general anesthetics(vk)

General Anesthesia

General Anesthesia Definition:The word

anaesthesia is derived from the Greek: meaning insensible or without feeling

Is the loss of response to & perception of all external stimuli.

General anaesthetics are the drugs which causes reversible loss of all the sensations and consciousness

Components of General Anesthesia:

1.Unconsciousness 2. Analgesia 3. Muscle relaxation

ROLE OF ROLE OF ANAESTHESIOLOGIST ANAESTHESIOLOGIST

So we can summarize the role of anaesthesiologist in:1. Knowing physiology of body well.2. Knowing the pathology of patient disease and co-existing

disease3. Study well the pharmacology of anaesthetic drugs and

other drugs which may be used intra-operatively.4. Use anaesthetics in the way and doses which is adequate to

patient condition and not modified by patient pathology with no drug toxicity.

5. Lastly but most importantly administrate drug to manipulate major organ system, to maintain homeostasis and protect patient from injury by surgeon or theatre conditions.

APPROACH TO APPROACH TO ANAESTHESIAANAESTHESIA

The empirical approach to anaesthetic drug administration consists of selecting an initial anaesthetic dose {or drug} and then titrating subsequent dose based on the clinical responses of patients, without reaching toxic doses.

The ability of anaesthesiologist to predict clinical response and hence to select optimal doses is the art of anaesthesia

Knowing physiology, pathology ,and pharmacology is not enough to communicate safe anesthesia

But there is need for two important tools:

1. Anaesthetic machine.

2. Monitoring system.

TOOLS OF TOOLS OF ANAESTHESIAANAESTHESIA

1. Oxygen gas supply.

2. Nitrous oxide gas supply.

3. Flow meter

4. Vaporizer specific for every agent

5. Mechanical ventilator

6. Tubes for connection.

ANAESTHETIC MACHINEANAESTHETIC MACHINE

1. Pulse, ECG

2. Blood pressure

3. Oxygen saturation.

4. End tidal CO2

5. Temperature

6. Urine output, CVP, EEG, bispectral index, muscle tone, ECHO, drug concentration.

MONITORINGMONITORING

Phases of Anesthesia

Induction: keeping the patient to sleep

Maintenance: keeping the patient asleep

Emergence: waking the patient up

STAGES OF GENERAL ANESTHESIA

STAGE 1 (Analgesia): From induction of anesthesia to loss of conciousness (loss of eyelid reflex). Pain is progressively abolished in this stage.

STAGE 2 (Delirium/Excitement): From loss of consiousness to beginning of regular respiration.Characterized by uninhibited excitation. Pupils are dilated and eyes divergent. Agitation, delirium, irregular respiration, and breatholding are commonly seen. Potentially dangerous responses can occur during this stage including vomiting, laryngospasm, HTN, tachycardia, and uncontrolled movement.

STAGE 3 (Surgical Anesthesia):

Regular respiration to caessation of spontaneous breathing

Central gaze, constricted pupils, and regular respirations. Target depth of anesthesia is sufficient when painful stimulation does not elicit somatic reflexes or deleterious autonomic reflexes.

Plane 1 From the return of regular respirations to the cessation of REM.

Plane 2 The Surgical Plane From the cessation of REM to the onset of

paresis of the intercostal muscles.

Plane 3 From the onset to the complete paralysis of the intercostal muscles.

Plane 4 From the paralysis of the intercostal of

this plane the patient will be apneic.

STAGE 4 (Impending Death/Overdose):

Onset of apnea, dilated and nonreactive pupils, and hypotension to complete circulatory failure.

Classic Stages of Anesthesia*

Stage 1: Analgesia

– decreased awareness of pain, amnesia Stage 2: Disinhibition

– delirium & excitation, enhanced reflexes, retching, incontinence, irregular respiration

Stage 3: Surgical Anesthesia

– unconscious, no pain reflexes, regular respiration, BP is maintained

Stage 4: Medullary Depression

– respiratory & CV depression requiring ventilation & pharmacologic support.

* Seen mainly with Ether. Not all stages are observed with modern GAs.

