Implications of differences between point-of-care blood gas analyser and laboratory analyser potassium results on hyperkalaemia diagnosis & treatment.

BACKGROUND: Hyperkalaemia is managed in the emergency department (ED) following measurement of potassium results by blood gas analysers (BGA) or laboratory analysers (LAB). AIMS: To determine the prevalence of clinically significant differences between BGA and LAB potassium results and the impact on ED hyperkalaemia management. METHODS: Retrospective analysis of time-matched ED BGA and LAB potassium samples from 2019 to 2020 (taken within 15 min, one or both results ≥6.0 mmol/L). Mean differences and 95% limits of agreement (LoA) were determined for pairs with one or both results ≥6.0 mmol/L and a separate 500 consecutive sample pairs. RESULTS: Four hundred eighty-eight matched BGA and LAB samples met the inclusion criteria. Of these, 201 (41.2%) differed by ≤0.5 mmol/L, 169 (34.6%) included a haemolysed LAB sample, and 12 (2.5%) had an unreportable BGA sample. One hundred six (21.7%) pairs differed by >0.5 mmol/L, and 60/106 (57%) had normal LAB potassium results, but BGA indicated moderate/severe hyperkalaemia (two of these pairs received hyperkalaemia treatment). Of patients with a haemolysed LAB sample, or where pairs differed by >0.5 mmol, 48 were treated with insulin and five (10.4%) experienced hypoglycaemia. Mean differences and LoA for pairs with LAB results <6.0 mmol/L but BGA ≥6.0 mmol/L demonstrated unacceptable agreement, with 18 (25.7%) BGA results exceeding 8.0 mmol/L. CONCLUSIONS: Potentially significant discordance may occur between BGA and LAB potassium results. Clinicians need to be aware of factors impacting both analytical methods' accuracy (such as poor venepuncture or sample handling, (K) EDTA interference) and undetectable haemolysis with BGA measurements. We recommend BGA hyperkalaemia be confirmed with LAB results using a non-haemolysed sample where time permits.

Measuring Suite for Vascular Response Monitoring during Hyperbaric Oxygen Therapy by Means of Pulse Transit Time (PTT) Analysis.

The efficacy of hyperbaric oxygen therapy in treating wound healing disorders is well established. The obvious explanation is the presence of elevated oxygen tissue tensions during the high-pressure oxygen exposure. This explanation omits that the effective agent, elevated oxygen tension, is only present for 6.25% of the time. To investigate possible prevailing vascular changes caused by HBOT, the presented device monitors the vascular response during therapy by Pulse-Transit-Time analysis. The device allows synchronous 1 kHz ECG and PPG measurements. The data are stored in a 1 GBit flash drive and retrieved post-therapy. Normoxic measurements on the authors with and without nicotine validate the device's functionality. Measurements during HBO therapy have been successfully performed.

Arterial blood gas analysis aids early differential diagnosis and treatment of primary and secondary hypokalaemic periodic paralysis.

This study aimed to examine changes in electrolytes and acid-base status in primary and secondary hypokalaemic periodic paralysis (HypoPP), which will help early differential diagnosis of HypoPP. A total of 64 HypoPP patients were enrolled and relevant data from clinical records was collected. Overall, 64 patients (mean age 28.2±7.3 years) of which 58(91%) were males, with 39, 11 and 14 patients, respectively, diagnosed as primary HypoPP, thyrotoxic HypoPP, and other secondary HypoPPs at discharge, were assessed. Those with HypoPP secondary to conditions other than hyperthyroidism were more likely to develop acid-base imbalance (p<0.001); they had higher pH (p=0.046) and HCO3 levels (p=0.014) at baseline, and needed a higher dose of potassium supplement before the serum potassium level returned to normal (p=0.007) and a longer time to regain full muscle strength (p=0.004), compared with those with primary or thyrotoxic HypoPP. Emergent arterial blood gas analysis may aid early differential diagnosis of patients with primary and secondary HypoPP.

Evaluation of Venous-to-Arterial Carbon Dioxide Tension Difference as a Complementary Parameter During Pediatric Septic Shock Resuscitation: A Prospective Observational Study.

