Hemolysis and blood gas analysis: it's time for a change!

Modern blood gas analyzers are not able to identify hemolysis, lipemia and icterus; therefore, the aim of this study was to assess the influence of hemolysis on blood gas samples. Blood gas analysis represents an essential part in the diagnosis and treatment of critically ill patients, including those affected by the pandemic coronavirus disease 2019 (COVID-19). Hemolysis, lipemia, and icterus, are causes of clinical misinterpretation of laboratory tests. A total of 1244 blood gas specimens were collected over a one-week period from different clinical wards, including the Emergency Department, and were assessed for serum indices on Cobas C6000 CE (Roche Diagnostics, Mannheim, Germany). The prevalence of hemolysis, lipemia, and icterus were 5%, 12%, and 14%, respectively. Sample storage at room temperature, delivery to central laboratory using pneumatic tube system, as well as small sample size, strongly affected blood gas parameters (p < .01). Hemolysis led to an increase in analytical bias for pH, pO2, and potassium, and a significant decrease for pCO2, HCO3-, sodium, and Ca2+ (p <.01). Currently, hemolysis detection systems are not yet widespread, and a rapid centrifugation of samples after blood gas analysis along with the assessment of serum indices represent the only prompt approach to identify unsuitable results, avoiding pitfalls in clinical decision-making, although it cannot be applied to the Emergency Department routine. Blood gas analyzers manufacturers and suppliers should implement automated built-in serum indices detection systems.

Lung distribution of gas and blood volume in critically ill COVID-19 patients: a quantitative dual-energy computed tomography study.

BACKGROUND: Critically ill COVID-19 patients have pathophysiological lung features characterized by perfusion abnormalities. However, to date no study has evaluated whether the changes in the distribution of pulmonary gas and blood volume are associated with the severity of gas-exchange impairment and the type of respiratory support (non-invasive versus invasive) in patients with severe COVID-19 pneumonia. METHODS: This was a single-center, retrospective cohort study conducted in a tertiary care hospital in Northern Italy during the first pandemic wave. Pulmonary gas and blood distribution was assessed using a technique for quantitative analysis of dual-energy computed tomography. Lung aeration loss (reflected by percentage of normally aerated lung tissue) and the extent of gas:blood volume mismatch (percentage of non-aerated, perfused lung tissue-shunt; aerated, non-perfused dead space; and non-aerated/non-perfused regions) were evaluated in critically ill COVID-19 patients with different clinical severity as reflected by the need for non-invasive or invasive respiratory support. RESULTS: Thirty-five patients admitted to the intensive care unit between February 29th and May 30th, 2020 were included. Patients requiring invasive versus non-invasive mechanical ventilation had both a lower percentage of normally aerated lung tissue (median [interquartile range] 33% [24-49%] vs. 63% [44-68%], p < 0.001); and a larger extent of gas:blood volume mismatch (43% [30-49%] vs. 25% [14-28%], p = 0.001), due to higher shunt (23% [15-32%] vs. 5% [2-16%], p = 0.001) and non-aerated/non perfused regions (5% [3-10%] vs. 1% [0-2%], p = 0.001). The PaO2/FiO2 ratio correlated positively with normally aerated tissue (ρ = 0.730, p < 0.001) and negatively with the extent of gas-blood volume mismatch (ρ = - 0.633, p < 0.001). CONCLUSIONS: In critically ill patients with severe COVID-19 pneumonia, the need for invasive mechanical ventilation and oxygenation impairment were associated with loss of aeration and the extent of gas:blood volume mismatch.

High troponin levels in patients hospitalized for coronavirus disease 2019: a maker or a marker of prognosis?

