EFFECTS OF INHALED ANESTHETICS ON CONTROL OF VENTILATION
The most obvious effects of inhaled anesthetics are alterations
of minute ventilation. Many different stimuli interact in a complex manner to determine
ventilation in humans. The traditional approach to studying effects of drugs on
ventilation has been to measure ventilatory responsiveness (e.g., expired minute
volume, respiratory frequency, arterial carbon dioxide tension) before and after
drug administration. A complete description of ventilatory control is beyond the
scope of this chapter, and several excellent reviews of this subject already exist.
[209]
[210]
[211]
[212]
[213]
[214]
However, an understanding of normal ventilatory responses and control mechanisms
is necessary to appreciate the actions of anesthetics and the methods by which these
effects are measured.
Control of Breathing
A control system that modulates ventilation is required to maintain
stability of arterial blood gas tensions and acid-base status and to integrate respiratory
rate and tidal volume to minimize the work of breathing in response to variations
in the total ventilatory requirements ( Fig.
6-12
). The system responsible for receiving and integrating a variety
of input signals and ultimately producing movement of air into and out of the lungs
is composed of the following elements:
- The sensory system may be chemical (i.e.,
peripheral and central chemoreceptors) or mechanical (i.e., distortion receptors
located in airways, alveoli, and respiratory muscles).
- The respiratory control system integrates
the signal inputs from the receptor sites, centers of consciousness, and other influences
(e.g., pain) and subsequently produces nerve traffic to the muscles of respiration.
- The motor system is composed of chest wall,
intercostal, diaphragmatic, and abdominal muscles, all of which respond to signals
from the control center through phrenic and spinal nerves.
The respiratory rhythm generator resides within the brainstem
and consists of two primary types of respiratory neurons: the dorsal respiratory
group (DRG), composed of cells active during inspiration; and the ventral respiratory
group (VRG), containing inspiratory and expiratory neurons. The precise mechanism
of rhythm generation remains unknown despite extensive study. Excitatory drive to
bulbospinal inspiratory neurons of the caudal ventral respiratory group is mediated
by tonic (acting through N-methyl-D-aspartate
[NMDA] receptors) and phasic inputs (primarily consisting of non-NMDA glutamate receptors).
[215]
Neurotransmission in bulbospinal expiratory
neurons is mediated through NMDA-type glutamate receptor input and modulated by γ-aminobutyric
acid type A (GABAA
) receptors.[216]
[217]
The isolated medulla oblongata is capable of generating a rhythmic, albeit abnormal,
respiratory pattern.[218]
Medullary regions involved
in the generation and modulation of respiratory and sympathetic nervous system vasomotor
output may also contain neurons functioning as central oxygen detectors.[219]
One such central site that may be involved in this process is the retrotrapezoid
nucleus of the rostral ventrolateral medulla. However, several other brainstem sites
that express FOS during hypercapnia or hypoxia have also been implicated.[220]
A particularly useful in vitro neonatal brain slice model was developed by Smith
and colleagues.[221]
Using this model, a group
of pacemaker (self-oscillating) respiratory neurons in the rostral VRG was identified
that may represent the elusive rhythm generator at least in the immature animals.
The rostral pons contains the pneumotaxic center that involves inspiratory and expiratory
neurons and plays a critical modulating role by integrating vagal and chemoreceptive
inputs. The inspiratory controller output independent of other mechanical factors
may be measured in humans as the pressure developed in the first 0.1 second of inspiration
at FRC by acute airway occlusion.[222]
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