pulse oximetry is used almost universally in the management of critically ill patients in the intensive care unit and operating theatre .
its uses include the detection of hypoxia , avoidance of hyperoxia , reduction in the frequency of blood gas analysis , titration of fractional inspired oxygen   and for weaning from mechanical ventilation .
an arterial oxygen saturation ( sao2 ) of 90% has been proposed as a target for adequate oxygenation during mechanical ventilation .
previous studies investigating the use of the pulse oximeter oxygen saturation ( spo2 ) in intensive care patients have reported that the minimum spo2 levels to maintain sao2 at 90% range between 92% and 96 % .
however , these studies have not answered the question of whether , after achieving a target sao2 , a subsequent change in spo2 predicts a corresponding change in sao2 in the critically ill .
some studies have reported that anaemia reduces the precision of pulse oximetry   by increasing the signal to noise ratio with low haemoglobin concentrations , whereas others failed to demonstrate this phenomenon .
the in vitro method employed by the carbon monoxide ( co)-oximeter requires red blood cell lysis , whereas the pulse oximeter analyzes haemoglobin in whole blood .
the difference between intracellular and extracellular hydrogen ion concentrations under normal physiological conditions has been incorporated into the pulse oximeter algorithms .
however , the robustness of this adjustment has not been evaluated in the critically ill and acidotic patient .
we therefore conducted a prospective observational study to test the hypothesis that a change in spo2 would predict an equivalent change in sao2 .
such a relation , if it exists , would be invaluable in deciding when to titrate fractional inspired oxygen and/or repeat arterial blood gases in the individual patient . furthermore , we examined the effects of anaemia and acidosis on the precision of using the pulse oximeter to predict the sao2 in a heterogeneous group of critically ill patients .
this study was considered by the local research and ethics committee and the need for informed consent was waived in view of the observational nature of the study . during a 2-month period all patients admitted to our intensive care unit ( icu ) who had an arterial line for the measurement of blood gases and who were being monitored by continuous pulse oximetry were recruited .
the following patients were excluded : those with significant jaundice ( bilirubin > 40 mol / l ) or a history of smoke inhalation ; those with an inadequate spo2 trace ( as determined by visual analysis of a flat , absent , or irregular signal waveform ) ; and those in whom fewer than two arterial blood gas readings were taken .
serial arterial blood gas samples were taken after 5 ml blood had been discarded when indicated as part of routine clinical care .
no samples were taken solely for the study nor was any attempt made to vary inspired oxygen concentration or mechanical ventilation for the purposes of the study .
arterial blood gas samples were analyzed using a co - oximeter ( abl725 , radiometer , copenhagen , denmark ) that was calibrated daily by laboratory staff and has a 2-hourly automatic internal calibration sequence .
haemoglobin concentration ( g / dl ) , hydrogen ion concentration ( nmol / l ) , and percentage sao2 were recorded for each sample .
precision and accuracy of a whole blood sample for sao2 , hydrogen ion concentration and haemoglobin concentration are 0.3 and 0% , 0.034 and 0.008
nmol / l , and 0.12 and 0.4 g / dl , respectively , within a haemoglobin range of 520 g / dl .
pulse oximetry readings were recorded simultaneously with blood gas sampling using a nellcor ( puritan bennett , pleasanton , nj , usa ) finger probe attached to a hewlett packard ( palo alto , ca , usa ) merlin monitor .
the pulse oximeter displays an average spo2 from the preceding 5-s beat by beat analysis .
the measurements between healthy individuals ( n= 12 ) had a coefficient of variation of 0.4% at a spo2 of 97% .
probes were attached to a finger , choosing the digit that gave the best trace and but not necessarily on the arm from which the arterial blood gas sample was drawn .
data were stored using microsoft excel 97 and analyzed using sigmastat for windows 95 ( spss inc .
chicago , il , usa ) and glim ( generalized linear interactive modeling ) version 4 , update 8 ( royal statistical society , london , uk ) , running on a dec alpha axp mainframe computer under the ultirx operating system ( osf/1 ) .
the linear relations between differences in two successive measurements of spo2 and sao2 in all patients were analyzed using pearson correlation coefficient ( r ) , linear regression and goodness - of - fit ( adjusted r ) .
the variations between and within the patients were examined using comparisons of the residual standard deviations ( sds ) between a single line from a common slope through all the changes for all 41 patients and a separate line to each patient .
