Which anesthetics lower ICP?

1. thiopental

2. opioids

3. propofol

4. etomidate

How can you speed inhalational induction of anesthesia?

1. During induction of anesthesia, gradient develops so that the partial pressure of the anesthetic in the lungs > partial pressure of the anesthetic in arterial blood > partial pressure of anesthetic in the brain. The partial pressure of the anesthetic in the lung is the force driving the anesthetic into the body.

2. Anesthetic induction will be inc.  as more anesthetic is delivered to the lung or less anesthetic is removed.
3. Factors that increase the rise in anesthetic partial pressure in the lung: minute ventilation, delivering unusually high concentrations of anesthetic agents (i.e., overpressure), using high gas flows or non-rebreathing anesthetic systems, and having a reduced FRC (functional residual capacity).

4. Coadministering high concentrations of NO may also speed induction through concentrating effect and/or second-gas effect.
5. Factors that decrease the rate anesthetics are removed from the lung:

      *CO: High cardiac output will slow the rate of induction.

      *Lipid solubility: high lipid solubility will slow induction (b/c anesthetic partial pressure in lung will rise more slowly)

6. Avoid high cardiac output, select agents with a low blood:gas solubility: will increase the rate of induction.

Describe the concentrating effect and second-gas effect?

1) Only occur on induction of anesthesia

2) Describes processes whereby the delivery of an inhalational anesthetic can be enhanced by the presence of a large amount of nitrous oxide.

What are the

1. Induction

2. Maintenance

3. Emergence (or Recovery)

phases of anesthesia?

Induction - the administration of a drug or combination of drugs at the beginning of an anesthetic that results in a state of general anesthesia.

Maintenance – the drugs used to initiate the anesthetic are beginning to wear off, and the patient must be kept anesthetized with a maintenance agent. In this stage the patient must be kept anesthetized enough so the surgeon may perform the operation.

Emergence – Reversing the NMB’s if used, and allowing the patient to wake up

In 1937 Arthur Guedel published a Depth of Anesthesia Classification System.

This original system was described for ether anesthesia following morphine and atropine premedication.

It is important to realize that muscle relaxants were not commonly employed in 1937.

Describe Guedel's classification system and other limitations of this system.

Stage I (Stage of Analgesia or the stage of Disorientation): from beginning of induction to loss of consciousness. 0 to ~0.4 MAC: first is analgesia (nitrous oxide is given in dental offices for analgesia, not for anesthesia), may also have amnesia at this stage.

Stage II (Stage of Excitement or the stage of Delirium): from loss of consciousness to onset of automatic breathing. Eyelash reflex disappear but other reflexes remain intact. Coughing/vomiting/struggling may occur; resps can be irregular with breath-holding. ~0.5 to ~ 1.0 MAC: then a drunken/confused/delirious/excited stage

Stage III (Stage of Surgical anesthesia): from onset of automatic respiration to respiratory paralysis. ~1.0 to ~ 1.3 MAC: then surgical anesthesia
Stage IV: from stoppage of respiration till death. Anesthetic overdose cause medullary paralysis with respiratory arrest and vasomotor collapse. Pupils are widely dilated and muscles are relaxed. Very large doses: and finally medullary paralysis (body does not regulate breathing, bloodpressure, etc).

What is Malignant Hyperthermia (MH)?

Describe the presenting symptoms and progression of MH.

Who is at risk for MH and what is the treatment of an acute episode of MH?

1. MH is primarily thought to be an autosomal dominant genetic disorder that causes a hypermetabolic state after administration of volatile anesthetics (i.e. halothane, sevoflurane, isoflurane, desflurane, enflurane) and succinylcholine.

2. Conditions such as Duchenne dystrophy, Central Core Disease, Osteogenesis Imperfecta, burns can cause MH.

3. Risk pts: previous problems with anesthesia, or immediate family member who has had anesthesia problems.
4. MH is caused by an abnormal release of Ca++ from SR, usually caused by a defect of the ryanodine receptor.

