Controversies in regional anaesthesia

Chris Nixon

Guidelines and Checklists have become more common in Anaesthesia practice. They seek to improve patient care by standardizing care along best practice guidelines and are evidence based.  ASRA guidelines are written by a panel of experts based on their clinical experience, the scientific literature available at the time of writing and their expert opinion.  It is acknowledged that other experts analyzing the same information may arrive at different recommendations. It is also stated that recommendations may change as new information becomes available(1,2).  The recommendations therefore are not intended to replace clinical judgment and specific risk-benefit discussions related to individual patients
Within this practice framework, concerns relating to clinical discretion are unclear and negligence may be contested based upon the guidelines(3).  The legal position is dependent on the Bolam principle in Law where a doctor is not held liable if he follows a responsible body of medical opinion.  This creates an interesting situation where we may feel obliged to follow a guideline even though the guidelines allow some latitude, because we are unsure of whether the body of medical opinion would differ. There is also the likelihood that legal counsel would use these guidelines to define “best practice”.

The Awake or Asleep controversy.

For the first 70 years of the 20th Century, regional anaesthesia was performed in conscious awake patients.  Neuraxial blockade was an alternative to General Anaesthesia, and peripheral nerve blockade depended on seeking paraesthesia. The advent of peripheral neurostimulation by Greenblatt and Denson changed regional anaesthesia. Motor stimulation responses could be elicited in patients whether they were awake or asleep.  This brought new converts to regional anaesthesia that, for patient acceptability preferred to perform blocks on patients whilst they were asleep. This became more accepted and widespread, and perhaps more acceptable to a public who preferred to be asleep. This was particularly true in the English-speaking world, whereas in many European countries, regional techniques were preferred by patients to avoid the risks associated with general anaesthesia.
In 1998, Bromage and Benumof reported the case of a 62 yr old patient who became paraplegic following the insertion of an epidural under general anaesthesia.  They concluded that had the patient been able to report paraesthesias, the complication could have been prevented(4). The epidural was sited above a laminectomy scar and required four attempts and several episodes of hypotension occurred.  This was accompanied by an editorial which raised serious questions about the conclusions if applied to the paediatric community. The four renowned authors of this editorial were supported by 54 paediatric anaesthetists spanning the USA, Europe, and Australasia(5).
In 2000, Jonathan Benumof reported 4 patients who had sustained spinal cord injuries as a result of Interscalene blocks performed whilst they were asleep(6). Three patients had blocks performed using peripheral nerve stimulation with responses at 0.8-1mA taken as the endpoint, and one patient had a technique in which the needle was walked off the posterior aspect of C6 transverse process.  In analyzing the four cases, Benumof concluded that general anaesthesia was a relative contraindication to the performance of interscalene brachial plexus block. 
In 2004, Drasner suggested logic dictated thoracic epidural catheter insertion should be performed in the awake patient since it is inevitable that needles (or catheters) will violate the cord(7).  Benumof again suggested this risk was also true for interscalene blockade(8). 
As a result of the ongoing controversy, ASRA published a practice advisory for regional anaesthesia in anaesthetized or heavily sedated patients and made specific recommendations.  Their paper discusses the literature and proposes guidelines (9).  In the same year, ASRA published a practice advisory on Neurologic Complications in Regional anaesthesia and pain medicine(10). In the discussion, they state:”
“While acknowledging the conflicting literature relevant to this topic, the Panel’s conservative opinion is that general anesthesia or heavy sedation removes all opportunity for the patient and/or physician to recognize, report and respond to an atypical symptom during block placement”. …….”Therefore, the weight of the Panel’s opinion is that regional anesthetic or pain blocks should not be performed in adults with concurrent general anesthesia or heavy sedation except in those circumstances when the physician and patient conclude that benefit clearly outweighs risk.”  They go on to state that risk of injury may differ, ”as a function of block site” with a separate recommendation specific to interscalene block.

Questions which need to be considered which may make heavy sedation or general anaesthesia less safe are;
1. Is Paraesthesia is an early warning sign before permanent neurological injury.  - Unreliable
2. Do paraesthesiae inform the anaesthetist that he has entered the subarachnoid space and is entering the spinal cord. - Unreliable
3. Paraplegia can be avoided if the patient is awake.  -  No data
4. Standard of care dictates all epidurals placed above the termination of the spinal cord should be in awake patients.  - No data
5. Peripheral nerve injury may be prevented if the patient is awake.  No data
6. Local Anaesthetic toxicity will be recognized earlier in the awake patient enabling cessation of injection and reduced risk of cardiac arrest.  No data although general anaesthesia or sedative medication may increase the seizure threshold and thus be protective.
What is the evidence?  The two major complications of local anaesthetic injection in a patient who is not allergic to local anaesthetics are systemic toxicity and neurological damage.

Local Anaesthetic Systemic Toxicity (LAST) – and consciousness.

