Intravenous regional anesthesia first century (1908-2008): Beggining, development, and current status

Abstracts

JUSTIFICATIVA E OBJETIVOS: A anestesia regional intravenosa completa neste ano de 2008 um século de existência. Sendo técnica anestésica amplamente utilizada, justifica-se recordar o fato, comemorar a data, lembrar aos anestesiologistas brasileiros o processo evolutivo pelo qual ela passou, sobretudo nos últimos 40 anos, e prestar um tributo àquele que a iniciou: August Karl Gustav Bier. CONTEÚDO: O texto relata a origem da anestesia locorregional em geral e da anestesia regional intravenosa em particular, desde a introdução do garroteamento de membros e da descoberta e do aperfeiçoamento das agulhas de punção, das seringas e dos anestésicos locais. São descritos os detalhes técnicos inicialmente utilizados por Bier e os conceitos fisiopatológicos e clínicos por ele emitidos em princípios do século XX. Retrata a evolução inicial e das décadas seguintes da anestesia regional intravenosa, cita os pioneiros nacionais e internacionais no seu uso, explica as razões do seu estudo científico relativamente tardio, descreve as principais contribuições havidas até hoje para sua utilização eficiente e segura. Finalmente, narra o estado atual dos principais conhecimentos adquiridos ao longo do tempo, como mecanismo e local de ação do anestésico e da isquemia, uso de soluções anestésicas modernas, aperfeiçoamento da analgesia pós-operatória e do bloqueio motor, conceitos farmacocinéticos e fisiopatológicos e melhor interpretação das principais complicações possíveis. CONCLUSÕES: A anestesia regional intravenosa é técnica anestésica criada por A.K.G. Bier há exatamente 100 anos. Evoluiu pouco e lentamente na primeira metade do século XX e muito nos últimos anos, graças a numerosos desenvolvimentos técnicos, fisiopatológicos, farmacológicos, farmacocinéticos e clínicos, para o que a Anestesiologia brasileira deu grande contribuição. Completando neste ano de 2008 seu primeiro centenário, a anestesia regional intravenosa merece ter sua história conhecida e a data não pode passar despercebida e sim ser lembrada e comemorada.

ANESTESIA, Regional; ANESTESIOLOGIA

SPECIAL ARTICLE

Almiro dos Reis Jr, TSA

Correspondence to

SUMMARY

BACKGROUND AND OBJECTIVES: Intravenous regional block is celebrating its 100^th anniversary in 2008. Since this is a widely used technique, this milestone should be recorded, the date celebrated, Brazilian anesthesiologists should be remembered of its evolutive process, especially in the last 40 years, and we should pay homage to the individual who started it: August Karl Gustav Bier.

CONTENTS: This report describes the beginning of locoregional anesthesia in general and regional intravenous block in particular, since the introduction of garroting of the extremities to the discovery and improvement of needles, syringes, and local anesthetics. The technical details used initially by Bier, and the pathophysiological and clinical concepts enounced by him at the beginning of the 20^th Century are described. It describes the initial evolution and that of the following decades of intravenous regional block, lists national and international pioneers, explains the reasons for the relatively late scientific studies on the technique, and describes the main contributions that made it an effective and safe technique. Finally, it describes the current state of the main knowledge acquired over the years, such as the mechanism and site of action of the anesthetic and ischemia, the use of modern anesthetic solutions, improvement of postoperative analgesia and motor block, pharmacokinetic and pathophysiological concepts, and the best interpretation of possible complications.

CONCLUSIONS: Intravenous regional block is the anesthetic technique created by A. K. G. Bier exactly 100 years ago. In the first half of the 20^th Century, it evolved little and slowly, but in the last several years, it has seen an accentuated improvement, thanks to countless technical, pathophysiological, pharmacological, pharmacokinetic, and clinical developments, for which Brazilian Anesthesiology has contributed considerably. Since it is celebrating its 100^th anniversary in 2008, intravenous regional block deserves to have its story told, and the date should not go unnoticed, but should be remembered and celebrated.

Key Words: ANESTHESIA, Regional: intravenous; ANESTHESIOLOGY: history.

RESUMEN

JUSTIFICATIVA Y OBJETIVOS: La anestesia regional intravenosa completa este año en 2008 un siglo de existencia. Siendo una técnica anestésica ampliamente utilizada, se justifica recordar el hecho, festejar la fecha, recordarle a los anestesiólogos brasileños el proceso evolutivo por el cual ella ha pasado, principalmente en los últimos 40 años, y prestarle un homenaje a aquel que la inició: August Karl Gustav Bier.

CONTENIDO: El texto relata el origen de la anestesia locorregional en general y de la anestesia regional intravenosa en particular, desde la introducción del torniquete de miembros y del descubrimiento y del perfeccionamiento de las agujas de punción, de las jeringuillas y de los anestésicos locales. Se describen los detalles técnicos inicialmente utilizados por Bier y los conceptos fisiopatológicos y clínicos por él emitidos a principios del siglo XX. Retrata la evolución inicial y de las décadas siguientes de la anestesia regional intravenosa, cita los pioneros nacionales e internacionales que la usaron, explica las razones de su relativamente tardío estudio científico, describe los principales aportes que hasta hoy existen para su utilización eficiente y segura. Finalmente, narra el estado actual de los principales conocimientos adquiridos a lo largo del tiempo, como el mecanismo e el local de acción del anestésico y de la isquemia, uso de soluciones anestésicas modernas, perfeccionamiento de la analgesia postoperatoria y del bloqueo motor, conceptos farmacocinéticos y fisiopatológicos y una mejor interpretación de las posibles principales complicaciones.

CONCLUSIONES: La anestesia regional intravenosa es una técnica anestésica creada por A. K. G. Bier hace exactamente 100 años. Evolucionó lentamente y bastante poco en la primera mitad del siglo XX y mucho en los últimos años, gracias a innumerables desarrollos técnicos, fisiopatológicos, farmacológicos, farmacocinéticos y clínicos, para lo que la Anestesiología brasileña dio un gran aporte. Completando este año en 2008 su primer centenario, la anestesia regional intravenosa merece tener su historia conocida y la fecha no puede pasar desapercibida sino que debe ser recordada y festejada.

INTRODUCTION

Intravenous regional block (IVRB) is celebrating its 100^th anniversary in 2008. Thus, it is important to tell its history, and the date should not go unnoticed, but should be remembered and celebrated because, as Castiglioni ¹ wrote in 1947, in his History of Medicine, "nobody can understand the present, exactly and deeply, and look intelligently into the future if one ignores the results of knowledge or is not capable to walk the pathways the knowledge of truth trailed to reach us."