OBJECTIVES: The aim of this study was to evaluate the venous-to-arterial carbon dioxide tension difference during early resuscitation in pediatric septic shock. METHODS: A prospective observational study was conducted in the pediatric intensive care unit of a tertiary care teaching. Children having septic shock aged from 3 to 60 months were studied within the first 24 hours of admission. Central venous and peripheral arterial blood samples for blood gases analysis at time of central venous catheter insertion and after 6 hours were obtained. Central venous carbon dioxide pressure, arterial carbon dioxide pressure, and their difference (delta Pco2) were recorded. Patients were categorized, accordingly to delta Pco2 after 6 hours of resuscitation, into high delta Pco2 group (≥6 mm Hg) and low delta Pco2 group (<6 mm Hg). RESULTS: Oxygen extraction ratio at 6 hours of resuscitation was significantly lower among the low delta Pco2 group. Arterial lactate showed marked improvement in the low delta Pco2 group to be less than 2 mmol/L at 12 hours of resuscitation. Low delta Pco2 group showed significant higher shock reversal with shorter shock reversal time. Mortality was significantly lower among low delta Pco2 group with shorter pediatric intensive care unit stay. CONCLUSIONS: Delta Pco2 after 6 hours of resuscitation of <6 mm Hg indicates normalization of tissue perfusion during pediatric septic shock management. It could be used as a complementary tool to guide the resuscitation in the early phase of pediatric septic shock.

Validation of Respiratory Rate-Oxygenation Index in Patients With COVID-19-Related Respiratory Failure.

OBJECTIVES: The respiratory rate-oxygenation (ROX) index is a fraction of oxygen saturation, Fio2, and respiratory rate that has been validated to predict receipt of invasive mechanical ventilation in patients receiving high-flow nasal cannula (HFNC). This study aimed to validate ROX in a cohort of inpatients with COVID-19-related respiratory failure. DESIGN: Retrospective validation of the ROX index. We calculated sensitivity, specificity, positive predictive value, negative predictive value, and 95% CIs of ROX for invasive mechanical ventilation any time during hospitalization. SETTING: Twenty-one hospitals of Kaiser Permanente Northern California, an integrated healthcare delivery system. PATIENTS: We identified adults with positive severe acute respiratory syndrome coronavirus 2 polymerase chain reaction test within 3 weeks of, or during, hospitalization between February 1, 2020, and December 31, 2020. We calculated ROX at 12 hours after HFNC initiation. We grouped patients as low (≥ 4.88), intermediate (< 4.88 and ≥ 3.85), or high (< 3.85) risk using previously published thresholds. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We identified 1,847 patients who had no limitation of life support. Of these, 525 (31.7%) received invasive mechanical ventilation any time during hospitalization and 511 died (27.7%). The sensitivity, specificity, positive predictive value, and negative predictive value of 12-hour ROX threshold (< 3.85) predicting invasive mechanical ventilation were 32.3% (95% CI, 28.5-36.3%), 89.8% (95% CI, 88.0-91.4%), 59.4% (95% CI, 53.8-64.9%), and 74.1% (95% CI, 71.8-76.3%), respectively. CONCLUSIONS: The 12-hour ROX index has a positive predictive value (59.4%) using threshold of less than 3.85 for COVID-19 patients needing invasive mechanical ventilation. Our health system has embedded ROX into the electronic health record to prioritize rounding during periods of inpatient surge.

Blood gas analyses in hyperbaric and underwater environments: a systematic review.

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). 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 arterial partial pressure of oxygen ([Formula: see text]) at pressure was calculated using the 1 ATA a:A, and the measured [Formula: see text] was plotted against the predicted value with Spearman correlation coefficients. Of 3,640 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 [Formula: see text], although underlying lung disease in patients treated with hyperbaric oxygen attenuated the rise. [Formula: see text] generally increased only slightly. In breath-hold divers, hyperoxemia generally occurred at maximum depth, with hypoxemia after surfacing. The a:A adequately predicted the [Formula: see text] under various conditions: dry (r = 0.993, P < 0.0001), rest versus exercise (r = 0.999, P < 0.0001), and breathing mixtures (r = 0.995, P < 0.0001). In conclusion, pulmonary oxygenation under hyperbaric conditions can be reliably and accurately predicted from 1 ATA a:A measurements.

Compound Danshen Dripping Pill inhibits high altitude-induced hypoxic damage by suppressing oxidative stress and inflammatory responses.

