Anesthesia and Critical Care (updated 09/06)

Transcription

1 Anesthesia and Critical Care (updated 09/06) 1. What is the mechanism of action of a local anesthetic? Discuss amides and esters. AL Local anesthetics produce anesthesia by inhibiting excitation of nerve endings or by blocking conduction in peripheral nerves. This is achieved by anesthetics reversibly binding to and inactivating sodium channels. Sodium influx through these channels is necessary for the depolarization of nerve cell membranes and subsequent propagation of impulses along the course of the nerve. When a nerve loses depolarization and capacity to propagate an impulse, the individual loses sensation in the area supplied by the nerve. The order of affinity of local anesthetics for different sodium channel states is open is better than inactivated, which is better than resting. Thus, the open state of the sodium channel is the primary target of local anesthetic molecules. The blocking of propagated action potentials is therefore a function of the frequency of depolarization. The mechanism for differential block, the block of pain perception without motor block, is still unclear. Amino esters and amino amides differ in several respects. Amino esters: are metabolized in the plasma via pseudocholinesterases, unstable in solution, much more likely than amino amides to cause allergic hypersensitivity reactions. Ex: lidocaine, mepivacaine, prilocaine, bupivacaine, etidocaine, and ropivacaine and levobupivacaine, shorter duration of action Amino amides: are metabolized in the liver with renal excretion, very stable in solution. Ex: cocaine, procaine, tetracaine, chloroprocaine, and benzocaine Physiologic activity of local anesthetics is a function of their lipid solubility, diffusibility, affinity for protein binding, percent ionization at physiologic ph, and vasodilating properties. Potency is directly related to lipid solubility, increased lipid solubility leads to faster nerve penetration and blockade of sodium channels.

2 Protein binding is related to the duration of action Ionized vs. Non ionized forms: non-ionized portion is the form that is capable of diffusing across nerve membranes and blocking sodium channels, causes a faster onset of action. Decreases in ph of tissues shifts equilibrium towards the ionized form causing delayed onset of action. All local anesthetics, with the exception of cocaine, are vasodilators. Vasodilation occurs via direct relaxation of peripheral arteriolar smooth muscle fibers. Greater vasodilator activity of a local anesthetic leads to faster absorption and, thus, shorter duration of action. To counteract this vasodilatation, epinephrine is often included in local anesthetic solutions 2. Are the effects of amides and esters additive? CB 3. You are operating on a 10-year-old who weighs 30 kg. How much Lidocaine can you give him? What are the symptoms of toxicity? How do you treat it? How does Lidocaine work? AL Lidocaine is an amide local anesthetic and a less commonly used antiarrhythmic that exerts its effects on nerve axon sodium channels, preventing depolarization. Lidocaine: 1% =10mg/ml Without Epi 5mg/kg = 150 mg or 15 ml with Epi or phenylephrine give 7 mg/kg = 210 mg or 21 ml Adverse reactions occur primarily in the CNS (neurotoxicity) and cardiovascular system (myotoxicity) because these tissues are also composed of excitable membranes, the target of local anesthetic action. In the CNS, a progression of signs and symptoms may be observed in the patient. The patient may report lightheadedness, tinnitus, circumoral numbness, a metallic taste, or double vision. Upon examination, the patient may become drowsy or slur speech and may develop nystagmus. At higher levels of anesthetics, the patient may become anxious and develop fine tremors of the muscles of the hands and/or face. These tremors may worsen and coalesce into a grand mal seizure. Ultimately, the patient may experience generalized CNS depression leading to hypoxia, acidosis, and respiratory arrest. Local anesthetics decrease the rate of depolarization of cardiac tissue, which is the rationale behind the use of lidocaine in treatment of ventricular arrhythmias. At higher concentrations, amplitude of the cardiac action potential is decreased, and the velocity of conduction is reduced. At toxic doses, the negative inotropic effects of local anesthetics may lead to bradycardia, ventricular fibrillation, or asystole. Other cardiovascular effects include hypotension, which occurs via the direct vasodilating effects of local anesthetics on peripheral arteriolar smooth muscle.

