The Place of Erythroidines in the History of Neuromuscular Blockers.

Between 1938 and 1951 erythroidine derivatives were seriously considered as alternatives to curare for the provision of muscle relaxation. This has been overlooked in the published history of anaesthesia. The first publication on the paralysing effect of an extract of Erythrina americana was in 1877, but this was in a Mexican journal, which was not widely read. Sixty years later erythroidine was isolated, and in 1938 it was first used clinically to treat spastic dystonia, preceding the use of Intocostrin for this purpose. By 1943 dihydro-ß-erythroidine was prepared in crystalline form, which was equipotent with curarine and of acceptable duration; it was used in clinical anaesthesia in 1946. In the 1940s curare was presented in solutions with potency stated in units, determined by bioassay, which was a disadvantage compared with the straightforward mg of dihydro-ß-erythroidine. However, by the early 1950s, improvement in the pharmaceutical presentation of d-tubocurarine and new neuromuscular blockers, displaced the erythroidines.

Historical development of modern anesthesia.

Of all milestones and achievements in medicine, conquering pain must be one of the very few that has potentially affected every human being in the world. It was in 1846 that one of mankind's greatest fears, the pain of surgery, was eliminated. This historical review article describes how the various elements of anesthesiology (gasses, laryngoscopes, endotracheal tubes, intravenous medications, masks, and delivery systems) were discovered and how some brilliant entrepreneurs and physicians of the past two centuries have delivered them to humanity. One name stands out amongst all others when the founder of modern anesthesia is discussed, William T.G. Morton (1819-1868). A young Boston Dentist, Dr. Morton had been in the search for a better agent than what had been used by many dentists: nitrous oxide. With Dr. Morton's tenacity driven by enthusiasm and discovery, he and renowned surgeon at Massachusetts General Hospital, John Collins Warren (1778-1856) made history on October 16, 1846 with the first successful surgical procedure performed with anesthesia. Dr. Morton had single-handedly proven to the world that ether is a gas that when inhaled in the proper dose, provided safe and effective anesthesia. One of the first accounts of an endotracheal tube being used for an airway comes from the pediatrician Joseph O'Dwyer (1841-1898). He used the metal "O'dwyer" tubes in diphtheria cases and passed them into the trachea blindly. Adding a cuff to the tube is credited to Arthur Guedel (1883-1956) and Ralph M. Waters (1883-1979) in 1932. This addition suddenly gave the practitioner the ability to provide positive pressure ventilation. The anesthesiologist Chevalier Jackson (1865-1958) promoted his handheld laryngoscope for the insertion of endotracheal tubes and its popularity quickly caught hold. Sir Robert Reynolds Macintosh's (1897-1989) breakthrough technique of direct laryngoscopy came after being appointed Nuffield professor of anesthetics at the University of Oxford in 1937. He was the first to describe the routinely placing of the tip of his newly re-designed laryngoscope in the epiglottic vallecula which is attached to the base of the tongue, thus when lifted exposed the entire larynx. Macintosh was genuinely astonished at what a great view he could achieve with his new blade and technique. The use of barbiturates as an intravenous anesthetic began in 1932. Sodium thiopental gained popularity after its use was described in detail by a Dr. John Lundy (1894-1973) of the Mayo Clinic. Other I.V. medications were tried over the past seventy years, but the newest induction drug which provided for a substantially shorter recovery period and seemed to actually suppress laryngeal reflexes has brought with it many benefits. Propofol, introduced clinically in 1977, demonstrated many positive effects even as an anti-emetic compound. Before October of 1846, surgery and pain were synonymous but not thereafter. As we entered the information age where the infrastructure of evidence based medicine and newer fields of genetics, transplantation, imaging radiology and even stem cells became quickly integrated into mainstream medicine, we can predict an excellent future on the progress to be made in anesthesia.

Needle-based blocks for the 21st century ophthalmology.

PURPOSE: This paper reviews history of the needle orbital blocks used in the earlier centuries and how they have evolved towards safer anaesthesia in the modern clinical practice. METHODS: Material is derived from literature searches from major ophthalmic and anaesthetic journals on the use of orbital needle blocks over earlier centuries. RESULTS: Needle-based anaesthetic techniques were described shortly after the invention of reliable medical needles. Atkinson popularized the classical retrobulbar block in a series of papers published in the early 20th century. This technique,which utilises a relatively long needle inserted towards the apex of the muscle cone behind the globe, has been criticized by some as unsuitable for modern 21st century ophthalmic surgery because of the extremely rare potential for serious complications. Satisfactory anaesthesia and akinesia can be obtained with short sharp or dull needles with slightly higher volumes of local anaesthetic agent placed in the farthest inferotemporal quadrant. CONCLUSION: Aside from relative safety, modern needle blocks offer the advantage of lid akinesia without a need for a second injection for the seventh nerve that is often performed con-comitantly with retrobulbar block.

