Regional anaesthesia for bilateral upper limb surgery: a review of challenges and solutions.
Abstract: Regional anaesthesia for bilateral upper limb surgery can be challenging, yet surgeons are becoming increasingly interested in performing bilateral procedures at the same operation. Anaesthetists have traditionally avoided bilateral brachial plexus block due to concerns about local anaesthetic toxicity, phrenic nerve block and pneumothorax. We discuss these three concerns and review whether advances in ultrasound guidance and nerve catheter techniques should make us reconsider our options. A search of Medline and EMBASE from 1966 to January 2009 was conducted using multiple search terms to identify techniques of providing anaesthesia or analgesia for bilateral upper limb surgery and potential side-effects. Ultrasound imaging and nerve catheter techniques have led to a reduction in dose requirements for effective blocks without side-effects. Effective regional anaesthesia can be performed for bilateral surgery while remaining within recommended safe dose limits. Spacing blocks apart in time can further reduce potential toxicity issues, such that peak absorption rates for each block do not coincide. Since phrenic nerve block remains an issue even with low doses of local anaesthesia, bilateral interscalene blocks are still not recommended. Peripheral nerve blocks have excellent safety profiles and are ideal for ultrasound guidance. Regional anaesthesia can be a suitable option for bilateral upper limb surgery. Key Words: regional anaesthesia techniques, local anaesthetic, peripheral nerve block, brachial plexus, ultrasound
Article Type: Report
Subject: Anesthesia (Dosage and administration)
Anesthesia (Complications and side effects)
Extremities (Anatomy) (Care and treatment)
Surgery (Management)
Authors: Holborow, J.
Hocking, G.
Pub Date: 03/01/2010
Publication: Name: Anaesthesia and Intensive Care Publisher: Australian Society of Anaesthetists Audience: Academic Format: Magazine/Journal Subject: Health Copyright: COPYRIGHT 2010 Australian Society of Anaesthetists ISSN: 0310-057X
Issue: Date: March, 2010 Source Volume: 38 Source Issue: 2
Topic: Event Code: 200 Management dynamics Computer Subject: Company business management
Product: Product Code: 8000410 Surgical Procedures NAICS Code: 62 Health Care and Social Assistance
Geographic: Geographic Scope: United States Geographic Code: 1USA United States
Accession Number: 225792540
Full Text: Surgeons are becoming increasingly interested in performing bilateral procedures at the same operation and this poses a challenge to the anaesthetist considering regional anaesthesia. While bilateral lower limb surgery has the easy option of central neuroaxial blockade, this is not a routine option for upper limb surgery. Concerns are raised regarding the large doses of local anaesthetic (LA) required and the risk of serious bilateral adverse effects such as phrenic nerve block or pneumothorax. However, there have been several advances in regional anaesthesia such that these concerns may need to be reconsidered.

Within the last decade, ultrasound-guided regional anaesthesia and continuous nerve catheter techniques have become increasingly popular. Use of ultrasound allows imaging of the needle, nerves, surrounding anatomical structures and LA spread. Needle insertion points are no longer constrained by reproducible external anatomical landmarks. Unlike landmark-based techniques, ultrasound allows the needle and LA to be placed where it is less likely to cause unwanted side-effects. Approaches previously less popular, such as the supraclavicular block and individual peripheral nerve blocks, have been undergoing a renaissance. Many anaesthetists are also becoming more confident using smaller doses of LA to achieve similar results (1-3). Continuous nerve catheter techniques allow doses to be titrated and extend the duration of the block well into the postoperative period. No longer do large doses of the long-acting (and potentially more toxic) LA need to be administered as a single bolus. By reducing the risk of toxicity and dose-related adverse effects (3), the option of bilateral blocks could be reconsidered. We now regularly undertake bilateral joint replacements in our area. While the demand for bilateral elective surgery may increase, it is probably in the field of trauma that bilateral regional anaesthesia of the upper limb will have most benefit. Avoidance of general anaesthesia can allow ongoing monitoring such as when there is coexistent head injury (4).

