Arterial Oxygen Pressure Research Articles

Efficacy and safety of extracorporeal membrane oxygenation combined with continuous renal replacement therapy in the management of pediatric acute respiratory distress syndrome

BackgroundThe efficacy and safety of combining extracorporeal membrane oxygenation with continuous renal replacement therapy remain controversial. This study aimed to evaluate the efficacy and safety of extracorporeal membrane oxygenation combined with continuous renal replacement therapy in the treatment of pediatric acute respiratory distress syndrome.MethodsThis retrospective study, conducted at Hunan Children's Hospital between January 2019 and December 2023, included 30 pediatric patients with acute respiratory distress syndrome who underwent extracorporeal membrane oxygenation treatment. The patients were divided into two groups based on whether continuous renal replacement therapy was used during treatment: 21 in the extracorporeal membrane oxygenation with continuous renal replacement therapy group and nine in the extracorporeal membrane oxygenation-only group. The groups were compared using t-test or Wilcoxon rank-sum test.ResultsThis study included 19 (63.3%) male and 11 (36.7%) female patients (mean age: 63.33 ± 54.41 months). The ratios of arterial partial pressure of oxygen to fraction of inspired oxygen before and at withdrawal of extracorporeal membrane oxygenation were 58.50 (40.75–70.31) and 257.00 (113.25–358.33) mmHg, respectively (P < 0.05). In the extracorporeal membrane oxygenation with continuous renal replacement therapy group, 21 patients (70.0%) underwent continuous renal replacement therapy, including those with acute renal injury (n = 5), fluid overload (n = 13), hyperkalemia (n = 3), and removal of inflammatory mediators (n = 3), and improvement was observed.ConclusionsThe combination of extracorporeal membrane oxygenation and continuous renal replacement therapy provides safe and effective respiratory support for pediatric patients with severe acute respiratory distress syndrome and enables effective fluid-balance management, removal of inflammatory factors, and maintenance of electrolyte equilibrium.

Effect of driving pressure-guided individualised positive end-expiratory pressure on postoperative atelectasis in patients with morbid obesity: study protocol of a randomised controlled trial

IntroductionAtelectasis is a common postoperative complication in patients with obesity, contributing to respiratory insufficiency, pneumonia and poor clinical outcomes. Studies have shown that driving pressure (DP)-guided individualised positive end-expiratory pressure...

Respiratory anatomy and physiology in diving penguins.

The anatomy and function of the respiratory systems of penguins are reviewed in relation to gas exchange and minimization of the risks of pulmonary barotrauma, decompression sickness and nitrogen narcosis during dives. Topics include available lung morphology and morphometry, respiratory air volumes determined with different techniques, review of possible physiological and biomechanical mechanisms of baroprotection, calculations of baroprotection limits and review of air sac and arterial partial pressure of oxygen (PO2) profiles in relation to movement of air during breathing and during dives. Limits for baroprotection to 200, 400 and 600 m in Adélie, king and emperor penguins, respectively, would require complete transfer of air sac air and reductions in the combined tracheobronchial tree-parabronchial volume of 24% in Adélie, 53% in king penguins and 76% in emperor penguins. Air sac and arterial PO2 profiles at rest and during surface activity were consistent with unidirectional air flow through the lungs. During dives, PO2 profiles were more complex, but were consistent with compression of air sac air into the parabronchi and air capillaries with or without additional air mixing induced by potential differential air sac pressures generated by wing movements.This article is part of the theme issue 'The biology of the avian respiratory system'.

Baricitinib combined with methylprednisolone on inflammatory factors in patients with severe pneumonia

