Local Anesthetics

王審之

Basic review

Most local anaesthetics block nerve impulses by blocking the voltage-gated sodium channels in the cell membrane.

Potency correlates with lipid solubility. Onset of action depends on many factors,

including lipid solubility and the relative concentration of the nonionized lipid-soluble form (pKa).

Local anesthetics structure

Ester: allergen metabolites– Cocaine– Tetracaine

Amide: metabolized in the liver– Lidocaine– Bupivacaine– Ropivacaine

Agents we are using

Lidocaine – pKa 7.7– Intrathecal: transient neurologic syndrome, severe radicular

back pain. Mechanism: unknown

– less controversy for epidural use. Bupivacaine – pKa 8.1

– more cardiotoxic in humans and animals. Ropivacaine – pKa 8.2

– for the purposes of reducing the potential toxicity and improving the relative sensory and motor block profiles

– relative analgesic potencies of ROP : BUP were 0.6 (less lipophilic)– relative motor block potency of ROP : BUP was 0.66

Ropivacaine versus Bupivacaine

Smaller effect on QRS duration than BUP in healthy volunteers. (+2.4% vs +6%; p < 0.05)

Mean maximum tolerated dose for CNS toxicity was higher with ROP than BUP in healthy volunteers (124 vs 99mg; p < 0.01)

the venous plasma concentration of local anaesthetic at which ECG changes occurred was 40% lower for BUP than for ROP. Mean maximum tolerated free arterial concentration of ROP was greater than BUP (0.56 vs 0.30 mg/L; p < 0.001)

Less impairment of mitochondrial energy metabolism than BUP in isolated rabbit myocardium and rat cardiac mitochondria.

Allergic reaction

True hypersensitivity reactions to local anesthetic agents are quite uncommon.

Clinical diagnosis– IgE, eosinophil count: unreliable

Supportive care– Airway– Breathing– Circulation: epinephrine 30-50 microgram

CNS toxicity

The CNS is the site of premonitory signs of overdose in awake patients.– Circumoral numbness, tongue paresthesia, and

dizziness.– Tinnitus, blurred vision.– Excitatory signs (restlessness, agitation, nervousness)

often precede central nervous system depression (slurred speech, drowsiness, unconsciousness)

– Muscle twitching, tonic-clonic seizure

Cardiovascular toxicity

The cardiovascular system will exhibit arrhythmias and eventual collapse as local anaesthetic concentrations increase.– Major cardiovascular toxicity usually requires about

three times the concentration of blood that produces seizures.

– circulatory collapse-CNS ratio: this ratio tends to be small in the more potent, long-acting local anaesthetics

Maximum recommended dose

Lidocaine: 4.5mg/kg Irrelevant

– it is not a question of ‘if’ an intravascular injection will occur, just a question of ‘when’.

Blood absorption of local anaesthetic is greatest from intercostal > caudal > epidural >brachial plexus > femoral – sciatic > subcutaneous >intra-articular > spinal.

Case report sciatic nerve block with bupivacaine

Lipid rescue

Search for lipidrescue

At our hospital

select techniques designed to minimise intravascular injection while always being prepared appropriate treatments for its eventual occur.

– Sonoguide nerve block If patient safety was the only issue, involved in

long-acting local anaesthetic selection, the use of less toxic options other than bupivacaine for large volume blocks would seem intuitive.

– Lidocaine and bupivacaine is what we get.

Total intravenous anesthesia (TIVA)

Painless dental retraction

TIVA

Total intravenous anesthesia– Amnesia and analgesia

Sedation in intensive care unit Day surgery Office based anesthesia

– Target controlled infusion (TCI)– Close loop system

What is TCI ?

Effect site alfentanil concentration

Time (min)

Infusion mode for Propofol

Marsh– Derived from Gept’s model (1987)

Regional anesthesia combined propofol infusion Total 18 patients No BMI data Covariate: weight

– Scarecely adequate in the elderly Anaesthesia 1998;53:Suppl. 1:61-67 Ann Fr Anesthn Reanim 2000;19:R027 For patients less than 70y/o

Infusion mode for Propofol

Schnider– Anesthesiology 1998; 88: 1170-1182– Patient population: 25-81y/o health volunteers

Patient number: 24 Body weight: 44.4~123 kg

– Covariates Age, gender, height and body weight, lean body mass BMI: <43 (M) and <35(F)

Update in pediatric TIVA

Pediatric Anesthesia 2004; 14: 374-379– Propofol is not indicated for use in children < 3y/o.– Larger induction doses and higher infusion rates

Large central compartment

In PICU in Australia and NZ

The majority of practitioners (82%) use propofol infusion in children in PICU

– the main indication being for short-term sedation in children requiring procedures.

67% of paediatric intensivists use maximum infusion doses that may be considered dangerously high (> or = 10 mg/kg/h)

19% use propofol infusion for prolonged periods (> 72 hours). A smaller proportion (15%) of respondents indicate that they may

use both higher doses and prolonged periods of infusion Anaesth Intensive Care. 2002 Dec;30(6):786-93.

Propofol infusion syndrome

Defined as acute bradycardia progressing to asystole combined with lipemic plasma, fatty liver enlargement, metabolic acidosis with negative base excess > 10mmol/l, rhabdomyolysis or myoglobinuria associated with propofol infusion.

– Large dose, prolonged duration. A hereditary mitochondrial fatty acid metabolism impairment

resembling medium chain acyl-CoA dehydrogenase deficiency is responsible for the susceptibility to the development of propofol infusion syndrome.