AIMS: Controversial data have been published regarding the prognostic role of cardiac troponins in patients who need hospitalization because of coronavirus disease 2019 (COVID-19). The aim of the study was to assess the role of high-sensitivity troponin plasma levels and of respiratory function at admission on all-cause deaths in unselected patients hospitalized because of COVID-19. METHODS: We pooled individual patient data from observational studies that assessed all-cause mortality of unselected patients hospitalized for COVID-19. The individual data of 722 patients were included. The ratio of partial pressure arterial oxygen to fraction of inspired oxygen (PaO2/FiO2) and high-sensitivity troponins was reported at admission in all patients. This meta-analysis was registered on PROSPERO (CRD42020213209). RESULTS: After a median follow-up of 14 days, 180 deaths were observed. At multivariable regression analysis, age [hazard ratio (HR) 1.083, 95% confidence interval (CI) 1.061-1.105, P < 0.0001], male sex (HR 2.049, 95% CI 1.319-3.184, P = 0.0014), moderate-severe renal dysfunction (estimated glomerular filtration rate  < 30 mL/min/m2) (HR 2.108, 95% CI 1.237-3.594, P = 0.0061) and lower PaO2/FiO2 (HR 0.901, 95% CI 0.829-0.978, P = 0.0133) were the independent predictors of death. A linear increase in the HR was associated with decreasing values of PaO2/FiO2 below the normality threshold. On the contrary, the HR curve for troponin plasma levels was near-flat with large CI for values above the normality thresholds. CONCLUSION: In unselected patients hospitalized for COVID-19, mortality is mainly driven by male gender, older age and respiratory failure. Elevated plasma levels of high-sensitivity troponins are not an independent predictor of worse survival when respiratory function is accounted for.

Monitoring lung injury with particle flow rate in LPS- and COVID-19-induced ARDS.

In severe acute respiratory distress syndrome (ARDS), extracorporeal membrane oxygenation (ECMO) is a life-prolonging treatment, especially among COVID-19 patients. Evaluation of lung injury progression is challenging with current techniques. Diagnostic imaging or invasive diagnostics are risky given the difficulties of intra-hospital transportation, contraindication of biopsies, and the potential for the spread of infections, such as in COVID-19 patients. We have recently shown that particle flow rate (PFR) from exhaled breath could be a noninvasive, early detection method for ARDS during mechanical ventilation. We hypothesized that PFR could also measure the progress of lung injury during ECMO treatment. Lipopolysaccharide (LPS) was thus used to induce ARDS in pigs under mechanical ventilation. Eight were connected to ECMO, whereas seven animals were not. In addition, six animals received sham treatment with saline. Four human patients with ECMO and ARDS were also monitored. In the pigs, as lung injury ensued, the PFR dramatically increased and a particular spike followed the establishment of ECMO in the LPS-treated animals. PFR remained elevated in all animals with no signs of lung recovery. In the human patients, in the two that recovered, PFR decreased. In the two whose lung function deteriorated while on ECMO, there was increased PFR with no sign of recovery in lung function. The present results indicate that real-time monitoring of PFR may be a new, complementary approach in the clinic for measurement of the extent of lung injury and recovery over time in ECMO patients with ARDS.

Assessment of the SpO2/FiO2 ratio as a tool for hypoxemia screening in the emergency department.

OBJECTIVE: We assessed the performance of the ratio of peripheral arterial oxygen saturation to the inspired fraction of oxygen (SpO2/FiO2) to predict the ratio of partial pressure arterial oxygen to the fraction of inspired oxygen (PaO2/FiO2) among patients admitted to our emergency department (ED) during the SARS-CoV-2 outbreak. METHODS: We retrospectively studied patients admitted to an academic-level ED in France who were undergoing a joint measurement of SpO2 and arterial blood gas. We compared SpO2 with SaO2 and evaluated performance of the SpO2/FiO2 ratio for the prediction of 300 and 400 mmHg PaO2/FiO2 cut-off values in COVID-19 positive and negative subgroups using receiver-operating characteristic (ROC) curves. RESULTS: During the study period from February to April 2020, a total of 430 arterial samples were analyzed and collected from 395 patients. The area under the ROC curves of the SpO2/FiO2 ratio was 0.918 (CI 95% 0.885-0.950) and 0.901 (CI 95% 0.872-0.930) for PaO2/FiO2 thresholds of 300 and 400 mmHg, respectively. The positive predictive value (PPV) of an SpO2/FiO2 threshold of 350 for PaO2/FiO2 inferior to 300 mmHg was 0.88 (CI95% 0.84-0.91), whereas the negative predictive value (NPV) of the SpO2/FiO2 threshold of 470 for PaO2/FiO2 inferior to 400 mmHg was 0.89 (CI95% 0.75-0.96). No significant differences were found between the subgroups. CONCLUSIONS: The SpO2/FiO2 ratio may be a reliable tool for hypoxemia screening among patients admitted to the ED, particularly during the SARS-CoV-2 outbreak.

