Anaesthesia, 1982, Volume 37, pages 285-288

Nitrous oxide analgesia and altitude

M . F. M . J A M E S , E . D. M . M A N S O N AND J . E. D E N N E T T

Summary
The analgesic ej/ectiveness of 50% nitrous oxide and oxygen or oxygen-enriched air, measured by
variations in pain threshold, was studied at an altitude of 1460 m and simulated altitudes of sea level
and 3300 m.
At sea level pressures, SO% nitrous oxide exerted a similar anulgesic effect to that found for morphine,
raising the pain thresholds by a mean o f 71.5%. At 1460 m, the increase in puin threshold produced
was 40% and at 3300 m the increase in pain threshold was only 19%.
The difference between the analgesic elfects qfnitrous oxide at each ultitude was statistically significant.
It is concluded that moderate altitudes signijkantly reduce the effectiveness of nitrous oxide in a manner
directly related to the partial pressure of nitrous oxide at each altitude.

Key words
Analgesia; measurement.
Hypobaria; altitude.

There is a widely held clinical impression that the two who appeared inadequately anaesthetised,
effectiveness of nitrous oxide is considerably one of whom recalled the procedure. They con-
reduced at moderate altitudes as a consequence of cluded that unsupplemented nitrous oxide in
the reduction in barometric pressure and thus oxygen was not an adequate or safe anaesthetic
of the partial pressure of any given concentration at their altitude. At the altitude in Salisbury,
of the gas. There has, however, been very little Zimbabwe (1460 m) the use of unsupplemented
scientific study of the problem. Safar & Tenicela' nitrous oxide/oxygenjrelaxant techniques for
concluded that, a t altitudes of 3000 m and above. Caesarean section was abandoned after a short
nitrous oxide could not be employed effectively study showed an incidence of awareness of five
without the risk of hypoxia and advised against cases out of 30.
its use. In an attempt to evaluate the problem,
Powell & GingrichZ studied the use of 70% Cleaton-Jones et aL3 studied a number of
nitrous oxide in oxygen using a relaxant/ variables in volunteers given nitrous oxide at sea
ventilation technique on 14 patients at an altitude level and at 1700 m and found only marginal
of 1 mile (1600 m). They found an arterial Poz differences. However, their study was conducted
of less than 9 kPa in two patients and a further by different observers with different subjects at

M.F.M. James, MB, ChB, FFARCS, Senior Lecturer, E.D.M. Manson, MB, ChB, Registrar, J.E. Dennett, SRN,
Nursing Sister, Department of Anaesthetics, Godfrey Huggins School of Medicine, P.O. Box A 178, Avondale,
Salisbury, Zirnbabwc.
0003-2409/82/030285 + 04 SOZ.OO/O @ 1982 The Association of Anaesthetists of Gt Britain and Ireland 285
286 M.F.M. James, E.D.M. Munson und J.E. Dennett

each altitude, making direct comparisons diffi- system which was equipped with a n anti-pollution
cult. In addition, analgesia, which is perhaps the hooded expiratory value from which the expired
most clinically useful action of nitrous oxide, was gases were collected in Douglas bags to prevent
not extensively studied. contamination of the chamber.
It was therefore decided to study the influence Tests of pain threshold were made after the
of altered barometric pressure on the degree of subjects had inhaled each gas for 10 minutes,
analgesia produced by 50% nitrous oxide using previous studies having shown that the maximum
the same subjects and observers at each pressure effect or nitrous oxide is achieved in this
levcl . At the time of testing expired carbon dioxide
levels were measured using a Beckman infrared
analyser. Both the altitude sequence and the
Methods order in which gases A and B were inhaled were
The study was conducted in a large pressure varied from subject to subject according to a
chamber capable of accommodating with ease six Latin square design and neither the volunteers
people and all necessary equipment. Three levels nor the investigator testing pain thresholds were
of barometric pressure were used: 84 kla, this aware of the altitude or gas sequence used.
being the ambient pressure at Salisburys altitude
of 1460 m (altitude 2); and simulated altitudes
Results
of sea level, a barometric pressure of 100 kPa
(altitude 1) and 3300 m, a barometric pressure of The results were tested using the analysis of
69 kPa (altitude 3). variance for repeated measurements. Whilst there
Pain thresholds were determined by the was considerable inter-subject variation in resting
application of pressure to the bare area of the pain threshold, there was no significant difference
tibia using a spring balance after the method of between the mean baseline values at the three
Dundee & Moore.4 Each 1 Ib division on the different altitudes.
balance scale was arbitrarily designated as one At sea level pressure nitrous oxide produced
pain unit. a significant increase in pain threshold of a mean
Twenty healthy adult volunteers of both sexes, of 71.5: from the baseline (Table 2) for gas A
all normally resident at 1460 m altitude, were and gas B (p<O.Ol). At this barometric
studied. At each pressure level pain threshold pressure three subjects complained of nausea and
measurements were made whilst subjects two other subjects became semi-comatose during
breathed air, 507; nitrous oxide in oxygen (gas the inhalation period.
A) and 507 nitrous oxide in oxygen-enriched air At a pressure of 85 kPa (1460 m altitude)
(gas B). The composition of gas B was adjusted nitrous oxide again produced a significant
so that at each altitude level it contained a partial increase in pain threshold of a mean of 40h for
pressure of oxygen of 21 kPa and the balance as the two gas mixtures but this increase was
nitrogcn (Table 1). Gas B was included in the markedly less than that found at sea level. There
study to reveal any variation as a result of altered were no side-effects at this altitude. When the
oxygen tension and to investigate any possible barometric pressure was reduced to 69 kPa (a
influence of nitrogen. simulated altitude of 3300 m) nitrous oxide
All gases were inhaled from a Mapleson A produced only a 197; increase in pain threshold
Table 1. Composition of gas A and gas B at each altitude level