Objective: This work aims to assess the effect of baricitinib in combination with methylprednisolone in patients with pneumonia in severe conditions and their impact on inflammation markers. Methods: From DECEMBER 2022 to AUGUST 2023, 182 patients diagnosed with severe pneumonia formed the sampling frame. These selected patients were then divided into two groups based on a random number table, with 91 patients in each group. Both groups underwent treatment under a traditional placebo. The control group received methylprednisolone, while the experimental group was treated with methylprednisolone in combination with baricitinib. They were treated similarly for seven days. The groups’ peri-operative blood gas, inflammatory parameters, and drug safety were compared. Results: On the seventh day of the intervention, both the groups had improved with the blood gas parameters. Additionally, the results showed that the experimental group possessed significantly higher peripheral oxygen saturation (SpO2), partial pressure of arterial oxygen (PaO2), and oxygenation index (OI) as compared to the control group (P < 0.05). The experimental group also showed a higher level of carbon dioxide than the control group, P < 0. The experimental group had a mean partial pressure (PaCO2) lower as compared to that of the control group (P < 0). Further, the finding of the observation group, on average, had a significantly lower concentration of CRP, IL-6, and IL-10 during the seventh day compared to the control group (P<0). The result showed no statistically significant difference in the frequency of adverse reactions in the two groups when the medication was given (P > 0.05). Therefore, the utilization of baricitinib in combination with methylprednisolone can ameliorate blood gas parameters and indicate the levels of inflammatory markers in patients with severe pneumonia. Therefore, the medicine is considered safe and has the potential for wider clinical application.

Effect of different positive end-expiratory pressure levels in patients undergoing laparoscopic cholecystectomy under general anesthesia.

To investigate the effect of different levels of positive end-expiratory pressure (PEEP) in patients undergoing laparoscopic cholecystectomy under general anesthesia. This retrospective study included patients who underwent laparoscopic cholecystectomy under general anesthesia in the Xuzhou Hospital of Traditional Chinese Medicine from January, 2023 to March, 2024. Based on the PEEP levels, patients were grouped into 0cm group (0cmH2O), 5cm group (5cmH2O), 8cm group (8cmH2O), and 10cm group (10cmH2O). Mean arterial pressure (MAP), mean airway pressure (Pmean), peak airway pressure (Ppeak), and blood gas status levels (oxygenation index[OI], arterial partial pressure of oxygen [PaO2], and arterial partial pressure of carbon dioxide [PaCO2]) of all four groups were measured at five minutes after the intubation (T1), five minutes after pneumoperitoneum (T2), and 30 minutes after pneumoperitoneum (T3). A total of 84 patients (37 males and 47 females) were included in this study. The number of patients in the 0cm group, 5cm group, 8cm group, and 10cm group were 24, 24, 21, and 15, respectively, and there were no significant differences in the baseline data among the four groups. There were significant differences in Pmean, Ppeak, and MAP between the four groups at T2 and T3. The increase in PEEP was accompanied by a gradual increase in Pmean and Ppeak (P<0.05). There were significant differences in OI, PaCO2, and PaO2 among the four groups at T2 and T3. With the increase in PEEP, OI and PaO2 values continued to increase while PaCO2 continued to decrease (P<0.05). During laparoscopic cholecystectomy under general anesthesia, PEEP = 5cmH2O can inhibit a significant decrease in MAP while ensuring the patient's blood gas and respiratory mechanics status, which can ensure hemodynamic stability.

Functional outcomes of inspiratory muscle training in elderly with intensive care unit-acquired weakness and severe walking disability.

Intensive care unit acquired-weakness syndrome (ICUAWS) leaves several complications in functional movements of patients such as severe walking disability. Assessment of functional outcomes of 1-month inspiratory muscle training (IMT) in elderly with ICUAWS and severe walking disability was our aim. The design, setting, participants, and intervention. This study is a randomized controlled trial. ICUAWS patients who complained of severe walking disability on the Modified Functional Ambulatory Category Test (MFACT) were randomly assigned into the IMT group or control group, n = 20 for each group. Both groups received the traditional physical therapy program. The results showed that the post-therapy between-group comparison of ICUAWS sufferers/groups' parameters showed a significant improvement toward the IMT group in six-minute walk test, inspiratory and expiratory muscle strength, forced vital capacity, time up and go test, 10-m walk test, forced expiratory volume in the first second, 30-s sit-to-stand test, partial pressure of arterial blood oxygen and carbon dioxide, MFACT, oxygen saturation of arterial blood, physical, and mental summary of short form 36. In conclusion, IMT improves functional outcomes in ICUAWS patients with walking disability. The clinical trial ID of this ICUAWS trial is NCT06210763.

Effects of very early hyperoxemia on neurologic outcome after out-of-hospital cardiac arrest: A secondary analysis of the TTM-2 trial.