CONTEXT: Previous studies indicate that compound Danshen Dripping Pill (CDDP) improves the adaptation to high-altitude exposure. However, its mechanism of action is not clear. OBJECTIVE: To explore the protective effect of CDDP on hypobaric hypoxia (HH) and its possible mechanism. MATERIALS AND METHODS: A meta-analysis of 1051 human volunteers was performed to evaluate the effectiveness of CDDP at high altitudes. Male Sprague-Dawley rats were randomized into 5 groups (n = 6): control at normal pressure, model, CDDP-170 mg/kg, CDDP-340 mg/kg and acetazolamide groups. HH was simulated at an altitude of 5500 m for 24 h. Animal blood was collected for arterial blood-gas analysis and cytokines detection and their organs were harvested for pathological examination. Expression levels of AQP1, NF-κB and Nrf2 were determined by immunohistochemical staining. RESULTS: The meta-analysis data indicated that the ratio between the combined RR of the total effective rate and the 95% CI was 0.23 (0.06, 0.91), the SMD and 95% CI of SO2 was 0.37 (0.12, 0.62). Pre-treatment of CDDP protected rats from HH-induced pulmonary edoema and heart injury, left-shifted oxygen-dissociation curve and decreased P50 (30.25 ± 3.72 vs. 37.23 ± 4.30). Mechanistically, CDDP alleviated HH-reinforced ROS by improving SOD and GPX1 while inhibiting pro-inflammatory cytokines and NF-κB expression. CDDP also decreased HH-evoked D-dimer, erythrocyte aggregation and blood hemorheology, promoting AQP1 and Nrf2 expression. DISCUSSION AND CONCLUSIONS: Pre-treatment with CDDP could prevent HH-induced tissue damage, oxidative stress and inflammatory response. Suppressed NF-κB and up-regulated Nrf2 might play significant roles in the mechanism of CDDP.

Capnometric feedback training decreases 24-h blood pressure in hypertensive postmenopausal women.

BACKGROUND: High normal resting pCO2 is a risk factor for salt sensitivity of blood pressure (BP) in normotensive humans and has been associated with higher resting systolic BP in postmenopausal women. To date, however, no known studies have investigated the effects of regular practice of voluntary mild hypocapnic breathing on BP in hypertensive patients. The objective of the present research was to test the hypothesis that capnometric feedback training can decrease both resting pCO2 and 24-h BP in a series of mildly hypertensive postmenopausal women. METHODS: A small portable end tidal CO2 (etCO2) monitor was constructed and equipped with software that determined the difference between the momentary etCO2 and a pre-programmed criterion range. The monitor enabled auditory feedback for variations in CO2 outside the criterion range. 16 mildly hypertensive postmenopausal women were individually trained to sustain small decreases in etCO2 during six weekly sessions in the clinic and daily sessions at home. 24-h BP monitoring was conducted before and after the intervention, and in 16 prehypertensive postmenopausal women in a control group who did not engage in the capnometric training. RESULTS: Following the intervention, all 16 capnometric training participants showed decreases in resting etCO2 (- 4.3 ± 0.4 mmHg; p < .01) while 15 showed decreases in 24-h systolic BP (- 7.6 ± 2.0 mmHg; p < .01). No significant changes in either measure was observed in the control group. In addition, nighttime (- 9.5 ± 2.6; p < .01) and daytime (- 6.7 ± 0.2 mmHg) systolic BP were both decreased following capnometric training, while no significant changes in nighttime (- 2.8 ± 2.2 mmHg; p = .11) or daytime (- 0.7 ± 1.0 mmHg; p ≤ .247) systolic BP were observed in the control group. CONCLUSIONS: These findings support the hypothesis that regular practice of mild hypocapnic breathing that decreases resting etCO2 reliably decreases 24-h blood pressure in hypertensive postmenopausal women. The extent to which these effects persist beyond the training period or can be observed in other hypertensive subgroups remains to be investigated.

Changes in acid-base status in oxygen toxicity at 230 kPa oxygen as a function of exposure time.

Breathing less than 50 kPa of oxygen over time can lead to pulmonary oxygen toxicity (POT). Vital capacity (VC) as the sole parameter for POT has its limitations. In this study we try to find out the changes of acid-base status in a POT rat model. Fifty male rats were randomly divided into five groups, exposed to 230 kPa oxygen for three, six, nine and 12 hours, respectively. Rats exposed to air were used as controls. After exposure the mortality and behavior of rats were observed. Arterial blood samples were collected for acid-base status detection and wet-dry (W/D) ratios of lung tissues were tested. Results showed that the acid-base status in rats exposed to 230 kPa oxygen presented a dynamic change. The primary status was in the compensatory period when primary respiratory acidosis was mixed with compensated metabolic alkalosis. Then the status changed to decompensated alkalosis and developed to decompensated acidosis in the end. pH, PCO2, HCO3-, TCO2, and BE values had two phases: an increase and a later decrease with increasing oxygen exposure time, while PaO2 and lung W/D ratio showed continuously increasing trends with the extension of oxygen exposure time. Lung W/D ratio was significantly associated with PaO2 (r = 0.6385, p = 0.002), while other parameters did not show a significant correlation. It is concluded that acid-base status in POT rats presents a dynamic change: in the compensatory period first, then turns to decompensated alkalosis and ends up with decompensated acidosis status. Blood gas analysis is a useful method to monitor the development of POT.

