GENERAL ANAESTHESIA

DUXIAO HONG DEPARTMENT OF ANESTHESIOLOGY THE SECOND AFFILIATED HOSPITAL OF NANCHANG UNIVERSITY

Anesthesia is a reversible condition of comfort, quiescence and physiological stability in a patient before, during and after performance of a procedure. General anesthesia for surgical procedure to render the patient unaware / unresponsive to the painful stimuli.

Introduction
General anesthesia is the induction of a balanced state of unconsciousness, accompanied by the absence of pain sensation and the paralysis of skeletal muscle over the entire body. It is induced through the administration of anesthetic drugs and is used during major surgery and other invasive surgical procedures.

Introduction
Balanced Anesthesia analgesia amnesia relaxation abolition of reflexes with maintenance of physiologic homoeostasis

Basic Anesthesia analgesia amnesia relaxation

Introduction
General anaesthesia is a complex procedure involving: Preanaesthetic assessments Administration of general anaesthetic drugs Cardiorespiratory monitoring Analgesia Airway management Fluid management Postoperative pain relief

Preanaesthetic evaluation

Prior to surgery, the anaesthetist interviews the patient to determine the best combination of drugs and dosages and the degree to which monitoring is required to ensure a safe and effective procedure.

The American Society of Anesthesiologists has compiled guidelines for classifying patients according to risk levels as follows: I: healthy patient II: patient with mild systemic disease without functional limitations III: patient with severe systemic disease with definite functional limitations IV: patient with severe systemic disease that is life-threatening V: dying patient not expected to survive for 24 hours without an operation

Stages of anaesthesia
The four stages of anaesthesia were described in 1937. Despite newer anaesthetic agents and delivery techniques, which have led to more rapid onset and recovery from anaesthesia, with greater safety margins, the principles remain.

Stage 1
Stage 1 anaesthesia, also known as the "induction", is the period between the initial administration of the induction medications and loss of consciousness. During this stage, the patient progresses from analgesia without amnesia to analgesia with amnesia. Patients can carry on a conversation at this time.

Stage 2 Stage 2 anaesthesia, also known as the "excitement stage", is the period following loss of consciousness and marked by excited and delirious activity. During this stage, respirations and heart rate may become irregular. In addition, there may be uncontrolled movements, vomiting, breath holding, and pupillary dilation. Since the combination of spastic movements, vomiting, and irregular respirations may lead to airway compromise, rapidly acting drugs are used to minimize time in this stage and reach stage 3 as fast as possible.

Stage 3 Stage 3, "surgical anesthesia". During this stage, the skeletal muscles relax, and the patient's breathing becomes regular. Eye movements slow, then stop, and surgery can begin. It has been divided into 4 planes: 1.rolling eye balls, ending with fixed eyeballs 2.loss of corneal and laryngeal reflexes 3.pupils dilate and loss of light reflex 4.intercostal paralysis, shallow abdominal respiration, dilated pupils

Stage 4 Stage 4 anesthesia, also known as "overdose", is the stage where too much medication has been given and the patient has severe brain stem or medullary depression. This results in a cessation of respiration and potential cardiovascular collapse. This stage is lethal without cardiovascular and respiratory support. This can be fatal

GA
Induction Maintenance Recovery

Induction
Definition The administration of a drug or combination of drugs at the beginning of an anesthetic that results in a state of general anesthesia. There are some complications or risks in this stage, e.g. reduction of blood pressure, arrhythmia, myocardial ischemia.

