Intrathecal drug spread

Abstract

Spinal anaesthesia has the definitive advantage that profound nerve block can be produced in a large part of the body by the relatively simple injection of a small amount of local anaesthetic. However, the greatest challenge of the technique is to control the spread of that local anaesthetic through the cerebrospinal fluid (CSF), to provide block that is adequate (in both extent and degree) for the proposed surgery but without producing unnecessarily extensive spread and so increasing the risk of complications. The great interpatient variability in spread was observed and described as ‘lauenhaft’ (waywardness) by August Bier,10Bier A. Versuche uber Kokainiserung des Ruchenmarkes.Dtsche Z Chir. 1899; 51: 361-369Crossref Scopus (0) Google Scholar the first person to use the technique clinically, and has challenged many subsequent workers. In fact, the definitive studies were performed nearly 100 years ago by Arthur Barker, a London surgeon who was the first to use solutions made hyperbaric by the addition of glucose,7Barker AE. Clinical experiences with spinal analgesia in 100 cases.Br Med J. 1907; 1: 665Crossref PubMed Google Scholar but his principles have had to be re-learned virtually each time a new drug has been introduced for the technique. This review focuses in particular on work published in the last decade (during which time ropivacaine and levobupivacine were introduced) in trying to provide guidance on making spinal anaesthesia as predictable as possible. Studies of drug distribution usually involve measurements of concentration in a relevant body fluid compartment over time. However, multiple sampling of CSF at one level, let alone at the several needed to build an image of drug distribution through the theca, is not practical and would significantly influence the observations anyway. Thus, indirect indicators of spread are used, the vast majority based on tests of neurological response. Bier's 1899 description of spinal anaesthesia documented the many tests that he used, including “…sensual perception of needle pricks to the thigh, tickling of the soles of the feet, a small incision in the thigh, pushing a large helved needle down to the femur, strong pinching with dental forceps, application of a burning cigar, pulling out pubic hairs, a strong blow with an iron hammer against the tibia, vigorous blows with the knuckles against the tibia, and strong pressure on a testicle”.10Bier A. Versuche uber Kokainiserung des Ruchenmarkes.Dtsche Z Chir. 1899; 51: 361-369Crossref Scopus (0) Google Scholar Most of these tests cause overt tissue damage and are unacceptable clinically, but some indicator of the degree and extent of nerve block is needed before surgery can start, as well as in comparative studies. An apparently ‘adequate’ (in extent) spinal may fail because the block has been tested using a stimulus of significantly different modality or intensity than the planned surgery. A simple single stimulus (e.g. pinprick, cold) may be blocked, but spinal cord mechanisms may result in repeated stimuli (temporal summation) or stimuli from adjacent regions (spatial summation), evoking pain and revealing a ‘failed block’. Intrathecal block is better than epidural at inhibiting spatial summation,31Curatolo M Petersen-Felix S Arendt-Nielsen L Zbinden AM. Spinal anaesthesia inhibits central temporal summation.Br J Anaesth. 1997; 78: 88-89Crossref PubMed Google Scholar and this partly explains the more profound block produced. In addition, demonstration of the segmental extent of block of one modality does not enable accurate prediction of any other.149White JL Stevens RA Beardsley D Teague PJ Kao TC. Differential epidural block. Does the choice of local anesthetic matter?.Reg Anesth. 1994; 19: 335-338PubMed Google Scholar In general, however, loss of cold sensation is observed at a higher dermatomal level than pinprick,83Malinovsky JM Renaud G Le Corre P et al.Intrathecal bupivacaine in humans: influence of volume and baricity of solutions.Anesthesiology. 1999; 91: 1260-1266Crossref PubMed Scopus (0) Google Scholar, 114Rocco AG Raymond SA Murray E Dhingra U Freiberger D. Differential spread of blockade of touch, cold, and pinprick during spinal anesthesia.Anesth Analg. 