SYSTEMIC EFFECTS OF INHALATIONAL AGENTS

Halothane has little analgesic properties but ↑ vagal tone resulting in bradycardia,vasodilatation and hypotension.

The frequency of postoperative hepatitis is approximately 1 in 4000 for multiple exposures.

 Halothane sensitizes the heart to the arrhythmogenic effects of epinephrine

, so that doses of epinephrine above 1.5 g/kg should be avoided.

Halothane causes an idiosyncratic type of liver injury. It is genetically predisposed.

• Jaundice is usually noted 7-10 days after the exposure.
• Because of the cross-reaction between halothane and methoxyflurane, it should not be used in a patient with a halothane reaction.

Ans. is ‘a’ i.e., Halothane; ‘b’ i.e., Chronic venous congestion

Centrilobular necrosis (CN) is a nonspecific histological finding caused by hepatotoxins such as :

• Acetaminophen
• Paracetamol
• Thioacetamide
• Halothane
• Tetrachloride
• Congestive hepatic injury in veno‐occlusive disease 
• Cardiac hepatopathy due to acute right-sided cardiac failure 
• Hypoxic injury due to ischemia

Ans. is ‘b’ i.e., Enflurane

Enflurane is known to produce seizures.

D i.e. Halothane 

A i.e. Ketamine

Ans: B i.e. Etomidate 

Etomidate causes adreno – cortical suppressionQ by inhibiting enzymes 11/3 hydroxylase (mainly) & 17 a hydroxylase involved in cortisol and aldosterone (mineralocorticoid) productionQ. Vit C supplimentation restores cortisol level.

Etomidate and midazolam provide cardiovascular stabilityQ. But etomidate is most cardiostable agentQ that causes the least hemodynamic disturbance of any of the intravenous anesthetic agents. So it is intravenous anesthetic agent of choice for patients with cardiac disease and aneurysm surgeryQ.

Direct myocardial depression is caused by halothane (severe), nitrous oxide (moderate), iso/sevo/des-flurane (mild), thiopental (marked), propofol (dose dependent) and ketamineQ (but this is masked by cardiotonic sympathetic stimulatory action). Etomidate > midazolem are most cardiostable agentsQ.

B i.e. Ether

B.)It senitizes heart to catecholamines .

Extent of metaholism of inhalational anesthetics

• • Methoxyflurane > 70% (maximum metabolism)
• • Halothane > 40%
• • Enflurane 8%
• • Sevoflurane 2-5%
• • Isoflurane < 2%
• • Desflurane < 0.05% (least metabolism)
• • N2O does not undergo any metabolism.

Halothane sensitises the heart to catecholamines, so it is liable to cause cardiac arrhythmias.

Halothane ontains 0.01% thymol for stability.

HALOTHANE (2, bromo, 2 chloro, 1, 1, 1 trifluoroethane)

• • Least expensive & least pungent.
• • Potent anesthetic, no analgesia.It is a potent anesthetic with a MAC of 0.74%
• • Dissolve rubber and corrodes metals.
• • Drager Narko test is done for halothane.
• • Contains 0.01% thymol for stability.
• • Decomposed by light but is stable in amber coloured bottles.
• • 15-20% is metabolized.
• • May persist in the liver upto 12 days & not given in same patient within 3 months (potent hepato toxic).
• • Relaxes skeletal and uterine muscle & blood vessels.
• • Not hepatotoxic in children and combined with its pleasant odor, suitable in children for inhalation induction.
• • Causes 5’H’
  • o Malignant Hyperthermia,
  • o Hepatitis (centrilobular necrosis) extremely rare (1 per 35,000 cases)
  • o Hypotension
  • o Hypercapnia
  • o Heart rate decreases (myocardial depression)
• • Decreases I0P, but ICT is increased
• • Shivering & tremors common (H-shakes) in early post-operative period
• • Myocardial depression of halothane is exacerbated by β-blockers and calcium channel- blocking agents.
• • The combination of halothane and aminophylline serious ventricular arrhythmias.
• Contraindications for halothane:
  • • Pregnancy because it increases the risk of post -partum hemorrhage
  • • Liver dysfunction & Previous use within 3 months: due to halothane hepatitis
  • • Hypovolemia & severe cardiac disease (aortic stenosis); due to negative ionotropic effect
  • • Pheochromocytoma & exogenous catecholamines administration as it sensitize heart to catecholamines.
• Best uterine relaxant is Halothane followed by ether.
• Best muscle relaxant is ether followed by halothane.