5. The inc. ICF Ca++ --> sustained muscle contraction, hypermetabolism, ATP depletion, heat production, cell death.

6. Early signs of MH include: unexplained inc.  ETCO2 and dec. SpO2, hypoxemia, tachycardia, HTN, and muscular rigidity --> acidosis, elevated body temp, hyperK+, rhabdo, myoglobinuria, and dysrhythmias.

7.Symptoms occur within 1 hr of administration of triggering substance, in rare cases, several hours have elapsed.
8.Treatment of MH includes: Dantrolene which blocks the release of calcium from the SR

       *the ryanodine receptor is located within sarcoplasmic reticulum

       *dantrolene blocks release of calcium from sarcoplasmic reticulum

       *dantrolene is first line therapy for MH.

How are local anesthetics classified?

Chemical structure: either amides or esters, determined by the molecule attached to the intermediate chain.

1. The ester type local anesthetics:

     *rapid hydrolysis by plasma cholinsterases: less toxic due to its rapid metabolism.

     *ester type local anesthetics have a short duration due to their rapid metabolism.

     *contain para-amino benzoic acid (PABA)

     *(cocaine is only exception: it contains benzoic acid, not para-amino benzoic acid).

2. The amides types of local anesthetics:

     *broken down in the liver.

     *require hepatic extraction --> higher blood concentration causing toxicity.
Duration of Action
1. Short duration: lasting 30 to 60 minutes
2. Intermediate duration: lasting 60-120 min
3. Long acting duration: lasting 2-6 hours
Clinical duration can be dependent on dosage, site of injection, and use of vasopressors.

What is the mechanism of action of local anesthetics?

1. Local anesthetics bind to voltage gated sodium channels from the INSIDE of the cell leading to their inactivation.

2. Preventing subsequent channel activation/depolarization
3. LAs with a low pKa have a faster onset of action. (Fast onset of action then low pKa.)
4. LAs with high protein binding have a longer duration of action.(Long duration of action then high lipid solubility + high protein binding.)
5. LAs with high lipid solubility are more potent and have a longer duration of action. (High potency then high lipid solubility)

The dose of lidocaine when given IV = 1 - 1.5 mg/kg
The maximum lidocaine dose when administered s.q. = 5 mg/kg
The maximum lidocaine dose when administered s.q. with EPI = 7 mg/kg

Which nerve fibers are more resistant to local anesthetics?

1. All nerve fibers are sensitive to LA, but nerve fibers that are larger in diameter and are myelinated tend to be more resistant to LA.

2. From high sensitization to low sensitization:

          *small myelinated axons

          *nonmyelinated axons

          *large myelinated axons

How are local anesthetics metabolized?

1. Ester type local anesthetics are metabolized via hydrolysis rapidly by pseudo cholinesterase. Hydrolysis is very rapid --> water soluble metabolite is excreted in urine.

         *conjugation and hydrolysis reactions are Phase 2

2. Amide type local anesthetics are metabolized by P-450 enzymes in the liver. The rate of amide metabolism is dependent on the drug, but overall metabolism is much slower than those of the ester LA. Since metabolism is slower than ester LA, amide LA can lead to toxicity, esp. in patients with hepatic insufficiency.

           *oxidative metabolism is Phase 1 reaction

           *Phase 1 more complex than Phase 2 -- pts with liver disease (cirrhosis) are more likely to have problems metabolizing an amide like lidocaine than an ester like tetracaine.

           *The amount of metabolism of lidocaine and some other amides is limited by liver blood flow. If there is more liver blood flow, clearance is increased (and vice versa).

What are the toxic effects of local anesthetics?

What is the role of intralipid in the treatment of local anesthetic toxicity?

CNS: As plasma concentration continues to inc. -->symptoms of restlessness, vertigo, and tinnitus occur. Further increases in the CNS result in slurred speech and skeletal muscle twitching --> tonic-clonic seizures.

