LA toxicity and Nerve Injury 2.15.pptx

4/24/15 Disclosures Local Anesthe�c Toxicity and Nerve Injury David B. Auyong, MD Virginia Mason Medical Center Sea�le, WA Clinical Scenario 0  24 y/o healthy male presents for ORIF radius and ulna 0  30mL 0.5% bupivacine injected for supraclavicular nerve blockade Clinical Scenario 0  <1 minute a�er comple�on of injec�on, loss of consciousness followed by tonic-­‐clonic seizures 0  Apnea, ventricular fibrilla�on 0  Chest compressions, epinephrine, ACLS Closed Claims and Peripheral Nerve Blocks Lee et al, RAPM 2008
0  Evalua�on from 1980 – 2000 0  Peripheral nerve blocks were primarily associated with temporary injuries 0  Local Anesthe�c Toxicity was associated with 7 / 19 claims with death and brain damage 1 4/24/15 History of Cocaine 0  1887, Ma�son reviewed 50 cases of “cocaine toxaemia” Lipid Rescue 0  Guy Weinberg, intrigued by a case of cardiotoxicity from 22mg bupivacaine hypothesized that carni�ne deficiency led to enhanced local anesthe�c toxicity 0  Dr. Weinberg hypothesized that because bupivacaine inhibits carni�ne acylcarni�ne translocase, the addi�on of lipid (which also inhibits this enzyme) would poten�ate toxicity 0  These cases associated with respiratory depression, seizures, cardiac “distress” 0  Recommended frac�onated injec�on and iden�fied the need to have resuscita�on drugs immediately available Lipid Rescue 0  Guy Weinberg, intrigued by a case of cardiotoxicity from 22mg bupivacaine hypothesized that carni�ne deficiency led to enhanced local anesthe�c toxicity 0  Dr. Weinberg hypothesized that because bupivacaine inhibits carni�ne acylcarni�ne translocase, the addi�on of lipid (which also inhibits this enzyme) would poten�ate toxicity Weinberg et al, Anesthesiology 2000; 92(2) 0  Rats were pre-­‐treated with saline or lipid 0  Infusion of 0.75% bupivacaine to asystole 0  Dose response 0  Increased LD50 of bupivacaine 48% RAPM 2003; 28:198-­‐202 Video courtesy Dr. Guy Weinberg LIPID EMULSIONS INCREASE THE LD50 OF BUPIVACAINE IN SMALL ANIMALS LIPID EMULSIONS INCREASE SURVIVAL AFTER TOXIC DOSES OF BUPIVACAINE IN DOGS 2 4/24/15 Lipid vs Standard Resuscita�on WHAT OTHER RESUSCITATION MEDICATIONS SHOULD BE USED WITH LIPID? 0 
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Study resuscita�ng rats with either lipid, vasopressin, or vasopressin
+epinephrine Lipid showed improved spontaneous return of circula�on, progressive increase of systolic pressure, lower lactate levels, higher venous satura�on CONCLUSION: Lipid provides superior hemodynamic and metabolic recovery from bupivacaine-­‐induced cardiac arrest than do vasopressors Di Gregorio et al, Crit Care Med 2009; 37; 993-­‐9. Lipid vs Standard Resuscita�on Lipid Epi Vasopressin LIPID THERAPY SHOWS IMPROVED OUTCOMES COMPARED TO EPINEPHRINE OR VASOPRESSIN IN ANIMAL MODELS OF TOXICITY LOW DOSE EPINEPHRINE MAY HAVE SOME BENEFIT BUT VASOPRESSIN IS LIKELY HARMFUL Courtesy of Dr. Guy Weinberg Does lipid work for all local anesthe�cs? Zausig et al, Anesth Analg 2009; 1323-­‐6 0  Isolated rat hearts given LA to arrest 0  Bupi-­‐, ropi-­‐, mepi-­‐