Until around the mid XIX Century, a technique of locoregional block did not exist. However, inhalational anesthesia, initiated by Crawford Williamson Long on March 30, 1842, in Georgia, USA, and later, with more divulgation, by William Thomas Green Morton on October 16, 1846, in Boston, Massachusetts, was already being used². Therefore, to understand the reasons by which only on a determined evolutive stage of Medicine locoregional blocks and in particular IVRB were developed one has to go back in time to understand the evolution of limb garroting and the initial development of needles for puncture, syringes, and, later, local anesthetics.

HISTORY OF LIMB GARROTING

Limb ischemia by garroting was introduced in surgery a little over one century ago; however, its history is much older ^3,4. In the II Century BC, narrow cloth bands were tied close to the incision ^3-5 to control surgical bleeding⁵. Afterwards, and for many centuries, significant changes in this field did not occur. In the XVI Century, Ambroise Paré used a strong and wide bandage to constrict the limbs ^3,4. In 1593, Fabry created a garrote with a bat for the constrictive torsion of the bandage ³. In 1610, Girault used a tourniquet to amputate extremities ³. In 1674, Morrell introduced the use of a padded Spanish reel in surgical procedures, which at that time was used only as a strangling device, but some experts attribute this to Fabry ^3,4; this device was used with several modifications until the end of the XIX Century. At the time of the Crimean War British forces adopted once more simple devices, such as the adjustable belt ^3,4.

The word tourniquet, derived from the French word tourner, appeared in 1718 and was proposed by Petit for his invention ^3-6. Around 1864, Lister probably became the first surgeon to use garroting in surgical interventions other than amputations; he recorded the usefulness of gravitational exsanguination when observed good drainage of venous blood and arteriolar vasoconstriction on his own hand and during exposure of the horse metacarpal artery ³.

At the end of the XIX Century, Johan Friederich August von Esmarch, professor of surgery in Kiel, described the elastic bandage that bears his name but which has suffered considerable modifications ^3,4. The original Esmarch garrote was made of strong rubber, was approximately one inch wide and 1/8 inch thick, had a metal chain in one of the extremities and a hook on the other ^3,4; later, he added a piece of vulcanite for better fixation of the tourniquet ^4,6. Since 1855, Esmarch had used garroting for amputation of the extremities but he was not the first one to use the method of venous blood expression (exsanguination) associated with garroting; he admitted this himself when he mentioned Sartorius, Brunninghouse, Gradesse-Sylvestri, and Bell as his predecessors ^3,4. Esmarch's bandage, widely used nowadays, much simpler and softer than the original, was actually suggested by Langenbeck ⁴. Shortly after, Corning proposed garroting of the limb to prolong the blockade of peripheral nerves for surgical purposes; this technique, which Halsted considered himself as the inventor, accusing Corning of having appropriate his idea, was presented in one of the scientific sessions of the Roosevelt Hospital in New York ³. The procedure inspired Braun, who created the expression "conduction anesthesia", to associate epinephrine to the local anesthetic to obtain what he called chemical tourniquet ^7-9. In 1904 Harvey Cushing abandoned the use of the elastic band and in an attempt to reduce the incidence of muscle paralysis caused by nerve compression built the first pneumatic garrote for surgical hemostasis based on the device of Riva-Rocci to measure blood pressure ^5,10; later, this tourniquet was improved by Kirschner ^3,6.

THE INVENTION OF THE HOLLOW NEEDLE AND SYRINGE

In 1853, Alexander Wood, who was born in Cupar of Fife (Scotland), professor of the Medical School of Edinburgh, created the hollow needle; for him, the main virtue of his invention, which had an injector system, was to allow the placement of morphine in close contact with the nerves involved in pain processes ¹¹. It is believed that the syringe was invented in the same year by the French orthopedist, Charles Gabriel Pravaz, born in Beauvoisin, and who disappeared suddenly without seeing the manufacture of the metal instrument he designed. A few years later the glass syringe which substituted the metal syringe was introduced by Georg Wilhelm Amathus Luer, an English from Brunswick ¹¹.

THE DISCOVERY OF LOCAL ANESTHETICS

The history of those drugs starts in South America, in the XIX Century, more specifically in Peru and Bolivia. Natives in the region chewed the leaves of a plant that stimulated the central nervous system (Erithroxylum coca), which caused numbing of the lips. This plant, studied in Europe since 1850, led Gaedicke five years later to isolate erythroxyline from which Niemann obtained cocaine (benzylmethylecgonine) in 1860. In 1868, Moreno y Maiz, a Peruvian military physician, published his experiments with cocaine acetate ^3,12. A German, Fick, and two French, Coupard and Borderan, had made similar experiments¹¹. In 1879, von Arep studied the pharmacological properties of the drug and noticed its local anesthetic effects after subcutaneous administration but this observation did not have the divulgation it deserved ³.

In 1884, Sigmund Freud initiated his studies with cocaine and had the intuition of local and topical anesthesia and wrote: "The capability of cocaine, and its salts, used in concentrated solutions, to anesthetize cutaneous and mucosal tissues, allows us to think that it will be possible to use it in the future, particularly in cases of localized infections Thanks to this anesthetic property, the use of cocaine will spread in the near future" ¹¹. At the time, Freud, who had traveled to visit his fiancée, instructed Köningstein, an ophthalmologist, to study the anesthetic properties of cocaine on the eyes, but, when he returned, he found out that Köller, and not Köningstein, had discovered topical anesthesia ³.

Carl Köller, a young physician only 27 years old, who worked with Freud at the Royal General Hospital of Vienna, was searching for a local anesthetic for ophthalmologic surgeries and for this reason had been studying several drugs, such as chloral hydrate and morphine without results ³. In August 1884, he discovered the references to the topical anesthesia produced by cocaine, including a publication by Freud and, like Freud, he experimented on his tongue and afterwards on the eyes of animals and, later, on his own eyes (it seems it was accidental), as well as in some patients ¹¹. Those studies were presented during the Ophthalmologic Congress of the German Society in Heidelberg, in September 1884 ¹³, by the ophthalmologist Josef Brettauer since Köller was unable to attend for economic reasons ¹¹. One month later, the same study was presented at the Medical Society of Vienna but this time it was for ophthalmologic surgeries, when Köller recognized that cocaine attracted the interest of Viennese physicians, especially thanks to the detailed compilation and to the interesting medical report of Sigmund Freud ^13,14. The following year, Köller and Freud operated the glaucoma of the father of the famous psychiatrist using cocaine as a local anesthetic ^3,11. After residing in Holland, Köller, following the advice of Freud, immigrated to the United States in 1888 where he worked at the Mount Sinai Hospital in New York^11,14. In 1921, the American Ophthalmologic Society created a gold medal for Köller ¹⁴ and, in 1927, the International Anesthesia Research Society presented him with a commemorative scroll on his 70^th birthday ¹⁴. In 1934, the New York Academy of Medicine celebrated the 50^th anniversary of his discovery by giving him the first gold medal of the institution ¹⁴. Köller was indicated several times for the Nobel Prize of Medicine but never received it probably due to statutory reasons ^3,14. Carl Köller died in 1944 in the United States ^3,14.