[Efficacy and safety of giant emphysematous bulla volume reduction via medical thoracoscope].

Objective: To evaluate the efficacy and safety of giant emphysematous bulla (GEB) volume reduction via medical thoracoscope. Methods: This was a prospective, single-arm study conducted between July 2018 and September 2020 in Ri Zhao Hospital of Traditional Chinese Medicine. Patients who met the inclusion criteria were treated with GEB volume reduction via medical thoracoscope and were followed up to evaluate the efficacy and safety of the technique. According to comparison of preoperative and postoperative chest CT results, the self-designed evaluation criteria of imaging efficacy were as follows: complete or nearly complete disappearance of GEB (GEB volume reduction ≥90%), significant reduction of GEB (75%≤GEB volume reduction<90%), reduction of GEB (50%≤GEB volume reduction<75%) and no change (GEB volume reduction<50%). Results: A total of 47 patients were included, among whom 43 were males, with an age M (Q1, Q3) of 63.0 (55.0, 67.0). The CT results showed complete or nearly complete disappearance of GEB in 43 patients, significant reduction of GEB in 3 patients and reduction of GEB in 1 patient before discharge. The degree of dyspnea improved significantly (P<0.05). Arterial partial pressure of carbon dioxide (PaCO2) decreased from (48.2±8.4)mmHg (1 mmHg=0.133 kPa) to (45.4±7.3)mmHg (P<0.05). The 6-minute walk test (6MWT) increased from (245.6±162.4)m to (283.5±152.2)m (P<0.05). Six-month postoperative follow-up was completed in 24 patients, and CT results showed that the efficacy of volume reduction was continuous compared with that before discharge. GEB was further reduced or even disappeared in 3 of the cases. Besides, the degree of dyspnea, 6MWT (384.4±148.2)m and PaCO2 (42.7±6.6)mmHg were improved significantly (P<0.05). The oxygenation index (356.86±61.21)mmHg was significantly higher than that before surgery (295.20±67.16)mmHg and before discharge (294.50±76.69)mmHg (P<0.05). No perioperative deaths occurred. Conclusions: GEB volume can be completely eliminated or significantly reduced by this innovative technique, while PaCO2, the degree of dyspnea and exercise endurance can be significantly improved after operation. The 6-month follow-up after surgery showed that the above benefits continued, and that the oxygenation index improved significantly.

D-Cystine di(m)ethyl ester reverses the deleterious effects of morphine on ventilation and arterial blood gas chemistry while promoting antinociception.

We have identified thiolesters that reverse the negative effects of opioids on breathing without compromising antinociception. Here we report the effects of D-cystine diethyl ester (D-cystine diEE) or D-cystine dimethyl ester (D-cystine diME) on morphine-induced changes in ventilation, arterial-blood gas chemistry, A-a gradient (index of gas-exchange in the lungs) and antinociception in freely moving rats. Injection of morphine (10 mg/kg, IV) elicited negative effects on breathing (e.g., depression of tidal volume, minute ventilation, peak inspiratory flow, and inspiratory drive). Subsequent injection of D-cystine diEE (500 µmol/kg, IV) elicited an immediate and sustained reversal of these effects of morphine. Injection of morphine (10 mg/kg, IV) also elicited pronounced decreases in arterial blood pH, pO2 and sO2 accompanied by pronounced increases in pCO2 (all indicative of a decrease in ventilatory drive) and A-a gradient (mismatch in ventilation-perfusion in the lungs). These effects of morphine were reversed in an immediate and sustained fashion by D-cystine diME (500 µmol/kg, IV). Finally, the duration of morphine (5 and 10 mg/kg, IV) antinociception was augmented by D-cystine diEE. D-cystine diEE and D-cystine diME may be clinically useful agents that can effectively reverse the negative effects of morphine on breathing and gas-exchange in the lungs while promoting antinociception. Our study suggests that the D-cystine thiolesters are able to differentially modulate the intracellular signaling cascades that mediate morphine-induced ventilatory depression as opposed to those that mediate morphine-induced antinociception and sedation.

The effect of omega-3 fatty acid supplementation on clinical and biochemical parameters of critically ill patients with COVID-19: a randomized clinical trial.

