转载6月危通笔记20220620_Newsccm

这个周末不太平，主要的震动就是来自下面的第一篇文章——这次维生素C用于脓毒性休克的的研究不仅不是阴性了，而是“有害”了——按道理，重症的免疫调理治疗，也就是维生素C±激素和维生素B1的疗法这些年已经式微，几个大样本的研究都是阴性，本次这项很可能已经能预计到大体结果的研究，换句话说，几乎就是“炒冷饭”的临床研究，能发到NEJM上我挺理解不了的，就因为是“反向有害”的结果？这里面有一个悖论，如果本次研究是最新证据，那么之前的PAUL MARIK的回顾性的阳性的临床研究和之后的几项阴性的前瞻性研究怎么解释？如此，多少患者不应接受免疫调理治疗，这个代价谁来抵偿？这个问题同样是问给其他一会阴性、一会阳性的重症临床疗法！临床医生凭据的“疗法”究竟是根据经验还是证据，如果经验和证据都不一定是对的又如何？

这些年，重症医学和其他专业一样，凭借“询证证据”指导临床是大的趋势。但现在好了，不仅这次的维生素C是有害结果，想想之前的—— 强化血糖控制不是如此吗？替加环素不是如此吗？……

• 1. 呼吸大疫时的ECMO应用——既往、当下与未来
• 2. 招募前的补液类型、入院类型以及平衡盐对成人重症预后的影响 对BASIC研究的二次分析
• 3. 静推补液对气管插管时血压下降的效果
• 4. ICU感染性休克限制性补液的效果
• 5. 综述：脓毒症相关性心肌病中与线粒体功能异常为靶向的目标治疗
• 6.硫噻嗪（Sulthiame）治疗睡眠呼吸暂停的随机对照试验
• 7.荟萃分析：PEEP与所选肺复张策略与ARDS的病死率关联性
• 8. 控制性通气中肺吸气时的右心负荷
• 9. 脱机困难者临时性膈肌刺激的随机研究
• 10. COPD患者通气效率、呼吸困难与运动耐受的损害
• 11. 综述：分步呼吸波形分析评估肺部病理生理
• 12. 综述：舒缓医学 内科学医生知识更新
• 13. ICU中专科舒缓治疗的启动——内科医生的观点
• 14.  中重度脑外伤的治疗——内科医生知识更新
• 15. 综述：重症患者的血糖控制 less is more 
• 16. 综述：ICU患者的神经心理评价与治疗
• 17. 目标模拟实验：红霉素对脓毒症重症患者的宿主反应与病死率的影响
• 18. 机械通气的心源性休克患者早晚肠内营养的比较
• 19. 对REDOX研究的二次分析 重症患者的代谢 
• 20. 早期神经肌肉电刺激加早期活动可改善危重病人的机能状态，减少住院天数
• 21. 综述：ICU的体温管理
• 22. 全球开源疾病严重度评分 GOSIS
• 23. 呼吸道合胞病毒与流感感染ICU患者的特点及预后
• 24. 成人脓毒症中以1-3β葡聚糖为靶向的抗真菌治疗
• 25. 立场文件：液体耐受性的概念产生
• 26. 多中心随机双盲试验：重度坏死性胰腺炎的免疫增强治疗
• 27. 综述：机械通气的ARDS患者的俯卧位通气与神经肌肉阻滞的辅助治疗
• 28. 洞察ARDS柏林定义 
• 29. 机械通气患者的院内获得性肺炎

号外:ICU脓毒症患者静点维生素C的疗效

号外：ICU脓毒症患者静点维生素C的疗效 Intravenous Vitamin C in Adults with Sepsis in the Intensive Care Unit

François Lamontagne,

DOI: 10.1056/NEJMoa2200644

BACKGROUND Studies that have evaluated the use of intravenous vitamin C in adults with sepsis who were receiving vasopressor therapy in the intensive care unit (ICU) have shown mixed results with respect to the risk of death and organ dysfunction.

METHODS In this randomized, placebo-controlled trial, we assigned adults who had been in the ICU for no longer than 24 hours, who had proven or suspected infection as the main diagnosis, and who were receiving a vasopressor to receive an infusion of either vitamin C (at a dose of 50 mg per kilogram of body weight) or matched placebo administered every 6 hours for up to 96 hours. The primary outcome was a composite of death or persistent organ dysfunction (defined by the use of vasopressors, invasive mechanical ventilation, or new renal-replacement therapy) on day 28.

RESULTS A total of 872 patients underwent randomization (435 to the vitamin C group and 437 to the control group). The primary outcome occurred in 191 of 429 patients (44.5%) in the vitamin C group and in 167 of 434 patients (38.5%) in the control group (risk ratio, 1.21; 95% confidence interval [CI], 1.04 to 1.40; P=0.01). At 28 days, death had occurred in 152 of 429 patients (35.4%) in the vitamin C group and in 137 of 434 patients (31.6%) in the placebo group (risk ratio, 1.17; 95% CI, 0.98 to 1.40) and persistent organ dysfunction in 39 of 429 patients (9.1%) and 30 of 434 patients (6.9%), respectively (risk ratio, 1.30; 95% CI, 0.83 to 2.05). Findings were similar in the two groups regarding organ-dysfunction scores, biomarkers, 6-month survival, health-related quality of life, stage 3 acute kidney injury, and hypoglycemic episodes. In the vitamin C group, one patient had a severe hypoglycemic episode and another had a serious anaphylaxis event.

CONCLUSIONS In adults with sepsis receiving vasopressor therapy in the ICU, those who received intravenous vitamin C had a higher risk of death or persistent organ dysfunction at 28 days than those who received placebo. (Funded by the Lotte and John Hecht Memorial Foundation; LOVIT ClinicalTrials.gov number, NCT03680274）.

1. 呼吸疾病大疫时的ECMO应用——既往、当下与未来 Extracorporeal Membrane Oxygenation during Respiratory Pandemics: Past, Present, and Future

Daniel Brodie

https://doi.org/10.1164/rccm.202111-2661CP

The role of extracorporeal membrane oxygenation (ECMO) in the management of severe acute respiratory failure, including acute respiratory distress syndrome, has become better defined in recent years in light of emerging high-quality evidence and technological advances. Use of ECMO has consequently increased throughout many parts of the world. The coronavirus disease (COVID-19) pandemic, however, has highlighted deficiencies in organizational capacity, research capability, knowledge sharing, and resource use. Although governments, medical societies, hospital systems, and clinicians were collectively unprepared for the scope of this pandemic, the use of ECMO, a highly resource-intensive and specialized form of life support, presented specific logistical and ethical challenges. As the pandemic has evolved, there has been greater collaboration in the use of ECMO across centers and regions, together with more robust data reporting through international registries and observational studies. Nevertheless, centralization of ECMO capacity is lacking in many regions of the world, and equitable use of ECMO resources remains uneven. There are no widely available mechanisms to conduct large-scale, rigorous clinical trials in real time. In this critical care review, we outline lessons learned during COVID-19 and prior respiratory pandemics in which ECMO was used, and we describe how we might apply these lessons going forward, both during the ongoing COVID-19 pandemic and in the future.