1985; 64: 917-923Crossref PubMed Google Scholar which in turn is higher than the level at which touch is lost,17Brull SJ Greene NM. Time-courses of zones of differential sensory blockade during spinal anesthesia with hyperbaric tetracaine or bupivacaine.Anesth Analg. 1989; 69: 342-347Crossref PubMed Google Scholar although there is variation even in this observation.18Brull SJ Greene NM. Zones of differential sensory block during extradural anaesthesia.Br J Anaesth. 1991; 66: 651-655Crossref PubMed Google Scholar Many methods can be used to test a block, but they fall broadly into one of two groups: assessment of either afferent (sensory) or efferent (motor or autonomic) function. Pinprick and cold are probably used most often, but mechanical stimuli such as touch, skin pinch,152Yukioka H Terai T Fujimori M. Self-assessment of the cephalad analgesia level after spinal or epidural anesthesia.Reg Anesth. 1992; 17: 95-98PubMed Google Scholar pressure,41Fassoulaki A Sarantopoulos C Zotou M Karabinis G. Assessment of the level of sensory block after subarachnoid anesthesia using a pressure palpator.Anesth Analg. 1999; 88: 398-401PubMed Google Scholar Von Frey hairs76Liu SS Ware PD. Differential sensory block after spinal bupivacaine in volunteers.Anesth Analg. 1997; 84: 115-119Crossref PubMed Google Scholar and gas jets59Hughes JC Harmer M. A new gas jet method for the assessment of sensory block after spinal anaesthesia.Anaesthesia. 1998; 53: 197-200Crossref PubMed Google Scholar can be used. Generally, loss of sensation to cold occurs before pinprick, and both of these before touch, each stage correlating with inhibition of C, Aδ and Aβ fibres, respectively.75Liu S Kopacz DJ Carpenter RL. Quantitative assessment of differential sensory nerve block after lidocaine spinal anesthesia.Anesthesiology. 1995; 82: 60-63Crossref PubMed Scopus (0) Google Scholar Thus, temperature perception is lost before pinprick, is generally at a higher level and is usually assessed by the application of ‘cold’ using alcohol,114Rocco AG Raymond SA Murray E Dhingra U Freiberger D. Differential spread of blockade of touch, cold, and pinprick during spinal anesthesia.Anesth Analg. 1985; 64: 917-923Crossref PubMed Google Scholar ethyl chloride, a cold gel bag,30Curatolo M Petersen-Felix S Arendt-Nielsen L et al.Adding sodium bicarbonate to lidocaine enhances the depth of epidural blockade.Anesth Analg. 1998; 86: 341-347Crossref PubMed Google Scholar ice75Liu S Kopacz DJ Carpenter RL. Quantitative assessment of differential sensory nerve block after lidocaine spinal anesthesia.Anesthesiology. 1995; 82: 60-63Crossref PubMed Scopus (0) Google Scholar or cooling thermodes,12Brennum J Nielsen PT Horn A Arendt-Nielsen L Secher NH. Quantitative sensory examination of epidural anaesthesia and analgesia in man; dose-response effect of bupivacaine.Pain. 1994; 56: 315-326Abstract Full Text PDF PubMed Scopus (0) Google Scholar although warming thermodes and warm air123Shah J Ayorinde BT Rowbotham DJ Buggy DJ. Warm air sensation for assessment of block after spinal anaesthesia.Br J Anaesth. 2000; 84: 399-400Crossref PubMed Google Scholar can be used. Loss of vibration and proprioceptive sensation have also been used.101Parry MG Fernando R Bawa GP Poulton BB. Dorsal column function after epidural and spinal blockade: implications for the safety of walking following low-dose regional analgesia for labour.Anaesthesia. 1998; 53: 382-387Crossref PubMed Scopus (0) Google Scholar More definitive assessment of pain sensation has been attempted with tetanic stimulation using peripheral nerve stimulators,44Gerancher JC Carpenter RL. The peripheral nerve stimulator: a monitor during continuous spinal anesthesia. Case report.Reg Anesth. 1996; 21: 480-481PubMed Google Scholar, 87Meyer RM McCune WJ. Assessing the level of spinal anesthesia using a neuromuscular stimulator.Anesthesiology. 1987; 67: 125-127Crossref PubMed Google Scholar and transcutaneous electrical nerve stimulation,36Dyhre H Renck H Andersson C. Assessment of sensory block in epidural anaesthesia by electric stimulation.Acta Anaesthesiol Scand. 