Induction
Rapid-sequence Intravenous Induction Inhalational Induction Induction with spontaneous ventilation Intravenous induction following conscious intubation Induction with spontaneous ventilation

 Rapid-sequence Intravenous Induction

The objective is to secure the airway rapidly and prevent soiling of the lungs with gastric contents. Disadvantage and Complications Regurgitation and Vomiting Cardiovascular depression Respiratory depression Histamine release Pain on injection Hiccup and muscle movements

 Inhalational Induction

Indications young children myasthenia gravies upper airway obstruction, e.g. Epiglottises lower airway obstruction with foreign body ronchopleural fistula or empyema no accessible veins

Inhalational Induction-- Methods

Initially, nitrous oxide 70% in oxygen is used and anesthesia is deepened by gradual introduction of increments of a volatile agent, e.g. Halothane 1-3%, Enflurane 1.5-2.5%, Isoflurane 1-2%

characteristics
Spontaneous ventilation is to be maintained. the face mask is applied firmly as consciousness is lost and the airway is supported manually. Insertion of an oropharyngeal airway , a laryngeal mask airway or a tracheal tube may be considered when anesthesia has been established.

Inhalational Induction

Disadvantage and Complications

Slow induction of anesthesia Airway obstruction , bronchospasm Laryngeal spasm , hiccups Environmental pollution

 Induction with spontaneous ventilation

-- Indications Airway obstruction anticipant difficult intubation -- Characteristics Maintaining spontaneous ventilation throughout the procedure Sufficient surface anesthesia

Intravenous induction following conscious intubation

Indications Patient with the risk of regurgitation Patient with postural hypotension following anesthesia (e.g. paraplegia)

 Other induction methods

intramuscular injection of ketamine take midazolam orally administration of fentanyl via mucosa

GA
Induction Maintenance Recovery

Maintenance of general anesthesia

sedation analgesia muscle relaxation

Maintenance of general anesthesia

Inhalational agents Intravenous anesthetics Opioids Muscle relaxants

Recovery

Antagonizing residual neuromuscular blockade Extubation Airway supporting Recovery position is benefit to avoid airway obstruction The time to full recovery is dependent on the length of the anaesthetic, and may be anything from five minutes to an hour.

Before discharging patients back to the ward the anaesthetist will once again check that the vital signs are stable and that the patients are fully recovered. Anaesthetist will perform some simple checks: Asking patients to lift head up for five seconds, Asking name and other questions such as age, or what day of the week it is. Ensuring that patients are not distressed by pain or nausea

PACU

Airway management

airway management devices

Airway management
Opening the airway Remove crash helmet with manual in-line stabilization of the cspine Chin lift with manual in-line stabilization of the c-spine Jaw thrust with manual in-line stabilization of the c-spine Suction with manual in-line stabilization of the c-spine

Airway management

Sizing an oropharyngeal airway

Oropharyngeal airway insertion

Postoperative care

The anaesthesia should conclude with a pain-free awakening and a management plan for postoperative pain relief. This may be in the form of regional analgesia, oral, transdermal or parenteral medication. Minor surgical procedures are amenable to oral pain relief medications such as paracetamol and NSAIDs such as ibuprofen. Moderate levels of pain require the addition of mild opiates such as tramadol.

Inhalational Agents
The inhalant anesthetics are unique among the anesthetic drugs because they are administered, and in large part removed from the body, via the lungs. The primary advantage of their use arises because their pharmacokinetic characteristics favor predictable and rapid adjustment of the anesthetic depth of the patient. Metabolism is very minimal. Excreted by exhalation.

The main target of inhalation anesthetics is the brain.

Inhalational induction

This may be used when i.v. induction of anesthesia is not practical, for example in an uncooperative child or a patient with a lack of suitable veins. Anesthesia is induced relatively slowly and respiration is preserved. This is therefore a useful technique inpatients with airway compromise, when an i.v. agent may cause apnea, and ventilation and oxygenation become impossible with catastrophic results. .

Distribution

For most anesthetics equilibrium is essentially reached in about 0.5 2 h

MAC
The term potency refers to the quantity of an inhalant anesthetic that must be administered to cause a desired effect (i.e. general anesthesia). The standard quantitative index of anesthetic potency for inhalation anesthetics is inversely related to the "minimum alveolar concentration" (MAC).