We recently managed several cases of bilateral upper limb trauma using a variety of regional anaesthetic techniques. Consequently, we decided to review the literature to determine what evidence exists to guide management of bilateral upper limb surgery. The three main concerns of bilateral brachial plexus blockade are LA toxicity, phrenic nerve block and pneumothorax. The aim of this review is to discuss strategies to minimise these problems, and to determine whether the use of ultrasound and continuous nerve catheter techniques have added benefits. We also aim to make suggestions to guide anaesthetists.

METHODS

A search of Medline and EMBASE from 1966 to January 2009 was conducted using the terms "bilateral", "upper limb", "brachial plexus", "analgesia", "anaesthesia", "local anaesthesia", "toxicity", "pharmacokinetics", "phrenic nerve", "pneumothorax", "nerve block" and combinations of these keywords. We limited the search to articles written in the English language. The aim of this search was to identify those papers referring to techniques of providing anaesthesia or analgesia for bilateral upper limb surgery and potential side-effects. Articles obtained were reviewed for relevance and the reference lists checked for additional papers. Once the relevant issues associated with the techniques were identified, further checks of Medline and EMBASE were performed to identify additional papers.

Local anaesthetic toxicity

Local anaesthetic toxicity is complex and is determined by multiple factors including individual susceptibility and the magnitude and rate of change in plasma concentration of the free fraction of LA. The incidence of LA-induced seizure after a peripheral nerve block is approximately 0.01 to 0.2% (5-7) and decreasing. Avoidance of toxicity involves knowledge of the minimum effective dose to achieve reliable surgical anaesthesia, maximum allowable dose and strategies for avoiding rapid changes or high peak plasma concentrations.

In most cases, we do not need to exceed the recommended safe dose as both upper limbs can be effectively blocked within these limits. Simple measures can be employed that make toxicity even more unlikely. Regional techniques supplemented by general anaesthesia remove full reliance on the block to provide prompt, complete surgical anaesthesia. Intraoperative and postoperative analgesia can be achieved with smaller doses of LA. The surgery on each side can be performed as two separate operations under regional anaesthesia alone, early and late on the same day or on separate days. The two blocks are therefore spaced widely apart such that the second is performed when plasma LA concentrations from the first block are approaching baseline. In some cases this delay may not be clinically appropriate.

Toxicity becomes a potential issue if regional anaesthesia is used as the sole technique when bilateral surgery needs to be performed during the same operation. Fortunately this is an uncommon situation. The dose used needs to ensure block reliability but minimise the risk of systemic toxicity. For bilateral blocks, we are forced to use twice an effective anaesthetic dose, potentially increasing the risk of LA toxicity as we approach the maximum recommended dose. These patients require education regarding symptoms of toxicity, close monitoring, minimal sedation during performance of the block and other high-risk periods and an individualised approach for dose selection.

Minimum effective dose to achieve reliable surgical anaesthesia

The minimum dose requirement for each approach to the brachial plexus is not known and probably highly variable for a given individual patient and operator. Before the introduction of real-time ultrasound, large volumes and doses had often been used. This may have improved success rates by compensating for suboptimal needle placement. Doses of 300 mg ropivacaine for a single brachial plexus block were common (8,9). However, these doses of LA are unnecessary for effective nerve blockade. Ultrasound guidance compared to a multiple injection nerve stimulation technique for axillary brachial plexus blockade has similar efficacy with a success rate of 97% using ropivacaine 150 mg (10). Ultrasound provides the ability to watch the LA spread during injection, and to stop injecting once adequate spread has been observed. This has reduced dose requirements and with that, the potential for toxicity (1-3). In our institution, in conjunction with general anaesthesia, we routinely perform ultrasound-guided interscalene blocks with 75 mg of ropivacaine (20 ml 0.375%) or less. Ultrasound-guided interscalene block with only 25 mg of ropivacaine (5 ml of 0.5%) can provide equivalent analgesia to higher doses up to 24 hours postoperatively (3) and 36 mg of levobupivacaine (36 ml of 0.1%) produces similar effects to higher doses and volumes (11). Although these doses are for analgesia rather than anaesthesia, it illustrates that with accurate selective placement, the large doses previously used are unnecessary. Adjuncts are often added to local anaesthetic to increase the duration of analgesia but there is little evidence to determine whether adjuncts can specifically allow dose reduction.