Mechanisms of Action1. Enhanced GABA effect on GABAA Receptors

– Inhaled anesthetics - Etomidate– Barbiturates - Propofol– Benzodiazepines

2. Block nicotinic receptor subtypes (analgesia) – Moderate to high conc’s of inhaled anesthetics

3. Activate K channels (hyperpolarize )– Nitrous oxide, ketamine, xenon

4. Inhibit NMDA (glutamate) receptors – Nitrous oxide, ketamine, xenon, high dose barbiturates

5. Enhance glycine effect on glycine R’s (immobility)

Immobilization in response to surgical incision

(spinal cord)

Sedation, loss of consciousness (thalamic firing)

Amnesia (hippocampal neurotransmission)

Regional Effects

CLASSIFICATION

INTRAVENOUS

INDUCING AGENTSThiopentone sodium

MethohexitalPropofol

Etomidate

SLOWER ACTINGDiazepamLorazepamMidazolam

DISSOCIATIVE ANAESTHESIAKetamine

OPIOID ANALGESIAFentanyl

INHALATIONAL

GASNitrous oxide

LIQUIDEther

HalothaneEnfluraneDesfluraneSevoflurane

Parenteral Anesthetics (Intravenous)

Most commonly used drugs to induce anesthesia– Barbiturates (Thiopental* & Methohexital)– Benzodiazepines (Midazolam)– Opioids (Morphine & Fentanyl)– Propofol*– Etomidate

* Most commonly used for induction

Barbiturates & Benzodiazepines MOA:Barbiturate

BZDS

GABA

1) Both bind to GABAA

receptors, at different sites• Both cause increase Cl- influx in presence of GABA• BNZ binding can be blocked by flumazenil.

2) Barbs at high doses - are also GABA mimetic, block Na channels NMDA/glutamate R

CN

S E

ffec

ts

Increasing dose

Coma Barbiturates

Benzodiazepines

Hypnosis

Sedation, disinhibition, anxiolysis

Possible selective anticonvulsant & muscle-relaxing activity

Dose Response Relationships

Anesthesia

Medullary depression

Barbiturates

Thiopental & methohexital are highly lipid soluble & can produce unconsciousness & surgical anesthesia in <1 min.

Rx: induction of anesthesia & short procedures

Actions are terminated by redistribution

With single bolus - emergence from GA occurs in ~ 10 mins

Hepatic metabolism is required for elimination

Thiopental (3-5mg/kg)

Barbs are respiratory & circulatory depressants (Contraindicated: hypovolemia, cardiomyopathy, beta-blockade,etc.)

Psychomotor impairment may last for days after use of a single high dose

Taste of garlic prior to anesthesia

Potentially fatal attacks of porphyria in pts with a history of acute or intermittent porphyria.

Delay giving other drugs (e.g. NMJ blockers) until barb has cleared the i.v. line to avoid precipitation.

Propofol

Propofol is a diisopropylphenol intravenous hypnotic agent that produces rapid induction of anesthesia with minimal excitatory activity

It undergoes extensive distribution and rapid elimination by the liver

Propofol Produces anesthesia as rapidly as i.v. barb’s & but recovery is

more rapid than barb’s.

Recovery is not delayed after prolonged infusion (due to more rapid clearance).**

Patients are able to ambulate sooner & patients “feel better” in the post-op period compared to other i.v. anesthetics.

Antiemetic effects (pts w/ risk of nausea), marked hypotension (>barbs)

Commonly used as component of “balanced anesthesia” for maintenance of anesthesia following induction of anesthesia.

** More rapid discharge from the recovery room

INDICATIONS

Conscious sedation Induction agent of anesthesiaMaintenance of anesthesiaAntiemetic

DOSE AND ROUTES

Conscious sedation25 - 50 mg IV, Titrate slowly to desired effect(on set of slurred speech) Induction2 - 2.5 mg/kg IV, given slowly over 30seconds in 2 - 3 divided doses Maintenance25 - 50 mg IV bolusInfusion 100 - 200 mcg/kg/min Antiemetic10mg IV

ADVERSE REACTIONS, PRECAUTIONS, AND INTERACTIONS

Reduce doses in elderly, hypovolemic, high risk surgical patients and with use of narcotics and sedative hypnotics

Minimize pain by injecting into a large vein and/or mixing IV lidocaine (0.1 mg/kg) with the induction dose of Propofol

ADVERSE REACTIONS, PRECAUTIONS, AND INTERACTIONS

Not recommended for patient with increased intracranial pressure

Should be administered with caution to patients with a history of epilepsy or seizures disorder

Etomidate Rapid induction (~1 min), Short duration of action (3-5

mins)

Used as a supplement with nitrous oxide for short surgical procedures

Hypnotic, but not analgesic

Little effect on CV & Respiration

Can cause post-op nausea & decrease cortisol production w/ long term infusion*.

Primarily used in pts w/ limited cardiac or respiratory reserve (safer than barbs or propofol in pts w/ coronary artery dx., cardiomyopathy, etc.)

Benzodiazepines

Midazolam (> Diazepam & Lorazepam)

– Used to produce anxiolysis, amnesia & sedation prior to induction of GA w/ another agent.

– Sedative doses achieved w/in 2 min, w/ 30 min duration of action (short duration).

– Effects are reversed with flumazenil.

