ANESTHESIA Hadzic's Peripheral Nerve Blocks Hadzic parte 04

 

Thrombin Inhibitors

Recombinant hirudin derivatives, such as desirudin (Revasc), lepirudin (Refludan), and bivalirudin

(Angiomax), inhibit both free and clot-bound thrombin.4

 Argatroban, although an L-arginine

derivative, is also a thrombin inhibitor. These drugs are used in the treatment of heparin-induced

thrombocytopenia and as an adjunct when angioplasty is performed.33 Their anticoagulant effect is

present for 1 to 3 hours after intravenous administration and is monitored by the aPTT. There is no

pharmacologic reversal to the effect of these drugs. Desirudin is used as thromboprophylaxis after

total hip replacement.34 There are no published reports of spinal hematoma related to neuraxial

anesthesia in patients who have received a thrombin inhibitor, probably because of the hesitancy of

clinicians to perform neuraxial injections in patients taking the drugs, which is probably related to

their unfamiliarity with the drugs. The most recent ASRA guidelines recommend against the

performance of neuraxial techniques in patients who received thrombin inhibitors.

Newer Anticoagulants

Dabigatran Etexilate

Dabigatran is an oral direct thrombin inhibitor. Its bioavailability is only 5%, peak plasma levels

occur at 2 hours, and its half-life is 8 hours after a single dose but up to 17 hours after multiple doses.

The drug is approved for clinical use in Europe. Studies showed dabigatran (150 or 220 mg daily) to

be less effective than enoxaparin (30 mg twice daily) when used for thromboprophylaxis after total

joint surgery.35,36A 48-hour interval is recommended before a neuraxial injection.

Rivaroxaban

Rivaroxaban is an oral factor Xa inhibitor approved for use in Europe and Canada. It is awaiting

approval by the Food and Drug Administration (FDA) in the United States. It has an 80%

bioavailability; its peak effect occurs after 1 hour; the duration of effect is 12 hours; and it has a halflife of 9 to 13 hours. Clinical studies comparing rivaroxaban, at doses of 5 to 40 mg, to enoxaparin

showed similar or superior efficacy.37–40 There were no reports of spinal hematoma in these studies.

Apparently, a 24-hour interval (2 × half-life) was observed between the rivaroxaban dose and

epidural catheter placement or removal; subsequent dosing of the drug was 6 hours after removal of

the catheter (personal communication with the company). The drug offers several salutary

characteristics including efficacy and simplicity with once-daily oral dosing.

Prasugrel

Prasugrel is an oral anticoagulant approved for use by the FDA in July 2009. Its mechanism of action

is similar to clopidogrel; that is, it acts as a noncompetitive antagonist of P2Y12, inhibiting the ability

of platelet ADP to induce aggregation for the life of the platelet.41 Prasugrel and clopidogrel are

prodrugs; however, prasugrel has a quicker onset of action, a longer duration (the effect of 60 mg is

1–1.5 hours compared with 6 hours with 300 mg clopidogrel); it is 10 times more potent; and less

prone to drug–drug interactions and variability in patient response than clopidogrel.41,42 A 7–10 day

interval is recommended before a neuraxial injection. Other novel antiplatelet drugs are in

development, including ticagrelor and cangrelor, which are under study for use in patients with acute

coronary syndromes.43

Anticoagulation and Peripheral Nerve Blocks

Spontaneous hematomas have been reported in patients who took anticoagulants. Abdominal wall

hematomas, intracranial hemorrhage, psoas hematoma, and intrahepatic hemorrhage have occurred

after LMWH.44–47 Major hemorrhagic complications occur in 1.9 to 6.5% of patients on enoxaparin.48

The increased bleeding that occurs after vascular or cardiac procedures and regional nerve blocks in

these patients can result in an expanding hematoma with resultant ischemia of the nerve.

TABLE 8-1 Summary of Guidelines on Anticoagulants and Neuraxial Blocks*

There has been no prospective study on peripheral nerve blocks in the presence of anticoagulants.

However, there have been several case reports of hematomas when peripheral blocks are performed

in patients who are on these drugs. The hematomas occurred in patients with abnormal and normal

coagulation status, and in patients who were given LMWH, ticlopidine and clopidogrel, warfarin,

heparin, or a combination of the drugs.49–55 In most cases, however, recovery of neurologic deficits

occurred within a year.

The diagnosis of bleeding after peripheral nerve block in patients on anticoagulants include pain

(flank, paravertebral, or in the groin with psoas bleeding), tenderness in the area, fall in

hemoglobin/hematocrit, fall in blood pressure, and sensory and motor deficits. Although definite

diagnosis is made by computed tomography, ultrasound can be a diagnostic aid, and its increasing use

will make this modality a useful tool for the diagnosis and subsequent monitoring of peripheral

hematomas. Treatment of peripheral hematomas usually includes surgical consult, blood transfusion

as necessary, and watchful waiting versus surgical drainage.

The most recent ASRA guidelines recommended that the same guidelines on neuraxial injections

apply to deep plexus or peripheral nerve blocks. Some clinicians may find this to be too restrictive

and apply the same guidelines only to deep plexus and noncompressible blocks (e.g., lumbar plexus

block, deep cervical plexus blocks) or to blocks near vascular areas, such as celiac plexus blocks or

superior hypogastric plexus blocks. If peripheral nerve blocks are performed in the presence of

anticoagulants, the anesthesiologist must discuss the risks and benefits of the block with the patient

and the surgeon, and follow the patient very closely after the block.

Guidelines of Various Societies

Guidelines on use of regional anesthesia in the presence of anticoagulants have been published by a

number of societies throughout the world to better fit them to the realm of the local practices. By

necessity, there are similarities and differences among them. A good example is the new ASRA

guidelines56 and the Belgian and German guidelines.57,58 The guidelines of the three organizations are

similar with regard to antiplatelet medications, unfractionated heparin, and thrombolytic agents. With

regard to LMWH, the ASRA guidelines are more conservative, partly due to the differences in the

dosing of the drug. For fondaparinux, the German guidelines allow an indwelling epidural catheter,

whereas the ASRA and the Belgian guidelines recommend against it. The Belgian and German

guidelines allow neuraxial injections in patients on direct thrombin inhibitors; the ASRA guidelines

do not. Finally, some of the newer anticoagulants have been approved for use in Europe and are

awaiting approval in the United States so the guidelines for these drugs are forthcoming.

Summary

Adherence to the discussed guidelines should lead to a lesser risk of hemorrhagic complications after

regional anesthesia, including spinal hematomas. Likewise, implementation of the guidelines leads to

improved vigilance and better care of patients on anticoagulants in whom nerve blocks are performed

or entertained. Consensus guidelines, however, should be viewed only as recommendations; specific

decisions on nerve blocks in patients on anticoagulants should be individualized. Adequate

monitoring, follow-up, and timely treatment should be implemented in patients on anticoagulants who

are receiving neuraxial or peripheral nerve blocks (see algorithms on the following pages).

DECISION MAKING ALGORITHM IN THE SELECTION OFNEURAXIAL OR PERIPHERAL

NERVE BLOCKADE

FOLLOW-UP OF PATIENTS WHO ARE AT RISK FOR SPINAL OR PERIPHERAL HEMATOMA

ANTICOAGULANTS: MECHANISM OF ACTION AND RECOMMENDED GUIDELINES FOR

PRACTICE OF NEURAXIAL ANESTHESIA

REFERENCES

. Hejazi N, Thaper PY, Hassler W. Nine cases of nontraumatic spinal epidural hematoma. Neurol Med

Chir. 1998;38:718-723.

. Mattle H, Sieb JP, Rohner M, Mumenthaler M. Nontraumatic spinal epidural and subdural

hematomas. Neurology. 1987;37:1351-1356.

. Heit JA, Horlocker TT, eds. Neuraxial anesthesia and anticoagulation. Reg Anesth Pain Med.

1998;23:S129-193.

. Horlocker TT, Wedel DJ, Benzon HT, et al. Regional anesthesia in the anticoagulated patient:

defining the risks (The second ASRA Consensus Conference on Neuraxial Anesthesia and

Anticoagulation). Reg Anesth Pain Med. 2003;28:172-197.

. Benzon HT, Brunner EA, Vaisrub N. Bleeding time and nerve blocks after aspirin. Reg Anesth.

1984;9:86-90.

. Vandermeulen EP, Van Aken H, Vermylen J. Anticoagulants and spinal-epidural anesthesia. Anesth

Analg. 1994;79:1165-1177.

. CLASP (Collaborative Low-Dose Aspirin Study in Pregnancy) Collaborative Group. CLASP: a

randomized trial of low-dose aspirin for the prevention and treatment of pre-eclampsia among 9364

pregnant women. Lancet. 1994;343:619-629.

. Horlocker TT, Wedel DJ, Offord KP. Does preoperative antiplatelet therapy increase the risk of

hemorrhagic complications associated with regional anesthesia? Anesth Analg. 1990;70:631-634.

. Horlocker TT, Wedel DJ, Schroeder DR, et al. Preoperative antiplatelet therapy does not increase

the risk of spinal hematoma associated with regional anesthesia. Anesth Analg. 1995;80:303-309.

0. Horlocker TT, Bajwa ZH, Ashraft Z, et al. Risk assessment of hemorrhagic complications

associated with nonsteroidal antiinflammatory medications in ambulatory pain clinic patients

undergoing epidural steroid injection. Anesth Analg. 2002;95:1691-1697.

1. Benzon HT, Wong HY, Siddiqui T, Ondra S. Caution in performing epidural injections in patients

on several antiplatelet drugs. Anesthesiology. 1999;91:1558-1559.

2. Helft G, Osende JI, Worthley SG, et al. Acute antithrombotic effect of a front-loaded regimen of

clopidogrel in patients with atherosclerosis on aspirin. Arterioscler Thromb Vasc Biol.

2000;29:2316-2321.

3. Mayumi T, Dohi S. Spinal subarachnoid hematoma after lumbar puncture in a patient receiving

antiplatelet therapy. Anesth Analg. 1983;62:777-779.

4. Benzon HT, Wong HY, Siddiqui T, Ondra S. Caution in performing epidural injections in patients

on several antiplatelet drugs. Anesthesiology. 1999;91:1558-1559.

5. Broad L, Lee T, Conroy M, et al. Successful management of patients with a drug-eluting coronary

stent presenting for elective, non-cardiac surgery. Br J Anaesth. 2007;98:19-22.

6. Benzon HT, Fragen R, Benzon HA, Savage J, Robinson J, Puri L. Clopidogrel and neuraxial block:

the role of the PFA II and P2Y12 assays. Reg Anesth Pain Med. 2010;35:115.

7. Ansell J, Hirsh J, Hylek E, Jacobson A, Crowther M, Palareti G. Pharmacology and management of

the vitamin K antagonists. Chest. 2008;133:160S-190S.

8. Benzon HT, Benzon HA, Kirby-Nolan M, Avram MJ, Nader A. Factor VII levels and risk factors

for increased international normalized ratio in the early phase of warfarin therapy. Anesthesiology.

2010;112:298-304.

9. Horlocker TT, Wedel DJ, Schlichting JL. Postoperative epidural analgesia and oral anticoagulant

therapy. Anesth Analg. 1994;79:89-93.

0. Wu CL, Perkins FM. Oral anticoagulant prophylaxis and epidural catheter removal. Reg Anesth.

1996;21:517-524.

1. Horlocker TT. When to remove a spinal or epidural catheter in an anticoagulated patient. Reg

Anesth. 1993;18:264-265.

2. Rao TL, El-Etr AA. Anticoagulation following placement of epidural and subarachnoid catheters:

an evaluation of neurologic sequelae. Anesthesiology. 1981;55:618-620.

3. Ruff DL, Dougherty JH. Complications of anticoagulation followed by anticoagulation. Stroke.

1981;12:879-881.

4. Geerts WH, Bergqvist D, Pineo GF, et al. Prevention of venous thromboembolism. American

College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest.

2008;133:381S-453S.

5. King CS, Holley AB, Jackson JL, et al. Twice versus three times daily heparin dosing for

thromboembolism prophylaxis in the general population: a metaanalysis. Chest. 2007;131:507-516.

6. Horlocker TT, Heit JA. Low molecular weight heparin: biochemistry, pharmacology, perioperative

prophylaxis regimens, and guidelines for regional anesthetic management. Anesth Analg.

1997;85:874-885.

7. Rosenquist RW, Brown DL. Neuraxial bleeding: fibrinolytics/thrombolytics. Reg Anesth Pain Med.

1998;23S:152-156.

8. Basila D, Yuan CS. Effects of dietary supplements on coagulation and platelet function. Thromb

Res. 2005;117:49-53.

9. Bauer KA. Fondaparinux: basic properties and efficacy and safety in venous thromboembolism

prophylaxis. Am J Orthop. 2002;31:4-10.

0. Turpie AG, Gallus AS, Hoek JA. Pentasaccharide investigators. A synthetic pentasaccharide for the

prevention of deep-vein thrombosis after total hip replacement. N Engl J Med. 2001;344:619-625.

1. Singelyn FJ, Verheyen CC, Piovella F, Van Aken HK, Rosenceher N. EXPERT Study Investigators.

The safety and efficacy of extended thromboprophylaxis with fondaparinux after major orthopedic

surgery of the lower limb with or without a neuraxial or deep peripheral nerve catheter: the EXPERT

Study. Anesth Analg. 2007;105:1540-1547.

2. Rosencher N, Bonnet MP, Sessler DI. Selected new antithrombotic agents and neuraxial anesthesia

for major orthopedic surgery: management strategies. Anaesthesia. 2007;62:1154-1160.

3. Greinacher A, Lubenow N. Recombinant hirudin in clinical practice: focus on lepirudin.

Circulation. 2001;103:1479-1484.

4. Ericksson BI, Wille-Jorgensen P, Kalebo P, et al. A comparison of recombinant hirudin with a lowmolecular-weight heparin to prevent thromboembolic complications after total hip replacement. N

Engl J Med. 1997;337:1329-1335.

5. Ericksson BI, Dahl OE, Rosencher N, et al. RE-MODEL Study Group: Oral dabigatran etexilate vs.

subcutaneous enoxaparin for the prevention of venous thromboembolism after total knee replacement:

the RE-MODEL randomized trial. J Thromb Haemost. 2007;5:2178-2185.

6. The RE-MOBILIZE Writing Committee. Oral thrombin inhibitor dabigatran etexilate versus North

American enoxaparin regimen for prevention of venous thromboembolism after knee arthroplasty

surgery. J Arthroplasty. 2009;24:1-9.

