• The state of General Anaesthesia usually includes Analgesia; Amnesia; Loss of consciousness and autonomic reflexes and skeletal muscle relaxation.• No single anaesthetic drug is capable of achieving all of these desirable effects without some disadvantages when used alone.• Thus the modern practice of anaesthesia involves the use of a combination of drugs.
• Balanced anaesthesia includes the administration of medications preoperatively for sedation and analgesia; the use of neuromuscular blocking drugs intraoperatively; and the use of both intravenous and inhaled anaesthetic drugs.
TYPES OF GENERAL ANAESTHETICS• Inhalational agents.• Intravenous agents.
INHALATIONAL AGENTS GASES:• Nitrous oxide- important component of many anaesthesia regimens.• Cyclopropane – limited current use because of potential inflammability closed circuit. VOLATILE LIQUIDS:• Halothane; enflurane; Isoflurane and Methoxyflurane are used commonly.• Ether has limited use because it is potentially inflammable.• Chloroform has limited use because of organ toxicity.
SIGNS AND STAGES OF ANAESTHESIA• These were described from observations on patients who were being anaesthetized by Diethyl-ether alone. The stages can be observed because Ether has slow onset of central action due to its high solubility in blood.• The signs are not readily seen with the more rapidly acting Modern inhaled anaesthetics and are unusual with intravenous agents.• Anaesthesia effects are divided into 4 stages of increasing depth of CNS depression.
STAGE OF ANALGESIA:• Patient experiences Analgesia without amnesia but later Amnesia ensues.STAGE OF SURGICAL ANAETHESIA:• Delirium; Excitement and Amnesia….Respiration is irregular both in volume and rate.• Retching and vomiting may occur.• Incontinence and struggling may occur.• Stage ends with re-establishment of regular breathing.
STAGE OF SURGICAL ANAESTHESIA:• Begins with regular respiration and extends to complete cessation of spontaneous respiration….There are four planes representing signs of increasing depth of anaethesia.STAGE OF MEDULLARY DEPRESSION:• Begins with cessation of spotantenous respiration. There is severe depression of the respiratory centre in the medulla and vasomotor centre as well ..Without full circulatory and respiratory support- coma and death ensue.
• Most reliable indications that stage 111 (surgical Anaesthesia ) has been achieved are loss of the eye-lash reflex and establishment of a respiratory pattern that is regular in rate and depth.
MECHANISM OF ACTION:• Increased the threshold of cells to firing; resulting in decreased activity.• Reduce the rate of rise of the action potential by interfering with Sodium influx.
PHARMACOKINETICS OF INHALED ANAESTHETICSUPTAKE AND DISTRIBUTION:• The rate at which a given concentration of anaesthetic in the brain is reached depends on -;• The solubility properties of the anaesthetic.• Its concentration in the inspired in the inspired air.
• Pulmonary ventilation rate.• Pulmonary blood flow…and• The concentration gradient of anaesthetic between arterial and mixed venous blood.
SOLUBILITY• Nitrous oxide with low solubility in blood reaches high arterial tensions rapidly which in turn results in more rapid equilibrium with the brain and faster induction of anaesthesia. In contrast even after 40 minutes Methoxyflurane has reached only 20 % of the equibrium concentration.
ANAESTHETIC CONCENTRATION IN INSPIRED AIR• Increases in the inspired anaesthetic concentration will increase the rate of induction of anaethesia by increasing the rate of transfer into blood.
PULMONARY VENTILATION• An increase in pulmonary ventilation is accompanied by only slight increase in arterial tension of anaesthetic with low solubility but can significantly increase tension of agents with moderate or high blood solubility.
PULMONARY BLOOD FLOW• An increase in pulmonary blood flow slows the rate of rise in arterial tension particularly for those anaesthetics with moderate to high blood solubility.
ARTERIAL-VENOUS CONCENTRATION GRADIENT• Venous blood returning to the lungs may contain significantly less anaesthetic than that present in arterial blood the greater this difference in tensions the more time it takes to achieve equilibrium.• 15 to 20 % of inspired Halothane is metabolized during an average anaesthetic procedure.
• 2 to 3 % of Enflurane is metabolized over the same period.• Halothane is normally oxidized to Trifluoroacetic acid and release bromide and chloride ions.• Under condition of low oxygen tension Halothane is metabolized to the Chlorotrifluo- ethyl free radical which is capable of reacting with hepatic membrane components.
• Methoxyflurane is metabolized rapidly to release Fluoride ions at levels that can be nephrotoxic.• Nitrous oxide is metabolized to a very small extent.
MINIMUM ALVEOLAR ANAESTHETIC CONCENTRATION• (MAC)….Of an anaesthetic is that concentration which results in immobility in 50 % of patients when exposed to a noxious stimulus such as surgical incision.• MAC values decrease in elderly patients but are not affected greatly by sex; height and weight. Drugs like the opioid analgesics or sedative- hypnotics decrease MAC value.
CLINICAL PHARMACOLOGY OFINHALED ANAESTHETICS EFFECTS ON CARDIOVASCULAR SYSTEM:• BLOOD PRESSURE….Decrease by Halothane and Enflurane due to a reduction in cardiac output; Isoflurane due a decrease in systemic vascular resistance ( not cardiac output ).• Diethyl ether and Cyclopropane raise the BP by their ability to liberate catecholamines.
• HEART RATE:…..Halothane causes bradycardia by direct depression of atrial rate.• Methoxyflurane ; Enflurane and Isoflurane increase heart rate.• All inhaled anaesthetics tend to increase right atrial pressure which reflects depression of myocardium.• Enflurane and Halothane are very depressant. Nitrous oxide is also depressant. Cyclopropane; Diethyl ether and Fluroxene are not.