1994; 38: 594-600Crossref PubMed Google Scholar both of which correlate well with surgical incision,116Sakura S Sakaguchi Y Shinzawa M Hara K Saito Y. The assessment of dermatomal level of surgical anesthesia after spinal tetracaine.Anesth Analg. 2000; 90: 1406-1410Crossref PubMed Google Scholar and assessment of somatosensory evoked potentials.82Lund C Selmar P Hansen OB Kehlet H. Effect of intrathecal bupivacaine on somatosensory evoked potentials following dermatomal stimulation.Anesth Analg. 1987; 66: 809-813PubMed Google Scholar Chemical stimulation with capsaicin, mustard oil, hypertonic saline, bradykinin, serotonin or substance P induce experimental pain but are ineffective on intact skin. Ischaemic limb pain103Petersen-Felix S Luginbuhl M Schnider TW Curatolo M Arendt-Nielsen L Zbinden AM. Comparison of the analgesic potency of xenon and nitrous oxide in humans evaluated by experimental pain.Br J Anaesth. 1998; 81: 742-747Crossref PubMed Google Scholar is too diffuse to be of any use in defining extent of block. As a block extends cephalad, there is progressive impairment of motor as well as sensory function. The commonest method of assessment is the modified Bromage scale15Bromage PR. A comparison of the hydrochloride and carbon dioxide salts of lidocaine and prilocaine in epidural analgesia.Acta Anaesthesiol Scand Suppl. 1965; 16: 55-69Crossref PubMed Google Scholar (Table 1). This gives no more than a crude mix of information on both the spread and degree of motor block in the lumbosacral distribution. Force transducer systems can be used to measure the degree of motor block at specific joints,46Graham AC McClure JH. Quantitative assessment of motor block in labouring women receiving epidural analgesia.Anaesthesia. 2001; 56: 470-476Crossref PubMed Scopus (0) Google Scholar, 154Zaric D Nydahl PA Philipson L Samuelsson L Heierson A Axelsson K. The effect of continuous lumbar epidural infusion of ropivacaine (0.1%, 0.2%, and 0.3%) and 0.25% bupivacaine on sensory and motor block in volunteers: a double-blind study.Reg Anesth. 1996; 21: 14-25PubMed Google Scholar but the complexities of muscle actions and levels of innervation mean that any estimation of the precise level of block will be poor. Thoracic nerve block paralyses the abdominal wall and intercostal muscles, and can be quantified using electromyography153Zaric D Axelsson K Philipson L et al.Blockade of the abdominal muscles measured by EMG during lumbar epidural analgesia with ropivacaine—a double-blind study.Acta Anaesthesiol Scand. 1993; 37: 274-280Crossref PubMed Google Scholar and pulmonary function tests,43Freund FG. Respiratory effects of subarachnoid and epidural block.Clin Anesth. 1969; 2: 97-107PubMed Google Scholar respectively. Although the effects are proportional to the height of the block, they are too non-specific to be used to identify the level accurately.Table 1Modified Bromage score used to assess motor power15Bromage PR. A comparison of the hydrochloride and carbon dioxide salts of lidocaine and prilocaine in epidural analgesia.Acta Anaesthesiol Scand Suppl. 1965; 16: 55-69Crossref PubMed Google ScholarGradeDefinition0No motor block1Inability to raise extended leg; able to move knees and feet2Inability to raise extended leg and move knee; able to move feet3Complete block of motor limb Open table in a new tab Sympathetic block leads to cardiovascular changes. Hypotension and bradycardia are related to block height, but again are too non-specific. Vasomotor responses47Gratadour P Viale JP Parlow J et al.Sympathovagal effects of spinal anesthesia assessed by the spontaneous cardiac baroreflex.Anesthesiology. 1997; 87: 1359-1367Crossref PubMed Scopus (29) Google Scholar can be used to detect neuronal integrity, and can be detected by colour and temperature changes in the affected area using thermography,26Chamberlain DP Chamberlain BD. Changes in the skin temperature of the trunk and their relationship to sympathetic blockade during spinal anesthesia.Anesthesiology. 1986; 65: 139-143Crossref PubMed Google Scholar but are less reliable signs39Faes TJ Wagemans MF Cillekens JM Scheffer GJ Karemaker JM Bertelsmann FW. The validity and reproducibility of the skin vasomotor test–studies in normal subjects, after spinal anaesthesia, and in diabetes mellitus.Clin Auton Res. 1993; 3: 319-324Crossref PubMed Scopus (0) Google Scholar and occur at a higher level of block than sensory changes.26Chamberlain DP Chamberlain BD. Changes in the skin temperature of the trunk and their relationship to sympathetic blockade during spinal anesthesia.Anesthesiology. 