2. 招募前的补液类型、入院类型以及平衡盐对成人重症预后的影响 对BASIC研究的二次分析Association between Type of Fluid Received Prior to Enrollment, Type of Admission, and Effect of Balanced Crystalloid in Critically Ill Adults: A Secondary Exploratory Analysis of the BaSICS Clinical Trial

Fernando G. Zampieri for the BaSICS Investigators and the BRICNet

https://doi.org/10.1164/rccm.202111-2484OC

Rationale: The effects of balanced crystalloid versus saline on clinical outcomes for ICU patients may be modified by the type of fluid that patients received for initial resuscitation and by the type of admission.

Objectives: To assess whether the results of a randomized controlled trial could be affected by fluid use before enrollment and admission type.

Methods: Secondary post hoc analysis of the BaSICS (Balanced Solution in Intensive Care Study) trial, which compared a balanced solution (Plasma-Lyte 148) with 0.9% saline in the ICU. Patients were categorized according to fluid use in the 24 hours before enrollment in four groups (balanced solutions only, 0.9% saline only, a mix of both, and no fluid before enrollment) and according to admission type (planned, unplanned with sepsis, and unplanned without sepsis). The association between 90-day mortality and the randomization group was assessed using a hierarchical logistic Bayesian model.

Measurements and Main Results: A total of 10,520 patients were included. There was a low probability that the balanced solution was associated with improved 90-day mortality in the whole trial population (odds ratio [OR], 0.95; 89% credible interval [CrI], 0.66–10.51; probability of benefit, 0.58); however, probability of benefit was high for patients who received only balanced solutions before enrollment (regardless of admission type, OR, 0.78; 89% CrI, 0.56–1.03; probability of benefit, 0.92), mostly because of a benefit in unplanned admissions due to sepsis (OR, 0.70; 89% CrI, 0.50–0.97; probability of benefit, 0.96) and planned admissions (OR, 0.79; 89% CrI, 0.65–0.97; probability of benefit, 0.97).

Conclusions: There is a high probability that balanced solution use in the ICU reduces 90-day mortality in patients who exclusively received balanced fluids before trial enrollment.

3. 静推补液对气管插管时血压下降的效果 Effect of Fluid Bolus Administration on Cardiovascular Collapse Among Critically Ill Patients Undergoing Tracheal Intubation A Randomized Clinical Trial

Derek W. Russell

JAMA. Published online June 16, 2022.

doi:10.1001/jama.2022.9792

Importance  Hypotension is common during tracheal intubation of critically ill adults and increases the risk of cardiac arrest and death. Whether administering an intravenous fluid bolus to critically ill adults undergoing tracheal intubation prevents severe hypotension, cardiac arrest, or death remains uncertain.

Objective  To determine the effect of fluid bolus administration on the incidence of severe hypotension, cardiac arrest, and death.

Design, Setting, and Participants  This randomized clinical trial enrolled 1067 critically ill adults undergoing tracheal intubation with sedation and positive pressure ventilation at 11 intensive care units in the US between February 1, 2019, and May 24, 2021. The date of final follow-up was June 21, 2021.

Interventions  Patients were randomly assigned to receive either a 500-mL intravenous fluid bolus (n = 538) or no fluid bolus (n = 527).

Main Outcomes and Measures  The primary outcome was cardiovascular collapse (defined as new or increased receipt of vasopressors or a systolic blood pressure <65 mm Hg between induction of anesthesia and 2 minutes after tracheal intubation, or cardiac arrest or death between induction of anesthesia and 1 hour after tracheal intubation). The secondary outcome was the incidence of death prior to day 28, which was censored at hospital discharge.

Results  Among 1067 patients randomized, 1065 (99.8%) completed the trial and were included in the primary analysis (median age, 62 years [IQR, 51-70 years]; 42.1% were women). Cardiovascular collapse occurred in 113 patients (21.0%) in the fluid bolus group and in 96 patients (18.2%) in the no fluid bolus group (absolute difference, 2.8% [95% CI, −2.2% to 7.7%]; P = .25). New or increased receipt of vasopressors occurred in 20.6% of patients in the fluid bolus group compared with 17.6% of patients in the no fluid bolus group, a systolic blood pressure of less than 65 mm Hg occurred in 3.9% vs 4.2%, respectively, cardiac arrest occurred in 1.7% vs 1.5%, and death occurred in 0.7% vs 0.6%. Death prior to day 28 (censored at hospital discharge) occurred in 218 patients (40.5%) in the fluid bolus group compared with 223 patients (42.3%) in the no fluid bolus group (absolute difference, −1.8% [95% CI, −7.9% to 4.3%]; P = .55).

Conclusions and Relevance  Among critically ill adults undergoing tracheal intubation, administration of an intravenous fluid bolus compared with no fluid bolus did not significantly decrease the incidence of cardiovascular collapse.

4. ICU感染性休克限制性补液的效果Restriction of Intravenous Fluid in ICU Patients with Septic Shock

Tine S. Meyhoff,  … for the CLASSIC Trial Group*

DOI: 10.1056/NEJMoa2202707

BACKGROUND Intravenous fluids are recommended for the treatment of patients who are in septic shock, but higher fluid volumes have been associated with harm in patients who are in the intensive care unit (ICU).

METHODS In this international, randomized trial, we assigned patients with septic shock in the ICU who had received at least 1 liter of intravenous fluid to receive restricted intravenous fluid or standard intravenous fluid therapy; patients were included if the onset of shock had been within 12 hours before screening. The primary outcome was death from any cause within 90 days after randomization.

RESULTS We enrolled 1554 patients; 770 were assigned to the restrictive-fluid group and 784 to the standard-fluid group. Primary outcome data were available for 1545 patients (99.4%). In the ICU, the restrictive-fluid group received a median of 1798 ml of intravenous fluid (interquartile range, 500 to 4366); the standard-fluid group received a median of 3811 ml (interquartile range, 1861 to 6762). At 90 days, death had occurred in 323 of 764 patients (42.3%) in the restrictive-fluid group, as compared with 329 of 781 patients (42.1%) in the standard-fluid group (adjusted absolute difference, 0.1 percentage points; 95% confidence interval [CI], −4.7 to 4.9; P=0.96). In the ICU, serious adverse events occurred at least once in 221 of 751 patients (29.4%) in the restrictive-fluid group and in 238 of 772 patients (30.8%) in the standard-fluid group (adjusted absolute difference, −1.7 percentage points; 99% CI, −7.7 to 4.3). At 90 days after randomization, the numbers of days alive without life support and days alive and out of the hospital were similar in the two groups.

CONCLUSIONS Among adult patients with septic shock in the ICU, intravenous fluid restriction did not result in fewer deaths at 90 days than standard intravenous fluid therapy. (Funded by the Novo Nordisk Foundation and others; CLASSIC ClinicalTrials.gov number, NCT03668236. opens in new tab.)