Effects of very early hyperoxemia on neurologic outcome after out-of-hospital cardiac arrest: A secondary analysis of the TTM-2 trial.

Decreased Arterial Oxygen Pressure Indicates Hypoxemia, a Well-Known Clinical Sign of Pulmonary Embolism [Letter

Decreased Arterial Oxygen Pressure Indicates Hypoxemia, a Well-Known Clinical Sign of Pulmonary Embolism [Letter

Oxygenation improvement and duration of prone positioning are associated with ICU mortality in mechanically ventilated COVID-19 patients

BackgroundProne position has been diffusely applied in mechanically ventilated COVID-19 patients. Our aim is ascertaining the association between the physiologic response and the length of the first cycle of prone position and intensive care unit (ICU) mortality.MethodsInternational registry including COVID-19 adult patients who underwent prone positioning. We measured the difference for arterial partial pressure of oxygen to inspired fraction of oxygen ratio (PaO2/FiO2), ventilatory ratio, and respiratory system compliance (Crs) between baseline supine position and at either the end of the first cycle of prone position (Delta-PP) or re-supination (Delta-PostPP).ResultsWe enrolled 1816 patients from 53 centers. Delta-PP and Delta-PostPP for PaO2/FiO2 were both associated with ICU mortality [OR (95% CI) 0.48 (0.38, 0.59), and OR (95% CI) 0.60 (0.52, 0.68), respectively]. Ventilatory ratio had a non-linear relationship with ICU mortality for Delta-PP (p = 0.022) and Delta-PostPP (p = 0.004). Delta-PP, while not Delta-PostPP, for Crs was associated with ICU mortality [OR (95% CI) 0.80 (0.65, 0.98)]. The length of the first cycle of prone position showed an inverse relationship with ICU mortality [OR (95% CI) 0.82 (0.73, 0.91)]. At the multivariable analysis, the duration of the first cycle of prone position, Delta-PP and Delta-PostPP for PaO2/FiO2, and Delta-PostPP for ventilatory ratio were independently associated with ICU mortality.ConclusionIn COVID-19 patients with acute respiratory failure receiving invasive mechanical ventilation and prone positioning, the physiological response to prone position is associated with ICU mortality. Prolonging the duration of the first cycle of prone position is associated with improved survival.

Perioperative changes in lung re-transplantation: a single-centre observational study.

Reports describing the management of lung re-transplantation (Re-LTx) are lacking. Therefore, this study evaluated the characteristics of Re-LTx to guide perioperative management. This study retrospectively analysed the clinical data of patients who underwent primary lung transplantation (primary-LTx) and Re-LTx in the First Affiliated Hospital of Guangzhou Medical University from 2016 to 2023. The key perioperative changes after Re-LTx (primary outcome) and the short-term postoperative rehabilitation characteristics (secondary outcome) were evaluated. The study included 26 patients who underwent primary LTx who were propensity score-matched (1:2) with 13 patients who underwent Re-LTx. The preoperative Acute Physiology and Chronic Health Evaluation (APACHE) score was higher in the Re-LTx group (P=0.001). The intraoperative conditions, incidence of postoperative extracorporeal membrane oxygenation (ECMO) support, intensive care unit (ICU) stay, duration of postoperative hospital stay, total hospital stay, and complications on postoperative day seven did not differ between the groups (P>0.05). However, the intraoperative haemoglobin and fibrinogen levels were lower (P=0.002 and P=0.03, respectively), and the blood urea nitrogen and serum creatinine levels were higher in the Re-LTx group (both P<0.001). The pH, arterial oxygen pressure, partial pressure of carbon dioxide, and haemodynamic values did not differ between the groups (P>0.05). The perioperative management of Re-LTx may be similar to that of primary LTx based on comparable intraoperative conditions and postoperative rehabilitation characteristics. However, patients undergoing Re-LTx were prone to renal dysfunction and intraoperative anaemia.

