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Hypoxemia During Extreme Hyperleukocytosis: How Spurious? Andry Van De Louw MD Phd, Ruchi J Desai MD, Coursen W Schneider MD, and David F Claxton MD

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Hypoxemia During Extreme Hyperleukocytosis: How Spurious? Andry Van De Louw MD Phd, Ruchi J Desai MD, Coursen W Schneider MD, and David F Claxton MD Hypoxemia During Extreme Hyperleukocytosis: How Spurious? Andry Van de Louw MD PhD, Ruchi J Desai MD, Coursen W Schneider MD, and David F Claxton MD BACKGROUND: Spurious hypoxemia has been described in case reports during extreme hyper- leukocytosis and has led to recommendations for immediate cooling and analysis of arterial blood gases (ABGs). We sought to determine, in samples processed as recommended, the magnitude of spurious hypoxemia in acute leukemia subjects with hyperleukocytosis. METHODS: A retrospec- tive chart review was conducted of all subjects admitted between 2003 and July 2014 for acute leukemia, who presented with white blood cell (WBC) count > 50 ؋ 109 cells/L and had ABGs performed. For each ABG, we collected P ,S , simultaneous WBC count, and S when aO2 aO2 pO2 available. Bland and Altman analysis was used to assess the agreement between S and S . pO2 aO2 RESULTS: One-hundred forty-six samples (from 45 subjects) were included, of which 57 samples ,from 18 subjects) had data available for Bland and Altman analysis. Mean (S ؊ S ) was 2.5%) pO2 aO2 and 95% CI for limits of agreement between S and S was (؊10.1,15.1)%. The mean pO2 aO2 S –S ) was significantly higher for WBC count > 100 ؋ 109/L as compared with WBC) pO2 aO2 and the 95% CIs for limits of agreement were ,(04. ؍ count < 100 ؋ 109/L (3.8% vs 0.4%, P whereas the ,(0.19 ؍ ؊10.3,18)% versus (؊7.9,8.6)%. S and S were poorly correlated (r2) pO2 aO2 Overall, 11 of 19 samples .(0.44 ؍ difference (S –S ) was fairly correlated with WBC count (r2 pO2 aO2 with WBC count > 150 ؋ 109/L had P < 55 mm Hg whereas S was > 94%, the proportion being aO2 pO2 of 62 samples for WBC count < 150 ؋ 109/L (P < .001). Three subjects with WBC count > 150 ؋ 109/L 5 exhibited large S to S differences (10–20%) before leukapheresis, which decreased to below 5% pO2 aO2 afterward. CONCLUSIONS: In subjects with acute leukemia and hyperleukocytosis, despite cooling and quickly analyzing the samples, we observed poor correlation and agreement between S and S , pO2 aO2 unacceptably low for WBC count > 100 ؋ 109/L. Our results suggest that current guidelines may not totally prevent the diagnosis of spurious hypoxemia. Key words: hypoxemia; blood gas analysis; leukocy- tosis; acute leukemia; oximetry; oxygen. [Respir Care 2016;61(1):8–14. © 2016 Daedalus Enterprises] Introduction vival but is also associated with increased early mortality, due to cerebral and pulmonary leukostasis.2 Patients re- Between 10 and 30% of patients newly diagnosed with quiring ICU admission and mechanical ventilation for acute acute leukemia present with hyperleukocytosis, usually de- respiratory failure have an overall poor survival3,4; thus, fined as a white blood cell (WBC) count Ͼ 100 ϫ 109/L.1 the respiratory status of acute leukemia patients with hy- Hyperleukocytosis not only negatively impacts overall sur- perleukocytosis is a major concern. In acute leukemia, early detection of pulmonary com- promise may prompt invasive intervention aimed at de- Dr Van de Louw is affiliated with the Division of Pulmonary and Critical creasing WBC count (leukapheresis) or improving gas ex- Care Medicine, Drs Desai and Schneider are affiliated with the Depart- change (mechanical ventilation). As clinical signs and chest ment of Internal Medicine, and Dr Claxton is affiliated with the Division x-ray findings may be subtle in immunocompromised hosts, of Hematology and Oncology, Penn State Milton S Hershey Medical Center and College of Medicine, Hershey, Pennsylvania. the assessment of patient‘s oxygenation via arterial blood gas (ABG) measurement and/or pulse oximetry is crucial. The The authors have disclosed no conflicts of interest. finding of artifactual decrease in P due to increased oxy- aO2 Correspondence: Andry Van de Louw MD PhD, Division of Pulmonary gen consumption by WBCs in collected samples, has been and Critical Care Medicine, Milton S Hershey Medical Center, 500 Uni- 5 versity Drive, Hershey, PA 17033. E-mail: [email protected]. described and referred to as spurious hypoxemia. A clini- cally relevant decay in P may occur as soon as 2 min in aO2 DOI: 10.4187/respcare.04196 samples with WBC count as low as 55 ϫ 109/L and seems 8RESPIRATORY CARE • JANUARY 2016 VOL 61 NO 1 HYPOXEMIA DURING EXTREME HYPERLEUKOCYTOSIS proportional to WBC count.5 Several case reports have been published,6-9 but other authors have emphasized that the hy- QUICK LOOK poxemia observed during hyperleukocytosis might actually Current knowledge be real and reflect subtle pulmonary leukostasis.10 Published data come from small series, but no study has ever system- Patients newly diagnosed with acute leukemia may pres- ent