General Anesthesia

Chapter 14:  General Anesthesia

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Factors Influencing Rate of Induction

Four factors determine the partial pressure in arterial blood and therefore in the brain:

  1. Anesthetic concentration in the inspired air

  • Note that for Nitrous Oxide, the arterial gas tension rises rapidly to approximate that of the inspired tension.
    •  By contrast, the arterial gas tension rises much more slowly for Halothane or Ether
  • These differences are related to differences in anesthetic physical properties.
    •  For example, Nitrous Oxide is relatively insoluble, enabling its tension (partial pressure) to rise very rapidly.
  • The rate of rise of anesthetic concentration in the brain is influenced by the rate of rise of arterial blood anesthetic tension.
  • Differences in the rate of arterial gas tension increase between agents is only part of the story in terms of anesthesia because different anesthetics have different potencies.  
    • As a result, different anesthetics exhibit different MAC values.  
    • Underlying these differences would be differences at the level of the anesthetic-receptor interaction.
[Adapted from :Kennedy, S.K. and Longnecker, D.E., History and Principles of Anesthesiology In, Goodmanand Gillman's The Pharmacologial Basis of Therapeutics,(Hardman, J.G, Limbird, L.E, Molinoff, P.B., Ruddon, R.W, and Gilman, A.G.,eds) The McGraw-Hill Companies, Inc.,1996, pp.297, Figure 13-1..

 

  1.  Pulmonary ventilation

  1. Transfer of the gas from the alveoli to the bloodIn the absence of ventilation-perfusion mismatching* three factors determine how quickly anesthetics pass from the inspired gas to the blood:

    1. Anesthetic solubility in the blood

      • Inhalational agent solubility in blood is the single most important factor in determining the speed of induction and recovery

      • The more soluble an agent is in the blood the more must be dissolved to raise its partial pressure (tension).

      • For a very soluble agent, the partial pressure rises slowly.

        • An example of a very soluble agent is methoxyflurane (blood:gas partition coefficient = 12). Induction times may be prolonged.

        • An example of a sparingly-soluble agent is nitrous oxide (blood gas partition coefficient = 0.47). The arterial blood partial pressure for nitrous oxide will rise rapidly

      *Ventilation-perfusion mismatching refers to the condition in which regions of the lung may not be functional and as a result blood flow is shunted away from these regions.  The extent to which blood is not shunted as in effect on the rate of rise of arterial anesthetic tension because blood flowing through non-functional lung regions cannot pickup anesthetic molecules.

    2. Pulmonary Blood Flow

      • Pulmonary blood flow is closely related to cardiac output.

      • Higher pulmonary flow results in an initial relative decrease in the rate of rise of anesthetic tension (since there is less time for transport of gas from the alveoli into blood).  Despite this effect, there is little influence of pulmonary flow on the total time to reach equilibrium

    3. Partial Pressures in Arterial and Mixed Venous Blood

      • The amount of dissolved anesthetic in mixed venous blood returning to the lung influences the rate of transfer of anesthetic gas into blood.

      • Initially, when the process is far from equilibration (little dissolved gas), transfer rates are highest.  We can appreciate this relationship since the flux of molecules across the membrane will be influenced by the concentration gradient (C1 - C2).  As  the difference between becomes less the flux will be reduced. Recalling Fick's equation--

        • Flux (molecules per unit time) = (C1 - C2) · (Area ·Permeability coefficient) / Thickness

        • Therefore, as equilibrium is approached and the concentration difference is reduced, the net flux (in the direction of increasing arterial gas tension) is reduced.

      • With time, equilibrium is approaches and net transfer rates decline, accounting for the relatively slower rise in final portions of arterial tension curves.

[Adapted from :Kennedy, S.K. and Longnecker, D.E., History and Principles of Anesthesiology In, Goodmanand Gillman's The Pharmacologial Basis of Therapeutics,(Hardman, J.G, Limbird, L.E, Molinoff, P.B., Ruddon, R.W, and Gilman, A.G.,eds) The McGraw-Hill Companies, Inc.,1996, pp.297, Figure 13-1.]

[Kennedy, S.K. and Longnecker, D.E., History and Principles of Anesthesiology In, Goodmanand Gillman's The Pharmacologial Basis of Therapeutics,(Hardman, J.G, Limbird, L.E, Molinoff, P.B., Ruddon, R.W, and Gilman, A.G.,eds) TheMcGraw-Hill Companies, Inc.,1996, p. 298.

Ezekiel, M.R., Handbook of Anesthesiology, Pharmacology, Current Clinical Strategies Publishing, 1997, p. 26.

