Spinal anaesthesia during the 19th and 20th Centuries – cocaine and controversy

Thomas Boulton anaesthesia history prize-winning essay 2020

Spinal anaesthesia (subarachnoid radicular conduction block): principles & technique by Charles H. Evans. Wellcome Collection. Attribution 4.0 International (CC BY 4.0)

Read a shorter version of the essay

Introduction

Spinal anaesthesia is a popular alternative to general anaesthesia for surgical procedures below the umbilicus. Almost 360,000 spinals and 23,500 combined spinal-epidural blocks were performed in the UK in 2014 [1]. Advances in needle design, coupled with the emergence of new local anaesthetic agents, have been key to the development of this technique over the years. However, its popularity has fluctuated since it was first performed successfully in humans around 120 years ago. This essay evaluates the major developments in spinal anaesthesia, with the aim of assessing which event had the most significant impact on practice.

Overview - principles and indications

Spinal anaesthesia is achieved by inserting a needle through the dura and arachnoid mater and injecting local anaesthetic into the spinal (subarachnoid) space. A midline approach is generally preferred unless anatomical factors such as narrowing of the intervertebral disks necessitate a paramedian approach instead [2, 3]. It is performed using the intervertebral spaces from L3/4 to L5/S1 to ensure that the spinal cord is avoided.

Unlike epidural anaesthesia where the local anaesthetic has to spread in a potential tissue space, the local anaesthetic is placed in the cerebrospinal fluid (CSF) allowing good spread of the solution [4]. Currently, spinal anaesthesia is employed for obstetric procedures (almost 40% of spinal blocks performed in the UK in 2014 [1]) and surgery to the lower abdomen, perineal region, and legs [5]. One notable advantage of spinal anaesthesia is that it avoids the risks of airway instrumentation associated with general anaesthesia, particularly in pregnant and obese patients, and those with difficult airways.

Origins and 19th Century developments

For a time, there was debate about whether it was the German surgeon August Bier or the American J. Leonard Corning who performed the first true spinal anaesthesia. In 1885, whilst investigating the effects of cocaine on the peripheral nervous system in a dog, Corning injected the drug between two lumbar spinous processes with the intention that the cocaine would be transported along ‘communicating blood vessels’ to the spinal cord itself. He then performed a similar injection between the T11/12 vertebrae of a male patient with ejaculatory problems, causing temporary leg weakness. Fortunately, the patient survived the life-threatening dose of medication (110 mg of 3% cocaine). Further spinal injections in other patients with neurological disorders led Corning to coin the term ‘spinal anesthesia’ [6]. He developed a spinal needle made of gold, with a sharp, short-bevelled needle tip and a short introducer. The tip design was a modification of the original hollow hypodermic needle created by Alexander Wood in 1853 [6]. However, despite justifying his choice of needle tip design very clearly, Corning did not mention the gauge of his needle nor the depth of insertion. Indeed, researchers have concluded that his injections did not reach the spinal space and were more likely to have been epidural [7].

Corning’s experiments were based on the flawed concept that communicating blood vessels linked the epidural circulation to the spinal space. It is unclear where Corning had derived this knowledge, given that one of the leading English language anatomy textbooks of the time included a section on the neuroanatomy of the spinal cord. One theory is that Corning was simply never exposed to this information, given that he studied medicine in Germany and their anatomy textbooks did not mention specific details about the meninges. He would not have observed CSF leakage during his experiment, as the syringe containing the cocaine remained connected to the needle with rubber tubing during the procedure [8]. One other interesting point to note is that Corning was a neurologist, and as such he was primarily interested in the use of cocaine to treat neurological disorders rather than for surgery. Considering that almost all the other early developments in spinal anaesthesia involved surgeons, who would perform both the anaesthesia and the subsequent surgery themselves [8], Corning remains an interesting rarity in that sense.

