Br. J. Anaesth. (1981), 53, 777
CORRESPONDENCE
CALIBRATION OF PEAK FLOW METERS
Sir,—Fisher and Shaw (1980) criticize the standard and MiniWright Peak Flow Meters (PFM) for not reading correctly
when tested with their flow and volume calibrator (Shaw,
Fisher and Hughes, 1979).
Had they read the paper by the late Dr C. B. McKerrow and
myself (Wright and McKerrow, 1959) more carefully, they
would have seen that their criticism is unjustified. We did not
claim that the PFM measured air flow correctly in absolute
units, but that it estimated, with sufficient precision for clinical
purposes, the Peak Expiratory Flow (PEF) that the subject
would produce when tested with an ideal instrument of
negligible resistance and inertia. We obtained a calibration
curve for this purpose by asking 20 subjects with widely
varying PEF to blow alternately into a pneumotachograph and
the PFM. This laborious and rather imprecise procedure was
adopted because it was not technically possible to connect the
two instruments in series. It was not clearly realized at the time
that this is the only valid and satisfactory procedure. All
portable, and most non-portable PFM have appreciable resistance or inertia, or both, and therefore modify the PEF to a
varying extent. If they were calibrated to read the actual flow
through them, the PEF of an individual would depend on the
instrument used, which would be most unsatisfactory. As it is,
any kind of PFM can be used to estimate the "ideal" PEF
provided that it has been calibrated, either directly against an
"ideal" instrument such as we used, or against an already
calibrated instrument such as the Wright PFM. The latter
procedure was adopted when calibrating the Minimeter
(Wright, 1978; Oldham, Bcvan and McDermott, 1979; Perks ct
al., 1979) and makes it possible to substitute the Mini for the
Standard PFM without any confusion or appreciable loss of
accuracy.
I do not, however, claim that our original calibration of the
PFM was absolutely correct and it i&open to anyone to repeat it.
There are two sources of doubt. First, 20 subjects is a niggardly
number on which to base the calibration of an instrument in
world-wide use and a recalibration using a much larger number
of subjects and a wider range of PEF, especially at the lower end
of the scale, is long overdue. Second, the pneumotachograph
we used had a resistance of only 15 mm H 2 O at 700 litre min "',
which was considered to be negligible compared with
120mmH 2 O for the PFM, but its steady flow calibration was
carried out with a 1000-litre min "' rotameter which had been
calibrated on water and not on air. Fisher and Shaw's method
could be used to obtain absolute calibration on air for flows up
to 1000 litre min1 and I hope this will be done. If, as a result, our
original calibration is found to have been seriously in error the
Wright PFM will be adjusted accordingly. It must be remembered, however, that the estimate of PEF with secondary
instruments is an inherently imprecise procedure. The resistance of the PFM modifies the PEF in different and unpredictable ways with different people. For example, the much higher
resistance of the Minimeter does not usually reduce the PEF as
much as would be expected, presumably because of the
flexibility of the airways, whereas it has a marked effect on a
rigid mechanical flow generator of the type used by Fisher and
Shaw. In addition, low PEF cannot often be repeated because
they exhaust the subject, so that calibration in this range will
always be uncertain.
For the time being, therefore, and perhaps for ever, the
Wright PFM scales will continue to be calculated as they are
now.
B.
M.
WRIGHT
Harrow, Middx
REFERENCES
Fisher, J., and Shaw, A. (1980). Calibration of some Wright
peak flow meters. Br. J. Anaesth., 52, 461.
Oldham, H. G., Bevan, M. M., and McDermott, M. (1979).
Comparison of the new miniature Wright peak flow meter
with the standard Wright peak flow meter. Thorax, 34, 807.
Perks, W. H., Tarns, I. P., Thompson, D. A., and Prowse, K.
(1979). An evaluation of the mini-Wright peak flow meter.
Thorax, 34, 79.
Shaw, A., Fisher, J., and Hughes, D. W. (1979). A flow and
volume calibrator for respiratory measuring equipment. J.