Ultimately the dose required for a given patient is individual and depends on the accuracy of LA deposition, experience and skill of the operator and inter-individual variability in LA sensitivity.

Maximum allowable doses

Anaesthetists are becoming more comfortable using smaller doses of LA to achieve equivalent results. This allows bilateral blocks to be performed and still remain within the maximum recommended safe dose for an individual. However, determination of the maximum allowable dose for a given individual can be difficult. Maximum recommended doses advised by pharmaceutical companies or drug advisory boards are not as scientific as we would like, since studies in this field are difficult (12). For ethical reasons, human subjects can be given only mildly toxic doses of LA and studies are terminated when initial subjective symptoms of central nervous system (CNS) toxicity start to develop. Toxicity data therefore comes mainly from animal studies or case reports and our knowledge in this area is far from complete (13). Information on more serious toxicity comes from laboratory animal studies and assumptions have to be made regarding the external validity of such results to humans. The maximal allowable dose for an individual is dependant upon the toxic threshold of the LA, the pharmacokinetics and the individual susceptibility to toxicity.

Toxic threshold

The toxic threshold is agent-specific and is the point at which a subject first starts to develop unacceptable symptoms or clinical signs due to high plasma LA concentration. Arterial and venous plasma concentrations measured in 12 healthy volunteer males following rapid intravenous infusions (10 mg/min) of ropivacaine and bupivacaine (Table 1) provide a guide to the maximum tolerated arterial and venous concentrations and intravenous dose (13). Symptoms of CNS toxicity became a problem when the arterial plasma concentration reached 0.56 mg/l (0.34 to 0.85) for ropivacaine and 0.3 mg/l (0.13 to 0.51) for bupivacaine. Venous concentrations were approximately 50% lower and far more variable. The mean tolerated intravenous dose was 115 mg of ropivacaine and 103 mg of bupivacaine. It is comforting to see that many blocks are performed using lower doses than can potentially be tolerated following direct intravenous injection.

Use of LA with the lowest toxicity is desirable but not always practical. Less toxic agents such as lignocaine, mepivacaine and prilocaine also have a shorter duration of action. These agents may suffice for quick surgical procedures but may be inappropriate for longer procedures or postoperative analgesia unless continuous nerve catheter techniques are used (2). Of the commonly used longer acting LA, ropivacaine is the least toxic followed by levobupivacaine then bupivacaine (13). In addition, early symptoms of CNS toxicity are easier to detect with ropivacaine than bupivacaine (14).

The early signs of cardiac toxicity coincide with the CNS excitatory phase and activation of the sympathetic nervous system. This can mask early myocardial depression, which only becomes apparent after arrhythmias and circulatory collapse develop (15). While all LA drugs have cardiovascular effects there is evidence that ropivacaine, unlike the others, does not reduce the ejection fraction or cardiac index (16).

Animal studies suggest that the addition of general anaesthesia exacerbates LA-induced cardiovascular depression and alters the pharmacokinetics leading to doubling of LA plasma concentrations through altered distribution and clearance (17,18). However, fatalities have occurred only in conscious study animals. Anaesthesia also elevates the threshold for CNS toxicity and early cardiovascular toxicity in humans (19).

Pharmacokinetics

By examining the rate of change in plasma LA concentration following brachial plexus blockade, we gain a better understanding of the dose that can be used before concentrations from the study by Knudsen (our best guess of a toxic threshold) are Reached (13).

Unfortunately, the pharmacokinetics of LA following brachial plexus blockade are variable and unpredictable. They are determined by multiple factors such as the drug, dose, adiposity and capillary density of the site of injection, addition of adrenaline and other patient factors such as pregnancy and uraemia. The brachial plexus has an intermediate rate of systemic absorption--lower than intercostal or epidural administration but higher than subcutaneous injection (12).

Human pharmacokinetic studies following brachial plexus blockade with ropivacaine are summarised in Table 2. Total ropivacaine levels are reported rather than 'free' levels.