INDICATIONS Midazolam

pre-op sedative induction of anesthesiaConscious sedationcommonly used for short diagnostic or

endoscopic procedures

DOSE AND ROUTES Midazolam

may be given IM, PO, or IVPre-op sedation: 0.07-0.08 mg/kg IM 1 hr

prior Induction of anesthesia: 0.050 - 0.350

mg/kg IVBasal sedation: 0.035 mg/kg initially, then

titrated slowly to a total dose of 0.1 mg/kg

• Recovery half times from anesthesia can be “Context Sensitive”

150

100

50

0

Rec

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alf

Tim

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Infusion Duration (hours)0 2 4 6 8 10

DiazepamThiopental*

Midazolam

Propofol

Etomidate

*Unconsciousness can last for days after prolonged administration

Opioids (Fentanyl & Remifentanil*) GAs do not produce effective analgesia (except for ketamine).

Given before surgery to minimize hemodynamic changes produced by painful stimuli. This reduces GA requirements.

High doses can cause chest wall rigidity & post-op respiratory depression

Therapeutic doses will inhibit respiration (CO2)

Used for post-op analgesia, supplement anesthetic in balanced anesthesia.

Remifentanil is an ester opioid metabolized by plasma esterases. It is very potent but w/ a short t1/2 (3-10 mins).

Ketamine

Nonbarbiturate, rapid acting general anesthetic

Dissociated from the environment, immobile, and unresponsive to pain

Profound analgesic

Ketamine

Selectively blocks the associative pathways producing sensory blockade

Preserved pharyngeal-laryngeal reflexesNormal or slightly enhanced skeletal

muscle toneCardiovascular and respiratory stimulation

INDICATIONS Ketamine

Sole agent for procedures that do not require skeletal muscle relaxation

Induction of anesthesia prior to the administration of other anesthetic agents

Supplementation of low potency agents

DOSE AND ROUTES Ketamine

may be injected IM or IV Induction: 1-2 mg/kg Slow IVMaintenance: 30-90 mcg/kg/min IV drip Intramuscular: 6.5-13 mg/kg IM10 mg/kg IM will produce approximately

12-25 min of surgical plane.

ADVERSE REACTIONS, PRECAUTIONS, AND INTERACTIONS Ketaminecontraindicated in pts. with known

hypersensitivity or can't tolerate a significant increase in blood pressure

IV dose should be administered over 60 seconds. Rapid administration may cause respiratory depression or apnea

ADVERSE REACTIONS, PRECAUTIONS, AND INTERACTIONS Ketamine

BP, pulse rate, and respiratory rate are often stimulated

Concomitant use of barbiturates or narcotics prolong recovery time

Ketamine (1.5mg/kg)

A “dissociative anesthetic” that produces a cataleptic state that includes intense analgesia, amnesia, eyes open, involuntary limb movement, unresponsive to commands or pain.

Increases heart rate & blood pressure (opposite of other GAs)

Can be used in shock states (hypotensive) or patients at risk for bronchospasm.

Used in children & young adults for short procedures

Side Effects: nystagmus, pupillary dilation, salivation, hallucinations & vivid dreams

Inhaled Anesthetics

Inhaled Anesthetics Easily vaporized liquid halogenated hydrocarbons Administered as gases

(gas)

Inhaled Anesthetics

Partial pressure or “tension” in inspired air is a measure of their concentration

The speed of induction of anesthesia depends on:

– Inspired gas partial pressure (GA concentration)

– Ventilation rate

– GA solubility (less soluble GAs equilibrate more quickly with blood & into tissues such as the brain)

Minimum Alveolar Concentration

The minimum alveolar anesthetic concentration required to eliminate the response to a painful stimulus in 50% of patients

A measure of GA potency.

It’s “a population average”.

1.3 MAC - 100% will not respond to stimuli.

When several GAs are mixed, their MAC values are additive (e.g. nitrous oxide is commonly mixed w/ other anesthetics).

Elimination Anesthesia is most commonly terminated by redistribution

of drug from brain to the blood & out through the lungs.

The rate of recovery from anesthesia for GAs with low blood: gas PCs is faster than for highly soluble Gas.

Time is $$ in the O.R. & recovery roomBlood: Gas P. Coeff– Haltothane 2.30– Desflurane 0.42– Sevoflurane 0.69

Halothane & methoxyflurane undergo hepatic metabolism & can cause liver toxicity.

