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a Address correspondence to this author at: P.O. Box 3015, Duke University Medical Center, Durham, NC 27710. Fax 919-681-7786; e-mail toffa002{at}mc.duke.edu
1 Clinical Laboratories, Department of Pathology, Duke University Medical Center, Durham, NC 27710
To the Editor:
Shepherd and Steinke (1) reported that perflubron emulsion, a potential blood substitute soon to be in clinical use, interferes with measurements by several CO-oximeters. The analyzer affected most was the AVL Omni: at 29 g/L perflubron, oxyhemoglobin was decreased by 12.3%, carboxyhemoglobin was decreased by 3.5%, and methemoglobin was increased by 1.0%. At higher concentrations of perflubron, the AVL Omni gave error messages without results. Although the Radiometer OSM3 Hemoximeter reported results at all concentrations of perflubron studied, it too was affected: at 29 g/L perflubron, oxyhemoglobin was decreased by 5.3%, carboxyhemoglobin was increased by 4.1%, and methemoglobin was increased by 2.3%.
At about the time of this report, we observed that an occasional heparinized blood sample analyzed by the AVL Omni would give a valid total hemoglobin result but report "interference" for the oxy-, carboxy-, and methemoglobin measurements. We associated these results to patients who were receiving Propofol, a sedative used in intensive care settings and administered as a turbid emulsion. In discussions with AVL Scientific Corporation, they believed the interference was attributable to turbidity and had developed an algorithm to correct for turbidity. Because perflubron emulsion is also turbid, we investigated whether the algorithm for the AVL Omni would also correct the interferences caused by perflubron.
We obtained perflubron-based emulsion (600 g/L; product no. AF0144) from Alliance Pharmaceutical Corporation, San Diego, CA. The blood gas and CO-oximeter analyzers were an AVL Omni 9 blood gas analyzer and a CO-oximeter from AVL Scientific, and a Radiometer OSM3 hemoximeter attached to an ABL 505 blood gas analyzer from Radiometer America.
To heparinized whole blood samples from patients in operating rooms or intensive care, we added perflubron within 5 min after the sample was analyzed for blood gases. We anaerobically transferred 0.2 mL of either saline or perflubron mixed with saline to 0.8 mL of each sample of whole blood to give final perflubron concentrations of 10, 30, 40, and 60 g/L. Each specimen was kept thoroughly mixed. We made no other adjustments to the samples, which had PO2 values ranging from 5.1 to 30.7 kPa (38 to 231 mmHg) and oxyhemoglobin values of 87–98%. The difference in the CO-oximeter or blood gas results between the sample mixed with saline and the same sample mixed with perflubron was used to determine the analytical effects of perflubron.
To minimize changes in the sample during the analyses, we analyzed individual blood samples to which we added saline and perflubron rather than a series of samples prepared from a larger pool of blood. With only ~2 mL of blood available in each leftover sample, we used 60 different samples for the study: 15 different blood samples for each of the four concentrations of perflubron studied.
We used the paired t-test to determine the significance of differences in means between results for samples with saline and those with perflubron (2).
The use of perflubron has the therapeutic effect of both replacing blood volume and supplementing the oxygen and carbon dioxide transport capabilities of blood. The concentrations of perflubron we studied covered the range expected in clinical practice. Based on an expected dosage of 0.9–2.7 g of perflubron per kilogram of body weight, the concentration of perflubron in blood is estimated to be 10–40 g/L (1).
Perflubron up to 40 g/L produced no significant changes in the
blood gas or CO-oximeter measurements on the AVL (Table 1
). At 60 g/L, all changes were statistically significant (all
P values <0.005), and changes for pH,
PCO2,
PO2, hematocrit, and total
hemoglobin were greater than the SDs of the respective methods. These
differences at 60 g/L represent changes of marginal clinical
significance.
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Our results on the Radiometer OSM3 (not shown) confirmed the reported effects (1) on oxyhemoglobin, carboxyhemoglobin, and methemoglobin.
The algorithm for turbidity correction has been incorporated in our analyzers for nearly 1 year. With this algorithm in place, we have had only two or three samples that have given error messages. Therefore, we conclude that this algorithm has significantly improved the ability of the AVL Omni to report valid CO-oximeter data in turbid samples and has virtually eliminated the effect of perflubron emulsion in blood at concentrations up to 40 g/L.
Acknowledgments
We appreciate the help of Shari Morgan and Dr. Peter Keipert of Alliance Pharmaceutical Corporation for providing the perflubron emulsion used in this study. We also appreciate the information provided by Dr. A. P. Shepherd regarding his protocol. Dr Toffaletti receives funding for research from AVL Scientific Corporation.
References
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