The data from arterial sampling suggests that when brachial plexus blocks are performed distal to the level of the clavicle, they have a lower peak plasma concentration (Cmax) and longer time to reach this peak (Tmax) (23). Whether or not this difference has clinical implications for the risk of toxicity is unknown.

Individual susceptibility

Dose selection should be individualised. Factors which increase susceptibility have been extensively reviewed elsewhere (12) and include older age, lower weight, pregnancy, organ dysfunction, hypoxia, acidaemia and possibly epilepsy. All of these factors warrant dose reduction of 20 to 30% (12). Failure to consider these factors has resulted in examples of CNS toxicity following administration of apparently acceptable doses (24-27).

Avoiding rapid changes and minimising peak concentrations

Rapid changes in plasma LA concentration lower the toxic threshold (28). Peak concentrations and rapid changes can be minimised by avoiding intravascular injection, spacing the blocks apart in time and using continuous nerve catheter techniques. Adrenaline has also been used to reduce systemic absorption following lignocaine administration in various sites. Although the effect in the brachial plexus is less impressive than other sites, there is thought to be a reduction in the rate of absorption by 20 to 30% (12). There is limited evidence that adrenaline reduces systemic absorption of other LAs. However, when large doses of LA are being used, addition of adrenaline adds minimal risk and may provide early warning of intravascular injection. We believe adding adrenaline to LA should be considered when bilateral brachial plexus blocks are performed as the sole anaesthetic technique and close to maximum doses of LA are being used.

Avoiding intravascular injection

Onset of LA toxicity from direct intravascular injection is faster and more severe but has a shorter duration than from systemic absorption (29). Earlier detection of intravascular injection can be aided by a test dose with the addition of adrenaline, aspiration before injection and dose fractionation. Performing the regional technique in an awake, informed patient may be beneficial (29) since sedation can mask early symptoms of toxicity (30). These factors have probably contributed to the declining incidence of systemic LA toxicity.

Ultrasound imaging assists the anaesthetist to identify vascular structures and visualise the LA spread around nerves. There is currently no evidence that ultrasound reduces the risk of intravascular injection, although lack of spread in an accepted pattern may be an indicator of intravascular placement and cause the anaesthetist to stop injection, thus limiting the dose delivered.

Temporal spacing of blocks

One of the highest risk times for LA toxicity from systemic absorption is soon after performance of the block. Long-acting LA will provide surgical anaesthesia for a prolonged period such that it is not essential to block both arms sequentially. Leaving a time gap between each injection could help ensure that peak absorption from each block site does not coincide, thereby further reducing the risk of toxicity.

What remains unclear is for how long the second block should be delayed, and many timescales have been reported (Table 3). Arterial levels peak within 30 minutes (23) while venous concentrations peak at 30 to 90 minutes after unilateral brachial plexus blocks (21,22).

Most cases of CNS toxicity following unilateral brachial plexus blockade, when intravascular injection has been excluded, have occurred within 20 minutes following the injection (24,25,27,37). Satsumae performed two blocks 15 minutes apart with symptoms becoming apparent 10 minutes after the second block (26). If performing two brachial plexus blocks, it seems reasonable to allow 60 minutes between them when plasma LA concentration is decreasing. If there is significant time pressure the minimum would be 30 minutes to ensure the two peaks do not coincide. Theoretically, since peak levels from brachial plexus blocks proximal to the clavicle may occur faster than from a block distal to the clavicle (23), the more proximal block could be done first to avoid both peaks in plasma levels occurring simultaneously. This could add a further margin of safety although studies would be needed to confirm this hypothesis.

Continuous nerve catheter techniques

Continuous nerve catheter techniques offer several advantages. These allow titrated dosing of a less toxic LA to produce surgical anaesthesia. These agents tend to have a shorter duration of action. Repeated boluses of LA administered through the nerve catheter allow surgical anaesthesia to be maintained and analgesia continued into the postoperative period (2). In theory this reduces the risk of toxicity through lower LA dose requirements and reduction in the peak and rate of change in drug concentration.