Clinical complications associated with the clinical use of cocaine, some of them tragic, stimulated the research for less toxic local anesthetics. After investigating more than one hundred amino esters derived from para-aminobenzoic acid, Einhorn ³ in 1904 synthesized procaine (diethylaminoethyl ester), achieving a great scientific and practical advance in the field of regional anesthesia. Other local anesthetics were synthesized until 1932 such as benzocaine, piperocaine, and tetracaine. The phase of modern local anesthetics amino-amides such as lidocaine, prilocaine, etidocaine, bupivacaine, levobupivacaine, and ropivacaine started in 1943.

THE BEGINNING OF LOCOREGIONAL ANESTHESIA

The way for the creation of locoregional anesthesia was opened with the advent of the needle and syringe and, afterwards, anesthetics. Peripheral nerve blocks initiated with Halstead and Hall who, in the best tradition of those times, tried cocaine in several anesthetic techniques. Both paid a terrible price because they became dependent on the drug; Halstead, however, partially defeated the problem when he transferred to the Johns Hopkins Hospital ^3,14.

In 1885, the American neurologist James Leonard Corning ¹⁵, born in Stanford, Connecticut, took the first steps for the creation of spinal blocks experimenting in dogs and in one man. In 1898, Bier created the subarachnoid block for surgical use after having undergone it and practiced it in his assistant, Hildebrandt ^3,14. In 1901, Cathelin and Tuffier, and Sicard and Forestier separately introduced the sacral epidural block ³. Tuffier tried the lumbar approach that same year but the natural difficulties to locate the epidural space worked against it use; however, in 1906 Forestier succeeded although precariously ³. In 1921, Sicard and Forestier ³ described a system to locate the lumbar epidural space using the loss of resistance technique; this represented a great clinical advance for the technique, and the procedure became well known and was popularized from 1933 on by Dogliotti ³. On the same year, Seresi and Gutierrez, independently, described the drop aspiration technique ³. Between 1911 and 1973, besides subarachnoid and epidural blocks, other types of regional blocks such as cervical and brachial plexus block by different approaches, paravertebral block, 3-in-1 paravascular block, and intra-osseous anesthesia were introduced; Babitsky, Blinov, Burnham, Danis, Dogliotti, Forestier, Fraiman, Gutierrez, Hirschell, Kappis, Kullenkanpff, Pagés, Rovenstine, Seresi, Sicard, Spiegel, Werthein, and Winnie participated actively in this process ³. In 1984, the first 100^th anniversary of the regional block was celebrated ^3,16.

ORIGIN OF INTRAVENOUS REGIONAL BLOCK

August Karl Gustav Bier introduced IVRB in 1908; this was immediately followed by another similar technique, the intra-arterial regional block created by Goyanes in 1909. From what was previously exposed, the introduction of IVRB preceded several anesthetic techniques currently available, which partially explains the huge interest it triggered at the beginning of the XX Century. From what it is known, it is possible that although Bier was aware of the work of Corning ¹⁸ he did not base his invention on it, and he probably did not hear about the studies of Alms who, in 1886, was able to anesthetize paws of frogs with an intra-arterial injection of cocaine ^3,18.

Intravenous regional block as initially proposed by Bier included ^17-19: 1) exsanguination using a 3.5-meter long elastic band for the upper limbs or 6.5-metter elastic band for the lower limbs; 2) proximal garroting on the arm or thigh with a 2.0- or 3.5-meter long Esmarch's bandage, respectively; 3) the distal placement of a second bandage 10 to 30 cm apart from the first one on the forearm or leg, which was indispensable when it was possible to administer the local anesthetic in a wrist or ankle vein (observe that, for specific situations, he proposed the use of a single tourniquet); 4) dissection under local anesthesia of the cephalic, basilica, or median vein on the antecubital fold, or great saphenous vein at the level of the knee as close as possible to the proximal tourniquet; when accessible, any large superficial vein on the forearm could be used; 5) insertion of a cannula in the distal direction and placement of appropriate ligatures; 6) injection of 50 or 100 mL according to the volume of the upper or lower limb being anesthetized of 0.5% procaine solution at body temperature; 7) removal of the distal tourniquet shortly after anesthesia had been instituted; 8) removal of the second tourniquet at the end of the surgery to minimize the toxic effects of the local anesthetic. This was done intermittently by loosening the tourniquet to allow the penetration of arterial blood in the area, exsanguination, and the consequent loss of local anesthetic through the surgical wound or trying to achieve the same objective by washing the vascular bed with large amounts of normal saline.

The first reports by Bier ^17-19 proposed several technical, pathophysiological, and clinical concepts. He recognized that injection of the anesthetic solution in the central or distal direction did not change the characteristics of the anesthesia. He demonstrated that the area close to the garroting did not anesthetize well. He admitted the importance of limb exsanguination for the rate of installation and effectivity of anesthesia. He demonstrated the presence of motor blockade and emphasized the feelings reported by the patient when the anesthetic was administered. He verified that thermal, painful, and tactile sensitivity disappeared in this order and returned in the opposite order. He described the occurrence of anesthetic failure and temporary muscular paralysis, and that post-ischemic anesthesia did not change substantially with 0.5% or 1.0% novocaine. He proposed preventing the pain caused by garroting by the subcutaneous infiltration of anesthetics around the proximal edge of the upper tourniquet or, by suggestion of a medical student, by placing another tourniquet distal to the first one, followed by removal of the upper tourniquet. He studied the intravenous pressure in animals, demonstrating that it can increase above the pressure produced by garroting, allowing the local anesthetic to escape into the general circulation. He proved, experimentally, the homogenous spread of 50 mL of a solution of indigocarmin injected in the great saphenous vein of the amputated limb, staining the subcutaneous, muscular, bone, and nerve tissues; he believed that the local anesthetic had the same diffusion allowing the slow release of the drug into the general circulation, which did not prevent him from observing occasional mild toxic systemic reactions. He discussed the mechanism of action of IVRB and described its installation in two phases: an immediate phase, usually 2 minutes, between the two tourniquets, which he called direct anesthesia, and another slow, in up to 20 minutes, beyond the distal tourniquet, which he called indirect anesthesia. Several of those technical, pathophysiological, and clinical details are still valid, while others were modified or are still not fully explained ^3,6.