the effects of anaemia and acidosis on the agreement between the two measurement techniques were examined using a bland 
altman plot   in which the difference between spo2 and sao2 was plotted against their average .
bias was calculated as the mean of the differences between the co - oximeter and pulse oximeter readings ( sao2spo2 ) .
positive bias indicated that the pulse oximeter underestimated the sao2 , whereas negative bias indicated that the pulse oximeter was overestimating the sao2 .
the limits of agreement were taken as the bias  ( 1.96  sd ) .
approximately 95% of data fell within the haemoglobin concentration range 811.9 g / dl and the hydrogen ion concentration range 2562.9 nmol / l ( ph7.27.6 ) . therefore , haemoglobin concentrations  7.9 or  12 g / dl or hydrogen ion concentrations  63
the differences of biases between these three groups were analyzed using one - way , repeated measure analysis of variance .
data were stored using microsoft excel 97 and analyzed using sigmastat for windows 95 ( spss inc .
chicago , il , usa ) and glim ( generalized linear interactive modeling ) version 4 , update 8 ( royal statistical society , london , uk ) , running on a dec alpha axp mainframe computer under the ultirx operating system ( osf/1 ) .
the linear relations between differences in two successive measurements of spo2 and sao2 in all patients were analyzed using pearson correlation coefficient ( r ) , linear regression and goodness - of - fit ( adjusted r ) .
the variations between and within the patients were examined using comparisons of the residual standard deviations ( sds ) between a single line from a common slope through all the changes for all 41 patients and a separate line to each patient .
the effects of anaemia and acidosis on the agreement between the two measurement techniques were examined using a bland 
altman plot   in which the difference between spo2 and sao2 was plotted against their average .
bias was calculated as the mean of the differences between the co - oximeter and pulse oximeter readings ( sao2spo2 ) .
positive bias indicated that the pulse oximeter underestimated the sao2 , whereas negative bias indicated that the pulse oximeter was overestimating the sao2 .
the limits of agreement were taken as the bias  ( 1.96  sd ) .
approximately 95% of data fell within the haemoglobin concentration range 811.9 g / dl and the hydrogen ion concentration range 2562.9 nmol / l ( ph7.27.6 ) .
therefore , haemoglobin concentrations  7.9 or  12 g / dl or hydrogen ion concentrations  63 nmol / l were regarded in the study as extremes .
the differences of biases between these three groups were analyzed using one - way , repeated measure analysis of variance .
forty - one ( 22 male ) patients ( age [ mean  sd ] 70  14 years ) were recruited into the study .
a total of 1132 simultaneous arterial blood gas and pulse oximeter readings were taken ( mean [ range ] 27 [ 391 ] readings per patient ) .
sequential readings in each patient were grouped together into pairs , which gave 1085 paired readings ( 47 readings were excluded because they were either not paired or unidentifiable to a particular patient , or the patient had fewer than two readings taken ) .
these data were analyzed to determine the relation between changes in spo2 ( spo2 ) and changes in sao2 ( sao2 ) .
the mean  sd for spo2 was 94.6  2.7% and the mean for sao2 was 95.9  2.4% . in terms of predicting sao2 from spo2 , fitting a single line from all the 41 patients , gives a residual sd of 1.303 and fitting a separate line to each patient gives a residual sd of 1.288 ( p = 0.999 ) .
although we found moderate correlation between spo2 and sao2 ( r = 0.606 ; p < 0.01 ; fig .
1 ) , only 36.7% of the variation in this relation was due to the association of changes in spo2 with changes in sao2 ( adjusted r= 0.367 ) . the prediction of sao2 from spo2 ( sao2 = 0.003 + 0.477 spo2 ) demonstrates that the pulse oximeter overestimates actual changes in sao2 .
the 1085 simultaneous arterial blood gas and pulse oximeter readings from the 41 patients were analyzed to determine the effects of anaemia and acidosis on bias and limits of agreement .
for the data altogether , the bias was 1.34 and the limits of agreement were -2.29 and + 4.97 ( fig .
there were only small changes in bias with anaemia ( + 2.09 ) and acidosis ( + 0.38 ) , as shown in table 1 .
the difference in bias between hydrogen ion concentrations of 2563 nmol / l and  63 nmol / l ( p < 0.01 ) , and between haemoglobin concentrations of < 8 g / dl , 811.9 g / dl and > 12 g / dl ( p < 0.01 ) all achieved statistical significance .