5. 综述：脓毒症相关性心肌病中与线粒体功能异常为靶向的目标治疗Therapeutic Strategies Targeting Mitochondrial Dysfunction in Sepsis-induced Cardiomyopathy

Oluwabukunmi Modupe Salami

https://doi.org/10.1007/s10557-022-07354-8

Sepsis is an increasingly worldwide problem; it is currently regarded as a complex life-threatening dysfunction of one or more organs as a result of dysregulated host immune response to infections. The heart is one of the most affected organs, as roughly 10% to 70% of sepsis cases are estimated to turn into sepsis-induced cardiomyopathy (SIC). SIC can be defined as a reversible myocardial dysfunction characterized by dilated ventricles, impaired contractility, and decreased ejection fraction. Mitochondria play a critical role in the normal functioning of cardiac tissues as the heart is highly dependent on its production of adenosine triphosphate (ATP), its damage during SIC includes morphology impairment, mitophagy, biogenesis disequilibrium, electron transport chain disturbance, molecular damage from the actions of pro-inflammatory cytokines and many other different impairments that are major contributing factors to the severity of SIC. Although mitochondria-targeted therapies usage is still inadequate in clinical settings, the preclinical study outcomes promise that the implementation of these therapies may effectively treat SIC. This review summarizes the different therapeutic strategies targeting mitochondria structure, quality, and quantity abnormalities for the treatment of SIC.

6.硫噻嗪（Sulthiame）治疗睡眠呼吸暂停的随机对照试验 A Randomized Controlled Clinical Trial Exploring Safety and Tolerability of Sulthiame in Sleep Apnea

Jan Hedner

https://doi.org/10.1164/rccm.202109-2043OC

Rationale: Current therapies for obstructive sleep apnea (OSA) are limited by insufficient efficacy, compliance, or tolerability. An effective pharmacological treatment for OSA is warranted. Carbonic anhydrase inhibition has been shown to ameliorate OSA.

Objectives: To explore safety and tolerability of the carbonic anhydrase inhibitor sulthiame (STM) in OSA.

Methods: A 4-week double-blind, randomized, placebo-controlled dose-guiding trial was conducted in patients with moderate and/or severe OSA not tolerating positive airway pressure treatment.

Measurements and Main Results: Intermittent paresthesia was reported by 79%, 67%, and 18% of patients receiving 400 mg STM (n = 34), 200 mg STM (n = 12), and placebo (n = 22), respectively. Dyspnea was reported after 400 mg STM (18%). Six patients in the higher dose group withdrew because of adverse events. There were no serious adverse events. STM reduced the apnea–hypopnea index from 55.2 to 33.0 events/h (−41.0%) in the 400-mg group and from 61.1 to 40.6 events/h (−32.1%) after 200 mg (P < 0.001 for both). Corresponding placebo values were 53.9 and 50.9 events/h (−5.4%). The apnea–hypopnea index reduction threshold of ⩾50% was reached in 40% of patients after 400 mg, 25% after 200 mg, and 5% after placebo. Mean overnight oxygen saturation improved by 1.1% after 400 and 200 mg (P < 0.001 and P = 0.034, respectively). Patient-related outcomes were unchanged.

Conclusions: STM showed a satisfactory safety profile in moderate and/or severe OSA. STM reduced OSA, on average, by more than 20 events/h, one of the strongest reductions reported in a drug trial in OSA. Larger scale clinical studies of STM in OSA are justified.

7.荟萃分析：PEEP与所选肺复张策略与ARDS的病死率关联性 Association of Positive End-Expiratory Pressure and Lung Recruitment Selection Strategies with Mortality in Acute Respiratory Distress Syndrome: A Systematic Review and Network Meta-analysis

Jose Dianti

https://doi.org/10.1164/rccm.202108-1972OC

Rationale: The most beneficial positive end-expiratory pressure (PEEP) selection strategy in patients with acute respiratory distress syndrome (ARDS) is unknown, and current practice is variable.

Objectives: To compare the relative effects of different PEEP selection strategies on mortality in adults with moderate to severe ARDS.

Methods: We conducted a network meta-analysis using a Bayesian framework. Certainty of evidence was evaluated using grading of recommendations assessment, development and evaluation methodology.

Measurements and Main Results: We included 18 randomized trials (4,646 participants). Compared with a lower PEEP strategy, the posterior probability of mortality benefit from a higher PEEP without lung recruitment maneuver (LRM) strategy was 99% (risk ratio [RR], 0.77; 95% credible interval [CrI], 0.60–0.96, high certainty), the posterior probability of benefit of the esophageal pressure–guided strategy was 87% (RR, 0.77; 95% CrI, 0.48–1.22, moderate certainty), the posterior probability of benefit of a higher PEEP with brief LRM strategy was 96% (RR, 0.83; 95% CrI, 0.67–1.02, moderate certainty), and the posterior probability of increased mortality from a higher PEEP with prolonged LRM strategy was 77% (RR, 1.06; 95% CrI, 0.89–1.22, low certainty). Compared with a higher PEEP without LRM strategy, the posterior probability of increased mortality from a higher PEEP with prolonged LRM strategy was 99% (RR, 1.37; 95% CrI, 1.04–1.81, moderate certainty).

Conclusions: In patients with moderate to severe ARDS, higher PEEP without LRM is associated with a lower risk of death than lower PEEP. A higher PEEP with prolonged LRM strategy is associated with increased risk of death when compared with higher PEEP without LRM.

8. 控制性通气中肺吸气时的右心负荷 Right Ventricular Loading by Lung Inflation during Controlled Mechanical Ventilation

Douglas Slobod

https://doi.org/10.1164/rccm.202111-2483OC

Rationale: The inspiratory rise in transpulmonary pressure during mechanical ventilation increases right ventricular (RV) afterload. One mechanism is that when Palv exceeds left atrial pressure, West zone 1 or 2 (non–zone 3) conditions develop, and Palv becomes the downstream pressure opposing RV ejection. The Vt at which this impact on the right ventricle becomes hemodynamically evident is not well established.

Objectives: To determine the magnitude of RV afterload and prevalence of significant non–zone 3 conditions during inspiration across the range of Vt currently prescribed in clinical practice.

Methods: In postoperative passively ventilated cardiac surgery patients, we measured right atrial, right ventricle, pulmonary artery, pulmonary artery occlusion pressure, plateau pressure, and esophageal pressure during short periods of controlled ventilation, with Vt increments ranging between 2 and 12 ml/kg predicted body weight (PBW). The inspiratory increase in RV afterload was evaluated hemodynamically and echocardiographically. The prevalence of non–zone 3 conditions was determined using two definitions based on changes in esophageal pressure, pulmonary artery occlusion pressure, and plateau pressure.

Measurements and Main Results: Fifty-one patients were studied. There was a linear relationship between Vt, driving pressure, transpulmonary pressure, and the inspiratory increase in the RV isovolumetric contraction pressure. Echocardiographically, increasing Vt was associated with a greater inspiratory increase in markers of afterload and a decrease in stroke volume. Non–zone 3 conditions were present in >50% of subjects at a Vt ⩾ 6 ml/kg PBW.