Gas A Gas B
Barometric
pressure Nitrous oxide Oxygcn Nitrous oxide Oxygen Nitrogen
kPa k Pa k Pa kPa kPa kPd
~~

Altitude 1 101.5 50.5 50.5 50.5 21.3 29.2

(sea level)
Altitude 2 85.0 42.5 42.5 42.5 21.3 21.2
(I460 m)
Altitude 3 69.0 34.5 34.5 34.5 21.3 13.7
(3300 m)
 Nitrous oxide analgesia and altitude 287

Table 2. Changes in pain threshold (SEM) produced by each gas at each altitude level, and the mean carbon
dioxide levels. All figures other than percentages and carbon dioxide levels are expressed in arbitrary pain units
(see text)

Mean 7; Mean expired

Air Gas A Increase Gas B Increase increase PCO, (kPa)

Altitude 1 8.6 14.8 + 6.2 14.7 + 6.1 71.5 4.59

(sea level) (4.26) (3.01) (p < 0.01) (3.51) (p i0.01)
Altitude 2 8.8 12.3 + 3.5 12.4 t 3.6 40.0 4.51
(1460 m) (3.13) (3.12) (p < 0.01) (2.25) (p < 0.01)
Altitude 3 9.0 10.5 + 1.5 10.9 + 1.9 19.0 4.59
(3300 m) (3.59) (2.03) (p>0.05) (2.40) (p > 0.05)

which failed to reach statistical significance

Discussion
(p > 0.05).
There was a significant difference between the From these results it would appear that altitude
elevation of pain threshold produced a t sea level does exert a considerable influence on the
and that found at the other two levels (p < 0.01 analgesic effectiveness of nitrous oxide. It is also
for altitudes 2 and 3). There was also a significant likely that this effect is due mainly to the
difference between the analgesia produced at reduction in partial pressure that occurs at
1460 and that at 3300 m (p < 0.05; Fig. 1. Table altitude. As may be seen from Table 1, the partial
2). At no altitude level was there any difference pressures of nitrous oxide a t the three altitude
between the analgesia produced by nitrous oxide levels studied approximate to sea level concentra-
in oxygen (gas A) or that of nitrous oxide and tions of 50, 42 and 34%. The fact that nausea
oxygen in air (gas B). Expired carbon dioxide and semi-comatose states occurred only at sea
levels were unchanged at each altitude (Table 2). level is in reasonable agreement with Parbrook's
Subjects commented that the maximum sub- classification of the levels of nitrous oxide
jective effects of nitrous oxide were achieved analgesia.'
rapidly and either remained the same or in some In addition, the degree of analgesia produced
cases appeared to diminish towards the end of by SO"/, nitrous oxide at sea level was slightly
the inhalational period. greater than that produced by morphine 0.2
mg/kg in a previous study using the same testing
apparatus.g This is in agreement with other
studies which found SO% nitrous oxide to be
superior to 100 mg pethidines and 25% nitrous
oxide to be better than morphine 0.16 mg/
kg.*
The only study of which we are aware in which
direct comparisons were made of the analgesic
effects of various concentrations of nitrous oxide
was by Whitwam et d SIn their study 33%
nitrous oxide produced an increase in pain
threshold of 23.5%, 407i nitrous oxide raised the
pain threshold by 27.2% and 50% nitrous oxide
produced an increase in pain threshold of 74.1%
when the nitrous oxide was increased in stepwise
manner. These figures are in reasonable agree-
ment with ours a t each altitude level (Table 2).
Altitude level
However, when 33 or 50% nitrous oxide was
administered ab initio in their study, no difference
Fig. 1. Histogram (SD) showing effect of altitude on was found between the analgesia produced at
changes in pain threshold for each gas mixture. either concentration. We were unable to confirm
* p < 0.01 (altitude 1 and 2 for both gases); f p < 0.01
(altitude 1 and 3 for both gases); f p < 0.05 (altitude this. Our finding that, in some cases, the
2 and 3 for both gases). 0 Gas A; gas B. subjective effect of nitrous oxide appeared to
288 M . F . M . James. E.D.M. Manson and J.E. Dennett

