General Anesthesia

General Anesthetics GENERAL ANESTHETICS Anesthesia – denotes a lose of sensibility Surgical Anesthesia – is a controlled degree of CNS depression with the following component • Analgesia – lack of pain • Amnesia – lack of memory • Inhibition from reflexes such as bradycardia and laryngospasm • Skeletal muscle relaxation • (altered state consciousness) state of unconsciousness.

Depth of Surgical Anesthesia – can be divided into a series of four sequential stages: Depth of Surgical Anesthesia – can be divided into a series of four sequential stages: Stage I: Analgesia Loss of pain sensation results from interference. With sensory transmission Stage Analgesia in the I:spinothalamic tract. The patient is conscious and conversational. A Loss of pain sensation results from interference. With sensory transmission reduced awareness of pain occurs as stage II is approached. in the spinothalamic tract. The patient is conscious and conversational. A reduced awareness of pain occurs as stage II is approached. Stage II: Excitement The patient experience delirium and violent combative behaviour. There is a Stage II: Excitement rise and irregularity in blood pressure. Thecombative respiratorybehaviour. rate may be increase The patient experience delirium and violent There is a rise and irregularity in blood pressure. The respiratory rate may be increase Stage III: Surgical anesthesia Regular and relaxation of the skeletal muscle occur in this stage. Stage III:respiration Surgical anesthesia Eye reflexes decreases progressively, themuscle eye movements cease Regular respiration and relaxation of the until skeletal occur in this stage.and the pupil is fixed. Surgery may proceeduntil during Eye reflexes decreases progressively, the this eye stage. movements cease and the pupilIV: is Medullary fixed. Surgery may proceed during this stage. Stage paralysis

Anesthetic Potency of Inhaled General Anesthetic: -is defined quantitatively as the minimum alveolar concentration. (MAC) which is the concentration of anesthetic gas needed to eliminate movement among 50% of patients challenge to a noxious stimulus. The more potent an anesthetic, the lower its value for MAC.

Properties of Modern inhalational Anesthetics MAC % atm Blood/gas solubility coefficient A. GAS Nitrous Oxide

1. Halothane 2. Enflurane 3. Isoflurane 4. Methoxyflurane

General Anesthetic

Cardiac Effects

1. Halothane

slows heart rate due to reduction of cardiac Sympathetic activity cardiac output is 

B. Intravenous

N2O (Nitrous oxide) – laughing gas Halothane Enflurane Isoflurane Methyoxyflurane Diethyl ether

Newer Inhalational General Anesthetics Never Inhalational Gen Anesthetics 1. Desflurane 2. Seroflurane Mechanism of Action of Inhalational General Anesthetics 1. Desflurane Mechanism Action of Inhalational General Anesthetics Theseofagents decrease the firing rate of nerve cells by 2. Seroflurane Thesethe agents decrease the potential. firing rate of nerve cells the by decreasing rise of the action They inhibit decreasing theinrise of the action potential. Theyion. inhibit the rapid increase membrane premeability to sodium rapid increase in membrane premeability to sodium ion. No receptors have been found to interact with the anesthetic No have been found to interact the anesthetic andreceptors no neurotransmitters are involve in theirwith action. and no neurotransmitters are involve in their action.

KINETICS OF ANESTHESIA Kinetics of Anesthesia 1. Induction 2. Maintenance

Kinetics of Anesthesia

0.75 – 0.77

2.3 – 2.4

1.68

1.9

1.15

1.4

0.16

12

Comparison of the different Pharmacologic effects of Inhaled General Anesthetics

Inhalational Gen Anesthetics 1. 2. 3. 4. 5. 6.

0.43 – 0.47

B. Halogenated gases (volatile)

Severe depression of Anesthetics the resp. center & vasomotor center. Death can Stage Medullary paralysis Two IV: Kinds General rapidly ensure. Severe depression of the resp. center & vasomotor center. Death can rapidly ensure. A.Kinds Inhalational Two of General Anesthetics

B. Intravenous A. Inhalational

110 or 105

Sensitization of Myocardium to Actions of Epinephrine Increases sensitization of myocardium esp to adrenergic agonist, cardiac dis, hypoxia and electrolyte imbalance –may Induce ventricular arrhythmias