  1. Transfer of the gas from the blood to body tissues (brain)

Anesthetic Potency

More about MAC:

  • increasing age
  • induced hypotension (MAP < 50 mm Hg)
  • lithium
  • acute ethanol use
  • ketamine (Ketalar)
  • pancuronium (Pavulon)
  • physostigmine (Antilirium) [at 10 times clinical dose]
  • hydroxyzine (Atarax,Vistaril)
  • metabolic acidosis
  • decreased central neurotransmitter concentration*
  • hypo-osmolality
  • pregnancy
  • neostigmine (Prostigmin)  [at 10 times clinical dose]
  • diazepam (Valium)
  • verapamil (Isoptin, Calan)
  • hypoxia (PaO2, 38 mm Hg)
  • alpha2 adrenergic receptor agonists
  • hypothermia
  • hyponatremia
  • lidocaine (Xylocaine)
  • opioids
  • barbiturates
  • chlorpromazine (Thorazine)
  • anemia (< 4.3 ml/O2/dl-1 blood)

 

*A decrease in central neurotransmitter level can be caused by many drugs, including chronic d- amphetamine use, reserpine (Serpasil), alpha-methyldopa)

[Kennedy, S.K. and Longnecker, D.E., History and Principles of Anesthesiology In, Goodmanand Gillman's The Pharmacologial Basis of Therapeutics,(Hardman, J.G, Limbird, L.E, Molinoff, P.B., Ruddon, R.W, and Gilman, A.G.,eds) TheMcGraw-Hill Companies, Inc.,1996, p. 298.]

[Ebert, Thomas J and Phillip G Schmid III, Inhalation Anesthesia in Clinical Anesthesia (4/e),edited by Paul G. Barash, Bruce F. Cullen and Robert K. Stoelting, Lippincott Williams & Wilkins, Philadelphia (c) 2001.]

Pharmacological and clinical differences among the inhalational anesthetics

Differences between Inhalational Agents
[Kennedy, S.K. and Longnecker, D.E., History and Principles of Anesthesiology In, Goodman and Gillman's The Pharmacologial Basis of Therapeutics,(Hardman, J.G, Limbird, L.E, Molinoff, P.B., Ruddon, R.W, and Gilman, A.G.,eds) TheMcGraw-Hill Companies, Inc.,1996, p 313.
[Kennedy, S.K. and Longnecker, D.E., History and Principles of Anesthesiology In, Goodman and Gillman's The Pharmacologial Basis of Therapeutics,(Hardman, J.G, Limbird, L.E, Molinoff, P.B., Ruddon, R.W, and Gilman, A.G.,eds) TheMcGraw-Hill Companies, Inc.,1996, p 311 - 315.
[Kennedy, S.K. and Longnecker, D.E., History and Principles of Anesthesiology In, Goodman and Gillman's The Pharmacologial Basis of Therapeutics,(Hardman, J.G, Limbird, L.E, Molinoff, P.B., Ruddon, R.W, and Gilman, A.G.,eds) TheMcGraw-Hill Companies, Inc.,1996, p 315 - 317.
[Kennedy, S.K. and Longnecker, D.E., History and Principles of Anesthesiology In, Goodman and Gillman's The Pharmacologial Basis of Therapeutics,(Hardman, J.G, Limbird, L.E,Molinoff, PUB., Ruddon, R.W, and Gilman, A.G.,eds) TheMcGraw-Hill Companies, Inc.,1996, p 317 -318.
[Kennedy, S.K. and Longnecker, D.E., History and Principles of Anesthesiology In, Goodman and Gillman's The Pharmacologial Basis of Therapeutics,(Hardman, J.G, Limbird, L.E, Molinoff, P.B., Ruddon, R.W, and Gilman, A.G.,eds) TheMcGraw-Hill Companies, Inc.,1996, p 318 - 319.

Concentration and Second Gas Effect

Concentration Effect

  1. If the concentration of an anesthetic gas is high, the rate of increase of gas tension in arterial blood is high.

  2. As this volume of gas is removed from the lung, fresh gas is pulled into the lung from the breathing circuit of the anesthetic delivery equipment.

  3. This effect further increases the delivery of gas mixture and therefore the rate of rise of arterial tension for nitrous oxide is increased.

  4. Speed of induction is therefore increased since the faster the arterial tension rises, the faster the rate of rise of gas tension in the brain.

  5. This effect is dependent on the high concentration of inhaled gas.

 Second Gas Effect:

  1. If the above condition is present, but a second anesthetic gas is present, the rate of rise of arterial tension of the second gas is enhanced also.

  2. If the first gas is nitrous oxide and the second enflurane, the concentration effect due to NO which pull more gas from the breathing circuit into the lung, pulls both fresh NO and fresh enflurane.

  3. Thus the rate of rise of arterial tension of enflurane is faster as well.

[Kennedy, S.K. and Longnecker, D.E., History and Principles of Anesthesiology In, Goodman and Gillman's The Pharmacologial Basis of Therapeutics,(Hardman, J.G, Limbird, L.E, Molinoff, P.B., Ruddon, R.W, and Gilman, A.G.,eds) TheMcGraw-Hill Companies, Inc.,1996, p 300.

Diffusional Hypoxia

[Kennedy, S.K. and Longnecker, D.E., History and Principles of Anesthesiology In, Goodman and Gillman's The Pharmacologial Basis of Therapeutics,(Hardman, J.G, Limbird, L.E, Molinoff, P.B., Ruddon, R.W, and Gilman, A.G.,eds) TheMcGraw-Hill Companies, Inc.,1996, p 300.

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