Conclusions: In the Vt range currently prescribed, RV afterload increases with increasing Vt. A mechanical ventilation strategy that limits Vt and driving pressure is cardioprotective.

9. 脱机困难者临时性膈肌刺激的随机研究 Randomized Clinical Study of Temporary Transvenous Phrenic Nerve Stimulation in Difficult-to-Wean Patients

Martin Dres

https://doi.org/10.1164/rccm.202107-1709OC

Rationale: Diaphragm dysfunction is frequently observed in critically ill patients with difficult weaning from mechanical ventilation.

Objectives: To evaluate the effects of temporary transvenous diaphragm neurostimulation on weaning outcome and maximal inspiratory pressure.

Methods: Multicenter, open-label, randomized, controlled study. Patients aged ⩾18 years on invasive mechanical ventilation for ⩾4 days and having failed at least two weaning attempts received temporary transvenous diaphragm neurostimulation using a multielectrode stimulating central venous catheter (bilateral phrenic stimulation) and standard of care (treatment) (n = 57) or standard of care (control) (n = 55). In seven patients, the catheter could not be inserted, and in seven others, pacing therapy could not be delivered; consequently, data were available for 43 patients. The primary outcome was the proportion of patients successfully weaned. Other endpoints were mechanical ventilation duration, 30-day survival, maximal inspiratory pressure, diaphragm-thickening fraction, adverse events, and stimulation-related pain.

Measurements and Main Results: The incidences of successful weaning were 82% (treatment) and 74% (control) (absolute difference [95% confidence interval (CI)], 7% [−10 to 25]), P = 0.59. Mechanical ventilation duration (mean ± SD) was 12.7 ± 9.9 days and 14.1 ± 10.8 days, respectively, P = 0.50; maximal inspiratory pressure increased by 16.6 cm H2O and 4.8 cm H2O, respectively (difference [95% CI], 11.8 [5 to 19]), P = 0.001; and right hemidiaphragm thickening fraction during unassisted spontaneous breathing was +17% and −14%, respectively, P = 0.006, without correlation with changes in maximal inspiratory pressure. Serious adverse event frequency was similar in both groups. Median stimulation-related pain in the treatment group was 0 (no pain).

Conclusions: Temporary transvenous diaphragm neurostimulation did not increase the proportion of successful weaning from mechanical ventilation. It was associated with a significant increase in maximal inspiratory pressure, suggesting reversal of the course of diaphragm dysfunction.

10. COPD患者通气效率、呼吸困难与运动耐受的损害 Impaired Ventilatory Efficiency, Dyspnea, and Exercise Intolerance in Chronic Obstructive Pulmonary Disease: Results from the CanCOLD Study

Devin B. Phillips

https://doi.org/10.1164/rccm.202109-2171OC

Rationale: Impaired exercise ventilatory efficiency (high ventilatory requirements for CO2 [V˙e/V˙co2]) provides an indication of pulmonary gas exchange abnormalities in chronic obstructive pulmonary disease (COPD).

Objectives: To determine 1) the association between high V˙e/V˙co2 and clinical outcomes (dyspnea and exercise capacity) and its relationship to lung function and structural radiographic abnormalities; and 2) its prevalence in a large population-based cohort.

Methods: Participants were recruited randomly from the population and underwent clinical evaluation, pulmonary function, cardiopulmonary exercise testing, and chest computed tomography. Impaired exercise ventilatory efficiency was defined by a nadir V˙e/V˙co2 above the upper limit of normal (ULN), using population-based normative values.

Measurements and Main Results: Participants included 445 never-smokers, 381 ever-smokers without airflow obstruction, 224 with Global Initiative for Chronic Obstructive Lung Disease (GOLD) 1 COPD, and 200 with GOLD 2–4 COPD. Participants with V˙e/V˙co2 above the ULN were more likely to have activity-related dyspnea (Medical Research Council dyspnea scale ⩾ 2; odds ratio [5–95% confidence intervals], 1.77 [1.31 to 2.39]) and abnormally low peak V˙o2 (V˙o2peak below the lower limit of normal; odds ratio, 4.58 [3.06 to 6.86]). The Kco had a stronger correlation with nadir V˙e/V˙co2 (r = −0.38; P < 0.001) than other relevant lung function and computed tomography metrics. The prevalence of V˙e/V˙co2 above the ULN was 24% in COPD (similar in GOLD 1 and 2 through 4), which was greater than in never-smokers (13%) and ever-smokers (12%).

Conclusions: V˙e/V˙co2 above the ULN was associated with greater dyspnea and low V˙o2peak and was present in 24% of all participants with COPD, regardless of GOLD stage. The results show the importance of recognizing impaired exercise ventilatory efficiency as a potential contributor to dyspnea and exercise limitation, even in mild COPD.

11. 综述：分步呼吸波形分析评估肺部病理生理 Stepwise Ventilator Waveform Assessment to Diagnose Pulmonary Pathophysiology

Brigid C. Flynn

https://doi.org/10.1097/ALN.0000000000004220

Electronically displayed ventilator waveforms provide a wealth of insight into the physiology of the respiratory system. Pressure and flow values can be independent variables that reflect control by the ventilator or dependent variables that demonstrate the respiratory system’s response to mechanical ventilation. Diagrams of time-based pressure and flow curves may reveal underlying pathophysiology beyond more commonly assessed parameters such as peak airway pressure, respiratory rate, and tidal volume. In this narrative review, we introduce a stepwise approach clinicians can take to diagnose pulmonary pathophysiology by using ventilator waveforms in patients receiving pressure control ventilation or volume control ventilation. Understanding a patient’s pathophysiology (i.e., increased airway resistance) does not distinguish pathology (i.e., kinked endotracheal tube or bronchospasm). A pathology such as pulmonary edema may have more than one pathophysiologic process (i.e., increased airway resistance and low respiratory compliance). To interpret ventilator waveforms, we assume a one-compartment lung model with a linear response to a range of tidal volumes.1  We do not discuss identification of ventilation mode or adaptive ventilation.

12. 综述：舒缓医学 内科学医生知识更新Review Palliative care: An update for internists

Rachel D. Havyer

Cleveland Clinic Journal of Medicine May 2022, 89 (5) 262-268;

https://doi.org/10.3949/ccjm.89a.21075

All clinicians should maintain basic skills in general palliative care to help address the needs of patients and families. Because keeping up with the information provided by the growing palliative care literature can be challenging, we conducted a detailed search via Medline for palliative care articles published in 2020 in top peer-reviewed medical journals. Using a consensus-driven process of selection, we reviewed and summarized 11 articles to enhance knowledge of the practice-changing palliative care literature for general internists.

13. ICU中专科舒缓治疗的启动——内科医生的观点 Clinicians’ Views on the use of triggers for specialist palliative care in the ICU: A qualitative secondary analysis

Komal PatelMurali

https://doi.org/10.1016/j.jcrc.2022.154054

Highlights

Triggers for specialist palliative care consultation in the ICU were explored.

