Blood Gas Analyses in Hyperbaric and Underwater Environments: A Systematic Review

Background: Pulmonary gas exchange during diving or in a dry hyperbaric environment is affected by increased breathing gas density and possibly water immersion. During free diving there is also the effect of apnea. Few studies have published blood gas data in underwater or hyperbaric environments: this review summarizes the available literature and was used to test the hypothesis that arterial PO2 under hyperbaric conditions can be predicted from blood gas measurement at 1 atmosphere assuming a constant arterial/alveolar PO2 ratio (a:A). Methods: A systematic search was performed on traditional sources including arterial blood gases obtained on humans in hyperbaric or underwater environments. The a:A was calculated at 1 atmosphere absolute (ATA). For each condition, predicted PaO2 at pressure was calculated using the 1 ATA a:A, and the measured PaO2 was plotted against the predicted value with Spearman correlation coefficients. Results: Of 3640 records reviewed, 30 studies were included: 25 were reports describing values obtained in hyperbaric chambers, and the remaining were collected while underwater. Increased inspired O2 at pressure resulted in increased PaO2, although underlying lung disease in patients treated with hyperbaric oxygen attenuated the rise. PaCO2 generally increased only slightly. In breath-hold divers, hyperoxemia generally occurred at maximum depth, with hypoxemia after surfacing. The a:A adequately predicted the PaO2 under various conditions: dry (r=0.993, p< 0.0001); rest vs. exercise (r=0.999, p< 0.0001); and breathing mixtures (r=0.995, p< 0.0001). Conclusion: Pulmonary oxygenation under hyperbaric conditions can be reliably and accurately predicted from 1 ATA a:A measurements.

Frequency and Clinical Significance of Negative Anion Gap Values in an Academic Medical Center Population

Anion gap is a value calculated by determining the difference between major plasma cations (sodium, sometimes additionally potassium) and anions (namely bicarbonate and chloride), with “normal” levels falling somewhere between 8 and 16 mEq/L. Elevations in anion gap are classically described in a variety of different clinical disease states, including but not limited to uremia, ketoacidoses, lactic acidosis, and a number of drug toxicities. Comparatively little is understood about the etiology of low and negative (&lt;0) anion gap measurements; however, certain patient populations and pathologic states have been associated with negative anion gap measurements, such as multiple myeloma and hypertriglyceridemia (Kraut, 2007). We reviewed laboratory chemistries for 340,354 pediatric and adult patients over a ten-year period (2009-2018). Laboratory testing included values from basic and comprehensive metabolic panels and blood gas analyses. Chart review was performed on adult patients with anion gaps measuring less than 0 mEq/L to assess for medical trends or other explanations such as analytical interference or data errors. Additionally, blood gas analyses from patients being cared for in the neonatal intensive care unit (NICU) over the same ten-year period were also reviewed. Of the adult patients, 0.046% (157 samples) had an anion gap measuring below 0 mEq/L. Samples obtained as part of a blood gas analysis made up 52% of all negative gaps. While no definitive trends were noted, 23 samples were noted to be from patients with history of malignancy (solid tumor and hematopoietic), including multiple myeloma (4 patients).[mkrasows1] In addition to malignancy, 17 patients with hypertriglyceridemia were also found to have negative anion gaps. Negative anion gaps were rare in outpatient populations. Negative anion gaps as a result of a laboratory error were also rare, constituting only 1.3% of cases (2 patients). Negative anion gaps were comparatively more common in the NICU population, with 983 patients having a negative anion gap[mkrasows2] (0.289 %). NICU patients constituted 91% of all blood gas analyses with a negative anion gap, demonstrating that negative anion gaps are much more prevalent in this patient population than they are in other pediatric and adult populations. Negative anion gaps are relatively rare occurrences in the adult outpatient population; however, they can be seen in association with certain underlying disease states such as malignancy. By comparison, negative anion gaps are much more common in critically-ill populations, most notably NICU patients.

