key: cord-0867858-rfik4uz0
authors: Gürün Kaya, Aslıhan; Öz, Miraç; Akdemir Kalkan, İrem; Gülten, Ezgi; Çınar, Güle; Azap, Alpay; Kaya, Akın
title: Is pulse oximeter a reliable tool for non‐critically ill patients with COVID‐19?
date: 2021-10-21
journal: Int J Clin Pract
DOI: 10.1111/ijcp.14983
sha: b7e3144a288d9728f7dd0a82b27c60f77cb01c11
doc_id: 867858
cord_uid: rfik4uz0

INTRODUCTION: Guidelines recommend using a pulse oximeter rather than arterial blood gas (ABG) for COVID‐19 patients. However, significant differences can be observed between oxygen saturation measured by pulse oximetry (SpO(2)) and arterial oxygen saturation (SaO(2)) in some clinical conditions. We aimed to assess the reliability of the pulse oximeter in patients with COVID‐19. METHODS: We retrospectively reviewed ABG analyses and SpO(2) levels measured simultaneously with ABG in patients hospitalised in COVID‐19 wards. RESULTS: We categorised total 117 patients into two groups, in whom the difference between SpO(2) and SaO(2) was ≤4% (acceptable difference) and >4% (large difference). A large difference group exhibited higher neutrophil count, C‐reactive protein, ferritin, fibrinogen, D‐dimer and lower lymphocyte count. Multivariate analyses revealed that increased fibrinogen, increased ferritin and decreased lymphocyte count were independent risk factors for a large difference between SpO(2) and SaO(2). The total study group demonstrated the negative bias of 4.02% with the limits of agreement of −9.22% to 1.17%. The bias became significantly higher in patients with higher ferritin, fibrinogen levels and lower lymphocyte count. CONCLUSION: Pulse oximeters may not be sufficient to assess actual oxygen saturation, especially in COVID‐19 patients with high ferritin and fibrinogen levels and low lymphocyte count with low SpO(2) measurements.

Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has quickly become a global pandemic since it was first reported in December 2019.

Patients with COVID-19 need different levels of hospital care because of hypoxemic respiratory failure. 1 Monitoring oxygenation status and providing effective oxygen therapy on time are also essential on these patients. 2 Arterial blood gas analysis (ABG) is considered the gold standard in assessing oxygenation, but it is an invasive, painful and expensive procedure, therefore inconvenient for frequent monitoring. A pulse oximeter has been developed as a safer noninvasive alternative to ABG analysis and has become the standard of care to assess oxygenation in clinical practice, which utilises the different light absorption of spectra of oxygenated and deoxygenated haemoglobin. It was found that the expected error for a single measurement of oxygen saturation measured by pulse oximetry (SpO 2 ) is 3%-4%. However, the deviation of SpO 2 from oxygen saturation in the arterial blood (SaO 2 ) is even more significant at saturations below 70%. Furthermore, SpO 2 can underestimate SaO 2 in low perfusion states, arrhythmias, vasoconstriction, oedema and severe anaemia. [3] [4] [5] In our clinic, we observed that SpO 2 levels were lower than the SaO 2 in most COVID-19 patients. A study by Wilson-Baig et al suggested that SpO 2 does not reliably predict SaO 2 in critical care patients with COVID-19. 6 Also, previous data proposed that SpO 2 is an unreliable surrogate marker for SaO 2 in critically ill patients. 7 However, the data are lacking about SpO 2 accuracy in hospitalised non-critically ill COVID-19 patients.

We aimed to determine the reliability of pulse oximetry in noncritically ill patients who were hospitalised in wards due to COVID-19.

We retrospectively reviewed patients hospitalised in the COVID-19 wards of Ankara University Faculty of Medicine from 1 September 2020 to 31 

Demographic features and comorbid conditions of the patients, the date of hospitalisation, the date of symptom onset, the date of ABG sampling, the results of ABG analysis, SpO 2 level measured simultaneously with ABG, the laboratory results (hemogram, C-reactive protein-CRP, D-dimer, fibrinogen and ferritin) for the same day of ABG sampling, anticoagulant therapy status and the outcome of the disease (death, transfer to ICU or discharge) obtained from the patients' hospital file and the electronic medical record system of the hospital were recorded on a data form.