Biochemistry tests in hospitalized COVID-19 patients: Experience from a Canadian tertiary care centre.

BACKGROUND: Coronavirus Disease 2019 (COVID-19) has variable clinical presentation, from asymptomatic to severe disease leading to death. Biochemical markers may help with management and prognostication of COVID-19 patients; however, their utility is still under investigation. METHODS: A retrospective study was conducted to evaluate alanine aminotransferase, C-reactive protein (CRP), ferritin, lactate, and high sensitivity troponin T (TnT) levels in 67 patients who were admitted to a Canadian tertiary care centre for management of COVID-19. Logistic, cause-specific Cox proportional-hazards, and accelerated failure time regression modelling were performed to assess the associations of initial analyte concentrations with in-hospital death and length of stay in hospital; joint modelling was performed to assess the associations of the concentrations over the course of the hospital stay with in-hospital death. RESULTS: Initial TnT and CRP concentrations were associated with length of stay in hospital. Eighteen patients died (27%), and the median initial TnT concentration was higher in patients who died (55 ng/L) than those who lived (16 ng/L; P < 0.0001). There were no survivors with an initial TnT concentration > 64 ng/L. While the initial TnT concentration was predictive of death, later measurements were not. Only CRP had prognostic value with both the initial and subsequent measurements: a 20% increase in the initial CRP concentration was associated with a 14% (95% confidence interval (CI): 1-29%) increase in the odds of death, and the hazard of death increased 14% (95% CI: 5-25%) for each 20% increase in the current CRP value. While the initial lactate concentration was not predictive of death, subsequent measurements were. CONCLUSION: CRP, lactate and TnT were associated with poorer outcomes and appear to be useful biochemical markers for monitoring COVID-19 patients.

Clinical application of lung ultrasound score on COVID-19 setting: a regional experience in Southern Italy.

OBJECTIVE: We aimed to assess the correlation between LUS Soldati proposed score and clinical presentation, course of disease and the possible need of ventilation support/intensive care. PATIENTS AND METHODS: All consecutive patients with laboratory confirmed SARS-CoV-2 infection and hospitalized in two COVID Centers were enrolled. All patients performed blood gas analysis and lung ultrasound (LUS) at admission. The LUS acquisition was based on standard sequence of 14 peculiar anatomic landmarks with a score between 0-3 based on impairment of LUS picture. Total score was computed with their sum with a total score ranging 0 to 42, according to Soldati LUS score. We evaluated the course of hospitalization until either discharge or death, the ventilatory support and the transition in intensive care if needed. RESULTS: One hundred and fifty-six patients were included in the final analysis. Most of patients presented moderate-to-severe respiratory failure (FiO2 <20%, PaO2 <60 mmHg) and consequent recommendation to invasive mechanic ventilation (CPAP/NIV/OTI). The median ultrasound thoracic score was 28 (IQR 18-36) and most of patients could be ascertained either in a score 2 (40%) or score 3 pictures (24.4%). The bivariate correlation analysis displayed statistically significant and high positive correlations between the LUS score and the following parameters: ventilation (rho=0.481, p<0.001), lactates (rho=0.464, p<0.001), dyspnea (rho=0.398, p=0.001) mortality (rho=0.410, p=0.001). Conversely, P/F (rho= -0.663, p<0.001), pH (rho = -0.363, p=0.003) and pO2 (rho = -0.400 p=0.001) displayed significant negative correlations. CONCLUSIONS: LUS score improve the workflow and provide an optimal management both in early diagnosis and prognosis of COVID-19 related lung pathology.

Automatic real-time analysis and interpretation of arterial blood gas sample for Point-of-care testing: Clinical validation.