Guidelines:   ASRA (11);AAGBI (12,13)

The incidence of LAST was reported between 0.1to1 per thousand in 2008, from ARPEF study and the Mayo Clinic(14,15).  Barrington and Kluger reported an overall rate of 1 per 1000 in 25,336 patients in the AURORA database. Group analysis demonstrated Ultrasound accounted for 12 cases in 20,401 peripheral nerve blocks (0.58:1,000) with an odds ratio of 0.28(CI 0.12-0.65)(16). Only one case suffered a cardiac arrest during a Paravertebral block performed without ultrasound.  An interesting feature was the increasing use of ultrasound and decreased local anaesthetic dosage with time.  In 12,668  ultrasound-guided blocks, Sites recorded no seizures or cardiac arrests(17) with all patients receiving 1-4mg Midazolam and 25-100mcg fentanyl for patient comfort and anxiolysis (17). A third series reported the incidence of LAST for Ultrasound-guided peripheral nerve blockade was significantly less than for a nerve stimulator and landmark technique (0/9069 vs 6/5436; P=0.0061) (18).  The risk reduction seen in these studies may also be related to the changes in technique brought about by visualizing the target, reducing volumes and concentrations and multiple injections used for ultrasound techniques.
The warning signs of local anaesthetic toxicity are peri-oral tingling, hypertension, tachycardia, tinnitus, dizziness, seizures, coma hypotension, arrhythmia and death.  Does sedation or general anaesthesia affect the ability to detect these signs?  Firstly, only 60% of cases feature the classical signs and the risk period extends to 30 minutes after injection. (19).  Three forms of LAST are seen(20). ‘Instant’ LAST from direct IV injection of large volumes of local anaesthetic leading to rapid cardiovascular collapse and seizures. Secondly, ‘instant’ LAST from accidental intra-arterial injection of as little as 1.5ml in the neck, results in short-lived seizures and is rarely fatal. Less than 50% of LAST cases present within 1 minute of injection.  Thirdly, ‘Slow’ LAST due to absorption of local anaesthetic is dependent on the plasma free local anaesthetic concentration.  The effect may occur up to 30 minutes after injection, and is seen with large volumes of local anaesthetics.  Sedation may be protective as sensitivity is decreased to 20-40%.  The effects may not be seen until injection is completed, or may occur so rapidly the patient cannot recognize the effect. The propensity for an individual to develop LAST is not just based on dose, but also on the pharmacokinetics and pharmacodynamics of each individual and the cardiac disease is often implicated in the outcome.  Plasma concentrations of lidocaine are similar when 300mg is administered intercostally, 500mg epidurally or 1000mg subcutaneously. (Rosenberg PH et al, RAPM 2004;29:564-575)
The bottom line is that more than 50% of cases occur long after administration of the local anaesthetic. Sedation or general anaesthesia would not have influenced this. 
If detection is delayed by sedation or general anaesthesia is the outcome affected?  No data.
In summary, Ultrasound has been shown to reduce the incidence of LAST and the practice advisory from ASRA is still valid.
‘The potential ability of general anaesthesia or heavy sedation to obscure early signs of systemic local anesthetic toxicity is not a valid reason to forgo performing peripheral or epidural nerve blocks in anesthetized or heavily sedated patients. (Class 1).

