Intravenous Anesthesia

INTRAVENOUS ANESTHESIA

Induction Agents

Intravenous anesthesia required the invention of the hypodermic syringe and needle by Alexander Wood in 1855. Early attempts at intravenous anes-thesia included the use of chloral hydrate (by Oré in 1872), chloroform and ether (Burkhardt in 1909), and the combination of morphine and scopolamine (Bredenfeld in 1916). Barbiturates were first synthe-sized in 1903 by Fischer and von Mering. The first barbiturate used for induction of anesthesia was diethylbarbituric acid (barbital), but it was not until the introduction of hexobarbital in 1927 that barbi-turate induction became popular. Thiopental, syn-thesized in 1932 by Volwiler and Tabern, was first used clinically by John Lundy and Ralph Waters in 1934 and for many years remained the most com-mon agent for intravenous induction of anesthesia. Methohexital was first used clinically in 1957 by V. K. Stoelting and is the only other barbiturate used for induction of anesthesia in humans. After chlor-diazepoxide was discovered in 1955 and released for clinical use in 1960, other benzodiazepines— diazepam, lorazepam, and midazolam—came to be used extensively for premedication, conscious sedation, and induction of general anesthesia. Ket-amine was synthesized in 1962 by Stevens and first used clinically in 1965 by Corssen and Domino; it was released in 1970 and continues to be popular today, particular when administered in combina-tion with other agents. Etomidate was synthesized in 1964 and released in 1972. Initial enthusiasm over its relative lack of circulatory and respiratory effects was tempered by evidence of adrenal suppression, reported after even a single dose. The release of pro-pofol in 1986 (1989 in the United States) was a major advance in outpatient anesthesia because of its short duration of action . Propofol is cur-rently the most popular agent for intravenous induc-tion worldwide.

Neuromuscular Blocking Agents

The introduction of curare by Harold Griffith and Enid Johnson in 1942 was a milestone in anesthesia.Curare greatly facilitated tracheal intubation and muscle relaxation during surgery. For thefirst time, operations could be performed on patients without the requirement that relatively deep levels of inhaled general anesthetic be used to produce mus-cle relaxation. Such large doses of anesthetic often resulted in excessive cardiovascular and respiratory depression as well as prolonged emergence. More-over, larger doses were often not tolerated by frail patients.

Succinylcholine was synthesized by Bovet in 1949 and released in 1951; it has become a stan-dard agent for facilitating tracheal intubation during rapid sequence induction. Until recently, succinyl-choline remained unchallenged in its rapid onset of profound muscle relaxation, but its side effects prompted the search for a comparable substitute. Other neuromuscular blockers—gallamine, decamethonium, metocu-rine, alcuronium, and pancuronium—were subse-quently introduced. Unfortunately, these agents were often associated with side effects , and the search for the ideal NMB continued. Recently introduced agents that more closely resemble an ideal NMB include vecuronium, atracurium, rocuronium, and cis-atracurium.

Opioids

Morphine, isolated from opium in 1805 by Sertürner, was also tried as an intravenous anesthetic. The adverse events associated with large doses of opioids in early reports caused many anesthetists to avoid opioids and favor pure inhalation anesthesia. Inter-est in opioids in anesthesia returned following the synthesis and introduction of meperidine in 1939. The concept of balanced anesthesia was introduced in 1926 by Lundy and others and evolved to include thiopental for induction, nitrous oxide for amne-sia, an opioid for analgesia, and curare for muscle relaxation. In 1969, Lowenstein rekindled interest in “pure” opioid anesthesia by reintroducing the concept of large doses of opioids as complete anes-thetics. Morphine was the first agent so employed, but fentanyl and sufentanil have been preferred by a large margin as sole agents. As experience grew with this technique, its multiple limitations—unreliably preventing patient awareness, incompletely sup-pressing autonomic responses during surgery, and prolonged respiratory depression—were realized.Remifentanil, an opioid subject to rapid degradation by nonspecific plasma and tissue esterases, permits profound levels of opioid analgesia to be employed without concerns regarding the need for postopera-tive ventilation.