BACKGROUND: Omega-3 polyunsaturated fatty acids (n3-PUFAs) may exert beneficial effects on the immune system of patients with viral infections. This paper aimed to examine the effect of n3-PUFA supplementation on inflammatory and biochemical markers in critically ill patients with COVID-19. METHODS: A double-blind, randomized clinical trial study was conducted on 128 critically ill patients infected with COVID-19 who were randomly assigned to the intervention (fortified formula with n3-PUFA) (n = 42) and control (n = 86) groups. Data on 1 month survival rate, blood glucose, sodium (Na), potassium (K), blood urea nitrogen (BUN), creatinine (Cr), albumin, hematocrit (HCT), calcium (Ca), phosphorus (P), mean arterial pressure (MAP), O2 saturation (O2sat), arterial pH, partial pressure of oxygen (PO2), partial pressure of carbon dioxide (PCO2), bicarbonate (HCO3), base excess (Be), white blood cells (WBCs), Glasgow Coma Scale (GCS), hemoglobin (Hb), platelet (Plt), and the partial thromboplastin time (PTT) were collected at baseline and after 14 days of the intervention. RESULTS: The intervention group had significantly higher 1-month survival rate and higher levels of arterial pH, HCO3, and Be and lower levels of BUN, Cr, and K compared with the control group after intervention (all P < 0.05). There were no significant differences between blood glucose, Na, HCT, Ca, P, MAP, O2sat, PO2, PCO2, WBCs, GCS, Hb, Plt, PTT, and albumin between two groups. CONCLUSION: Omega-3 supplementation improved the levels of several parameters of respiratory and renal function in critically ill patients with COVID-19. Further clinical studies are warranted. Trial registry Name of the registry: This study was registered in the Iranian Registry of Clinical Trials (IRCT); Trial registration number: IRCT20151226025699N3; Date of registration: 2020.5.20; URL of trial registry record: https://en.irct.ir/trial/48213.

Mobilization Started Within 2 Hours After Abdominal Surgery Improves Peripheral and Arterial Oxygenation: A Single-Center Randomized Controlled Trial.

OBJECTIVE: The aim of this study was to investigate if mobilization out of bed, within 2 hours after abdominal surgery, improved participants' respiratory function and whether breathing exercises had an additional positive effect. METHODS: Participants were 214 consecutively recruited patients who underwent elective open or robot-assisted laparoscopic gynecological, urological, or endocrinological abdominal surgery with an anesthetic duration of >2 hours. They were recruited to a randomized controlled trial. Immediately after surgery, patients were randomly assigned to 1 of 3 groups: mobilization (to sit in a chair) and standardized breathing exercises (n = 73), mobilization (to sit in a chair) only (n = 76), or control (n = 65). The interventions started within 2 hours after arrival at the postoperative recovery unit and continued for a maximum of 6 hours. The primary outcomes were differences in peripheral oxygen saturation (SpO2, as a percentage) and arterial oxygen pressure (PaO2, measured in kilopascals) between the groups. Secondary outcomes were arterial carbon dioxide pressure, spirometry, respiratory insufficiency, pneumonia, and length of stay. RESULTS: Based on intention-to-treat analysis (n = 214), patients who received mobilization and breathing exercises had significantly improved SpO2 (mean difference [MD] = 2.5%; 95% CI = 0.4 to 4.6) and PaO2 (MD = 1.40 kPa; 95% CI = 0.64 to 2.17) compared with the controls. For mobilization only, there was an increase in PaO2 (MD = 0.97 kPa; 95% CI = 0.20 to 1.74) compared with the controls. In the per-protocol analysis (n = 201), there were significant improvements in SpO2 and PaO2 for both groups receiving mobilization compared with the controls. Secondary outcome measures did not differ between groups. CONCLUSION: Mobilization out of bed, with or without breathing exercises, within 2 hours after elective abdominal surgery improved SpO2 and PaO2. IMPACT: The respiratory effect of mobilization (out of bed) immediately after surgery has not been thoroughly evaluated in the literature. This study shows that mobilization out of bed following elective abdominal surgery can improve SpO2 and PaO2. LAY SUMMARY: Mobilization within 2 hours after elective abdominal surgery, with or without breathing exercises, can improve patients' respiratory function.

Non-invasive monitoring of carboxyhemoglobin during hyperbaric oxygen therapy.