decrease with time also agrees with previous References

1 SAFARP, TENICELA
R. High altitude physiology in
It is unlikely that factors other than altered relation to anesthesia and inhalation therapy.
partial pressure or nitrous oxide affected the Anesfhesiology 1964; 25: 5 15-3 1.
results. The fact that we obtained almost identical 2 POWELLJN, GINGRICHTF. Some aspects of
results with each gas mixture virtually excludes nitrous oxide anesthesia at an altitude of one mile.
Anesthesia and Anuigesia; Currenf Rcscurchcs 1969;
alterations in partial pressure of oxygen or
48: 68C.5.
nitrogen from playing a significant role. This 3 CLEATON-JONU: P. MOYESDG, WHITTAKER i\M.
latter observation is confirmed by the constancy Clinical effects of nitrous oxide and oxygen
of baseline readings at each altitude. mixtures at sea-level and at 1700 metres altitude.
Since hypoxia could not occur with any gas Anaesthesia 1979: 34: 859-62.
4 DUNDEEJW, MOOREJ. Alte~.ationsin response to
mixture, it is not surprising that expired carbon somatic pain associated with anaesthesia, I. An
dioxide levels should remain constant and thus evaluation of a method of analgesirnetry. Brifi.c.h
changes in the partial pressure of carbon dioxide Journal of Anaesthesia 1960; 32: 39&406.
did not affect the results. It should be noted, 5 DUNDEEJW, MOOREJ. Alterations in response lo
however, that all our subjects were acclimatised somatic pain associated with anaesthesia. IV. The
effect of sub-anaesthetic concentrations of in-
to moderate altitude where the normal arterial halation agents. British Journal nf Anae?thesiu
carbon dioxide tension is of the order of 4.5 kPa. 1960; 3 2 453-9.
It is conceivable that results slightly different from 6 PARBROOK G D , REESGAD. ROBERTSOY GS. Relief
those found in this acute experiment might be of post-operative pain: comparison of a 250/,,
nitrous-oxide and oxygen mixture with morphine.
found in people chronically adapted to each British Mecliccd Journul 1964; 2: 48&2.
altitudc, but as our results are in accord with 7 PARBROOKG D . The levels of nitroua oxide
clinical impressions of the effectiveness of nitrous analgesia. Brifish Journal of Anaesthesia 1967; 3 9
oxide at altitude, such differences are likely to 97482.
be minimal. X WHITWAM J G , MORGANM, HALLGM, PETRIEA.
Pain during continuous nitrous oxide administra-
It is concluded therefore that the effectiveness tion. British Journui ofAnaesthesia 1976; 48:425-9.
of any given concentration of nitrous oxide as 9 JAMESMFM. DIJTH16 AM. DUFN BL, MCKEAG
an analgesic is markedly reduced by altitude as AM. RICECP. Analgesic effcct of ethyl alcohol.
a result of the reduction in partial pressure. Brifish Journril o/ Anursthesia 1978; 50: 139-41.
10 KEKHF. HOSKIMMR, BROWNM G , EWINC DJ,
Anaesthetists working at even moderate altitudcs IRVINGJB, KIRBY BJ. A double-blind trial of
should allow for this effect in their use of this patient-controlled nitrous oxidejoxygen analgesia
agent. in myocardial infarction. Lancer 1975: 1: 1397-400.