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8 General anaesthetic agentsFollowing induction large quantities of NO are produced, which may be cytotoxic.
Inaddition, it may form radicals leading to cellular damage and capillary leakage.Effects
Cardiovascular – vasodilator tone in small arteries and arterioles is dependent
on a continuous supply of locally synthesized NO. Shear stresses in these ves-
sels increase NO production and may account for flow-dependent vasodilatation.
Nitric oxide derived from the endothelium inhibits platelet aggregation. In septic
shock there is overproduction of NO resulting in hypotension and capillary leakage.
Respiratory – endogenous NO provides an important basal vasodilator tone in pul-
monary and bronchial vessels, which may be reversed in hypoxia. When inhaled in
concentrations of up to 40 ppm it may reduce V/Q mismatching in acute respira-
tory distress syndrome (ARDS) and reduce pulmonary hypertension in neonates.
Inhaled NO has no effect on the systemic circulation due to its rapid inactivation
within red blood cells. Its affinity for haemoglobin is 1500 times that of carbon
monoxide. It has no bronchodilator properties.
Immune – NO synthesized in macrophages and neutrophils can be toxic to certain
pathogens and may be an important host defence mechanism.
Haematological – NO inhibits platelet aggregation.
Neuronal – nerves containing NO are widely distributed throughout the central
nervous system. Proposed roles include modulation of the state of arousal, pain
perception, programmed cell death and long-term neuronal depression and exci-
tation whereby neurones may ‘remember’ previous signals. Peripheral neurones
containing NO control regional blood flow in the corpus cavernosum.N-monomethyl-l-arginine (l-NMMA) is a guanidino substituted analogue of
l-arginine, which inhibits NOS. Whilel-NMMA has been used to antagonize NOS,
resulting in an increased blood pressure in septic shock, it does not alter the course
of the underlying pathology and has not been shown to alter survival.
Sodium nitroprusside and the organic nitrates (e.g. glyceryl trinitrate) exert their
effect by the spontaneous release of nitric oxide or metabolism to nitric oxide in
smooth muscle cells.UK guidelines for the use of inhaled NO in adult intensive care units
An expert group of physicians and representatives from the department of health
and industry issued the following guidelines in 1997:
Indications:severe ARDS (optimally ventilated, PaO 2 <12kPawith FIO 2 =1), or
right-sided cardiac failure.
Dose:maximum = 40 ppm, but use minimum effective dose.
Equipment:asynchronized inspiratory injection system is considered optimal.
Ifacontinuous delivery system is used it must be through a calibrated
flowmeter. Stainless steel pressure regulators and connectors should be used.