As a routine practice of our clinic, ABG samples were taken from punctures of the radial artery without placing an arterial catheter.

Brachial or femoral artery was punctured when arterial blood could not be taken from the radial artery. The indications of ABG sampling in our clinic were as follows: a SpO 2 below 90%, presence of unexplained or clinically inconsistent hypoxemia, a significant increase in the fraction of inspired oxygen (FiO 2 ) to achieve target oxygen saturation; the presence of acute dyspnoea, lethargy or other signs of carbon dioxide retention in a patient with risk factors for hypercapnic respiratory failure and patients at risk for metabolic conditions.

If the patient required any oxygen supplementation, oxygen therapy was administered via low flow oxygen systems, including a nasal cannula, simple face mask or non-rebreathing mask with the target oxygen saturation >90%. All the ABG samples were analysed within 15 minutes using the ABL800 blood gas analysers (Radiometer Medical ApS, Denmark).

As our standard of care in wards, blood pressure, heart rate, body temperature and SpO 2 of patients were measured and recorded to patients' files at least four times a day. The number of these measurements was increased according to the patients' clinical condition. In addition to these daily measurements, SpO 2 was measured simultaneously with ABG sampling and recorded. We routinely placed two pulse oximetry probes on both hands finger for at least two measurements of SpO 2 using finger pulse oximeters (Contec CMS50D Fingertip Pulse Oximeter, Qinhusangdao, China).

Then the mean of SpO2 measurements was recorded to reduce the risk of measurement error.

The data were analysed using SPSS 22.0 software (SPSS, Inc, Chicago, IL, USA). Continuous variables with normal distribution were presented as mean ± standard deviation and median [25th-75th percentiles, interquartile range (IQR)] for non-normal variables. Kolmogorov-Smirnov test was used to analyse the distribution of variables and a Levene test to assess the equality of variances. An unpaired Student's t-test or a Mann-Whitney U test was

• Arterial blood gas (ABG) analyses remain the gold standard for the measurement of oxygen saturation.

• The pulse oximeter is a non-invasive alternative to ABG analysis to assess oxygenation in clinical practice.

• Especially in patients with COVID-19, monitoring oxygenation status by pulse oximetry is essential to detect any clinical deterioration early.

• The pulse oximeter can underestimate the arterial oxygen saturation obtained from ABG analysis in noncritically ill patients who were hospitalised due to COVID-19.

• Increased fibrinogen and ferritin levels, and decreased lymphocyte count were associated with a large difference between SaO 2 and SpO 2 (>4%).

used to compare the two groups. Categorical data were expressed as numbers and percentages and compared by chi-square test or

Fisher's exact test as appropriate. We compared the demographic and clinical features between subjects that showed absolute difference between SpO 2 and SaO 2 ≤4% (acceptable difference) or >4% (large difference). This cut-off value was chosen due to a potential error of 3%-4% between SpO 2 and SaO 2 according to the previous data. [8] [9] [10] The relationships between age, gender and comorbid diseases and laboratory data with a large difference between SpO 2 and SaO 2 were analysed using binary logistic regression analyses.

We used a receiver operating characteristic curve analysis to determine the optimal cut-off value of fibrinogen, ferritin, D-dimer levels and lymphocyte counts to predict large differences between SpO 2 and SaO 2 (>4%), the best combination of sensitivity and specificity. The Bland-Altman method was performed to display bias (systematic error -mean difference between SpO 2 and SaO 2 ) and precision (random error -standard deviation of mean difference) and were calculated. Limits of agreement were defined at a mean difference ±2SD.

The statistical significance level was expressed as P < .05 for all tests.