The views of interdisciplinary ICU and palliative care clinicians were studied.

Broad agreement emerged for chronic critical illness and frequent ICU stays.

Clinicians had concerns about over-consultation and trigger overload.

Stakeholders’ buy-in and input were deemed important for implementation.

Purpose To understand clinicians’ views regarding use of clinical criteria, or triggers, for specialist palliative care consultation in the ICU.

Materials and methods Secondary analysis of a qualitative study that explored factors associated with adoption of specialist palliative care in the ICU. Semi-structured interviews with 36 ICU and palliative care clinicians included questions related to triggers for specialist palliative care. We performed a thematic analysis to identify participants’ views on use of triggers, including appropriateness of cases for specialists and issues surrounding trigger implementation.

Results We identified five major themes: 1) Appropriate triggers for specialist palliative care, 2) Issues leading to clinician ambivalence for triggers, 3) Prospective buy-in of stakeholders, 4) Workflow considerations in deploying a trigger system, and 5) Role of ICU clinicians in approving specialist palliative care consults. Appropriate triggers included end-of-life care, chronic critical illness, frequent ICU admissions, and patient/family support. Most clinicians had concerns about “trigger overload” and ICU clinicians wanted to be broadly involved in implementation efforts.

Conclusions ICU and palliative care clinicians identified important issues to consider when implementing triggers for specialist palliative care consultation. Future research is needed to longitudinally examine the most appropriate triggers and best practices for trigger implementation.

14.  中重度脑外伤的治疗——内科医生知识更新Management of moderate to severe traumatic brain injury: an update for the intensivist

Geert Meyfroidt

https://doi.org/10.1007/s00134-022-06702-4

Traumatic brain injury (TBI) remains one of the most fatal and debilitating conditions in the world. Current clinical management in severe TBI patients is mainly concerned with reducing secondary insults and optimizing the balance between substrate delivery and consumption. Over the past decades, multimodality monitoring has become more widely available, and clinical management protocols have been published that recommend potential interventions to correct pathophysiological derangements. Even while evidence from randomized clinical trials is still lacking for many of the recommended interventions, these protocols and algorithms can be useful to define a clear standard of therapy where novel interventions can be added or be compared to. Over the past decade, more attention has been paid to holistic management, in which hemodynamic, respiratory, inflammatory or coagulation disturbances are detected and treated accordingly. Considerable variability with regards to the trajectories of recovery exists. Even while most of the recovery occurs in the first months after TBI, substantial changes may still occur in a later phase. Neuroprognostication is challenging in these patients, where a risk of self-fulfilling prophecies is a matter of concern. The present article provides a comprehensive and practical review of the current best practice in clinical management and long-term outcomes of moderate to severe TBI in adult patients admitted to the intensive care unit.

15. 综述：重症患者的血糖控制 less is more—— Review Glycemic control in the critically ill: Less is more

Ghaith Alhatemi,

Cleveland Clinic Journal of Medicine April 2022, 89 (4) 191-199

https://doi.org/10.3949/ccjm.89a.20171

Hyperglycemia is associated with poor clinical outcomes in critically ill patients. Initial clinical trials of intensive insulin therapy targeting blood glucose levels of 80 to 110 mg/dL showed improved outcomes, but subsequent trials found no benefits and even increased harm with this approach. Emerging literature has evaluated other glycemic indices including time-in-target blood glucose range, glycemic variability, and stress hyperglycemia ratio. These indices, while well described in observational studies, have not been addressed in the initial trials. Additionally, the patient’s pre existing diabetes status and preadmission diabetic control may modulate the outcomes of stringent glycemic control, with worse outcomes of hyperglycemia being observed in patients without diabetes and in those with well-controlled diabetes. Most medical societies recommend less stringent glucose control in the range of 140 to 180 mg/dL for critically ill patients.

16. 综述：ICU患者的神经心理评价与治疗Review Neuropsychiatric assessment and management of the ICU survivor

Erin A. Dean

Cleveland Clinic Journal of Medicine December 2021, 88 (12) 669-679

https://doi.org/10.3949/ccjm.88a.20169

Any survivor among the millions of patients admitted to the intensive care unit (ICU) for critical illness each year is susceptible to persistent health problems that continue after discharge and may lead to post-intensive care syndrome (PICS), defined as new or worsening dysfunction from physical impairment, cognitive impairment, or emotional impairment, or a combination. Considering the increased rates of ICU survival and the growing elderly population more likely to utilize ICU resources, critical care practitioners have broadened their focus on outcomes and care of ICU survivors to include the acute post-ICU survival period as well as months and even years after ICU discharge. This review focuses on the neuropsychiatric aspects of PICS in ICU survivors including diagnostic, screening, and treatment recommendations. It also highlights the value of post-ICU clinics and the unique role of the consultation psychiatrist in the care of this patient population.

17. 目标模拟实验：红霉素对脓毒症重症患者的宿主反应与病死率的影响Effect of erythromycin on mortality and the host response in critically ill patients with sepsis: a target trial emulation

Tom D. Y. Reijnders

https://doi.org/10.1186/s13054-022-04016-x

Background Immunomodulatory therapies that improve the outcome of sepsis are not available. We sought to determine whether treatment of critically ill patients with sepsis with low-dose erythromycin—a macrolide antibiotic with broad immunomodulatory effects—decreased mortality and ameliorated underlying disease pathophysiology.

Methods We conducted a target trial emulation, comparing patients with sepsis admitted to two intensive care units (ICU) in the Netherlands for at least 72 h, who were either exposed or not exposed during this period to treatment with low-dose erythromycin (up to 600 mg per day, administered as a prokinetic agent) but no other macrolides. We used two common propensity score methods (matching and inverse probability of treatment weighting) to deal with confounding by indication and subsequently used Cox regression models to estimate the treatment effect on the primary outcome of mortality rate up to day 90. Secondary clinical outcomes included change in SOFA, duration of mechanical ventilation and the incidence of ICU-acquired infections. We used linear mixed models to assess differences in 15 host response biomarkers reflective of key pathophysiological processes from admission to day 4.

Results In total, 235 patients started low-dose erythromycin treatment, 470 patients served as controls. Treatment started at a median of 38 [IQR 25–52] hours after ICU admission for a median of 5 [IQR 3–8] total doses in the first course. Matching and weighting resulted in populations well balanced for proposed confounders. We found no differences between patients treated with low-dose erythromycin and control subjects in mortality rate up to day 90: matching HR 0.89 (95% CI 0.64–1.24), weighting HR 0.95 (95% CI 0.66–1.36). There were no differences in secondary clinical outcomes. The change in host response biomarker levels from admission to day 4 was similar between erythromycin-treated and control subjects.

Conclusion In this target trial emulation in critically ill patients with sepsis, we could not demonstrate an effect of treatment with low-dose erythromycin on mortality, secondary clinical outcomes or host response biomarkers.