1986; 65: 139-143Crossref PubMed Google Scholar The vasoconstrictive response in the skin of the upper limb to both pinprick and cold stimulation has been claimed to be a good indicator of block height,60Ikuta Y Shimoda O Ushijima K Terasaki H. Skin vasomotor reflex as an objective indicator to assess the level of regional anesthesia.Anesth Analg. 1998; 86: 336-340Crossref PubMed Google Scholar although whether it offers anything over subjective response to sensory stimulation is unclear. Some of the more complex methods described above are impractical in the routine clinical situation and require significant support for research purposes. They also assess very specific aspects of nerve function. At the other extreme, the experienced clinician may use very little formal testing, relying on little more than noting early onset of lower limb weakness and the expected cardiovascular changes, perhaps supplemented by a surreptitious pinch of the surgical wound site. Such confidence is, of course, underpinned by thorough knowledge of how drugs spread through the CSF and the result expected from a particular injection. However, some clinical situations require documentation of block extent (especially Caesarean section), and studies comparing different techniques demand a reliable method of assessment. Cold, most commonly applied as an ethyl chloride spray, is popular, but usually defines a level of block somewhat above that providing ‘surgical’ anaesthesia. In addition, ethyl chloride is an atmospheric pollutant. Gentle pinprick has the advantages of being simple, repeatable and reproducible and can be applied without patient awareness. It also allows discrimination between ‘sharp’ and ‘dull’, and if these two levels of block are close together then the level of ‘surgical’ anaesthesia is usually not far away either. This is the method of assessment used in the majority of studies considered below. The CSF of the vertebral canal occupies the narrow (2–3 mm deep) space surrounding the spinal cord and cauda equina, and enclosed by the arachnoid mater. As the local anaesthetic solution is injected, it will spread initially by displacement of CSF and as a result of any currents created within the CSF. The next stage, which may well be the most crucial, is spread due to the interplay between the densities of both CSF and local anaesthetic solution under the influence of gravity. Gravity will be ‘applied’ through patient position (supine, sitting, etc.) and, in any horizontal position, by the influence of the curves of the vertebral canal. Many factors are said to affect these mechanisms (Table 2),48Greene NM. Distribution of local anesthetic solutions within the subarachnoid space.Anesth Analg. 1985; 64: 715-730Crossref PubMed Google Scholar with some having greater impact than others. The key ones are the physical characteristics of CSF and the solution injected, the clinical technique used and the patient's general features. These interrelate in complex ways and it is important that comparative studies are designed in such a way that two groups of patients receive a technique that differs in one factor only. Often that is not the case.Table 2Factors affecting intrathecal spread of local anaesthetics, modified from Greene48Greene NM. Distribution of local anesthetic solutions within the subarachnoid space.Anesth Analg. 