7. Ericksson BI, Borris LC, Dahl OE, et al; ODIXa-HIP Study Investigators. A once-daily, oral, direct

factor Xa inhibitor, rivaroxaban (BAY 59-7939), for thromboprophylaxis after total hip replacement.

Circulation. 2006;114:2374-2381.

8. Eriksson BI, Borris LC, Friedman RJ, et al; RECORD1 Study group. Rivaroxaban versus

enoxaparin for thromboprophylaxis after hip arthroplasty. N Engl J Med. 2008;358:2765-2775.

9. Lassen MR, Ageno W, Borris LC, et al; RECORD3 Investigators. Rivaroxaban versus enoxaparin

for thromboprophylaxis after total knee arthroplasty. N Eng J Med. 2008;358:2776-2786.

0. Kakkar AK, Brenner B, Dahl O, et al. RECORD2 Investigators. Extended duration rivaroxaban

versus short-term enoxaparin for the prevention of venous thromboembolism after total hip

arthroplasty: a double-blind, randomized controlled trial. Lancet. 2008;372:31-39.

1. Reinhart KM, White CM, Baker WL. Pharmacotherapy. 2009;29:1441-1451.

2. Bhatt DL. Prasugrel in clinical practice. N Engl J Med. 2009;361:940-942.

3. Shalito I, Kopyleva O, Serebruany V. Novel antiplatelet agents in development: prasugrel,

ticagrelor, and cangrelor and beyond. Am J Ther. 2009;16:451-458.

4. Antonelli D, Fares L, Anene C. Enoxaparin associated with huge abdominal wall hematomas: a

report of two cases. Am Surgeon. 2000;66:797-800.

5. Dickinson LD, Miller L, Patel CP, Gupta SK. Enoxaparin increases the incidence of postoperative

intracranial hemorrhage when initiated preoperatively for deep vein thrombosis prophylaxis with

brain tumors. Neurosurgery. 1998;43:1074-1081.

6. Ho KJ, Gawley SD, Young MR. Psoas hematoma and femoral neuropathy associated with

enoxaparin therapy. Int J Clin Pract. 2003;57:553-554.

7. Houde JP, Steinberg G. Intrahepatic hemorrhage after use of low-molecular-weight heparin for total

hip arthroplasty. J Arthroplasty. 1999;14:372-374.

8. Noble S, Spencer CM. Enoxaparin: a review of its clinical potential in the management of coronary

artery disease. Drugs. 1998;56:259-272.

9. Klein SM, D’Ercole F, Greengrass RA, Warner DS. Enoxaparin associated with psoas hematoma

and lumbar plexopathy after lumbar plexus block. Anesthesiology. 1997;87:1576-1579.

0. Weller RS, Gerancher JC, Crews JC, Wade KL. Extensive retroperitoneal hematoma without

neurologic deficit in two patients who underwent lumbar plexus block and were later anticoagulated.

Anesthesiology. 2003;98:581-583.

1. Maier C, Gleim M, Weiss T, et al. Severe bleeding following lumbar sympathetic blockade in two

patients under medication with irreversible platelet aggregation inhibitors. Anesthesiology.

2002;97:740-743.

2. Nielsen CH. Bleeding after intercostal nerve block in a patient anticoagulated with heparin.

Anesthesiology. 1989;71:162-164.

3. Aida S, Takahashi H, Shimoji K. Renal subcapsular hematoma after lumbar plexus block.

Anesthesiology. 1996;84:452-455.

54. Mishio M, Matsumoto T, Okuda Y, Kitayama T. Delayed severe airway obstruction due to

hematoma following stellate ganglion block. Reg Anesth Pain Med. 1998;23:516-519.

55. Maier C, Gleim M, Weiss T, Stachetzki U, Nicolas V, Zenz M. Severe bleeding following lumbar

sympathetic block in two patients under medication with irreversible platelet aggregation inhibitors.

Anesthesiology. 2002;97:740-743.

56. Horlocker TT, Wedel DJ, Rowlingson JC, et al. Regional anesthesia in the patient receiving

antithrombotic or thrombolytic therapy: American Society of Regional Anesthesia and Pain Medicine

evidence-based guidelines (third edition). Reg Anesth Pain Med. 2010;35:64-101.

57. The Belgian Association for Regional Anesthesia Working Party on Anticoagulants and Central

Nerve Blocks: Vandermeulen E, Singelyn F, Vercauteren M, Brichant JF, Icks BE, Gautier P. Belgianguidelines concerning central neural blockade in patients with drug-induced alteration of coagulation:

an update. Acta Anaesth Belg. 2005;56:139-146.

58. Gogarten W, Van Aken H, Buttner J, Reiss H, Wulf H, Burkle H. Regional anesthesia and

thromboembolism prophylaxis/anticoagulation—revised recommendations of the German Society of

Anaesthesiology and Intensive Care Medicine. Anaesth Intensive Med. 2007;48:S109-S124.

9

Toxicity of Local Anesthetics

Steven Dewaele, and Alan C. Santos

Introduction

Systemic toxicity of local anesthetics can occur after administration of an excessive dose, with rapid

absorption, or because of an accidental intravenous injection. The management of local anesthetic

toxicity can be challenging, and in the case of cardiac toxicity, prolonged resuscitation efforts may be

necessary.1,2 Therefore, understanding the circumstances that can lead to systemic toxicity of local

anesthetics and being prepared for treatment is essential to optimize the patient outcome.

Systemic toxicity is typically manifested as central nervous system (CNS) toxicity (tinnitus,

disorientation, and ultimately, seizures) or cardiovascular toxicity (hypotension, dysrhythmias, and

cardiac arrest).3

 The dose capable of causing CNS symptoms is typically lower than the dose and

concentration result in cardiovascular toxicity. This is because the CNS is more susceptible to local

anesthetic toxicity than the cardiovascular system. However, bupivacaine toxicity may not adhere to

this sequence, and cardiac toxicity may precede the neurologic symptoms.4

 Although less common,

cardiovascular toxicity is more serious and more difficult to treat than CNS toxicity.

Other reported, but much less common, adverse effects of certain local anesthetics include allergic

reactions,5

 methemoglobinemia,6

 and bronchospasm.7

 Direct neural8

 and local tissue toxicity9

 have

been reported also; however, discussion about these topics is beyond the scope of this chapter.

Signs and Symptoms of Systemic Local Anesthetic Toxicity

The earliest signs of systemic toxicity are usually caused by blockade of inhibitory pathways in the

cerebral cortex.10 This allows for disinhibition of facilitator neurons resulting in excitatory cell

preponderance and unopposed (generally enhanced) excitatory nerve activity. As a result, initial

subjective symptoms of CNS toxicity include signs of excitation, such as lightheadedness and

dizziness, difficulty focusing, tinnitus, confusion, and circumoral numbnesss.11,12 Likewise, the

objective signs of local anesthetic toxicity are excitatory, for example, shivering, myoclonia, tremors,

and sudden muscular contractions.13 As the local anesthetic level rises, tonic-clonic convulsions

occur. Symptoms of CNS excitation typically are followed by signs of CNS depression: Seizure

activity ceases rapidly and ultimately is succeeded by respiratory depression and respiratory arrest.

In the concomitant presence of other CNS depressant drugs (e.g., premedication), CNS depression

can develop without the preceding excitatory phase.

The CNS toxicity is directly correlated with local anesthetic potency.14–17 However, there is an

inverse relationship between the toxicity of local anesthetics and the rate at which the agents are

injected: Increasing speed of injection will decrease the blood-level threshold for symptoms to

appear.

All local anesthetics can induce cardiac dysrhythmias,18,19 and all, except cocaine, are

myocardium depressants.20–25 Local anesthetic–induced arrhythmias can manifest as conduction

delays (from prolonged PR interval to complete heart block, sinus arrest, and asystole) to ventricular

dysrhythmias (from simple ventricular ectopy to torsades de pointes and fibrillation). The negative

inotropic action of local anesthetics is exerted in a dose-dependent fashion and consists of depressed

myocardial contractility and a decrease in cardiac output. Dysrhythmias due to local anesthetic

overdose may be recalcitrant to traditional therapies; the reduced myocardial contractility and low

output state further complicate the treatment.

The sequence of cardiovascular events is ordinarily as follows: Low blood levels of local

anesthetic usually generate a small increase in cardiac output, blood pressure, and heart rate, which is

most likely due to a boost in sympathetic activity and direct vasoconstriction. As the blood level of

local anesthetic rises, hypotension ensues as a result of peripheral vasodilation due to relaxation of

the vascular smooth muscles. Further rise of local anesthetic blood levels leads to severe

hypotension, resulting from the combination of reduced peripheral vascular resistance, reduced

cardiac output, and/or malignant arrhythmias. Eventually, extreme hemodynamic instability may lead

to cardiac arrest.

Acid–base status plays an important role in the setting of local anesthetic toxicity.26 Acidosis and

hypercarbia amplify the CNS effects of local anesthetic overdose and exacerbate cardiotoxicity.

Hypercarbia enhances cerebral blood flow; consequently, more local anesthetic is made accessible to

the cerebral circulation. Diffusion of carbon dioxide across the nerve membrane can cause

intracellular acidosis, and as such, it is promoting the conversion of the local anesthetic into the

cationic, or active, form. Because it is impossible for the cationic form to travel across the nerve

membrane, ionic trapping occurs, worsening the CNS toxicity of the local anesthetic. Hypercarbia

and/or acidosis also reduce the binding of local anesthetics by plasma proteins,27 and as a result, the

fraction of free drug readily available for diffusion expands.

Prevention

Prevention of toxicity is key to safer practice, and it starts with making sure that the work environment

is optimized for performing regional anesthesia.28 The logistics for treating an emergency, including

equipment for airway management and treating cardiac arrest, must be readily available and

functioning.

A judicious selection of the type, dose, and concentration of the local anesthetic, and the regional

anesthesia technique, is important. As a rule, the optimal dose and concentration is the lowest one that

achieves the aimed for effect. The effects of pretreatment with a benzodiazepine is often debated but

almost routinely used in our practice. Benzodiazepines lower the probability of seizures29–32 but can

mask early signs of toxicity.33 A sedated patient is theoretically less able to keep the physician

updated on the subjective symptoms of light toxicity, and severe toxicity can establish itself without a

recognizable toxic prodrome. This concern remains only theoretical; many symptoms of limited, mild

CNS toxicity can be prevented by routine premedication with benzodiazepines in addition to making

the PNB procedure more pleasant to patients.

Therefore, the presence of premedication or general anesthesia is not perceived to increase the

risk of local anesthetic toxicity. Considerable research has been invested into the subject of the ideal

test for detecting intravenous injection and to what constitutes the ideal test dose. Epinephrine (5–15

μg) is still widely in use as a marker of intravascular injection. End points with an acceptable

sensitivity are defined by an increase in heart rate >10 bpm, increase in systolic blood pressure by

>15 mm Hg,34 or a 25% decrease in lead II T-wave amplitude.35 However, elderly patients are less

responsive to beta stimulation36 as are those on beta-blocking agents. Low cardiac output can prolong

drug circulation and delay the clinical effect of the beta mimetic, and therefore, the sensitivity of the

test. Accordingly, the interpretation of the test result is not always as straightforward as one would

wish. The significant proportion of false negative test results warrants a reevaluation of the routine

use of this test as a sole determinant to detect inadvertent intravenous injection.

Regardless of whether epinephrine is used as a marker of an intravascular injection, it is of utmost

importance to use slow, incremental injections of local anesthetic, with frequent aspirations (every 3–

5 mL) between injections while monitoring the patient for signs of toxicity.37 A slow rate of injection

of divided doses at distinct intervals can decrease the possibility of summating intravascular

injections. With a rapid injection the seizures may occur at higher blood level because there is no

time for distribution of the drug as compared to a slow infusion where the seizure occurs at a lower

drug level because of the distribution. It is prudent to decrease the local anesthetic dosage in elderly

or debilitated patients and in any patient with diminished cardiac output. However, there are no firm

recommendations on the degree of dose reduction.

Treatment

Early recognition of the toxicity and early discontinuation of the administration is of crucial

importance.38 The administration of local anesthetics should be stopped immediately. The airway

should be maintained at all times, and supplemental oxygen is provided while ensuring that the

monitoring equipment is functional and properly applied. Neurologic parameters and cardiovascular

status should be assessed until the patient is completely asymptomatic and stable.39

Administration of a benzodiazepine to offset or ameliorate excitatory neurological symptoms or a

potential tonic-clonic seizure is indicated.40 Early treatment of convulsions is particularly meaningful

because convulsions can result in metabolic acidosis, thus aggravating the toxicity. Seizures should be

controlled at all times. Based on the recent data in animal studies,41–43 as well as mounting case

reports,44–53 starting an infusion of lipid emulsion (intralipid), especially in those cases where

symptoms of cardiac toxicity are present, should be contemplated early.54 Importantly, there is a

mounting consensus that infusion of intralipids may be initiated early, to also prevent, rather then treat

cardiac arrest. If available, arrangements for transfer to an operating room where cardiopulmonary

bypass can be instituted should also be contemplated in situations where the response to early

treatment is not favorable.55–58

Malignant arrhythmias and asystole are managed using standard cardiopulmonary resuscitation

protocols,59,60 acknowledging that a prolonged effort may be needed to increase the chance of

resuscitation. The rationale of this approach is to maintain the circulation until the local anesthetic is

redistributed or metabolized below the level associated with cardiovascular toxicity, at which time

spontaneous circulation should resume. Because the contractile depression is a core factor underlying

severe cardiotoxicity, it would be intuitive to believe that the use of sympathomimetics should be

helpful. Nonetheless, epinephrine can induce dysrhythmia or it can exacerbate the ongoing arrhythmia

associated with local anesthetic overdose.61,62 Consequently, in the setting of local anesthetic toxicity,

vasopressin may be more appropriate to maintain the blood pressure, support coronary perfusion, and

facilitate local anesthetic metabolism.63 The appropriateness of phosphodiesterase inhibitors

administration is not corroborated by published research results. Although these inhibitors can

promote hemodynamics, there is no evidence of a better outcome. As potent vasodilators,

phosphodiesterase inhibitors do no support blood pressure,64 and they have been associated with

ventricular arrhythmias.65

The current advanced cardiac life support algorithm emphasizes amiodarone as the mainstay drug

for treatment of arrhythmias.66,67 Also, for ventricular arrhythmias prompted by local anesthetic

overdose, current data favor amiodarone. Published studies of using lidocaine to treat arrhythmias

reveal conflicting results, but it is logical to think that treating local anesthetic–induced arrhythmias

with just another local anesthetic antiarrhythmic is likely to add to the cardiotoxicity. The use of

bretylium is no longer endorsed. Occurrence of Torsades des Pointes with bupivacaine toxicity may

require overdrive pacing if that rhythm predominates.