Neuromuscular block.

Descriptions of the South American arrow poisons known as curares were reported by explorers in the 16th century, and their site of action in producing neuromuscular block was determined by Claude Bernard in the mid-19th century. Tubocurarine, the most important curare alkaloid, played a large part in experiments to determine the role of acetylcholine in neuromuscular transmission, but it was not until after 1943 that neuromuscular blocking drugs became established as muscle relaxants for use during surgical anaesthesia. Tubocurarine causes a number of unwanted effects, and there have been many attempts to replace it. The available drugs fall into two main categories: the depolarising blocking drugs and the nondepolarising blocking drugs. The former act by complex mixed actions and are now obsolete with the exception of suxamethonium, the rapid onset and brief duration of action of which remain useful for intubation at the start of surgical anaesthesia. The nondepolarising blocking drugs are reversible acetylcholine receptor antagonists. The main ones are the atracurium group, which possess a built-in self-destruct mechanism that makes them specially useful in kidney or liver failure, and the vecuronium group, which are specially free from unwanted side effects. Of this latter group, the compound rocuronium is of special interest because its rapid onset of action allows it to be used for intubation, and there is promise that its duration of action may be rapidly terminated by a novel antagonist, a particular cyclodextrin, that chelates the drug, thereby removing it from the acetylcholine receptors.

Anaesthesia research is important.

The purpose of this paper is to describe the impact of anaesthesia research on clinical practice. The evolution of neuromuscular blocking drugs from the laboratory to the operating room is used as an example. Particular emphasis is given to the pioneers whose vision made this possible: H. R. Griffith and G. E. Johnson; D. Savage, J. B. Stenlake and W. C. Bowman and J. Viby-Mogensen. Our challenge is to ensure the supply of clinical scientists for the future.

Fifty years of muscle relaxants.

The introduction of curare improved surgical relaxation and encouraged anaesthetists to enlarge their vision. They became interested in the pharmacologic properties of their drugs and the physiologic changes associated with paralysis, and this led naturally to their involvement in intensive care and respiratory physiology. Since 1942, more than 50 muscle relaxants have been introduced: the current emphasis is on the short- to intermediate-duration agents that allow rapid recovery and avoid the problems associated with residual curarization, but we still await a nondepolarizing replacement for suxamethonium.

A historical perspective on ventilator management.

Paralysis via neuromuscular blockade in ICU patients requires mechanical ventilation. This review historically addresses the technological advances and scientific information upon which ventilatory management concepts are based, with special emphasis on the influence such concepts have had on the use of neuromuscular blocking agents. Specific reference is made to the scientific information and technological advances leading to the newer concepts of ventilatory management. Information from > 100 major studies in the peer-reviewed medical literature, along with the author's 25 yrs of clinical experience and academic involvement in acute respiratory care is presented. Nomenclature related to ventilatory management is specifically defined and consistently utilized to present and interpret the data. Pre-1970 ventilatory management is traced from the clinically unacceptable pressure-limited devices to the reliable performance of volume-limited ventilators. The scientific data and rationale that led to the concept of relatively large tidal volume delivery are reviewed in the light of today's concerns regarding alveolar overdistention, control-mode dyssynchrony, and auto-positive end-expiratory pressure. Also presented are the post-1970 scientific rationales for continuous positive airway pressure/positive end-expiratory pressure therapy, avoidance of alveolar hyperxia, and partial ventilatory support techniques (intermittent mandatory ventilation/synchronized intermittent mandatory ventilation). The development of pressure-support devices is discussed and the capability of pressure-control techniques is presented. The rationale for more recent concepts of total ventilatory support to avoid ventilator-induced lung injury is presented. The traditional techniques utilizing volume-preset ventilators with relatively large tidal volumes remain valid and desirable for the vast majority of patients requiring mechanical ventilation. Neuromuscular blockade is best avoided in these patients. However, adequate analgesia, amnesia, and sedation are required. For patients with severe lung disease, alveolar overdistention and hyperoxia should be avoided and may be best accomplished by total ventilatory support techniques, such as pressure control. Total ventilatory support requires neuromuscular blockade and may not provide eucapnic ventilation.