Association of Sublingual Microcirculation Parameters and Capillary Refill Time in the Early Phase of ICU Admission.

OBJECTIVES: This observational study was conducted to investigate capillary refill time (CRT) during the early phase of ICU admission in relationship with microvascular flow alteration and outcome in critically ill patients. DESIGN: Prospective, observational, pilot study. SETTING: ICU in a university hospital. PATIENTS: Two hundred eighty-two critically ill adult patients admitted to the ICU. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: All patients underwent simultaneous measurements by CRT and sidestream dark field imaging within 24 hours of ICU admission. Other clinical data such as demographic characteristics, hemodynamics, laboratory values, treatment, and physiologic parameters were also included simultaneously. Microcirculatory measurements were performed at 10.2 ± 5.7 hours after ICU admission. Of the 282 included patients, 106 (37.6%) were female, the median (interquartile range) age was 63 years (53-74 yr), and the median Sequential Organ Failure Assessment (SOFA) score was 5 (2-7). The primary finding was the association between CRT and simultaneous the condition of peripheral circulation (microvascular flow index [MFI]: r = -0.4430, p < 0.001; proportion of perfused vessels: r = -0.3708, p < 0.001; heterogeneity index: r = 0.4378, p < 0.001; perfused vessel density: r = -0.1835, p = 0.0020; except total vessel density: p = 0.9641; and De Backer score: p = 0.5202) in critically ill patients. In addition, this relationship was also maintained in subgroups. Microcirculatory flow abnormalities, 28-day mortality, and SOFA score appeared to be more severe for increasing CRT. In a multivariable analysis, prolonged CRT was independently associated with microvascular flow abnormalities (MFI < 2.6; odds ratio [OR], 1.608; 95% CI, 2.1-10.2; p < 0.001). Similarly, multivariable analysis identified CRT as an independent predictor of 28-day mortality (OR, 1.296; 95% CI, 1.078-1.558; p = 0.006). CONCLUSIONS: In our ICU population, a single-spot prolonged CRT was independently associated with abnormal microcirculation and increased mortality.

Integrated analysis of clinical and genetic factors on the interindividual variation of warfarin anticoagulation efficacy in clinical practice.

AIM: The anticoagulation effect of warfarin is usually evaluated by percentage of time in therapeutic range (PTTR), which is negatively correlated with the risk of warfarin adverse reactions. This study aimed to explore the effects of genetic and nongenetic factors on anticoagulation efficacy of warfarin during different therapeutic range. METHODS: We conducted an observational retrospective study aiming at evaluating the impact of clinical and genetic factors on PTTR from initial to more than six months treatment. This analysis included patients with heart valve replace (HVR) surgery who underwent long-term or life-long time treatment with standard-dose warfarin for anticoagulation control in Second Xiangya Hospital. All patients were followed for at least 6 months. We genotyped single nucleotide polymorphisms in VKORC1 and CYP2C9 associated with altered warfarin dose requirements and tested their associations with PTTR. RESULTS: A total of 629 patients with intact clinical data and available genotype data were enrolled in this study, and only 38.63% patients achieved good anticoagulation control (PTTR > 0.6). Clinical factors, including male gender, older age, overweight, AVR surgery and stroke history, were associated with higher PTTR. Patients with VKORC1 -1639AA genotype had significantly higher PTTR level compared with GA/GG genotype carriers only in the first month of treatment. Patients with CYP2C9*3 allele had higher PTTR compared with CYP2C9*1*1 carriers. Moreover, compared with VKORC1 -1639 AG/GG carriers, INR > 4 was more likely to be present in patients with AA genotype. The frequency of CYP2C9*1*3 in patients with INR > 4 was significantly higher than these without INR > 4. CONCLUSION: We confirmed the relevant factors of warfarin anticoagulation control, including genetic factors (VKORC1 -1639G > A and CYP2C9*3 polymorphisms) and clinical factors (male gender, older age, overweight, AVR surgery and stroke history), which could be helpful to individualize warfarin dosage and improve warfarin anticoagulation control during different treatment period.

Understanding Acute Respiratory Distress Syndrome in High-Altitude Environments: A Comprehensive Review of Diagnosis and Treatment.