Calcium channel blockers and phenytoin are contraindicated because their coadministration with

local anesthetics may increase the risk of mortality.68,69 Recovery from local anesthetic–induced

cardiac arrest can take enduring resuscitation efforts for more than an hour. Propofol is not an

adequate alternative for treatment with intralipid, although judicious administration to control

seizures when used in small divided doses is appropriate.70,71 Administration of the lipid emulsion

has become an important addition to the treatment of severe local anesthetic toxicity.72 Because it is

still an innovative therapy, future laboratory and clinical experiences are needed for a better

understanding of the mechanisms and further refinement of the treatment protocols.73

Allergic Reactions

The amino-esters, such as chloroprocaine, are all derivatives of the allergen paraaminobenzoic acid

(PABA). Accordingly, the local anesthetics belonging to the ester group may cause positive skin

reactions, ranging from toxic eruptions in situ to generalized rash or urticaria.74 Previous study results

indicate an incidence of 30%, but no subject developed anaphylaxis. However, true allergic reactions

to the local anesthetics of the amino-amide group are extremely rare. By and large, preparations of

amide anesthetics do not cause allergic reactions, unless they contain the preservative methylparaben,

which is in its chemical structure virtually the same as PABA.75 For patients who reported an allergy

to amino-amides, one can safely use a preservative-free amide anesthetic unless a well-documented

allergology reports point to an unambiguous allergy. Anaphylaxis due to local anesthetics remains a

rare event, even within the ester group. It should be considered if the patient starts wheezing or

develops respiratory distress instantly following injection. However, many symptoms can be

explained by a variety of other causes including anxiety, hyperventilation, toxic effects of the drug,

vasovagal reactions, reactions to epinephrine, or contamination with latex.

Management of local anesthetic triggered allergic reactions does not differ from the treatment

algorithms for other more common allergic reactions. Intravenous lidocaine can result in paradoxical

airway narrowing and bronchospasm in patients with asthma. The mechanism of this reaction is not

well understood. Apparently, it is not explained by an exacerbation of the asthmatic condition itself or

by some anaphylactoid cascade activated by lidocaine or its preservatives.

A unique side effect of some local anesthetics is methemoglobinemia.76,77 It has been associated

with the topical, epidural, and intravenous administration of prilocaine. Hepatic metabolism of

prilocaine produces orthotoluidine, which converts hemoglobin into methemoglobin. The doses

needed to effectuate diminished oxygen saturation levels that are clinically significant, however, are

typically above what is used in the clinical practice of regional anesthesia. Regardless, because of

this theoretical possibility, in some countries, the use of prilocaine in regional anesthesia is banned.

The condition of methemoglobinemia caused by prilocaine is spontaneously self-limiting and

reversible. Reversal can be accelerated with the administration of methylene blue intravenously (1

mg/kg).

Summary

Prevention

 Always maintain a high degree of suspicion.

 Monitor electrocardiogram, blood pressure, and arterial oxygen saturation.

 When feasible, communicate with the patient.

 Be conservative with local anesthetic (LA) dose in patients with advanced age, poor cardiac function,

conduction abnormalities, or abnormally low plasma protein concentration.

 Gently aspirate every 3–5 mL.

 Inject slowly (<20 mL/min), and avoid forceful high-pressure injections.

 Use a pharmacologic marker (e.g., epinephrine 5 μg/mL of LA) with high-volume blocks.

 Monitor the patient after high-dose blocks for 30 minutes.

 Be prepared: A plan for managing systemic local anesthetic toxicity should be established in facilities

where local anesthetics are used.

 Current recommendations are to have 20% lipid emulsion stocked close to sites where local

anesthetics are used.

 Consider infusing lipid emulsion early to help prevent cardiac toxicity.

Detection of Systemic LA Toxicity

 Maintain a high degree of suspicion.

 The single most important step in treating local anesthetic toxicity is to consider its diagnosis.

 CNS symptoms are often subtle or absent.

 Cardiovascular signs (e.g., hypertension, hypotension, tachycardia, or bradycardia) may be the first

signs of local anesthetic toxicity.

 CNS excitation (agitation, confusion, twitching, seizure), depression (drowsiness, obtundation, coma,

or apnea), or nonspecific neurologic symptoms (metallic taste, circumoral paresthesias, diplopia,

tinnitus, dizziness) are typical of LA toxicity.

 Ventricular ectopy, multiform ventricular tachycardia, and ventricular fibrillation are hallmarks of

cardiac toxicity of LA.

 Progressive hypotension and bradycardia, leading to asystole, are the hallmark of severe

cardiovascular toxicity.

Treatment of Systemic LA Toxicity

 Get help and call for 20% lipid emulsion.

 Perform airway management. Hyperventilate with 100% oxygen.

 Abolish the seizures.

 Perform cardiopulmonary resuscitation

 Epinephrine–controversial; may have to use higher doses then recommended in ACLS.

 Consider using vasopressin to support circulation

 Alert the nearest facility having cardiopulmonary bypass capability.

 Perform lipid emulsion treatment (for a 70-kg adult patient):

Bolus 1.5 mL/kg intravenously over 1 minute (about 100 mL)

Continuous infusion 0.25 mL/kg per minute (about 500 mL over 30 minutes)

Repeat bolus every 5 minutes for persistent cardiovascular collapse.

Double the infusion rate if blood pressure returns but remains low.

Continue infusion for a minimum of 30 minutes.

DIAGNOSIS AND TREATMENT OF LOCAL ANESTHETIC TOXICITY

REFERENCES

. Weinberg GL. Current concepts in resuscitation of patients with local anesthetic cardiac toxicity. Reg

Anesth Pain Med. 2002;27:568-575.

. Long WB, Rosenblum S, Grady IP. Successful resuscitation of bupivacaine-induced cardiac arrest

using cardiopulmonary bypass. Anesth Analg. 1989;69:403-406.

. Feldman HS. Toxicity of local anesthetic agents. In: Rice SA, Fish KJ, eds. Anesthetic Toxicity. New

York, NY: Raven Press; 1994.

. Albright GA. Cardiac arrest following regional anesthesia with etidocaine or bupivacaine.

Anesthesiology. 1979;51(4):285-287.

. Boren E, Teuber S, Naguwa S, Gershwin M. A critical review of local anesthetic sensitivity. Clin

Rev Allergy Immunol. 2007;32(1):119-127.

. Guay J. Methemoglobinemia related to local anesthetics: a summary of 242 episodes. Anest Analg.

2009;108(3):837-845.

. Burches B, Warner D. Bronchospasm after intravenous lidocaine. Anesth Analg. 2008;107(4):1260-

1262.

. Kalichman MW. Physiologic mechanisms by which local anesthetics may cause injury to nerve and

spinal cord. Reg Anesth. 1993;18(6 Suppl):448-452.

. Sadove S, Kolodny S. Local anesthetic agents in combination with vasoconstrictors part I,

epinephrine. Acta Anaesth Scand. 1961;5(1):13-19.

0. Scott DB. Toxic effects of local anaesthetic agents on the central nervous system. Br J Anaesth.

1986;58:732-735.

1. Scott DB. Evaluation of the toxicity of local anaesthetic agents in man. Br J Anaesth. 1975;47:56-

61.

2. Mather LE, Tucker GT, Murphy TM, Stanton-Hicks MD, Bonica JJ. Cardiovascular and subjective

central nervous system effects of long-acting local anaesthetics in man. Anaesth Intensive Care.

1979;7:215-221.

3. Scott DB. Evaluation of clinical tolerance of local anaesthetic agents. Br J Anaesth. 1975;47

Suppl:328-331.

4. Rutten AJ, Nancarrow C, Mather LE, et al. Hemodynamic and central nervous system effects of

intravenous bolus doses of lidocaine, bupivacaine, and ropivacaine in sheep. Anesth Analg.

1989;69:291-299.

5. Huang YF, Pryor ME, Mather LE, et al. Cardiovascular and central nervous system effects of

bupivacaine and levobupivacaine in sheep. Anesth Analg. 1998;86:797-804.

6. Feldman HS, Arthur GR, Covino BG. Comparative systemic toxicity of convulsant and

supraconvulsant doses of intravenous ropivacaine, bupivacaine, and lidocaine in the conscious dog.

Anesth Analg. 1989;69:794-801.

7. Liu P, Feldman H, Giasi R, Patterson M, Covino B. Comparative CNS toxicity of lidocaine,

etidocaine, bupivacaine, and tetracaine in awake dogs following rapid administration. Anesth Analg.

1983;62:375-379.

8. Reiz S, Nath S. Cardiotoxicity of local anaesthetic agents. Br J Anaesth. 1986;58:736-746.

9. Hogan Q. Local anesthetic toxicity: an update. Reg Anesth. 1996;21(6S):43-50.

0. Feldman HS, Covino BM, Sage DJ. Direct chronotropic and inotropic effects of local anesthetic

agents in isolated guinea pig atria. Reg Anesth. 1982;7:149-156.

1. Lynch C. Depression of myocardial contractility in vitro by bupivacaine, etidocaine, and lidocaine.

Anesth Analg. 1986;65:551-559.

2. Block A, Covino B. Effect of local anesthetic agents on cardiac conduction and contractility. Reg

Anesth. 1982;6:55-61.

3. Stewart D, Rogers W, Mahaffrey J, Witherspoon S, Woods E. Effect of local anesthetics on the

cardiovascular system in the dog. Anesthesiology. 1963;24:620-624.

4. Tanz RD, Heskett T, Loehning RW, Fairfax CA. Comparative cardiotoxicity of bupivacaine and

lidocaine in the isolated perfused mammalian heart. Anesth Analg. 1984;63:549-556.

5. Pitkanen M, Feldman HS, Authur GR, Covino BG. Chronotropic and inotropic effects of

ropivacaine, bupivacaine, and lidocaine in the spontaneously beating and electrically paced isolated,

perfused rabbit heart. Reg Anesth Pain Med. 1992;17:183-192.

6. Englesson S. The influence of acid-base changes on central nervous system toxicity of local

anaesthetic agents. I. An experimental study in cats. Acta Anaesth Scand. 1974;18:79-87.

7. Burney R, DiFazio C, Foster J. Effects of pH on protein binding of lidocaine. Anesth Analg. 1978;

57:478-480.

8. Mulroy M. Systemic toxicity and cardiotoxicity from local anesthetics: incidence and preventive

measures. Reg Anesth Pain Med. 2002;27(6):556-561.

9. de Jong RH, Heavner JE. Diazepam prevents local anesthetic seizures. Anesthesiology.

1971;34:523-531.

0. de Jong RH, Heavner JE. Diazepam prevents and aborts lidocaine convulsions in monkeys.

Anesthesiology. 1974;41:226-230.

1. de Jong RH, Bonin JD. Benzodiazepines protect mice from local anesthetic convulsions and deaths.

Anesth Analg. 1981;60:385-389.

2. Ausinsch B, Malagodi MH, Munson ES. Diazepam in the prophylaxis of lignocaine seizures. Br J

Anaesth. 1976;48:309-313.

3. Liguori G, Chimento GF, Borow L, Figgie M. Possible bupivacaine toxicity after intraarticular

injection for postarthroscopic analgesia of the knee: implications of the surgical procedure. Anesth

Analg. 2002; 94:1010-1013.

4. Kahn RL, Quinn TJ. Blood pressure, not heart rate, as a marker of intravascular injection of

epinephrine in an epidural test dose. Reg Anesth. 1991;16:292-295.

5. Tanaka M, Nishikawa T. A comparative study of hemodynamic and T-wave criteria for detecting

intravascular injection of the test dose (epinephrine) in sevoflurane-anesthetized adults. Anesth

Analg. 1999;89:32-36.

6. Schoenwald PK, Whalley DG, Schluchter MD, Gottlieb A, Ryckman JV, Bedocs NM. The

hemodynamic responses to an intravenous test dose in vascular surgical patients. Anesth Analg.

1995;80:864-868.

7. Weinberg G. Current concepts in resuscitation of patients with local anesthetic cardiac toxicity. Reg

Anesth Pain Med. 2002;27(6):568-575.

8. Feldman HS, Arthur GR, Pitkanen M, Hurley R, Doucette AM, Covino BG. Treatment of acute

systemic toxicity after the rapid intravenous injection of ropivacaine and bupivacaine in the conscious

dog. Anesth Analg. 1991;73:373-384.

9. Association of Anaesthetists of Great Britain and Ireland. Guidelines for the Management of

Severe Local Anaesthetic Toxicity. London, UK: AAGBI, 2007.

0. Crews JC, Rothman TE. Seizure after levobupivacaine for interscalene brachial plexus block.

Anesth Analg. 2003; 96:1188-1190.

1. Weinberg G, VadeBoncouer T, Ramaraju G, Garcia- Amaro M, Cwik M. Pretreatment or

resuscitation with a lipid infusion shifts the dose-response to bupivacaine-induced asystole in rats.

Anaesthesiology. 1998;88:1071-1075.

2. Weinberg G, Ripper R, Feinstein D, Hoffman W. Lipid emulsion infusion rescues dogs from

bupivacaine induced cardiac toxicity. Reg Anesth Pain Med. 2003; 8:198-202.

3. Weinberg G, Di Gregorio G, Ripper R, et al. Resuscitation with lipid versus epinephrine in a rat

model of bupivacaine overdose. Anesthesiology. 2008;108:907-913.

4. Rosenblatt M, Abel M, Fischer G, Itzkovich C, Eisenkraft J. Successful use of a 20% lipid emulsion

to resuscitate a patient after a presumed bupivacaine related cardiac arrest. Anaesthesiology.

2006;105:217-218.

5. Litz R, Popp M, Stehr S, Koch T. Successful resuscitation of a patient with ropivacaine-induced

asystole after axillary plexus block using lipid infusion. Anaesthesia. 2006;61:800-801.

6. McCutchen T, Gerancher J. Early Intralipid may have prevented bupivacaine associated cardiac

arrest. Reg Anaesth Pain Med. 2008;33:178-180.