MAC
1 MAC is the Minimum Alveolar Concentration at which 50% of humans have no response (movement) to surgical stimulus (skin incision) MACawake is the alveolar concentration when 50% of persons will awake to vocal stimulus MAC is directly proportional to the partial pressure of the anesthetic agent in the CNS MAC is consistent within a species and between species MAC is different for each inhaled agent

Activity Awake

Level of MAC < 0.2

Memory and Learning

Anesthesia No Movement

0.3 to 0.6
0.9 to 3.0 1.2 to 1.4

MAC decreases with decreasing body temperature MAC increases with increasing pressure more anesthetic agent required higher pressures to achieve same MAC Ion concentrations in CNS alter MAC Na MAC increases with concentration K no effect Ca no effect Mg inversely proportional increase with concentration MAC decreases with age (greatest at 6 months) MAC is altered by other drugs MAC decreases as patient medical condition deteriorates

Agent
Halothane Isoflurane Sevoflurane Desflurane

[agent] 1 MAC (ED50, STP) 0.75 % 1.46 % 1.80% 6.60 %

Nitrous Oxide

104%

Pharmacology
Uptake Pharmacokinetics Physiologic effects Metabolism Toxicity

Uptake
The uptake of an inhalant anesthetic by blood is related to three factors: solubility (the blood/gas partition coefficient ), cardiac output (CO), the difference in the anesthetic partial pressure between the alveolus and venous blood returning to the lungs.

Uptake and Solubility

The solubility of an anesthetic in blood and body tissues is a primary factor in the rate of uptake of the drug, and its distribution, within the body. Solubility of inhalation anesthetics is most commonly measured and expressed as a partition coefficient (PC). The PC is the concentration ratio of an anesthetic in the solvent and gas phases (e.g. blood and gas) or between two tissue solvents (e.g. brain and blood).

One of the most important PCs used in describing an inhalant anesthetic is the blood/gas PC. This measurement provides a means for predicting the speed of anesthetic induction, recovery, and change of anesthetic depth. The inhalant anesthetic with the higher PC value (as compared to the one with the lower PC value) will require a longer time of administration to attain a partial pressure in the body for a particular end point (such as anesthetic induction).

Uptake and Solubility

The more soluble the anesthetic agent is in blood the faster the drug goes into the body The more soluble the anesthetic agent is in blood the slower the patient becomes anesthetized (goes to sleep)
To some degree this can be compensated for by increasing the inhaled concentration but there are limits

Second Gas Effect

Second Gas Effect addition of a second more soluble gas (usually N2O) increases the rate of uptake

Partition Coefficients
Anesthetic Desflurane Nitrous Oxide Blood-Gas 0.45 0.47 BrainBlood 1.3 1.1 LiverBlood 1.4 0.8 KidneyBlood 1.0 MuscleBlood 2.0 1.2 Fat-Blood 27 2.3

Sevoflurane
Isoflurane Enflurane Halothane Ether Methoxyflurane

0.65
1.4 1.8 2.5 12 15

1.7
1.6 1.4 1.9 2.0 1.4

1.8
1.8 2.1 2.1 1.9 2.0

1.2
1.2 1.2 0.9 0.9

3.1
2.9 1.7 3.4 1.3 1.6

48
45 36 51 5 38

Inhalational anesthetics : Non-halogenated gas: Nitrous oxide Halogenated hydrocarbons: Halothane Enflurane Isoflurane Desflurane Sevoflurane

CVS (cardiovascular effects)

Heart Rate Halthane reduces HR Sevo and Enf are neutral Des >> Iso can cause an Initial tachycardia heart rate eventually slows initial SNS response leading to catecholamine release Dose dependent effect Rapid increases in MAC Rate of administration plays a role

 Contractility All agents are depressants To some degree lung attenuates this effect At 1 MAC the approximately order is: Halo = Enfl >> Des = Iso = Sevo
Cardiac Output is fairly well preserved Des and Iso > rest Baroreceptor reflexes are preserved