Approximately 2% of the global population lives above 1500 m, where low atmospheric pressure, decreased oxygen levels, harsh cold and dry conditions, strong radiation, and the effects of climate change present significant health challenges. Residents of these high-altitude areas display physiological adaptions, including smaller body size, enlarged ribs, improved oxygen delivery in hypoxic conditions, and adjustments in oxygen utilization and metabolism. Both acute and chronic hypoxia prevalent in such regions can trigger various diseases by stimulating hypoxia-inducible factors, boosting inflammatory responses, and impairing mitochondrial function.Acute Respiratory Distress Syndrome (ARDS) - a critical respiratory condition associated with high morbidity and mortality - occurs more frequently among the health risks in these environments. Hypoxia is a critical predisposing and aggravating factor for high-altitude ARDS. Despite similarities with its low-altitude counterpart, ARDS in high-altitude areas displays unique pathophysiology and clinical manifestations due to the specific environmental conditions.This review aims to shed light on how high-altitude environments influence the diagnosis and treatment of ARDS, providing a comprehensive understanding of the distinct challenges inherent to these regions.

Effect of NPC1L1 polymorphism on warfarin stable dose in Chinese patients under heart valve replacement surgery.

Warfarin is the most often anticoagulant choice for preventable thromboembolism. Notably, vitamin K plays a vital role in the process of warfarin's anticoagulant effect. Therefore, we presume NPC1L1, a key transporter of vitamin K (VK) intestinal absorption, may modulate the anticoagulant effect of warfarin. Studies have shown that NPC1L1(-762T>C, rs2073548) and p53 (P72R, rs1042522) variations are implicated in influencing NPC1L1 expression. This study aimed to assess the association between these two variants and warfarin stable dose (WSD). A two-stage extreme phenotype design was used to explore the influence of these two variants (rs2073548, rs1042522) on WSD variance in 655 Chinese patients undergoing heart valve replacement surgery. NPC1L1 rs2073548, p53 rs1042522, VKORC1 rs9923231 and CYP2C9*1/*3 polymorphisms were genotyped by polymerase chain reaction-restriction fragment polymorphism (PCR-RFLP) or Sanger sequencing, respectively. WSD was identified when target monitoring international normalized ratio (INR) value at 2.0-3.0. In the discovery phase, NPC1L1 rs2073548 A allele carriers occupied a significantly higher rate in the low dose group (P = .019). However, in the validation group, warfarin dosage in patients with the rs2073548 AA, AG and GG genotypes were 2.91 ± 0.97 mg/day, 3.02 ± 1.00 mg/day and 3.00 ± 1.06 mg/day, respectively. Multiple linear regression analysis results suggested that CYP2C9*3 and VKORC1 rs9923231, but not NPC1L1 rs2073548, were independent predictors of WSD in Chinese heart valve replacement (HVR) surgical patients.

[Microcirculation characteristics and humoral factors of healthy people from different populations at high altitude (4 100 m)].