A i.e. Causes bronchodialation

D i.e. Halothane

A i.e. Hepatitis 

Halothane causes two types ofhepatotoxicity:
Type I Hepatotoxicity:

• its rnild form with transient elevation of serum transaminases.
• Incidence afier halothane administration is 20-30%,

Type 2 Hepatotoxicity (Halothane hepatitb):

• It is severe form and is characterized by centrilobular necrosis.
• It is very rare winth incidence of apptoximately I: 35, (NO,
• Mortality rate is 30-70%.

A i.e. Halothane

C i.e. Halothane

D i.e. Halothane

D i.e. Halothane

Halothane (2- bromo – 2- chloro – 1, 1, 1 trifluoroethane) is a potent, non inflammable, non toxic (relatively), colourless liquid with relatively non pungent (pleasant) vapour. It is decomposed by light and stabilised by 0.01% thymolQ, but is stable when stored in amber coloured bottles. Although it is decomposed by soda lime, it may be used safely with this mixture. The vapour is absorbed by rubberQ (rubber/gas partition cofficient is 120). It corrodes metals in vaporizers and breathing systemsQ. In the presence of moisture, it corrodes aluminium, tin, lead, magnesium and alloysQ. It should be stored in a closed container away from light and heat. It is soluble in rubber, and plasticsQ commonly found in ansethetic circuits. This has obvious implications for patients with halothane sensitivity, or who are at risk for malignant hyperthermia, in whom anesthetic free circuit should be used.

Halothane, Ketamine & AtropineQ are bronchodialators. These agents decrease airway resistance and increase anatomical dead space.

Aspiration, regurgitation & intubation leads to reflex bronchospasm.

A i.e. Methoxy flurane

B i.e. Enflurane 

Ans:D i.e. Isoflurane.

CARDIAC EFFECTS OF ANESTHETIC AGENTS :
Anticholinergic agents – Atropine/glycopyrrolate: will cause an increase in heart rate, contractility, cardiac output and myocardial oxygen consumption. Often there will be no change
in blood pressure and a decrease in right atrial pressure.
Thiopental – Barbiturate
Reduction in blood pressure – peripheral vasodilation is the main action. Compensatory rise in heart rate – barorecptor response. Commonly associated with ventricular arrhythmias .
Benzodiazepines
Midazolam and diazepam: Cause little or no direct myocardial depressant effects.
Hypnotics- Etomidate: no direct myocardial depression. Safe to use with cardiac, critical and septic patients. .
Mu opioids– Fentanyl is a pure mu agonist causes dose dependant bradycardia (increase in vagal tone).
Mixed agonist/antagonist agents= Buprenorphine: a partial mu agonist/antagonist. Slow onset of action, duration of 6-8 hours.

Cardiovascular depression and respiratory depression not as profound as pure mu agonists. Butorphanol: partial agonist/antagonist. Similar to buprenorphine in cardiovascular/respiratory effects.
Dissociative Agents:Ketamine- Heart rate and arterial pressure increase due to an increase in sympathetic tone .
Inhalational Anesthetics:

• Isoflurane and sevoflurane preserved cardiac index, and isoflurane and fentanyl-midazolam preserved myocardial contractility at baseline levels in this group of patients with congenital heart disease.
• Halothane depressed cardiac index and myocardial contractility.

B i.e. Isoflurane

Isoflurane increases ICT but less than halothane & enflurane; which can be reversed by hyperventilation. So isoflurane is a preferable agent in raised ICT. Isoflurane is anaesthesia of choice (AOC) for neurosurgical procedureQ as it does not increase cerebral blood flow & CSF pressure.

Of various inhalation agents available, isoflurane has the advantage of providing stability of cardiac rhythm & lack of sensitizention of the heart to exogenous & endogenous adrenalineQ.

In coronary artery disease isoflurane should be avoided Wt coronary steel phenomenonQ.

In ischemia of cardiac muscle selective vasodialation of vessels of Ischemic zone and maintained tone of non ischemic zone //t selective increase of blood supply to ischemic areas.

But in coronary steal phenomenon (Isoflurane & Dipyridomole) there is dialation of vessels of non ischemic zone also so there is decrease of flow in ischemic zone.Q That is why isoflurane is avoided in ischemic heart disease.

• In Myocardial Infarction operation should be with held for 6 monthsQ.
• Goldman Index is for cardiac risk factor and when it is > 13 it is associated with poor prognosis.
• In hypertension, halothane is AOC (for hypotensive surgery)

In hypovolumia, Light G.A. (preferably Ether and Cyclopropane) with IPPV is method of choice

Isoflurane increases ICT but less than halothane & enflurane; which can be reversed by hyperventilation. So isoflurane is a preferable agent in raised ICT. Isoflurane is anaesthesia of choice (AOC) for neurosurgical procedureQ as it does not increase cerebral blood flow & CSF pressure.