1985; 64: 715-730Crossref PubMed Google ScholarCharacteristics of the injected solution Baricity Volume/dose/concentration Temperature of injectate Viscosity AdditivesClinical technique Patient position Level of injection Needle type/alignment Intrathecal catheters Fluid currents Epidural injectionPatient characteristics Age Height Weight Sex Intra-abdominal pressure Spinal anatomy Lumbosacral cerebrospinal fluid volume Pregnancy Open table in a new tab Once bulk spread of the injectate under the influence of the physical forces outlined above is complete, the final stage is diffusion of the drug through the CSF and into the nervous tissue. CSF is an isotonic, aqueous medium with a constitution similar to interstitial fluid. The terms density, specific gravity and baricity define its physical characteristics, but are often used loosely and interchangeably, causing confusion. Precise definitions are as follows. Density is the ratio of the mass of a substance to its volume. It varies with temperature, which must be specified. Specific gravity is the ratio of the density of a substance to a standard. It is usual to relate local anaesthetic solutions at 20°C to water at 4°C. Baricity is analogous to specific gravity, but the ratio is the densities of local anaesthetic and CSF, both at 37°C. The units of density are weight per unit volume; the other two characteristics, being ratios, have no units. The mean density of CSF at 37°C is 1.0003 g litre−1, with a range of 1.0000–1.0006 (± 2sd) g litre−1. It is worth noting that all the physiological variation is within the fourth place of decimals. Unfortunately, however, many investigators fail to measure density to the fourth decimal place, which makes interpretation of their studies difficult. Given the normal variation, it is necessary that solutions that are to be predictably hypobaric or hyperbaric in all patients have baricities below 0.9990 or above 1.0010, respectively.13Bridenbaugh PO Greene NM Brull SJ. Spinal (subarachnoid) neural blockade.in: Cousins MJ Bridenbaugh PO Neural Blockade in Clinical Anesthesia and Management of Pain. 3rd Edn. Lippincott Raven, Philadelphia1998: 203-241Google Scholar Most glucose-free solutions used intrathecally are just hypobaric95Nicol ME Holdcroft A. Density of intrathecal agents.Br J Anaesth. 1992; 68: 60-63Crossref PubMed Google Scholar, 100Parlow JL Money P Chan PS Raymond J Milne B. Addition of opioids alters the density and spread of intrathecal local anesthetics? An in vitro study.Can J Anaesth. 1999; 46: 66-70Crossref PubMed Google Scholar but behave in a hyperbaric manner if cooled to 5°C before injection.88Mignonsin D Tavares DA Kane M Bondurand A. The effect of the local anesthetic temperature on spinal anesthesia using 0.5% bupivacaine.Cah Anesthesiol. 1992; 40: 337-341PubMed Google Scholar, 128Stienstra R Gielen M Kroon JW Van Poorten F. The influence of temperature and speed of injection on the distribution of a solution containing bupivacaine and methylene blue in a spinal canal model.Reg Anesth. 1990; 15: 6-11PubMed Google Scholar Commercially available plain bupivacaine has a baricity of 0.9990,48Greene NM. Distribution of local anesthetic solutions within the subarachnoid space.Anesth Analg. 1985; 64: 715-730Crossref PubMed Google Scholar which means that it is only just on the edge of being hypobaric, and is best referred to as ‘plain’. CSF density is lower in women than in men,121Schiffer E Van Gessel E Gamulin Z. Influence of sex on cerebrospinal fluid density in adults.Br J Anaesth. 1999; 83: 943-944Crossref PubMed Google Scholar in pregnant than in non-pregnant women,113Richardson MG Wissler RN. Density of lumbar cerebrospinal fluid in pregnant and nonpregnant humans.Anesthesiology. 1996; 85: 326-330Crossref PubMed Google Scholar and in premenopausal women compared with postmenopausal women and men.81Lui AC Polis TZ Cicutti NJ. Densities of cerebrospinal fluid and spinal anaesthetic solutions in surgical patients at body temperature.Can J Anaesth. 1998; 45: 297-303Crossref PubMed Google Scholar Theoretically, these differences could lead to differences in the movement of a particular solution in the various patient groups (e.g. a solution that is isobaric in men may be hyperbaric in pregnant women), but the differences between groups are small and probably unimportant clinically. Almost 100 years ago, Barker was the first to study systematically the factors affecting intrathecal spread. Using glass models of the spinal canal and coloured solutions, he deduced that gravity and the curves of the vertebral column (Fig. 1) could be used to influence the spread of solutions made hyperbaric by the addition of glucose.7Barker AE. Clinical experiences with spinal analgesia in 100 cases.Br Med J. 1907; 1: 665Crossref PubMed Google Scholar Babcock employed the opposite approach, using solutions made hypobaric by the addition of alcohol,5Babcock WW. Spinal anaesthesia: with report of surgical clinics.Surg Gynaecol Obstet. 