The present study was aimed to observe the characteristics of sublingual microcirculation and the changes of humoral factors in healthy people of three different high altitude populations. Three groups of healthy subjects in Guoluo area of Qinghai province (4 100 m) were included: Tibetan group: 30 Tibetans, (45.62 ± 10.15) years old; Han group: 22 two-generation of Han immigrants, (46.23 ± 8.59) years old; migrant group: 23 migrants living at high altitude for 2-5 years, (43.45 ± 8.31) years old. Blood routine test was performed to determine white blood cell (WBC) count, red blood cell (RBC) count, hemoglobin (HGB), hematocrit (HCT), platelet (PLT) count, and neutrophil (NEUT) count. The changes of serum humoral factors including endothelin-1 (ET-1), CD31, CD34, CD105, vascular endothelial growth factor (VEGF), nitric oxide (NO) and noradrenaline (NE) were detected by ELISA. Continuous noninvasive hemodynamics monitor was used to continuously measure the changes of systemic circulation indexes: cardiac output (CO), cardiac index (CI), heart rate (HR), stroke volume (SV), pulse pressure variation (PPV), systemic vascular resistance index (SVRI), and mean arterial pressure (MAP). Blood oxygen was measured by pulse oximeter. Sublingual microcirculation indexes including total vascular density (TVD), perfused vessel density (PVD), proportion of perfused vessels (PPV), and microvascular flow index (MFI) were determined by sidestream dark field imaging. The results showed that there were no difference in systemic circulation among the 3 groups. Compared with Tibetan group, TVD and PVD of microcirculation in Han group and migrant group were significantly increased (P < 0.05). Compared with Tibetan group and Han group, WBC, RBC, HGB and HCT of migrant group were significantly increased (P < 0.05). Compared with Han group and Migrant group, PLT of Tibetan group was significantly increased (P < 0.05). Compared with the Tibetan group, the levels of serum humoral factors CD105 and VEGF were significantly higher in the migrant group (P < 0.05), while compared with Han and migration groups, NO in Tibetan group was significantly increased (P < 0.05). It is suggested that there were significant differences in microcirculation (TVD, PVD), blood routine (WBC, RBC, HGB, HCT) and humoral factors (CD105, VEGF) among different populations in high altitude area. Importantly, the increased microcirculation, erythrocytosis and increased pro-angiogenic factors due to hypoxic environment were observed in long-term residents and migrants, except for permanent residents. These physiological changes have clinical significance in the treatment of septic shock and chronic altitude sickness for different plateau populations.

Matrilin-2 regulates proliferation, apoptosis and cell cycle during radiation-induced injury in HPAEpiC cell.

Radiation pulmonary injury is related to the accumulation of extracellular matrix proteins in the alveolar interstitial space. Matrilin-2 as a component of extracellular filamentous networks, present higher level in the lung tissue from irradiated mice and irradiated pulmonary epithelial cell line, HPAEpiC cells. Knockdown of endogenous matrilin-2 prevents the apoptosis of HPAEpiC cell induced by the irradiation injury. Consistently, over-expression of matrilin-2 reduced the proliferation and induced apoptosis of HPAEpiC cells. Matrilin-2 promotes the expression of p21 via increasing the transcriptional activity of p53, by which induces the G1 phase arresting in HPAEpiC cells. In summary, matrilin-2, increased by irradiation, reduced the proliferation and induces apoptosis of pulmonary epithelial cells via p53/p21 pathway.

[Effect of high altitude hypoxia on fetal development during pregnancy and the reason analysis].

High altitude hypoxia is an important factor to affect fetal development during pregnancy. In the special environment, maternal physiological functions are regulated to maintain the maternal and fetal homeostasis, so that limited oxygen is to meet the needs of fetal growth and development. In this review, the literatures about the effects of hypoxic environment on fetal development during pregnancy in recent years were summarized, in which the fetal growth characteristics, maternal physiological regulation, genetic and placental influencing factors in high altitude areas were involved. This may be helpful for the reproductive healthcare of women in high altitude region, and also for the treatment and prevention of fetal growth retardation in the hypoxic environment.

A high mean arterial pressure target is associated with improved microcirculation in septic shock patients with previous hypertension: a prospective open label study.

INTRODUCTION: The effect of mean arterial pressure titration to a higher level on microcirculation in septic shock patients with previous hypertension remains unknown. Our goal is to assess the effect of mean arterial pressure titration to a higher level on microcirculation in hypertensive septic shock patients. METHODS: This is a single-center, open-label study. Hypertensive patients with septic shock for less than 24 hours after adequate fluid resuscitation and requiring norepinephrine to maintain a mean arterial pressure of 65 mmHg were enrolled. Mean arterial pressure was then titrated by norepinephrine from 65 mmHg to the normal level of the patient. In addition to hemodynamic variables, sublingual microcirculation was evaluated by sidestream dark field imaging. RESULTS: Nineteen patients were enrolled in the study. Increasing mean arterial pressure from 65 mmHg to normal levels was associated with increased central venous pressure (from 11 ± 4 to 13 ± 4 mmHg, P = 0.002), cardiac output (from 5.4 ± 1.4 to 6.4 ± 2.1 l/minute, P = 0.001), and central venous oxygen saturation (from 81 ± 7 to 83 ± 7%, P = 0.001). There were significant increases in small perfused vessel density (from 10.96 ± 2.98 to 11.99 ± 2.55 vessels/mm(2), P = 0.009), proportion of small perfused vessels (from 85 ± 18 to 92 ± 14%, P = 0.002), and small microvascular flow index (from 2.45 ± 0.61 to 2.80 ± 0.68, P = 0.009) when compared with a mean arterial pressure of 65 mmHg. CONCLUSIONS: Increasing mean arterial pressure from 65 mmHg to normal levels is associated with improved microcirculation in hypertensive septic shock patients. TRIAL REGISTRATION: Clinicaltrials.gov: NCT01443494; registered 28 September 2011.