THE EVOLUTION OF INTRAVENOUS REGIONAL BLOCK

THE FIRST DECADES

After the studies of Bier ^17-19, several studies reported slight modification on his method, many of which he had proposed ¹⁹, such as the use of a single tourniquet on the arm, thigh, forearm, or leg, exsanguination by gravity, and the use of a second tourniquet in an anesthetized area. Several local anesthetics were tried, but procaine continued to be the drug used more often. However, very little was added to what Bier had idealized or studied ^18,19, and very little important contributions were made to increase the awareness of the method.

Intravenous regional block was introduced in Brazil by Zephirino Alves do Amaral (1887-1962) shortly after he became aware of the studies of Bier in Germany ^3,20. One year later, Rosa ²¹ defended the first of only two theses on the subject ^21,22, at the Faculdade de Medicina de Porto Alegre (RS), reporting the results obtained with 50 patients. Shortly after, Mendonça ²³ considered the application of IVRB very restricted, complicated, dangerous, and capable of interfering considerably with hemostasis.

From 1920 on, and for almost half a century, the interest for intravenous regional block decreased. Anesthesiology books did not focus on it or when they did it was always succinct and only scattered communications were made public. The main reasons why intravenous regional block was not widely used include: 1) the introduction of brachial plexus blocks; 2) introduction of spinal and epidural blocks; 3) the inconveniences of the surgical catheterization of a superficial vein and isolation of a segment of the limb; 4) lack of more appropriate equipment, such as good elastic bandages and double parallel chamber pneumatic tourniquet; 5) fear of toxic reactions caused by the local anesthetic; 6) the results obtained with procaine are certainly not as good as the results of modern anesthetics; and 7) little knowledge on the pathophysiology and pharmacokinetics of the method.

In 1931, Morrison gave two important contributions ²⁴. He suggested abandoning vein dissection and giving up definitively the use of two tourniquets to isolate a segment of the limb, and recommended the administration of the anesthetic distal to a single tourniquet ²⁴. In fact, Morrison did not create this conduct ²⁵,as it was once thought but he gave the anesthetic method a greater dimension when he adopted it and recommended its systematic use ³. Anyway, the last proposal, which allowed the diffusion of the anesthetic solution throughout the venous system of the ischemic area simplified the original method, increased its efficacy, and was partly responsible for the future development of IVRB. Three decades later the origin of this technical modification was attributed to Holmes ^26-28, an equivoque recognized by him in a report on the history and development of IVRB ²⁹; in fact, a historical investigation conducted ³⁰ demonstrated that Bier ¹⁸, followed by Lenormant ³¹, had already used a single tourniquet in some cases as exposed in a report of 1910: "We also tried to eliminate the peripheral tourniquet and injected the solution in the entire ischemic area of the limb, but this is advisable only when a vein just above the foot or wrist joint can be catheterized."

In 1946, another modification of Bier's original method ^117-19 was suggested by Herreros ³² who proposed the use of a pneumatic tourniquet with a pressure below the systolic pressure but above the diastolic pressure, maintaining the arterial circulation in the extremity; Morrison ²⁴ had used a similar technique for specific indications. The technique of Herreros ³² was not well received and the most original accomplishment that can be attributed to this author was the introduction of tetracaine for IVRB in the search for a more perfect anesthesia ³³. Herreros ³² also insisted in the use of a second tourniquet immediately distal to the first one as proposed by Bier ^118,19 to improve the tolerance to limb compression. But he was not the inventor of the double-chamber tourniquet as it was once indicated ³⁴.

In 1932, in Brazil, Mendonça ³⁵ published a study on IVRB as it was recommended by Bier ^17-19. In 1951, Mabilde ³⁶ reported the results observed at the Traumatology Institute of Montevideo (Uruguay). In 1954, Pires ³⁷ reported his results after performing the procedure with Bado, an Uruguayan surgeon; he made a short film on the subject and years later presented it in one of the first Anesthesiology Rounds of Inner São Paulo State (RAIESP). In 1954, Fortuna ³⁸ presented his experience at the Anesthesiology Society of Rio de Janeiro and published a work on anesthetic blocks in which he included a discussion on IVRB. In 1962, Battaglia ³⁹ began to use intravenous regional block at the Hospital São Paulo of the Escola Paulista de Medicina (UNIFESP).

After the original studies by Bier ^117-19, approximately half a century went by before better conditions were in place for the use of IVRB. Paraphrasing Bromage ⁴⁰, until the end of that period, intravenous regional block just like the epidural block "was used for 50 years more as an art than science, with a deep ignorance of its mechanisms."

THE REDISCOVERY OF THE INTRAVENOUS REGIONAL BLOCK

In 1963, Cornaglia, Danielli, and Vermoni ⁴¹ used lidocaine in IVRB for the first time, a local anesthetic whose 50^th anniversary was celebrated in 1993 ⁴². However in the same year a report by Holmes ²⁶, who also used lidocaine, had great repercussion because he demonstrated a higher success rate than those who preceded him, thanks to the qualities of the drug with better penetration and potency/effectivity correlation. The work of Holmes ²⁶ had another consequence: it caused an immediate increase in the interest on the anesthetic technique, with the resultant increase in the number of studies undertaken, although most of them reported similar observations and included a small number of patients. Intravenous regional block was also extensively discussed in refresher or review papers, summaries, letters to the editor, or comments, and anesthesiology textbooks and compendia were responsible for detailing and focusing more the subject in more details ³. All those publications contributed to the world wide dissemination and the beginning of experimental studies on IVRB.

The interest on the technique increased considerably in Brazil from this period on, with studies by Branco, Battaglia, and Gereto ⁴³, Brito ⁴⁴, Castro ⁴⁵, Fortuna ⁴⁶, Reis Júnior ^47-54, Reis Júnior and Silva ⁵⁴, and Zerbinatti ⁵⁶.