1912; 15: 606-622Google Scholar while Pitkin used alcohol and strychnine in ‘Spinocain’.107Pitkin GP. Spinocain: the controllable spinal anaesthetic.Br Med J. 1929; 2: 189Crossref Scopus (3) Google Scholar Given the neurotoxic effects of such substances, it is not surprising that the addition of glucose is the only method of altering baricity to remain in routine use. The usual choice for the clinician is between a hyperbaric solution and one with a baricity at, or just below, that of the CSF. Hyperbaric solutions are more predictable, with greater spread in the direction of gravity138Tetzlaff JE O’Hara J Bell G Grimm K Yoon HJ. Influence of baricity on the outcome of spinal anesthesia with bupivacaine for lumbar spine surgery.Reg Anesth. 1995; 20: 533-537PubMed Google Scholar and less interpatient variability.16Brown DT Wildsmith JA Covino BG Scott DB. Effect of baricity on spinal anaesthesia with amethocaine.Br J Anaesth. 1980; 52: 589-596Crossref PubMed Scopus (0) Google Scholar In contrast, most plain solutions exhibit greater variability in effect and are less predictable,16Brown DT Wildsmith JA Covino BG Scott DB. Effect of baricity on spinal anaesthesia with amethocaine.Br J Anaesth. 1980; 52: 589-596Crossref PubMed Scopus (0) Google Scholar131Stienstra R van Poorten JF. Plain or hyperbaric bupivacaine for spinal anesthesia.Anesth Analg. 1987; 66: 171-176Crossref PubMed Google Scholar148Vercauteren MP Coppejans HC Hoffmann VL Saldien V Adriaensen HA. Small-dose hyperbaric versus plain bupivacaine during spinal anesthesia for cesarean section.Anesth Analg. 1998; 86: 989-993Crossref PubMed Google Scholar so that the block may either be too low, and therefore inadequate for surgery, or excessively high, causing side-effects.135Taivainen T Tuominen M Rosenberg PH. Spinal anaesthesia with hypobaric 0.19% or plain 0.5% bupivacaine.Br J Anaesth. 1990; 65: 234-236Crossref PubMed Scopus (0) Google Scholar The greater mean spread of hyperbaric solutions may be associated with an increased incidence of cardiorespiratory side-effects,91Moller IW Fernandes A Edstrom HH. Subarachnoid anaesthesia with 0.5% bupivacaine: effects of density.Br J Anaesth. 1984; 56: 1191-1195Crossref PubMed Google Scholar although this is not always the case,29Critchley LA Morley AP Derrick J. The influence of baricity on the haemodynamic effects of intrathecal bupivacaine 0.5%.Anaesthesia. 1999; 54: 469-474Crossref PubMed Scopus (0) Google Scholar, 148Vercauteren MP Coppejans HC Hoffmann VL Saldien V Adriaensen HA. Small-dose hyperbaric versus plain bupivacaine during spinal anesthesia for cesarean section.Anesth Analg. 1998; 86: 989-993Crossref PubMed Google Scholar and may depend on the concentration of the glucose. Commercially available solutions contain up to glucose 8%, but most of the evidence shows that any concentration in excess of 0.8% will produce a solution that behaves in a hyperbaric manner (Fig. 2), but with somewhat less extensive spread if the glucose concentration is at the lower end of the range.6Bannister J McClure JH Wildsmith JA. Effect of glucose concentration on the intrathecal spread of 0.5% bupivacaine.Br J Anaesth. 1990; 64: 232-234Crossref PubMed Google Scholar28Connolly C McLeod GA Wildsmith JA. Spinal anaesthesia for Caesarean section with bupivacaine 5 mg ml−1 in glucose 8 or 80 mg ml−1.Br J Anaesth. 2001; 86: 805-807Crossref PubMed Scopus (0) Google Scholar29Critchley LA Morley AP Derrick J. The influence of baricity on the haemodynamic effects of intrathecal bupivacaine 0.5%.Anaesthesia. 1999; 54: 469-474Crossref PubMed Scopus (0) Google Scholar71Kokki H Hendolin H. Hyperbaric bupivacaine for spinal anaesthesia in 7–18 yr old children: comparison of bupivacaine 5 mg ml−1 in 0.9% and 8% glucose solutions.Br J Anaesth. 2000; 84: 59-62Crossref PubMed Google Scholar91Moller IW Fernandes A Edstrom HH. Subarachnoid anaesthesia with 0.5% bupivacaine: effects of density.Br J Anaesth. 1984; 56: 1191-1195Crossref PubMed Google Scholar133Sumi M Sakura S Sakaguchi Y Saito Y Kosaka Y. Comparison of glucose 7.5% and 0.75% with or without phenylephrine for tetracaine spinal anaesthesia.Can J Anaesth. 