3 Adverse Reactions Significant Effects vary with route of administration. Many effects are dose related. Frequency not defined. Cardiovascular: Arrhythmia, bradycardia, arterial spasms, cardiovascular collapse, defibrillator threshold increased, edema, flushing, heart block, hypotension, sinus node supression, vascular insufficiency (periarticular injections) Central nervous system: Agitation, anxiety, apprehension, coma, confusion, disorientation, dizziness, drowsiness, euphoria, hallucinations, headache, hyperesthesia, hypoesthesia, lethargy, lightheadedness, nervousness, psychosis, seizure, slurred speech, somnolence, unconsciousness Dermatologic: Angioedema, bruising (transdermal system), contact dermatitis, depigmentation (transdermal system), edema of the skin, itching, petechia (transdermal system), pruritus, rash, urticaria Gastrointestinal: Metallic taste, nausea, vomiting Local: Burning (ophthalmic), irritation (transdermal system), thrombophlebitis Neuromuscular & skeletal: Pain exacerbation (transdermal system), paresthesia, transient radicular pain (subarachnoid administration; up to 1.9%), tremor, twitching, weakness Ocular: Conjunctival hyperemia (ophthalmic), corneal epithelial changes (ophthalmic), diplopia, visual changes Otic: Tinnitus Respiratory: Bronchospasm, dyspnea, respiratory depression or arrest Miscellaneous: Allergic reactions, anaphylactoid reaction, sensitivity to temperature extremes Following spinal anesthesia: Positional headache (3%), shivering (2%) nausea, peripheral nerve symptoms, respiratory inadequacy and double vision (<1%), hypotension, cauda equina syndrome Postmarketing and/or case reports: ARDS (inhalation), asystole, chondrolysis (continuous intraarticular administration), disorientation, methemoglobinemia, skin reaction Treatment of Toxicity: -If lidocaine toxicity is suspected, stop the injection immediately and prepare to treat the reaction. -Ensure adequate oxygenation, whether by face mask or by intubation.

4 -Anticonvulsants such as benzodiazepines and barbiturates (diazepam 5-10 mg, thiopental mg) are the drugs of choice for seizure control. Phenytoin is not effective and should be avoided. Succinylcholine is sometimes also used to terminate the neuromuscular effects of seizures. Because succinylcholine paralyzes all muscles, the patient requires intubation. -In severe reactions, monitor the cardiovascular system (CVS) and support the patient with intravenous fluids and vasopressors as required. -Metabolic acidosis may develop, and the use of sodium bicarbonate can be considered, although, as in other instances of acute metabolic acidosis, this is controversial. 4. How much Epinephrine do you need to produce vasoconstriction? Plast Reconstr Surg 1973;51:129. CB 5. Your patient s temperature goes to 104 and his heart rate is up after induction of anesthesia. What do you do for malignant hyperthermia (MH)? What do you do if you patient has had a history of MH in the past? CB 6. Tell us about Cocaine. How does it work? What is a toxic dose? What are the symptoms of an overdose? How is it metabolized? AL Cocaine is an alkaloid derivative from the coca plant in honor of Pete- Erythroxylon coca. First introduced in the 1800 s, Freud is a famous for his human and self experiments with this drug was used in ophthalmology and dentistry. Coca Cola contained 4.5mg/180mL but was pulled off the Market in 1914 by the narcotics act which banned distribution except for medical use. MOA: anesthesia achieved by reversibly binding to and inactivating sodium channels, at the peripheral nerve terminals, inhibiting the sodium influx that is necessary for depolarization and propagation of impulses along the nerve terminal. CNS effects are achieved by inhibition of reuptake of Dopamine in the midbrain regions responsible for rewad mediation- hence the euphoria and arousal effect, decrease of coaine levels decreases the dopamine leading to a depression and craving.

5 PNS effects: blocks reuptake of NE in ANS and thought to stimulate relase of catecholamine from the adrenal gland- resulting in increased stimulation of SNS- resulting in tachycardia, hypertension, diaphoresis, mydriasis and tremors, and locally produces the desired vasocontrictive effect also through NE reuptake blockade. The safe maximum dosage is reported to be 200 mg or 2-3 mg/kg, but this is based on anecdotal observations rather than controlled studies. Even 200 mg can cause adverse reactions if rapidly absorbed It is rapidly absorbed in the mucus membranes with peak plasma levels at 15-60min, half life in serum in 30-90min. Hydrolysis by plasma protein psuedocholinesterases is responsible for most of the metabolism with its metabolites primarily benzoylecgonine & cocaethylene. In the Liver it is oxidatively metabolized to norcocaine- which can cause severe hepatic toxicity. That which is not metabolized is excreted in the urine unmetabolized- though to be upawards of 20%. Overdose:All due to cardiac, repiratory and CNS adrenergic effects.may result in hyptertension, tachycardia, ventricular fibrillation, cardiac arrest, including direct cariotoxicity, angina, MI, CVI TIA, pulmonary edema, hepatotoxity (secondary to toxic metabolite) intestinal ischemia, seizures, CNS depression.tx: is supportive care- there is no antidote. Activate ACLS, propanolol, nitrates, CCB, alpha adrenergic blockers may be required to improve coronary Blood flow and restore normal rhythm. For seizures use diazepam, and aggressively treat hyperthermia with cooling blankets. 7. We often use Marcaine in tonsillectomies for longer acting analgesia. What is the dose? What are the particular side effects? AL Marcaine dosing per uptodate is Local anesthesia: Infiltration: 0.25% infiltrated locally. Maximun 175mg.