 Vasculature All inhaled agents are smooth muscle relaxants All cause vasodilatation (decreased SVR) Variable effects on different vascular leading to hypotension hypotension can result at high enough doses threshold varies for each patient ALL decrease SVR except Nitrous Oxide Some evidence that Inhaled anesthetics are cardio-protective following ischemic insult Mechanism? Dilation of coronaries Limits degree of ischemic insult

 All inhaled agents are cardio toxic will lead to death at high enough concentrations
Arrhythmias are induced by all anesthetic agents Halothane is worst Potentates Catecholamine induced arrhythmias Children are less affected than adults Lidocaine has been shown to double ED50 at 1.25 MAC ED50 of epinephrine at 1.25 MAC halothane 2.1 gkg-1 isoflurane 6.9 gkg-1 enflurane 10.9 gkg-1

 Coronary Blood Flow Isoflurane shown to be potent coronary vasodilator Sevoflurane and Desflurane seem to be less potent in animal models (not all tissue beds behave the same) Concern that blood can be directed away from stenotic coronaries Coronary Steal theoretically possible One vessel highly stenosed Practically, does not seem to be a real problem

Respiratory
Patients will only willingly breath Sevoflurane and Halothane All other agents are respiratory irritants Tidal Volume is decreased Respiratory rate is increased Minute ventilation is decreased No change in mucociliary clearance

Hypoxic pulmonary vasoconstriction impaired Increased shunting Gas exchange is less efficient (decreased FRC, increased shunt) Shunt and oxygenation largely not affected by one lung ventilation Nitrous oxide worsens pulmonary hypertension

CNS (central nervous system)

The CMRO2 is decreased by anesthetic agents Increased Cerebral Blood Flow auto regulation of cerebral blood flow is impaired Increased ICP Via blood flow Via induced hypercapnea Seizure activity may be increased (Enflurane at 2.0 MAC) Ventilatory Responses Blunted Sleep apnea Narcotics add synergistically Benzodiazepines add synergistically

 EEG Decreased Amplitude Increased Latency Neurologic function is effectively stopped EEG is flat line at high concentrations Useful in the treatment of status epilepticus Must give a very deep anesthetic Memory? Do deep anesthetics cause memory impairment?

Kidney
Dose dependant decreases in: Renal blood flow GFR Urine Output
Related to changes in Cardiac Output and BP not ADH

 Some agents (enflurane, sevoflurane) can be toxic due to Fproduction during metabolism in liver or in the kidney
Fluoride nephrotoxicity Sevoflurane produces Compound A which is a renal toxin

Anesthetized patients are heavily dependent on renin angiotensin system to regulate volume status

Liver
Hepatic blood flow decreased Drug metabolism is altered (slowed) Some agents are potentially hepatotoxic
Most agents cause a transient increase in liver function tests Cause is unknown Hypoxia? Reactive intermediates?

Muscle-relaxation
Inhaled agents cause an enhancement of the effects neuromuscular blocking drugs and ,consequently, reduce the muscle relaxants requirement.

Toxicity - Hepatitis
Halothane hepatitis was reported very shortly after anesthetic introduced Usually requires multiple exposures Most patients given halothane have evidence of liver injury Not as common with newer anesthetic agents One confirmed case with isoflurane Two case reports with desflurane some suspect Many with Sevoflurane

Toxicity Malignant Hyperthermia

Definition is an inherited (pharmacogenetic) disorder of skeletal muscle, characterized by a hypermetabolic state, triggered by all volatile anaesthetics

Main Clinical Features

The clinical features reflect massive uncontrolled metabolic activity. Muscle rigidity Rising PaCO2 Decreased SpO2 and PaO2 Tachypnoea, tachycardia, hypertension and cardiac arrhythmias. Increased body temperature . Hyperkalaemia Increased creatine phosphokinase Myglobinuria

 producing a myopathy Most patients are aware of family history of condition More common Europeans (northern) Multiple genes are involved Some patients can receive triggering agents and have no reaction Reactions tend to occur at extremes of age In some cases, a rise in Cpk following anesthesia is the only symptom of condition