A total of 174 patients with COVID-19 required ABG sampling in our hospital wards during the study period. After the exclusion of 57 patients, a total of 117 patients' data were evaluated patients. The patients were hospitalised at the median 4th [2] [3] [4] [5] [6] day, and the ABG samples were analysed at the median 11th [8] [9] [10] [11] [12] [13] [14] [15] 3-94.4 ], respectively. In 10 out of 117 patients, SpO 2 levels were higher than SaO 2 (mean difference 1.1 ± 0.7%). We categorised the patients into two groups, in whom the difference between SaO 2 and SpO 2 was ≤4% (acceptable difference group) and >4% (large difference group). In 59 patients (50.4%), the difference between SpO 2 and SaO 2 measurements was greater than 4% (large difference), and within this group, all SaO 2 levels measured were higher than SpO 2 . The baseline features and comorbid conditions of these two groups were given in Table 1 .

Patients with a large difference have higher neutrophil count ddimer, ferritin, fibrinogen and C-reactive protein (CRP) levels than the patients with an acceptable difference ( Table 2) . To determine the effect of clinical and laboratory parameters on a large difference risk, a binary logistic regression analysis was employed, revealing that increased d-dimer, fibrinogen, ferritin level and decreased lymphocyte count were significantly associated with large SaO 2 -SpO 2 (Table 3) .

We performed receiver operating characteristic (ROC) curve analyses to determine cut-off values for ferritin, fibrinogen and lymphocyte count that would predict the large difference between SpO 2 and SaO 2 . The best cut-off value was 4. Bland-Altman analysis comparing SpO 2 with SaO 2 within the total study group demonstrated the negative bias (mean difference) of 4.02% with an SD of 2.65 (precision) and the limits of agreement of −9.22% to 1.17% (Figure 2 ). This indicates that the 

The present study showed that oxygen saturation measured by pulse oximetry underestimated the arterial oxygen saturation obtained from ABG analysis in non-critically ill patients who were hospitalised due to COVID-19. Increased fibrinogen and ferritin level, and decreased lymphocyte count were independently associated with a large difference (SaO 2 -SpO 2 >4%). Bland-Altman analysis comparing SpO 2 with SaO 2 within the total study group demonstrated the negative bias of 4.02% with limits of agreement of −9.22% to 1.17%. Bold values indicate statistical significance with a P-value less than .05.

Abbreviations: ABG, arterial blood gases; CRP, C-reactive protein; HCO3 -, bicarbonate; PaCO 2 , partial arterial carbon dioxide pressure; PaO 2 , partial arterial oxygen pressure; SaO 2 , arterial oxygen pressure.

Comparing ABG and other laboratory parameters of patients with an acceptable difference (≤4%) and large difference (>4%)

The bias became significantly higher in patients with higher ferritin, fibrinogen and lower lymphocyte count.

Hypoxemia is one of the hallmarks of severe COVID-19. Patients hospitalised in hospital wards due to severe disease should be monitored closely for vital signs, including oxygen saturation to detect any worsening or respiratory failure. 11, 12 ABG analyses remain the gold standard for measurement of oxygen saturation, but it is invasive and painful, therefore inconvenient for frequent monitorisation.

Pulse oximeters are widely used as a standard medical instrument for noninvasively monitoring arterial oxygen saturation (SpO 2 %).

Previous studies suggested that pulse oximetry is an accurate method to assess SaO 2 in most adult patients in the clinical setting. However, studies indicated clinically meaningful differences between SaO 2 and SpO 2 in some clinical conditions such as sepsis, septic shock, hyperbilirubinemia, anaemia and hypovolemia. 4, 13, 14 Guidelines recommend using a pulse oximeter rather than invasive ABG for the monitoring of COVID-19 patients, unless there is a suspicion of carbon dioxide retention. 15 .084

Bold values indicate statistical significance with a P-value less than .05.

Abbreviation: CRP, C-reactive protein.