Mtd. Eng. Technol., 3, 248.
Wright, B. M. (1978). A miniature Wright peak-flow meter.
Br. Mtd. J., 2, 1627.
McKerrow, C. B. (1959). Maximum forced expiratory
flow rate as a measure of ventilatory capacity. Br. Mtd. J., 2,
1041.
Sir,—We can assure Dr Wright that we did read his paper most
carefully, but our paper was devoted to a constructive appraisal
of meters in present use. However, Dr Wright has raised some
points which should be clarified.
Meters are calibrated when their readings are compared with
a known standard under the same measuring conditions. The
tests described by Dr Wright only compare an individual meter
with another instrument the dynamic calibration of which is
also unknown. As each subject may not produce identical flows
when blowing into the meter and reference instrument,
standardization of measuring conditions is not achieved. Even
if a large number of subjects are used, all that can be said is that
the two instruments appear to give similar overall performances
for that particular group. If healthy subjects are studied, it
cannot be assumed that the correlation still holds good for those
with respiratory deficiencies. Also, substantial discrepancies in
performance may go undetected, for example at low flows.
There is no substitution for proper calibration, for this
enables an instrument's performance to be defined in terms of
accuracy and repeatability.
We cannot comment on the performance of the particular
meters referred to in Wright's original paper. However, we did
calibrate three of the original styled peak flow meters. For these
meters the errors were fairly modest, being ± 10% for flows
greater than 1501itremin"'. These errors were less than the
errors for the 10 restyled and six mini-meters reported by us.
This suggests a deterioration in the calibration over the years.
What matters is the performance of currently produced meters.
Our calibration allows a proper evaluation of this to be
achieved.
Dr Wright suggests that it is all right to disguise the
modifying effect of high resistance meters by alteration of the
scale. This only leads to confusion and will prevent progress in
our understanding of the important relationship between
BRITISH JOURNAL OF ANAESTHESIA
778
pressure and flow during the forced expiratory manoeuvre. It
also breaks a fundamental law of the science of measurement:
that units of measurement such as litre per minute should have
an absolute definition and meaning.
Finally, Dr Wright states that the resistance of the meter has
a marked effect on arigidmechanicalflowgenerator of the type
used by us. This is untrue, for our calibration is independent of
the resistance of the meter under test.
T _
J. FISHER
A. SKA1.1/
Glagow
DOES KETAMINE METABOLITE II EXIST IN
METABOLITE HI
NH-CH 3
R
NH,
r°KETAMINE
/*
NH,
r
I^ • " O H
R
NH,
CONJUGATED
R
N
Duration
of anaesthesia
(min)
Man
VlVOi
Sir,—In their review of the pharmacological properties of
ketamine, Chang and Glazko (1974) postulated a tentative
scheme for the biotransformation of this interesting anaesthetic
agent (fig. 1). An N-demethylation, yielding nor-ketamine
(MI) followed by a hydroxylation of the cyclohexane ring at two
optional positions yields hydroxy-nor-ketamine (Mill and
MIV, respectively). These two metabolites arc then conjugated
and excreted or dehydrated to dehydro-nor-ketamine (Mil).
R^
TABLE I. Concentrations (\wiollitre ') of ketamine, MI and
Mil in simultaneously collected samples ofplasma and c.s.f. in five
rats and one man during steady-state ketamine anaesthesia.
n.d. = not detectable
m
NH,
METABOLITE I
Ketamine
Ccrf
20
60
180
2.8
5.6
6.5
15
20
303
MI
Mil
c.
c«
CP
c«
cr
4.5
9.4
0.2
0.9
1.8
0.6
n.d.
n.d.
n.d.
0.2
0.5
1.2
1.5
1.6
8.4
4.4
3.8
n.d.
n.d.
n.d.
n.d.
n.d.
n.d.