the bias was not significantly different between haemoglobin concentrations of < 7.9 g / dl and 811.9 g / dl ( p= 0.24 ) .
there were insufficient numbers in the group with hydrogen ion concentration < 24.9 nmol / l ( n= 10 ) for analysis to be done .
the present study shows that changes in spo2 do not reliably predict equivalent changes in sao2 , with the pulse oximeter tending to overestimate actual changes in sao2 .
we also showed that spo2 underestimates sao2 to a greater extent with progressive anaemia , whereas acidosis increases the spo2 estimate of sao2 .
the titration of fractional inspired oxygen during weaning from mechanical ventilation is frequently adjusted with the goal of maintaining a target spo2 value .
jubran , in a study involving 54 icu patients , reported that levels of spo2 of 92% in white patients and 95% in black patients maintained arterial oxygen tension at 8 kpa or greater in 92% and 85% of patients , respectively .
seguin   defined a minimum spo2 of 96% to ensure that no patients had a sao2 below 90% .
this approach avoided hypoxia , but 15% of patients had a sao2 of 98% or greater .
although target values can be helpful , it would be valuable to know whether a change in spo2 would predict a similar change in sao2 in critically ill patients over time .
hypothetically , the relatively static patient factors that interfere with pulse oximetry ( skin colour , finger size , carboxyhaemoglobin , methaemoglobin ) do not change , and so the correlation between changes in sao2 and spo2 might be expected to be closer than that between absolute values from a mixed patient population .
this could allow individualized target spo2 to be set , based on a single , one - off sao2 reading .
only one small study has attempted to address this question in the intensive care setting . in a series of 45 patients ( 135 measurements ) ,
van de louw and coworkers   recently reported that changes in spo2 could not accurately predict changes in sao2 .
the prediction of sao2 from spo2 ( sao2 = 0.003 + 0.477spo2 ) demonstrates that , on average , the pulse oximeter overestimates actual changes in sao2 .
this suggests that a similar degree of caution is required in interpreting changes in pulse oximetry in the critically ill as in one - off readings .
progressive reductions in haemoglobin concentration may reduce the precision of the pulse oximeter as the signal : noise ratio from surrounding tissue increases .
early studies examining the effects of anaemia on the precision of the pulse oximeter found reduced precision in association with anaemia .
lee and coworkers   demonstrated a deterioration in bias and precision in dogs with a haematocrit below 10% , and severinghaus and coworkers   reported increased error in anaemic humans when the sao2 was less than 75% . in contrast , case reports have described cases in which the pulse oximeter remained precise at haemoglobin concentrations of 2.7 g / dl   and 3.0 g / dl .
a subsequent case series of 17 patients with acute anaemia due to haemorrhage ( haemoglobin concentration 2.38.7 g / dl ) did not detect any deterioration in the accuracy of measurements using the pulse oximeter in the absence of hypoxia .
our study did not include sufficient numbers with hypoxia ( spo2 < 90% ) for the influence of anaemia on bias and precision to be studied in this patient group . however , under normal physiological conditions ( spo2 > 90% ) our results support and extend previous findings in demonstrating that anaemia has only a minor impact on the precision of measurements using the pulse oximeter .
our data show that , in the presence of acidosis , the degree to which spo2 underestimates sao2 was reduced . one possible explanation for this finding may relate to the differences in the techniques used for measuring oxygen saturation .
the pulse oximeter analyzes haemoglobin saturation in whole blood in vivo , whereas sao2 measured by co - oximetry requires red blood cell lysis prior to analysis . under normal physiological conditions , algorithms incorporated in the pulse oximeter account for this ,
although the validity of this adjustment has not been tested outside normal physiological ranges . alternatively , the effects of the complex interactions between cardiac output , systemic vascular resistance , temperature   and vasoactive drugs   on precision of measurements using the pulse oximeter might have contributed to this finding . a further study looking at the precise contribution of each of these factors would be required to elucidate the aetiology of these findings definitively .
there are several potential confounding variables that were not controlled for in the study design .
first , like in other studies , we did not analyze the influence of carboxyhaemoglobin and methaemoglobin concentrations on bias and precision .
the pulse oximeter is unable to distinguish between these two forms of haemoglobin and oxyhaemoglobin , leading it to overestimate the actual sao2 if significant concentrations of either are present .