with hyperleukocytosis, usually defined as a white atically investigated the reliability of PaO and SaO in this 2 2 Ͼ ϫ 9 setting, probably because of the relative rarity of extreme blood cell (WBC) count 100 10 /L. The finding of artifactual decrease in PaO , due to increased oxygen hyperleukocytosis. Although the American Association for 2 consumption by WBCs in collected samples, has been Respiratory Care (AARC) has recommended immediate cool- described in this population and referred to as spurious ing and analysis of ABG for hyperleukocytic patients,11 these hypoxemia. A clinically relevant decay in PaO may guidelines rely on limited data, and their effect on the mag- 2 occur as soon as 2 min in samples with WBCs as low nitude of spurious hypoxemia has never been evaluated. as 55 ϫ 109/L and seems proportional to WBC count. SEE THE RELATED EDITORIAL ON PAGE 119 What this paper contributes to our knowledge In a retrospective review of acute leukemia subjects Given the limited published data, we included a large with hyperleukocytosis, despite cooling and quickly an- series of acute leukemia subjects with hyperleukocytosis alyzing the samples, there was poor correlation and in this retrospective study and systematically assessed (1) agreement between SpO and SaO , unacceptably low for the relationship between P ,S , and WBC count and Ͼ ϫ 2 9 2 aO2 aO2 WBC count 100 10 /L. These results suggest that (2) the agreement between S and S in cooled and aO2 pO2 current guidelines may not always prevent the diagno- quickly analyzed ABG. sis of spurious hypoxemia. Methods This retrospective study was approved by the Pennsyl- vania State University College of Medicine Institutional Statistical Analysis Review Board (IRB number 00000374), and informed con- Ϯ sent was waived. All results were reported as mean SD (SPSS 20, SPSS, Chicago, Illinois). To assess the agreement between S and aO2 S , we used the method described by Bland and Altman,13 Subjects pO2 calculating the mean difference (bias, d) and the SD of the The charts of all subjects admitted to our institution with a differences (precision, s) between S and S and the 95% pO2 aO2 newly diagnosed acute leukemia between January 2003 and CIs for limits of agreement between S and S (d Ϯ 2s). pO2 aO2 July 2014 were screened, and all subjects with at least one We used the 2-tailed Student t test to compare the bias, mean ABG performed with a concomitant hyperleukocytosis (WBC arterial pressure, and heart rate between samples with a WBC count Ͼ 50 ϫ 109/L) were included for further analysis. count below versus above 100 ϫ 109/L. A 2-tailed Fisher exact test was used to compare the proportion of cases with Data Collected hypoxemia (P Ͻ 55 mm Hg) and vasopressor requirements aO2 between samples with WBC below or above 100 ϫ 109/L, Baseline demographic data, significant comorbidities, type respectively. Analysis of variance for repeated measures was of acute leukemia, the use of invasive or noninvasive me- used to assess the effect of leukapheresis on (SpO –SaO ) chanical ventilation during admission, and 28-d and 6-month 2 2 differences. P Ͻ .05 was considered statistically significant. survival were collected. Whenever an ABG and a complete blood count were performed simultaneously, we collected Results P ,S , and WBC count, along with S recorded at the aO2 aO2 pO2 same time, when available. Mean arterial pressure, heart rate, Subjects and vasopressor requirements (yes/no) at the time of ABG were also recorded. As per hospital policy, ABGs were col- Of 874 patients admitted during the 111⁄2 year period lected in plastic syringes, stored in ice, and immediately sent with a newly diagnosed acute leukemia, 45 subjects were (via pneumatic tube system) and processed in the laboratory, included in this analysis. In total, these subjects had 146 in agreement with published recommendations.12 The type of simultaneous complete blood counts and ABGs performed. oxygen or ventilatory support was recorded as follows: no ox- All subjects had acute myeloid leukemia, and 6 had the ygen requirement, oxygen on nasal cannula, high-flow oxygen acute promyelocytic leukemia subtype. None of the 63 device (high-flow nasal cannula, Venturi mask), noninvasive patients with hyperleukocytic acute lymphoblastic leukemia mechanical ventilation, invasive mechanical ventilation. had an ABG performed. Baseline demographic, clinical, and RESPIRATORY CARE • JANUARY 2016 VOL 61 NO 19 HYPOXEMIA DURING EXTREME HYPERLEUKOCYTOSIS Table 1. Demographic, Clinical, Biological, and Survival Data for the 45 Subjects Parameters Values Age, y 60.0 Ϯ 12.9 Sex, male/female 25/20 Comorbidities, n Congestive heart failure 1 Coronary artery disease 7 Hypertension 20 Diabetes 10 Obstructive sleep apnea 5 COPD 3 Chronic liver disease 0 Chronic kidney disease 1 Fig. 1. Bland and Altman representation of the agreement between S and S . For the 57 samples (18 subjects), (S –S ) was Previous cancer 6 pO2 aO2 pO2 aO2 plotted on the Y axis versus (S ϩ S )/2 on the X axis.
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