11.0
1.9
3.4
Rat
1
2
3
4
5
70
90
120
21.3
32.1
33.8
27.5
44.4
41.3
48.6
52.5
43.8
13.1
12.7
15.6
25.0
22.5
0.5
7.5
12.0
14.2
diffuse slowly or not at all into the c.s.f., we believe there is a
strong argument for considering Mil as an artefact.
If Mil does not exist in vivo, there is no obvious reason to
postulate the presence of MVII.
If ketamine administration does not result in Mil or MVII in
vivo, man has never been exposed to these compounds unless
given them directly. Consequently, during future research in
this field, administration of Mil and MVII to man should be
carried out with extreme care.
P. STENBERG
METABOUTE I
T
OH
J . IDVALL
CONJUGATED IV
METABOLITE IV
FIG. 1. Postulated biotransformation of ketamine according
to Chang and Glazko (1974).
Following the work of Chang and Glazko, no further basic
research on this topic has appeared in the literature. Their
postulated scheme of biotransformation has been adopted and
reappears, although enlarged, in a recent update by Zsigmond
and Domino (1980). These authors postulated the presence of
another dehydrated metabolite, dehydroketamine (MVII).
In our opinion, there are several reasons to question the in
vivo existence of Mil. Using the bioassay of Chang and Glazko
(1972), we were not able to detect the presence of Mil in
cerebrospinal fluid, while simultaneously collected plasma
samples (man or rat) contained easily determined concentrations of this compound (table I). These experiments included
collections following prolonged anaesthesia times. In contrast,
ketamine and MI were easily determined in c.s.f., with
concentrations amounting to approximately 30-60% of those
seen in plasma even within 15—20min after induction of
anaesthesia. Since there is no obvious reason to believe that
Mil should be less lipophilic or more strongly bound to plasma
proteins than ketamine and MI, other explanations for this
apparent "inhibited diffusibility" of Mil across the
blood-brain barrier have to be considered.
The bioassay utilizes gas-liquid chromatography and includes benzene extraction of a strongly alkalized sample and
subsequent derivatization with heptafluorobutyric anhydride
in the presence of pyridine. Since alpha and betahydroxyketoncssuch as Mill and MIV respectively (and possibly also
their conjugates) would be expected to be converted easily to
Mil under the conditions described, and since there are
reasons to believe that these less lipophilic compounds would
Malmo, Sweden
REFERENCES
Chang, T., and Glazko, A. J. (1972). A gas chromatographic
assay for ketamine in human plasma. Anesthesiology, 36,401.
(1974). Biotransformation and disposition of ketaminc. Int. Anesthesiol. Clin., 12, 157.
Zsigmond, E. K., and Domino, E. F. (1980). Clinical pharmacology and current clinical uses of ketamine. 7th World
Congress of Anaesthcsiologists, Hamburg.
INHALATION OF GASTRIC CONTENTS
Sir,—We report two cases, one fatal, of aspiration pneumonias
following regurgitanon and inhalation of gastric content during
general anaesthesia for emergency evacuation of an incomplete
abortion.
A 24-yr-old African female of average size was admitted at
09.00 h with a septic incomplete abortion. She received
papaveretum 15mg and atropine 0.6 mg i.m. at 14.00 h. The
haemoglobin concentration was 10.5gdl~'. She had starved
for 15h. At 14.30h the patient inhaled pure oxygen for 3min
through a Maplcson A system. Anaesthesia was induced at
14.40 h with Althesin 3 ml and diazepam lOmg i.v. The patient
developed severe laryngospasm. Suxamethonium lOOmg was
injected i.v. to facilitate trachea! intubation. On direct larynoscopy, approximately 15 ml of clear fluid was seen in the
pharynx. After suction, a size 8 mm cuffed trachea] tube was
inserted and the cuff inflated. Endotracheal suction before
ventilation of the lungs revealed no obvious evidence of airway
contamination. Anaesthesia was maintained with 50% nitrous
oxide in oxygen with manual ventilation of the lungs; supplementary suxamethonium was given as required. Steroids were
not administered and neither bronchoscopy nor bronchial toilet
was performed.