Binary logistic regression analysis between the large difference on SaO2-SpO2 and other clinical variables F I G U R E 2 Bland-Altman plots for comparing SpO 2 with SaO 2 within the total study group. The X-axis represents the mean of SpO 2 and SaO 2 ((SpO 2 %+SaO 2 %)/2) and the Y-axis represents the difference between SpO 2 and SaO 2 (SpO 2 %-SaO 2 %). Red line shows the mean bias. Blue lines represent upper and lower limits of agreement at ±1.96 SD F I G U R E 3 Bland-Altman plots for comparing SpO 2 with SaO 2 among patients with normal serum fibrinogen (<4.8 g/dL) (A) and with high serum fibrinogen (≥4.8 g/dL) (B). The X-axis represents the mean of SpO 2 and SaO 2 ((SpO 2 %+SaO 2 %)/2) and the Y-axis represents the difference between SpO 2 and SaO 2 (SpO 2 %-SaO 2 %). Red line shows the mean bias. Blue lines represent upper and lower limits of agreement at ±1.96 SD. The mean difference was higher in patients with high fibrinogen levels than those with normal levels (5.07 ± 2.44% vs 2.98 ± 2.44%, P < .001)

Bland-Altman plots for comparing SpO 2 with SaO 2 among patients with normal serum ferritin level (<228 ng/mL) (A) and with increased serum ferritin (≥228 ng/mL) (B). The X-axis represents the mean of SpO 2 and SaO 2 ((SpO 2 %+SaO 2 %)/2) and the Y-axis represents the difference between SpO 2 and SaO 2 (SpO 2 %-SaO 2 %). Red line shows the mean bias. Blue lines represent upper and lower limits of agreement at ±1.96 SD. The mean difference was higher in patients with high ferritin levels than those with normal levels (4.88 ± 2.46% vs 2.41 ± 2.22%, P < .001)

Bland-Altman plots for comparing SpO 2 with SaO 2 among patients with normal lymphocyte count (>1.04 × 10 3 /mm 3 ) (A) and low lymphocyte count (≤1.04 × 10 3 /mm 3 ) (B). The X-axis represents the mean of SpO 2 and SaO 2 ((SpO 2 % + SaO 2 %)/2) and the Y-axis represents the difference between SpO 2 and SaO 2 (SpO 2 %-SaO 2 %). Red line shows the mean bias. Blue lines represent upper and lower limits of agreement at ±1.96 SD. The mean difference was higher in patients with low lymphocyte count than those with normal levels (5.07 ± 2.36% vs 2.66 ± 2.39%, P < .001)

properties of high ferritin, d-dimer or other proteins at 660 and 6, 17 This situation may also cause clinically inconsistent hypoxemia in a group of COVID-19 patients, which has also been described as silent hypoxemia. We think pulse oximetry may not be sufficient to assess actual oxygen saturation in hospitalised COVID-19 patients, especially with increased inflammatory and coagulation biomarkers.

To the best of our knowledge, this is the first study to compare SpO 2 and SaO 2 in non-critically ill COVID-19 patients. As distinct from two previous studies with COVID patients in intensive care, 9, 24 the present study included a higher number of patients and additionally the SpO 2 -SaO 2 difference was evaluated with the laboratory parameters.

Our study has some limitations. First, this study conducted retrospectively and we evaluated the blood pressure and body temperature on a daily record of patients' file, but real-time data were lacking. The other limitation was that we measured patients' SpO 2 via the same pulse oximeter type, and we do not know whether the results would differ if we used another model pulse oximeter. On the other hand, the pulse oximeters in our wards were approved by Food and Drug Administration (FDA) and European Conformity (CE). The third limitation of the study was that it did not have a control group with non-COVID to compare results.

To conclude, pulse oximetry may not be sufficient to assess actual oxygen saturation in hospitalised COVID-19 patients. Therefore, especially in patients with high ferritin and fibrinogen levels and low lymphocyte count, low SpO 2 measurements may be confirmed by ABG. Further studies are needed to assess discrepancies of SpO 2 and SaO 2 in COVID-19.

The authors declared no conflict of interest. 

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