58 / 242
58
Chapter 5
volume and SpO
2,
though without any clinically relevant respiratory depression. This effect
was aggravated by additionally sedation using benzodiazepines.
36
Nitrous oxide (N
2
O)
Nitrous Oxide is a gas of low solubility that is rapidly absorbed (within 60 s) and eliminated
unchanged via the lungs. Available in a fixed 50:50 combination with oxygen (Entonox
®
/
Relivopan
®
/Livopan
®
), it is widely used in obstetrics and dentistry for more than 160 years.
37
It is known for a rapid onset and termination of action and only minimal side effects. Its
analgesic properties are attributed to inhibition of N-Methyl-D-aspartate (NMDA)–receptors;
the anxiolytic and sedative properties are referred to activation of Gamma Amino Butyric
Acid (GABA)-receptors. In animal studies, N
2
O induced the release of opioid peptides in
the brainstem followed by the activation of descending noradrenergic inhibitory pathways.
Hence, N
2
Omodifies pain processing in the spinal cord and induces analgesia - without loss
of consciousness.
38,39
Welchman et al.
40
performed a systematic review addressing sedation during colonoscopies,
comparing N
2
O to opiates – given intravenously – partially combined with midazolam.
Unfortunately, only a small number of patients have been included, and among those a large
diversity existed. In addition, no validated scores were used to assess patients’ satisfaction.
40
The data showed that N
2
O use on demand was not sufficient enough to adequately reduce
pain, probably because a short lag time exists before analgesia is reached by N
2
O. Løberg et
al.
42
could show that N
2
O on demand is not really effective in the substitution of intravenous
medication in patients undergoing colonoscopy. However, combining a start dosage of
N
2
O for 2 minutes administered by the patient himself on demand showed that N
2
O was
superior to analgo-sedation with midazolam combined with fentanyl concerning pain
experiences, satisfaction, and compliance to undergo colonoscopy again.
44
In contrast,
Forbes et al.
44
reported that Entonox
®
was less effective than meperidine/midazolam with
respect to pain scores, but allowed for faster recovery. Prediction of painful manoeuvres
during colonoscopy is difficult, and the patient might use N
2
O too late to timely achieve
an adequate pulmonary concentration necessary for subsequent pain reduction. Maslekar
et al. compared continuous inhaled Entonox
®
with patient maintained target controlled
infusion with propofol. They found no differences between N
2
O and propofol regarding
pain relief, sedation, and mobility of the patients.
45
N
2
O for short acting procedures is considered safe.
46
Onody et al.
47
analysed 35.828
questionnaires and demonstrated a rate of all adverse effects of 4.4%, from which 86%
counted for gastrointestinal (nausea, vomiting) and neuropsychiatric (dizziness, headache,
hallucinations) disorders.
The only proven toxic effect of N
2
O concerns interaction with vitamin B12, which also
depends on duration (6 hours) and extent of exposure. Animal studies suggest a problem