Properties of Inhaled anesthetics

Nitrous Oxide

– MAC > 100% : Incomplete anesthetic

– Good analgesia

– No metabolism

– Rapid onset & recovery

– Used along w/ other anesthetic; fast induction & recovery

* fewer side effects also seen in children

Halothane

•The first halogenated inhalational anesthetic

•Not pungent (use for induction w/ children)*

•Medium rate of onset & recovery

•Although inexpensive, its use has declined

•Sensitizes the heart to epi-induced arrhythmias

•Rare halothane induced hepatitis

Desflurane– Most rapid onset of action & recovery of

the halogenated GAs – Widely used for outpatient surgery– Irritating to the airway in awake patients & causes coughing, salivation &

bronchospasm (poor induction agent)– Used for maintenance of anesthesia

Sevoflurane– Very low blood:gas partition coefficient w/ relatively rapid onset of action &

recovery *– Widely used for outpatient surgery*– Not irritating to the airway– Useful induction agent, particularly in children

* Similar to Desflurane

Isoflurane

– Medium rate of onset & recovery– Used for induction & maintenance of anesthesia– Isoflurane “was” the most commonly used inhalational GA in the US. Has been largely replaced

by Desflurane

Methoxyflurane

– Now widely considered obsolete– Slow onset & recovery– Extensive hepatic/renal metabolism, w/ release of F- ion causing renal dysfunction

Toxicity Malignant Hyperthermia

– Esp. when halogenated GA used with succinylcholine– Rx: dantrolene (immediately)

Halothane:– Halothane undergoes >40% hepatic metabolism– Rare cases of postoperative hepatitis occur– Halothane can sensitize the heart to Epi (arrhythmias)

Methoxyflurane– F release during metabolism (>70%) may cause renal insufficiency after prolonged

exposure.

Nitrous oxide– Megaloblastic anemia may occur after prolonged exposure due to decreases in methionine

synthase activity(Vit B12 deficiency).

PREANAESTHETIC MEDICATION Opioids: Morphine-10 mg

Pethidine 50-100mg i.m.

Sedatve antianxiety : Diazepam 5-10mg orallyLorazepam 2mg i.m.

Anticholinergics : Atropine 0.6mg i.m./ i.v Glycopyrolate 0.1-0.3mg i.m

Neuroleptics: Chlorpramazine 25mg

H2 blockers : Ranitidine 150mg Famotidine 40mg

Antiemetics : Metoclopramide 10-20mg i.m

Airway Alveoli Blood Brain

Airway Alveoli Blood Brain

Nitrous Oxide

Halothane

• Why induction of anesthesia is slower with more soluble anesthetic gases. In this schematic diagram, solubility in blood is represented by the relative size of the blood compartment (the more soluble, the larger the compartment). Relative partial pressures of the agents in the compartments are indicated by the degree of filling of each compartment. For a given concentration or partial pressure of the two anesthetic gases in the inspired air, it will take much longer for the blood partial pressure of the more soluble gas (halothane) to rise to the same partial pressure as in the alveoli. Since the concentration of the anesthetic agent in the brain can rise no faster than the concentration in the blood, the onset of anesthesia will be slower with halothane than with nitrous oxide.

Blood:Gas PC

0.47

2.30

Nitrous Oxide

Methoxyflurane

Halothane

Time (min)

Art

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• Tensions of three anesthetic gases in arterial blood as a function of time after beginning inhalation. Nitrous oxide is relatively insoluble (blood:gas partition coefficient = 0.47); methoxyflurane is much more soluble (coefficient = 12); and halothane is intermediate (2.3).

Solubility Effects Arterial Anesthetic Levels

Blood:Gas PC

0.47

2.30

12

Equilibration with a soluble GA may take hoursto achieve. Time is $$ in the O.R.

Ventilation Rate’s Effect on Arterial Anesthetic Tension

Nitrous Oxide

Halothane

Ventilation (L/min)

Art

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Time (min)

Hyperventilation increases the speed ofinduction for Gas with normally slow onset

• Ventilation rate and arterial anesthetic tensions. Increased ventilation (8 versus 2 L/min) has a much greater effect on equilibration of halothane than nitrous oxide.

NMJ BlockersSuccinylcholine, PancuroniumUsed to:

– relax skeletal muscle – facilitate intubation**– insure immobility

Reversed by neostigmine* & glycopyrrolate* during post-op period

* quaternary drugs; * intubation is usually needed for airway maintenance & to prevent aspiration.

Dantrolene Interfers with the release of calcium from the sarcoplasmic

reticulum through the SR calcium channel complex.

Used to prevent or reverse malignant hyperthermia (which is otherwise fatal in ~50% of cases w/o dantrolene).

Given by i.v. push at the onset of symptoms (e.g. an unexpected rise in CO2 levels)

Supportive measures & 100% O2 are also used to treat malignant hyperthermia

Nausea & Vomiting

General anesthetics effect the chemoreceptor trigger zone & brainstem vomiting center (cause nausea & vomiting)

Rx: - Ondansetron (5-HT3 antagonist) to prevent

- Avoidance of N2O

- Propofol for induction- Keterolac vs. opioid for analgesia- Droperidol, metaclopromide & dexamethasone