The next major development took place six years later when Heinrich Irenaeus Quincke performed the first lumbar punctures to reduce raised intracranial pressure in patients with meningitis. Quincke’s studies were based on the anatomical principle that the spinal space ended at around the S2 vertebral level but the spinal cord terminated at around L2, meaning a needle inserted in the L3/4 intervertebral space would avoid hitting the cord [8]. Of course, we now know more about the discrepancy in cord length between adults and children and the natural variability within the population, but Quincke’s reports did at least provide a safer and more standardised technique for lumbar puncture. Quincke was himself influenced by Essex Wynter who had employed a similar, but much less effective, technique six months earlier using a fine-calibre (Southey’s) tube and trocar [8]. Although lumbar puncture was initially used therapeutically to treat hydrocephalus and meningitis, it soon developed into an important diagnostic test. Some prominent physicians nevertheless remained opposed to its use in the early 1900s, including the German neurologists Korbinian Brodmann and Alois Alzheimer. In England, the famous neurologist Sir William Gowers was also fiercely opposed to the use of lumbar puncture, which may partly explain why the first English-language textbook on lumbar puncture did not appear until 15 years after Gowers’ retirement [9].

Fortunately, August Bier did not share such reservations when he performed what can be considered the first true spinal anaesthesia in humans in 1898. The patient in question needed an operation to resect a tuberculous ankle joint, but had experienced very severe side effects after general anaesthesia in the past. Bier therefore suggested a spinal injection of 15 mg cocaine using Quincke’s technique, a much smaller (and safer) dose compared with Corning’s experiments! During the procedure itself the patient did not report any pain, only an awareness that “something was being done” to his foot. Post-operatively he complained of headaches and vomiting, both of which improved within a couple of days [10].

Over the next two weeks, Bier performed a further five successful spinal anaesthetics. The most common postoperative side effects were transient pain at the site of the procedure, headaches and vomiting. Importantly, none of the patients experienced any intra-operative pain. Following these early attempts, Bier wished to comprehend better the side effects associated with his spinal cord ‘cocainisation’. In true scientific fashion, he decided to perform a series of experiments on himself. He enlisted the help of his assistant August Hildebrandt, who used the lumbar puncture technique to inject a solution of cocaine into Bier’s spine. Almost farcically, the syringe used to inject the cocaine did not actually fit the needle, causing the experiment to fail and Bier to lose a fair amount of his own CSF! Following this unsuccessful attempt, the roles were reversed, with Hildebrandt becoming the recipient of the lumbar puncture. This time the injection was successful, with Bier providing an intriguing and somewhat alarming account of the sensory tests he performed on Hildebrandt over the resulting 45 minutes ranging from ‘needle pricks in the thigh’, ‘strong pressure and traction on the testicles’, and hitting the shins with an iron hammer. Importantly, Hildebrandt did not report any pain during these tests, although perhaps unsurprisingly he did subsequently develop bruises in the areas where he had been hit. He also reported debilitating headaches and vomiting after procedure which lasted for several days before he recovered. As for Bier, he suffered from headaches and postural dizziness which lasted for nine days before resolving [10].

From these experiments Bier concluded that CSF leakage, rather than cocaine toxicity, was likely to be responsible for the side effects experienced [10]. Although he performed no further experiments in humans himself, word of his technique soon reached the renowned surgeon Theodore Tuffier, who is remembered today for Tuffier’s line that marks the L3/4 intervertebral space, a safe zone for lumbar puncture. Tuffier helped ensure its popularity both in Europe and across the Atlantic, and highlighted the importance of seeing CSF after needle insertion to confirm correct positioning [8].

Around the turn of the 19th Century, the physicians F. Dudley Tait and Guido E. Caglieri performed the first spinal anaesthesia in the USA, closely followed by Rudolph Matas a few weeks later (although Matas was the first to publish). Of the 11 patients in Tait and Caglieri’s study, three had the spinal inserted at the cervical level, with the surgeons not recognising the enhanced risk of spinal cord damage with this approach. They also incorrectly hypothesised that the post-procedure headaches were a result of raised CSF pressure [11] rather than reduced pressure [12]. The work of Tait, Caglieri and Matas was significant because it reflected the most up-to-date knowledge of the spinal space and spinal anaesthesia at that time, and their studies were amongst hundreds of other reports on spinal anaesthesia in the two years following Bier’s experiments [11]. However, although useful for demonstrating the feasibility of the technique, none of these early studies provided solutions for the associated side effects, notably post-dural puncture headache.