An animal model of severe acute respiratory distress syndrome for translational research

BackgroundDespite the fact that an increasing number of studies have focused on developing therapies for acute lung injury, managing acute respiratory distress syndrome (ARDS) remains a challenge in intensive care medicine. Whether the pathology of animal models with acute lung injury in prior studies differed from clinical symptoms of ARDS, resulting in questionable management for human ARDS. To evaluate precisely the therapeutic effect of transplanted stem cells or medications on acute lung injury, we developed an animal model of severe ARDS with lower lung function, capable of keeping the experimental animals survive with consistent reproducibility. Establishing this animal model could help develop the treatment of ARDS with higher efficiency.ResultsIn this approach, we intratracheally delivered bleomycin (BLM, 5 mg/rat) into rats’ left trachea via a needle connected with polyethylene tube, and simultaneously rotated the rats to the left side by 60 degrees. Within seven days after the injury, we found that arterial blood oxygen saturation (SpO2) significantly decreased to 83.7%, partial pressure of arterial oxygen (PaO2) markedly reduced to 65.3 mmHg, partial pressure of arterial carbon dioxide (PaCO2) amplified to 49.2 mmHg, and the respiratory rate increased over time. Morphologically, the surface of the left lung appeared uneven on Day 1, the alveoli of the left lung disappeared on Day 2, and the left lung shrank on Day 7. A histological examination revealed that considerable cell infiltration began on Day 1 and lasted until Day 7, with a larger area of cell infiltration. Serum levels of IL-5, IL-6, IFN-γ, MCP-1, MIP-2, G-CSF, and TNF-α substantially rose on Day 7.ConclusionsThis modified approach for BLM-induced lung injury provided a severe, stable, and one-sided (left-lobe) ARDS animal model with consistent reproducibility. The physiological symptoms observed in this severe ARDS animal model are entirely consistent with the characteristics of clinical ARDS. The establishment of this ARDS animal model could help develop treatment for ARDS.

Mountain sickness: physiological challenges, diagnosis and treatment

INTRODUCTION. The first descriptions of altitude sickness were made in (1540-1600). Nowadays, different cities in the world are at high altitude, for example Qinghai-Tibetan Plateau in China occupies an area of almost 2.5 million inhabitants km2, with an average elevation of over 4,500 m. Altitude sickness should be a major concern for anyone who normally resides at sea level. METHOD. A search for information was carried out in the period August-December 2024 in the SciELO, LILACS, Scopus, PubMed-MedLine databases, the Google Scholar search engine, as well as in the ClinicalKeys services. RESULTS AND DISCUSSION. The partial pressure of arterial oxygen (PaO2 ) decreases with altitude, which produces progressive tissue hypoxia. The normal compensatory response to hypobaric hypoxia is called acclimatization. Its main characteristic is increased ventilation. The ability to acclimatize varies widely among individuals and depends on many factors, including the degree of hypoxic stress (rate of ascent, altitude reached), the intrinsic ability of the individual to compensate for the decrease in PaO2, and extrinsic factors. Progressive ascent produces greater hypoxic stress, requiring greater degrees of physiological and behavioral adaptations to preserve function. The more rapid the ascent and the higher the altitude, the greater the stress. Below 1500 m, symptoms of high altitude illness are generally not manifest. From approximately 1500 to 2500 m, symptoms are generally mild, if experienced at all. From approximately 2500 m, mild to moderate symptoms become quite common among unacclimatized visitors after a rapid ascent. As a general rule, people who normally reside below 1500 m should avoid an abrupt ascent to altitudes above 2800 m for sleeping. Sedative-hypnotics should be avoided during acclimatization. Abstinence from alcohol is safest

A high fraction of inspired oxygen does not mitigate atelectasis-induced lung tissue hypoxia or injury in experimental acute respiratory distress syndrome

