Scientific Letter
Real and spurious hypoxemia in a patient with extreme hyperleukocytosis
Hipoxemia real y espuria en un paciente con hiperleucocitosis extrema
M. Angulo
, D. Machado, L. Larrosa, A. Biestro
Corresponding author
Cátedra de Medicina Intensiva, Hospital de Clínicas, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay
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Ambas muestras fueron extraídas al mismo tiempo (FiO<span class="elsevierStyleInf">2</span> 1, leucocitosis 688.000 células/μl). Se realizó análisis gasométrico inmediatamente después de la extracción y posteriormente a los 15 y 30<span class="elsevierStyleHsp" style=""></span>min.</p> <p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">FiO<span class="elsevierStyleInf">2</span>: fracción inspirada de oxígeno; PaO<span class="elsevierStyleInf">2</span>: presión parcial de oxígeno en sangre arterial; T. ambiente: temperatura ambiente.</p>" ] ] ] "autores" => array:1 [ 0 => array:2 [ "autoresLista" => "M. Angulo, D. Machado, L. Larrosa, A. Biestro" "autores" => array:4 [ 0 => array:2 [ "nombre" => "M." "apellidos" => "Angulo" ] 1 => array:2 [ "nombre" => "D." "apellidos" => "Machado" ] 2 => array:2 [ "nombre" => "L." "apellidos" => "Larrosa" ] 3 => array:2 [ "nombre" => "A." 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Angulo, D. Machado, L. Larrosa, A. Biestro" "autores" => array:4 [ 0 => array:4 [ "nombre" => "M." "apellidos" => "Angulo" "email" => array:1 [ 0 => "martin.angulo@hc.edu.uy" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "<span class="elsevierStyleSup">*</span>" "identificador" => "cor0005" ] ] ] 1 => array:2 [ "nombre" => "D." "apellidos" => "Machado" ] 2 => array:2 [ "nombre" => "L." "apellidos" => "Larrosa" ] 3 => array:2 [ "nombre" => "A." "apellidos" => "Biestro" ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Cátedra de Medicina Intensiva, Hospital de Clínicas, Facultad de Medicina, Universidad de la República, Montevideo, Uruguay" "identificador" => "aff0005" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Hipoxemia real y espuria en un paciente con hiperleucocitosis extrema" ] ] "resumenGrafico" => array:2 [ "original" => 0 "multimedia" => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 738 "Ancho" => 1573 "Tamanyo" => 69181 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Progression of leukocytosis and PaO<span class="elsevierStyleInf">2</span>/FiO<span class="elsevierStyleInf">2</span> at the ICU. ICU, intensive care unit; PaO<span class="elsevierStyleInf">2</span>/FiO<span class="elsevierStyleInf">2</span>, correlation between partial pressure of oxygen in arterial blood and fraction of inspired oxygen; WBC, white blood cell count.</p>" ] ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Hyperleukocytosis can cause respiratory failure due to pulmonary leukostasis. Additionally, gas tests can confirm the presence of pseudo-hypoxemia and the patient may end up receiving unnecessary treatments if undiagnosed.</p><p id="par0010" class="elsevierStylePara elsevierViewall">We hereby present the case of a 25-year-old male with chronic myeloid leukemia (CML) diagnosed 10 years ago and with poor adherence to medical treatment. The patient was admitted to the ER with asthenia and adynamia of 2-week duration complicated with dyspnea over the last 24<span class="elsevierStyleHsp" style=""></span>hours. The patient remained apyretic and lucid during the physical examination with polypnea at 29<span class="elsevierStyleHsp" style=""></span>rpm, diffuse crepitant rattle, and pulse oximetry (SpO<span class="elsevierStyleInf">2</span>) values no less than 90% with oxygen therapy through a low-flow face mask. Hemodynamically stable. Distended abdomen, hepatomegaly, and grade V splenomegaly. The blood test sample showed the following values: hemoglobin, 3.6<span class="elsevierStyleHsp" style=""></span>g/dL; leukocytosis, 688<span class="elsevierStyleHsp" style=""></span>000<span class="elsevierStyleHsp" style=""></span>cells/μL; platelets 321<span class="elsevierStyleHsp" style=""></span>000<span class="elsevierStyleHsp" style=""></span>cells/μL. Peripheral blood swab sample consistent with CML in chronic stage. The chest X-ray confirmed the presence of right