Nerve Injury, and Consciousness – What we know, and don’t know

Nerve damage following a regional block may be related to direct needle trauma to the nerve, neurotoxicity of the injected agent, compression of the nerve by haematoma, tourniquet, cast or patient positioning, Estimates of increased risk in patients with pre-existing neuropathy are based on very low numbers and may overestimate the risk. It is also important to recognize surgical factors may also be causative.  Jacob has shown that despite increased use of peripheral nerve blockade for hip and knee arthroplasty, the incidence of perioperative nerve injury has remained constant(21,22). Peripheral neuropathy following shoulder surgery related to the surgical procedure has also been reported with rates for regional block lower than without block(23,24).
The incidence of nerve injury appears to be related to the data collection method. Borgeat demonstrated after interscalene block the time course of neurological complications in 700 patients.  8% reported paraesthesia, dysthesia or pain 10 days post surgery which decreased to 2.4% at I month, 0.3% at 3 months and 0.1% at 6 months. 2 patients (0.2%) had sensori-motor deficit which recovered after 19 and 28 weeks(25).  In constrast, using similar methodology, there were no neurological sequelae following 1001 continuous popliteal nerve blocks with catheters(26). Traditional estimates of neuropathy following peripheral nerve blocks were published by Auroy et al who reported 56 major complications in 158,083 regional blocks (3.5/10,000) of which 26 (0.16/1000) were short lived neurological sequelae(14).  The rate varied between blocks: 3.15/1,000 for popliteal sciatic block; 0.3/1,000 for femoral block: 0.29/1,000 for interscalene block  and 0.18/1,000 for Axillary block.  No data is given on the use of sedatives or general anaesthesia.
Comparable data from Barrington and Sites in adults give rates of post operative nerve injury as 0.4/1,000 (CI0.08-1.1) and 0.9/1,000 (CI 0.5-1.7) respectively(17,27).
None of these studies have looked at the potential for risk reduction with ultrasound, nerve stimulation, injection pressure monitoring or electrical impedence.  What effect does the needle have.  It is likely given the low incidence that we will never find out(28).
Nerve stimulation appears to be inexact in determining the distance a needle is from a nerve.  The suggestion that stimulation at currents below 0.3mA reliably indicate intraneural placement is incorrect(29).  Nerve stimulation thresholds vary widely and may be >1mA. We have no data to show ultrasound is associated with any risk reduction for nerve puncture.  Bleeding around the nerve has been associated with local inflammation, and vascular puncture is less common with ultrasound. Whilst this may modify risk we have no data.
Paraesthesiae were sought for many years may indicate nerve needle contact but are not a reliable sign of nerve penetration(30).  Pain on injection usually results in movement of the patient or needle and we do not have reliable data to show this is associated with increased risk, although there is anecdotal evidence that this may indicate nerve injury.
Nerve penetration is not always associated with injury.  Bigeliesen challenged our view of direct intraneural injection and suggested it occurred commonly and was not usually associated with neurological sequelae(31).  Intraneural injection has however been associated with prolonged block and neurological deficit(32). The general consensus is that we should try to avoid sub-perineural injection of local anaesthetics.
Are some blocks more risky than others?  Certainly there is some evidence that blocks performed closer to the neuraxis are more risky than those more peripheral.  The Interscalene block has been associated with direct spinal cord injection. Yanovski et al describe a death following interscalene block and catheter placement under general anaesthesia.  The block was performed using the Winnie approach with nerve stimulator. A 18g Contiplex tuohy needle was advanced until biceps contraction was obtained and injection site confirmed as the  contraction disappeared below  a current level of 0.3mA. 40 ml of 0.25% Bupivacaine was slowly injected.  There was no resistance to injection or aspiration of fluid.  A 20g catheter was then threaded 7cm beyond the needle tip without resistance.  The patient regained consciousness at the end of the procedure and was pain free with full motor paralysis of the right upper extremity. Later that evening he was seen and described pain as 3-4 on a 10cm analogue scale. The resident elected to top up the catheter with 10ml of bupivacaine 0.25% in three fractionated boluses every 2-3min.  There was no change in the patient’s status and the resident left the ward.  The next morning the patient was found dead in his bed.  At post-mortem, radiography after dye injection into the catheter confirmed intrathecal placement.  Several points are important.  1.  The Winnie approach has been shown to direct the needle towards the neuraxis(33).  2. The catheter was inserted 7cm beyond the needle. 3. The original dose was not delivered via the catheter, so the top up was the first check of catheter,  4 The catheter was not imaged in any way,  5  The volumes were higher than currently used. 6. Patients should be observed for 20 minutes after top-up.
Would block performance in an awake patient prior to anaesthesia have prevented this?  No.
Would an ultrasound block with needle tip visible result in this complication?
A case report by Cohen and Gray describes intraneural injection in an awake patient which was apparently considered entirely normal.  The block was performed by a resident using an in-plane short axis Interscalene block with the attending specialist administering local anaesthetic and directing  the block.  The block was considered normal until the following day when on review the patient had motor weakness in C5/6 territory and pain in the shoulder region.  Review of the stored video showed intraneural injection had occurred. We therefore cannot be certain that intraneural injection would be eliminated by ultrasound, nor does this case help us confirm the advantage of an awake patient as there was no reported problem with the block procedure.
Would Pressure monitoring help?
Eight direct nerve root injections of 5ml performed in cadavers demonstrated epidural spread in one specimen. Of note, all injections required high pressures between 37 and 66psi.(34) Recently, Gadsden has demonstrated in pressure changes when the needle is close to a brachial plexus nerve root(35). The compressed air technique described by Ban Tsui is a simple way of achieving this but we still lack proof that injury is avoided if this monitoring is used during block performance.
Children have blocks placed under GA. Is there any evidence that they are at greater risk? 
Two recent papers from the Pediatric Regional Anesthesia Network (PRAN) have shown that placing blocks in an anaesthetized child is as safe as in sedated or awake patients(36,37). Children may not report symptoms reliably, and may not co-operate with block performance making awake siting of a block more risky, but the overall rates of  post-operative neurological symptoms 0.93/1000 (CI 0.7-1.2) under GA and 6.82/1000 (CI 4.2-10.5) in sedated and awake patients is reassuring. Similarly there were only 5 cases of LAST (0.09/1000 [CI 0-0.1] for all patients. The incidence under GA was 0.08/1000 (CI 0.02-0.2) and 0.34/1000 (CI 0-1.9) in awake or sedated patients.
The PRAN data from 518 interscalene blocks, 390 in anaesthetized patients showed no incidence of LAST, or neurological symptoms. The authors conclude that GA is no less safe than awake although these numbers are small and I believe not adequately powered.
A recent review (38) concludes there is no evidence that regional anaesthesia performed under general anaesthesia or deep sedation increased risk in adults. Similarly, another registry review from Germany shows similar rates of LAST, but decreased risk of post operative paraesthesia for peripheral blocks whilst postoperative paraesthesia related to catheter was more common after general anaesthesia.  They make the conservative conclusion that sedation may improve block safety and success, but blocks under general anaesthesia should be reserved for experienced anaesthetists and special situations(39).
ASRA Recommendations for performing regional anaesthesia is anaesthetized or heavily sedated patients. 2008

Limiting neural injury

Monitoring and prevention

● There are no data to support the concept that peripheral nerve stimulation or ultrasound guidance, and/or injection pressure monitoring, reduce the risk of peripheral nerve injury in patients under general anesthesia or heavy sedation. (Class I)   
Because ultrasound-guided peripheral nerve block and pressure monitoring are relatively new technologies, this recommendation may change with the acquisition of more clinical experience and data.   STILL VALID

Adult neuraxis

● Warning signs such as paraesthesia or pain on injection of local anesthetic inconsistently herald needle contact with the spinal cord. Nevertheless, some patients do report warning signs of needle-to-neuraxis proximity. General anesthesia or heavy sedation removes any ability for the patient to recognize and report warning signs. This suggests that neuraxial regional anesthesia should be performed rarely in adult patients whose sensorium is compromised by general anesthesia or heavy sedation. (Class II) .   Recent evidence from Taenzer from children suggests this may not be true

Pediatric neuraxis

● The benefit of ensuring a cooperative and immobile infant or child may outweigh the risk of performing neuraxial regional anesthesia in pediatric patients undergoing general anesthesia or heavy sedation. The overall risk of neuraxial anesthesia should be weighed against its expected benefit. (Class II)  RECENT EVIDENCE suggests GA is safer.