6 Bupivacaine (Marcaine) Bupivacaine with epinephrine Long ( min) Long ( min) Without epinephrine: 2.5 mg/kg; not to exceed 175 mg total dose With epinephrine: Not to exceed 225 mg total dose Side effects per emedicine confirmed with uptodate. All the side effects seemed to be similar to those of the other amide local anesthetics. Info is from the table of local anesthetic complications. Adverse reactions may occur following administration of local anesthetics and usually result from administration of too much drug. Adverse reactions may also occur following injection of very vascular sites or from accidental direct intravascular injection of the drug. Deaths following local anesthetic administration are always a result of overdosage. Tissue toxicity can be achieved by all local anesthetics if high concentrations are used. Adverse reactions occur primarily in the CNS (neurotoxicity) and cardiovascular system (myotoxicity) because these tissues are also composed of excitable membranes, the target of local anesthetic action. In the CNS, a progression of signs and symptoms may be observed in the patient. The patient may report lightheadedness, tinnitus, circumoral numbness, a metallic taste, or double vision. Upon examination, the patient may become drowsy or slur speech and may develop nystagmus. At higher levels of anesthetics, the patient may become anxious and develop fine tremors of the muscles of the hands and/or face. These tremors may worsen and coalesce into a grand mal seizure. Ultimately, the patient may experience generalized CNS depression leading to hypoxia, acidosis, and respiratory arrest. Local anesthetics decrease the rate of depolarization of cardiac tissue, which is the rationale behind the use of lidocaine in

7 treatment of ventricular arrhythmias. At higher concentrations, amplitude of the cardiac action potential is decreased, and the velocity of conduction is reduced. At toxic doses, the negative inotropic effects of local anesthetics may lead to bradycardia, ventricular fibrillation, or asystole. Other cardiovascular effects include hypotension, which occurs via the direct vasodilating effects of local anesthetics on peripheral arteriolar smooth muscle. Recognizing signs and symptoms of an adverse reaction to local anesthetics and administering emergency care in relation to the severity of the reaction are essential. With severe life-threatening reactions, immediately curtail the procedure. Activate advanced cardiac life support (ACLS) protocols immediately, including intubation and defibrillation if indicated. Hypotension may require intravenous fluids and vasoconstrictor drugs for circulatory support. Control seizure activity with diazepam 5-10 mg IV. Succinylcholine may be required to stop ongoing tremors, but its use requires intubation and mechanical ventilation. Atropine and epinephrine may be indicated to treat bradycardia. 8. Discuss Toradol and its use in tonsillectomy. Arch Otolaryngol Head Neck Surg 1996;122:937. CB 9. You need to sedate a child in the ER to repair a laceration. What is now recommended? HH 10. You are doing a bilobed flap on the nose for a BCCA. Should you inject the area w/lidocaine with Epinephrine or plain Lidcoaine? What will epinephrine do to the flap? TT 11. Discuss local anesthetics of facial surgery. Read and copy Plast Reconstr Surg 1998;101:840 for the group. TT 12. During a routine tonsillectomy in a 4-year-old (20kg), you find

8 that you are losing a lot of blood. The anesthesiologist is concerned. At what point should you consider transfusing the child. TT 13. You are planning a tonsillectomy in a pediatric patient with Down s Syndrome. Any special considerations? TT 14. Why has vasopressin been added to ACLS resuscitation protocols? Pharmacotherapy 2004;24: HH 15. Discuss the management of post-operative atrial fibrillation. Ann Thorac Surg 2005;79: HH