para hilar region discreet opacity. The patient was admitted to the intensive care unit (ICU) with low respiratory work and non-invasive mechanical ventilatory support (MVS) was initiated. Thirty (30) minutes later, the patient started feeling confused, polypneic (30–35<span class="elsevierStyleHsp" style=""></span>rpm) and with thoracoabdominal asynchrony. Even though the SpO<span class="elsevierStyleInf">2</span> was 95%, the arterial-blood gas test conducted (Radiometer ABL800 FLEX, Denmark) confirmed the presence of severe respiratory failure: PaO<span class="elsevierStyleInf">2</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>50<span class="elsevierStyleHsp" style=""></span>mmHg, PaCO<span class="elsevierStyleInf">2</span><span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>38<span class="elsevierStyleHsp" style=""></span>mmHg, values of arterial blood oxygen saturation (SaO<span class="elsevierStyleInf">2</span>) of 86% (fraction of inspired oxygen<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>0.6, pressure support ventilation<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>8<span class="elsevierStyleHsp" style=""></span>cmH<span class="elsevierStyleInf">2</span>O, positive end-expiratory pressure<span class="elsevierStyleHsp" style=""></span>=<span class="elsevierStyleHsp" style=""></span>9<span class="elsevierStyleHsp" style=""></span>cmH<span class="elsevierStyleInf">2</span>O). We proceeded with orotracheal intubation and invasive MVS. On suspicion of leukostasis-induced respiratory failure, cytoreductive therapy was started with the administration of hydroxyurea and leukapheresis associated with the molecular therapy of CML with dasatinib. Red-cell concentrates were transfused to solve the anemia.</p><p id="par0015" class="elsevierStylePara elsevierViewall">Upon admission to the ICU, there was a clear discrepancy between the pulse oximetry levels (SpO<span class="elsevierStyleInf">2</span><span class="elsevierStyleHsp" style=""></span>≥<span class="elsevierStyleHsp" style=""></span>95%) and the arterial-blood gas test levels (SaO<span class="elsevierStyleInf">2</span><span class="elsevierStyleHsp" style=""></span><<span class="elsevierStyleHsp" style=""></span>90%, PaO<span class="elsevierStyleInf">2</span><span class="elsevierStyleHsp" style=""></span>≤<span class="elsevierStyleHsp" style=""></span>50<span class="elsevierStyleHsp" style=""></span>mmHg). The levels of methemoglobin (0%) and carboxyhemoglobin (1.4%), and p50 (25.9<span class="elsevierStyleHsp" style=""></span>mmHg) were within normal ranges. Due to severe hyperleukocytosis, pseudo-hypoxemia or spurious hypoxemia were considered and discussed due to an excessive consumption of oxygen following the acquisition of the specimen. To put this hypothesis to the test, arterial-blood gas tests were performed simultaneously from specimens kept at room temperature or in ice (in an effort to slow metabolic consumption) for 30<span class="elsevierStyleHsp" style=""></span>min (leukocytosis, 688<span class="elsevierStyleHsp" style=""></span>000<span class="elsevierStyleHsp" style=""></span>cells/μL when the sample was collected). Whereas the PaO<span class="elsevierStyleInf">2</span> and SaO<span class="elsevierStyleInf">2</span> levels remained relatively constant in the blood that was preserved in ice, they dropped dramatically at room temperature which is consistent with the pseudo-hypoxemia hypothesis (<a class="elsevierStyleCrossRef" href="#fig0005">Fig. 1</a>). Both the ice preservation of the sample and its quick processing minimized this preanalytical mistake in further decisions.</p><elsevierMultimedia ident="fig0005"></elsevierMultimedia><p id="par0020" class="elsevierStylePara elsevierViewall">The patient received six session of leukapheresis associated with treatment with hydroxyurea showing favorable progression with gradual reduction of leukocytosis and gradual improvement of gas exchange (<a class="elsevierStyleCrossRef" href="#fig0010">Fig. 2</a>). The patient did not show any other infectious complications, organ dysfunctions or elements suggestive of tumor lysis syndrome (TLS) or disseminated intravascular coagulation (DIC). The MVS was removed six days after admission and the patient remained lucid and free from neurological alterations. After hospitalization in the internal medicine ward the patient was discharged from the hospital, remained asymptomatic, and with a significant improvement of his hematologic alterations (hemoglobin, 7.7<span class="elsevierStyleHsp" style=""></span>g/dL; leukocytosis, 60<span class="elsevierStyleHsp" style=""></span>700<span class="elsevierStyleHsp" style=""></span>cells/μL and platelets, 213<span class="elsevierStyleHsp" style=""></span>000<span class="elsevierStyleHsp" style=""></span>cells/μL).