Acid Base and Blood Gas Analysis in Term Neonates Immediately After Birth with Uncomplicated Neonatal Transition

Background: Acid base and blood gas measurements provide essential information, especially in critically ill neonates. After birth, rapidly changing physiology and difficulty to obtain blood samples represent unique challenges.Objectives: The aim of the present study was to establish normal values of capillary acid base and blood gas analysis immediately after birth in term neonates after uncomplicated neonatal transition.Method: This is a post-hoc- analysis of ancillary outcome parameter of a prospective observational study in term neonates immediately after caesarean section. Neonates were included after immediate neonatal transition without need of medical support and a capillary blood sample was taken by a heel-stick within 15-20 minutes after birth.Result: 132 term neonates were included with mean (SD) gestational age of 38.7±0.7 weeks. The blood was drawn mean (SD) 16±1.7 minutes after birth. The mean (SD) values of the analyses were: pH 7.30±0.04, pCO2 52.6±6.4, base excess -0.9±1.7 and bicarbonate 24.8±1.6.Conclusion: This is the first study describing acid base and blood gas analyses in term neonates immediately after birth with uncomplicated neonatal transition.

Oxygen Sparing Effect of Bacteriotherapy in COVID-19

Background: We previously reported that severe COVID-19 patients had higher chances of survival and a reduced risk of developing respiratory failure when administered with the probiotic formulation SLAB51. This study aimed to investigate further bacteriotherapy mechanisms and how early they are activated. Methods: We performed an analysis on the blood oxygenation parameters collected in sixty-nine severe COVID-19 patients requiring non-invasive oxygen therapy and presenting a CT lung involvement ≥50%. Twenty-nine patients received low-molecular-weight heparin, azithromycin and Remdesivir. In addition, forty subjects received SLAB51. Blood gas analyses were performed before the beginning of treatments and at 24 h. Results: The patients receiving only standard therapy needed significantly increased oxygen amounts during the 24 h observation period. Furthermore, they presented lower blood levels of pO2, O2Hb and SaO2 than the group also supplemented with oral bacteriotherapy. In vitro data suggest that SLAB51 can reduce nitric oxide synthesis in intestinal cells. Conclusions: SARS-CoV-2 infected patients may present lesions in the lungs compromising their gas exchange capability. The functionality of the organs essential for these patients’ survival depends mainly on the levels of pO2, O2Hb and SaO2. SLAB51 contains enzymes that could reduce oxygen consumption in the intestine, making it available for the other organs.

Postoperative Changes in Pulmonary Function after Valve Surgery: Oxygenation Index Early after Cardiopulmonary Is a Predictor of Postoperative Course

Objective: To determine pulmonary functional changes that predict early clinical outcomes in valve surgery requiring long cardiopulmonary bypass (CPB). Methods: This retrospective study included 225 consecutive non-emergency valve surgeries with fast-track cardiac anesthesia between January 2014 and March 2020. Blood gas analyses before and 0, 2, 4, 8, and 14 h after CPB were investigated. Results: Median age and EuroSCORE II were 71.0 years (25–75 percentile: 59.5–77.0) and 2.46 (1.44–5.01). Patients underwent 96 aortic, 106 mitral, and 23 combined valve surgeries. The median CPB time was 151 min (122–193). PaO2/FiO2 and AaDO2/PaO2 significantly deteriorated two hours, but not immediately, after CPB (both p < 0.0001). Decreased PaO2/FiO2 and AaDO2/PaO2 were correlated with ventilation time (r2 = 0.318 and 0.435) and intensive care unit (ICU) (r2 = 0.172 and 0.267) and hospital stays (r2 = 0.164 and 0.209). Early and delayed extubations (<6 and >24 h) were predicted by PaO2/FiO2 (377.2 and 213.1) and AaDO2/PaO2 (0.683 and 1.680), measured two hours after CPB with acceptable sensitivity and specificity (0.700–0.911 and 0.677–0.859). Conclusions: PaO2/FiO2 and AaDO2/PaO2 two hours after CPB were correlated with ventilation time and lengths of ICU and hospital stays. These parameters suitably predicted early and delayed extubations.