Of various inhalation agents available, isoflurane has the advantage of providing stability of cardiac rhythm & lack of sensitizention of the heart to exogenous & endogenous adrenalineQ.

In coronary artery disease isoflurane should be avoided Wt coronary steel phenomenonQ.

In ischemia of cardiac muscle selective vasodialation of vessels of Ischemic zone and maintained tone of non ischemic zone //t selective increase of blood supply to ischemic areas.

But in coronary steal phenomenon (Isoflurane & Dipyridomole) there is dialation of vessels of non ischemic zone also so there is decrease of flow in ischemic zone.Q That is why isoflurane is avoided in ischemic heart disease.

• In Myocardial Infarction operation should be with held for 6 monthsQ.
• Goldman Index is for cardiac risk factor and when it is > 13 it is associated with poor prognosis.
• In hypertension, halothane is AOC (for hypotensive surgery)

In hypovolumia, Light G.A. (preferably Ether and Cyclopropane) with IPPV is method of choice

B i.e. Sevoflurane

B i.e. Halothane

Among all these options only halothane is hepatotoxic so it should be avoided Lets revise some important facts.

• All coagulation factors with exception of factor VIII (8) & von wille brand factor are produced by liverQ
• Vit K is necessary for synthesis of prothrombin (factor II) and factor VII, IX and XQ.
• PT is normally 11-14 seconds, mesures the activity of fibrinogen, prothrombin and factors, V, VII, and XQ
• All opioids cause spasm of sphincter of oddi & increase biliary pressure
• Halothane hepatitis is more common in middle age, obese, female sex, and a repeated exposure (esp with in 28 days)

B i.e. Halothane

All volatile anesthetic agents reduce portal hepatic blood flow. This decrease is greatest with halothane and least with isofluraneQ.

C i.e. Halothane

Ans. A: Unsuitable for pediatric population

Halothane/Fluothane is an inhalational general anaesthetic.

It is the only inhalational anaesthetic agent containing a bromine atom.

It is colourless and pleasant-smelling, but unstable in light. It is packaged in dark-coloured bottles and contains 0.01% thymol as a stabilising agent.

It is a potent anaesthetic.

It is not a good analgesic or muscle relaxant; however it potentiates competitive neuromuscular blockers.

Repeated exposure to halothane in adults results in severe liver injury (Halothane hepatitis) due to the metabolism of halothane to trifluoroacetic acid via oxidative reactions in the liver.

All volatile anaesthetics such as halothane can trigger malignant hyperthermia in genetically susceptible individuals.

Its properties include cardiac depression at high levels, cardiac sensitisation to catecholamines such as norepinephrine, and potent bronchial relaxation.

Its lack of airway irritation made it a common inhalation induction agent in pediatric anaesthesia.

Due to its cardiac depressive effect, it is contraindicated in patients with cardiac failure.

Halothane is also contraindicated in patients susceptible to cardiac arrythmias, or in situations related to high catecholamine levels such as pheochromocytoma.

Ans. is ‘c’ i.e., Constricts bronchi

Halothane

• It is a volatile liquid with a sweet odour, nonirritating, and noninflammable.
• It is a potent anesthetic with poor analgesic and muscle relaxant properties.
• Halothane causes direct depression of myocardial contractility by reducing intracellular Ca. 
• It causes a fall in BP and CO.
• Heart rate decreases due to vagal stimulation.
• It tends to sensitize the heart to the arrhythmogenic action of adrenaline → contraindicated in pheochromocytoma.
• It causes greater depression of respiration and ventilation-perfusion mismatch.
• It dilates the bronchi → inhalation agent of choice in asthmatics (intravenous anesthetic of choice in asthmatics is ketamine).
• It is a hepatotoxic drug and can also cause malignant hyperthermia (Succinylcholine accentuate it).
• Recovery is smooth and reasonably quick.
• It causes postanaesthetic shivering and chills.
• It inhibits intestinal and uterine contractions → agent of choice for assisting external or internal version during late pregnancy.
• Because of its uterine relaxant action, it is contraindicated during labour.
• It is particularly suitable for induction and maintenance in children and as maintenance anesthetic in adults.

Ans. b. Nitrous oxide

. No change in CMRO2 . No effect on GSF production or absorption
. Cerebral vasodilating effects inhibited by hyperventilation
. Expands intradural air .
. Expands venous air emboli

Ans. is ‘d’ i.e., Halothane

• Some inhalational agent sensitize the heart to adrenaline —> Arrhythmias can occur —> Therefore these agents are contraindicated in Pheochromocytoma and along with adrenaline.
• Halothane has maximum propensity .
• Other agents sensitizing the heart to adrenaline are Trilene, Cyclopropane, Chloroform, Enflurane

Ans. is ‘a’ i.e., Ketamine

Ans. is ‘b’ i.e., N₂0

Ans. is ‘d’ i.e., All the above

• Halothane, enflurane and isoflurane produce a dose dependent decrease in uterine tone (tocolysis).
• Studies of isoflurane demonstrate that halogenated compounds reduce both the frequency of uterinecontractions and the interval between them.

