Spurious hypoxemia, a pre-analytical error of blood gas analysis examined

Blood gas analysis provides the means for assessing patient oxygenation status by measurement of two parameters: the partial pressure of oxygen in arterial blood (pO₂(a)) and % oxygen saturation of hemoglobin in arterial blood (sO₂(a)).

Most accurate reflection of in vivo pO₂(a) and sO₂(a)  requires that measurement be made as soon as is practically possible after blood collection, because oxygen continues to be consumed by blood cells - most notably white blood cells (leukocytes) and platelets - after sampling.

The rate of this in-vitro oxygen consumption is a function of the number of metabolically active blood cells in the sampled blood, and the time and temperature the sample is stored between collection and measurement. (Maintaining blood samples at 0OC rather than at room temperature inhibits cellular metabolism, and thereby the rate of in-vitro oxygen consumption).

This provides the rationale for the recommendation that for most accurate measurement of pO₂(a) and sO₂(a), blood gas analysis should be performed within 15 minutes of blood collection if the sample is maintained at room temperature, but if measurement is likely to be delayed beyond 15 minutes, the sample should be stored on ice.

The phenomenon of in-vitro oxygen consumption poses a particular problem for accurate measurement of pO₂(a) and sO₂(a) among patients with haematological malignant disease, who can have extremely high white cell counts (extreme hyperleukocytosis) and/or extremely high platelet counts (extreme thrombocytosis).

For this very small subset of patients who require blood gas analysis, the rate of in-vitro oxygen consumption consequent on the massively increased concentration of blood cells is so high that it can result in spurious hypoxemia (falsely marked reduction in pO₂(a) and sO₂(a)), even if samples are handled in the recommended way.

In order to combat the potential problem of spurious hypoxemia, it is recommended that samples from patients with extreme hyperleukocytosis and/or extreme thrombocytosis be placed on ice immediately after they are taken and analyzed without delay.

According to the authors of a recently published study, this advice has never been systematically evaluated.

They designed this retrospective study to provide an answer to the question:

Is spurious hypoxemia among patients with very high blood cell counts avoided by placing the samples on ice and analyzing them without delay?

Investigators interrogated hospital records dating back 11.5 years (2003-2014) to identify all patients with acute leukaemia who had arterial blood gas performed at the time they had a very high white cell count (> 50x109/L).

Inclusion in the study required that the patient’s oxygen status was being monitored by pulse oximetry at the time blood for gas analysis was sampled, so that two contemporaneous oxygen saturation values were available: one (SpO₂) by pulse oximetry, which is unaffected by high white cell count, and the other (sO₂(a)) by blood gas analysis.

The retrieval process revealed the blood gas results (pO₂(a), sO₂(a)) and white cell count of 57 blood samples (with concurrent SpO₂ values) from 18 patients.

In accordance with expert recommendation, all samples for blood gas analysis had been treated as per hospital protocol for patients with hyperleukocytosis (i.e. iced and analyzed without delay).

Analysis of retrieved data revealed poor correlation between the SpO₂ and sO₂(a)   (r= 0.19). Mean difference (SpO₂ – sO₂(a)) was relatively small, just 2.5 %; but 95 % limits of agreement were wide (-10 % to + 15 %).

A better correlation (r=0.44) was found when difference (SpO₂ – sO₂(a)) was plotted against white cell count. The higher the white cell count, the greater was the difference between the two measures of oxygen saturation (SpO₂ > sO₂(a)).

The poor agreement between sO₂(a) and SpO₂ was thus directly related to the severity of the hyperleukocytosis. In the absence of spurious hypoxemia, agreement between the two measures of oxygen saturation would be expected; SpO₂ usually reflects pO₂(a) and its actual value approximates to sO₂(a).

This agreement was clearly not evident in study results, allowing the authors to conclude that current recommendations for avoidance of spurious hypoxemia among patients with hyperleukocytosis may not always be effective.

In discussion of their study, the authors concede that because of the logistics of blood gas analysis at their hospital, there was an inevitable delay of approximately 10-15 minutes between sampling and measurement due to sample transport to the laboratory.

Results of this study may have been different if blood gases had been measured immediately after the sample was collected at the patient’s bedside. 

A useful accompanying editorial places the problem of spurious hypoxemia in a wider context by discussing, more generally, the sources of pre-analytical errors in blood gas analysis, other than an extreme increase in the number of blood cells.