whom tracheal intubation was planned. Although decreases in blood pressure of 10 to 30 mm Hg were noted after administration of RO 21-3981, systolic pressure was not recorded below 90 mm Hg. RO 21-3981, because of its amnesic, sedative, and anxiolytic properties, appears to be an excellent premedicant although the 5 mg dose studied was probably larger than necessary. For induction of anesthesia, RO 21-3981 may be an effective alternative to thiopental.

Potentiation of neuromuscular blockade by verapamil.

The effects of intravenous (iv) verapamil (0.01 to 1.0 mg/kg) on the constant neuromuscular block produced by an iv infusion of either pancuronium or succinylcholine were studied on the indirectly stimulated gastrocnemius and tibialis-anterior muscles of the rabbit anesthetized with halothane in oxygen. Verapamil alone (n = 6) had no significant effect. However, the drug did significantly potentiate the 50% twitch depression of the gastrocnemius muscle produced by a constant iv infusion of either pancuronium (n = 5) or succinylcholine (n = 5) to 36 ± 6% and 45 ± 1% of control, respectively. This effect of verapamil occurred with doses of 0.1 mg/kg for pancuronium and 0.01 mg/kg for succinylcholine; these doses of verapamil were the lowest which produced a significant effect. In contrast, verapamil had no significant effect on the progression of the neuromuscular blockade of either the gastrocnemius or tibialis-anterior muscles produced by alpha-bungarotoxin (n = 5). Verapamil also significantly prolonged the P-R interval of the ECG from a control value of 71 ± 2 ms to 78 ± 3 ms at a dose of 0.1 mg/kg and to 93 ± 6 ms at a dose of 0.3 mg/kg. The possible mechanisms of the neuromuscular actions of verapamil are discussed and it is concluded that verapamil can produce potentiation of either pancuronium- or succinylcholine-induced neuromuscular block at doses within the therapeutic range.

Neuromuscular effects of atracurium in man.

The neuromuscular effects of atracurium were studied in 25 A. S. A. class I or II patients anesthetized by a N2O-O2narcotic technique. In five patients incremental doses of 0.05 to 0.1 mg/kg of atracurium were given intravenously every 3 minutes until approximately 95% depression of the evoked electromyographic (EMG) response of the adductor policus muscle was produced. This required 0.25 to 0.35 mg/kg of atracurium. The duration of block (return to 95% of control) was 25 to 50 minutes. In addition, four groups of five patients each received 0.15, 0.25, 0.375, or 0.6 mg/ kg of atracurium. The block produced by 0.15 mg/kg was 10% to 92% and lasted 8 to 55 minutes. The block produced by 0.25, 0.375, and 0.6 mg/kg was 95% or greater with a duration of action of 30 to 68 minutes, 52 to 70 minutes, and 65 to 95 minutes, respectively. Tracheal intubation was easily carried out in all patients in whom there was a block of 90% or greater. The block could be antagonized by the common clinical combination of atropine and neostigmine. Changes in heart rate and blood pressure following atracurium were less than 5%.

Dynamics of Local-anesthetic Compounds in Regional Anesthesia

The clinical effectiveness and safety of compounded mixtures of lidocaine + bupivacaine and chloroprocaine + bupivacaine for either epidural or brachial-plexus block was studied in 48 adult patients. Of the several alternatives, chloroprocaine + bupivacaine with epinephrine was found the best choice for patients with typical plasma cholinesterase.

Characteristics of nondepolarizing neuromuscular block: (I) post-junctional block by alpha-bungarotoxin

SummaryThe characteristics of neuromuscular block produced by alpha-bungarotoxin, a post-junctionally active polypeptide toxin purified from snake venoms, have been studiedin vivo in 12 anaesthetized cats, using the sciatic nerve-tibialis anterior muscle preparation. The onset of the neuromuscular block was slow and without fasciculation. The block was persistently progressive. The time course of the block depended on the dosage. In general, 0.1 mg/kg of alpha-BuTX appeared to approximate the threshold dosage while 0.2 mg/kg completely eliminated the twitch response in 2-5 hours. No recovery was observed in 8-30 hours. Larger doses accelerated the progression of the block. During the block, tetanic contractions and train-of-four twitches did not fade. The post-tetanic twitches were markedly facilitated. The block was antagonized by edrophonium, neostigmine, pyridostigmine, and succinylcholine, but the antagonism was less effective and shorter-lasting than that observed on curare-block, and the block always resumed the projected progression. Attempts were made to explain the observed difference between alpha-BuTX-and dTc-induced neuromuscular blocks by the practically permanent nature of block and the purely post-junctional site of action of alpha-BuTX. It was concluded that a pure post-junctional block is not characterized by fade, which rather might be a pre-junctional effect of some nondepolarizing neuromuscular blocking agents like d-tubocurarine.RésuméLa d-Tubocurarine agit à la fois à ľextrémité du nerf moteur et à la plaque motrice de la fibre musculaire (actions pré et post-synaptique). Le bloc musculaire qu’elle produit se caractérise par une absence de fasciculations, un affaiblissement de la “série de quatre” (train of four), une facilitation post-tétanique et, enfin, ce bloc est renversé par les anti-cholinesterases.Dans le but de mettre en relation ces différentes caractéristiques avec un mécanisme ďaction pré et post-synaptique, nous avons fait ľétude ďun agent dont ľaction se limite à la région post-synaptique.Ľalpha-bungarotoxine, une polypeptide extraite de venins de serpents, répond à ce critère en agissant uniquement à la région post-synaptique. Aussi, nous avons précisé les caractéristiques du bloc qu’elle produit in vivo, au moyen de préparation sciatique-tibial antérieur, ceci chez 12 chats anesthésiés.Le bloc s’installait lentement sans que ľon observe de fasciculations et augmentait ďintensité avec le temps, en fonction de la dose. Une dose de 0.1 mg/kg était la dose-seuil nécessaire pour obtenir unblocage au moins partiel, alors qu’une dose de 0.2 mg/kg éliminait complètement la réponse au “twitch” au bout de deux à cinq heures. Ľabsence de réponse persistait de 8 à 30 heures. Les doses plus importantes accéleraient la vitesse de ľétablissement du blocage.Durant la période du bloc, on n’a pas observé ďaffaiblissement des contractions tétaniques et de la “série de quatre.” La facilitation post-tétanique était augmentée de façon importante.Ľedrophonium, la neostigmine, la pyridostigmine et la succinylcholine renversent ce bloc mais de façon moins complète et de façon plus courte que lorsqu’il s’agit ďun bloc au curare; le bloc réapparaît toujours pour continuer à progresser.Nous avons tenté ďexpliquer les différences observées par la nature presque permanente du bloc produit et par le fait que ľaction est exclusivement postsynaptique. On en conclut qu’un bloc limité à la région post-synaptique ne se caractérise pas par un affaiblissement de la série de quatre, contrairement au bloc de la d-tubocurarine.