vacaine 0  Lipid followed 0  Conclusion: Lipid rescue works best for highly lipid soluble drugs (bupivacaine) Lipid solubility of local anesthe�cs 0  Bupivacaine – [butylic – C4H9] –  Lipid/H20 par��on coefficient = 27.5 0  Ropivacaine – [propylic –C3H7] –  Lipid/H20 par��on coefficient = 2.8 0  Mepivacaine – [methylic –CH3] –  Lipid/H20 par��on coefficient = 0.8 0  Lipid solubility, analgesic potency, toxicity = bupivacaine > ropivacaine > mepivacaine 3 4/24/15 0  Rats given infusions of varying lipid loads, 20% lipid 0  Dixon up-­‐down methodology 0  LD50 = 67 mL/kg 0  Microscopic abnormali�es were found in lung and liver at doses >60 mg/kg Reg Anesth Pain Med 2010;35: 140-­‐144 EXPERIMENTALLY, LIPID IS MOST EFFECTIVE WITH BUPIVACAINE TOXICITY CLINICALLY, LIPID HAS REVERSED MULTIPLE TYPES OF LOCAL ANESTHETIC TOXICITY AT RECOMMENDED DOSING, LIPID EMULSIONS ARE UNLIKELY TO CAUSE HARM www.lipidrescue.org 4 4/24/15 What local anesthe�c drug doses should we be using? Atlanta Child, 5, Dies From Local Anesthesia June 2011 0  Recommenda�ons for maximum doses of LA are NOT evidence based –  Grade C (case series or poor quality cohort) 0  Historically, maximum doses have been a total amount for a drug 0  Do not take into account site of injec�on, age, or renal/hepa�c/cardiac dysfunc�on –  Affect blood levels and clearance »  Rosenberg, et al. Reg Anesth and Pain 2004; 29:6 564-­‐575 Finland
2-Chloroprocaine
—
Germany
—
Japan
—
Sweden
—
US
mg/kg dosing 800 mg
With epi
—
—
1,000 mg
—
1,000 mg
Procaine
—
500 mg
600 mg (epidural)
—
500 mg
With epi
—
600 mg
—
—
—
Bupivacaine
175 mg (200 mg*) (400
mg/24 h)
150 mg
100 mg (epidural)
150 mg
175 mg
With epi
175 mg
150 mg
—
150 mg
225 mg
Levobupivacaine
150 mg (400 mg/24 h)
150 mg
—
150 mg
150 mg
With epi
—
—
—
—
—
Lidocaine
200 mg
200 mg
200 mg
200 mg
300 mg
With epi
500 mg
500 mg
—
500 mg
500 mg
Mepivacaine
—
300 mg
400 mg (epidural)
350 mg
400 mg
With epi
—
500 mg
—
350 mg
550 mg
Prilocaine
400 mg
—
—
400 mg
—
With epi
600 mg
—
—
600 mg
—
Ropivacaine
225 mg (300 mg*) (800
mg/24 h)
No mention
200 mg (epidural) 300 mg
(infiltr.)
225 mg
225 mg (300mg*)
With epi
225 mg
No mention
—
225 mg
225 mg (300mg*)
(-) Epi
(+) Epi
Lido
Mepiv
5 mg/kg
7 mg/kg
5mg/kg
6mg/kg
Bupiv
2.5 mg/kg
3 mg/kg
Ropiv
2.5 mg/kg
3 mg/kg
Epinephrine 1:400,000 (2.5mcg/ml) can slow the systemic uptake and peak blood levels of local anesthe�c a�er bolus injec�on Ropivacaine plasma concentrations after infusions
Local Anesthe�c Toxicity 0 
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Airway support, avoid hypoxia and acidosis Benzodiazepines Avoid propofol, vasopressin ACLS –  Chest compressions –  Small doses of epinephrine (<1mg) 0  Lipid 20% Bleckner et al 2010 A&A
Brodner et al 2007 A&A –  1.5mL/kg 20% lipid emulsion bolus –  0.25mL/kg/min infusion, con�nue even a�er improvement –  Maximum of 10mL/kg over 30 minutes (OK to repeat bolus 1-­‐2x) 0  Cardiopulmonary bypass Neal et al, ASRA Prac�ce Advisory, RAPM 2010;35: 152-­‐161. 5 4/24/15 Epinephrine ASRA Checklist 2012 Dosing: 0  1:400,000 (2.5mcg/mL) adults 0  1:200,000 (5mcg/mL) pediatrics Clinical Effects: 0  Decreases peripheral nerve blood flow 0  Increases concentra�on of local anesthe�c around the nerve by decreasing clearance* ASRA *Bernards and Kopacz, Anesthesiology 1999 Epinephrine # Nerve Injury Clinical Effects: 0  Increases block dura�on for lidocaine, mepivacaine, and bupivacaine (2-­‐6 hours) 0  Does not increase dura�on of ropivacaine Nerve Injury: 0  Poten�ates local anesthe�c toxicity 0  