7. Foxall G, McCahon R, Lamb J, Hardman J, Bedforth N. Levobupivacaine-induced seizures and

cardiovascular collapse treated with Intralipid. Anaesthesia. 2007;62:516–518.

8. Whiteside J. Reversal of local anaesthetic induced CNS toxicity with lipid emulsion. Anaesthesia.

2008;63:203–204.

9. Spence A. Lipid reversal of central nervous system symptoms of bupivacaine toxicity.

Anaesthesiology. 2007;107:516–517.

0. Litz R, Roessel T, Heller A, Stehr S. Reversal of central nervous system and cardiac toxicity

following local anaesthetic intoxication by lipid emulsion injection. Anesth Analg. 2008;106:1575–

1577.

1. Zimmer C, Piepenbrink K, Riest G, Peters J. Cardiotoxic and neurotoxic effects after accidental

intravascular bupivacaine administration. Therapy with lidocaine propofol and lipid emulsion.

Anaesthesist. 2007;56(5):449-453.

2. Ludot H, Tharin JY, Belouadah M, Mazoit JX, Malinovsky JM. Successful resuscitation after

ropivacaine and lidocaine-induced ventricular arrhythmia following posterior lumbar plexus block in

a child. Anesth Analg. 2008;106(5):1572-1574.

3. Warren JA, Thoma RB, Georgescu A, Shah SJ. Intravenous lipid infusion in the successful

resuscitation of local anesthetic-induced cardiovascular collapse after supraclavicular brachial

plexus block. Anesth Analg. 2008;106(5):1578-1580.

4. Picard J, Meek T. Lipid emulsion to treat overdose of local anaesthetic: the gift of the glob.

Anaesthesia. 2006;61:107–109.

5. Tsai MH, Tseng CK, Wong KC. Successful resuscitation of a bupivacaine-induced cardiac arrest

using cardiopulmonary bypass and mitral valve replacement. J Cardiothorac Anesth. 1987;1:454-

456.

6. Long WB, Rosenblum S, Grady IP. Successful resuscitation of bupivacaine-induced cardiac arrest

using cardiopulmonary bypass. Anesth Analg. 1989;69:403-406.

7. Freedman MD, Gal J, Freed CR. Extracorporeal pump assistance—novel treatment for acute

lidocaine poisoning. Eur J Clin Pharmacol. 1982;22:129-135.

8. Soltesz EG, van Pelt F, Byrne JG. Emergent cardiopulmonary bypass for bupivacaine

cardiotoxicity. J Cardiothorac Anesth. 2003;17:357-358.

9. Chazalon P, Tourtier JP, Villevieille T, et al. Ropivacaine-induced cardiac arrest after peripheral

nerve block: successful resuscitation. Anesthesiology. 2003;99:1449–1451.

0. Huet O, Eyrolle LJ, Mazoit JX, Ozier YM. Cardiac arrest and plasma concentration after injection

of ropivacaine for posterior lumbar plexus blockade. Anesthesiology. 2003;99:1451–1453.

1. Heavner JE, Pitkanen MT, Shi B, Rosenberg PH. Resuscitation from bupivacaine-induced asystole

in rats: comparison of different cardioactive drugs. Anesth Analg. 1995;80:1134-1139.

2. Bernards CM, Carpenter RL, Kenter ME, Brown DL, Rupp SM, Thompson GE. Effect of

epinephrine on central nervous system and cardiovascular system toxicity of bupivacaine in pigs.

Anesthesiology. 1989;71:711-717.

3. Krismer AC, Hogan QH, Wenzel V, et al. The efficacy of epinephrine or vasopressin for

resuscitation during epidural anesthesia. Anesth Analg. 2001;93:734-742.

4. Arnold JM. The role of phosphodiesterase inhibitors in heart failure. Pharmacol Ther.

1993;57:161-161.

5. DiBianco R, Shabetai R, Kostuk W, Moran J, Schlant RC, Wright R. A comparison of oral

milrinone, digoxin, and their combination in the treatment of patients with chronic heart failure. N

Engl J Med. 1989;320:677-683.

6. Nolan JP, Deakin CD, Soar J, Böttiger BW, Smith G. European Resuscitation Council Guidelines

for Resuscitation 2005 Section 4. Adult advanced life support. Resuscitation. 2005;67S1:S39-S86.

7. 2005 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency

Cardiovascular Care: Part 7.3: Management of Symptomatic Bradycardia and Tachycardia.

Circulation. 2005;112:IV-67-IV-77.

8. Tallman RD Jr, Rosenblatt RM, Weaver JM, Wang YL. Verapamil increases the toxicity of local

anesthetics. J Clin Pharmacol. 1988;28:317-321.

9. Simon L, Kariya N, Pelle-Lancien E, Mazoit JX. Bupivacaine-induced QRS prolongation is

enhanced by lidocaine and by phenytoin in rabbit hearts. Anesth Analg. 2002; 94:203-207.

0. Heavner JE, Arthur J, Zou J, McDaniel K, Tyman-Szram B, Rosenberg PH. Comparison of propofol

with thiopentone for treatment of bupivacaine-induced seizures in rats. Br J Anaesth. 1993;71:715-

719.

1. Momota Y, Artru AA, Powers KM, Mautz DS, Ueda Y. Posttreatment with propofol terminates

lidocaine induced epileptiform electroencephalogram activity in rabbits: effects on cerebrospinal

fluid dynamics. Anesth Analg. 1998;87:900-906.

72. Weinberg GL. Lipid infusion therapy: translation to clinical practice. Anesth Analg.

2008;106(5):1340-1342.

73. Cave G, Harvey M. Intravenous lipid emulsion as antidote beyond local anesthetic toxicity: a

systematic review. Acad Emerg Med. 2009;16(9):815-824.

74. Aldrete JA, Johnson DA. Evaluation of intracutaneous testing for investigation of allergy to local

anesthetic agents. Anesth Analg. 1970;49:173-183.

75. Cashman AL, Warshaw EM. Parabens: a review of epidemiology, structure, allergenicity, and

hormonal properties. Dermatitis. 2005;16(2):57-66.

76. Lund PC, Cwik JC. Propitocaine (Citanest) and methemoglobinemia. Anesthesiology. 1965;

26:569-571.

77. Scott DB, Owen JA, Richmond J. Methemoglobinemia due to prilocaine. Lancet. 1964;284:728-

729.

10

Neurologic Complications of Peripheral Nerve Blocks

Jeff Gadsden

Nerve injury following peripheral nerve blockade (PNB) is a potentially devastating complication

that can result in permanent disability.1

 Data from a recent review of published studies suggest that

the incidence of neurologic symptoms following PNB varies depending on the anatomic location,

ranging from 0.03% for supraclavicular blocks to 0.3% for femoral blocks to up to 3% for

interscalene blocks.2

 Fortunately, the vast majority of these neuropathies appear to be temporary

rather than permanent neuropathy and resolve over weeks to months.

The exact etiology of neurologic injury related to PNB remains unclear in many instances.

Suggested etiologies include mechanical trauma from the needle, nerve edema and/or hematoma,

pressure effects of the local anesthetic injectate, and neurotoxicity of the injected solutions (both local

anesthetics and adjuvants, e.g., epinephrine).3

 Confounding factors that may play a role in nerve injury

include preexisting neuropathies (e.g., diabetes mellitus), surgical manipulation, prolonged tourniquet

pressure, or compression from postoperative casting.4

It is well-established that direct injection into peripheral nerves (i.e., accidentally during

intramuscular administration) can result in nerve injury.5

 This is one of the reasons why intraneural

injections are avoided during peripheral nerve blockade. More recent data however, suggest that

intraneural injections are not always associated with nerve injury. This chapter summarizes the

clinically relevant considerations regarding the etiology of nerve injury during peripheral nerve

blockade.

Histology and Histopathology of Peripheral Nerves

Knowledge of the functional histology of nerves is essential to understanding the consequences of

intraneural injection. Nerves are made up of fascicles supported and enveloped by perineurium and a

loose collection of collagen fibers termed the epineurium. The epineurium is easy permeable and

carries the nutritive vessels of larger nerves. Each fascicle is made up of bundles of nerve fibers

(axons) and their associated Schwann cells held together by a tough squamous epithelial sheath called

the perineurium, which acts as a semipermeable barrier to local anesthetics. The nerve fibers are

supported within the perineurium by a delicate connective tissue matrix called the endoneurium,

which contains capillaries that arise from the larger epineurial vessels. Figure 10-1 features normal

anatomy of a mixed peripheral nerve and relationship of the epineurium and perineurium.

FIGURE 10-1. Anatomy of the peripheral nerve as seen on an electron microscopy image. 1-

Epineurium, 2-Fascicle, 3-Fascicular bundles (several fascicles bound together), Arrowsperineurium.

Peripheral nerve lesions can be classified in terms of their degree of functional disruption.6

Neurapraxia refers to a mild insult in which the axons and connective tissue structures supporting

them remain intact. This type of injury is often associated with focal demyelination and generally

reversible over the course of weeks to several months. Axonal interruption with conservation of the

neural connective tissues is termed axonotmesis. Regeneration at a rate of 1 to 2 mm/day occurs, and

recovery is generally favorable although not always complete. Neurotmesis represents complete

fascicular interruption, including the axons and the connective tissue supporting tissues. Because the

nerve is severed, recovery depends on surgical reapproximation of the two stumps. Even with prompt

surgical intervention, recovery is often poor. It is important to note that most nerve injuries are mixed,

with different fascicles exhibiting characteristics of these three different injury types.

The Problem, or Is It?

Selander et al provided evidence of the deleterious effects of intraneural injection over 30 years ago7

Indeed, the objective during peripheral nerve blockade has been to deposit local anesthetic in the

vicinity, but not within, the substance of the nerve. This tacit convention has been challenged in recent

years with the publication of a series of reports suggesting that intraneural needle placement, and

indeed injection of local anesthetic, may not necessarily result in detectable clinical injury. In 2004

Sala-Blanch et al described two cases of placement of a catheter within the epineurium of the sciatic

nerve, confirmed by computerized tomographic imaging.8

 Both patients demonstrated clinically

efficacious blocks without postoperative neurologic deficit. The advent of ultrasound guidance for

nerve blocks has likely led to an increase in the recognition of inadvertent intraneural injections.

Accidental femoral9

 and musculocutaneous10 intraneural injections have been described, as

evidenced by nerve swelling on the ultrasound image, both without lasting neurologic effect.

In 2006, Bigeleisen published a series of axillary brachial plexus blocks performed on 22 patients

undergoing thumb surgery.11 Using ultrasound guidance, the authors deliberately placed the needle

intraneurally and injected 2 to 3 mL of local anesthetic, which resulted in 72 intraneural injections as

evidenced by nerve swelling. Despite the common occurrence of paresthesia or dysesthesia (66

times), none of the patients developed an overt neurologic deficit up to 6 months postoperatively.

Similarly, Robards et al studied 24 patients receiving sciatic nerve blocks in the popliteal fossa

using both nerve stimulation and ultrasound guidance.12 The end point for needle advancement was a

motor response using a current intensity of 0.2 to 0.5 mA, or an apparent intraneural needle tip

location, whichever came first. These investigators found that the motor response could only be

obtained upon entry of the needle into the nerve in 83.3% of patients; in the remaining 16.7%, a motor

response with a stimulating current of 1.5 mA could not be obtained, even when the needle tip was

intraneural. There was no postoperative neurologic dysfunction.

Taken together, these studies suggest that an intraneural needle placement with resultant injection

of the local anesthetic within internal epineurium does not lead to an imminent neurologic injury. The

data by Robards et al, suggest that many nerve blocks without the benefit of ultrasound visualization,

have likely resulted in intraneural (intra-epineural) injections. The reason why nerve injury is

infrequent is that the vast majority of these injections do not occur within fascicles.

Extrafascicular versus Intrafascicular Injections

A needle placed within a peripheral nerve can be in one of two locations: within the loose epineurial

matrix that surrounds the fascicles or inside a fascicle itself. It is well-established that injection of

even very small amounts of local anesthetic within the fascicle can lead to widespread axonal

degeneration and permanent neural damage in animals, whereas extrafascicular injection does not

disrupt the normal nerve architecture.7,13 Part of this can be explained mechanically because the

perineurium, a tough multilayer epithelial sheath, is not easily distensible to compensate to an

increase in intrafascicular pressure. Intrafascicular pressure rises on injection and can remain higher

than the capillary perfusion pressure longer than the duration of the injection itself, predisposing to

neural ischemia and inflammation.14 Furthermore, pressure curves derived from intrafascicular versus

extrafascicular injections in canine sciatic nerves show that a pattern of very high initial injection

pressures followed by a sharp drop to baseline is associated with poor outcome and severe neural

histologic damage, and may suggest fascicular rupture.15 In contrast, injections into the compliant

epineurial space appear to be associated with a minimal rise in pressure, which can be explained by

its loose and accommodating stromal architecture.

The risk of an intrafascicular injection differs from site to site in the peripheral nervous system,

and it correlates with the cross-sectional fascicle-epineurium ratio. For example, the sciatic nerve at

the popliteal fossa contains more nonneural tissue than fascicles in its cross-sectional area, which

corresponds with its low incidence of post-PNB neuropathy.16 By contrast, the brachial plexus at the

level of the trunks contains much more neural than connective tissue; a needle entering the nerve here

is more likely to encounter a fascicle on its trajectory that may contribute to the disproportionately

higher rate of postoperative neuropathy following PNB with interscalene blocks.17 As peripheral

nerves move away from the neuraxis, the ratio of connective tissue to neural tissue within the nerve

tends to increase. The brachial plexus elements below the clavicle have a ratio of connective tissue to

neural tissue of approximately 2:1, whereas the more proximal trunks and divisions have a ratio of

1:1.18

Mechanisms of Nerve Injury Following Intraneural Injection

Once the perineurium is breached, the spectrum of subsequent injury is wide and multifactorial.