CV: Toxic levels can lead to hypoTN d/t relaxation of arteriolar vascular smooth muscle and direct myocardial depression. When plasma LA concentrations are excessive, sufficient cardiac sodium channels become blocked so that conduction and automaticity become adversely depressed.

Intralipid (fat emulsion) has been used to treat cardiovascular collapse in LA toxicity. Lipid soluble local anesthetic drugs partition out of plasma and into lipid after intralipid is administered. As plasma levels of the drug fall, toxic symptoms improve.
           *Prilocaine is a local anesthetic that is metabolised to o-toluidine.

           *This metabolite may cause methemoglobinema --> treat w/ methylene blue

How does adding bicarbonate solution or epinephrine affect the pharmacokinetics of local anesthetics? Explain.

1. This allows increase of neuronal uptake

2. Enhances quality of analgesia

3. Prolongs duration of action

4. Limits toxic side effects.
5. The addition of NaHCO3- to epi containing LAs have been known to cause:

                *alkalinization of the LA solution therefore speeding onset

                *improving quality of the block

                *prolonging blockage by inc. the amt of free base in the solution.
6. Bicarb causes local anesthetics to begin working faster

7. EPI increases duration of action.

If patient is highly allergic to sunscreen, which of these local anesthetics would you not administer:

1. procaine (Novacaine)

2. tetracaine

3. lidocaine

4. bupivacaine (Marcaine)

5. mepivacaine

6. prilocaine,

7. ropivacaine

8. 2-chloro-procaine (Nesacaine)

9. piperocaine

1. Procaine (Novocaine) is metabolized to p-aminobenzoic acid (PABA). PABA is a common ingredient in sunscreen.

2. If the generic name has one "i" in it the drug is an ester.

3. If it has two "i's" it is an amide.

4. The exception to this rule is piperocaine (which is an ester).

5. Therefore procaine, tetracaine and piperocaine are esters (that are metabolized to PABA) and should not be administered to someone with a PABA allergy.

What are common features of modern inhalational anesthetics?

1. Non-flammable and non-explosive

2. Dec. cerebrovascular resistance --> increased perfusion of the brain

3. Cause bronchodilation

4. Decrease minute ventilation

5. Decrease hypoxic pulmonary vasoconstriction

6. Movement throughout the body depends on their solubility in blood & tissues as well as blood flow

Describe the pharmacology and indications for ketamine.

1. Ketamine = short acting, non-barb anesthetic causes dissociated state, pt is unconscious but awake/does not feel pain.

2. It provides sedation, amnesia, and immobility.

3. Interacts with the N-methyl-D-asparate receptor. (Ketamine is an NMDA antagonist.)

4. Lipophilic and enters brain circulation very quickly.

5. Metabolized by the liver; in small amounts it can be excreted unchanged.
6. It is not widely used b/c it inc. cerebral blood flow -->postop hallucinations
7. Ketamine stimulates SNS outflow-->stimulates the heart-->inc.BP/CO

8. Used when circulatory depression is undesireable

It acts as an uncompetitive NMDA receptor antagonist thus causing anesthesia. Ketamine also binds to opioid receptors giving it an analgesic effect. Indications for ketamine are based on its capacity to stimulate sympathetic outflow which causes increase heart rate, blood pressure and cardiac output. This property is of value for patients with hypovolemic or cardiogenic shock as well as patients with asthma.

HALOGENATED ANESTHETICS MAY PRODUCE MALIGNANT HYPERTHERMIA:

A: PATIENTS WITH POOR RENAL FUNCTION

B: PATIENTS ALLERGIC TO THE ANESTHETIC

C: PREGNANT WOMEN

D: ALCOHOLICS

E: PATIENTS WITH A GENETIC DEFECT IN MUSCLE CALCIUM REGULATION

Answer: E

MH OCCURS IN A SMALL POPULATION WHO HAVE A GENETIC DEFECT AND ALSO RECEIVE SUCCINYLCHOLINE. THE OTHER CONDITIONS ARE NOT KNOWN TO DISPOSE TO MH.