Genes are involved in intracellular Ca regulation Uncontrolled muscle contraction results from exposure to trigger causing hyper metabolism and skeletal muscle necrosis Renal failure Hyperthermia can also cause direct tissue damage
Treatment is active cooling of patient and dantrolene (2 mg/Kg doses q 15 minutes up to 10-12 mg/kg)

Toxins Sevoflurane and Compound A

Sevoflurane reacts with soda lime used in anesthetic circuit to form compound A Compound A is renal toxin Large mounts are produced at low gas flow rates Recommended 2 L / min flow rate Little evidence of harm unless Low flows Long exposure Some evidence for changes in markers of damage but not clinically significant

NITROUS OXIDE (N2O)

Nitrous oxide is a colorless, sweet-smelling, non-irritant gas. It is a good analgesic but a poor anesthetic. The maximum safe concentration that can be administered (without the risk if hypoxia) is approximately 70% which does not guarantee unconsciousness or anesthesia sufficient to allow surgery to proceed. At the end of anesthesia, rapid excretion of nitrous oxide into the alveoli dilutes any oxygen present. It the patient is breathing air then significant hypoxia can occur. This can be overcome by increasing the inspired oxygen concentration during recovery.

Systemic effects Has little effect on cardiac output or blood pressure unless patient has severe cardiac disease. Causes a slight increase in the respiratory rate and a decrease in the tidal volume. It decreases the ventilator response to carbon dioxide and hypoxia. It diffuses more rapidly into air-filled cavities than any nitrogen can escape, causing either a rise in pressure (e.g. in the middle ear) or an increase in volume (e.g. within the gut or of an air embolus). May cause bone-marrow suppression by inhibiting the production of factors necessary for the synthesis of DNA.

HALOTHANE (FLUOTHANE)

This is a colorless, volatile liquid with a pleasant odor. It is relatively non-irritant to the respiratory tract. Induction of anesthesia can be achieved with 2-4% and maintenance with 0.5-1.5% inspired concentration when administered with 70% nitrous oxide and 30% oxygen. It has no analgesic action and is most commonly used with nitrous oxide and oxygen in spontaneously breathing patients or as part of a balanced technique.

Systemic effects Halothane causes a dose-related fall in blood pressure as a result of myocardial depression and vasodilation. Dysrhythmias are common and include sinus bradycardias and nodal rhythm. The myocardium is sensitized to circulating levels of adrenaline Causes depression of ventilation and the ventilator response to both hypercarbia and hypoxia is lost.

Systemic effects
There is slight bronchial dilatation and both pharyngeal and laryngeal protective reflexes are depressed. Nonirritant to the respiratory tract. Increases cerebral blood flow and the intracranial pressure. Relaxation of skeletal and smooth muscle, including the pregnant uterus, which may increase blood loss during Caesarian section. Significant amounts of halothane are metabolized in the liver (=20%) and excreted over many days.

Disadvantages

The main disadvantages are that it can trigger malignant hyperpyrexia and has been implicated as a cause of hepatotoxicity halothane hepatitis Halothane hepatitis The precise link between the use of halothane and the subsequent development of hepatitis remains unclear. The clinical picture is one of jaundice with a massive rise in plasma aminotransferases several days after the exposure to halothane, associated with severe hepatic necrosis. The mortality rate is approximately 50%.

ENFLURANE (ETHRANE)

Enflurane is a colorless liquid, with a pungent smell. It is slightly more irritant than halothane. It is less potent than halothane, with 1.5-2% needed for maintenance of anesthesia when used with 70% nitrous oxide and 30% oxygen. Induction, recovery and changes in depth of anesthesia can be achieved relatively quickly, although the former is limited by its pungency.