we excluded patients with a history of smoke inhalation , in whom carboxyhaemoglobin levels may be high . in nonsmokers
carboxyhaemoglobin levels are normally less than 2% and methaemoglobin levels are less than 1%    levels that are already accounted for by the built - in algorithms of pulse oximeters . in cigarette smokers carboxyhaemoglobin is initially elevated ( average 4.78% ) but falls over time ( half life 56 hours ) .
the clearance of carboxyhaemoglobin is also accelerated by ventilation . because most patients had been ventilated for several hours before entry into the study
we excluded patients with significant jaundice  a group known to have high carboxyhaemoglobin levels    in order to minimize this potential error , and no patients were admitted following smoke inhalation during the study period .
anaemia and acidosis have not been found to influence car - boxyhaemoglobin or methaemoglobin concentrations .
although we believe that the influence of carboxyhaemoglobin levels in the study was minimal , we are unable to rule it out as a potential confounding variable .
second , we did not classify patients according to skin colour or race , which may impact on accuracy of the pulse oximeter . because skin colour is constant , comparisons of changes in spo2 are unlikely to have been affected .
data for the assessments for bias and precision caused at the extremes of anaemia and acidosis were collected from 19 and 14 patients , respectively , and there did not appear to be any systematic difference in the groups ' racial composition from that in the overall study population .
no patients to our knowledge had sickle cell anaemia / trait , although this was not specifically tested for .
third , the mean spo2 reading for the total data was 94.6% , with a corresponding sao2 value of 95.9% .
this is consistent with previous investigators ' recommendations for minimal target values for spo2 during mechanical ventilation .
however , less than 5% of data fell in the range of spo2 levels below 90% .
this is consistent with a worsening of bias and precision with pulse oximetry when the sao2 is less than 90% . at lower saturations the effects of anaemia and acidosis
may become more prominent , and our results should therefore be applied with caution in this situation .
finally , the pulse oximeter presents spo2 data as integers whereas the co - oximeter presents sao2 data to 1 decimal place . with over 1000 data points , it is likely that the oximeter rounded up and rounded down a similar number of times , and so these differences will most likely cancel each other out . at most ,
the maximum differences due to the measurement of spo2 in integers will account for less than 1% of the observed bias as compared with sao2 .
in conclusion , in a heterogeneous group of icu patients , we showed that changes in pulse oximetry do not reliably predict equivalent changes in sao2 .
we also demonstrated that neither anaemia nor acidosis alters the precision of measurements between the nellcor pulse oximeter and co - oximeter to any clinically important extent .
the pulse oximeter remains a valuable tool in the care of intensive care patients , but an awareness of its limitations is an important component of enhancing the quality of care .
 changes in spo2 do not reliably predict equivalent changes in sao2 in the critically ill  anaemia and acidosis have only a minor influence on the precision of measurements of spo2 and sao2
icu = intensive care unit ; sao2 = arterial oxygen saturation ; sd = standard deviation ; spo2 = pulse oximeter oxygen saturation .
linear relations between changes in pulse oximeter oxygen saturation ( spo2 ) and arterial oxygen saturation ( sao2 ) . bland and altman plot for bias and limits of agreement for total data .
the effects of anaemia and acidosis on bias and limits of agreement p < 0.01 , versus * haemoglobin > 12 g / dl , haemoglobin < 8 g / dl , haemoglobin 812 g / dl and hydrogen 2563 nmol / l .
 introductionthis study investigates the relation between changes in pulse oximeter oxygen saturation ( spo2 ) and changes in arterial oxygen saturation ( sao2 ) in the critically ill , and the effects of acidosis and anaemia on precision of using pulse oximetry to predict sao2.patients and methodsforty - one consecutive patients were recruited from a nine - bed general intensive care unit into a 2-month study . 
 patients with significant jaundice ( bilirubin > 40 mol / l ) or inadequate pulse oximetry tracing were excluded.resultsa total of 1085 paired readings demonstrated only moderate correlation ( r= 0.606 ; p < 0.01 ) between changes in spo2 and those in sao2 , and the pulse oximeter tended to overestimate actual changes in sao2 . 
 anaemia increased the degree of positive bias whereas acidosis reduced it . 
 however , the magnitude of these changes was small.conclusionchanges in spo2 do not reliably predict equivalent changes in sao2 in the critically ill . 
 neither anaemia nor acidosis alters the relation between spo2 and sao2 to any clinically important extent . 
Introduction
Patients and methods
Statistical analysis
Results
Discussion
Conclusion
Competing interests
Key messages
Abbreviations
Acknowledgement
Figures and Tables