</p><elsevierMultimedia ident="fig0010"></elsevierMultimedia><p id="par0025" class="elsevierStylePara elsevierViewall">Hyperleukocytosis is defined as white blood cell counts (WBC) above 100<span class="elsevierStyleHsp" style=""></span>000<span class="elsevierStyleHsp" style=""></span>cells/μL and is associated with an increase of morbimortality in patients with different types of leukemia.<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">1</span></a> Its main clinical manifestations are leukostasis-related (organ infiltration by leukemic cells), TLS and/or DIC.<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">2</span></a> At pulmonary level, leukostasis can cause respiratory failure due to microvascular obstruction by altering the ventilation/perfusion relationship and the diffusion of gases.<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">3</span></a> Regardless of this, the arterial-blood gas tests run in patients with hyperleukocytosis can confirm the presence of pseudo-hypoxemia or spurious hypoxemia, that is, in patients who don’t really show decreased PaO<span class="elsevierStyleInf">2</span> levels. The main explanation to this phenomenon was given back in 1979 and has to do with the high metabolic consumption of blood cells following the collection of the sample.<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">4,5</span></a> As a matter of fact, its magnitude is somehow associated with the WBC.<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">6</span></a> If not properly estimated it can lead to errors of interpretation through diagnoses of respiratory failure in patients who don’t have this condition or by overestimating the severity of this respiratory condition.<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">7</span></a> This can have a negative impact on the patients when PaO<span class="elsevierStyleInf">2</span> is considered as the main criterion to define the need for diagnostic or therapeutic procedures such as MVS. Therefore, the physician should be aware of this phenomenon to be able to recognize it, being the SpO<span class="elsevierStyleInf">2</span> and SaO<span class="elsevierStyleInf">2</span> discrepancy a key observation here.</p><p id="par0030" class="elsevierStylePara elsevierViewall">Several authors have reported that keeping the sample in ice and processing it immediately can minimize this error.<a class="elsevierStyleCrossRefs" href="#bib0065"><span class="elsevierStyleSup">4,5,8</span></a> However, this finding was not consistent with other studies that confirmed a certain reduction of PaO<span class="elsevierStyleInf">2</span> yet despite the icing of the blood specimen.<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">6</span></a> On the other hand, the addition of sodium fluoride or potassium cyanide to the specimen can inhibit metabolic consumption and stop the development of spurious hypoxemia.<a class="elsevierStyleCrossRefs" href="#bib0070"><span class="elsevierStyleSup">5,9</span></a> In this type of patients pulse oximetry follow-up is especially relevant but only as long as the presence of methemoglobinemia and carboxyhemoglobinemia is ruled out since it may affect the measurement of SpO<span class="elsevierStyleInf">2</span>.<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">7</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">In sum, hyperleukocytosis can cause true and/or spurious hypoxemia. It is essential to keep a high index of suspicion here and rule-out the existence of the latter. If undiagnosed it can condition the prescription of unnecessary and potentially dangerous therapies for patients.