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Rare Case of Transcutaneous Oxygen Desaturation in a Cancer Patient: A Case Report and Diagnostic Approach for a Recurrent Problem

Bachmann, Kaspar F. MD*; Nebiker, Mathias MD; Johner, Caroline MD; Bregy, Rachel MSc§; Schaller, André PhD; Novak, Urban PhD; Jakob, Stephan M. PhD

doi: 10.1213/XAA.0000000000000855
Case Reports

We present a case of a 73-year-old cancer patient with low transcutaneous oxygen saturation who was transferred to the intensive care unit after deployment of the rapid response team. Differential diagnosis remained broad until methemoglobinemia (MetHb) was detected.

MetHb was induced by administration of rasburicase, which was given to prevent tumor lysis syndrome. In a follow-up examination, glucose-6-phosphate dehydrogenase deficiency was found to be the cause of MetHb after rasburicase exposure.

Diagnosis was made by either measuring arterial MetHb or CO oximeter. Treatment options involve transfusion and methylene blue, if glucose-6-phosphate dehydrogenase deficiency is not present.

From the *Department of Anaesthesiology & Pain Medicine

Department of Intensive Care Medicine

Department of Cardiology, Swiss Cardiovascular Center

§Department of Pharmacy

Division of Human Genetics

Department of Medical Oncology, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland.

Accepted for publication June 18, 2018.

Funding: None.

The authors declare no conflicts of interest.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website.

Address correspondence to Kaspar F. Bachmann, MD, Department of Anaesthesiology & Pain Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, Switzerland. Address e-mail to

Low transcutaneous oxygen saturation (Spo2) is among one of the major reasons rapid response teams are called to evaluate patients for intensive care unit (ICU) admission.1,2 Differential diagnosis usually includes pulmonary arterial embolism, cardiac failure, respiratory failure (eg, pneumonia, chronic obstructive pulmonary disease, and/or sepsis), and other possibilities. Here, we present a patient admitted to our ICU because of low transcutaneous Spo2 of unsuspected origin. Methemoglobinemia (MetHb) after rasburicase exposure later proved to be the cause of low Spo2 due to glucose-6-phosphate dehydrogenase deficiency (G6PDD). Diagnosis of G6PDD is usually made in patients presenting with an acute hemolytic reaction caused by infectious disease or after ingestion of a known oxidative substance.3

This case report delivers a diagnostic and therapeutic approach toward low Spo2 due to MetHb and highlights genetic predisposition and pharmaceutical implications of the condition.

Written informed consent for publication of the case was obtained from the patient.

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Our rapid response team was called to evaluate a 73-year-old patient with known lymphoma and low transcutaneous Spo2 values of around 80% that did not improve through oxygen administration. During the evaluation, the patient presented with only slight dyspnea, but the low Spo2 values persisted. The patient was anemic due to lymphoma and the treatment he was receiving. At first, the diagnosis was unclear, thus a transfer to our ICU followed. The patient presented with an initial Spo2 of 81%, normal blood pressure and pulse (118/66 mm Hg, 67/min), and a respiratory rate of 18/min.

Our approach began with stabilization of the patient using noninvasive ventilation. Our primary differential diagnosis included pulmonary embolisms, lung edema, pneumonia, and right-to-left shunt. We had planned to perform a computed tomography scan after initial stabilization, but the first Po2 value, measured with blood gas analysis, was 193 mm Hg, and this increased to 428 mm Hg under noninvasive ventilation. Blood gas analyses showed persistently high Po2 values and good Hb Spo2 that failed to match Spo2 values.

Further clinical examination did not reveal specific symptoms, but blood gas samples revealed MetHb of 5.1% and demonstrated a decline of MetHb over time. After further evaluation of his history and a short period of observation, the patient was returned to the ward (Table).



MetHb in adults is usually induced by drugs. The patient was being treated for an aggressive lymphoma, with significant neurological symptoms, including tetraparesis. Although no lesions had been seen on a magnetic resonance imaging scan of the brain, chemotherapy with rituximab, methotrexate, and cytarabine had been initiated. To prevent tumor lysis syndrome (TLS), rasburicase had been administered 24 hours before the above-mentioned episode of low Spo2, making it the most likely cause of MetHb. We suspected G6PDD as a cause of the MetHb after rasburicase exposure. Patient history showed no other candidates for MetHb induction.

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The rapid response team was deployed for a patient with low Spo2. This carries a broad differential diagnosis, including the uncommon occurrence of MetHb. In our patient, the clinical sign of low Spo2 led to a transfer to our ICU, and a computed tomography scan was planned before blood gas analysis showed the actual underlying medical problem.

