General anesthesia (GA) 2

General anesthesia (GA) 2 Dr.Entisar Al-Mukhtar

Inhalation anesthetics:

Halothane:
• Prototype to which newer inhalation anesthetics haven been compared.
• Produces rapid induction of anesthesia and rapid recovery.
• It has largely been replaced by other anesthetics that cause fewer complications.
Pharmacokinetics:
• Produce toxic metabolized (eg. trifluoroethanol & bromide ion) that can cause toxic reaction (fever, followed by anorexia, nausea, vomiting & patients may exhibit signs of hepatitis & death may occur due to hepatic necrosis) especially in females.
• Thus halothane anesthesia is not repeated at intervals of less than 2 – 3 weeks.
Note: all halogenated inhalation anesthetics have been reported to cause hepatitis, but at a much lower incidence than with halothane.
Advantages:
1. Potent anesthetic.
2. Potent bronchodilator.
3. Relaxes skeletal & uterine muscles (used in obstetrics when uterine relaxation is indicated).
4. Not hepatotoxic in pediatric patients (unlike its potential effect on adults) & combined with its pleasant odor, this makes it suitable in children for inhalation induction (now sevoflurane is the agent of choice for inhalation induction if cost is not a factor).
Disadvantages:
1. Weak analgesic (coadministered with N2O, opioids, or local anesthetics).
2. Reduces hepatic & renal blood flow.
3. Halothane, like the other halogenated anesthetics, produces concentration- dependent hypotension (phenylephrine administration is recommended) .
4. Hepatotoxicty in adult.
5. Halothane, like other halogenated hydrocarbons is vagomimetic & causes atropine-sensitive bradycardia. In addition, halothane has the undesirable property of causing cardiac arrhythmias because it sensitizes the myocardium to the actions of catecholamines.
6. Malignant hyperthermia (MH): A rare life-threatening condition that may occur due to exposure to any of the halogenated hydrocarbon anesthetics & succinylcholine in susceptible individuals (burn victims & individuals with Duchenne muscular dystrophy, myotonia, osteogenesis imperfecta and central-core disease).
• Susceptibility to MH is often inherited as an autosomal dominant disorder.
• These drugs can induce a drastic & uncontrolled increase in skeletal muscle oxidative metabolism, which overwhelms the body’s capacity to supply O2, remove CO2 & regulate body temperature, leading to circulatory collapse & death.
• Therefore, dantrolene should always be available for emergency use (investigations have identified a dramatic increase in the myoplasmic calcium ion conc. Result in an excitation–contraction coupling defect).



Enflurane:
Comparing to halothane, enflurane is less potent, cause less sensitization of the heart to catecholamines & fewer arrhythemia, but it cause more muscle relaxation (more potent curare-like effect)
Advantages;
Rapid induction & recovery.
Disadvantages:
1. CNS excitation, thus it is not used in patient with seizure disorders.
2. 2 % of enflurane is metabolized to fluoride ion, so it is contraindicated in patient with kidney failure.
Isoflurane:
Advantages:
1. Rapid recovery.
2. Unlike other halogenated inhalation anesthetics it neither induce cardiac arrhythmias nor sensitize the heart to catecholamines.
3. Dilates coronary vasculature (beneficial in patient with IHD).
4. No increase in ICP.
5. Undergoes little metabolism (little fluoride) therefore, it is not toxic to the liver or kidney.
6. Good muscle relaxant.
7. Cause less hepatotoxicity.
Disadvantages: Like the other halogenated gases, it produces dose-dependent hypotension due to peripheral vasodilation.
Desflurane:
Advantages:
1. Due to its low blood solubility, it has very rapid onset of anesthesia & recovery, so it is the popular anesthetic for emergency anesthesia.
2. Decreases vascular resistance & perfuses all major tissues very well.
3. Its degradation is minimal & therefore tissue toxicity is rare.
Disadvantages:
1. Has a low volatility (must be delivered using a special heated vaporizer).
2. Because it is airway irritant, it is not used for inhalation induction.
3. Expensive (not used for maintenance of extended anesthesia).
Sevoflurane:
Advantages:
1. Due to low blood solubility, sevoflurane has rapid onset /recovery (recovery is faster than with other anesthetics).
2. Produce rapid induction without airway irritation (has low pungency) thus it replaces halothane for inhalation induction in pediatric patients.
Disadvantages: Metabolized to fluoride ions, thus like enflurane it may be nephrotoxic.