CHILDREN WITH ASTHMA UNDERGOING A SURGICAL PROCEDURE ARE FREQUENTLY ANESTHETIZED WITH SEVOFLURANE, BECAUSE IT:

A: IS RAPIDLY TAKEN UP

B: DOES NOT IRRITATE THE AIRWAY

C: HAS A LOW NEPHROTOXIC POTENTIAL

D: DOES NOT UNDERGO METABOLISM

Answer: B

Sevoflurane is an inhalation anesthetic with low pungency. It is nonirratative and less likely to cause laryngospasm.

(A is true buy induction and recovery are rapid but C/D are false)

WHICH OF THE FOLLOWING IS MOST LIKELY TO REQUIRE ADMINISTRATION OF A MUSCLE RELAXANT?

A: ETHYL ETHER

B: HALOTHANE

C: METHOXTFLURANE

D: BENZOS

E: NITROUS OXIDE

Answer: E

NITROUS OXIDE HAS NO MUSCLE-RELAXANT PROPERTIES. ETHYLETHER, METHOXYFLURANE AND BENZOS PRODUCE GOOD MUSCLE RELAXANT; HALOTHANE PRODUCES MODERATE MUSCLE RELAXATION

WHICH ONE OF THE FOLLOWING IS A POTENT IV ANESTHETIC BUT A WEAK ANALGESIC?

A: THIOPENTAL

B: BENZOS

C: KETAMINE

D: ETOMIDATE

E: ISOFLURANE

Answer: A

THIOPENTAL IS A POTENT ANESTHETIC BUT A WEAK ANALGESIC. IT IS THE MOST WIDELY USED IV GENERAL ANESTHETIC. IT IS AN ULTRA SHORT ACTING BARBITURATE AND HAS A HIGH LIPID SOLUBILITY.

WHICH ONE OF THE FOLLOWING IS A POTENT ANALGESIC BUT A WEAK ANESTHETIC?

A: METHOXYFLURANE

B: SUCCINYLCHOLINE

C: DIAZEPAM

D: HALOTHANE

E: NITROUS OXIDE

Answer: E

NITROUS OXIDE IS A POTENT ANALGESIC BUT A WEAK GENERAL ANESTHETIC. IT IS FREQUENTLY EMPLOYED AT CONCENTRATIONS OF 30% IN COMBINATION WITH OXYGEN FOR ANALGESIA, PARTICULARLY IN DENTAL SURGERY

What is MAC?

What is the blood gas solubility?

1. MAC is the minimum concentration necessary to cause unresponsiveness in 50% of the general population (variables include: age, co-morbidities, metabolism). The higher the MAC the less potent the anesthetic

2. Blood gas solubility refers to how soluble the agent is in the blood. The lower the solubility the fater the onset and recovery.

For each of the following inhalational anesthetics, describe MAC, blood-gas solubility, and the clinical pros and cons of the agent:

1. Nitrous Oxide

2. Ether

3. Cyclopropane

4. Halothane

5. Isoflurane

6. Sevoflurane

7. Desflurane

8. Xenon

Nitrous Oxide:

MAC 10

BGS 0.47

Clinical Pros: moves very rapidly in/out, provides “second gas effect” for other agents, good analgesia, minimal CV effects, least hepatotoxic, does not trigger MH

Clinical Cons: Increases ICP and CBF (according to Morgan & Mikhail, not Lippincott), weak general anesthetic

For each of the following inhalational anesthetics, describe MAC, blood-gas solubility, and the clinical pros and cons of the agent:

1. Nitrous Oxide

2. Ether

3. Cyclopropane

4. Halothane

5. Isoflurane

6. Sevoflurane

7. Desflurane

8. Xenon

Ether:

MAC 2.0%

BGS 12

Clinical Pros: rarely used in the U.S. (still used in 3rd world countries), little respiratory depression or CV effects, bronchodilitation

Clinical Cons: flammable, slow onset/recovery, secretions, PONV

For each of the following inhalational anesthetics, describe MAC, blood-gas solubility, and the clinical pros and cons of the agent:

1. Nitrous Oxide

2. Ether

3. Cyclopropane

4. Halothane

5. Isoflurane

6. Sevoflurane

7. Desflurane

8. Xenon

Cyclopropane:

MAC 0.77

BGS unavailable

Clinical Pros: very low blood solubility, favorable pharmacokinetics

Clinical Cons: No longer available, highly explosive

For each of the following inhalational anesthetics, describe MAC, blood-gas solubility, and the clinical pros and cons of the agent:

1. Nitrous Oxide

2. Ether

3. Cyclopropane

4. Halothane

5. Isoflurane

6. Sevoflurane

7. Desflurane

8. Xenon

Halothane:

MAC 0.75

BGS 2.3

Clinical Pros: no chronotropic effect (SA node), no dromotropic effect (AV node), potent, non-flammable (all newer agents are non-flammable)

Clinical Cons: highly arrhythmogenic, increases CBF and ICP, hypotension, hepatotoxic

For each of the following inhalational anesthetics, describe MAC, blood-gas solubility, and the clinical pros and cons of the agent:

1. Nitrous Oxide

2. Ether

3. Cyclopropane

4. Halothane

5. Isoflurane

6. Sevoflurane

7. Desflurane

8. Xenon

Isoflurane:

MAC 1.2

BGS 1.4

Clinical Pros: dilates coronary vessels, not tissue toxic, not arrhythmogenic

Clinical Cons: positive chronotrope (SA node), hypotension, increase CBF and ICP

For each of the following inhalational anesthetics, describe MAC, blood-gas solubility, and the clinical pros and cons of the agent:

1. Nitrous Oxide

2. Ether

3. Cyclopropane

4. Halothane

5. Isoflurane

6. Sevoflurane

7. Desflurane

8. Xenon

Sevoflurane:

MAC 2.0

BGS 0.65

Clinical Pros: non-irritating to airways (useful for children), fast onset, recovery is not fast, similar to isoflurane

Clinical Cons: positive chronotropy (SA node), increases CBF and ICP, nephrotoxicity (nephrotoxic effects are debatable)

For each of the following inhalational anesthetics, describe MAC, blood-gas solubility, and the clinical pros and cons of the agent:

1. Nitrous Oxide

2. Ether

3. Cyclopropane

4. Halothane

5. Isoflurane

6. Sevoflurane

7. Desflurane

8. Xenon

Desflurane:

MAC 6.0

BGS 0.42

Clinical Pros: fast onset/recovery (fastest of all available volatile anesthetics)

Clinical Cons: positive chronotropy, increases CBF and ICP, pungent/airway irritant

For each of the following inhalational anesthetics, describe MAC, blood-gas solubility, and the clinical pros and cons of the agent:

1. Nitrous Oxide

2. Ether

3. Cyclopropane

4. Halothane

5. Isoflurane

6. Sevoflurane

7. Desflurane

8. Xenon

Xenon:

MAC 70

BGS 0.115

Clinical Pros: lowest BGS, rapid induction/recovery, little CV effects, non-toxic, produces unconsciousness with analgesia, some muscle relaxation, neuroprotection, does not trigger MH, environmentally friendly (only agent on this list that is not a major greenhouse gas)

Clinical Cons: High cost, complex delivery systems necessary for administration

For each of the following inhalational anesthetics, describe MAC, blood-gas solubility, and the clinical pros and cons of the agent:

1. Nitrous Oxide

2. Ether

3. Cyclopropane

4. Halothane

5. Isoflurane

6. Sevoflurane

7. Desflurane

8. Xenon

1. All of these agents decrease blood pressure (except Nitrous and Xenon)

2. Decrease SVR (exception Halothane, Nitrous, Xenon).

3. All increase CBF and ICP (according to Morgan & Mikhail).

4. All increase respiratory rate and decrease tidal volume.

5. All decrease renal and hepatic blood flow.
6. Which can be used in MH?

          *Xenon

          *Nitrous oxide