Sandhu described a series of eight patients scheduled for bilateral upper limb surgery (2). Each patient received bilateral infraclavicular blocks using a 20 ml mixture of lignocaine, adrenaline (1:200,000) and sodium bicarbonate on each side. Surgical anaesthesia lasted 1.5 to 2.5 hours but repeated boluses of LA mixture through the nerve catheters prolonged the blocks for longer procedures lasting up to 7.5 hours.

The major limiting factor of this technique is the accuracy of catheter tip positioning, which is poorly visualised on ultrasound, and technically difficult to advance under real time imaging. Despite the advent of stimulating catheters and techniques such as injecting air or agitated dextrose to visualise the tip, this advanced regional technique can be problematic for inexperienced practitioners.

Phrenic nerve block

Phrenic nerve block is considered almost inevitable with traditional interscalene blocks. For this reason, bilateral blocks cause some concern. A technique likely to cause total diaphragmatic paralysis should be avoided where possible, especially in the presence of any additional condition impairing ventilation. There may be times however, when this may be unavoidable, such as bilateral proximal upper limb trauma. An appropriate risk benefit analysis of the options for anaesthesia must take place.

There are minimal data to show the effect of total diaphragmatic paralysis on ventilation caused by bilateral phrenic nerve block in humans. While we may be concerned that vital capacity can be reduced by half (38), studies in awake dogs show ventilation is preserved because of a marked increase in rib cage expansion, reflecting intercostal and accessory muscle activity (39). Patients are also able to survive with bilateral idiopathic diaphragmatic paralysis (40).

Bilateral interscalene catheters have been used as an analgesic adjunct to general anaesthesia for bilateral shoulder arthroplasty (35). Total diaphragmatic paralysis reduced the forced vital capacity by 60%. Oxygen saturations were maintained above 92% while supine but the patient required postoperative monitoring of ventilatory function in the intensive care unit. Diaphragmatic dysfunction persisted at 72 hours, although there was a difference between sides, which could be explained by more proximal placement of the catheter tip on the left. The economic and logistical cost of this management would be inappropriate in most cases of routine bilateral upper limb surgery. Although acceptable outcomes can be achieved following bilateral phrenic nerve block, not all our patients will have the ventilatory reserve to compensate for diaphragmatic paralysis, especially with the increasingly obese population.

Phrenic nerve block may be reduced with ultrasound guidance and low volumes of LA. Ultrasound-guided interscalene blocks using 20 ml and 5 ml of 0.5% ropivacaine were compared (3). The incidence of phrenic nerve block was reduced from 100 to 45% respectively with significant improvements in postoperative respiratory function. Ultrasound guidance reduced dose requirements and dose dependent side-effects (1-3). This is a promising improvement but it is still too high to recommend bilateral interscalene block routinely.

The incidence of phrenic nerve block after supraclavicular block is lower than for interscalene block although reported rates are highly variable. Knoblanche and Pham-Dang reported 60 to 67% for traditional supraclavicular blocks (41,42) while Cornish reported 1.5% using a bent needle technique (43). It is likely that smaller doses and volumes used as an analgesic adjunct with ultrasound guidance may also result in a lower incidence but evidence to support this is still lacking.

Phrenic nerve block following vertical infraclavicular block has been described (44). Rettig found abnormal ipsilateral hemidiaphragmatic movement in 26% of patients following 0.5 ml/kg of 0.75% ropivacaine (45). Other reports describe successful bilateral infraclavicular blocks without phrenic nerve block or deterioration in respiratory function (2,31,46), which is consistent with our own personal experience.

The obvious way to avoid bilateral phrenic nerve block is to avoid approaches that predispose to this complication and choose an alternative such as infraclavicular, axillary or individual peripheral nerve blockade. This would be more difficult in cases of proximal upper limb surgery.

Pneumothorax

The classical supraclavicular approach, with paraesthesia for nerve localisation, has an incidence of pneumothorax of 0.3 to 6% (47). The incidence using ultrasound is not yet known, but is widely regarded to be much lower. To our knowledge there is no published case of pneumothorax with ultrasound-guided supraclavicular nerve blocks, however, one case has been indirectly mentioned (48). Given the resurgence of this block now that ultrasound is more widespread, lack of reported complications would suggest a much lower incidence.