THE LAST DECADES

The scientific evolution of IVRB started in the beginning of the decade of 1970. Huge advances were obtained in different fields of study, and the modifications on clinical conducts, theoretical information, procedures, and equipment increased the efficacy and safety of the anesthetic technique ^57-62, and several of those contributions were made by Brazilian anesthesiology ^12,60. Several studies dedicated to its perfection were condensed in two books published in 1996 ³ and 1998 ⁴. Therefore, the objective of this study, besides reporting the history of IVRB, was to show that in the last years of the 20^th Century and first years of the current century the advances on the knowledge of this technique are still ongoing.

Synonymy

Since its beginning, IVRB received several designations; however, for several reasons discussed on an earlier publication ³ the name intravenous regional block, currently in use, is considered more correct.

Indications

Relative and absolute indications and contra-indications, as well as advantages and disadvantages of IVRB, which are well known include, nowadays more than before, besides clinical factors its lower cost when compared with general anesthesia ^3,57,58; however, new modifications on IVRB are still being proposed. The response to a questionnaire sent to 1,000 American and Canadian anesthesiologists a few years ago showed that this technique is still practiced with the same indications but with a great variety of technical details ⁶³, which also happens in other places ^64-69. Lately, IVRB has also been used with different objectives in research. Its use has been proposed for the treatment of palmar hyperhidrosis, as an effective method to prevent the severe pain caused by the injection of botulinum toxin type A (BTX-A) in the palms (100 U in each hand) that could improve considerably the symptoms of this condition ^70,71. Another recent study concluded that IVRB with lidocaine associated with methylprednisolone does not have long-term benefits on complex regional pain syndrome type I ⁷². The metabolic vasodilation in the forearm after exsanguination in IVRB with phentolamine has been studied ⁷³. Its effects on metabolic and hemodynamic changes by adding bretylium to the anesthetic solution were studied, and it was concluded that the sympathetic stimulation of forearm muscles during exercise does not moderate the blood flow and restricts the anaerobic metabolism and the release of H⁺, presumably by recruiting, preferentially, oxidative pathways ⁷⁴.

Exsanguination

The introduction of the latex elastic bandage, easier to manipulate, more efficient, and less traumatic than older bandages made with rigid rubber, both for exsanguination and garroting, was very important and, besides improving the procedures, it also facilitated them ^3,4,75. The volume of blood dislocated with different methods of exsanguination was measured once more, which confirmed the better performance of the method when Esmarch's bandage is used ⁷⁶.

As for the second exsanguination, proposed several years ago, done by the surgeon after the administration of the anesthetic solution and preparation of the surgical field, three valid advantages have been suggested ^{3,67,75,77,78}: 1) improvement of the quality of anesthesia by forcing more anesthetic into deep tissues; 2) a more efficient prevention of pain caused by the prolonged intraoperative use of the tourniquet, by forcing more anesthetic to the region of the tourniquet; and 3) a dryer surgical field by sending to the systemic circulation the excess of blood and anesthetic solution present in regional blood vessels. It has important disadvantages, such as marked elevation of the venous pressure in the area adjacent to the first tourniquet and consequently possible sudden evasion of large amounts of the local anesthetic into the systemic circulation, and the discomfort caused to the patient by the delay in the change of tourniquets ^3,75.

Garroting

Since the final years of the last century, the advances in garroting have been enormous; the double-chamber tourniquet with two parallel and independent cuffs, microprocessors, and alarms indicating pressure and duration of garroting was developed ^3,4,75. Vantages and disadvantages of elastic and double-chamber pneumatic tourniquets have been clearly determined regarding indications, areas of application, possibility of sterilization, specific pressures, cost, etc ^3,4,75.

Recently, cultures of material collected from tourniquets from a teaching hospital in London and two other large general hospitals in the United Kingdom detected the presence of important pathogenic microorganisms resulting from contamination of this material with blood or secretions from patients in whom they were used on ⁷⁹. This study demonstrated, once more, that this equipment when used without prior sterilization can potentially transmit severe infectious diseases to patients and health care personnel ⁷⁹; and furthermore, this same study recommended that, when it is not possible to sterilize reusable tourniquets, they should be discarded ⁷⁹. The use of disposable covers for pneumatic tourniquets, substantial reservoirs of potentially pathogenic microorganisms, had been proposed already ³. Many Brazilian hospitals that use elastic and pneumatic tourniquets have been following both conducts for several years.

The levels for application of tourniquets, allowed or prohibited, as well as the indications for each one, have been definitively established ⁷⁵. The concern about placing tourniquets on the forearm or leg no longer exits, since it has been proven that it can be done and it is better tolerated than arm or thigh tourniquets, and it was concluded that one should consider the vantages and advantages of their use ^3,4,75; it has also been recently confirmed, once more, that the procedure does not increase the possibility of the local anesthetic reaching the systemic circulation, and that the risks of neuromuscular lesion and pain caused by the tourniquet are decreased when the tourniquet is placed on the forearm or leg ^3,4,80-83.

Garroting pressures that have to be used, and the discomfort or even pain they cause have been widely studied. It has been demonstrated that those pressures depend on several factors that should be well known by those that use IVRB, such as the quality of exsanguination, width and type of tourniquet, the region it is applied on, initial systolic pressure, age, emotional state, and physical development of the patient, as well as volume and rate of administration of the anesthetic solution ^3,4,75,82,83. Garroting pressures should never be determined empirically, but the lowest pressure possible should be compatible with the effective pressure needed for a proper anesthetic-surgical procedure; one should never forget that, by using an elevated tension when applying the elastic bandage and using more than 5 turns, extremely elevated tissue pressures, of up the 900 mmHg, are produced ^3,75. It has been demonstrated, once again, that the pain caused by the tourniquet is inversely proportional to its width, i.e., a wider tourniquet is associated with less pain, if the tourniquet is inflated with low pressure ⁸³, and the temporary use of a third distal tourniquet on the forearm to concentrate more local anesthetic in the hand followed by another exsanguination to canalize the drug below the double-chamber tourniquet and therefore improve the tolerance of the patient to the equipment has been suggested ⁶⁸. The use of a eutectic mixture of local anesthetics has been proposed. however, it is not commonly used ⁸⁴.

It has been known for a long time that the temperature in the ischemic region tends to be reduced but returns to pre-ischemic conditions a few minutes after tourniquet removal; however, prolonged exposure to the heat of potent surgical lights can cause changes in tissue conditions in the ischemic area ⁷⁵. Anesthesiologists and orthopedic surgeons are not aware that garroting of the limbs does not change core temperature in adult patients ^85-87; however, in very young patients, it can rise progressively to very high levels and it is directly dependent on the duration of garroting, especially on the lower limb or bilateral ^88-90. A study with children with myopathies and, therefore at greater risk of developing hyperthermia ⁹¹, confirmed the dangers of an important elevation in core temperature by garroting a limb ^88,89; the same study showed that, similar to adults ^85-87, children develop a patent reduction in core temperature during the immediate post-ischemic period ⁹¹.