Needle Trauma

The mechanical disruption of the perineurial sheath may result in injury to the axons and/or the

leakage/herniation of endoneural contents.19 However, the composition of the injectate may play a

larger role in the outcome of intrafascicular injection. For example, normal saline injected into

fascicles did not cause any damage in one study, suggesting that mere puncture of the perineurium

does not necessarily result in clinically overt injury.13 In contrast, nerve puncture with intravenous

cannulae or electroneurography needles has been shown to result in lasting neurologic deficit.20–22 A

variety of cellular changes accompany needle trauma, including alterations in membrane channel

expression, activation of signal transduction, neuropeptide production, and an overall increase in

excitability at the dorsal horn.23,24 The effect of the needle size on the likelihood and severity of the

injury is controversial, however, smaller needles (24 gauge) may lead to less nerve injury than larger

needles (19 gauge).25

Despite the concern over fascicular puncture, due to their compact nature, fascicles are more likely

to escape the advancing needle, rather than be penetrated under normal PNB conditions. Early work

by Selander et al in rabbits demonstrated that needle tip characteristics influenced the likelihood of

fascicular penetration.26 This study demonstrated that long-bevel (12–15°) needles were more likely

to puncture the fascicle than short-bevel (45°) needles, and resulted in the author advocating for their

use during PNB. A more recent study compared blunt (30°) versus sharp (15°) needles by passing

these needles through a cadaveric sciatic nerve and examining the nerve microscopically afterward

for signs of fascicular damage.27 Although a total of 134 fascicles were identified as being in contact

with the needle tracks, only 4 fascicles were damaged, all of which belonged to the sharp-tip group.

These data suggest that a needle passing through a fascicle is more likely only to encounter

epineurium and may in fact displace the tough fascicles away from the needle path. Although blunt

needles are less likely to enter the fascicle, once penetrated, blunt needles appear to cause a greater

degree of injury compared with sharp needles, especially if the sharp needles are oriented with the

bevel in the same direction as the nerve fibers (i.e., not cutting transversely across the fibers).28

Regardless of which needle type or size enters the nerve, a needle insertion into nerve and consequent

injection invariably leads to inflammation and cellular infiltration regardless of whether a clinical

injury occurs.

Toxicity of Local Anesthetics and Additives

Although all local anesthetics are potentially neurotoxic,29 the mechanism remains unclear. Proposed

mechanisms include increases in intracellular calcium concentration, disturbance in mitochondrial

function, interference with membrane phospholipids, and cell apoptosis.30–33 The perineurium and

blood vessel endothelium serve as a barrier to entry into the fascicle. However, even local

anesthetics placed within the epineurium have been shown to cause altered perineural permeability

and fascicular edema, leading to compression of the fascicle and reduced neural blood flow.13,34 This

effect appears to be dose dependent.

Intraneural administration of local anesthetics exposes the axons to higher concentrations of drug

than extraneural application. One study comparing the extraneural, extrafascicular, and intrafascicular

administration of ropivacaine 0.75% showed that histologic damage was least severe extraneurally

and most severe intrafascicularly.35 However, even when injected inside the epineurium, others have

shown ropivacaine 0.75% to have no adverse effect on functional recovery.36 Ester local anesthetics

such as tetracaine and chloroprocaine were shown in some studies to cause a greater degree of injury

than those of the amide group, but recent data have challenged those conclusions.34,37 What is well

known is that the injection of local anesthetics into the fascicle results in widespread and immediate

axonal injury.14

Local anesthetics alone are also capable of decreasing neural blood flow. Lidocaine 2% reduces

neural blood flow in rat sciatic nerves by 20–40%, and this difference persists after washout of the

local anesthetic solution.38,39 Increasing concentrations of lidocaine appear to reduce neural blood

flow further; the reverse is true for bupivacaine. Altering the concentration of tetracaine appears to

have no effect on neural blood flow. Various concentrations of levobupivacaine and ropivacaine have

been found to reduce rat sciatic nerve blood flow significantly.40

Epinephrine is a common adjuvant used to prolong the duration of blockade and to warn of

intravascular injection/absorption. At concentrations of 5 μg/mL and 10 μg/mL, epinephrine reduces

neural blood flow by 20% and 35%, respectively.39 In contrast, at lower concentrations (2.5 μg/mL),

neural blood flow increases by 20% transiently before returning to baseline, suggesting that at lower

concentrations the β-adrenergic effects predominate. The effects of combining lidocaine and

epinephrine are additive: A solution of 2% lidocaine plus 5 μg/mL of epinephrine reduced neural

blood flow by 80%.38

The clinical significance of the effects of various local anesthetics and additives is unknown. The

experimental data must be weighed within the context of clinical practice; countless of nerve blocks

of blocks are performed in daily practice using a combination of local anesthetic and epinephrine

with no neurologic consequences. This reinforces the hypothesis that nerve injury is multifactorial,

and one theoretical aspect may be insufficient to cause injury consistently.

Prevention of Peripheral Nerve Injury

Several techniques have been advocated to enhance safety during the performance of PNBs. The

merits of each technique in preventing nerve injury are addressed individually.

Pain on Injection

Pain on injection has traditionally been taught as a reliable and effective means to guard against

intraneural injection because intraneural injections are thought to be exquisitely painful. However,

there are multiple problems with this logic. First, pain is notoriously difficult to evaluate in terms of

intensity and quality. Consequently, differentiating between a benign, commonly present discomfort

during injection of local anesthetic (pressure paresthesia) and that of intrafascicular injection can be

elusive. Second, various patient conditions (e.g., diabetes mellitus, peripheral neuropathy) and

premedication may interfere with pain perception. Third, there appears to be little evidence that pain

on injection is either sensitive or specific. Fanelli et al conducted a prospective study of nearly 4000

patients receiving multiple-injection PNBs and found that the overall rate of neurologic complications

was 1.7%, independent of whether the patient reported a paresthesia or not.41 In other words, it does

not appear to matter whether the patient reports a paresthesia or not—they have an equal likelihood of

postoperative neuropathy. Bigeleisen’s report of 72 intraneural injections was associated with 66

reports of paresthesia or dysesthesia, yet none of the patients had neurologic complications,

suggesting the symptom itself has a low specificity for complications.11 Fourth, the nature of nerve

injury might preclude its use as a useful monitor: By the time a patient registers pain, communicates it

to the anesthesiologist, and the injection is halted, the damage is likely to have been done. Because a

fraction of a milliliter is sufficient to cause irreversible fascicular damage, the patient’s subjective

symptom may be too late.7,15 Finally, there are situations in which performing PNBs in an

asleep/heavily sedated/blocked patient might be the safest approach, for example, pediatric cases,

mentally incompetent patients, the traumatically injured, patients needing rescue or repeat blocks, and

so on. The use of more objective monitors, as listed here, may provide increased confidence that an

intrafascicular injection can be avoided when compared with a subjective patient symptom.

Electrical Nerve Stimulation

Electrical stimulation is a means to locate nerves but also may be used to rule out an intraneural

(intrafascicular) location of the needle. Voelckel et al demonstrated that sciatic blocks in pigs

performed with a motor response at <0.2 mA resulted in inflammatory nerve changes in 50% of the

specimens, compared with none when the motor response was achieved at 0.3 to 0.5 mA.42 Others

have investigated the relationship between current intensity and needle-nerve distance in pigs and

found that, although the relationship is unpredictable outside the epineurium, a motor response at a

current intensity of <0.3 mA occurs only with intraneural needle placement.43,44 These findings have

been substantiated in a clinical study of patients undergoing ultrasound-guided supraclavicular block,

in which minimal threshold currents were recorded at “extraneural” and “intraneural” positions.45

The investigators found that no motor response could be elicited at a current of ≤0.2 mA unless the

needle tip was intraneural.

These studies suggest that, although neurostimulation techniques may not be a highly sensitive

method of detecting intraneural needle tip position (i.e., high current intensities may still be required

to elicit motor responses even with intra-epineural needle placement), neurostimulation has a high

specificity for identifying intraneural needle tip placement (i.e., motor response at ≤0.2 mA obtained

only with intraneural needle tip location) Based on the cumulative experimental and clinical data,

using no motor response at <0.2–0.3 mA as a cutoff for safe practice before injecting local anesthetic

makes clinical sense as a routine monitoring method for most nerve blocks.

Ultrasonography

Ultrasound guidance is theoretically an attractive means of preventing intraneural injection due to

real-time imaging of the needle and nerve. Indeed, nerve swelling visualized on the sonographic

image appears to represent true histologic intraneural injection as evaluated by the presence of India

ink staining within the epineurium.44,46 However, the clinical implications of this are also unclear

because nerve swelling and even histologic changes associated with nerve injury appear not to result

in detectable neurologic deficit in pigs, although there may be subtle changes that cannot be assessed

by the evaluators.47

Ultrasound guidance may not be a substantially effective means of preventing nerve injury. The

reliability of ultrasound to keep the needle tip extraneural depends largely on the skill of the operator

and the imaging characteristics of the needle and tissue. Several case reports of accidental nerve (and

vascular) puncture despite the use of ultrasound guidance highlight the fact that ultrasound monitoring

is not a fail-proof method of avoiding neurologic (and other mechanical) complications.9,10,48

Furthermore, at the present time the resolution of the sonographic image is such that it would be

impossible to tell if the needle tip was intrafascicular or extrafascicular, which is the critical

anatomic differentiation to make to avoid nerve injury. Finally, as is the case with paresthesia, by the

time the nerve is seen swelling on the image, the damage may have already been done if the injection

is made with the needle tip inside the fascicle.

Injection Pressure Monitoring

The crux of the intraneural injection problem thus far appears to lie in the avoidance of penetrating the

perineurium and entering the fascicle. The presence of a high opening injection pressure (>20 psi) in

a canine model is a very sensitive (if not highly specific) sign of intrafascicular needle tip placement,

whereas extrafascicular needle tip placement is associated with low (<10 psi) pressures.15 Another

dog study showed that some, but not all, intraneural injections resulted in high (>20 psi) pressures,

whereas high pressures were absent during extraneural injection.49 More importantly, high pressure

injection was associated with neurologic deficits and severe axonal damage after the block, in

contrast to normal neurologic and histologic findings following any low-pressure injection (extra or

intraneural). Indeed, PNBs associated with high injection pressure, despite a lack of paresthesia, have

been reported to result in permanent neurologic injury.50 Although objective injection pressure

monitoring and documentation has not yet been universally adopted, assessment of resistance to

injection is a standard clinical practice. Unfortunately, clinical data on the role of injection pressure

monitoring may never become available as it would be unethical to randomize patients to receive a

high versus low pressure nerve block injection. However, the available clinical and experimental

evidence points that injection pressure is useful in detecting needle-nerve contact (Table 10-1).

TABLE 10-1

Given this, safe practice should include the objective assessment of the resistance to injection with

most single injection peripheral nerve blocks. An assessment of injection resistance is often assessed

using a “syringe-hand-feel” technique. However, it has been well documented (in at least two

models) that practitioners are unable to gauge injection pressure by using a syringe-hand-feel

subjective technique.51,52 Therefore, if monitoring of resistance to injection is to have clinical merit,

objective monitoring of injection pressure should be used to standardize the injection force. This may

be achieved by use of commercially available inline devices or with the use of a “compressed air

injection technique.”53 One shortcoming of injection pressure monitoring is that injection pressure is

highly sensitive but lacks specificity. In other words, absence of high injection pressure appears to

effectively rule out an intrafascicular injection. However, high injection pressure also can be caused

by PNB needle obstruction, attempted injection into a tendon, or tissue compression caused by the

ultrasound transducer.

Future Directions

The regional anesthesia community is witnessing the beginning of a paradigm shift in the thinking

surrounding intraneural injection during PNB. Clearly they can be performed safely in certain

patients. The question is: Should they? Even intranueral extrafascicular injection of local anesthetic

often results in histologic evidence of inflammation in animal experiments. However, intraneural

extrafascicular injection in patients often does not result in symptoms. The risk may be different in

patients who have preexisting or subclinical neuropathy. It is important to note that the studies

demonstrating safe intraneural injections in humans deliberately excluded patients with preexisting

neuropathy.

Deliberate injection of local anesthetic into peripheral nerves and plexuses is controversial with

regards to its safety and clinical advantages. Such injections in distal nerves may be more forgiving,

owing to their increased ratio of nonneural tissue to neural tissue. In particular, injuries to the sciatic

nerve at the popliteal fossa appear to be uncommon following intraneural injection or intraneural

catheter placement.54,55 In fact, it has been noted that intraneural injection of local anesthetic in the

popliteal sciatic nerve leads to a rapid onset of sensory and motor blockade, without complications.55

Some practitioners now routinely attempt to place the needle tip within the epineurium at this

location, in an attempt to hasten onset, improve block success, and decrease the total amount of local

anesthetic required. However, this practice should be done only with a combination of objective

monitoring because the need to remain extrafascicular is paramount.

One of the challenges is to elucidate the precise factors that provide for a safe intraneural

injection, whether anatomic (popliteal sciatic versus subgluteal), technological (injection pressure

monitoring, improved resolution of ultrasound imaging), educational (improved training), or

otherwise. More clinical research is needed to clarify the safety of intraneural injection in various

nerves such as the femoral nerve, and distal nerves of the upper and lower limbs. This should be

undertaken with care and with proper safeguards to prevent penetration of the perineurium. Lastly,

intraneural injection may allow for reduction in the volume and/or concentration of local anesthetic

required for effective nerve block.54 This is a worthwhile avenue to explore, both in terms of the

implications for nerve injury and for reducing the potential for systemic local anesthetic toxicity. A

combination of monitoring to decrease the risk of an intrafascicular injection during peripheral nerve

blocks is demonstrated in Figure 10-2 as well as in Chapter 5.

MONITORING DURING NERVE BLOCKS: COMBINING ULTRASOUND (US), NERVE

STIMULATION (NS) AND INJECTION PRESSURE MONITORING

FIGURE 10-2.

Practical Management of Postoperative Neuropathy

Despite the best precautions, a postoperative sensory or motor deficit that outlasts the expected

duration of the PNB may occur. It is important to note that the vast majority of neuropathies resolve

spontaneously, and patient reassurance is vital.36 Processes that are either evolving (i.e. compartment

syndrome) or are reparable (i.e. surgical transection of a nerve) should be ruled out. Here are a few

principles to bear in mind when managing a postoperative neuropathy:

. Good communication is essential, both from a patient care and medicolegal standpoint.

. Approximately 95% of postoperative sensory changes will resolve within 4–6 weeks, and most of

these will occur during the first week. 99% of sensory changes will resolve within the first year.

. Early diagnosis of postoperative peripheral nerve injury can be challenging due to:

 residual sedation and/or PNB

• pain that limits the examination

• casts, dressings, splints, slings

• movement restrictions

• patient expectations regarding block—"I didn’t know how long it was supposed to last"

. Neuropathies can also be caused by prolonged tourniquets, casting, excessive intraoperative traction,

or a misplaced surgical clip. Early involvement of the surgical team is prudent.

. In general, the presence of motor deficits is an ominous sign, and a referral to a neurologist and/or

neurosurgeon is indicated.