The incidence for infraclavicular blocks is not known. There are several published cases (49,50), however none of these utilised ultrasound guidance. More distal approaches to the brachial plexus, including individual peripheral nerve blocks, should avoid this complication altogether.

Individual peripheral nerve blocks

Prior to the introduction of ultrasound, individual peripheral nerve blockade in the upper limb was rarely practised, except to salvage incomplete brachial plexus blockade. However, these blocks can be effectively used as regional techniques in their own right, as is becoming increasingly common in our institution.

We often perform individual peripheral nerve blocks in the proximal forearm bilaterally or in conjunction with a contralateral brachial plexus block to reduce or eliminate the concerns associated with bilateral brachial plexus block. Small doses of LA are required to block each individual nerve. Recent studies suggest peripheral nerves can be blocked using less than 1 ml of LA (51). Ultrasound guidance also allows the nerves to be targeted at sites where they do not lie next to vessels, eliminating the risk of intravascular injection. We postulate that the use of a block distal to the tourniquet may further decrease the risk of LA absorption but separate measures, such as deep sedation or general anaesthesia, would be needed to deal with tourniquet-induced pain.

Peripheral nerve blocks are superficial and ergonomically favourable for ultrasound guidance. Provided that doses are kept within accepted recommendations, the only serious side-effects are nerve and blood vessel injury, both of which are very rare in these locations. Performing individual peripheral nerve blocks with ultrasound guidance gives added flexibility. Once the nerve has been identified, it can be traced proximally or distally to choose the best needle insertion site.

The use of ultrasound for individual peripheral nerve blocks reduces block performance and onset time of complete sensory block allowing surgery to progress earlier (10,52-61). This may be an important consideration in some situations. Ultrasound guidance may also reduce the number of needle passes (10,60,62) and prolong block duration (54,63). Whether ultrasound reduces the risk of rare complications such as haematoma or nerve injury is extremely difficult to prove and currently there is inadequate evidence in the literature to assess this.

Performance of multiple peripheral nerve blocks has the disadvantage of multiple injections. There is also considerable variation and overlap in the different peripheral nerve distributions, making it slightly less reliable in covering the surgical field while continuous nerve catheter techniques are less applicable.

Individual peripheral nerve blockade therefore maximises the benefits of ultrasound-guided regional anaesthesia and may provide a simple and safe alternative option on one or both sides.

RECOMMENDATIONS

Regional anaesthesia for bilateral upper limb surgery can be challenging and may increase risk. Simultaneous bilateral surgery should ideally be necessary rather than simply surgical preference. However, most patients can be managed easily while remaining well within recommended safe dose limits. The following factors should be considered before deciding on a management plan.

* Regional anaesthesia, as an analgesic adjunct to general anaesthesia, allows dose reduction, minimises the risk of toxicity or unwanted side-effects, while still providing analgesic benefit. Peripheral nerve blocks distal to the brachial plexus can be used without tourniquetrelated problems when combined with general anaesthesia. There may also be slower LA absorption as the blocks are distal to a surgical tourniquet.

* Regional blocks can be spaced apart to prevent concurrent peak absorption from each site.

* Consider adding adrenaline to slow the rate of systemic absorption and provide earlier indication of intravascular injection.

* Consider using a continuous nerve catheter technique to allow titration of LA or the use of a less toxic drug such as lignocaine. Use one of the safer longer-acting drugs, such as ropivacaine or levobupivacaine to minimise the possibility of toxicity.

* Bilateral interscalene blockade still cannot be recommended for economic and logistical reasons due to the high level of postoperative ventilatory surveillance needed.

* Bilateral supraclavicular blockade without ultrasound should be avoided. Pneumothorax with ultrasound-guided supraclavicular blockade is probably very rare, so bilateral blocks could be performed with caution using ultrasound guidance in experienced hands.

* Bilateral infraclavicular blockade, with or without ultrasound guidance, appears to be safe in experienced hands.

* Consider mixing brachial plexus blockade on one side with peripheral nerve blocks on the other if possible.