Induced dipole moments in amorphous ZnCdS catalysts facilitate photocatalytic H2 evolution.

Amorphous semiconductors without perfect crystalline lattice structures are usually considered to be unfavorable for photocatalysis due to the presence of enriched trap states and defects. Here we demonstrate that breaking long-range atomic order in an amorphous ZnCdS photocatalyst can induce dipole moments and generate strong electric fields within the particles which facilitates charge separation and transfer. Loading 1 wt.% of low-cost Co-MoSx cocatalysts to the ZnCdS material increases the H2 evolution rate to 70.13 mmol g-1 h-1, which is over 5 times higher than its crystalline counterpart and is stable over the long-term up to 160 h. A flexible 20 cm × 20 cm Co-MoSx/ZnCdS film is prepared by a facile blade-coating technique and can generate numerous observable H2 bubbles under natural sunlight, exhibiting potential for scale-up solar H2 production.

Imperfect makes perfect: defect engineering of photoelectrodes towards efficient photoelectrochemical water splitting.

Photoelectrochemical (PEC) water splitting for hydrogen evolution has been considered as a promising technology to solve the energy and environmental issues. However, the solar-to-hydrogen (STH) conversion efficiencies of current PEC systems are far from meeting the commercial demand (10%) due to the lack of efficient photoelectrode materials. The recent rapid development of defect engineering of photoelectrodes has significantly improved the PEC performance, which is expected to break through the bottleneck of low STH efficiency. In this review, the category and the construction methods of different defects in photoelectrode materials are summarized. Based on the in-depth summary and analysis of existing reports, the PEC performance enhancement mechanism of defect engineering is critically discussed in terms of light absorption, carrier separation and transport, and surface redox reactions. Finally, the application prospects and challenges of defect engineering for PEC water splitting are presented, and the future research directions in this field are also proposed.

The mechanism and treatment of targeted anti-tumour drugs induced cardiotoxicity.

As the intensive anti-tumour therapy and combination of multiple anti-tumour drugs, cardiotoxicity events caused by anti-tumour drugs have also increased significantly, and the incidence of cardiotoxicity also increased with survival time. Different types of anti-tumour drugs could cause all kinds of cardiotoxicity which increase the difficulties in treatment and even live threatening. In this review, we concentrated in the targeted anti-tumour drugs such as human epidermal growth factor receptor-2 (HER2) inhibitors, tyrosine kinase inhibitors (TKIs), immune checkpoint inhibitors (ICIs), and proteasome inhibitors (Pls). The molecular mechanism of how these drugs induce cardiotoxicity is introduced which includes several signal pathways. These drugs induced cardiotoxicity involved heart failure, hypertension, atherosis and thrombosis, QT interval prolongation, and myocarditis. Some of the cardiotoxicity could be moderate and reversible but others could have happened severely.The aim of this review is to summarise the targeted anti-tumour drugs induced cardiotoxicity and treatment strategies.

Dose-related effects of norepinephrine on early-stage endotoxemic shock in a swine model.