Although alveolar hyperoxia exacerbates lung injury, clinical studies have failed to demonstrate the beneficial effects of lowering the fraction of inspired oxygen (FIO2) in patients with acute respiratory distress syndrome (ARDS). Atelectasis, which is commonly observed in ARDS, not only leads to hypoxemia but also contributes to lung injury through hypoxia-induced alveolar tissue inflammation. Therefore, it is possible that excessively low FIO2 may enhance hypoxia-induced inflammation in atelectasis, and raising FIO2 to an appropriate level may be a reasonable strategy for its mitigation. In this study, we investigated the effects of different FIO2 levels on alveolar tissue hypoxia and injury in a mechanically ventilated rat model of experimental ARDS with atelectasis. Rats were intratracheally injected with lipopolysaccharide (LPS) to establish an ARDS model. They were allocated to the low, moderate, and high FIO2 groups with FIO2 of 30, 60, and 100%, respectively, a day after LPS injection. All groups were mechanically ventilated with an 8 mL/kg tidal volume and zero end-expiratory pressure to induce dorsal atelectatic regions. Arterial blood gas analysis was performed every 2 h. After six hours of mechanical ventilation, the rats were euthanized, and blood, bronchoalveolar lavage fluid, and lung tissues were collected and analyzed. Another set of animals was used for pimonidazole staining of the lung tissues to detect the hypoxic region. Lung mechanics, ratios of partial pressure of arterial oxygen (PaO2) to FIO2, and partial pressure of arterial carbon dioxide were not significantly different among the three groups, although PaO2 changed with FIO2. The dorsal lung tissues were positively stained with pimonidazole regardless of FIO2, and the HIF-1α concentrations were not significantly different among the three groups, indicating that raising FIO2 could not rescue alveolar tissue hypoxia. Moreover, changes in FIO2 did not significantly affect lung injury or inflammation. In contrast, hypoxemia observed in the low FIO2 group caused injury to organs other than the lungs. Raising FIO2 levels did not attenuate tissue hypoxia, inflammation, or injury in the atelectatic lung region in experimental ARDS. Our results indicate that raising FIO2 levels to attenuate atelectasis-induced lung injury cannot be rationalized.

Cerebral tissue oxygen saturation and its potential relationship with neurodevelopmental delay in pediatric liver transplant recipients.

To discover the potential association between diminished intraoperative average SctO2 levels and postoperative neurodevelopmental delays among patients after pediatric living-donor liver transplantation. Patients undergoing living-donor liver transplantation were recruited for this trial. The neurodevelopment status of patients was assessed using the Ages Stages Questionnaires. The primary outcome was the occurrence of neurodevelopmental delay among patients at different intervals following pediatric liver transplantation. Secondary outcomes included the duration of mechanical ventilation, rates of re-intubation, length of ICU stay, postoperative hospitalization, and intraoperative comparisons of mean arterial pressure (MAP), arterial partial pressure of oxygen (PaO2), arterial partial pressure of carbon dioxide (PaCO2), and hemoglobin (Hb) concentration. A total of 119 patients were included in the statistical analysis and assigned to high saturation group (HS) and low saturation group (LS) according to the average intraoperative cerebral tissue oxygen saturation values. Following adjustment for PELD scores, significant differences between the two groups were observed for the incidence of neurodevelopmental delay in communication at 1 and 3 months follow-up (P = 0.019 and P = 0.020, respectively), fine motor at six months follow-up (P = 0.014), and problem-solving abilities at one year follow-up (P = 0.047). Moverover, the length of ICU stay (P = 0.009) and postoperative hospitalization (P = 0.029) in LS group were also significant prolonged. This prospective observational study revealed that the patients with low average SctO2 values were more predisposed to experiencing postoperative neurodevelopment delays, suggesting a potential association between decreased average SctO2 and neurodevelopmental delay.

Acute respiratory distress syndrome : Pathophysiology, definition and treatment strategies

Acute respiratory distress syndrome (ARDS) is defined as an acute inflammatory syndrome leading to increased pulmonary capillary leakage and subsequent interstitial and alveolar pulmonary edema. Hypoxia is the predominant symptom. The definition of ARDS comprises acute onset, bilateral patchy infiltration on chest X‑ray and areduction of the ratio of arterial partial pressure of oxygen (PaO2) to the fraction of inspired oxygen (FiO2), which also determines the classification into mild (≤ 300), moderate (≤ 200) and severe (≤ 100) ARDS. Treating the underlying cause is the only causal treatment measure. The aim of adjunctive therapy is the maintenance of life or organ functions by ensuring an adequate gas exchange without further damaging the lungs. Adjunctive therapy consists mainly of individually adapted "protective" ventilation treatment and the prone position. In severest ARDS, the use of venovenous extracorporeal membrane oxygenation (VV-ECMO) can improve survival if strict criteria for indications and contraindications are followed.