Early 20th Century

Oskar Kreis was the first physician to use spinal anaesthesia for women in labour in 1900; before this, only inhalational anaesthesia using ether or chloroform had been used, despite concerns about both maternal and fetal effects [13]. Kreis performed spinals with 10 mg cocaine on six women in the second stage of labour, which resulted in sensory paraesthesia and an absence of pain but maintained leg motor function. The women did not start to feel pain until several hours following delivery, along with the expected side effects of headache, nausea and vomiting. Kreis’ observation that uterine contractions were unaffected helped discount the previously-held belief that contractions and pain were inseparable, and helped inspire further research into the neuroanatomy of childbirth and the synthesis of new drugs for spinal anaesthesia [13]. There is no doubt that his efforts represent one of the major milestones in the history of obstetric anaesthesia. However, a lack of knowledge surrounding the complications of spinal anaesthesia, and possible effects on labour, meant that many obstetricians remained unconvinced for several years following this [14].

Up to this point the only local anaesthetic in widespread use was cocaine, although there was growing evidence of the systemic risks associated with its use including peripheral vasoconstriction, cardiac and central nervous system excitability, as well as addiction or dependency [15]. Although several researchers during the 1890s promoted the use of safer infiltration techniques and lower doses, there remained a need to develop alternatives that were less toxic and addictive. One of the earliest such drugs was Novocaine, invented in 1905 by Alfred Einhorn and first used medically by Heinrich Braun. Despite being safer and less addictive, the anaesthetic potency of Novocaine was weaker. It was also associated with a higher risk of hypersensitivity reactions owing to its metabolite para-aminobenzoic acid [16]. Novocaine was later given the generic name of procaine and remains in use in parts of the world today [17].

Amylocaine (brand name Stovaine) was another drug introduced in the early 1900s and used for spinal anaesthesia. Synthesised by Ernest Fourneau, it was first used clinically by the French surgeon Paul Reclus [18], and later embraced by Arthur Barker. Barker was notable for incorporating the concept of baricity into his technique of spinal anaesthesia. By mixing 5% amylocaine with 5% glucose in normal saline, he created a hyperbaric solution that allowed him to influence the spread of the anaesthetic within the CSF [8]. Barker, amongst others, also contributed to improvements in needle design and safety. His needle had a sharp, hollowed-out point to reduce the risk of the needle penetrating too far, while also keeping the length of the bevel short. He also designed a blunt cannula that could fit inside the wide bore needle and deliver the entire anaesthetic solution into the spinal space, helping to minimise leakage into the epidural space [19].

Needle design advanced during the first part of the 20th century. In the 1920s the French clinician Gaston Labat designed a hard nickel needle that was much more durable than its predecessors, many of which were nickel-plated steel needles prone to corrosion. His investigations into the effect of spinal anaesthesia on blood pressure were also key for understanding and improving safety, and for improving its popularity across Europe and the USA [6, 20]. Also during the 1920s, Herbert Merton Greene developed the first ‘atraumatic’ needle tip. He hypothesised that using a needle tip that passed between the dural fibres, rather than cutting through them, would reduce the leakage of CSF, and in turn reduce the risk of post-dural puncture headache. This needle design remained popular until the development of the Whitacre needle in the 1950s [6].

In 1928 a new, longer-acting local anaesthetic known as dibucaine was first used in clinical practice by Uhlmann, followed by a similar compound, tetracaine, four years later. Both were more potent than cocaine and less prone to hypersensitivity reactions than procaine. However, the benefit of added potency was offset by the increased risk of systemic toxicity, particularly if used for peripheral nerve blocks, and limited their use almost exclusively to spinal anaesthesia [21]. Predicting how these anaesthetic agents would spread within the spinal space was also difficult, particularly if presented as isobaric solutions. In 1935 Lincoln Sise, who drew inspiration from Barker’s efforts, created a more reliable hyperbaric solution of tetracaine mixed with 10% glucose, and injected the solution with the patient positioned head down. The table angle was then adjusted according to the level of anaesthesia desired [8].

Mid-20th century

In 1943 the first amide-linked anaesthetic agent, lidocaine, was synthesised by Nils Lofgren and Bengt Lundquist. It proved to be an excellent spinal anaesthetic for short-to-moderate length surgery as a result of its potency, low risk of hypersensitivity reactions, and ability to resist degradation at high temperatures. This thermal stability meant that lidocaine could withstand repeated sterilisation much better than its predecessors [8]. It remains one of the most popular choices for local anaesthesia today, although its use as a spinal anaesthetic has been challenged by recent studies reporting a higher incidence of postoperative transient neurological symptoms compared with other agents [22].