Background: The benefits of early use of norepinephrine in endotoxemic shock remain unknown. We aimed to elucidate the effects of different doses of norepinephrine in early-stage endotoxemic shock using a clinically relevant large animal model. Methods: Vasodilatory shock was induced by endotoxin bolus in 30 Bama suckling pigs. Treatment included fluid resuscitation and administration of different doses of norepinephrine, to induce return to baseline mean arterial pressure (MAP). Fluid management, hemodynamic, microcirculation, inflammation, and organ function variables were monitored. All animals were supported for 6 h after endotoxemic shock. Results: Infused fluid volume decreased with increasing norepinephrine dose. Return to baseline MAP was achieved more frequently with doses of 0.8 µg/kg/min and 1.6 µg/kg/min (P <0.01). At the end of the shock resuscitation period, cardiac index was higher in pigs treated with 0.8 µg/kg/min norepinephrine (P <0.01), while systemic vascular resistance was higher in those receiving 0.4 µg/kg/min (P <0.01). Extravascular lung water level and degree of organ edema were higher in animals administered no or 0.2 µg/kg/min norepinephrine (P <0.01), while the percentage of perfused small vessel density (PSVD) was higher in those receiving 0.8 µg/kg/min (P <0.05) and serum lactate was higher in the groups administered no and 1.6 µg/kg/min norepinephrine (P <0.01). Conclusions: The impact of norepinephrine on the macro- and micro-circulation in early-stage endotoxemic shock is dose-dependent, with very low and very high doses resulting in detrimental effects. Only an appropriate norepinephrine dose was associated with improved tissue perfusion and organ function.

Preclinical evidence of reno-protective effect of quercetin on acute kidney injury: a meta-analysis of animal studies.

Objective: This study evaluated the reno-protective effects of quercetin in animal models of acute kidney injury (AKI). Methods: We conducted a systematic search of literature published before April 2023 in PubMed, Web of Science, and EMBASE databases. Methodological quality was assessed by SYRCLE's RoB tool. Funnel plot, Egger's test, and Begg's test were used to determine publication bias. Results: A total of 19 studies with 288 animals were included in this meta-analysis. The methodology quality scores of the included studies ranged from 4 to 7. The results indicated that quercetin reduced blood urea nitrogen (SMD = -4.78; 95% CI: 6.45, -3.12; p < 0.01; I2 = 84%) and serum creatinine (SMD: 2.73, 95% CI: 3.66, -1.80; p < 0.01; I2 = 80%) in AKI models. The result of sensitivity analysis was stable, while the results of funnel plot indicated asymmetric. In addition, we further analyzed inflammatory cytokines, oxidative stress levels, and kidney injury scores, and found that quercetin treatment had antioxidant and anti-inflammatory effects and improved kidney injury scores in animal models of AKI. Conclusion: Quercetin exhibited a promising reno-protective effect in AKI animal models. Systematic Review Registration: PROSPERO (CRD42023433333).

[Bundle program of treatment for acute severe type high altitude disease].

OBJECTIVE: To discuss Bundle treatment of the acute severe type high altitude disease. METHODS: The prospective and randomized controlled trial was conducted. Two hundred and three patients with high altitude pulmonary edema (HAPE) or high altitude cerebral edema (HACE) met inclusion criteria were included, and were randomly divided into Bundle treatment group (n = 125) and conventional treatment control group (n = 78). Critical patients with multiple organ dysfunction syndrome (MODS) were admitted to intensive care unit (ICU); with respiratory failure or serious hypoxia of the patients were given mechanical ventilation (invasive or noninvasive); fluid resuscitation and vasoactive agents were given in the unstable hemodynamics patients; diuretics and continuous veno-venous hemofiltration were given in acute renal dysfunction or failure. The gastrointestinal bleeding and blood coagulation disorders were concerned. The hospital stay time, cure rate and mortality were compared according to the stages and classification of HAPE or HACE among two groups. RESULTS: The hospital stay time was significantly decreased 1.66 days in the Bundle treatment group (days: 5.28 ± 3.17) compared with conventional treatment control group (6.94 ± 4.05, P < 0.05), the cure rate was significantly increased 7.06% (96.80% vs. 89.74%, P < 0.05), mortality of severe and fatal patients were decreased 5.59% and 31.15%, the mortality of patients in Bundle treatment group was significantly lower than conventional treatment control group (3.20% vs. 10.26%, P < 0.05). CONCLUSION: The standardized treatment which was integrated with plateau medicine and critical care medicine can effectively reduce the mortality of critical or severe patients with HAPE or HACE.

[Dead space fraction for treatment guidance and prognosis evaluation of acute respiratory distress syndrome].