. Neuropathies that are evolving, and those that are severe/complete should be seen immediately by a

neurologist and/or neurosurgeon.

Referral for electrophysiologic testing may be indicated when the symptoms are not purely

sensory, or when the neuropathy is severe and/or long-lasting. Studies performed usually consist of

the following:

. Electromyography. This is undertaken to determine which muscle units are affected by a denervation

lesion. Small needle electrodes are placed in various muscles and the pattern of electrical activity

both at rest and with contraction is analyzed. The results can help to localize a lesion, and, depending

on the pattern, suggest a time frame for the injury.

. Nerve conduction studies. In these tests, a device similar to the peripheral nerve stimulator used by

anesthesiologists to monitor the degree of neuromuscular blockade is attached over various nerves in

the affected area. A characteristic waveform is generated following stimulation of the nerve, which

may allow the neurologist to pinpoint a conduction block.

The optimal timing of these tests depends on the indication. An exam within 2–3 days of the onset

of injury may give information regarding the completeness of the lesion (and therefore prognosis), as

well as clues about the duration of the lesion, which often has medicolegal ramifications, particularly

if the lesion is deemed to predate the nerve block or surgical procedure. As such, this can be seen as

a “baseline” exam. More information is obtained at approximately 4 weeks post-injury, when the

electrophysiologic changes have had an opportunity to evolve more fully.

A practical algorithm for the management of postoperative neuropathy is shown in Figure 10-3.

PRACTICAL APPROACH TO MANAGEMENT OF A PATIENT WITH NEUROLOGIC DEFICIT

AFTER PERIPHERAL NERVE BLOCK

FIGURE 10-3.

REFERENCES

. Borgeat A, Blumenthal S. Nerve injury and regional anaesthesia. Curr Opin Anaesthesiol.

2004;17(5):417-421.

. Brull R, McCartney CJL, Chan VWS, El-Beheiry H. Neurological complications after regional

anesthesia: contemporary estimates of risk. Anesth Analg. 2007;104(4):965-974.

. Hogan QH. Pathophysiology of peripheral nerve injury during regional anesthesia. Reg Anesth Pain

Med. 2008;33(5):435-441.

. Sorenson EJ. Neurological injuries associated with regional anesthesia. Reg Anesth Pain Med.

2008;33(5):442-448.

. Clark K, Williams PE, Willis W, McGavran WL. Injection injury of the sciatic nerve. Clin

Neurosurg. 1970;17:111-125.

. Seddon HJ. Three types of nerve injury. Brain. 1943;66(4): 237-288.

. Selander D, Brattsand R, Lundborg G, Nordborg C, Olsson Y. Local anesthetics: importance of mode

of application, concentration and adrenaline for the appearance of nerve lesions. An experimental

study of axonal degeneration and barrier damage after intrafascicular injection or topical application

of bupivacaine (Marcain). Acta Anaesthesiol Scand. 1979;23(2):127-136.

. Sala-Blanch X, Pomés J, Matute P, et al. Intraneural injection during anterior approach for sciatic

nerve block. Anesthesiology. 2004;101(4):1027-1030.

. Schafhalter-Zoppoth I, Zeitz ID, Gray AT. Inadvertent femoral nerve impalement and intraneural

injection visualized by ultrasound. Anesth Analg. 2004;99(2):627-628.

0. Russon K, Blanco R. Accidental intraneural injection into the musculocutaneous nerve visualized

with ultrasound. Anesth Analg. 2007;105(5):1504-1505.

1. Bigeleisen PE. Nerve puncture and apparent intraneural injection during ultrasound-guided axillary

block does not invariably result in neurologic injury. Anesthesiology. 2006;105(4):779-783.

2. Robards C, Hadzic A, Somasundaram L, et al. Intraneural injection with low-current stimulation

during popliteal sciatic nerve block. Anesth Analg. 2009;109(2):673-677.

3. Gentili F, Hudson AR, Hunter D, Kline DG. Nerve injection injury with local anesthetic agents: a

light and electron microscopic, fluorescent microscopic, and horseradish peroxidase study.

Neurosurgery. 1980;6(3):263-272.

4. Selander D, Sjöstrand J. Longitudinal spread of intraneurally injected local anesthetics. An

experimental study of the initial neural distribution following intraneural injections. Acta

Anaesthesiol Scand. 1978;22(6):622-634.

5. Hadzic A, Dilberovic F, Shah S, et al. Combination of intraneural injection and high injection

pressure leads to fascicular injury and neurologic deficits in dogs. Reg Anesth Pain Med.

2004;29(5):417-423.

6. Moayeri N, Groen GJ. Differences in quantitative architecture of sciatic nerve may explain

differences in potential vulnerability to nerve injury, onset time, and minimum effective anesthetic

volume. Anesthesiology. 2009;111(5):1128-1134.

7. Liu SS, Zayas VM, Gordon MA, et al. A prospective, randomized, controlled trial comparing

ultrasound versus nerve stimulator guidance for interscalene block for ambulatory shoulder surgery

for postoperative neurological symptoms. Anesth Analg. 2009;109(1):265-271.

8. Moayeri N, Bigeleisen PE, Groen GJ. Quantitative architecture of the brachial plexus and

surrounding compartments, and their possible significance for plexus blocks. Anesthesiology.

2008;108(2):299-304.

9. Sugimoto Y, Takayama S, Horiuchi Y, Toyama Y. An experimental study on the perineurial

window. J Peripher Nerv Syst. 2002;7(2):104-111.

0. Fredrickson MJ. Case report: Neurological deficit associated with intraneural needle placement

without injection. Can J Anaesth. 2009;56(12):935-938.

1. Inglis JT, Leeper JB, Wilson LR, Gandevia SC, Burke D. The development of conduction block in

single human axons following a focal nerve injury. J Physiol (Lond). 1998;513(Pt 1): 127-133.

2. Eckberg DL, Wallin BG, Fagius J, Lundberg L, Torebjörk HE. Prospective study of symptoms after

human microneurography. Acta Physiol Scand. 1989;137(4):567-569.

3. Hogan Q. Animal pain models. Reg Anesth Pain Med. 2002;27(4):385-401.

4. Gold MS. Spinal nerve ligation: what to blame for the pain and why. Pain. 2000;84(2-3):117-120.

5. Steinfeldt T, Nimphius W, Werner T, et al. Nerve injury by needle nerve perforation in regional

anaesthesia: does size matter? Br J Anaesth. 2010;104(2):245-253.

6. Selander D, Dhunér KG, Lundborg G. Peripheral nerve injury due to injection needles used for

regional anesthesia. An experimental study of the acute effects of needle point trauma. Acta

Anaesthesiol Scand. 1977;21(3):182-188.

7. Sala-Blanch X, Ribalta T, Rivas E, et al. Structural injury to the human sciatic nerve after

intraneural needle insertion. Reg Anesth Pain Med. 2009;34(3):201-205.

8. Rice AS, McMahon SB. Peripheral nerve injury caused by injection needles used in regional

anaesthesia: influence of bevel configuration, studied in a rat model. Br J Anaesth. 1992;69(5):433-

438.

9. Lambert LA, Lambert DH, Strichartz GR. Irreversible conduction block in isolated nerve by high

concentrations of local anesthetics. Anesthesiology. 1994;80(5):1082-1093.

0. Kitagawa N, Oda M, Totoki T. Possible mechanism of irreversible nerve injury caused by local

anesthetics: detergent properties of local anesthetics and membrane disruption. Anesthesiology.

2004;100(4):962-967.

1. Johnson ME, Saenz JA, DaSilva AD, Uhl CB, Gores GJ. Effect of local anesthetic on neuronal

cytoplasmic calcium and plasma membrane lysis (necrosis) in a cell culture model. Anesthesiology.

2002;97(6):1466-1476.

2. Floridi A, Di Padova M, Barbieri R, Arcuri E. Effect of local anesthetic ropivacaine on isolated rat

liver mitochondria. Biochem Pharmacol. 1999;58(6):1009-1016.

3. Sturrock JE, Nunn JF. Cytotoxic effects of procaine, lignocaine and bupivacaine. Br J Anaesth.

1979;51(4):273-281.

4. Myers RR, Kalichman MW, Reisner LS, Powell HC. Neurotoxicity of local anesthetics: altered

perineurial permeability, edema, and nerve fiber injury. Anesthesiology. 1986;64(1):29-35.

5. Whitlock EL, Brenner MJ, Fox IK, et al. Ropivacaine-induced peripheral nerve injection injury in

the rodent model. Anesth Analg. 2010;111(1):214-220.

6. Iohom G, Lan GB, Diarra DP, et al. Long-term evaluation of motor function following intraneural

injection of ropivacaine using walking track analysis in rats. Br J Anaesth. 2005;94(4):524-529.

7. Kalichman MW, Moorhouse DF, Powell HC, Myers RR. Relative neural toxicity of local

anesthetics. J Neuropathol Exp Neurol. 1993;52(3):234-240.

8. Myers RR, Heckman HM. Effects of local anesthesia on nerve blood flow: studies using lidocaine

with and without epinephrine. Anesthesiology. 1989;71(5):757-762.

9. Partridge BL. The effects of local anesthetics and epinephrine on rat sciatic nerve blood flow.

Anesthesiology. 1991;75(2):243-250.

0. Bouaziz H, Iohom G, Estèbe J, Campana WM, Myers RR. Effects of levobupivacaine and

ropivacaine on rat sciatic nerve blood flow. Br J Anaesth. 2005;95(5):696-700.

1. Fanelli G, Casati A, Garancini P, Torri G. Nerve stimulator and multiple injection technique for

upper and lower limb blockade: failure rate, patient acceptance, and neurologic complications. Study

Group on Regional Anesthesia. Anesth Analg. 1999;88(4):847-852.

2. Voelckel WG, Klima G, Krismer AC, et al. Signs of inflammation after sciatic nerve block in pigs.

Anesth Analg. 2005;101(6):1844-1846.

3. Tsai TP, Vuckovic I, Dilberovic F, et al. Intensity of the stimulating current may not be a reliable

indicator of intraneural needle placement. Reg Anesth Pain Med. 2008;33(3):207-210.

4. Chan VWS, Brull R, McCartney CJL, et al. An ultrasonographic and histological study of

intraneural injection and electrical stimulation in pigs. Anesth Analg. 2007;104(5):1281-1284.

5. Bigeleisen PE, Moayeri N, Groen GJ. Extraneural versus intraneural stimulation thresholds during

ultrasound-guided supraclavicular block. Anesthesiology. 2009;110(6):1235-1243.

6. Altermatt FR, Cummings TJ, Auten KM, et al. Ultrasonographic appearance of intraneural injections

in the porcine model. Reg Anesth Pain Med. 2010;35(2):203-206.

7. Lupu CM, Kiehl T, Chan VWS, et al. Nerve expansion seen on ultrasound predicts histologic but not

functional nerve injury after intraneural injection in pigs. Reg Anesth Pain Med. 2010;35(2):132-139.

8. Loubert C, Williams SR, Hélie F, Arcand G. Complication during ultrasound-guided regional

block: accidental intravascular injection of local anesthetic. Anesthesiology. 2008;108(4):759-760.

9. Kapur E, Vuckovic I, Dilberovic F, et al. Neurologic and histologic outcome after intraneural

injections of lidocaine in canine sciatic nerves. Acta Anaesthesiol Scand. 2007;51(1):101-107.

0. Shah S, Hadzic A, Vloka JD, et al. Neurologic complication after anterior sciatic nerve block.

Anesth Analg. 2005;100(5): 1515-1517.

1. Claudio R, Hadzic A, Shih H, et al. Injection pressures by anesthesiologists during simulated

peripheral nerve block. Reg Anesth Pain Med. 2004;29(3):201-205.

2. Theron PS, Mackay Z, Gonzalez JG, Donaldson N, Blanco R. An animal model of “syringe feel”

during peripheral nerve block. Reg Anesth Pain Med. 2009;34(4):330-332.

3. Tsui BCH, Knezevich MP, Pillay JJ. Reduced injection pressures using a compressed air injection

technique (CAIT): an in vitro study. Reg Anesth Pain Med. 2008;33(2):168-173.

4. Rodríguez J, Taboada M, Blanco M, et al. Intraneural catheterization of the sciatic nerve in humans:

a pilot study. Reg Anesth Pain Med. 2008;33(4):285-290.

55. Sala Blanch X, López AM, Carazo J, et al. Intraneural injection during nerve stimulator-guided

sciatic nerve block at the popliteal fossa. Br J Anaesth. 2009;102(6):855-861.

SECTION 2

Nerve Stimulator and Surface-Based Nerve Block Techniques

Chapter 11 Cervical Plexus Block

Chapter 12 Interscalene Brachial Plexus Block

Chapter 13 Supraclavicular Brachial Plexus Block

Chapter 14 Infraclavicular Brachial Plexus Block

Chapter 15 Axillary Brachial Plexus Block

Chapter 16 Wrist Block

Chapter 17 Cutaneous Nerve Blocks of the Upper Extremity

Chapter 18 Lumbar Plexus Block

Chapter 19 Sciatic Block

Part 1. Transgluteal Approach

Part 2. Anterior Approach

Chapter 20 Popliteal Sciatic Block

Part 1. Intertendious Approach

Part 2. Lateral Approach

Chapter 21 Femoral Nerve Block

Chapter 22 Ankle Block

Chapter 23 Thoracic Paravertebral Block

Chapter 24 Intercostal Block

11

Cervical Plexus Block

FIGURE 11-1. Needle insertion for superficial cervical plexus block. The needle is inserted behind

the posterior border of the sternocleidomastoid muscle.

General Considerations

Cervical plexus block can be performed using two different methods. One is a deep cervical plexus

block, which is essentially a paravertebral block of the C2-4 spinal nerves (roots) as they emerge

from the foramina of their respective vertebrae. The other method is a superficial cervical plexus

block, which is a subcutaneous blockade of the distinct nerves of the anterolateral neck. The most

common clinical uses for this block are carotid endarterectomy and excision of cervical lymph nodes.

The cervical plexus is anesthetized also when a large volume of local anesthetic is used for an

interscalene brachial plexus block. This is because local anesthetic invariably escapes the

interscalane groove and layers out underneath the deep cervical fascia where the branches of the

cervical plexus are located.

The sensory distribution for the deep and superficial blocks is similar for neck surgery, so there is

a trend toward favoring the superficial approach. This is because of the potentially greater risk for

complications associated with the deep block, such as vertebral artery puncture, systemic toxicity,

nerve root injury, and neuraxial spread of local anesthetic.