Interscalene blocks

● Case reports document spinal cord injury during the placement of interscalene blocks in patients under general anesthesia, which heightens concern associated with this practice. Interscalene blocks should not be performed in anesthetized or heavily sedated adult or pediatric patients. (Class I).    I believe the majority of these were related to the Winnie approach.  Providing the patient accepts a possible increased risk, and is otherwise keen to have a block, I would be happy to perform a block using Ultrasound, HOWEVER, I would be unhappy for this to be done by an inexperienced anaesthetist. 

Adult peripheral nerve block

● Because general anesthesia or heavy sedation removes all opportunity for adults to communicate symptoms of potential nerve injury, peripheral nerve blockade should not be routinely performed in most adults during general anesthesia or heavy sedation. However, the risk-to-benefit ratio of performing peripheral nerve blockade under these conditions may improve in select patient populations (e.g., dementia, developmental delay, or when unintended movement could compromise vital
structures). (Class II)  STILL VALID

Pediatric peripheral nerve blocks

● Regardless of wakefulness, infants and children may be unable to communicate symptoms of potential peripheral nerve injury. However, uncontrolled movement may increase the risk of injury. Therefore, the placement of peripheral nerve blocks in children undergoing general anesthesia or heavy sedation may be appropriate after duly considering individual risk-to-benefit ratio. (Class II)   VALID

The controversy of Intraneural injections – Current status

Prior to the use of Ultrasound, the injection of local anaesthetic during peripheral nerve blockade was not visualized.  Indirect evidence of needle proximity to the nerve was achieved by electrical nerve stimulation or the search for paraesthesias. Paul Bigeliesen(31) described inadvertent intraneural injection occurred frequently.  This paper resulted in considerable “noise” in the anaesthesia literature centered around two aspects, the desirability and safety of performing intraneural injections, and the nomenclature used to describe intraneural injection(40).
Several comments can be made:
1. The search for paraesthesia is associated with increased risk of neuropathy. Plevak described an increased rate in axillary block.  Chan demonstrated that paraesthesiae and electrical nerve stimulation were poor indicators of needle position
2. Motor thresholds are not reliable(29)
3. Intraneural injection is associated with increased pressure(34)
4. Successful nerve blockade does not always require close proximity of needle and nerve(41)
5. Electrial impedence can differentiate intraneural and extraneural needle placement(42)
6. Nerve swelling on ultrasound denotes intraneural needle placement(43)
7. Neurological injury has been related to confirmed intraneural injection(32). Equally Liu et al reported a study of 257 patients with 17% intraneural injection rate and no postoperative neurological complications. This typifies our current evidence, anecdotal and underpowered.
8. What constitutes intraneural needle placement remains controversial(44).
There is no conclusive evidence that any modality is capable of preventing nerve damage or inadvertent needle placement.

What about Pre-existing neural injury – knowledge based on low grade evidence
ASRA (45,46)
ASRA guidelines suggest care in patients with pre-existing neurological disease. Who does this apply to?  We regularly place blocks in patients with Diabetes, despite neurophysiological evidence and ultrasound evidence of abnormal nerves.  Nerve stimulation thresholds are higher and the nerves are more sensitive to local anaesthetics.  The advisory from ASRA is based on the theory of double crush injury, and the evidence base exists in case reports.
ASRA suggests if regional anaesthesia is employed risk reduction may require reduced volume and concentration of local anaesthetic and avoidance of vasoconstrictors.  There is no data to confirm of repute this.

Controversies in Infection control

PS28 2013 Guidelines on Infection control in Anaesthesia  ASRA (47-49); AAGBI(50)

Ultrasound equipment may pose a risk of nosocomial infection. For contact with an intact skin surface a clean probe is required.  Once a needle is inserted we have now have non-intact skin and the possibility of probe contamination with blood and “semi-critical”exposure of the probe. PS28 3.1 advises the use of a sterile probe cover.  Sterile gel should be used and the probe cleaned after sheath removal with soap and water or detergent wipes.  Gel bottles may harbour bacteria and therefore sterile gel is a sensible precaution, although sterile saline may also provide adequate coupling of probe to skin.   Many operators have used a transparent film over the probe to prevent probe soiling, and a simple no touch approach where the skin is wiped with a sterile swab for needle insertion away from the probe. 