Clinical risk is minimal in normal nerves 0  Consider decreasing dose if poten�al for pre-­‐exis�ng nerve injury (diabe�c, chemotherapy, atherosclerosis) # Levy et al, Plast Reconstr Surg 2003 Nerve Injury Ultrasound Can Detect Intraneural Injec�on Neuropraxia – 0  Damage to the myelin sheath which disrupt the ac�on poten�al 0  As the axon is intact, the myelin sheath can be repaired 0  Be�er prognosis and faster resolu�on 0  Examples: compression, stretch injury Axonal Loss – Bicpes Fem P T Semi-­‐membranosus 0  Axon is destroyed 0  Recovery dependent on collateral reinnerva�on or axonal regrowth 0  Slow, incomplete recovery 0  Examples: blunt trauma, ischemic 6 4/24/15 Ultrasound Can Detect Intraneural Injec�on Biceps brachii MC Coracobrachialis Ultrasound Can’t Keep Anesthesiologists from performing Intraneural Injec�ons Inten�onally A Anesthesiology 2009; 110(6):1235-­‐43. Intraneural Needle Placement A review of nerve s�mula�on alone shows: 0  Needle-­‐nerve distance is not reliably reflected 0  Intraneural vs. Extraneural needle �p loca�on cannot be dis�nguished reliably 0  Does not prevent needle-­‐nerve contact 0  Does not prevent intraneural needle placement 0  A minimum s�mula�ng current is not a reliable marker of intraneural needle placement. 0  There is no agreed upon minimum s�mula�ng current for intraneural �p loca�on (compared to extraneural) 0  Cadaver model of human scia�c nerve 0  10 needle punctures (blunt and sharp needles) were evaluated microscopically 0  4/134 fascicles were damaged (3.4%) 0  1/112 vessels were damaged (0.9%) Conclusion: Intraneural needle placement usually results in needles passing around the fascicles, not through them Nerve S�mula�on Sala-­‐Blanch 2009 RAPM Macfarlane RAPM 2011 Injec�on Pressure A review of Injec�on pressure shows: 0  Monitoring for high injec�on pressure seems neither sensi�ve nor specific enough to reliably detect intraneural / intrafascicular needle placement 0  There are many causes for high injec�on pressure including fascial layers, tendon, or compressed �ssues 0  Low pressure injec�ons have caused histologic injury in animal models Ultrasound A review of ultrasound shows: 0  Using ultrasound to detect nerve expansion suggests intraneural injec�on has already occurred 0  Ultrasound resolu�on is not adequate to dis�nguish intraneural from intrafascicular injec�on 0  Ultrasound can detect very small volumes of intraneural injectate but the clinical significance of this has yet to be studied Macfarlane RAPM 2011 Macfarlane RAPM 2011 7 4/24/15 Evidence: Ultrasound and Nerve Injury Asleep/Heavy seda�on vs Awake Bernards et al, RAPM 2008 0  Intraneural injec�on (sub-­‐epineurium) has been correlated with histologic injury but not clinical injury Lupu et al, RAPM 2009; Bigeleisen et al, Anesthesiology 2006; Hara et al RAPM 2012 0  Underpowered results from RCTs and large case series show no difference in nerve injury when comparing localiza�on technique Barrington et al, RAPM 2009; Liu et al, RAPM 2009; Abrahams et al, BJA 2009 0  Permanent nerve injury is so rare (0-­‐4/10,000) it is impossible to study in a randomized fashion Nerve Injuries: Mechanism of Ac�on Pediatric Regional Anesthesia Network (PRAN) 0  Evaluated interscalene blocks for LAST (Local anesthe�c systemic toxicity) and PONS (Post-­‐op