Besides the pharmacological advances, other developments during the 1940s included William Lemmon’s method of continuous spinal anaesthesia using malleable needles connected to rubber tubing. The first description of continuous spinal anaesthesia was in 1907 by the British surgeon Henry Dean, although his report attracted comparatively little interest at the time. Lemmon’s method gained more publicity in the field, although it was difficult to keep the needle in the correct position within the spinal space [23]. A few years later, Edward Tuohy introduced the concept of a catheter, rather than a needle and tubing, to deliver repeated anaesthetic boluses, more closely resembling the devices in use today [6]. Despite offering the obvious benefit of tighter control over dosage, and therefore less chance of side effects, Tuohy’s technique for continuous spinal anaesthesia did not gain popularity for another 40 years or so owing to its technical difficulty, the risk of needle breakage and the continued issue with complications [24]. One other notable development during this period occurred in 1946 when Roman-Vega and Adriani described a simplified technique using hyperbaric anaesthetic solutions to provide spinal anaesthesia to the saddle region only. The key benefits were a reduced incidence of hypotension compared with conventional spinal anaesthesia. Saddle blocks were initially used for rectal and genital procedures, and later applied in obstetrics [25].

Controversy of the mid-20th century

By the end of the 1930s, several case reports had emerged of serious neurological complications (cauda equina syndrome, paraplegia and spinal cord infections) following spinal anaesthesia. In 1945, Kennedy, Somberg and Goldberg reported three cases of paralysis and cord inflammation after spinal anaesthesia, and postulated that chemotoxicity of the anaesthetic drugs themselves was the cause. Indeed, five years later Kennedy et al. reported a further twelve instances of paraplegia and neurological damage following spinal anaesthesia and highlighted their significant reservations with the safety of the technique [26].

However, at the time Albert Woolley and Cecil Roe were given spinal anaesthesia on October 13th 1947 at Chesterfield Royal Hospital, the potential neurological complications had still not been well-characterised. Roe required an operation to remove a hydrocoele, and Woolley underwent surgery for a torn meniscus. Both patients were anaesthetised with 10 ml hypobaric dibucaine 1:1500 in the same operating theatre by the same anaesthetist, Dr Malcolm Graham. They reported very different intra-operative experiences; whilst Woolley did not experience any discomfort at all, Roe suffered severe head and back pain that persisted until the evening. However, the next day both patients developed an acute cauda equina syndrome that progressed to painful paraplegia. Interestingly, a third patient also received the same anaesthesia that day, and although he died five days later from the effects of his illness, he had also begun to show signs of neurological complications [26]. No other cases of a similar nature were reported at this hospital. Six years after the incident, Woolley and Roe sued for damages; the subsequent court case gained substantial publicity. The court ultimately ruled in favour of the anaesthetist, with the explanation at the time that the ampoules of local anaesthetic had become contaminated by phenol used for sterilisation by the means of invisible cracks in the glass. This explanation was treated with scepticism outside the courts, and when the case was re-examined in 1990 by Hutter he concluded that contamination of the syringes and needles by acid de-scaler was more probable. This could have occurred if the descaling solution in the sterilisation container had not been replaced with water before the syringes and needles were placed inside [27]. Despite the 1953 ruling, the case generated such fear amongst doctors about spinal anaesthesia that its use fell significantly in the UK, and did not fully recover for another 25 years [28].

The popularity of spinal blocks was not helped by advances in general anaesthesia at around the same time. Daniel Bovet was awarded the Nobel Prize for Medicine in 1957 for his research into the neuromuscular blocking drugs gallamine and suxamethonium [29]. The 1950s also saw the introduction of the non-flammable inhalational anaesthetic halothane. This replaced ether and chloroform, and remained popular for many years after [30].

Developments after Woolley and Roe

Despite the controversy surrounding the Woolley and Roe case in the UK, spinal anaesthesia became the most common anaesthetic technique for obstetric procedures in the USA during the 1950s owing to its ease of use, reliability and lower incidence of serious side effects, such as neonatal respiratory depression, compared with general anaesthesia [31]. Dripps and Vandam published a report in 1954 aiming to reassure the scientific community over the use of spinal anaesthesia. They performed a long-term follow-up of over 10,000 patients receiving spinal anaesthesia, concluding that there was not a significantly increased risk of serious neurological complications [32].