Minerva anestesiol 2009;75:339

2008 ASA statement

A reliable source of oxygen and backup oxygen sources. An adequate and reliable source of suction. Reliable system for scavenging waste anesthetic gases. Adequate illumination of the patient, anesthesia machine and

monitoring equipment. Sufficient space to accommodate necessary equipment and

personnel. Sufficient electrical outlets

2008 ASA statement

Anesthetic equipment– a self-inflating hand resuscitator bag capable of administering at least

90 percent oxygen as a means to deliver positive pressure ventilation– adequate anesthesia drugs, supplies and equipment for the intended

anesthesia care– adequate monitoring equipment

Ventilation: Monitoring for the presence of exhaled carbon dioxide should be utilized

An emergency cart– a defibrillator– emergency drugs– equipment adequate to provide cardiopulmonary resuscitation

adequate staff trained to support the anesthesiologist and a reliable means of two-way communication to request assistance.

2008 ASA statement

Appropriate postanesthesia management should be provided.

Dental procedures for kids

Little people, big problems

All sedatives and narcotics have caused problems even in “recommended doses”.

All areas using sedation have reported adverse events. Children 1-5 yr of age are at most risk. Most had no severe

underlying disease. Respiratory depression and obstruction are the most frequent

causes of adverse events. Adverse events involved - multiple drugs, drug errors or overdose,

inadequate evaluation, inadequate monitoring, inadequate practitioner skills, and premature discharge.

Upper respiratory infections

The average child gets 6-7 URI’s per year and each URI lasts about 7 to 10 days. Further, there is evidence to suggest that airway reactivity is increased for at least 7 weeks after a URI .

– only about 9 weeks may be left in which the average does not have a URI episode or after a URI episode.

symptoms– sore throat– Sneezing– rhinorrhea and congestion– nonproductive cough– temp > 38.3– laryngitis & malaise

Risk factors– asthma,– bronchopulmonary dysphasia,– history of prematurity– under one year of age– sickle cell disease– surgery involving the airway.

Perioperative Myocardial Infarction in Patients Undergoing Noncardiac surgery

A cohort study of participants in the POISE trialAnn Intern Med. 2011; 154: 523-528

POISE trial

PeriOerative ISchemia Evaluation: a blinded, randomized, and control trial of controlled-release metoprolol versus placebo in 10000 patients at risk for a perioperative cardiovascular event undergoing noncardiac surgery

• Lancet 2008;371:1839-47

Methods

In POISE trial– All patients received electrocardiography (ECG) 6 to 12 hours

as well as on the 1st, 2nd, and 30th days after surgery– Troponin levels were measured 6 to 12 hours as well as on

the first, second, and third days after surgery.

What did the paper point out?

MI definition

Results of cardiac enzyme

Defining features

Pre-operative survey

Medication

“Continue beta blocker medication on the operation day” is still class I recommendation in AHA clinical guideline.

Multivariable regression analysis among patients who had an MI suggested that acetylsalicylic acid and statin use were each associated with a reduction in the risk for 30-day mortality.

Perioperative management

Risk factor

Malignant hyperthermia (MH)

在我們國土上漫遊的眾多可怕野獸與怪物裡面，其中最稀罕，同時也是最危險的種類就是蛇妖。 ~~摘錄自哈利波特 ; 消失的密室

Change of HR and EtCO2

: fentanyl : bicarbonate : dantroleneStop inhalation agent

36 36.8 37.2

39

ABG data1hr

30min3hr 3hr45min 4hr 4hr15min 5hr

PaO2 248.6 202.7 207.4 344.5 398.4

PaCO2 36.4 37.7 44.7 75.3 107.7 33.5

PH 7.381 7.266 7.240 7.108 7.004 7.467

BE -3.5/-4.0 -10/-8.4 -8.3/-7.2 -4.4/-5.4 0.3

Na/K 135/3.43 141/4.19 146/3.93 143/3.93 145/4.92 140/5.0

glucose 236 147 234 175

managementBicarbona

3ampBicarbona

6ampTV: 640RR:14

DantroleneInfusion

CK: 38

Equipment malfunction

A&A 1994 78:590– 27y/o male, acoustic neuroma

Epidemiology

Incidence– A Danish survey indicates an incidence of fulminant MH of one

case per 250,000 anesthetics.– considering only potent anesthetics and succinylcholine, one

case of fulminant MH occurred per 62,000 anesthetics.– Potent volatile agents in combination with succinylcholine: one

case per 16,000 anesthetics or one case per 4,200 anesthetics.

the earliest reaction confirmed by testing is six months of age. The oldest is 78 years.

– Orphanet Journal of Rare Diseases 2007, 2:21

MH diagnosis

MH is not expected to occur when nontriggers are administered.

MH should be suspected if there is increased end-expired carbon dioxide, undue tachycardia, tachypnea, arrhythmias, mottling of the skin, cyanosis, increased temperature, muscle rigidity, sweating, or unstable blood pressure.

– If end-tidal carbon dioxide increases and ventilation is then increased to maintain normal end-tidal values, diagnosis of MH may be delayed.

Analysis of arterial blood gases demonstrates metabolic acidosis and may show respiratory acidosis.

Management

Discontinue all anesthestic agent and hyperventilation with 100% oxygen.

Dantrolene 2mg/kg, every 5 minutes to a total dose of 10mg/kg.

Bicarbonate (2 to 4 mEq/kg) Control fever: cooling should be halted at 38 ℃ Monitor urine output Analyze electrolytes; CK; liver profile; BUN; lactate and

glucose; coagulation; hemoglobin and myoglobin (both serum and urine)

Supportive treatment

Thanks for your concentration