Chlorhexidine 2% vs 0.5% - Judicial decision in Australia
3.2 Chlorhexidine
‘Chlorhexidine has been encouraged as the antiseptic preparation of choice from the infection control perspective. However, the Australian and New Zealand Anaesthetic Allergy Group and ANZCA Anaesthetic Allergy Subcommittee have alerted ANZCA to the increasing incidence of significant allergic reactions to chlorhexidine, some of which have been delayed reactions occurring in the post anaesthesia care unit. Consequently these guidelines provide alternatives to chlorhexidine where relevant’.
Attention has recently been drawn to infection control guidelines as a result of several high profile legal cases.  On August 23rd 2010, the Sydney Morning Herald headlined “an outdated medical procedure behind catastrophic epidural injury”(51).  Chlorhexidine (CHG) had been inadvertently injected into the epidural space.  UK guidelines have focused attention on the risk of chronic adhesive arachnoiditis where chlorhexidine is considered one of the most likely causes(52).  Practice change has been recommended, with 2% chorhexidine no longer being considered appropriate for skin disinfection, separation of disinfectants to prevent contamination of needles and the possibility of contamination by sprays supporting the use of swab sticks.  The suitable product to address these issues in not available in Australia or New Zealand.  A paper in 2012 from ASRA found short term neurological complications after spinal anaesthesia after CHG skin antisepsis in 57 of 12,465 cases (0.04%)(53). In the background they write,”there are currently no published reports within the literature describing CHG neurotoxicity in humans”, although in the same year we have reports of devastating injury(54,55). The absolute risk is unknown although NAP3 found 1 case after 700,000 neuraxial blocks.
ASRA Guidelines written in 2006 still recommend 2% chlorhexidine in alcohol(49,56).
When dealing with levels of risk of such small magnitude it is almost impossible to prove practice changes affect outcomes.  Data does show chlorhexidine in concentrations as low as 0.01% is neurotoxic, however alcohol also may cause neurological injury.  Splashes from liquids may be dangerous and impregnated swab sticks are preferred for skin preparation(57).

STOP BEFORE YOU BLOCK  - Do we need a mark?

ANZCA  guideline  PS03 – 2014; ASRA (58)
This issue was raised in 2005 by a report detailing two cases of wrong sided block, suggesting guidelines but excluded a site mark on the skin.(59). After  a survey of experts and sampling at an ASRA meeting an ASRA checklist was produced(58).  The RCA UK and ANZCA have also included this in recent guidelines
Section 2.10  ‘Prior to performing a regional block, a “block time out” should be performed. This requires verification of the site and side of the proposed block with another clinician (nurse/anaesthesia technician or medical practitioner) prior to performing the block. This verification requires identification of the patient and check of the surgical consent form, identification of a surgical site mark, discussion with the patient (when possible) and placement of a mark close enough to the block site to be visible when performing the block. The proceduralist should then pause just prior to needle insertion to reverify the presence of the anaesthesia site mark and verbally confirm the site and side with the assistant. There should be a pause before needle insertion for each new block site if patient position is changed or the blocks are separated in time.’
Irrespective of how checks are performed, a wrong side block is a medical error. Failure to perform the Stop before you block or incorrect check result in the same problem.  Is a mark on the skin sensible – neuraxial block is midline. 
Does the mark or the written confirmation alter the risk?
What is the risk?  Documented rate is 2 per 10,000 blocks.  In the UK, 40% of patients were responsive at the time of the wrong sited block.
Peripheral block – we may not know exactly where we will perform the block when using US and so the marked site may not be the one used.  The important aspect of the check is to relate the correct anaesthetic intervention to the anticipated surgical intervention.

Needle choice   Do we really know if one needle is safer than another?
Selander (60) suggested that short bevel needles were the least likely to cause nerve injury.  Damage produced by long bevel needles appears to resolve more quickly (Rice and McMahon BJA 1992).  Studies have shown damage occurs to nerve fascicles when needles are placed through nerves but these studies are usually in animals or isolated nerves(61).  We do not have data to prove any advantage for any particular needle. The models used for this research are crude and do not accurately mimic what happens in the body. We use Tuohy needles for many blocks as they are rigid, have a characteristic tip shape confirmed by ultrasound, and MAY be less likely to penetrate a nerve. Our other preference is a 20g Quincke spinal needle. The cutting tip enables precise manipulation in tissues but we do not aim the needle at the nerve.
The demonstration of frequent nerve injection without evidence of nerve injury does not help define individual needle risk. 

Regional Anaesthesia and Anticoagulation

Guideline:  ASRA (62);  AAGBI (63); European (64)

ASRA published its first evidence based guideline in 2007.  This concerned the guidance for neuraxial blockade in the presence of anti-thrombotic medication. The lastest  (Third edition) in 2010 gives guidance for neuraxial techniques. The risks of haematoma with Clipdogrel and GP11b/111a antagonists is unknown.
In general the advice for block performance is to wait until the coagulation is normal either based on coagulation monitoring or on pharmacological data. Clinical studies are unlikely to ever be undertaken.
Peripheral regional anaesthesia is mentioned briefly thus:
‘For patients undergoing deep plexus or peripheral block we recommend that recommendations regarding neuraxial techniques be similarly applied.’
The UK guidelines provide similar guidance and rank peripheral nerve blocks according to a relative risk scale.  Specific guidance relates to the relative risk of regional block in this situation to a general anaesthetic.  Catheter techniques may be higher risk.  I would consider that fascial plane blocks and superficial blocks are low risk.  Perivascular blocks performed under ultrasound by experienced clinicians may be safe.  Deep blocks may be less so although I think personal experience of the block is probably most important. 