EFFECTS ON RESPIRATORY SYSTEM:• With the exception of Nitrous oxide and Diethyl ether which liberate catecholamines all inhaled anaesthetics are respiratory depressants and they cause an increase in resting PaCO2 with Isoflurane an Enflurane being most depressants.• Inhaled anesthetics depresss mucocilliary function with the resultant pooling of mucus; atelectasis ( no air in alveoli ) and respiratory infections.• Inhaled agents are bronchodilators, Halothane being most potent
EFFECT ON BRAIN• Inhaled anaesthetics decrease metabolism in the brain;• They increase cerebral blood flow by decreasing cerebral vascular resistance.• Hyperventilation of the patient before the anesthetic is given avoids increase in intracranial pressure from inhaled anaesthetics.
EFFECT ON THE KIDNEY• All decrease GFR, increase renal vascular resistance and cause a decrease in renal blood flow which may be due to an impairment of auto-regulation of renal flow.
EFFECT ON LIVER• All cause a decrease in hepatic blood flow which range from 15 to 45 %. Transient changes in liver function tests have been observed.
EFFECTS ON UTERINE SMOOTH MUSCLE• Isoflurane; Halothane and Enflurane are potent uterine muscle relaxants-• Useful in intrauterine foetal manipulation but will cause increased bleeding during Dilatation and Curretage.
TOXICITY• Hepatotoxicity common following the use of Halothane and Chloroform.• Nephrotoxicity common with Methoxyflurane.
CHRONIC TOXICITY• MUTAGENICITY:…Anaesthetic that contain Vinyl moiety ( fluroxene and Divinyl-ether ) may be mutagens.• CARCINOGENS:• No study has demonstrated the existence of cause and effect relationship between anaesthetic and cancer.
EFFECT ON REPRODUCTION• Miscarriages are common in operating room female staff than expected in general population but the evidence is not strong.
INTRAVENOUS ANAESTHETICS• Thiobarbiturate ( Thiopentone and Methohexital ).• Opioid analgesics and neuroleptics.• Arylcyclohexylamines ( Ketamine ) which produces a state called dissociative anaesthesia.• Miscellaneous ( Etomidate, Steroids anesthetics, Propanidid )
ULTRA SHORT ACTING BARBITIRATES• THIOPENTONE:…Metabolised at a rate of 12 to 16 % per hour.• Large doses cause a fall in BP; stroke volume and cardiac output…due to depression of myocardium• It is a potent respiratory depressant.• Cerebral metabolism and oxygen utilization are decreased also cerebral blood flow is decreased.• It also decrease blood flow and GFR.
OPIOID ANALGESICS ANAESTHETICS AND NEUROLEPTANAESTHESIA• Intravenous Morphine 1 Mg/Kg and subsequently Fentanyl 50µg/ Kg is useful in patients with minimal circulatory reserve.• Problems….Awareness during anaesthesia or post-operative recall and respiratory depression requiring assisted ventilation.
• Dose of Opioid may be reduced with simultaneous administration of short acting Barbiturate or Benzodiazepine with Nitrous oxide to acieve balanced anaesthesia.
NEUROLEPTANAESTHESIA• Patient becomes completely disinterested and detached from environment..loss consciousness or ability to obey commands or communicate with others. The desire to move or change position is lost.• Droperidol ( a butyrophenone ) and Fentanyl (an opioid analgesic ). This drug combination is usually used with Nitrous oxide to produce general anaesthesia.
KETAMINE• Produce dissociative anaesthesia characterized by catonia, amnesia, and analgesia.• It is lipophilic and rapidly distributed to highly vascular brain and then redistributed to other tissues.• Undergoes hepatic metabolism and renal and biliary excretion.• Produces cardiovascular stimulation via central sympthatetic stimulation and is a powerful analgesic.
• Increases cerebral blood flow ( increase intracranial pressure ).• Emergence phenomenon ( disorientetion, sensory and perceptual illusion and vivid dreams following anaesthesia ) is a problem …This can be avoided by giving Diazepam 0.2 to 0.3 Mg/Kg I.V. 5 minutes before administration of Ketamine.
ETOMIDATE• Causes rapid induction of anaesthesia with minimal CVS and respiratory changes.• It is lipid soluble with Vd of 4.5L/Kg.• Excreted mainly as metabolites in the urine.• Produces hypnosis within 2 Seconds. Hypotension and a low frequency of apnoea.• Causes high incidence of myoclonia and pain during injection. It may cause adreno-cortical suppression via inhibitory effects on steroidogenesis.
BENZODIAZEPINES• Diazepam, Lorazepam and Midazole.• Diazepam and Lorazepam are not water soluble and their I.V. use necessitates a nnon-aqueous vehicle whuch may be irritating.• Benzodiazepines are most useful in anaesthesia as premedication and can be used for intraoperative sedation.
PROPANIDID• Produce anaesthesia as rapid as Thiopentone.• Recovery is more complete and accumulation less likely with Propanidid than with Thiopentone.• It is rapidly metabolized by cholinesterase.• Causes hypotension ( due to peripheral dilatation ) and negative inotropic effect on the heart.• Major problemis epilepticform convulsios occur occasionally in patients without epilepsy.
DIISOPROPYLPHENOL• Produces anaesthesia at rate similar to that of I.V. barbiturates.• Investigational drug.• Plasma half-life 2 to 3 minutes.