Functional Anatomy

The cervical plexus is formed by the anterior rami of the four upper cervical nerves. The plexus lies

just lateral to the tips of the transverse processes in the plane just behind the sternocleidomastoid

muscle, giving off both cutaneous and muscular branches. There are four cutaneous branches, all of

which are innervated by roots C2-4. These emerge from the posterior border of the

sternocleidomastoid muscle at approximately its midpoint, and they supply the skin of the

anterolateral neck (Figures 11-2 and 11-3). The second, third, and fourth cervical nerves typically

send a branch each to the spinal accessory nerve or directly into the deep surface of the trapezius to

supply sensory fibers to this muscle. In addition, the fourth cervical nerve may send a branch

downward to join the fifth cervical nerve and participates in formation of the brachial plexus. The

motor component of the cervical plexus consists of the looped ansa cervicalis (C1-C3), from which

the nerves to the anterior neck muscles originate, and various branches from individual roots to

posterolateral neck musculature (Figure 11-4). The C1 spinal nerve (the suboccipital nerve) is

strictly a motor nerve, and is not blocked with either technique. One other significant muscle

innervated by roots of the cervical plexus includes the diaphragm (phrenic nerve, C3,4,5) (Table 11-

1).

FIGURE 11-2. The superficial cervical plexus and its terminal nerves. Anatomy of the superficial

cervical plexus and its branches are shown emerging behind the posterior border of the

sternocleidomastoid muscle.

FIGURE 11-3. Anatomy of the superficial cervical plexus. Sternocleidomastoid muscle

mastoid process clavicle external jugular vein.

FIGURE 11-4. The roots origin of the cervical plexus.

TABLE 11-1 Cervical Plexus

Distribution of Blockade

Cutaneous innervation of both the deep and the superficial cervical plexus blocks includes the skin of

the anterolateral neck and the ante- and retroauricular areas (Figure 11-5). In addition, the deep

cervical block anesthetizes three of the four strap muscles of the neck, geniohyoid, the prevertebral

muscles, sternocleidomastoid, levator scapulae, the scalenes, trapezius, and the diaphragm (via

blockade of the phrenic nerve).

FIGURE 11-5. Sensory innervation of the lateral aspect of the head and neck and contribution of the

superficial cervical plexus.

Superficial Cervical Plexus Block

Equipment

A standard regional anesthesia tray is prepared with the following equipment:

 Sterile towels and gauze packs

 A 20-mL syringe with local anesthetic, attached to a 1½-in, 25-gauge needle, typically via a flexible

tubing

 Sterile gloves, marking pen

Landmarks and Patient Positioning

The patient is in a supine or semi-sitting position with the head facing away from the side to be

blocked. These are the primary landmarks (Figure 11-6) for performing this block:

FIGURE 11-6. Surface landmarks for superficial cervical plexus block. White dot: insertion of the

clavicular head of the sternocleidomastoid muscle. Blue dot: Mastoid process. Uncolored circle:

Transverse process of C6 vertebrate. Red dot: Needle insertion site at the midpoint between C6 and

mastoid process behind the posterior border of the sternocleidomastoid muscle.

. Mastoid process

. Clavicular head of the sternocleidomastoid

. The midpoint of the posterior border of the sternocleidomastoid (this is aided by identifying the first

two landmarks)

Maneuvers to Facilitate Landmark Identification

The sternocleidomastoid muscle can be better differentiated from the deeper neck structures by asking

the patient to raise their head off the table.

TIP

 The proportions of the shoulder girdle, size of the neck, prominence of the muscles, and other areas

vary among patients. When in doubt, always perform a “reality check” and estimate the two bony

landmarks, the clavicle and the mastoid process.

Technique

After cleaning the skin with an antiseptic solution, the needle is inserted along the posterior border of

the sternocleidomastoid, and three injections of 5 mL of local anesthetic are injected behind the

posterior border of the sternocleidomastoid muscle subcutaneously, perpendicularly, cephalad, and

caudad in a “fan” fashion (Figure 11-7).

FIGURE 11-7. Injection of local anesthetic for superficial cervical plexus. The injection is made

fan-wise behind the posterior border of the sternocleidomastoid muscle at a depth of approximately 1

cm in average-size patients.

GOAL

The goal of the injection is to infiltrate the local anesthetic subcutaneously but deep to the

cervical fascia and behind the sternocleidomastoid muscle. Deep needle insertion (i.e., >1–2 cm)

should be avoided to minimize the risk of subarachnoid or vertebral artery injection.

Block Dynamics and Perioperative Management

A superficial cervical plexus block is associated with minor patient discomfort. Small doses of

midazolam 1 to 2 mg for sedation and alfentanil 250 to 500 μg for analgesia just before needle

insertion should result in a comfortable, cooperative patient during block injection. The onset time for

this block is 10 to 15 minutes. Excessive sedation should be avoided before and during head and neck

procedures because airway management, when necessary, can prove difficult because access to the

head and neck is shared with the surgeon. Due to the complex arrangement of the sensory innervation

of the neck and the cross-coverage from the contralateral side, the anesthesia achieved with a cervical

plexus block is rarely complete. Although this should not discourage the use of the cervical block, the

surgeon must be willing to supplement the block with a local anesthetic if necessary.

TIPS

 A subcutaneous midline injection of local anesthetic extending from the thyroid cartilage distally to the

suprasternal notch will block the branches crossing from the opposite side. This injection can be

considered a “field” block. It is useful for preventing pain from surgical skin retractors on the medial

aspect of the neck.

 Carotid surgery requires blockade of the glossopharyngeal nerve branches. The surgeon can

accomplish this intraoperatively by injecting local anesthetic inside the carotid artery sheath.

Deep Cervical Plexus Block

Equipment

A standard regional anesthesia tray is prepared with the following equipment:

 Sterile towels and gauze packs

 A 20-mL syringe with local anesthetic, attached via tubing to 1½ to 2 in, 22-gauge short bevel needle

 A 3-mL syringe plus 25-gauge needle with local anesthetic for skin infiltration

 Sterile gloves, marking pen, ruler

Landmarks and Patient Positioning

The patient is in the same position as for the superficial cervical plexus block. The three landmarks

for a deep cervical plexus block are similar to those for the superficial cervical plexus block:

. Mastoid process

. Chassaignac tubercle (transverse process of C6) (Figure 11-8)

FIGURE 11-8. Palpation technique to determine location of the transverse process of C6. The head

is rotated away from the palpated side while the palpated fingers explore for the most lateral bony

prominence, often in the vicinity of the external jugular vein.

. Posterior border of the sternocleidomastoid muscle (Figure 11-9)

FIGURE 11-9. Palpation technique to determine the posterior border of the sternocleidomastoid

muscle. With the head of the patient rotated away from the palpation side, the patient is asked to lift

his or her head off of the bed to accentuate the sternocleidomastoid muscle.

To estimate the line of needle insertion overlying the transverse processes, the mastoid process

and the transverse process of C6 are identified and marked. The latter is easily palpated behind the

clavicular head of the sternocleidomastoid muscle just below the level of the cricoid cartilage.

Next, a line is drawn connecting the mastoid process to the C6 transverse process. The palpating

hand is best positioned just behind the posterior border of the sternocleidomastoid muscle. Once this

line is drawn, the insertion sites over C2 through C4 are labeled as follows: C2: 2 cm caudad to the

mastoid process, C3: 4 cm caudad to the mastoid process, and C4: 6 cm caudad to the mastoid

process (Figure 11-10).

FIGURE 11-10. The landmarks for the deep cervical plexus block. White circle indicates the

transverse process of C6 The pen is outlining the transverse process of C4.

Maneuvers to Facilitate Landmark Identification

The sternocleidomastoid muscle can be accentuated by asking the patient to raise his or her head off

of the table.

Technique

After cleaning the skin with an antiseptic solution, local anesthetic is infiltrated subcutaneously along

the line estimating the position of the transverse processes. The local anesthetic is infiltrated over the

entire length of the line, rather than at the projected insertion sites. This allows reinsertion of the

needle slightly caudally or cranially when the transverse process is not contacted, without the need to

infiltrate the skin at a new insertion site.

A needle is connected via flexible tubing to a syringe containing local anesthetic. The needle is

inserted between the palpating fingers and advanced at an angle perpendicular to the skin plane

(Figure 11-11). The needle should never be oriented cephalad. A slightly caudal orientation of the

needle is important to prevent inadvertent insertion of the needle toward the cervical spinal cord. The

needle is advanced slowly until the transverse process is contacted. At this point, the needle is

withdrawn 1 to 2 mm and firmly stabilized, and 4 to 5 mL of local anesthetic is injected after a

negative aspiration test for blood. The needle is removed, and the entire procedure is repeated at

consecutive levels.

FIGURE 11-11. Needle insertion for the deep cervical plexus block. The needle is inserted between

fingers palpating individual transverse processes.

TIPS

 The transverse processes are typically contacted at a depth of 1–2 cm in most patients. This distance

can be further shortened by exerting pressure on the skin during needle advancement.

 The needle should never be advanced beyond 2.5 cm to avoid the risk of cervical cord injury or

carotid or vertebral artery puncture.

GOAL

• Contact with the posterior tubercle of the transverse process.

• Slightly withdraw the needle after the contact and before making an injection.

Troubleshooting Deep Cervical Plexus Blocks

When insertion of the needle does not result in contact with the transverse process within 2 cm, the

following maneuvers are used:

. While avoiding skin movement, keep the palpating hand in the same position and the skin between the

fingers stretched.

. Withdraw the needle to the skin, redirect it 15° inferiorly, and repeat the procedure.

. Withdraw the needle to the skin, reinsert it 1 cm caudal, and repeat the procedure.

TIPS

 When these maneuvers fail to result in contact with the transverse process, the needle should be

withdrawn and the landmarks reassessed.

 Redirecting the needle cephalad in an attempt to contact the transverse process should be avoided

because it carries a risk of cervical cord injury when the needle is advanced too deeply.

Block Dynamics and Perioperative Management

Premedication is useful for patient comfort; however, excessive sedation should be avoided. During

neck surgery, airway management can be difficult because the anesthesiologist must share access to

the head and neck with the surgeon. Surgeries like carotid endarterectomy require the patient to be

fully conscious, oriented, and cooperative during the entire procedure. In addition, excessive sedation

and the consequent lack of patient cooperation can result in restlessness and create difficulty for the

surgeon. The onset time for this block is 10 to 20 minutes. The first sign is decreased sensation in the

area of distribution of the respective components of the cervical plexus. Complications of cervical

plexus blocks and strategies to avoid them are listed in Table 11-2.

TABLE 11-2 Complications and How to Avoid Them

DEEP CERVICAL PLEXUS BLOCK

SUGGESTED READING

Superficial Cervical Plexus Block

Aunac S, Carlier M, Singelyn F, De Kock M. The analgesic efficacy of bilateral combined superficial

and deep cervical plexus block administered before thyroid surgery under general anesthesia. Anesth

Analg. 2002;95:746-750.

Brogly N, Wattier JM, Andrieu G, et al. Gabapentin attenuates late but not early postoperative pain after

thyroidectomy with superficial cervical plexus block. Anesth Analg. 2008;107:1720-1725.

Choi DS, Atchabahian A, Brown AR. Cervical plexus block provides postoperative analgesia after

clavicle surgery. Anesth Analg. 2005;100:1542-1543.

e Sousa AA, Filho MA, Faglione W Jr, Carvalho GT. Superficial vs combined cervical plexus block

for carotid endarterectomy: a prospective, randomized study. Surg Neurol. 2005;63 Suppl 1:S22-25.

D’Honneur G, Motamed C, Tual L, Combes X. Respiratory distress after a deep cervical plexus block.

Anesthesiology. 2005;102:1070.

Dieudonne N, Gomola A, Bonnichon P, Ozier YM. Prevention of postoperative pain after thyroid

surgery: a double-blind randomized study of bilateral superficial cervical plexus blocks. Anesth

Analg. 2001;92:1538-1542.

Eti Z, Irmak P, Gulluoglu BM, Manukyan MN, Gogus FY. Does bilateral superficial cervical plexus

block decrease analgesic requirement after thyroid surgery? Anesth Analg. 2006;102:1174-1176.

Guay J. Regional anesthesia for carotid surgery. Curr Opin Anaesthesiol. 2008;21:638-644.

Herbland A, Cantini O, Reynier P, et al. The bilateral superficial cervical plexus block with 0.75%

ropivacaine administered before or after surgery does not prevent postoperative pain after total

thyroidectomy. Reg Anesth Pain Med. 2006;31:34-39.

Heyer EJ, Gold MI, Kirby EW, et al. A study of cognitive dysfunction in patients having carotid

endarterectomy performed with regional anesthesia. Anesth Analg. 2008;107:636-642.

ankovic D, Wells C, eds. Regional Nerve Blocks. 2nd ed. Berlin, Germany: Blackwell Scientific

Publications; 2001.

unca A, Marret E, Goursot G, Mazoit X, Bonnet F. A comparison of ropivacaine and bupivacaine for

cervical plexus block. Anesth Analg. 2001;92:720-724.

Kim YK, Hwang GS, Huh IY, et al. Altered autonomic cardiovascular regulation after combined deep

and superficial cervical plexus blockade for carotid endarterectomy. Anesth Analg. 2006;103:533-

539.

Kwok AO, Silbert BS, Allen KJ, Bray PJ, Vidovich J. Bilateral vocal cord palsy during carotid

endarterectomy under cervical plexus block. Anesth Analg. 2006;102:376-377.

Luchetti M, Canella M, Zoppi M, Massei R. Comparison of regional anesthesia versus combined

regional and general anesthesia for elective carotid endarterectomy: a small exploratory study. Reg

Anesth Pain Med. 2008;33:340-345.

Masters RD, Castresana EJ, Castresana MR. Superficial and deep cervical plexus block: technical

considerations. AANA J. 1995;63:235-243.

Mulroy M. Regional Anesthesia: An Illustrated Procedural Guide. 3rd ed. Philadelphia, PA:

Lippincott, Williams & Wilkins; 2002.

Murphy T. Somatic blockade of head and neck. In: Cousins MJ, Bridenbaugh PO, eds. Neuronal

Blockade in Clinical Anesthesia and Management of Pain. Philadelphia, PA: Lippincott-Raven;

1988:489-514.

Nash L, Nicholson HD, Zhang M. Does the investing layer of the deep cervical fascia exist?