</p></span>" "pdfFichero" => "main.pdf" "tienePdf" => true "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Angulo M, Machado D, Larrosa L, Biestro A. Hipoxemia real y espuria en un paciente con hiperleucocitosis extrema. Med Intensiva. 2019;43:435–436.</p>" ] ] "multimedia" => array:2 [ 0 => array:7 [ "identificador" => "fig0005" "etiqueta" => "Figure 1" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr1.jpeg" "Alto" => 860 "Ancho" => 1406 "Tamanyo" => 47867 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">PaO<span class="elsevierStyleInf">2</span> measurements in arterial blood samples kept at room temperature or in ice. Both specimens were acquired at the same time (FiO<span class="elsevierStyleInf">2</span> 1, leukocytosis, 688<span class="elsevierStyleHsp" style=""></span>000<span class="elsevierStyleHsp" style=""></span>cells/μL). One arterial-blood gas test was performed immediately after the collection of the specimen and two more at 15 and 30<span class="elsevierStyleHsp" style=""></span>minutes. FiO<span class="elsevierStyleInf">2</span>, fraction of inspired oxygen; PaO<span class="elsevierStyleInf">2</span>, partial pressure of oxygen in arterial blood; room temp., room temperature.</p>" ] ] 1 => array:7 [ "identificador" => "fig0010" "etiqueta" => "Figure 2" "tipo" => "MULTIMEDIAFIGURA" "mostrarFloat" => true "mostrarDisplay" => false "figura" => array:1 [ 0 => array:4 [ "imagen" => "gr2.jpeg" "Alto" => 738 "Ancho" => 1573 "Tamanyo" => 69181 ] ] "descripcion" => array:1 [ "en" => "<p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Progression of leukocytosis and PaO<span class="elsevierStyleInf">2</span>/FiO<span class="elsevierStyleInf">2</span> at the ICU. ICU, intensive care unit; PaO<span class="elsevierStyleInf">2</span>/FiO<span class="elsevierStyleInf">2</span>, correlation between partial pressure of oxygen in arterial blood and fraction of inspired oxygen; WBC, white blood cell count.</p>" ] ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0015" "bibliografiaReferencia" => array:9 [ 0 => array:3 [ "identificador" => "bib0050" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Therapeutic apheresis in hyperleukocytosis and hyperviscosity syndrome" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "W. Blum" 1 => "P. 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| Year/Month | Html | Total | |
|---|---|---|---|
| 2024 November | 9 | 12 | 21 |
| 2024 October | 63 | 47 | 110 |
| 2024 September | 68 | 45 | 113 |
| 2024 August | 127 | 55 | 182 |
| 2024 July | 126 | 53 | 179 |
| 2024 June | 98 | 65 | 163 |
| 2024 May | 76 | 38 | 114 |
| 2024 April | 57 | 35 | 92 |
| 2024 March | 91 | 45 | 136 |
| 2024 February | 88 | 72 | 160 |
| 2024 January | 153 | 48 | 201 |
| 2023 December | 142 | 47 | 189 |
| 2023 November | 126 | 56 | 182 |
| 2023 October | 86 | 53 | 139 |
| 2023 September | 73 | 38 | 111 |
| 2023 August | 54 | 19 | 73 |
| 2023 July | 55 | 32 | 87 |
| 2023 June | 44 | 18 | 62 |
| 2023 May | 56 | 42 | 98 |
| 2023 April | 64 | 32 | 96 |
| 2023 March | 84 | 48 | 132 |
| 2023 February | 75 | 36 | 111 |
| 2023 January | 69 | 18 | 87 |
| 2022 December | 61 | 40 | 101 |
| 2022 November | 81 | 52 | 133 |
| 2022 October | 80 | 38 | 118 |
| 2022 September | 65 | 35 | 100 |
| 2022 August | 64 | 37 | 101 |
| 2022 July | 54 | 41 | 95 |
| 2022 June | 54 | 28 | 82 |
| 2022 May | 45 | 35 | 80 |
| 2022 April | 39 | 36 | 75 |
| 2022 March | 59 | 40 | 99 |
| 2022 February | 49 | 39 | 88 |
| 2022 January | 61 | 37 | 98 |
| 2021 December | 59 | 56 | 115 |
| 2021 November | 53 | 41 | 94 |
| 2021 October | 67 | 94 | 161 |
| 2021 September | 54 | 30 | 84 |
| 2021 August | 49 | 43 | 92 |
| 2021 July | 57 | 24 | 81 |
| 2021 June | 31 | 37 | 68 |
| 2021 May | 54 | 67 | 121 |
| 2021 April | 76 | 100 | 176 |
| 2021 March | 71 | 36 | 107 |
| 2021 February | 76 | 34 | 110 |
| 2021 January | 51 | 20 | 71 |
| 2020 December | 52 | 32 | 84 |
| 2020 November | 37 | 37 | 74 |
| 2020 October | 32 | 26 | 58 |
| 2020 July | 14 | 12 | 26 |
| 2020 June | 44 | 14 | 58 |
| 2020 May | 33 | 10 | 43 |
| 2020 April | 40 | 21 | 61 |
| 2020 March | 13 | 19 | 32 |
| 2020 February | 24 | 44 | 68 |
| 2020 January | 10 | 4 | 14 |
| 2019 November | 1 | 0 | 1 |
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