BACKGROUND: Point-of-care arterial blood gas (ABG) is a blood measurement test and a useful diagnostic tool that assists with treatment and therefore improves clinical outcomes. However, numerically reported test results make rapid interpretation difficult or open to interpretation. The arterial blood gas algorithm (ABG-a) is a new digital diagnostics solution that can provide clinicians with real-time interpretation of preliminary data on safety features, oxygenation, acid-base disturbances and renal profile. The main aim of this study was to clinically validate the algorithm against senior experienced clinicians, for acid-base interpretation, in a clinical context. METHODS: We conducted a prospective international multicentre observational cross-sectional study. 346 sample sets and 64 inpatients eligible for ABG met strict sampling criteria. Agreement was evaluated using Cohen's kappa index, diagnostic accuracy was evaluated with sensitivity, specificity, efficiency or global accuracy and positive predictive values (PPV) and negative predictive values (NPV) for the prevalence in the study population. RESULTS: The concordance rates between the interpretations of the clinicians and the ABG-a for acid-base disorders were an observed global agreement of 84,3% with a Cohen's kappa coefficient 0.81; 95% CI 0.77 to 0.86; p < 0.001. For detecting accuracy normal acid-base status the algorithm has a sensitivity of 90.0% (95% CI 79.9 to 95.3), a specificity 97.2% (95% CI 94.5 to 98.6) and a global accuracy of 95.9% (95% CI 93.3 to 97.6). For the four simple acid-base disorders, respiratory alkalosis: sensitivity of 91.2 (77.0 to 97.0), a specificity 100.0 (98.8 to 100.0) and global accuracy of 99.1 (97.5 to 99.7); respiratory acidosis: sensitivity of 61.1 (38.6 to 79.7), a specificity of 100.0 (98.8 to 100.0) and global accuracy of 98.0 (95.9 to 99.0); metabolic acidosis: sensitivity of 75.8 (59.0 to 87.2), a specificity of 99.7 (98.2 to 99.9) and a global accuracy of 97.4 (95.1 to 98.6); metabolic alkalosis sensitivity of 72.2 (56.0 to 84.2), a specificity of 95.5 (92.5 to 97.3) and a global accuracy of 93.0 (88.8 to 95.3); the four complex acid-base disorders, respiratory and metabolic alkalosis, respiratory and metabolic acidosis, respiratory alkalosis and metabolic acidosis, respiratory acidosis and metabolic alkalosis, the sensitivity, specificity and global accuracy was also high. For normal acid-base status the algorithm has PPV 87.1 (95% CI 76.6 to 93.3) %, and NPV 97.9 (95% CI 95.4 to 99.0) for a prevalence of 17.4 (95% CI 13.8 to 21.8). For the four-simple acid-base disorders and the four complex acid-base disorders the PPV and NPV were also statistically significant. CONCLUSIONS: The ABG-a showed very high agreement and diagnostic accuracy with experienced senior clinicians in the acid-base disorders in a clinical context. The method also provides refinement and deep complex analysis at the point-of-care that a clinician could have at the bedside on a day-to-day basis. The ABG-a method could also have the potential to reduce human errors by checking for imminent life-threatening situations, analysing the internal consistency of the results, the oxygenation and renal status of the patient.

The semantic of a pandemic: Are cardiovascular patients dying "with" or "from" COVID-19? Reflections from a case report.

RATIONALE: Northern Italy has been particularly hit by the current Covid-19 pandemic. Italian deceased patients have a mean age of 78.5 years and only 1.2% have no comorbidities. These data started a public debate whether patients die "with" or "from" Covid-19. If on one hand the public opinion has been persuaded to believe that Covid-19 infection has poor outcomes just in elderly and/or fragile subjects, on the other hand, hospitals are admitting an increasing number of healthy young patients needing semi-intensive or intensive care units. PATIENT CONCERNS: At the end of March 2020, a 79-year-old patient (M.G.) was admitted to the emergency department of our hospital with a 5 days history of fever, dyspnea, and cough. He was known for hypertension and coronary artery disease with a previous coronary artery stenting. Both the comorbidities were carried out without complications and the patient was previously asymptomatic and in good health. At admission, he was febrile and showed signs of respiratory failure with hypoxia and hypocapnia at blood gas analysis. DIAGNOSIS: The day after, he was tested for SARS-CoV-2 with a real-time reverse transcriptase-polymerase chain reaction assay of nasopharyngeal swab, which turned positive and a chest CT-Scan was consistent with the diagnosis of interstitial pneumonia. INTERVENTIONS: He was treated with i.v. diuretics, paracetamol, prolonged noninvasive ventilation (CPAP), and empiric antibiotic therapy on top of his chronic treatment. OUTCOMES: A treatment with heparin and corticosteroids was started; however, he developed irreversible respiratory failure. Invasive ventilation was not considered appropriate due to his comorbidities, low chances of recovery, and intensive care unit overcrowding. The patient died 9 days after admission. LESSONS: Health conditions that are most reported as risk factors are common cardiovascular diseases that can be managed in modern clinical practice. Through a brief illustrative clinical case, we would like to underline how Covid-19 can be per se the cause of death in patients that would otherwise have had an acceptable life expectancy.