Acute respiratory distress syndrome (ARDS) is a common cause of critical illness and high mortality from respiratory failure. Increased dead space fraction (VD/VT) was independently associated with lung injury and mortality of ARDS. VD/VT is readily obtained by bedside measurements of arterial blood gas and end-tidal carbon dioxide. Early attention and application of VD/VT as an indicator will help to better understand the pathophysiological of ARDS, guide clinical treatment, and better assess the severity and clinical prognosis of the disease.

Association of Thiamine Use with Outcomes in Patients with Sepsis and Alcohol Use Disorder: An Analysis of the MIMIC-III Database.

INTRODUCTION: The association between thiamine use and clinical outcomes among patients with sepsis and alcohol use disorder (AUD) is unclear. METHODS: In this retrospective cohort study of patients from Medical Information Mart for Intensive Care III (MIMIC-III, version 1.4), we evaluated the association of thiamine use with clinical outcomes in patients with AUD and sepsis. The primary outcome was 28-day survival, and secondary outcomes included ICU, in-hospital, and 90-day mortality, ICU and hospital length of stay, duration of vasopressor use, need and duration of continuous renal replacement therapy (CRRT), and dynamic changes for variables up to day 7 after ICU admission. RESULTS: A total of 944 patients with sepsis and AUD were included in this cohort [median age, 53.1 years; women, 26.0% (245 of 944)]. Among all patients, 24.6% (233 of 944) received thiamine with a dose of 200 mg (IQR 100-345 mg). The 28-day mortality was 11.2% (26 of 233) in the thiamine use group compared with 18.6% (132 of 711) in the no thiamine use group (P = 0.009). After adjustment for a series of confounders, the mixed-effects Cox proportional hazards models showed that administration of thiamine was associated with a lower risk of 28-day mortality compared with no administration of thiamine. CONCLUSIONS: In critically ill patients with alcohol use disorder admitted for sepsis, treatment with thiamine may be associated with a decreased risk of death. However, the present results should be interpreted with caution due to the limitations of retrospective design. Additional larger, multicenter randomized controlled trials are needed to confirm our findings.

Effects of apolipoprotein E on regulating insulin sensitivity via regulating insulin receptor signalosome in caveolae.

AIMS: Although impaired insulin signaling at a post-receptor level was a well-established key driver of insulin resistance, the role of surface abnormal insulin receptor (INSR) location in insulin resistance pathogenesis tended to be ignored and its molecular mechanisms remained obscure. Herein, this study aimed to investigate hepatic apolipoprotein E (APOE) impaired cellular insulin action via reducing cell surface INSR, especially in caveolae. KEY FINDINGS: Downregulation of APOE enhanced the caveolae translocation of INSR and glucose transporter 2 (GLUT2), and improved hepatic cells' sensitivity to insulin. Consistently, mice with selective suppression of liver tissue APOE showed lower fasting insulin and fasting glucose levels, better homeostatic model assessment (HOMA) index (HOMA-IS, HOMA-IR, HOMA-ß) and quantitative insulin sensitivity check index (QUICKI). Furthermore, the co-localization of INSR and CAV1 in the liver of these mice were more substantial than controls. SIGNIFICANCE: APOE might adversely set the basal gain of INSR signaling implied that APOE could be a new endogenous INSR regulator.

Chrysophanol Relieves Cisplatin-Induced Nephrotoxicity via Concomitant Inhibition of Oxidative Stress, Apoptosis, and Inflammation.

Cisplatin (CDDP) is one of the most frequently prescribed chemotherapy medications. However, its nephrotoxicity which often leads to acute kidney injury (AKI), greatly limits its clinical application. Chrysophanol (CHR), a mainly active anthraquinone ingredient, possesses various biological and pharmacological activities. In this study, we aimed to investigate the underlying protective mechanisms of CHR against CDDP-induced AKI (CDDP-AKI) using C57BL/6 mouse and human proximal tubule epithelial cells. In vivo, we found that pre-treatment with CHR greatly relieved CDDP-AKI and improved the kidney function and morphology. The mechanistic studies indicated that it might alleviate CDDP-AKI by inhibiting oxidative stress, apoptosis, and IKKß/IκBα/p65/transcription factor nuclear kappa B (NF-κB) inflammation signaling pathway induced by CDDP. Moreover, we found that the cell viability of HK2 cells reduced by CDDP was partially rescued by CHR pre-incubation. Flow cytometry results further indicated that CHR pre-incubation suppressed CDDP induced cellular reactive oxygen species (ROS) generation and inhibited cell apoptosis in a dose-dependent manner. In summary, our results suggested that CHR might be a novel therapy for CDDP-induced AKI.