Nitrous oxide (N2O) " laughing gas ":
Advantages:
1. Potent analgesic (30–50 % of N2O combined with O2 for analgesia, particularly in dental surgery).
2. Rapid onset / recovery because it is poorly solube in blood & other tissues.
Note: due to of its fast uptake from the alveolar gas, it can concentrate the halogenated anesthetics in the alveoli when they are concomitantly administered. This phenomenon is known as the "second gas effect ".
3. No airway irritation or respiratory depression.
4. Moderate to no effect on the CVS or on increasing cerebral blood flow.
5. It is the least hepatotoxic (safest inhalation anesthetics).
Disadvantages:
1. Weak general anesthetic (must be used with more potent anesthetics for surgical anesthesia).
2. No muscle relaxation.
3. Within closed spaces of body compartments, it replaces nitrogen faster than the nitrogen leaves, thus it increases the volume (eg, pneumothorax) or the pressure (eg., in the sinuses), furthermore, its speed of movement allows it to retard oxygen uptake during recovery, thereby causing "diffusion hypoxia," which can be overcome by administering significant concentrations of inspired oxygen during recovery.

IV anesthetics:
Provide rapid induction of anesthesia, thus they must be injected slowly. The metabolism of the useful agents dose not occur rapidly, thus recovery which depend on both metabolism & redistribution is slow as compared to inhalation anesthetics.
Barbiturates:
• Thiopental the ultrashort-acting barbiturate with high lipid solubility is a potent anesthetic but a weak analgesic.
• When thiopental & methohexital are administered IV, they quickly depress the CNS, their diffusion out of the brain can also occur very rapidly due to redistribution to other tissues (skeletal muscle & ultimately, adipose tissue) which result in a short duration of anesthesia.
• These drugs may remain in the body for long time, because the metabolism of thiopental is much slower than its tissue redistribution.

Advantages:
Thiopental has minor effects on the CVS, but it may contribute to severe hypotension in patients with hypovolemia or shock.
Disadvantages:
• Barbiturates are not significantly analgesic (analgesic is required to avoid objectionable changes in BP & autonomic function).
• All barbiturates can cause apnea, coughing, chest wall spasm, laryngospasm & bronchospasm.
• Barbiturates are contraindicated in patients with acute intermittent or variegate porphyria.
Benzodiazepines (BZDs):
• Used to sedate the patient. The most commonly used is midazolam.
• Diazepam & lorazepam are alternatives.
• All three facilitate amnesia while causing sedation.
Opioids:
• Opioids are used as analgesic in combination with N2O or halogenated anesthetics.
• The choice of opioid is based on the duration of action needed.
• Fentanyl & its congeners, sufentanil & remifentanil are the most commonly used opioids because they induce analgesia more rapidly than morphine does.
• They can be given either IV, epidurally or intrathecally.
Disadvantages:
1. Not good amnesics.
2. They can cause hypotension, respiratory depression, and muscle rigidity as well as postanesthetic nausea & vomiting.
• Naloxone is an opioid antagonist.
Etomidate:
• Hypnotic with no analgesic activity. Used to provides rapid induction, it is short acting drug.
• It is usually only used for patients with coronary artery disease or CV dysfunction such as shock because it has little to no effect on the heart and circulation.
Adverse effects:
1. Decrease plasma levels of cortisol & aldosterone, so it should not be infused for an extended time.
2. Venous pain can occur on injection.
3. Involuntary skeletal muscle movements may occur (managed by BZDs & opioids.)
Ketamine:
• Short-acting, nonbarbiturate anesthetic.
• Produces a dissociative anesthetic state [characterized by sedation, amnesia, analgesia & immobility, with or without loss of consciousness (hypnosis)].
• Stimulates the central sympathetic outflow, which in turn stimulate the heart & increasing BP & COP, thus it is beneficial in patients with either hypovolemic or cardiogenic shock as well as in patients with asthma.
• Therefore its use is precluded in hypertensive or stroke patients.
• It is main use is for short procedures in children & young adults.
• However, it is not widely used, because it increases cerebral blood flow & induces postoperative hallucinations (“nightmares”), particularly in adults.
Propofol:
• IV sedative/ hypnotic used for induction or maintenance of anesthesia.
• Provides smooth rapid onset.
• Poor analgesic so, narcotic analgesic is required.
• Facilitates CNS depression, but it is occasionally accompanied by excitatory phenomena (such as muscle twitching, spontaneous movement or hiccups).
• Decreases BP without depressing the myocardium, also it decreases intracranial pressure.
• Replaces thiopental for anesthesia induction & sedation (because propofol produces an euphoric feeling & does not cause nausea & vomiting).
• Useful for resection of spinal tumors surgeries (because unlike volatile anesthetic, propofol has much less depressant effect on the CNS-evoked potentials such as somatosensory evoked potentials which are monitored to assess spinal cord functions).