The effect of rivaroxaban as an anticoagulant therapy for acute pulmonary embolism and the predictive role of vascular endothelial markers in assessing anticoagulant efficacy before treatment.

Acute pulmonary embolism (PE) is a life-threatening condition requiring effective anticoagulation therapy. Rivaroxaban, a direct oral anticoagulant, offers advantages over warfarin, yet individual patient responses vary. This study examined the efficacy of rivaroxaban compared to warfarin and evaluated vascular endothelial markers as predictors of anticoagulant efficacy. We conducted a retrospective cross-over cohort study involving 295 patients with acute PE, comparing rivaroxaban (n = 158) and warfarin (n = 137) treatments. Clinical efficacy was assessed based on symptomatic improvement and imaging results. Vascular endothelial markers, including soluble thrombomodulin (sTM), circulating endothelial cells (CEC), and endothelin-1 (ET-1), were examined for their predictive capability in treatment outcomes, then the data of 97 additional patients were used for external validation. Patients who received rivaroxaban showed higher overall treatment response (93.04%) compared to those who took warfarin (74.45%; P < 0.001), and greater improvement in arterial partial pressure of oxygen (PaO2; P = 0.003). Rivaroxaban significantly altered coagulation parameters such as prothrombin time (PT) and international normalized ratio (INR). In addition, elevated sTM and reduced CEC were found to be associated with poorer anticoagulation outcomes. The areas under the receiver operating characteristic curve (AUCs) for predicting efficacy using vascular endothelial markers were 0.913 in the training cohort and 0.888 in the external validation cohort, respectively. Rivaroxaban was more effective than warfarin in treating acute PE, with specific vascular endothelial markers serving as promising predictors of therapeutic response.

Comparison of post-induction arterial partial oxygen pressure versus respiratory system compliance for predicting postanesthetic hypoxemia in 168 mechanically ventilated dogs

Comparison of post-induction arterial partial oxygen pressure versus respiratory system compliance for predicting postanesthetic hypoxemia in 168 mechanically ventilated dogs

Effect of blood purification combined with antibiotics on CC-16 and SP-D levels and prognosis in patients with severe acute pancreatitis complicated by acute respiratory distress syndrome.

To investigate the effects of continuous blood purification (CBP) combined with antibiotics on pulmonary surfactant protein D (SP-D), Clara cell protein-16 (CC-16), and prognosis in patients with severe acute pancreatitis (SAP) complicated by acute respiratory distress syndrome (ARDS). A total of 128 patients with SAP and ARDS treated at Fudan University Shanghai Cancer Center from June 2021 to June 2023 were enrolled. Patients were divided into two groups: a control group (n=64) receiving routine treatment (gastrointestinal decompression, somatostatin administration, nutritional support, correction of water-electrolyte imbalance, and microcirculation improvement) and an observation group (n=64) treated with CBP combined with antibiotics. Clinical data, including the pancreatic edema resolution time, ventilator weaning time, and hospital stay, were compared between groups. Additional comparisons included intra-abdominal pressure (IAP), blood amylase (AMS), urinary amylase (UAMY), inflammatory markers [tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), interleukin-1β (IL-1β)], respiratory mechanics indices [airway peak pressure (Peak), airway plateau pressure (Plat), respiratory rate (F)], and blood oxygen levels [partial pressure of arterial oxygen (PaO2), PaO2/fraction of inspired oxygen (FiO2)] before and after treatment. The observation group demonstrated significantly better outcomes compared to the control group in terms of pancreatic edema resolution time, ventilator weaning time, hospital stay, and other indicators (all P<0.05). The 28-day mortality rate in the observation group was significantly lower than in the control group (P<0.05). Post-treatment levels of CC-16, SP-D, Peak, Plat, and other indicators improved significantly in both groups compared to baseline (all P<0.05). The observation group exhibited significantly greater improvements in PaO2 and PaO2/FiO2 compared to the control group (all P<0.05). CBP combined with antibiotics significantly improves clinical symptoms, reduces inflammatory markers, enhances prognosis, and lowers mortality rates in patients with SAP complicated by ARDS.

Diagnostic Value of the Alveolar-Arterial Oxygen Gradient in Pulmonary Embolism: A Cross-Sectional Study.