18. 机械通气的心源性休克患者早晚肠内营养的比较 Early versus delayed enteral nutrition in mechanically ventilated patients with circulatory shock: a nested cohort analysis of an international multicenter, pragmatic clinical trial

Luis Ortiz-Reyes

https://doi.org/10.1186/s13054-022-04047-4

Introduction Real-world evidence on the timing and efficacy of enteral nutrition (EN) practices in intensive care unit (ICU) patients with circulatory shock is limited. We hypothesized early EN (EEN), as compared to delayed EN (DEN), is associated with improved clinical outcomes in mechanically ventilated (MV) patients with circulatory shock.

Methods We analyzed a dataset from an international, multicenter, pragmatic randomized clinical trial (RCT) evaluating protein dose in ICU patients. Data were collected from ICU admission, and EEN was defined as initiating < 48 h from ICU admission and DEN > 48 h. We identified MV patients in circulatory shock to evaluate the association between the timing of EN initiation and clinical outcomes. The regression analysis model controlled for age, mNUTRIC score, APACHE II score, sepsis, and Site.

Results We included 626 patients, from 52 ICUs in 14 countries. Median age was 60 years [18–93], 55% had septic shock, 99% received norepinephrine alone, 91% received EN alone, and 50.3% were randomized to a usual protein dose. Forty-two percent of EEN patients had persistent organ dysfunction syndrome plus death at day 28, compared to 53% in the DEN group (p = 0.04). EEN was associated with more ICU-free days (9.3 ± 9.2 vs. 5.7 ± 7.9, p = 0.0002), more days alive and free of vasopressors (7.1 ± 3.1 vs. 6.3 ± 3.2, p = 0.007), and shorter duration of MV among survivors (9.8 ± 10.9 vs. 13.8 ± 14.5, p = 0.0002). This trend was no longer observed in the adjusted analysis. There were no differences in ICU/60-day mortality or feeding intolerance rates between groups.

Conclusion In MV patients with circulatory shock, EEN, as compared to DEN, was associated with improved clinical outcomes, but no longer when adjusting for illness severity. RCTs comparing the efficacy of EEN to DEN in MV patients with circulatory shock are warranted.

19. 对REDOX研究的二次分析 重症患者的代谢 Catabolism in Critical Illness: A Reanalysis of the REducing Deaths due to OXidative Stress (REDOXS) Trial*

Haines, Ryan W.

doi: 10.1097/CCM.0000000000005499

OBJECTIVES: Ongoing risk of death and poor functional outcomes are important consequences of prolonged critical illness. Characterizing the catabolic phenotype of prolonged critical illness could illuminate biological processes and inform strategies to attenuate catabolism. We aimed to examine if urea-to-creatinine ratio, a catabolic signature of prolonged critical illness, was associated with mortality after the first week of ICU stay.

DESIGN: Reanalysis of multicenter randomized trial of glutamine supplementation in critical illness (REducing Deaths due to OXidative Stress [REDOXS]).

SETTING: Multiple adult ICUs.

PATIENTS: Adult patients admitted to ICU with two or more organ failures related to their acute illness and surviving to day 7.

INTERVENTIONS: None.

MEASUREMENTS AND MAIN RESULTS: The association between time-varying urea-to-creatinine ratio and 30-day mortality was tested using Bayesian joint models adjusted for prespecified-covariates (age, kidney replacement therapy, baseline Sequential Organ Failure Assessment, dietary protein [g/kg/d], kidney dysfunction, and glutamine-randomization). From 1,021 patients surviving to day 7, 166 (16.3%) died by day 30. After adjustment in a joint model, a higher time-varying urea-to-creatinine ratio was associated with increased mortality (hazard ratio [HR], 2.15; 95% credible interval, 1.66–2.82, for a two-fold greater urea-to-creatinine ratio). This association persisted throughout the 30-day follow-up. Mediation analysis was performed to explore urea-to-creatinine ratio as a mediator-variable for the increased risk of death reported in REDOXS when randomized to glutamine, an exogenous nitrogen load. Urea-to-creatinine ratio closest to day 7 was estimated to mediate the risk of death associated with randomization to glutamine supplementation (HR, 1.20; 95% CI, 1.04–1.38; p = 0.014), with no evidence of a direct effect of glutamine (HR, 0.90; 95% CI, 0.62–1.30; p = 0.566).

CONCLUSIONS: The catabolic phenotype measured by increased urea-to-creatinine ratio is associated with increased risk of death during prolonged ICU stay and signals the deleterious effects of glutamine administration in the REDOXS study. Urea-to-creatinine ratio is a promising catabolic signature and potential interventional target.

20. 早期神经肌肉电刺激加早期活动可改善危重病人的机能状态，减少住院天数  Early Neuromuscular Electrical Stimulation in Addition to Early Mobilization Improves Functional Status and Decreases Hospitalization Days of Critically Ill Patients

Campos, Débora R.

doi: 10.1097/CCM.0000000000005557

OBJECTIVES: To evaluate the impact of the additional use of early neuromuscular electrical stimulation (NMES) on an early mobilization (EM) protocol.

DESIGN: Randomized controlled trial.

SETTING: ICU of the Clinical Hospital of Ribeirão Preto, University of São Paulo, Brazil.

PATIENTS: One hundred and thirty-nine consecutive mechanically ventilated patients were included in the first 48 hours of ICU admission.

INTERVENTIONS: The patients were divided into two groups: EM and EM+NMES. Both groups received EM daily. In the EM+NMES group, patients additionally received NMES 5 days a week, for 60 minutes, starting in the first 48 hours of ICU admission until ICU discharge.

MEASUREMENTS AND MAIN RESULTS: Functional status, muscle strength, ICU and hospital length of stay (LOS), frequency of delirium, days on mechanical ventilation, mortality, and quality of life were assessed. Patients in the EM+NMES group presented a significant higher score of functional status measured by the Functional Status Score for the ICU scale when compared with the EM group in the first day awake: 22 (15–26) versus 12 (8–22) (p = 0.019); at ICU discharge: 28 (21–33) versus 18 (11–26) (p = 0.004); and hospital discharge: 33 (27–35) versus 25 (17–33) (p = 0.014), respectively. They also had better functional status measured by the Physical Function Test in the ICU scale, took less days to stand up during the ICU stay, and had a significant shorter hospital LOS, lower frequency of ICU-acquired weakness, and better global muscle strength.

CONCLUSIONS: The additional application of early NMES promoted better functional status outcomes on the first day awake and at ICU and hospital discharge. The patients in the EM+NMES group also took fewer days to stand up and had shorter hospital LOS, lower frequency of ICU-acquired weakness, and better muscle strength. Future studies are still necessary to clarify the effects of therapies associated with EM, especially to assess long-term outcomes.

21. 综述：ICU的体温管理Temperature Management in the ICU

Drewry, Anne

doi: 10.1097/CCM.0000000000005556

OBJECTIVE: Temperature abnormalities are recognized as a marker of human disease, and the therapeutic value of temperature is an attractive treatment target. The objective of this synthetic review is to summarize and critically appraise evidence for active temperature management in critically ill patients.