1. Solubility of anesthetic – this is expressed as the blood / gas concentration of gas in the blood, relative to the gas equilibrium phase. The greater the blood / gas partition coefficient the more soluble is the anesthetic agent in the blood. a. If a drug has a low solubility (low-blood / gas partition coefficient) little of the drug is dissolve in the blood. Therefore the equilibrium between inhaled anesthetic and arterial blood is rapidly achieve, and only a few additional molecules of the anesthetic is required to raise the arterial tension. This results to rapid induction and short recovery. Example – Nitrous Oxide (NaO) = 0.47 B/G coefficient

b. If the anesthetic has high solubility – it is more dissolve completely in the blood – so greater amounts of the anesthetic and longer periods of time are required to raise arterial tension. This results in increase times of induction and recovery also slower to changes in the cone of the inhaled drug. Ex. Halothane – 2.3 B/G coefficient 2. Rate of ventilation – an increase rate of delivery of anesthetic gas to the lungs results in most anesthetic being delivered to the alveoli. This increases the rate at which the arterial blood approaches equilibrium. The effect of - ventilation is most pronounced for anesthetics with high solubility in blood. 3. Increase alveolar blood flow – high blood flow causes more of the anesthetic agent to be removed from the alveoli hastening anesthesia. B. Maintenance of Anesthesia – maintenance is the time during which the patient is surgically anesthetized, anesthesia is usually maintained by the administration of gases or volatile anesthetics since these agents offer good minute to minute control over the depth of anesthesia.

Rapid/shallow resp ventilatory depression

Comparison of the different Pharmacologic effects of Inhaled No Brady  B.P Dose-dependent Lower incidence General Anesthetics cardia, No  of arrhythmias resp depression

General Anesthetic

in C.O Cardiac Effects

and less Sensitization sensitization to to of Myocardium the myocardium Actions of toEpinephrine catecholamines

BP

3. Isoflurane Causes direct coronary vascular redistribution. Capable of worsening ischemia

does not cause sensitization of myocardium rarely causes Arrhythmias

 B.P

4. Nitrous oxide

Little effect but combination with a more potent anesthetic leads to  sympathetic stimulation

 BP and total Peripheral resistance when in Combination of more Potent anesthetic

Minimal C.O

A Induction and Recovery from Anesthesia Three stages of Anesthesia

1. Induction Maintenance Recovery – is the time 2. form discontinuation of adm.3.ofRecovery anesthetic until consciousness is regained .It depends on how fast the anesthetic is removed from the brain. drugs administered by inhalation; the rate of onset & recovery are influenced by the following factors:

 B.P Dose dependent

Respiration

2. Enflurane

3. Recovery

Induction – is the period of time from onset of administration of the Three stages of Anesthesia anesthetic to the development of effective surgical anesthesia in the patient. It depends on how the anesthetic reaches the brain. 1. Induction 2.fast Maintenance 3. Recovery

BP

 C.O

Causes bronchodilatation Respiration

- Significant resp Depression - due to the hypercapnia

Minimal effect

Comparison of the different Pharmacologic effects of Inhaled General Anesthetics Other Differences

Halothane

Potency/induction Muscle relaxation recovery onset – Analgesia

Organ toxicity and other adverse effect

Potent

Extensively metabolize and Biotransformation intermediates may result to hepatotoxic metabolites – “ Halothane Hepatitis” -malignant hyperthermia

Good muscle relaxation but lacks significant Analgesia

Comparison of thethan different of Inhaled Enflurane Less potent Good Pharmacologic muscle 2% is effects me tabolized to fluoride halothane but itGeneral relaxation relaxes ion which is excreted by the Anesthetics produces more the uterus kidney Other Differences rapid induction -contraindicated in pnts with and recovery Renal Failure. pattern – Potency/induction Muscle relaxation Organ toxicity EEC and other char. ofeffect seizure activity – may recovery onset – Analgesia adverse lead to Frank Seizure Isoflurane

More potent than Enflurane

Good muscle relaxation

Low biotransformation low organ toxicity

Nitrous Oxide

Not very potent when use alone but produce the fastest induction and recovery

Poor surgical anesthetic if use alone but good Analgesic

May diffuse into body cavities –  the pressure or expand the volume of gas in air pockets may lead to: a. Distention of the bowel b. Expansion or rupture of a pulmonary cyst c. Rupture of the tympanic membrane in an occluded middle ear d. Pneumoce phalus -when it is dissolve in the blood may enlarge the volume of air emboli

Properties of Halogenated Inhalation Anesthetics

Halothane

Enflurane

Isoflurane

Sevoflurane

Desflurane

Induction speed ( λ)