Anesthetic solutions

Two simple but important instruments introduced more than 30 years ago facilitated considerably the administration of the anesthetic solution and especially venipuncture, besides preventing loss of the venipuncture during limb exsanguination: the butterfly needle and the peripheral catheter.

As for anesthetics, it should be mentioned that procaine was used only for a short period ³. Although chlorprocaine is rapidly inactivated by hydrolysis, it can be alkalinized, what does not improve its performance ^3,92, and its use was virtually discontinued since it caused frequent endothelial lesions and thrombophlebitis ^3,75. Lidocaine was widely used but prilocaine, which was introduced during a specific symposium in Santos, SP in 1964, which preceded the International Anesthesiology Congress (São Paulo – Brazil), replaced it, and was considered the best local anesthetic for IVRB especially because it was less toxic than lidocaine and other local anesthetics ^3,61,75. Mepivacaine was introduced at the same time, but it was not widely used; however, its use has been recently reported ⁹³. Bupivacaine was introduced afterwards but due to its cardiotoxicity and lack of advantages on IVRB over other local anesthetics, it was discontinued ^3,75. Levobupivacaine and articaine have been scarcely used in IVRB ^57,75. It has been discussed whether the substitution of lidocaine by ropivacaine, a relatively recent anesthetic with less cardio- and neurotoxicity than bupivacaine, would be useful and relevant ^75,95-98; in Brazil and abroad, the discussion on the vantages and disadvantages of both anesthetics, especially on quality of analgesia on the immediate postoperative period, is ongoing. The discussion on the substitution of the local anesthetic by meperidine continued until the end of the last century, but that drug was not widely accepted ^99,100. The superiority of prilocaine as the ideal local anesthetic for IVRB has been reaffirmed^61,75; unfortunately, it is no longer available in Brazil but it is still used in Europe ⁵⁷. The mixture of local anesthetics did not show to be advantageous and could possibly increase the toxicity of the anesthetic solution ^3,75,101.

Regarding the concentration and volume of the anesthetic solution that should be used, it has been definitively established that they depend on several factors, such as the level of garroting, age of the patient, physical development and volume of the limb, area to be operated on, and possibility or quality of exsanguination ^3,667,75. The use of the relationship between body weight and dose of the local anesthetic in adults showed to be inadequate for the results of IVRB, but it is valid only to calculate the maximal dose to be employed; but in children it is reasonable to adopt this rule adjusting the dose in function of the apparent volume of the region to be anesthetized and the age of the patient ^3,75. The maximal doses of prilocaine, lidocaine, and ropivacaine were determined to be 4 to 5 mg.kg^-1, 3 to 4 mg.kg^-1, and 1.2 to 1.7 mg.kg^{-1 3,75}, respectively.

It is accepted that latencies depend very little on the anesthetic agents, but are directly related with a good exsanguination of the limb and with increases in the concentration of the local anesthetic and the volume of the anesthetic solution used ^3,50,102,103; however, it has been observed that installation of anesthesia is slower with ropivacaine than with prilocaine ¹⁰⁴. In general, latencies are shorter in the distribution of the musculocutaneous nerve and more prolonged in the regions innervated by the median and ulnar nerves; controlled clinical studies on the latency times for the different regions of the lower limbs have not been done ^3,75.

The addition of other drugs to the anesthetic solution, to improve the quality of the block, reduce the pain caused by the tourniquet, increase muscle relaxation, treat specific chronic pains of the limbs, and especially to prolong postoperative analgesia has been suggested; the drugs mentioned include morphine, fentanyl, lysine, buprenorphine, meperidine, ketamine, ketorolac, guanethidine, reserpine, potassium, sodium bicarbonate, tramadol, methylprednisolone, tenoxicam, clonidine, and nitroglycerine, which have demonstrated varying results and with the possibility of additional complications ^3,57,105-109.

Older but still current studies on regional venous pressure during the administration of the anesthetic solution have proven definitively that increases until it achieves a plateau; this can lead to paresthesias and warming of distal areas of the limbs, almost always mild and of short duration ^3,75,120. However, if the solution is injected too fast, it can cause pain due to the sudden distension of the vessel, mechanical irritation of the endothelium, and an important increase in venous pressure that under certain technical conditions can exceed garroting pressures, allowing the anesthetic to escape into the systemic circulation with several consequences ^3,75,120.

The concept that IVRB does not increase intra-compartmental pressure, but for a brief moment during and immediately after the anesthesia, persists ^3,75,121. However, it has been proven that the accidental use of hypertonic crystalloid solution to dilute the local anesthetic can cause post-ischemic compartment syndrome by increasing extracellular volume, caused by changes in osmotic balance, and an identical situation could occur during reduction of lower limb fractures ^75,121. A recent study demonstrated that fibrinolysis in the ischemic limb, which is activated by the tourniquet, can be increased by the presence of high concentrations of lidocaine, but this drug does not change the platelet dysfunction caused by garroting ¹²². Besides the well-known increase in P_ETCO₂ after tourniquet removal ^3,4, a study undertaken a few years ago demonstrated, once again, that this increases the blood flow to the brain, which can be effectively reduced by pulmonary hyperventilation if necessary ¹²³.

Technical flaws

The causes of technical flaws have been determined based on the accumulated worldwide experience; they are almost always due to incorrect technical actions, such as puncture of a vein in the antecubital fold or major saphenous vein in the ankle, imperfect exsanguination, insufficient garroting pressure, inadequate anesthetic solution, non-observance of the latency time, and IVRB in lacerated or crushed limbs ^3,75.

Muscle relaxation

No one can deny that, after garroting the arm and administering 40 mL of 0.5% lidocaine, muscle relaxation develops perfectly well. It has been shown that motor blockade begins immediately after the injection of the local anesthetic, with a 50%-70% and 90%-100% reduction in motor strength in 2 and 15 minutes, respectively ^3,75,124, and that muscle relaxation depends little on the local anesthetic, which is also valid for ropivacaine ¹⁰⁴. However, it has been determined that this can be modified by other technical details, such as the quality of exsanguination, characteristics of the anesthetic solution, addition of other drugs to the solution, and especially the level of the tourniquet and duration of ischemia; female patients present early reduction in motor strength probably due to differences in muscular development between both genders ^3,52,75. Usually, motor recovery begins immediately after tourniquet removal, and it is complete in a few minutes ^3,75.