DATA SOURCES: We searched MEDLINE for publications relevant to body temperature management (including targeted temperature management and antipyretic therapy) in cardiac arrest, acute ischemic and hemorrhagic stroke, traumatic brain injury, and sepsis. Bibliographies of included articles were also searched to identify additional relevant studies.

STUDY SELECTION: English-language systematic reviews, meta-analyses, randomized trials, observational studies, and nonhuman data were reviewed, with a focus on the most recent randomized control trial evidence.

DATA EXTRACTION: Data regarding study methodology, patient population, temperature management strategy, and clinical outcomes were qualitatively assessed.

DATA SYNTHESIS: Temperature management is common in critically ill patients, and multiple large trials have been conducted to elucidate temperature targets, management strategies, and timing. The strongest data concerning the use of therapeutic hypothermia exist in comatose survivors of cardiac arrest, and recent trials suggest that appropriate postarrest temperature targets between 33°C and 37.5°C are reasonable. Targeted temperature management in other critical illnesses, including acute stroke, traumatic brain injury, and sepsis, has not shown benefit in large clinical trials. Likewise, trials of pharmacologic antipyretic therapy have not demonstrated improved outcomes, although national guidelines do recommend treatment of fever in patients with stroke and traumatic brain injury based on observational evidence associating fever with worse outcomes.

CONCLUSIONS: Body temperature management in critically ill patients remains an appealing therapy for several illnesses, and additional studies are needed to clarify management strategies and therapeutic pathways.

22. 全球开源疾病严重度评分 GOSIS The Global Open Source Severity of Illness Score (GOSSIS)*

Raffa, Jesse D.

doi: 10.1097/CCM.0000000000005518

OBJECTIVES: To develop and demonstrate the feasibility of a Global Open Source Severity of Illness Score (GOSSIS)-1 for critical care patients, which generalizes across healthcare systems and countries.

DESIGN: A merger of several critical care multicenter cohorts derived from registry and electronic health record data. Data were split into training (70%) and test (30%) sets, using each set exclusively for development and evaluation, respectively. Missing data were imputed when not available.

SETTING/PATIENTS:Two large multicenter datasets from Australia and New Zealand (Australian and New Zealand Intensive Care Society Adult Patient Database [ANZICS-APD]) and the United States (eICU Collaborative Research Database [eICU-CRD]) representing 249,229 and 131,051 patients, respectively. ANZICS-APD and eICU-CRD contributed data from 162 and 204 hospitals, respectively. The cohort included all ICU admissions discharged in 2014–2015, excluding patients less than 16 years old, admissions less than 6 hours, and those with a previous ICU stay.

INTERVENTIONS: Not applicable.

MEASUREMENTS AND MAIN RESULTS: GOSSIS-1 uses data collected during the ICU stay’s first 24 hours, including extrema values for vital signs and laboratory results, admission diagnosis, the Glasgow Coma Scale, chronic comorbidities, and admission/demographic variables. The datasets showed significant variation in admission-related variables, case-mix, and average physiologic state. Despite this heterogeneity, test set discrimination of GOSSIS-1 was high (area under the receiver operator characteristic curve [AUROC], 0.918; 95% CI, 0.915–0.921) and calibration was excellent (standardized mortality ratio [SMR], 0.986; 95% CI, 0.966–1.005; Brier score, 0.050). Performance was held within ANZICS-APD (AUROC, 0.925; SMR, 0.982; Brier score, 0.047) and eICU-CRD (AUROC, 0.904; SMR, 0.992; Brier score, 0.055). Compared with GOSSIS-1, Acute Physiology and Chronic Health Evaluation (APACHE)-IIIj (ANZICS-APD) and APACHE-IVa (eICU-CRD), had worse discrimination with AUROCs of 0.904 and 0.869, and poorer calibration with SMRs of 0.594 and 0.770, and Brier scores of 0.059 and 0.063, respectively.

CONCLUSIONS: GOSSIS-1 is a modern, free, open-source inhospital mortality prediction algorithm for critical care patients, achieving excellent discrimination and calibration across three countries.

23. 呼吸道合胞病毒与流感感染ICU患者的特点及预后 Characteristics and Outcomes of Patients in the ICU With Respiratory Syncytial Virus Compared With Those With Influenza Infection A Multicenter Matched Cohort Study

Julien Coussement

Https://doi.org/10.1016/j.chest.2021.12.670

Background The characteristics and outcomes of adult patients with respiratory syncytial virus (RSV) infection who require ICU admission are poorly defined. Although several studies in adults with RSV infection have been published in recent years, they did not focus specifically on patients with critical illness.

Research Question  What are the characteristics and outcomes of adult patients in the ICU with RSV infection and how do they compare with those of patients in the ICU with influenza infection?

Study Design and Methods This retrospective, multicenter study in France and Belgium (17 sites) compared the characteristics and outcomes of adult patients in the ICU with RSV infection vs those with influenza infection between November 2011 and April 2018. Each patient with RSV infection was matched by institution and date of diagnosis with a patient with influenza infection. In-hospital mortality was compared between the two groups, with adjustment for prognostic factors in a multivariate model (sex, age, main underlying conditions, and concurrent bloodstream infection).

Results Data from 618 patients (309 with RSV infection and 309 with influenza infection) were analyzed. Patients with RSV infection were significantly more likely to have an underlying chronic respiratory condition (60.2% vs 40.1%; P < .001) and to be immunocompromised (35% vs 26.2%; P = .02) than patients with influenza infection. Several differences in clinical signs and biological data at diagnosis were found between the groups. In-hospital mortality was not significantly different between the two groups (23.9% in the RSV group vs 25.6% in the influenza group; P = .63), even after adjustment for prognostic factors in a multivariate model.

Interpretation Adult patients in the ICU with RSV infection differ from adult patients in the ICU with influenza in terms of comorbidities and characteristics at diagnosis. RSV infection was associated with high in-hospital mortality, approaching 25%. In multivariate analysis, RSV infection was associated with a similar odds of in-hospital death compared with influenza infection.

24. 成人脓毒症中以1-3β葡聚糖为靶向的抗真菌治疗   (1 → 3)-β-D-Glucan-guided antifungal therapy in adults with sepsis: the CandiSep randomized clinical trial

 the SepNet Study Group

https://doi.org/10.1007/s00134-022-06733-x

Purpose To investigate whether (1 → 3)-β-d-Glucan (BDG)-guidance shortens time to antifungal therapy and thereby reduces mortality of sepsis patients with high risk of invasive Candida infection (ICI).

Methods Multicenter, randomized, controlled trial carried out between September 2016 and September 2019 in 18 intensive care units enrolling adult sepsis patients at high risk for ICI. Patients in the control group received targeted antifungal therapy driven by culture results. In addition to targeted therapy, patients in the BDG group received antifungals if at least one of two consecutive BDG samples taken during the first two study days was ≥ 80 pg/mL. Empirical antifungal therapy was discouraged in both groups. The primary endpoint was 28-day-mortality.