An Evolving Clinical Need: Discordant Oxygenation Measurements of Intubated COVID-19 Patients.

Since the first appearance of the severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) earlier this year, clinicians and researchers alike have been faced with dynamic, daily challenges of recognizing, understanding, and treating the coronavirus disease 2019 (COVID-19) due to SARS-CoV-2. Those who are moderately to severely ill with COVID-19 are likely to develop acute hypoxemic respiratory failure and require administration of supplemental oxygen. Assessing the need to initiate or titrate oxygen therapy is largely dependent on evaluating the patient's existing blood oxygenation status, either by direct arterial blood sampling or by transcutaneous arterial oxygen saturation monitoring, also referred to as pulse oximetry. While the sampling of arterial blood for measurement of dissolved gases provides a direct measurement, it is technically challenging to obtain, is painful to the patient, and can be time and resource intensive. Pulse oximetry allows for non-invasive, real-time, continuous monitoring of the percent of hemoglobin molecules that are saturated with oxygen, and usually closely predicts the arterial oxygen content. As such, it was particularly concerning when patients with severe COVID-19 requiring endotracheal intubation and mechanical ventilation within one of our intensive care units were observed to have significant discordance between their predicted arterial oxygen content via pulse oximetry and their actual measured oxygen content. We offer these preliminary observations along with our speculative causes as a timely, urgent clinical need. In the setting of a COVID-19 intensive care unit, entering a patient room to obtain a fresh arterial blood gas sample not only takes exponentially longer to do given the time required for donning and doffing of personal protective equipment (PPE), it involves the consumption of already sparce PPE, and it increases the risk of viral exposure to the nurse, physician, or respiratory therapist entering the room to obtain the sample. As such, technology similar to pulse oximetry which can be applied to a patients finger, and then continuously monitored from outside the room is essential in preventing a particularly dangerous situation of unrealized hypoxia in this critically-ill patient population. Additionally, it would appear that conventional two-wavelength pulse oximetry may not accurately predict the arterial oxygen content of blood in these patients. This discordance of oxygenation measurements poses a critical concern in the evaluation and management of the acute hypoxemic respiratory failure seen in patients with COVID-19.

Physiological and quantitative CT-scan characterization of COVID-19 and typical ARDS: a matched cohort study.

PURPOSE: To investigate whether COVID-19-ARDS differs from all-cause ARDS. METHODS: Thirty-two consecutive, mechanically ventilated COVID-19-ARDS patients were compared to two historical ARDS sub-populations 1:1 matched for PaO2/FiO2 or for compliance of the respiratory system. Gas exchange, hemodynamics and respiratory mechanics were recorded at 5 and 15 cmH2O PEEP. CT scan variables were measured at 5 cmH2O PEEP. RESULTS: Anthropometric characteristics were similar in COVID-19-ARDS, PaO2/FiO2-matched-ARDS and Compliance-matched-ARDS. The PaO2/FiO2-matched-ARDS and COVID-19-ARDS populations (both with PaO2/FiO2 106 ± 59 mmHg) had different respiratory system compliances (Crs) (39 ± 11 vs 49.9 ± 15.4 ml/cmH2O, p = 0.03). The Compliance-matched-ARDS and COVID-19-ARDS had similar Crs (50.1 ± 15.7 and 49.9 ± 15.4 ml/cmH2O, respectively) but significantly lower PaO2/FiO2 for the same Crs (160 ± 62 vs 106.5 ± 59.6 mmHg, p < 0.001). The three populations had similar lung weights but COVID-19-ARDS had significantly higher lung gas volume (PaO2/FiO2-matched-ARDS 930 ± 644 ml, COVID-19-ARDS 1670 ± 791 ml and Compliance-matched-ARDS 1301 ± 627 ml, p < 0.05). The venous admixture was significantly related to the non-aerated tissue in PaO2/FiO2-matched-ARDS and Compliance-matched-ARDS (p < 0.001) but unrelated in COVID-19-ARDS (p = 0.75), suggesting that hypoxemia was not only due to the extent of non-aerated tissue. Increasing PEEP from 5 to 15 cmH2O improved oxygenation in all groups. However, while lung mechanics and dead space improved in PaO2/FiO2-matched-ARDS, suggesting recruitment as primary mechanism, they remained unmodified or worsened in COVID-19-ARDS and Compliance-matched-ARDS, suggesting lower recruitment potential and/or blood flow redistribution. CONCLUSIONS: COVID-19-ARDS is a subset of ARDS characterized overall by higher compliance and lung gas volume for a given PaO2/FiO2, at least when considered within the timeframe of our study.