Anesthesia, Amnesia, and the Memory/awareness Distinction

Several studies have shown that surgical patients cannot consciously recall or recognize events to which they had been exposed during general anesthesia. Might evidence of memory for intraoperative events be revealed through the performance of a postoperative test that does not require remembering to be deliberate or intentional? Results of the present study, involving the recognition and spelling of semantically biased homophones, suggest a negative answer to this question and imply that intraoperative events cannot be remembered postoperatively, either with or without awareness.

Effects of diazepam on succinylcholine-induced myalgia, potassium increase, creatine phosphokinase elevation, and relaxation.

Diazepam in a dose of 0.05 mg/kg was studied to determine its effect on a subsequently administered dose of 1 mg/kg of succinylcholine. This dose of diazepam prior to succinylcholine (1) significantly diminished the incidence of postoperative muscle pain; (2) decreased the usual increase in serum potassium; (3) did not prevent the rise in creatine phosphokinase; (4) reduced the incidence of muscle fasciculation; and (5) did not affect the magnitude or duration of the succinylcholine neuromuscular block. It was concluded that diazepam had several advantages over d-tubocurarine in the prevention of succinylcholine-induced muscle pain.

Thrombophlebitis after intravenous diazepam--can it be prevented?

Although pain and subsequent thrombophlebitis are complications in patients receiving intravenous (IV) diazepam, the mechanism and accompanying histology are unknown. To further elucidate the pathogenesis for this and determine whether it can be minimized, adult female rats received IV diazepam, diazepam vehicle, lidocaine, a combination of lidocaine and diazepam, or N saline solution, and underwent subsequent tissue light microscopy. Vascular tissue from animals receiving IV diazepam alone revealed marked inflammation with inflammatory edema and intramural polymorphonuclear-cell infiltration. Intravascular thrombosis and complete vein-wall destruction were also present in some animals as early as 48 hours after IV diazepam. Diazepam vehicle and diluted diazepam produced similar morphologic alterations. Lidocaine or saline IV resulted in no histologic alterations, while lidocaine added to diazepam did not reduce the inflammatory response. These results represent the first systematic morphologic evaluation of vein response to intravascular diazepam and suggest that it produces rapid and detrimental morphologic alterations. The dilution of diazepam or combination with lidocaine does not appear to alter these findings, and diazepam vehicle appears to assume a role in the production of the vascular injury.

Diazepam and Lorazepam for Intravenous Surgical Premedication

Diazepam, 10 and 20 mg, and 2 and 4 mg lorazepam were studied as intravenous surgical premedicants in 120 patients. Relief of anxiety, sedation, patient acceptance, lack of recall, and side effects were the variables evaluated. Both diazepam and lorazepam proved to be excellent surgical premedicants. The basic difference between the two drugs is temporal. Both medications produce similar relief of anxiety, sedation, patient acceptance, and lack of recall. The clinical effects of intravenous diazepam peaks in 2 to 3 minutes and diminishes thereafter. Intravenous lorazepam has a latent period of 8 to 15 minutes, with increasing effects at 15 to 30 minutes.

Hiccup and ephedrine.

SummaryTwelve patients who developed hiccup during anaesthesia and surgery were treated with an intravenous injection of ephedrine 5 mg (eleven cases) or 10 mg (one case). In nine patients ephedrine was successful after traditional methods had been tried and failed, and in three patients ephedrine was the only agent given.We conclude that ephedrine is a safe and easy mode of treatment for intractable hiccup during anaesthesia and surgery.RésuméDouze malades atteints ďun hoquet pendant ľanesthésie et la chirurgie ont été traités avec succès par une injection intra-veineuse ďephédrine 5 mg (dans onze cas) ou de 10 mg (dans un cas). Pour neuf malades, ľéphédrine a réussi là où les méthodes usuelles avaient échoué et, pour trois maiades, ľéphédrine a été le seul médicament utilisé.Nous concluons que ľéphédrine est un moyen sûr et facile de traiter le hoquet rebelle pendant ľanesthésie et la chirurgie.