1996; 43: 1138-1143Crossref PubMed Scopus (9) Google Scholar150Whiteside JB Burke D Wildsmith JA. Spinal anaesthesia with ropivacaine 5 mg ml−1 in glucose 10 mg ml−1 or 50 mg ml−1.Br J Anaesth. 2001; 86: 241-244Crossref PubMed Scopus (0) Google Scholar The interplay between baricity and posture is considered later.Fig 2Range of maximum spinal block heights seen with three different solutions of ropivacaine 0.5%, containing glucose 0, 10 and 50 mg ml−1, and with densities of 0.99940, 1.00273 and 1.01531 g ml−1 respectively, injected at L2/3 or L3/4. Figure reproduced, with permission, from Whiteside and colleagues.150Whiteside JB Burke D Wildsmith JA. Spinal anaesthesia with ropivacaine 5 mg ml−1 in glucose 10 mg ml−1 or 50 mg ml−1.Br J Anaesth. 2001; 86: 241-244Crossref PubMed Scopus (0) Google ScholarView Large Image Figure ViewerDownload (PPT) Clearly, it is impossible to change one of these factors without changing another, but this is not always appreciated. For example, many studies purporting to show an effect of volume fail to change the concentration of local anaesthetic, with a consequent increase in the dose administered. When the effect of volume (up to 14 ml) is isolated from other factors, most studies suggest there is no significant influence on mean spread.8Ben David B Levin H Solomon E Admoni H Vaida S. Spinal bupivacaine in ambulatory surgery: the effect of saline dilution.Anesth Analg. 1996; 83: 716-720Crossref PubMed Google Scholar9Bengtsson M Malmqvist LA Edstrom HH. Spinal analgesia with glucose-free bupivacaine—effects of volume and concentration.Acta Anaesthesiol Scand. 1984; 28: 583-586Crossref PubMed Google Scholar73Lanz E Schmitz D. No effect of injection volume on sensory and motor blockade in isobaric spinal anesthesia.Reg Anesth. 1990; 13: 153-158Google Scholar79Logan MR McClure JH Wildsmith JA. Plain bupivacaine: an unpredictable spinal anaesthetic agent.Br J Anaesth. 1986; 58: 292-296Crossref PubMed Google Scholar83Malinovsky JM Renaud G Le Corre P et al.Intrathecal bupivacaine in humans: influence of volume and baricity of solutions.Anesthesiology. 1999; 91: 1260-1266Crossref PubMed Scopus (0) Google Scholar144Van Zundert AA Grouls RJ. Korsten HH. Lambert DH. Spinal anesthesia. Volume or concentration—what matters?.Reg Anesth. 1996; 21: 112-118PubMed Google Scholar However, one study has reported that volume is an important determinant of the spread of a truly isobaric solution.68King HK Wooten DJ. Effects of drug dose, volume, and concentration on spinal anesthesia with isobaric tetracaine.Reg Anesth. 1995; 20: 45-49PubMed Google Scholar Low volume injections (1.5–2 ml) may reduce mean spread.4Axelsson KH Edstrom HH Sundberg AE Widman GB. Spinal anaesthesia with hyperbaric 0.5% bupivacaine: effects of volume.Acta Anaesthesiol Scand. 1982; 26: 439-445Crossref PubMed Scopus (36) Google Scholar, 122Schmidt A Schwagmeier R Broja E Nolte H. The effect of volume and dosage of isobaric bupivacaine on the sensory spread of spinal anesthesia.Reg Anesth. 1990; 13: 159-162Google Scholar Similar basic concerns apply to studies of the effects of different doses: a change in dose will be accompanied by a change in either volume or concentration. Some studies designed to control for changes in the other factors have shown that increased dose is associated with increased spread,8Ben David B Levin H Solomon E Admoni H Vaida S. Spinal bupivacaine in ambulatory surgery: the effect of saline dilution.Anesth Analg. 1996; 83: 716-720Crossref PubMed Google Scholar34De Simone CA Leighton BL. Norris MC. Spinal anesthesia for cesarean delivery. A comparison of two doses of hyperbaric bupivacaine.Reg Anesth. 1995; 20: 90-94PubMed Google Scholar66Khaw KS Ngan Kee WD Wong EL Liu JY Chung R. Spinal ropivacaine for cesarean section: a dose-finding study.Anesthesiology. 2001; 95: 1346-1350Crossref PubMed Google Scholar77Liu SS Ware PD Allen HW Neal JM Pollock JE. Dose-response characteristics of spinal bupivacaine in volunteers. Clinical implications for ambulatory anesthesia.Anesthesiology. 1996; 85: 729-736Crossref PubMed Scopus (0) Google Scholar109Povey HM Olsen PA Pihl H Jacobsen J. High dose spinal anaesthesia with