Follow up of patients with severe coronavirus disease 2019 (COVID-19): Pulmonary and extrapulmonary disease sequelae.

BACKGROUND: Since December 2019 the novel coronavirus disease 2019 (COVID-19) has been burdening all health systems worldwide. However, pulmonary and extrapulmonary sequelae of COVID-19 after recovery from the acute disease are unknown. MATERIAL AND METHODS: Hospitalized COVID-19 patients not requiring mechanical ventilation were included and followed 6 weeks after discharge. Body plethysmography, lung diffusion capacity (DLco), blood gas analysis (ABG), 6-min walk test (6MWT), echocardiography, and laboratory tests were performed. Quality of life (QoL), depression, and anxiety were assessed using validated questionnaires. RESULTS: 33 patients with severe disease were included. Patients were discharged without prophylactic anticoagulation. At follow-up there were no thromboembolic complications in any patient. 11 patients (33%) had dyspnea, 11 (33%) had cough, and 15 (45%) suffered from symptoms of fatigue. Pulmonary function tests including ABG did not reveal any limitations (TLC: median=94% of predicted {IQR:85-105}; VC: 93% {78-101}; FEV1: 95% {72-103}; FEV1/FVC 79% {76-85}; PaO2: 72 mmHg {67-79}; PaCO2: 38 mmHg {35-38}), except for slightly reduced DLco (77% {69-95}). There were no echocardiographic impairments. 6MWT distance was reduced in most patients without oxygen desaturation. According to standardized questionnaires, patients suffered from reduced QoL, mainly due to decreased mobility (SGRQ activity score: 54 {19-78}). There were no indicators for depression or anxiety (PHQ-9: 7 {4-11}, GAD-7: 4 {1-9}, respectively). CONCLUSIONS: Hospitalized patients with severe COVID-19, who did not require mechanical ventilation, are unlikely to develop pulmonary long-term impairments, thromboembolic complications or cardiac impairments after discharge but frequently suffer from symptoms of fatigue.

Dyspnea perception and neurological symptoms in non-severe COVID-19 patients.

INTRODUCTION: The relationship between dyspnea and COVID-19 is unknown. In COVID-19 patients, the higher prevalence of neurological symptoms and the lack of dyspnea may suggest common underlying pathogenetic mechanisms. The aim of this preliminary study is to address whether there is a lack of dyspnea in COVID-19 patients and if there is a relationship between neurological symptoms and the perception of dyspnea. METHODS: A structured interview regarding the occurrence of subjective neurological symptoms was performed and coupled with a questionnaire about the intensity and qualities of dyspnea. Respiratory rate (RR) and an arterial blood gas on room air were concurrently evaluated. RESULTS: Twenty-two patients (age 68.4 ± 13.9 years, 13 males and 9 females) were included and divided into two groups according to the Borg dyspnea scale: dyspneic patients BU ≥ 1(DYSP) and non-dyspneic patients BU < 1 (NDYSP). The prevalence of dyspnea overall was 31.8%. The prevalence of neurological symptoms, dyspnea descriptors, RR, pH, PaCO2, PaO2, or lactate was similar between groups. CONCLUSION: This study confirms that the prevalence of dyspnea is low in non-severe COVID-19 patients, but contrary to our hypothesis of a relationship between shortness of breath and neurological symptoms, we have not been able to find any evidence of an impairment in dyspnea perception, either in the DYSP or NDYSP group.