Anesthesiology. 2005;103:962-968.

andit JJ, Bree S, Dillon P, Elcock D, McLaren ID, Crider B. A comparison of superficial versus

combined (superficial and deep) cervical plexus block for carotid endarterectomy: a prospective,

randomized study. Anesth Analg. 2000;91:781-786.

intaric TS, Hocevar M, Jereb S, Casati A, Jankovic VN. A prospective, randomized comparison

between combined (deep and superficial) and superficial cervical plexus block with levobupivacaine

for minimally invasive parathyroidectomy. Anesth Analg. 2007;105:1160-1163.

chneemilch CE, Bachmann H, Ulrich A, Elwert R, Halloul Z, Hachenberg T. Clonidine decreases

stress response in patients undergoing carotid endarterectomy under regional anesthesia: a

prospective, randomized, double-blinded, placebo-controlled study. Anesth Analg. 2006;103:297-

302.

toneham MD, Doyle AR, Knighton JD, Dorje P, Stanley JC. Prospective, randomized comparison of

deep or superficial cervical plexus block for carotid endarterectomy surgery. Anesthesiology.

1998;89:907-912.

uresh S, Templeton L. Superficial cervical plexus block for vocal cord surgery in an awake pediatric

patient. Anesth Analg. 2004;98:1656-1657.

Umbrain VJ, van Gorp VL, Schmedding E, et al. Ropivacaine 3.75 mg/ml, 5 mg/ml, or 7.5 mg/ml for

cervical plexus block during carotid endarterectomy. Reg Anesth Pain Med. 2004;29:312-316.

Winnie AP, Ramamurthy S, Durrani Z, Radonjic R. Interscalene cervical plexus block: a singleinjection technic. Anesth Analg. 1975;54:370-375.

Deep Cervical Plexus Block

Benzon HT, Raja SN, Borsook D, Molloy RE, Strichartz G. Essentials of Pain Medicine and Regional

Anesthesia. Philadelphia, PA: Churchill Livingstone; 1999.

Brown D. Atlas of Regional Anesthesia. Philadelphia, PA: Saunders; 1992.

Carling A, Simmonds M. Complications from regional anaesthesia for carotid endarterectomy. Br J

Anaesth. 2000;84:797-800.

Davies MJ, Silbert BS, Scott DA, Cook RJ, Mooney PH, Blyth C. Superficial and deep cervical plexus

block for carotid artery surgery: a prospective study of 1000 blocks. Reg Anesth. 1997;22:442-446.

Emery G, Handley G, Davies MJ, Mooney PH. Incidence of phrenic nerve block and hypercapnia in

patients undergoing carotid endarterectomy under cervical plexus block. Anaesth Intensive Care.

1998;26:377-381.

ohnson TR. Transient ischaemic attack during deep cervical plexus block. Br J Anaesth. 1999;83:965-

967.

Kulkarni RS, Braverman LE, Patwardhan NA. Bilateral cervical plexus block for thyroidectomy and

parathyroidectomy in healthy and high risk patients. J Endocrinol Invest. 1996;19:714-718.

Lo Gerfo P, Ditkoff BA, Chabot J, Feind C. Thyroid surgery using monitored anesthesia care: an

alternative to general anesthesia. Thyroid. 1994;4:437-439.

Stoneham MD, Wakefield TW. Acute respiratory distress after deep cervical plexus block. J

Cardiothorac Vasc Anesth. 1998;12:197-198.

Weiss A, Isselhorst C, Gahlen J, et al. Acute respiratory failure after deep cervical plexus block for

carotid endarterectomy as a result of bilateral recurrent laryngeal nerve paralysis. Acta Anaesthesiol

Scand. 2005;49:715-719.

12

Interscalene Brachial Plexus Block

FIGURE 12-1. Needle insertion for interscalene brachial plexus block. The needle is inserted

between palpating fingers that are positioned in the scalene groove (between anterior and middle

scalene muscles). 1 = sternal head of the sternocleidomastoid muscle. 2 = clavicular head of the

sternocleidomastoid muscle.

General Considerations

An interscalene block relies on the spread of a relatively large volume of local anesthetic within the

interscalene groove to accomplish blockade of the brachial plexus. In our practice, we almost always

use a low interscalene block technique, which consists of inserting the needle more caudally than in

the commonly described procedure performed at the level of the cricoid cartilage. Our reasoning is

that at the lower neck, the interscalene groove is more shallow and easier to identify, and the

distribution of anesthesia is also adequate for elbow and forearm surgery. In addition, the needle

insertion is more lateral, which makes puncture of the carotid artery less likely and performance of

the block easier to master by trainees. Low approach to interscalene block is used in shoulder, arm,

and forearm surgery. In our practice, the most common indications for this procedure are shoulder and

humerus surgery and the insertion of an arteriovenous graft for hemodialysis.

Functional Anatomy

The brachial plexus supplies innervation to the upper limb and consists of a branching network of

nerves derived from the anterior rami of the lower four cervical and the first thoracic spinal nerves.

Starting from their origin and descending distally, the components of the plexus are named roots,

trunks, divisions, cords, and, finally, terminal branches. The five roots of the cervical and the first

thoracic spinal nerves (anterior rami) give rise to three trunks (superior, middle, and inferior) that

emerge between the medial and anterior scalene muscles to lie on the floor of the posterior triangle of

the neck (Figure 12-2). The roots of the plexus lie deep to the prevertebral fascia, whereas the trunks

are covered by its lateral extension, the axillary sheath. Each trunk divides into an anterior and a

posterior division behind the clavicle, at the apex of the axilla (Figure 12-3). The divisions combine

to produce the three cords, which are named lateral, median, and posterior according to their

relationship to the axillary artery. From this point on, individual nerves are formed as these neuronal

elements descend distally (Figure 12-3 and Table 12-1).

FIGURE 12-2. Anatomy of the brachial plexus. The sternocleidomastoid muscle is removed and the

brachial plexus is seen emerging between the scalene muscles. internal jugular vein. carotid

artery. subclavian artery. Retracted pectoralis muscle. medial and lateral pectoral nerves.

The number “1” also indicates the approximate level at which the block is performed where the roots

of the muscles are emerging between the scalene muscles.

FIGURE 12-3. Functional organization of the brachial plexus and formation of the terminal nerves.

TABLE 12-1 Distribution of the Brachial Plexus

Distribution of Blockade

The interscalene approach to brachial plexus blockade results in anesthesia of the shoulder, arm, and

elbow (Figure 12-4). Note that the skin over and medial to the acromion is supplied by the

supraclavicular nerve, which is a branch of the cervical plexus. Supraclavicular nerves are usually

blocked with the brachial plexus when an interscalene block is performed. This is because the local

anesthetic invariably spills over from the interscalene space into the prevertebral fascia and blocks

the branches of the cervical plexus. The classic interscalene block is not recommended for hand

surgery due to potential sparing of the inferior trunk and the lack of blockade of the C8 and T1 roots.

FIGURE 12-4. Sensory distribution of the brachial plexus. The innervation is shown for didactic

purposes; the exact extent of anesthesia with interscalane block varies considerably and often spares

the hand.

Single-Injection Interscalene Block

Equipment

A standard regional anesthesia tray is prepared with the following equipment:

 Sterile towels and gauze packs

 2 × 20-mL syringes containing local anesthetic

 A 3-mL syringe and 25-gauge needle with local anesthetic for skin infiltration

 A 3.5-cm, 22-gauge, short-bevel insulated stimulating needle

 Peripheral nerve stimulator

 Sterile gloves; marking pen

Landmarks and Patient Positioning

The patient is in a supine or semi-sitting position with the head facing away from the side to be

blocked (Figure 12-5). The arm should rest comfortably on the bed, abdomen, or arm-board to allow

detection of responses to nerve stimulation. Removal of a cast (when present) can help to detect

motor response, although removal is not essential because the responses to nerve stimulation are

usually mixed (stimulation of trunks and divisions rather than specific nerves) and proximal motor

response is adequate (e.g., deltoid, pectoralis).

FIGURE 12-5. Landmarks for the interscalene brachial plexus. White arrows: clavicle. Red arrows:

posterior border of the sternocleidomastoid muscle. Blue arrow: external jugular vein. The palpating

fingers are positioned lateral and posterior to the clavicular head of the sternocleidomastoid muscle

in the space between anterior and middle scalene muscles. The scalene groove is often palpated just

in front or behind the external jugular vein.

These are the primary landmarks for performing this block:

. The clavicle

. Posterior border of the clavicular head of the sternocleidomastoid muscle

. External jugular vein (usually crosses the interscalene groove at the level of the trunks)

Maneuvers to Facilitate Landmark Identification

Identification of the interscalene groove can be made easier by performing the following steps:

 Ask the patient to reach for the ipsilateral knee with the limb to be blocked or passively pull the

patient’s wrist inferiorly. This maneuver flattens the skin of the neck and helps identify both the

scalene muscles and the external jugular vein.

 The sternocleidomastoid muscle can be accentuated by asking the patient to raise the head off the table

(Figure 12-6).

FIGURE 12-6. Maneuver to extenuate the posterior border of the sternocleidomastoid muscle and

external jugular vein by asking the patient to lift her head off of the table while looking away from the

side to be blocked.

 The external jugular vein can be accentuated by asking the patient to perform a brief Valsalva

maneuver.

 While palpating the interscalene groove, ask the patient to sniff forcefully. Sniffing tenses the scalene

muscles, and the fingers of the palpating hand often fall into the interscalene groove.

The described landmarks should routinely be marked on the patient’s skin prior to performing the

block.

TIP

 The proportions of the shoulder girdle, size of the neck, prominence of the muscles, and other

anatomic features vary among patients. When in doubt, always perform a “reality check” and estimate

three bony landmarks: the sternal notch, clavicle, and mastoid process. This helps identify the

sternocleidomastoid muscle and its relations.

Technique

After cleaning the skin with an antiseptic solution, 1 to 3 mL of local anesthetic is infiltrated

subcutaneously at the determined needle insertion site.

TIP

 During skin infiltration, care should be taken to infiltrate local anesthetic into the subcutaneous tissue

plane only because the brachial plexus is very shallow at this location. A deeper needle insertion can

result in deposition of local anesthetic into the plexus; this can result in nerve injury and/or make

attempts at obtaining a motor response unsuccessful.

The fingers of the palpating hand should be gently but firmly pressed between the anterior and

middle scalene muscles to shorten the skin-brachial plexus distance. The skin over the neck can be

very mobile, and care should be taken to stabilize the fingers as well as to stretch the skin gently

between the two fingers to ensure accuracy in needle advancement and redirection. The palpating

hand should not be allowed to move during the entire block procedure to allow for precise

redirection of the needle when necessary.

GOAL

The goal is stimulation of the brachial plexus with a current intensity of 0.2–0.5 mA (0.1 ms). The

following motor responses result in a similar success rate:

• Pectoralis muscle

• Deltoid muscle

• Triceps muscles

• Biceps muscle

• Any twitch of the hand or forearm

The needle is inserted 3–4 cm (approximately 2 fingerbreadths) above the clavicle and advanced

at an angle almost perpendicular to the skin plane (Figure 12-7). The needle must never be oriented

cephalad; a slight caudal orientation reduces a chance for an inadvertent insertion of the needle into

the cervical spinal cord. The nerve stimulator should be initially set to deliver 0.8 to 1.0 mA (2 Hz,

0.1 ms). The needle is advanced slowly until stimulation of the brachial plexus is obtained. This

typically occurs at a depth of 1 to 2 cm in most all patients. Once appropriate twitches of the brachial

plexus are elicited, 25 to 35 mL of local anesthetic are injected slowly with intermittent aspiration to

rule out intravascular injection.

FIGURE 12-7. Needle insertion for interscalene brachial plexus block. The needle is inserted

between fingers positioned in the interscalene groove with a slight caudad orientation to decrease the

chance of entrance in the cervical spinal cord. White arrow: insertion of the sternal head of the

sternocleidomastoid muscle. Red arrows: posterior border of the sternocleidomastoid muscle. Blue

arrow: external jugular vein. The insertion point for the block is often immediately posterior to the

external jugular vein.

This “low-interscalene” approach differs from the classic description of the interscalene block,

which uses the cricoid cartilage as a landmark. The principal advantage to the low approach is that

the brachial plexus is more compact at the lower levels, and reliable coverage of the upper, middle,

and lower trunks can be achieved with a single injection (Figure 12-8). In contrast, the classic

approach may spare the lower trunk, which limits its use for forearm and elbow surgery.

FIGURE 12-8. Distribution of the mixture of local anesthetic and a radiopaque contrast after an

interscalene brachial plexus injection. The arrows and the circle indicate “negative” contrast image

of the roots of the brachial plexus.

When insertion of the needle does not result in upper extremity muscle stimulation, the following

maneuvers can be used (Figure 12-9):

FIGURE 12-9. Maneuvers to obtain a motor response of the brachial plexus during electric nerve

localization. When the motor response is not obtained on the initial needle pass, the needle is

redirected anteriorly or posteriorly to the original insertion plane as shown in the figure.

. Keep the palpating hand in the same position and the skin between the fingers stretched.

. Withdraw the needle to the skin level, redirect it 15° posteriorly, and repeat the needle advancement.

. Withdraw the needle to the skin level, redirect it 15° anteriorly, and repeat the needle insertion.

TIPS

 The needle should never be advanced beyond 2.5 cm to avoid the risk of mechanical complications

(cervical cord injury, pneumothorax, vascular puncture).

Never inject when resistance (high pressure) on injection of local anesthetic is met. High resistance to

injection (>15 psi) may indicate an intrafascicular needle placement. Instead, withdraw and/or rotate

the needle slightly and reattempt the injection to assure absence of resistance.

 Stimulation of the brachial plexus with a higher stimulating current (e.g., >1.0 mA) results in an

exaggerated response and unnecessary discomfort for the patient. In addition, an unpredictably strong

response often causes dislodgment of the needle and a withdrawal reaction by the patient.

 Local anesthetic should not be injected when a motor response is obtained at a current intensity <0.2

mA because this is associated with intraneural needle placement.

 Intraneural injection of the trunks can lead not only to nerve injury but also retrograde backflow of

local anesthetic toward neuraxial space, resulting in total spinal anesthesia.

 Care should always be taken to avoid attributing diaphragmatic and trapezius twitches to stimulation

of the brachial plexus. Misinterpretation of these twitches is one of the most common causes of block

failure.

 When in doubt, palpate the muscle that appears to be twitching to ensure the proper response.

Troubleshooting

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