Systemic effects Enflurane causes a dose-dependent fall in blood pressure and ventilation. The heart rate is well maintained and the cardiac rhythm is stable, even in the presence of raised levels of catecholamines, making it safer for use when adrenaline-containing solutions are also being administered. .

Systemic effects Increases cerebral blood flow and at high concentrations causes an abnormal increase in EEG activity. Not recommended for use in patients known to suffer from, or who are prone to epilepsy. Similar effects to halothane on skeletal and smooth muscle. Malignant hyperpyrexia may be triggered, but at a lower incidence than following halothane.

ISOFLURANE (FORANE) This is a colorless liquid with a very pungent smell. It is mildly irritant to breathe which limits its use for inhalation induction. Isoflurane lies between halothane and enflurane in its potency; up to 5% is required for induction and 1-1.5% for maintenance of anesthesia when used with 70% nitrous oxide and 30% oxygen. It is associated with a rapid recovery from anesthesia with minimal hangover effects, making it popular for use in day-case surgery. Currently, isoflurane is the inhalational agent of choice for neurosurgical anesthesia because of its minimal effect on cerebral blood flow and intracranial pressure.

Systemic effects Isoflurane causes a dose-dependent fall in blood pressure due mainly to peripheral vasodilatation. The pulse rate is maintained, with a tendency to tachycardia in young patients due to maintenance of the baroreceptor reflexes. Cardiac rhythm is stable, even in the presence of high levels of catecholamines.

Systemic effects Ventilation is depressed with tidal volume affected more than respiratory rate and the ventilator response to hypoxia and hypercarbia is also reduced. It has minimal effect on cerebral blood flow and intracranial pressure at low concentrations (<1 MAC). Isoflurane provides good relaxation of skeletal muscle, potentiating the effects of non-depolarizing muscle relaxants and causes relaxation of uterine muscles.

DESFLURANE (SUPRANE)

This is one of the two most recently introduced volatile agents but is very irritant to breathe. It has a boiling point of only 23C which makes administration technically more complex. Desflurane is a weak anesthetic agent, compensated for by the fact that it has the lowest solubility of all the current agents, allowing a more rapid induction, change in depth of anesthesia and recovery than with the other inhalational agents.

Systemic effects At low concentrations vasodilatation may cause the blood pressure to fall, but at higher concentrations (2 MAC) cardiac performance may actually be increased. There is no effect on heart rhythm. Ventilator depression occurs with a reduction in tidal volume, a slight increase in respiratory rate and a reduction in the ventilator response to carbon dioxide. It has similar effects on cerebral blood flow and intracranial pressure as isoflurane. As a result of the molecules stability, it undergoes virtually no metabolism and is unlikely to have any adverse hepatic or renal effects.

SEVOFLURANE

This is the second recent inhalational agent introduced, and is a colorless liquid which is non-irritant to the respiratory tract. It is a relatively week anesthetic agent, but like desflurane this is compensated for by its low solubility which facilitates induction, changes in depth and recovery from anesthesia. Ease of inhalation and its insolubility make sevoflurane attractive for use in short cases, for example anesthesia for day-case surgery where speed and quality of recovery is important, and for inhalational induction.

Systemic effects

Sevoflurane decreases the blood pressure in a doserelated manner, primarily due to peripheral vasodilatation. There is relatively little effect on heart rate and cardiac rhythm remains stable. Ventilator depression occurs with a decrease in the ventilator response to carbon dioxide. The effects on cerebral blood flow are similar to those for isoflurane.

Properties of the ideal inhalational anesthetic Pleasant odour, non-irritant to respiratory depression low blood/solubilityrapid induction and recover from anesthesia Neither flammable nor explosive Producing unconsciousness with analgesia and some degree of muscle relaxation Not be metabolized in the body, non-toxic, not provoke allergic reactions Minimal depression of cardiovascular and respiratory system and not interact with the other drugs used commonly during anesthesia

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