2.3

1.8

1.4

0.7

0.4

Irritation of respiratory tract

Low

Low

Moderate

Low

Moderate

Muscle relaxation

Low

Moderate

Moderate

Moderate

Moderate

Myocardial depression

High

Moderate

Low

High

Low

Sensitization of myocardium

High

Moderate

Low

Low

Low

% Metabolized

20

2

0.2

3

0.02

Summary of Therapeutic Advantages and Disadvantages of Anesthetic Agents Inhalation Anesthetics 1. Nitrous Oxide

2. Halothane

 Diffusion hypoxia – can occur at the termination of nitrous oxide anesthesia if a patient abruptly breaths room air. (There is a rapid outward diffusion of nitrous oxide from tissues into the bloodstream and then into the alveoli where it decreases the alveolar tension – lowers arterial oxygen levels).  Treatment or Remedy – administration of 100% O2 for a short time at the termination of Nitrous Oxide Anesthesia.

Summary Inhalation Anesthetics 3.

 Methoxyflurane – fruity odor – most potent (MAC 0.16) but high blood – gas coeff about 12 results to prolonged induction and recovery. High renal toxicity – (High output Renal Failure) due to liberation of significant amount of Fluoride ion as Biotransformation product.  Diethyl ether – highly flammable & explosive;  sympathetic activity, bronchodilatation but may cause laryngospasm. It is a myocardial depressant – but C.O and B.P is  due to the  sympathetic activity.

Intravenous General Anesthetics : are often use for the rapid induction of anesthesia A.Barbiturates – Ultra-short Acting: 1. Thiopental 2. Thiamylal 3. Methohexital  Acts less than one (1) minute,  B.P due to myocardial depression. Depresses the resp center in a dose dependent manner may cause laryngospasm – not an analgesic. B. Ketamine (Ketalar) – Dissociative anesthesia – a short – acting non barbiturate – induces a dissociative state in which the patient appears to be awake consist of Amnesia. Analgesia and often catatonia (rigidity). There is disorientation, hallucinations and changes in perception.

Combination Anesthetics – lighter stage of anesthesia is produce using 2 or more drugs. A.Balanced Anesthesia : Full loss of consciousness and pain – induced reflexes with muscle relaxation using: a. Ultra – short acting barbiturate b. Opioid analgesic (Meperidine, Morphine, Fentanyl or Sufentamil) c. Muscle relaxation d. Nitrous Oxide + Oxygen B. Neuroleptanesthesia – is induced by the combined actions of a narcotic analgesic (Fentanyl) and a neuroleptic agent (Droperidol), together with N2O & Oxygen. Consciousness is not lost, there is tranquility and reduce motor activity. Useful in pnt wherein cooperation is needed (diagnostic procedures) but may cause resp. depression.

Pre-Anesthetic Medications : - Administered prior to anesthesia to reduce pain, relieve anxiety decrease excess salivation and to combat nausea. A. Anxiolytic drugs – provides sedation, relieve anxietyBenzodiazepam - diazepam, Lorazepam and Midazolam B. Narcotic Analgesic - reduces pain – Morphine Fentanyl C. Neuroleptics promethazine, trimeprazine or chlorpromazine; use to sedate and for its anti-emetic properties. D. Anticholinergic Atropine and Scopolamine decreases bronchial and salivary secretions, and promote bronchodilatation.

- good analgesia - rapid onset/recovery -safe non-irritating

Disadvantages -Diffusion hypoxia and other complications - Incomplete anesthesia -no muscle relaxation -must be use with other anesthesia for surgical anesthesia

-best agent in -reduces hepatic and Pediatric pnts renal flow -prod. Bronchodilatation -hepatotoxic, malignant for AsthmaticsAdvantages hyperthermia ofgood Therapeutic and Disadvantages B.P of Anesthetic- Agents -dysarrhythmias (vent. Fibrillation)

Enflurane

Advantages

Disadvantages

Good muscle relaxation -prod. Bronchodilation rapid induction/recovery

-Frank seizure -potential renal toxicity

4. Isoflurane

-good muscle relaxation -rapid recovery -stability of cardiac output -does not raise intracranial pressure

-significant resp depression.

5.Thiopental

-rapid onset

-no analgesia -little muscle relaxation -laryngospasm

6. Ketamine

-potent analgesia

-disorientation hallucination changes in perception

 N2O is also associated with high incidence of post-operative nausea & vomiting.  N2O – can cause leucopenia & Megaloblastic anemia due to in activation of Vit. B12

Advantages