neurologic symptoms) 0  518 blocks iden�fied: 390 under GA, 123 under seda�on 0  88% ultrasound use 0  0 complica�ons reported 0  Sta�s�cal Incidence of complica�ons: 0 -­‐ 7.7/1000 Nerve Injuries: Mechanism of Ac�on 0  Compressive injury 0  Ischemia From Tourniquet 0 Trauma Nerve Injuries and Tourniquets 0  Tourniquet Design: Wider, cylindrical shaped tourniquets use less pressure to occlude blood flow 0  Tourniquet Pressure: Should be set to limb occusion pressure + 40-­‐60mmHg 0  Dura�on of use: 2 hours is considered to be safe; >3 hours is concerning. 0  Tourniquet infla�on/defla�on: Limited evidence for benefit if total �me is less than 3 hours. It is unknown what is the best dura�on to leave cuff down before re-­‐infla�ng (most range from 3-­‐20 minutes) CONCLUSION: Higher levels of tourniquet pressure and higher pressure gradients beneath tourniquet cuffs are associated with a higher risk of nerve-­‐related injury Noordin et al J Bone Joint Surg Am. 2009;91:2958-­‐67 8 4/24/15 Double-­‐Crush Injury Pre-­‐exis�ng Nerve Damage 0  Pre-­‐exis�ng peripheral neuropathy: –  No real evidence to support the “double-­‐crush” theory. However, careful risk/benefit assessment should be considered. 0  Pre-­‐exis�ng CNS disorders: –  No evidence links neuraxial anesthesia worsened outcomes with CNS disorders (e.g, MS), but assess risk/benefit of the procedure. If the pa�ent has a mass lesion of the spinal canal or severe spinal stenosis, care should be exercised with high volume anesthe�cs (epidurals) 0  In pa�ents with pre-­‐exis�ng neurologic deficits consider: lower dose/concentra�on/volume of local anesthe�cs, and using a lower concentra�on of vasoconstric�ve addi�ves RAPM 2008 33(5) 404-­‐415 Regional Anesthesia with Pre-­‐exis�ng Disease Diagnosis of Peripheral Nerve Injury 0  Evaluate: –  Intensity and dura�on of symptoms 0  Complete or progressive neural deficits should prompt urgent evalua�on by a neurologist 0  Mild (�ngling) and/or resolving symptoms indicate excellent prognosis 0  If symptoms fail to improve, neurological consulta�on should be sought within 2-­‐3 weeks –  Consider MRI or nerve conduc�on studies 0  Motor compromise more worrisome than sensory ASRA Guidelines 2008 Diagnosis of Peripheral Nerve Injury 0  Nerve conduc�on studies / EMG –  Can give quan�ta�ve evalua�on of nerve func�on –  Can assist in giving a be�er idea of prognosis –  Early EMG is less informa�ve about the injury compared to EMG at 2-­‐3 weeks as impairment evolves over �me 0  Early EMG can establish if the nerve has injury at baseline prior to the current insult 0  MRI preferred over CT –  MRI is be�er at evalua�on of nerves and so� �ssue structures Sorenson RAPM 2008 9 4/24/15 Diagnosis / Treatment Guidelines: Peripheral Barrington et al RAPM 2009 ASRA Guidelines 2008 Document well Gerancher RAPM 2005 Care of the Pa�ent 0 
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Communicate Do Not Place Blame Referral as needed Keep in contact with pa�ent Documenta�on of con�nued interac�ons with pa�ent Summary of Suspected Nerve Injury 0  Nerve injuries are rare but can be significant 0  Most cases will improve and resolve without deficit 0  Urgent consult to neurology / neurosurgery for suspected neuraxial compromise or peripheral sensorimotor deficits that are severe /complete 10