Introduction: This study aimed to assess the capability of a pulse CO-oximeter to continuously monitor carboxyhemoglobin (COHb) during hyperbaric oxygen (HBO2) therapy. We estimated limits of agreement (LOA) between blood gas analysis and pulse CO-oximeter for COHb during HBO2 therapy in patients suffering from acute CO poisoning. Furthermore, we did a medicotechnical evaluation of the pulse CO-oximeter in hyperbaric conditions. Methods: We conducted a prospective, non-clinical, observational study in which we included n=10 patients with acute CO poisoning referred for HBO2 therapy. We did five repeated measurements of COHb for each patient during the HBO2 therapy. Bland-Altman analysis for multiple observations per individual was used to assess the agreement. The a priori LOA was ±6% for COHb. For the medicotechnical evaluation continuous measurements were obtained throughout each complete HBO2 therapy. The measurements were visually inspected and evaluated. Results: The Bland-Altman analysis showed that the pulse CO-oximeter overestimated COHb by 2.9 % [±1.0%] and the LOA was ±7.3% [±1.8%]. The continuous measurements by pulse CO-oximetry showed fluctuating levels of COHb and summarized saturations reached levels above 100%. Measurements were not affected by changes in pressure. Conclusion: To our knowledge, this study is the first to assess LOA and demonstrate use of a non-invasive method to measure COHb during HBO2 therapy. The pulse CO-oximeter performed within the manufactures reported LOA (±6%) despite hyperbaric conditions and was unaffected by changes in pressure. However, summarized saturations reached levels above 100%.

Evaluation of the association between extravascular lung water and prognosis of sepsis: A protocol of systematic review.

BACKGROUND: The purpose of this study is to explore the association between extravascular lung water (EVLW) and prognosis of sepsis (PS). METHODS: We will carry out comprehensive literature search in electronic databases (PUBMED/MEDLINE, EMBASE, CENTRAL, WorldSciNet, PsycINFO, Allied and Complementary Medicine Database, CBM, and CNKI) and additional sources. All electronic databases will be searched from their initial to the present without language restrictions. Case-controlled studies reporting the association between EVLW and PS will be evaluated for inclusion. Outcomes of interest will include mortality rate, extravascular lung water index, pulmonary vascular permeability index, blood lactate clearance, oxygenation index, blood gas analysis, PaO2/FiO2, cardiac output index, global end diastolic volume index, intrathoracic blood volume index, systemic resistance index, acute physiology and chronic health scoring system II, and infection-related organ failure scoring system. Study quality will be evaluated using Newcastle-Ottawa Tool, and statistical analysis will be performed utilizing RevMan 5.4 software. RESULTS: This study will summarize the most recent evidence to investigate the association between EVLW and PS. CONCLUSIONS: The results of this study will provide an exhaustive view of the association between EVLW and PS. STUDY REGISTRATION OSF: osf.io/vhnxw.

Application of Molecular Hydrogen as an Antioxidant in Responses to Ventilatory and Ergogenic Adjustments during Incremental Exercise in Humans.

We investigated effects of molecular hydrogen (H2) supplementation on acid-base status, pulmonary gas exchange responses, and local muscle oxygenation during incremental exercise. Eighteen healthy, trained subjects in a randomized, double-blind, crossover design received H2-rich calcium powder (HCP) (1500 mg/day, containing 2.544 µg/day of H2) or H2-depleted placebo (1500 mg/day) for three consecutive days. They performed cycling incremental exercise starting at 20-watt work rate, increasing by 20 watts/2 min until exhaustion. Breath-by-breath pulmonary ventilation (V˙E) and CO2 output (V˙CO2) were measured and muscle deoxygenation (deoxy[Hb + Mb]) was determined via time-resolved near-infrared spectroscopy in the vastus lateralis (VL) and rectus femoris (RF). Blood gases' pH, lactate, and bicarbonate (HCO3-) concentrations were measured at rest and 120-, 200-, and 240-watt work rates. At rest, the HCP group had significantly lower V˙E, V˙CO2, and higher HCO3-, partial pressures of CO2 (PCO2) versus placebo. During exercise, a significant pH decrease and greater HCO3- continued until 240-watt workload in HCP. The V˙E was significantly lower in HCP versus placebo, but HCP did not affect the gas exchange status of V˙CO2 or oxygen uptake (V˙O2). HCP increased absolute values of deoxy[Hb + Mb] at the RF but not VL. Thus, HCP-induced hypoventilation would lead to lower pH and secondarily impaired balance between O2 delivery and utilization in the local RF during exercise, suggesting that HCP supplementation, which increases the at-rest antioxidant potential, affects the lower ventilation and pH status during incremental exercise. HPC induced a significantly lower O2 delivery/utilization ratio in the RF but not the VL, which may be because these regions possess inherently different vascular/metabolic control properties, perhaps related to fiber-type composition.

Evaluation of the efficacy and safety of inhaled magnesium sulphate in combination with standard treatment in patients with moderate or severe COVID-19: A structured summary of a study protocol for a randomised controlled trial.