The Affinity of Hemoglobin for Oxygen Is Not Altered During COVID-19

Background: A computational proteomic analysis suggested that SARS-CoV-2 might bind to hemoglobin (Hb). The authors hypothesized that this phenomenon could result in a decreased oxygen (O2) binding and lead to hemolytic anemia as well. The aim of this work was to investigate whether the affinity of Hb for O2 was altered during COVID-19.Methods: In this retrospective, observational, single-center study, the blood gas analyses of 100 COVID-19 patients were compared to those of 100 non-COVID-19 patients. Fifty-five patients with carboxyhemoglobin (HbCO) ≥8% and 30 with sickle cell disease (SCD) were also included (“positive controls” with abnormal Hb affinity). P50 was corrected for body temperature, pH, and PCO2.Results: Patients did not differ statistically for age or sex ratio in COVID-19 and non-COVID-19 groups. Median P50 at baseline was 26 mmHg [25.2–26.8] vs. 25.9 mmHg [24–27.3], respectively (p = 0.42). As expected, P50 was 22.5 mmHg [21.6–23.8] in the high HbCO group and 29.3 mmHg [27–31.5] in the SCD group (p &lt; 0.0001). Whatever the disease severity, samples from COVID-19 to non-COVID-19 groups were distributed on the standard O2-Hb dissociation curve. When considering the time-course of P50 between days 1 and 18 in both groups, no significant difference was observed. Median Hb concentration at baseline was 14 g.dl–1 [12.6–15.2] in the COVID-19 group vs. 13.2 g.dl–1 [11.4–14.7] in the non-COVID-19 group (p = 0.006). Among the 24 COVID-19 patients displaying anemia, none of them exhibited obvious biological hemolysis.Conclusion: There was no biological argument to support the hypothesis that SARS-CoV-2 could alter O2 binding to Hb.

Súlyos hypoxaemia légszomj nélkül COVID–19-pneumoniában

Összefoglaló. Számos közlemény született arról, hogy a COVID–19-pneumoniás betegek jelentős hányadában az artériás parciális oxigéntenzió kifejezetten alacsony, mégsem jellemző a dyspnoe, és a pulzusoximetria sem mutat – a csökkent oxigéntenzióval arányos – súlyos hypoxaemiát. A jelenséget „happy hypoxaemia” néven említik. Ugyanakkor a légszomjról nem panaszkodó, de súlyos alveolocapillaris O2-felvételi zavarban szenvedő COVID–19-pneumoniás betegek a legkisebb fizikai megterhelést sem tűrik, és állapotuk gyorsan kritikussá válhat, tehát a hypoxaemia mértékének időben való felismerése kulcskérdés. A jelen közleményben egy ilyen eset rövid ismertetése után összefoglaljuk a súlyos, de tünetmentes hypoxaemia hátterében meghúzódó élettani okokat. Ezek között szerepel a hypocapnia (respiratoricus alkalosis) is, mely alacsony oxigéntenzió mellett is a hemoglobin viszonylag megtartott oxigénszaturációját eredményezi. Ezért a mindennapi COVID–19-ellátásban a megismételt artériásvérgáz-meghatározások jelentősége nem hangsúlyozható eléggé. Orv Hetil. 2021; 162(10): 362–365. Summary. Many COVID-19 patients have very low arterial partial oxigen tension while severe dyspnoe does not develop. Pulse oxymetry indicates only moderate reduction of arterial O2 saturation in these patients. The phenomenon is named “happy hypoxaemia”. Lack of (severe) dyspnoe and only moderately decreased O2 saturation in severely impaired alveolo-capillary O2 uptake may partially be explained by an increased oxygen affinity of hemoglobin in the presence of low arterial partial pressure of CO2. The latter results from increased alveolar ventilation, while low partial pressure of O2 in COVID-19 patients reflects right-to-left shunting of pulmonary blood flow and ventilation-perfusion mismatch of the diseased lungs. While such patients may have mild complaints as related to the real impairment of alveolo-capillary oxygen exchange, severe hypoxaemia is a negative prognostic factor of outcome in this state where severe clinical deterioration may rapidly appear. The latter circumstance together with the unusual relationship of O2 partial pressure and O2 saturation of hemoglobin in COVID-19 emphasize the importance of repeated complete arterial blood gas analyses in these patients. Orv Hetil. 2021; 162(10): 362–365.