Small doses of neuromuscular blockers, such as galamine, pancuronium, mivacurium, rocuronium, atracurium or succinylcholine are no longer associated with the local anesthetic; the concept that this association accelerates and amplifies the regional muscle relaxation, which, besides unnecessary prolongs muscle relaxation after tourniquet removal, and increases the risk of unpleasant and dangerous systemic complications, is still valid ^{52,57,75,125-127}.

Site and mechanism of action of the local anesthetic

The notion that anesthesia results from the combination of local anesthetic and limb ischemia is still valid ^3,75. Studies still try to demonstrate whether IVRB results from the action of the local anesthetic on peripheral nerve endings, nerve trunks, or both. Clinical and phlebographic studies, studies that measure the conduction of nerve impulses, using radioisotopes and CT, have been trying to answer this question; however, their results are contradictory without a definitive conclusion ^3,75. From the available evidence, one can conclude that the local anesthetic affects mainly nerve endings and small peripheral nerves, and that blockade of nerve trunks can occur concomitantly, especially when high concentrations of local anesthetics are used ^3,75,128-132. It is possible that the pressure exerted directly on sensitive nerves collaborates to effectively improve anesthesia ^3,75. Interruption of blood circulation, which affects the neuromuscular junction and peripheral nerve branches, interrupts nerve conduction and the function of the terminal motor plate, decreases the partial pressure of oxygen, increases the partial pressure of carbon dioxide, and decreases pH, besides the accumulation of acid metabolites in the tissues, is one of the most important factors that potentiate anesthesia by affecting the ionization and distribution of the anesthetic agent ⁷⁵. However, ischemia isolatedly produces only late anesthesia, which is unreliable ^3,4,75.

It is still believed that local anesthetics reduce the release of acetylcholine in peripheral nerve endings, which would result in muscle relaxation ^3,75. However, it is known that motor blockade can result from the action of anesthetics on the muscle fiber, motor nerve, peripheral nerve branches, and motor end-plate, and that, depending on their distribution and concentration in motor structures of the limb, they are unselective depressors of pre- and postsynaptic structures; it is possible that, with enough doses and time, all excitable structures could be affected ^3,75. Ischemia-induced neuromuscular blockade is probably secondary to the inhibition of acetylcholine synthesis, since it is an aerobic reaction, and motor paralysis is installed when the stores of this ester are depleted. It seems unlikely that changes in the electrical properties of the nerve endings are responsible for the blockade ^3,4,75.

In fact, IVRB should continue to be considered a combination of peripheral infiltration and conductive block or, even better, as a trunk-infiltrative-ischemic anesthesia ^3,75.

Pharmacokinetics

The most important pharmacokinetic concepts were established more than 20 years ago ³; it is now known that those related to ropivacaine are no different than other local anesthetics ¹⁰⁴. There are no doubts that arterial concentrations are the best indicators of the concentrations that reach the brain and myocardium in the first minutes of the post-ischemic period. Maximal plasma concentrations of 0.5% lidocaine (3 mg.kg^-1) in arterial and venous blood in the contra-lateral upper limb reach a mean of 2.4 µg.mL^-1 and 1.0 µg.mL^-1 after 2 to 10 minutes, respectively; contralateral venous concentrations are therefore usually lower than those obtained during axillary or epidural blocks ^3,75,133-136.

The notion of a biphasic release of the anesthetic in the systemic circulation after tourniquet removal in ischemias lasting 20 minutes or more is still valid; only the amount of drug that remained in the vascular bed (25% to 50%) leaves the limb rapidly, indicating that a significant percentage of the drug stays in the area for a prolonged time ^3,75. It has been proved that plasma levels of local anesthetics from the anesthetized limb are always higher than in the blood from the contralateral limb, even after 40 minutes or more ^3,75,134. A clinical sign that proves the staying of the anesthetic in the operated limb is that it is possible to reinstitute a good anesthesia (continuous IVRB), with approximately half of the initial dose, 5 to 10 minutes after removal of the tourniquet ("respiratory period") ^67,75.

The characteristics of each local anesthetic, as well as concentrations and volumes used, modify mean plasma concentrations ⁷⁵. A study comparing local anesthetics, published two years ago, demonstrated higher arterial concentrations of ropivacaine than prilocaine, despite using concentrations (mg) 60% smaller of the most recent drug ¹⁰⁴. However, other factors are capable of modifying the pharmacokinetic profile, such as pregnancy, site of venipuncture, patient age and general condition, quality of exsanguination, garroting level, intra-anesthetic manipulation of the fractured limb, spontaneous or provoked post-ischemic motor activity, liver disease, cardiac output, tourniquet removal conduct, and duration of ischemia ^3,75. In IVRB, under the pharmacokinetic viewpoint, both the maximal duration of ischemia and minimal duration of anesthesia should be taken into consideration ^3,67,75. Besides, adding other drugs to the anesthetic solution increases mean plasma concentrations and consequently the post-ischemic risk of systemic toxic reactions probably due to alterations in regional diffusion, fixation in the tissue, distribution in the systemic circulation, and the biotransformation of local anesthetics ⁷⁵.

As for garroting technique, it has been proven that the intermittent release of circulatory interruption reduces the arterial levels of local anesthetics; this is more significant when the tourniquet is eased off for 10 to 15 seconds, repeated twice or more times, and intercalated with reinstitution of ischemia for 3 to 4 minutes ⁷⁵. It continues to be demonstrated that contralateral venous levels have a precarious correlation with the process of tourniquet release ⁷⁵. Another efficient method for the pharmacokinetic control of the IVRB with tourniquet on the arm or leg consists in the placement of one or more tourniquets distal to the one used intraoperatively followed by the individual removal of each tourniquet every 3 to 4 minutes in the proximal/distal direction (flood-gate system) ⁷⁵.

It has been demonstrated that post-ischemic hyperemia increases the rate of exit of the anesthetic from the anesthetized area and contributes considerably for the immediate limb swelling, but its influence is decreased by local anesthetics, such as mepivacaine and procaine, probably due to the partial blockade of post-ischemic vasodilation ^3,75,137. The increased in blood flow in the region for 5 to 10 minutes is probably secondary to the accumulation of vasodilator substances produced by the ischemic tissue, vascular compromise caused by the increase in anaerobic metabolism, and adverse changes in vascular tonus ⁷⁵.