Corrigendum: Chrysophanol Relieves Cisplatin-Induced Nephrotoxicity via Concomitant Inhibition of Oxidative Stress, Apoptosis, and Inflammation.

[This corrects the article DOI: 10.3389/fphys.2021.706359.].

[Continuous prone position ventilation in patients with severe acute respiratory distress syndrome at high altitude].

OBJECTIVE: To investigate the therapeutic effect of different prone position ventilation (PPV) on patients with severe acute respiratory distress syndrome (ARDS) at high altitude. METHODS: The severe ARDS patients who met the Berlin standard admitted to the department of intensive care unit (ICU) of Qinghai Provincial People's Hospital from January 2017 to January 2020 were enrolled. The patients with classic PPV treatment (i.e. alternate prone supine position, about 16 hours per day) were included in the discontinuous PPV group; the patients with modified PPV treatment (i.e. alternate left and right prone positions 20 degree angle-30 degree angle, every 4 hours and continuous treatment for 24 hours per day) were included in the continuous PPV group. The oxygenation index (PaO2/FiO2), mechanics of breathing, ventilator parameters before treatment and 72 hours after treatment, and mechanical ventilation time, the length of ICU stay, and related complications between the two groups were analyzed. RESULTS: Eighteen cases were treated with continuous PPV and 20 cases were treated with discontinuous PPV. There were no significant differences in gender, age, acute physiology and chronic health evaluation II (APACHE II), PaO2/FiO2, lung compliance, driving pressure (ΔP) and positive end expiratory pressure (PEEP) before treatment between the two groups. Compared with before treatment, PaO2/FiO2 in discontinuous PPV group and continuous PPV group was increased significantly after 72-hour treatment [mmHg (1 mmHg = 0.133 kPa): 99.7±15.4 vs. 55.5±6.3, 121.8±25.3 vs. 55.1±7.1, both P < 0.05], lung compliance was improved significantly (mL/cmH2O: 36.8±2.4 vs. 28.0±2.0, 43.4±6.7 vs. 27.7±2.1, both P < 0.05), and ΔP was decreased significantly [cmH2O (1 cmH2O = 0.098 kPa): 10.5 (10.0, 12.0) vs. 13.0 (12.3, 14.0), 10.0 (8.0, 12.0) vs. 13.0 (12.0, 14.0), both P < 0.05], PEEP was also decreased [cmH2O: 12 (12, 14) vs. 14 (13, 14), 10 (8, 10) vs. 14 (12, 15), both P < 0.05], and the indexes in continuous PPV group were improved more significantly than those in discontinuous PPV group [PaO2/FiO2 (mmHg): 121.8±25.3 vs. 99.7±15.4, lung compliance (mL/cmH2O): 43.4±6.7 vs. 36.8±2.4, ΔP (cmH2O): 10.0 (8.0, 12.0) vs. 10.5 (10.0, 12.0), PEEP (cmH2O): 10 (8, 10) vs. 12 (12, 14), all P < 0.05]. The duration of mechanical ventilation and the length of ICU stay in the continuous PPV group were significantly shorter than those in the intermittent PPV group [days: 6.0 (5.0, 7.3) vs. 8.0 (7.0, 9.0), 9.7±1.5 vs. 12.1±2.2, both P < 0.01]. During the PPV treatment, there were 3 cases of cheek skin damage and 2 cases of ear skin damage in the continuous PPV group, and 3 cases of facial skin damage in the intermittent PPV group. There was no significant difference in the incidence of complications between the two groups (χ2 = 0.321, P = 0.571). All patients were repaired normally after PPV, without adverse consequences. CONCLUSIONS: Continuous PPV is more effective than discontinuous PPV in the treatment of severe ARDS patients at high altitude, and the related complications are did not increased in prolonged time of PPV.