Diagnosis of MetHb can be established by either measuring arterial MetHb saturation or using CO oximetry, which measures multiple wavelengths.4,5 MetHb may develop into a life-threatening condition, especially if anemia or coronary disease is present. Transcutaneously measured Spo2 trends toward 80%–85%, independent of actual MetHb concentration and hemoglobin Spo2.4

Studies generally recommend treatment of MetHb if levels rise above 30%.4 If the patient suffers from an already impaired oxygen transport capability (eg, anemia) or if signs of cellular hypoxia such as hyperlactatemia are present, treatment should be initiated earlier.6 No valid treatment options other than blood transfusion and, if G6PDD is not present, methylene blue are available.7

The maximum level of MetHb seen in our patient was 5.1%, with no signs of cellular hypoxia and a decreasing trend. Serum lactate level did not rise above normal values. Therefore, no further observation or treatment was necessary (Figure).



The broad differential diagnosis of low Spo2 can lead to unnecessary laboratory and radiographic testing if the underlying cause is not appropriately recognized. The oncological, genetic, and pharmacological implications of the disease are elaborated in the following section.

According to treatment guidelines for lymphoma, rasburicase is recommended as a supplementary drug to prevent TLS.8 TLS is seen in hematological tumors rather than solid tumors. Untreated, it can lead to renal failure and possibly death.8 Rasburicase is generally a safe and effective treatment option for TLS, but it is known to induce MetHb on rare occasions. There are at least 21 publications describing MetHb after rasburicase administration, most of them associated with G6PDD. For a list, see the Supplemental Digital Content ( At least 2 of these cases resulted in death.9,10

Our patient did not receive any other medication known to induce MetHb. Specifically, the chemotherapy did not include cytostatic drugs such as doxorubicin, cyclophosphamide, or ifosfamide. Other know inducers of MetHb, especially with G6PDD present, include fava beans or exposure to high-risk drugs or chemicals, such as rasburicase, as well as some chemotherapeutics (eg, nitrofurantoin), antimalaria drugs (eg, pamaquine), anti-inflammatory drugs (eg, dapsone), methylene blue, and certain disinfectants (eg, hydrogen peroxide).11 The time frame is plausible, as rasburicase oxidizes hemoglobin through accumulating hydrogen peroxide rather than directly producing methemoglobin, thus the appearance of MetHb after 24 hours is likely. Alternatively, TLS itself might cause MetHb, although in our patient that seems unlikely, because no symptoms or signs of TLS were present.

Our patient’s clinical presentation led us to suspect G6PDD in this case. This was confirmed in later testing. G6PDD, the most common enzyme deficiency in humans, is a known risk factor for MetHb. In this patient from Laos, the hemizygous pathogenic variant c.1388G>A p. (Arg463His) of the G6PDD gene locus was identified. G6PDD is linked to a selective advantage for malaria infections in this area.12

MetHb is an uncommon side effect of treatment with rasburicase. Testing for G6PDD before its administration is not standard and not feasible, because the need for treatment with rasburicase is usually urgent. If G6PDD is present, rasburicase should be avoided entirely or only be administered with caution, and closer monitoring of the patient may be warranted.

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MetHb is a rare but known adverse effect of rasburicase. If the clinical presentation and/or the blood gas analysis does not match the transcutaneously measured Spo2, different types hemoglobin, especially methemoglobin, should be considered. Patient history must be carefully evaluated for any risk factors for MetHb. Diagnosis should be made either by measuring arterial MetHb or using a CO oximeter. Treatment options involve transfusion, as well as methylene blue, if G6PDD is not present. In patients with known G6PDD, substances that can cause oxidant stress should be avoided.

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Name: Kaspar F. Bachmann, MD.

Contribution: This author helped write and edit the manuscript.

Name: Mathias Nebiker, MD.

Contribution: This author helped analyze patient history and edit the manuscript.

Name: Caroline Johner, MD.

Contribution: This author helped care for the patient, analyze patient history, and edit the manuscript.

Name: Rachel Bregy, MSc.

Contribution: This author helped assess pharmacological implications and edit the manuscript.

Name: André Schaller, PhD.

Contribution: This author helped with the genetic testing and background and edit the manuscript.

Name: Urban Novak, PhD.

Contribution: This author helped with the oncological aspects of the case report and edit the manuscript.

Name: Stephan M. Jakob, PhD.

Contribution: This author helped edit the manuscript.

This manuscript was handled by: BobbieJean Sweitzer, MD, FACP.

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