CONCLUSION

Ultrasound guidance and continuous nerve catheter techniques appear to have reduced the challenges of bilateral upper limb surgery. Local anaesthetic drugs with safer side-effect profiles are now widespread and can provide effective anaesthesia and analgesia at lower doses. Regional anaesthesia by an experienced operator can be a useful option to consider.

Accepted for publication on August 30, 2009.

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J. HOLBOROW *, G. HOCKING [[dagger]]

Department of Anaesthesia, Sir Charles Gairdner Hospital, Nedlands, Perth, Western Australia, Australia

* M.B., Ch.B., D.C.H., F.A.N.Z.C.A., Regional Fellow.

[[dagger]] M.B., Ch.B., D.A., D.M.C.C., F.R.C.A., F.A.N.Z.C.A., F.F.P.M.A.N.Z.C.A., Staff Specialist, Associate Professor, School of Medicine, University of Notre Dame Australia.

Address for correspondence: A/Prof G. Hocking, Department of Anaesthesia, Sir Charles Gairdner Hospital, Nedlands, Perth, WA 6009.
Table 1
Maximum tolerated plasma levels during intravenous infusion of
local anaesthesia in healthy volunteers. Modified from Knudsen (13).

Sample     Drug          Plasma concentration (mg/ml)
                         mean (SD) min-max

                         Total       Free

Arterial   Ropivacaine   4.3 (0.6)   0.56 (0.14) 0.34-0.85
                         3.4-5.3

           Bupivacaine   4.0 (1.4)   0.3 (0.11) 0.13-0.51
                         1.1-6.2

Venous     Ropivacaine   2.2 (0.8)   0.15 (0.08) 0.01-0.24
                         0.5-3.2

           Bupivacaine   2.1 (1.2)   0.11 (0.1) 0.01-0.38
                         0.8-4.5

Table 2
Human pharmacokinetic studies following brachial plexus blockade with
ropivacaine

Author            Size     Block           Dose

Hickey (20)       8        SCB             165 mg
Vainionpaa (21)   60       AXB             175-225 mg
Salonen (22)      60       AXB             5.1 mg/kg
Rettig (23)       30       ISB             3.75 mg/kg
Rettig (23)       30       AXB/ICB         3.75 mg/kg

Author            Sample   Cmax (mg/ml)         Tmax (min)

Hickey (20)       Ven      1.26                 52
Vainionpaa (21)   Ven      1.46 [+ or -] 0.25   36-88
Salonen (22)      Ven      2.6 [+ or -] 0.7     48
Rettig (23)       Art      3.3                  5-25
Rettig (23)       Art      2.5                  15-30

SCB=supraclavicular block, AXB=axillary block, ISB=interscalene
block, ICB=infraclavicular block, Ven=venous, Art=arterial,
Cmax=maximum plasma total ropivacaine concentration, Tmax=time to Cmax.

Table 3
Techniques reported using bilateral brachial plexus block for upper
limb surgery showing the time interval (minutes) between blocks

Author           Year            Block     Drug(s)    Dose (mg)

Dhir (31)        2008            ICB       Rop+ad     50+50
Cabellos (32)    2008            AXB       Mep        270+150
Neuburger (33)   2007            AXB       Mep+Rop    500+150
Sandhu (2)       2006            ICB       Lig+ad+B   800
Franco (34)      2004            SCB+AXB   Mep+ad     200+300
Maurer (35)      2002            ISB       Rop        150+150
Maurer (36)      2002            ISB+ICB   Rop        175+175

Author           Time interval   US        GA

Dhir (31)        30              Yes       Yes
Cabellos (32)    80              No        No
Neuburger (33)   15              No        No
Sandhu (2)       0               Yes       No
Franco (34)      10              No        No
Maurer (35)      15              No        Yes
Maurer (36)      20              No        No

US=ultrasound-guided nerve block, GA=general anaesthesia,
ICB=infraclavicular block, Rop=ropivacaine, ad=adrenaline,
AXB=axillary block, Mep=mepivacaine, Lig=lignocaine, B=bicarbonate,
SCB=supraclavicular block, ISB=interscalene block.
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