Postoperative analgesia

It was concluded a long time ago that analgesia in the immediate postoperative period (it should not be mistaken for residual analgesia ³) depends little on the drug used, lasts a mean of 15 minutes, but could last for only 1 minute or less frequently up to 30 minutes, and postoperative pain initially affects the extremities, followed by the proximal areas of the limbs ^3,50,75,138. In the last few years, some authors have obtained suggestive results, while others have not, that ropivacaine is capable of prolonging analgesia in the immediate post-ischemic period than other local anesthetics ^{60,75,94-98,139}, probably due to its more prolonged and greater tissue binding ^75,85. However, postoperative analgesia can vary due to other factors, such as patient age and emotional status, site of venipuncture, quality of exsanguination, area of the surgery, duration of the surgery, tissue temperature, characteristics of the anesthetic solution, and undetermined clinical conditions ^{3,75,93,96-110}. As for the addition of other drugs to the anesthetic solution, a review of the literature demonstrated that only tenoxicam (20 mg) and especially clonidine (0.06 to 0.15 mg) seem to improve analgesia, although they do so only in the first hours of the postoperative period.

Complications

Severe complications of IVRB are rare. However, cutaneous lesions have resulted from entrapment of a skin fold between adjacent turns of the elastic bandage or by its compression against bony prominences, antiseptic burning under the tourniquet, contamination by improperly disinfected or sterilized tourniquet, post-anesthetic hematomas, arterial spasm due to the improper use of anesthetic solution containing epinephrine, vascular thrombosis and loss of the hand by using alcohol-containing anesthetic solution, compartmental syndrome, allergic reactions, dermographism, and development of phantom limb syndrome during anesthesia ^{67,75,140-148}. Many of those complications are also seen in other techniques of locoregional block. On the other hand, IVRB is not associated with different severe complications seen during lumbar or sacral epidural, subarachnoid, and brachial plexus blocks often used as an alternative for surgical interventions in which IVRB is also indicated.

Similar to other locoregional blocks, systemic neurologic reactions (tremors, dysarthria, dysphoria, visual disturbances, perioral anesthesia, tinnitus, and others), and electrocardiographic abnormalities (bradycardia, junctional rhythm, premature ventricular contraction, and transient ST segment depression) are increasingly less common; they depend mainly on the local anesthetic and doses used, are more frequent with bupivacaine than with ropivacaine and lidocaine, and very rare with prilocaine. Those complications also depend on pre-anesthetic medication, and patient age and general condition but most of the time they are secondary to improper conducts, such as in tourniquet removal and non-observance of the time between the administration of the drug and its release into the blood stream, i.e., under 20 to 30 minutes ^3,75,149. Respiratory depression and post-ischemic seizures have never been observed in our Service, which has done approximately 7,000 IVRB ^3,75. Methemoglobinemia triggered by lidocaine is not clinically important with the doses recommended for IVRB ^3,75.

Postoperative muscular paralysis that occurs after garroting the limb for IVRB or other objectives is extremely rare and almost always temporary, and very seldom it is definitive ^3,75. The pneumatic tourniquet decreases but it does not abolish this complication ^3,75; however, it results almost always on the lack of knowledge about the use of elastic and pneumatic tourniquets in relation to the age of the patient, circulatory conditions of the limb, area to be applied on, width and quality of the material, number of turns and tension used with elastic bandages, adequate pressure when using the pneumatic tourniquet, protecting the area with orthopedic cotton, and duration of garroting ^3,4,75,150.. It was determined, a long time ago, that ischemia causes hypoxia of the limb, increases the tension of carbon dioxide, reduces pH, and causes small histological changes other subtle biochemical changes in sodium, potassium, calcium, glucose, and sodium bicarbonate concentration. When garroting is properly done, biochemical and histological conditions return to normal immediately after tourniquet removal ^3,4,75; however, prolonged or incorrect ischemias are associated with inflammatory cellular reactions, more severe histological changes, edema, degenerative processes, bleeding, in the form of petechiae, fibrin deposits, and even muscle paralysis.

There are still doubts on the causes of muscle paralysis that develops after limb garroting. The discussion on whether it is related with ischemic necrosis of nerve tissue or direct mechanical compression of nerve trunks against the bone is current. The second hypothesis is deemed the most likely because it allows a better understanding of the blockade of nerve impulse conduction in the area of compression, the normal response of nerves distal to the affected area, greater sensitivity of radial ("hand drop") and fibular ("foot drop") nerves, decreased suffering and faster recovery of sensitive nerve fibers when compared with the motor fibers of a mixed nerve, decreased frequency of paralysis caused by placing tourniquets in areas with two bones, and a reduction in this complication but not its elimination by the more frequent use of pneumatic tourniquets ^3,4,75.

There are reports of two cases of cardiac arrest as a consequence of the IVRB, in 1965 and in 1971, both with full recovery without sequelae ^3,75; a third case of cardiac arrest, during the administration of bupivacaine (0.25% - 100 mg) in an elderly female patient with a history of hypertension with equally good evolution was reported in 1986 ^3,75.

Some cases of IVRB-related deaths in emergency rooms in England between 1979 and 1983 of young people or children were associated with high doses of bupivacaine when pneumatic tourniquets were improperly deflated by non-anesthesiology residents and that, in certain occasions, performed simultaneously the surgical procedures ^{3,57,63,75,151}. Another death was reported more recently in North America after seizures caused by the use of high concentration and dose of lidocaine by an inexperienced anesthesiologist in an institution without experience with IVRB ⁶³. There does not seem to be other reports on deaths associated with this anesthetic technique, at least since the beginning of the second half of the last century. It is significant that, in 1989 and in 2004, some authors indicated that those factors were unknown to many anesthesiologists.

CONCLUSIONS

Although some of the questions regarding IVRB remain unanswered, the knowledge about this technique has increased considerably over the years, and most questions are complete or partially answered, but the search for solutions continues. The last few years have seen a considerable increase in the efficiency and safety of the technique ^57,59-62, and it is noteworthy that after 100 years the technique continues to maintain its place among the different locoregional blocks available ^57,61,75,152.

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Intravenous regional anesthesia – first century (1908-2008). Beggining, development, and current status

A anestesia regional intravenosa primer centenario (1908-2008). Inicio, desarrollo y estado actual

Publication Dates

• Publication in this collection
  15 Sept 2008
• Date of issue
  June 2008

History

• Accepted
  19 Feb 2008
• Received
  25 Sept 2007