Prone Position in Mechanically Ventilated COVID-19 Patients: A Multicenter Study

Background: The prone position (PP) is increasingly used in mechanically ventilated coronavirus disease 2019 (COVID-19) acute respiratory distress syndrome (ARDS) patients. However, studies investigating the influence of the PP are currently lacking in these patients. This is the first study to investigate the influence of the PP on the oxygenation and decarboxylation in COVID-19 patients. Methods: A prospective bicentric study design was used, and in mechanically ventilated COVID-19 patients, PP was indicated from a partial pressure of oxygen in arterial blood (PaO2)/fraction of inspired oxygen (FIO2) ratio of <200. Patients were left prone for 16 h each. Pressure levels, FIO2, were adjusted to ensure a PaO2 greater than 60 mmHg. Blood gas analyses were performed before (baseline 0.5 h), during (1/2/5.5/9.5/13 h), and after being in the PP (1 h), the circulatory/ventilation parameters were continuously monitored, and lung compliance (LC) was roughly calculated. Responders were defined compared to the baseline value (PaO2/FIO2 ratio increase of ≥15%; partial pressure of carbon dioxide (PaCO2) decrease of ≥2%). Results: 13 patients were included and 36 PP sessions were conducted. Overall, PaO2/FIO2 increased significantly in the PP (p < 0.001). Most PaO2/FIO2 responders (29/36 PP sessions, 77%) were identified 9.5 h after turning prone (14% slow responders), while most PaCO2 responders (15/36 PP sessions, 42%) were identified 13 h after turning prone. A subgroup of patients (interval intubation to PP ≥3 days) showed less PaO2/FIO2 responders (16% vs. 77%). An increase in PaCO2 and minute ventilation in the PP showed a significant negative correlation (p < 0.001). LC (median before the PP = 38 mL/cm H2O; two patients with LC >80 mL/cm H2O) showed a significant positive correlation with the 28 day survival of patients (p = 0.01). Conclusion: The PP significantly improves oxygenation in COVID-19 ARDS patients. The data suggest that they also benefit most from an early PP. A decrease in minute ventilation may result in fewer PaCO2 responders. LC may be a predictive outcome parameter in COVID-19 patients. Trial registration: Retrospectively registered.

Mathematical modelling of post-filter ionized calcium during citrate anticoagulated continuous renal replacement therapy

Background/Aims Post-filter ionized calcium (iCa) measured on a blood gas analyzer (BGA) during regional citrate anticoagulated continuous renal replacement therapy (CRRT) are needed to control the regime. This increases the workload and requires attention including interpretation of blood analyses. Two algorithms were developed to calculate the post-filter iCa instead. The first algorithm used measured systemic total calcium and the second used a selected set of values from an initial blood gas sample as input. Methods Calculated post-filter iCa values were compared to real blood gas analyses. 57 patients treated at the intensive care unit at Skåne University Hospital in Lund during 2010–2017 were included after applying inclusion and exclusion criteria. Clinical and machine parameters were collected from the electronic medical records. Non-quality checked data contained 1240 measurements and quality checked data contained 1034 measurements. Results The first algorithm using measured systemic total calcium resulted in slightly better precision and trueness with an average difference between the predicted and measured post-filter iCa concentration of 0.0185±0.0453 mmol/L for quality checked data, p<0.001. Neither algorithm could detect all instances requiring intervention. Conclusion The algorithms were able to estimate in range postfilter iCa values with great trueness and precision. However, they had some difficulties to estimate out-of-range postfilter iCa values. More work is needed to improve the algorithms especially in their citrate-modelling.

Modifying the PELOD-2 score to predict mortality in critically ill patients

Background The PELOD-2 score, which has been widely used to predict multiple organ dysfunction, may be used to predict mortality. Nevertheless, blood gas analyses (BGA) and lactate measurements required for the PELOD-2 cannot be performed in most limited resource settings. Objective To evaluate the performance of modified PELOD-2, without BGA and lactate, to predict mortality in critically ill children. Methods This retrospective cohort study in critically ill children admitted to the pediatric intensive care unit (PICU), Dr. Sardjito Hospital, Yogyakarta, was undertaken from January to December 2018. The modifications to the PELOD-2 score were PELOD-2A (without BGA), PELOD-2B (without lactate), and PELOD-2C (without BGA and lactate). The modified PELOD-2 scores were evaluated using receiver operating characteristic (ROC) curve for discrimination, and Hosmer-Lemeshow goodness-of-fit test for calibration. Results Of 130 subjects, 68 (52.3%) died. A PELOD-2 score cut-off of 6.5 and modified PELOD-2A, 2B, and 2C had sensitivities for predicting mortality of 73.5%, 67.7%, 70.6%, and 63.2%, respectively, and specificities of 75.8%, 77.4%, 77.4%, and 79%, respectively. The area under curve (AUC) of the PELOD-2 score was 78.3 (95%CI 70.5 to 86.2). The AUCs of the modified PELOD-2 scores ranged from 76.8 (95%CI 68.7 to 84.9) to 77.9 (95% CI 69.9 to 85.8). The positive predictive values of PELOD-2 and modified PELOD-2A, 2B, 2C were 76.9%, 76.7%, 77.4% and 76.8%, respectively. The Hosmer-Lemeshow goodness-of-fit test showed good calibration for PELOD-2 (x2=8.74; P=0.27) and modified PELOD-2A (x2=4.91; P=0.67). Conclusion The PELOD-2A, modified without BGA, can still predict mortality well in critically ill PICU patients when using a cut-off score ≥ 6.5.