OBJECTIVES: Basic and clinical studies have shown that magnesium sulphate ameliorates lung injury and controls asthma attacks by anti-inflammatory and bronchodilatory effects. Both intravenous and inhaled magnesium sulphate have a clinical impact on acute severe asthma by inhibition of airway smooth muscle contraction. Besides, magnesium sulphate can dilate constricted pulmonary arteries and reduce pulmonary artery resistance. However, it may affect systemic arteries when administered intravenously. A large number of patients with covid-19 admitted to the hospital suffer from pulmonary involvement. COVID-19 can cause hypoxia due to the involvement of the respiratory airways and parenchyma along with circulatory impairment, which induce ventilation-perfusion mismatch. This condition may result in hypoxemia and low arterial blood oxygen pressure and saturation presented with some degree of dyspnoea and shortness of breath. Inhaled magnesium sulphate as a smooth muscle relaxant (natural calcium antagonist) can cause both bronchodilator and consequently vasodilator effects (via a direct effect on alveolar arterioles in well-ventilated areas) in the respiratory tract. We aim to investigate if inhaled magnesium sulphate as adjuvant therapy to standard treatment can reduce ventilation-perfusion mismatch in the respiratory tract and subsequently improve arterial oxygen saturation in hospitalized patients with COVID-19. TRIAL DESIGN: A multi-centre, open-label, randomised controlled trial (RCT) with two parallel arms design (1:1 ratio) PARTICIPANTS: Patients aged 18-80 years hospitalized at Masih Daneshvari Hospital and Shahid Dr. Labbafinejad hospital in Tehran and Shahid Sadoughi Hospital in Yazd will be included if they meet the inclusion criteria of the study. Inclusion criteria are defined as 1. Confirmed diagnosis of SARS-CoV-2 infection based on polymerase chain reaction (PCR) of nasopharyngeal secretions or clinical manifestations along with chest computed tomography (chest CT) scan 2. Presenting with moderate or severe COVID-19 lung involvement confirmed with chest CT scan and arterial oxygen saturation below 93% 3. Length of hospital stay ≤48 hours. Patients with underlying cardiovascular diseases including congestive heart failure, bradyarrhythmia, heart block, the myocardial injury will be excluded from the study. INTERVENTION AND COMPARATOR: Participants will be randomly divided into two arms. Patients in the intervention arm will be given both standard treatment for COVID-19 (according to the national guideline) and magnesium sulphate (5 cc of a 20% injectable vial or 2 cc of a 50% injectable vial will be diluted by 50 cc distilled water and nebulized via a mask) every eight hours for five days. Patients in the control (comparator) arm will only receive standard treatment for COVID-19. MAIN OUTCOMES: Improvement of respiratory function and symptoms including arterial blood oxygen saturation, dyspnoea (according to NYHA functional classification), and cough within the first five days of randomization. RANDOMISATION: Block randomisation will be used to allocate eligible patients to the study arms (in a 1:1 ratio). Computer software will be applied to randomly select the blocks. BLINDING (MASKING): The study is an open-label RCT without blinding. NUMBERS TO BE RANDOMISED (SAMPLE SIZE): The trial will be performed on 100 patients who will be randomly divided into two arms of control (50) and intervention (50). TRIAL STATUS: The protocol is Version 5.0, January 05, 2021. Recruitment of the participants started on July 30, 2020, and it is anticipated to be completed by February 28, 2021. TRIAL REGISTRATION: The trial was registered in the Iranian Registry of Clinical Trials (IRCT) on July 28, 2020. It is available on https://en.irct.ir/trial/49879 . The registration number is IRCT20191211045691N1. FULL PROTOCOL: The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest of expediting the dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.

Diagnosis of Hepatopulmonary Syndrome in a Large Integrated Health System.