Ans. is `d’ i.e., Propofol

Zimmermann p. 458]

Following are the groups of hepatotoxic anesthetic agents:

• Group I : Drugs with well known hepatotoxic potential and containing Chlorine or bromine. Eg: chloroform.
• Group II : Drugs which contain fluorine Eg: halothane, methoxyflurane.
• Desflurane, enflurane, sevoflurane, isoflurane, nitrous oxide and carbon tetrachloride are also linked with hepatotoxicity.

Ans. is ‘b’ i.e., N20

Ans. ‘d’ i.e., Halothane

• Halogenated inhalational anaesthetic agents like halothane are powerful tocolytic agents. Halothane is anaesthetic of choice for internal version and manual removal of placenta.

Ans. is ‘d’ i.e., All of the above

Halothane

• It is a volatile liquid with sweet odour, nonirritating and noninflammable.
• It is a potent anaesthetic with poor analgesic and muscle relaxant properties.
• Halothane causes direct depression of myocardial contractility by reducing intracellular Ca+2.
• It causes fall in BP and CO.
• Heart rate decreases due to vagal stimulation.
• It tends to sensitize the heart to arrhythmogenic action of adrenaline –> contraindicated in pheochromocytoma.
• It causes greater depression of respiration and ventilation perfusion mismatch.
• It dilates the bronchi -4 inhalation agent of choice in asthmatics (intravaneous anaesthetic of choice in asthmatics is ketamine).
• It is a hepatotoxic drug and can also cause malignant hyperthermia (Succinylcholine accentuate it).
• Recovery is smooth and reasonably quick.
• It causes postanaesthetic shivering and chills.
• It inhibits intestinal and uterine contractions -4 agent of choice for assisting external or internal version during late pregnancy.
• Because its uterine relaxant action it is contraindicated during labour.
• It is particularly suitable for induction and maintenance in children and as maintenance anaesthetic in adults.

Ans. is ‘a’ i.e., Halothane

• All inhalational agent cause mild hepatotoxicity by decreasing hepatic blood flow.
• Isoflurane is the agent of choice in liver disease as it has least effect on Hepatic blood flow.
• Direct hepatotoxicity (Hepatitis,Hepatic necrosis) is caused by :- Halothane, Chloroform, trilene, methoxyflurane

Ans. is ‘a’ i.e., Halothane

Halothane

• It is a volatile liquid with sweet odour, nonirritating and noninflammable.
• It is a potent anaesthetic with poor analgesic and muscle relaxant properties.
• Halothane causes direct depression of myocardial contractility by reducing intracellular Ca+2.
• It causes fall in BP and CO.
• Heart rate decreases due to vagal stimulation.
• It tends to sensitize the heart to arrhythmogenic action of adrenaline —* contraindicated in pheochromocytoma.
• It causes greater depression of respiration and ventilation perfusion mismatch.
• It dilates the bronchi —> inhalation agent of choice in asthmatics (intravaneous anaesthetic of choice in asthmatics is ketamine).
• It is a hepatotoxic drug and can also cause malignant hyperthermia (Succinylcholine accentuate it).
• Recovery is smooth and reasonably quick.
• It causes postanaesthetic shivering and chills.
• It inhibits intestinal and uterine contractions —> agent of choice for assisting external or internal version during late pregnancy.
• Because its uterine relaxant action it is contraindicated during labour.
• It is particularly suitable for induction and maintenance in children and as maintenance anaesthetic in adults.

Ans. is ‘c’ i.e., Isoflurane

Anaesthetic agents of choice for vaous conditions Day care :

Ans. is ‘a’ i.e., Methooxyflurane 

Ans. is ‘d’ i.e., Methoxyflurne

Methoxyflurane

• It was most potent inhalation agent (least MAC), but not used not (now Halothane is most potent). o It should not be used in closed circuit (reacts with rubber tubing of the losed circuit).
• It has slowest onset & recovery (however now ether has slowest onset & recovery as methoxyflurane is not used). o Boiling point is more than water (104°C).
• Intrarenal metabolism of methoxyflurane and subsequent intrarenal production of fluoride ion is the significant cause of methoxyflurane renal toxicity.
• It can cause high output renal failure and hepatotoxicity