Results 339 patients were enrolled. ICI was diagnosed in 48 patients (14.2%) within the first 96 h after enrollment. In the BDG-group, 48.8% (84/172) patients received antifungals during the first 96 h after enrollment and 6% (10/167) patients in the control group. Death until day 28 occurred in 58 of 172 patients (33.7%) in the BDG group and 51 of 167 patients (30.5%) in the control group (relative risk 1.10; 95% confidence interval, 0.80–1.51; p = 0.53). Median time to antifungal therapy was 1.1 [interquartile range (IQR) 1.0–2.2] days in the BDG group and 4.4 (IQR 2.0–9.1, p < 0.01) days in the control group.

Conclusions Serum BDG guided antifungal treatment did not improve 28-day mortality among sepsis patients with risk factors for but unexpected low rate of IC. This study cannot comment on the potential benefit of BDG-guidance in a more selected at-risk population.

25. 立场文件：液体耐受性的概念产生 The emerging concept of fluid tolerance: A position paper

Eduardo Kattan

https://doi.org/10.1016/j.jcrc.2022.154070

Fluid resuscitation is a core component of emergency and critical care medicine. While the focus of clinicians has largely been on detecting patients who would respond to fluid therapy, relatively little work has been done on assessing patients’ tolerance to this therapy. In this article we seek to review the concept of fluid tolerance, propose a working definition, and introduce relevant clinical signals by which physicians can assess fluid tolerance, hopefully becoming a starting point for further research.

26. 多中心随机双盲试验：重度坏死性胰腺炎的免疫增强治疗  Immune enhancement in patients with predicted severe acute necrotising pancreatitis: a multicentre double-blind randomised controlled trial

the Chinese Acute Pancreatitis Clinical Trials Group (CAPCTG)

https://doi.org/10.1007/s00134-022-06745-7

Purpose Infected pancreatic necrosis (IPN) is a highly morbid complication of acute necrotising pancreatitis (ANP). Since there is evidence of early-onset immunosuppression in acute pancreatitis, immune enhancement may be a therapeutic option. This trial aimed to evaluate whether early immune-enhancing Thymosin alpha 1 (Tα1) treatment reduces the incidence of IPN in patients with predicted severe ANP.

Methods We conducted a multicentre, double-blind, randomised, placebo-controlled trial involving ANP patients with an Acute Physiology and Chronic Health Evaluation II (APACHE II) score ≥ 8 and a computed tomography (CT) severity score ≥ 5 admitted within 7 days of the advent of symptoms. Enrolled patients were assigned to receive a subcutaneous injection of Tα1 1.6 mg every 12 h for the first 7 days and 1.6 mg once a day for the subsequent 7 days or matching placebos (normal saline). The primary outcome was the development of IPN during the index admission.

Results A total of 508 patients were randomised, of whom 254 were assigned to receive Tα1 and 254 placebo. The vast majority of the participants required admission to the intensive care unit (ICU) (479/508, 94.3%). During the index admission, 40/254(15.7%) patients in the Tα1 group developed IPN compared with 46/254 patients (18.1%) in the placebo group (difference -2.4% [95% CI − 7.4 to 5.1%]; p = 0.48). The results were similar across four predefined subgroups. There was no difference in other major complications, including new-onset organ failure (10.6% vs. 15%), bleeding (6.3% vs. 3.5%), and gastrointestinal fistula (2% vs. 2.4%).

Conclusion The immune-enhancing Tα1 treatment of patients with predicted severe ANP did not reduce the incidence of IPN during the index admission.

27. 综述：机械通气的ARDS患者的俯卧位通气与神经肌肉阻滞的辅助治疗Prone Positioning and Neuromuscular Blocking Agents as Adjunctive Therapies in Mechanically Ventilated Patients with Acute Respiratory Distress Syndrome

Claude Guérin

DOI: 10.1055/s0042-1744304

Neuromuscular blocking agents (NMBAs) and prone position (PP) are two major adjunctive therapies that can improve outcome in moderate-to-severe acute respiratory distress syndrome. NMBA should be used once lung-protective mechanical ventilation has been set, for 48 hours or less and as a continuous intravenous infusion. PP should be used as early as possible for long sessions; in COVID-19 its use has exploded. In nonintubated patients, PP might reduce the rate of intubation but not mortality. The goal of this article is to perform a narrative review on the pathophysiological rationale, the clinical effects, and the clinical use and recommendations of both NMBA and PP.

28. 洞察ARDS柏林定义Insights Regarding the Berlin Definition of ARDS from Prospective Observational Studies

Ciara Hanley

DOI: 10.1055/s-0042-1744306

The definition of acute respiratory distress syndrome (ARDS), has evolved since it was first described in 1967 by Ashbaugh and Petty to the current “Berlin” definition of ARDS developed in 2012 by an expert panel, that provided clarification on the definition of “acute,” and on the cardiac failure criteria. It expanded the definition to include patients receiving non-invasive ventilation, and removed the term “acute lung injury” and added a requirement of patients to be receiving a minimum 5 cmH2O expiratory pressure.

Since 2012, a series of observational cohort studies have generated insights into the utility and robustness of this definition. This review will examine novel insights into the epidemiology of ARDS, failures in ARDS diagnosis, the role of lung imaging in ARDS, the novel ARDS cohort that is not invasively ventilated, lung compliance profiles in patients with ARDS, sex differences that exist in ARDS management and outcomes, the progression of ARDS following initial diagnosis, and the clinical profile and outcomes of confirmed versus resolved ARDS. Furthermore, we will discuss studies that challenge the utility of distinguishing ARDS from other causes of acute hypoxemic respiratory failure (AHRF) and identify issues that may need to be addressed in a revised definition.

29. 机械通气患者的院内获得性肺炎 Nosocomial Pneumonia in the Mechanically Ventilated Patient

Jonathon Fanning

DOI: 10.1055/s-0042-1749448

Ventilator-associated pneumonia (VAP) is a common complication occurring in critically ill patients who are mechanically ventilated and is the leading cause of nosocomial infection-related death. Etiologic agents for VAP widely differ based on the population of intensive care unit patients, duration of hospital stay, and prior antimicrobial therapy. VAP due to multidrug-resistant pathogens is associated with the highest morbidity and mortality, likely due to delays in appropriate antimicrobial treatment. International guidelines are currently available to guide diagnostic and therapeutic strategies. VAP can be prevented through various pharmacological and non-pharmacological interventions, which are more effective when grouped as bundles. When VAP is clinically suspected, diagnostic strategies should include early collection of respiratory samples to guide antimicrobial therapy. Empirical treatment should be based on the most likely etiologic microorganisms and antibiotics likely to be active against these microorganisms. Response to therapy should be reassessed after 3 to 5 days and antimicrobials adjusted or de-escalated to reduce the burden of the disease. Finally, considering that drug resistance is increasing worldwide, several novel antibiotics are being tested to efficiently treat VAP in the coming decades.