A final note.  Controversy exists because of differences in opinion, and this will ineveitably occur when our knowledge base lacks certainty.  Most of the issues presented here refer to events which have a low frequency and may never truly be reconciled(65,66). Since large scale randomized trials are unlikely or impossible to perform, the value of regional anaesthesia registries assumes major importance and is our main hope for evidence based regional anaesthesia.


1. Horlocker TT, Neal JM, Rathmell JP. Practice advisories by the American Society of Regional Anesthesia and Pain Medicine: grading the evidence and making the grade. Regional Anaesthesia and Pain Medicine. 2011 Jan;36(1):1–3.
2. Fleischmann KH, Kuter DJ, Coley CM, Rathmell JP. Practice guidelines often fail to keep pace with the rapid evolution of medicine: a call for clinicians to remain vigilant and revisit their own practice patterns. Regional Anaesthesia and Pain Medicine. 2010 Jan;35(1):4–7.
3. Fearnley RA, Bell MDD, Bodenham AR. Status of national guidelines in dictating individual clinical practice and defining negligence. British Journal of Anaesthesia. 2012 Apr;108(4):557–61.
4. Bromage PR, Benumof JL. Paraplegia following intracord injection during attempted epidural anesthesia under general anesthesia. Regional Anaesthesia and Pain Medicine. 1998 Jan;23(1):104–7.
5. Krane EJ, Dalens BJ, Murat I, Murrell D. The safety of epidurals placed during general anesthesia. Regional Anaesthesia and Pain Medicine. 1998 Sep;23(5):433–8.
6. Benumof JL. Permanent loss of cervical spinal cord function associated with interscalene block performed under general anesthesia. Anesthesiology. 2000 Dec;93(6):1541–4.
7. Drasner K. Thoracic epidural anesthesia: asleep at the wheal? Anesth Analg. 2004 Aug;99(2):578–9.
8. Benumof JL. Regional anesthesia under general anesthesia and spinal cord injury. Anesth Analg. 2005 Apr;100(4):1214–5.
9. BERNARDS C, HADZIC A, SURESH S, NEAL J. Regional Anesthesia in Anesthetized or Heavily Sedated Patients. Regional Anaesthesia and Pain Medicine. 2008 Sep;33(5):449–60.
10. NEAL J, BERNARDS C, HADZIC A, HEBL J, HOGAN Q, HORLOCKER T, et al. ASRA Practice Advisory on Neurologic Complications in Regional Anesthesia and Pain Medicine. Regional Anaesthesia and Pain Medicine. 2008 Sep;33(5):404–15.
11. Neal JM, Bernards CM, Butterworth JF IV, Di Gregorio G, Drasner K, Hejtmanek MR, et al. ASRA Practice Advisory on Local Anesthetic Systemic Toxicity. Regional Anaesthesia and Pain Medicine. 2010 Mar;35(2):152–61.
12. AAGBI la_toxicity_notes_2010_0. 2010 Jan 13;:1–1.
13. AAGBI la_toxicity_notes_2010_0. 2010 Jan 13;:1–1.
14. Auroy Y, Benhamou D, Bargues L, Ecoffey C, Falissard B, Mercier F, et al. Major Complications of Regional Anesthesia in France. Anesthesiology. 2002 Oct 16;97:1274–80.
15. Brown DL, Ransom DM, Hall JA, Leicht CH, Schroeder DR, Offord KP. Regional anesthesia and local anesthetic-induced systemic toxicity: seizure frequency and accompanying cardiovascular changes. Anesth Analg. 1995 Aug;81(2):321–8.
16. Barrington MJ, Kluger R. Ultrasound guidance reduces the risk of local anesthetic systemic toxicity following peripheral nerve blockade. Regional Anaesthesia and Pain Medicine. 2013 Jul;38(4):289–97.
17. Sites BD, Taenzer AH, Herrick MD, Gilloon C, Antonakakis J, Richins J, et al. Incidence of local anesthetic systemic toxicity and postoperative neurologic symptoms associated with 12,668 ultrasound-guided nerve blocks: an analysis from a prospective clinical registry. Regional Anaesthesia and Pain Medicine. 2012 Sep;37(5):478–82.
18. Orebaugh SL, Kentor ML, Williams BA. Adverse outcomes associated with nerve stimulator-guided and ultrasound-guided peripheral nerve blocks by supervised trainees: update of a single-site database. Regional Anaesthesia and Pain Medicine. 2012 Nov;37(6):577–82.
19. Di Gregorio G, Neal JM, Rosenquist RW, Weinberg GL. Clinical presentation of local anesthetic systemic toxicity: a review of published cases, 1979 to 2009. Regional Anaesthesia and Pain Medicine. 2010 Mar;35(2):181–7.
20. Lirk P, Picardi S, Hollmann MW. Local anaesthetics: 10 essentials. European Journal of Anaesthesiology. 2014 Nov;31(11):575–85.
21. Jacob AK, Mantilla CB, Sviggum HP, Schroeder DR, Pagnano MW, Hebl JR. Perioperative Nerve Injury after Total Hip Arthroplasty. Anesthesiology. 2011 Nov 3;115(6):1172–8.