BACKGROUND & AIMS: Data on the accuracy of the diagnosis of hepatopulmonary syndrome (HPS) in cirrhosis is limited. We evaluated the clinical characteristics of patients with International Classification of Diseases (ICD) codes for hepatopulmonary syndrome (HPS) in a large integrated health system. METHODS: A retrospective review of encounters was performed of all patients with ICD-9-CM and/or ICD-10-CM diagnosis of cirrhosis and HPS from 2014-2019 in a multi-state health system. Demographics and cardiopulmonary testing closest to the time of HPS diagnosis were recorded. HPS was defined using standard criteria. RESULTS: A total of 42,749 unique individuals with cirrhosis were identified. An ICD diagnosis of HPS was found in 194 patients (0.45%), of which 182 had clinically confirmed cirrhosis. 143 (78.5%) underwent contrast-enhanced transthoracic echocardiography, and 98 (54%) had delayed shunting. Among them, 61 patients had a documented arterial blood gas, with 53 showing abnormal oxygenation (A-a gradient of >15 mm Hg). 12 were excluded due to significant pulmonary function test abnormalities and abnormal oxygenation from other cardiopulmonary diseases. Ultimately, 41 (22.5%) fulfilled the criteria for HPS. When stratifying those with an ICD code diagnosis of HPS into HPS, no HPS and indeterminate HPS groups, based on standard diagnostic criteria for HPS, we found that the confirmed HPS patients had similar complications except for less portopulmonary hypertension, worse gas exchange, less cardiopulmonary disease and were more often diagnosed in transplant centers. CONCLUSIONS: The diagnosis of HPS by ICD code is made in an extremely small subset of a sizeable cirrhotic cohort. When made, only a minority of these patients meet diagnostic criteria. Our findings highlight the need for improved education and more effective screening algorithms.

Bicarbonate Unlocks the Ergogenic Action of Ketone Monoester Intake in Endurance Exercise.

PURPOSE: We recently reported that oral ketone ester (KE) intake before and during the initial 30 min of a 3 h 15 min simulated cycling race (RACE) transiently decreased blood pH and bicarbonate without affecting maximal performance in the final quarter of the event. We hypothesized that acid-base disturbances due to KE overrules the ergogenic potential of exogenous ketosis in endurance exercise. METHODS: Nine well-trained male cyclists participated in a similar RACE consisting of 3 h submaximal intermittent cycling (IMT180') followed by a 15-min time trial (TT15') preceding an all-out sprint at 175% of lactate threshold (SPRINT). In a randomized crossover design, participants received (i) 65 g KE, (ii) 300 mg·kg-1 body weight NaHCO3 (BIC), (iii) KE + BIC, or (iv) a control drink (CON), together with consistent 60 g·h-1 carbohydrate intake. RESULTS: KE ingestion transiently elevated blood D-ß-hydroxybutyrate to ~2-3 mM during the initial 2 h of RACE (P < 0.001 vs CON). In KE, blood pH concomitantly dropped from 7.43 to 7.36 whereas bicarbonate decreased from 25.5 to 20.5 mM (both P < 0.001 vs CON). Additional BIC resulted in 0.5 to 0.8 mM higher blood D-ß-hydroxybutyrate during the first half of IMT180' (P < 0.05 vs KE) and increased blood bicarbonate to 31.1 ± 1.8 mM and blood pH to 7.51 ± 0.03 by the end of IMT180' (P < 0.001 vs KE). Mean power output during TT15' was similar between KE, BIC, and CON at ~255 W but was 5% higher in KE + BIC (P = 0.02 vs CON). Time to exhaustion in the sprint was similar between all conditions at ~60 s (P = 0.88). Gastrointestinal symptoms were similar between groups. DISCUSSION: The coingestion of oral bicarbonate and KE enhances high-intensity performance at the end of an endurance exercise event without causing gastrointestinal distress.

Carbohydrate and Glutamine Supplementation Attenuates the Increase in Rating of Perceived Exertion during Intense Exercise in Hypoxia Similar to 4200 m.

The rating of perceived exertion (RPE) indicates the feeling of fatigue. However, hypoxia worsens the condition and can worsen RPE. We evaluated whether carbohydrate and glutamine supplementation alters RPE and physiological markers in running at 70% peak oxygen uptake until exhaustion in a simulated altitude of 4500 m. Nine volunteers underwent three running tests at 70% peak oxygen uptake until exhaustion: (1) hypoxia and placebo, (2) hypoxia and 8% maltodextrin, and (3) hypoxia after six days of glutamine supplementation (20 g/day) and 8% maltodextrin. The exercise and supplementation were randomized and double-blinded. Lactate, heart rate, haemoglobin O2 saturation (SpO2%), and RPE (6-20 scale) were analyzed at the 15th and 30th min. The level of significance was set at p ≤ 0.05. SpO2% decreased at the 15th and 30th minutes compared to resting in placebo, carbohydrate, and glutamine supplementation. RPE increased at the 30th minute compared to the 15th minute in placebo and carbohydrate supplementation; however, there was no difference in the glutamine supplementation condition. Heart rate and lactate increased after the 15th and 30th minutes compared to resting, similar to the three conditions studied. We conclude that previous supplementation with glutamine and carbohydrate during intense exercise in hypoxia similar to 4500 m can attenuate the increase in RPE by the increase in glycemia and can be a useful strategy for people who exercise in these conditions.