There were some other positive developments for spinal anaesthesia during the 1950s. 1951 saw the introduction of pencil-point needles that had a non-cutting, tapered point designed to reduce the risk of damage to the dura and the subsequent risk of post-dural puncture headache. The Swedish doctor Sixten Haraldson described such a needle several months before Hart and Whitacre published their well-known paper. Whilst Haraldson’s needle failed to gain widespread popularity, potentially because it was only manufactured locally in small quantities, the Whitacre needle became the standard design and is still in use today with only a few minor modifications [6]. Hart and Whitacre drew inspiration from the atraumatic needle described by Greene back in the 1920s.

2-chloroprocaine was another spinal anaesthetic agent developed during the early-mid 1950s. A rapid onset of action and rapid resolution of its effects meant that it was a popular alternative to lidocaine for short surgical procedures [33]. Several amide-type anaesthetics followed, including bupivacaine and mepivacaine (both synthesised by Bo af Ekenstam et al. in 1957) and later prilocaine (1959) [17]. The synthesis of bupivacaine represented another significant breakthrough in regional anaesthesia, and it remains the drug of choice for spinal blocks today owing to its fast onset and relatively lower incidence of transient neurological symptoms [34]. Further research also led to the development in the 1990s of the stereoisomer levobupivacaine, and the chemically-similar ropivacaine [33].

In contrast to the breakthroughs in local anaesthetic drugs, there were few noteworthy developments in spinal needle design in the period between the Whitacre needle and the Sprotte needle 37 years later. Large scale production of disposable needles and syringes began during the late 1950s, although they were expensive and there were issues with quality control. Tapered needles were trialled in the 1960s, but failed to gather much support owing to the relatively high incidence of post-dural puncture headache and difficulty of needle insertion. Growing interest in epidural anaesthesia, particularly in obstetrics, and the lingering impact of the Woolley and Roe case may have explained the lack of developments during this period [6, 35, 36]. In 1987, the German anaesthetist Guenter Sprotte modified the Whitacre needle by elongating and widening the tip. His aim was to facilitate the ease of injection and reduce dural trauma. Concerns over the fragility of Sprotte’s needle and the implications for patient safety led to a refinement of the needle design in 1993; this later version remains a popular choice today [6, 37, 38].

Implications for modern-day practice

A good example of how these advances have contributed to modern practice is the use of spinal anaesthesia during day surgery. This has become possible thanks partly to the refinements in the pencil-point needle design mentioned above, which have reduced the incidence of post-dural puncture headache [39]. Alongside this, the recent introduction of a hyperbaric preparation of prilocaine and, in 2013, the licensing of a preservative-free preparation of 1% 2-chloroprocaine have proved significant. Both drugs are short-acting compared with bupivacaine and levobupivacaine, and so are better suited for day surgery. They also have better side effect profiles compared with earlier preparations, which involved higher concentrations and the addition of preservatives such as sodium bisulphite. Both drugs may help reduce the need for adjuvant spinal opioid and are associated with less severe nausea and pain postoperatively [40].

Finally, obstetrics is another area that continues to benefit from advances in spinal anaesthesia. In 2010 a case series of 25 ‘rapid sequence spinal’ anaesthetics in Category-1 caesarean section was published. General anaesthesia is associated with increased maternal complications during Category-1 caesarean sections, but is quicker to administer. The rapid sequence spinal approach, based on several principles including a ‘no-touch’ technique and a simplified combination of anaesthetic drugs, saves considerable time compared with a standard approach. Importantly, the authors still recommended switching to general anaesthesia early if spinal attempts were unsuccessful [41]. In the context of the current coronavirus pandemic, rapid sequence spinal anaesthesia may prove to be a valuable alternative to general anaesthesia, particularly in the emergency setting [42].

Conclusions

In conclusion, it is evident that the development of spinal anaesthesia has not been entirely smooth since Corning’s experiments in the 1880s. The controversy of the 1940s played a key role in delaying progress in this field, and subsequent improvements in general and epidural anaesthesia further restricted its popularity. On the other hand, advances in needle design and the discovery of safer, more efficacious local anaesthetics have had beneficial implications for all forms of regional anaesthesia, spinal included. On balance, although Quincke’s standardisation of the lumbar puncture technique, Kreis’ advocation of spinal blocks in obstetrics, and the invention of lidocaine are all notable events in the history of spinal anaesthesia, Bier’s success in 1898 was such a landmark moment and drew such widespread interest that it can arguably be considered the most significant event amongst them all.

Serkan Cakir
Medical Student
Blandford Forum

A shortened version of this essay was published in Anaesthesia News, April 2021, pages 8-9.

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