22. Jacob AK, Mantilla CB, Sviggum HP, Schroeder DR, Pagnano MW, Hebl JR. Perioperative Nerve Injury after Total Knee Arthroplasty. Anesthesiology. 2011 Jan 18;114(2):311–7.
23. Thomasson BG, Matzon JL, Pepe M, Tucker B, Maltenfort M, Austin L. Distal peripheral neuropathy after open and arthroscopic shoulder surgery: an under-recognized complication. J Shoulder Elbow Surg. 2015 Jan;24(1):60–6.
24. Sviggum HP, Jacob AK, Mantilla CB, Schroeder DR, Sperling JW, Hebl JR. Perioperative nerve injury after total shoulder arthroplasty: assessment of risk after regional anesthesia. Regional Anaesthesia and Pain Medicine. 2012 Sep;37(5):490–4.
25. Borgeat A, Dullenkopf A, Ekatodramis G, Nagy L. Evaluation of the lateral modified approach for continuous interscalene block after shoulder surgery. Anesthesiology. 2003 Aug;99(2):436–42.
26. Borgeat A, Blumenthal S, Lambert M, Theodorou P, Vienne P. The Feasibility and Complications of the Continuous Popliteal Nerve Block: A 1001-Case Survey. Anesth Analg. 2006 Jul;103(1):229–33.
27. Barrington MJ, Watts SA, Gledhill SR, Thomas RD, Said SA, Snyder GL, et al. Preliminary results of the Australasian Regional Anaesthesia Collaboration: a prospective audit of more than 7000 peripheral nerve and plexus blocks for neurologic and other complications. Regional Anaesthesia and Pain Medicine. 2009 Nov;34(6):534–41.
28. Barrington MJ, Snyder GL. Neurologic complications of regional anesthesia. Curr Opin Anaesthesiol. 2011 Oct;24(5):554–60.
29. Klein SM, Melton S, Grill WM, Neilsen KC. Peripheral nerve stimulation in regional anaesthesia. Regional Anaesthesia and Pain Medicine. 2012 Jun 17;37(4):383–92.
30. Choyce A, Chan VW, Middleton WJ, Knight PR, Peng P, McCartney CJ. What is the relationship between paresthesia and nerve stimulation for axillary brachial plexus block? Regional Anaesthesia and Pain Medicine. 2001 Mar;26(2):100–4.
31. Bigeleisen PE. Nerve Puncture and Apparent Intraneural Injection duringUltrasound-guided Axillary Block Does Not InvariablyResult in Neurologic Injury. Anesthesiology. 2006 Sep 16;105:779–83.
32. Cohen JM, Gray AT. Functional deficits after intraneural injection during interscalene block. Regional Anaesthesia and Pain Medicine. 2010 Jul;35(4):397–9.
33. Sardesai AM, Patel R, Denny NM, Menon DK, Dixon AK, Herrick MJ, et al. Interscalene brachial plexus block: can the risk of entering the spinal canal be reduced? A study of needle angles in volunteers undergoing magnetic resonance imaging. Anesthesiology. 2006 Jul;105(1):9–13.
34. Orebaugh SL, Mukalel JJ, Krediet AC, Weimer J, Filip P, McFadden K, et al. Brachial plexus root injection in a human cadaver model: injectate distribution and effects on the neuraxis. Regional Anaesthesia and Pain Medicine. 2012 Sep;37(5):525–9.
35. Gadsden JC, Choi JJ, Lin E, Robinson A. Opening injection pressure consistently detects needle-nerve contact during ultrasound-guided interscalene brachial plexus block. Anesthesiology. 2014 May;120(5):1246–53.
36. Taenzer A, Walker BJ, Bosenberg AT, Krane EJ, Martin LD, Polaner DM, et al. Interscalene Brachial Plexus Blocks Under General Anesthesia in Children. Regional Anaesthesia and Pain Medicine. 2014;39(6):502–5.
37. Taenzer AH, Walker BJ, Bosenberg AT, Martin L, Suresh S, Polaner DM, et al. Asleep Versus Awake. Regional Anaesthesia and Pain Medicine. 2014;39(4):279–83.
38. Kessler P, Steinfeldt T, Gogarten W, Schwemmer U, Büttner J, Graf BM, et al. [Peripheral regional anesthesia in patients under general anesthesia : Risk assessment with respect to parasthesia, injection pain and nerve damage]. Anaesthesist. 2013 Jun;62(6):483–8.
39. Kubulus C, Schmitt K, Albert N, Raddatz A, Gräber S, Kessler P, et al. Awake, sedated or anaesthetised for regional anaesthesia block placements? European Journal of Anaesthesiology. 2016 Oct;33(10):715–24.
40. Choquet O, Morau D, Biboulet P, Capdevila X. Where should the tip of the needle be located in ultrasound-guided peripheral nerve blocks? Curr Opin Anaesthesiol. 2012 Oct;25(5):596–602.
41. Albrecht E, Kirkham KR, Taffé P, Endersby RVW, Chan VWS, Tse C, et al. The maximum effective needle-to-nerve distance for ultrasound-guided interscalene block: an exploratory study. Regional Anaesthesia and Pain Medicine. 2014 Jan;39(1):56–60.
42. Tsui BCH, Pillay JJ, Chu KT, Dillane D. Electrical impedance to distinguish intraneural from extraneural needle placement in porcine nerves during direct exposure and ultrasound guidance. Anesthesiology. 2008 Sep;109(3):479–83.