Background/Objectives: Pulmonary embolism (PE) is a potentially serious condition characterized by the blockage of blood vessels in the lungs, often presenting significant diagnostic challenges due to its non-specific symptoms. This study aimed to evaluate the utility of the alveolar-arterial (A-a) oxygen gradient as a diagnostic tool for PE, hypothesizing that it could enhance early detection when combined with other clinical markers. Methods: We retrospectively analyzed 168 patients at the University Hospital Center Split. This study correlated A-a gradients with PE confirmed by CT pulmonary angiography. Key clinical and biochemical markers, including heart rate, C-reactive protein (CRP), pro-brain natriuretic peptide (NT-proBNP), D-dimer, high-sensitivity troponin (hs-troponin), and arterial oxygen pressure (PaO2), were assessed. Results: Our findings revealed that patients with PE had significantly higher A-a gradients than those without PE. The observed-to-expected ratio for the A-a gradient was notably increased in the PE group. Additionally, patients with PE exhibited elevated heart rate, CRP, NT-proBNP, D-dimer, and hs-troponin levels, while PaO2 levels were notably lower. Conclusions: This study demonstrates that an elevated A-a gradient reflects the severity of gas exchange impairment in PE. The results suggest that early diagnosis of PE may be improved by incorporating A-a gradient analysis alongside other clinical markers, potentially leading to more effective and timely interventions.

Repeated High-dose Fentanyl Administration in Rats Reveals Minimal Tolerance to Unconsciousness, Bradycardia, Muscle Rigidity, and Respiratory Depression.

Fentanyl is a synthetic opioid that is widely used in anesthesiology, but its illicit use is rapidly increasing. At high doses, fentanyl induces unconsciousness and muscle rigidity, the mechanisms of which are poorly understood. Since animal models are needed to study these effects, the aim of this study was to establish a rat model of fentanyl abuse and investigate the effects of repeated high-dose fentanyl injections on loss of righting reflex, heart rate, respiratory depression, muscle, and brain activity. Male and female Sprague-Dawley rats were studied (n = 40). A bolus of 100 µg/kg fentanyl was administered intravenously twice a week for 5 consecutive weeks. Time to return of righting reflex after fentanyl injection and changes in electromyography/electroencephalography activity as well as heart rate were analyzed. Additionally, arterial blood gas analysis for evaluation of ventilation was performed. Mixed-effect models with Dunnett test and effect sizes were used for statistical analysis. Repeated injections resulted in a U-shaped change in time to return of righting reflex with the longest latency after the first exposure (median, 50 [first to third quartile, 36 to 56] min) and the shortest after the fifth exposure (16 [13 to 33] min). After fentanyl administration, heart rate dropped immediately by 225 beats/min (95% CI, 179 to 271; F = 3,952.16; P < 0.001), while electromyography activity increased by 291% (95% CI, 212 to 370; F = 27.51; P < 0.001) and partial pressure of arterial carbon dioxide increased by 49.4 mmHg (95% CI, 40.6 to 58.2; F = 75.97; P < 0.001) within 5 min after injection. Additionally, pH decreased by 0.48 (95% CI, 0.41 to 0.54; F = 142.00; P < 0.01), and partial pressure of arterial oxygen decreased by 50.4 mmHg (40.8 to 60.0; F = 57.90; P < 0.001). Repeated fentanyl exposures did not significantly affect the extent of these changes (EMG, F = 1.63, P = 0.237; partial pressure of arterial carbon dioxide, F = 1.23, P = 0.312; heart rate, F = 1.05, P = 0.400; pH, F = 3.05, P = 0.066; arterial partial pressure of oxygen, F = 3.35, P = 0.052). Electroencephalography analysis revealed that repeated fentanyl exposures elicited significantly higher absolute power in frequencies greater than 20 Hz as indicated by an area under the receiver operator characteristics curve greater than 0.7. The authors established a rodent model of repeated high-dose fentanyl administration. Overall, significant evidence of tolerance was not observed after 10 exposures of high-dose fentanyl for any of the analyzed parameters. These results suggest that tolerance does not develop for fentanyl-induced unconsciousness, muscle rigidity, or respiratory depression.