43. Brull R, Chan VWS, McCartney CJ, Perlas A, Xu D. Ultrasound detects intraneural injection. Anesthesiology. 2007 May 10;106(6):1244.
44. Sala-Blanch X, Vandepitte C, Laur JJ, Horan P, Xu D, Reina MA, et al. A practical review of perineural versus intraneural injections: a call for standard nomenclature. Int Anesthesiol Clin. 2011;49(4):1–12.
45. Horlocker TT. Neuraxial blockade in patients with spinal stenosis: between a rock and a hard place. Anesth Analg. 2010 Jan 1;110(1):13–5.
46. Hebl JR, Horlocker TT, Schroeder DR. Neuraxial Anesthesia and Analgesia in Patients with Preexisting Central Nervous System Disorders. Anesth Analg. 2006 Jul;103(1):223–8.
47. WEDEL D, HORLOCKER T. Regional Anesthesia in the Febrile or Infected Patient. Regional Anaesthesia and Pain Medicine. 2006 Jul;31(4):324–33.
48. HORLOCKER T, WEDEL D. Regional Anesthesia in the Immunocompromised Patient. Regional Anaesthesia and Pain Medicine. 2006 Jul;31(4):334–45.
49. Hebl JR. The Importance and Implications of Aseptic Techniques During Regional Anesthesia. Regional Anaesthesia and Pain Medicine. 2006 Jul;31(4):311–23.
50. Membership of the Working Party:, Campbell JP, Plaat F, Checketts MR, Bogod D, Tighe S, et al. Safety guideline: skin antisepsis for central neuraxial blockade. Anaesthesia. 2014 Sep 3;69(11):1279–86.
51. Outdated medical procedure behind catastrophic epidural injury [Internet]. 2015 [cited 2015 Feb 10]. Available from:
52. Membership of the Working Party:, Campbell JP, Plaat F, Checketts MR, Bogod D, Tighe S, et al. Safety guideline: skin antisepsis for central neuraxial blockade. Anaesthesia. 2014 Sep 3;69(11):1279–86.
53. Sviggum HP, Jacob AK, Arendt KW, Mauermann ML, Horlocker TT, Hebl JR. Neurologic complications after chlorhexidine antisepsis for spinal anesthesia. Regional Anaesthesia and Pain Medicine. 2012 Mar;37(2):139–44.
54. Bogod D. The sting in the tail: antiseptics and the neuraxis revisited. Anaesthesia. 2012 Dec;67(12):1305–9.
55. Killeen T, Kamat A, Walsh D, Parker A, Aliashkevich A. Severe adhesive arachnoiditis resulting in progressive paraplegia following obstetric spinal anaesthesia: a case report and review. Anaesthesia. 2012 Dec;67(12):1386–94.
56. Hebl JR, Niesen AD. Infectious complications of regional anesthesia. Curr Opin Anaesthesiol. 2011 Oct;24(5):573–80.
57. Bogod D. Chlorhexidine droplet splash - time to revisit the swabstick? Anaesthesia. 2014 Mar;69(3):284.
58. Mulroy MF, Weller RS, Liguori GA. A checklist for performing regional nerve blocks. Regional Anaesthesia and Pain Medicine. 2014 May;39(3):195–9.
59. EDMONDS C, LIGUORI G, STANTON M. Two cases of a wrong-site peripheral nerve block and a process to prevent this complication. Regional Anaesthesia and Pain Medicine. 2005 Feb;30(1):99–103.
60. Selander D. Peripheral nerve injury caused by injection needles. British Journal of Anaesthesia. 1993 Aug;71(2):323–5.
61. Sala-Blanch X, Ribalta T, Rivas E, Carrera A, Gaspa A, Reina MA, et al. Structural injury to the human sciatic nerve after intraneural needle insertion. Regional Anaesthesia and Pain Medicine. 2009 May;34(3):201–5.
62. Horlocker TT. Regional anaesthesia in the patient receiving antithrombotic and antiplatelet therapy. British Journal of Anaesthesia. 2011 Dec;107 Suppl 1:i96–106.
63. Harrop-Griffiths W, Cook TM, Gill H, Hill D, Ingram M. Regional Anaesthesia and Patients with Abnormalities of Coagulation. Anaesthesia. 2013 Nov 5;68:966–72.
64. Gogarten W, Vandermeulen E, Van Aken H, Kozek S, Llau JV, Samama CM, et al. Regional anaesthesia and antithrombotic agents: recommendations of the European Society of Anaesthesiology. Vol. 27, European Journal of Anaesthesiology. 2010. pp. 999–1015.
65. Hopwood MB. Statistics: Can we prove an association for a rare complication. Regional Anaesthesia and Pain Medicine. 1993 Dec 31;18:428–33.
66. HO A, DION P, KARMAKAR M, LEE A. Estimating with confidence the risk of rare adverse events, including those with observed rates of zero☆. Regional Anaesthesia and Pain Medicine. 2002 Mar;27(2):207–10.


Administrative contact

Please contact Karen Patching -
Desk phone: +64 (0) 9 375 7085

c/- Department of Anaesthesia & Perioperative Medicine
Level 8 - Support Building, Auckland City Hospital
PO Box 92024, Auckland, New Zealand