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2015-11-24 摘自CSCCM 呼吸重症

Editorial |

The Changing Landscape of Noninvasive Ventilation in the Intensive Care Unit

Bhakti K. Patel, MD; John P. Kress, MD

JAMA. 2015;314(16):1697-1699. doi:10.1001/jama.2015.12401

Traditionally, endotracheal intubation has been used as a treatment for patients with respiratory failure who require mechanical ventilation. Although intubation can be lifesaving, it is also associated with significant morbidity.1 Immunocompromised patients with acute hypoxemic respiratory failure are at particularly high risk; these patients often require high levels of ventilatory support (ie, positive end-expiratory pressure [PEEP] and fractions of inspired oxygen [Fio2]). Intubated patients usually require sedative medications, analgesic agents, or both and are at risk for many complications seen in the intensive care unit (ICU), such as ventilator-associated pneumonia, ICU-acquired weakness,2 venous thromboembolism,3 delirium, and cognitive dysfunction.4 As such, these patients typically have a high associated mortality, estimated at approximately 50%.5

传统上,气管插管用于治疗需要机械通气的呼吸衰竭患者。尽管气管插管能够挽救生命,但也伴有很多并发症[1]。伴随急性低氧性呼吸衰竭的免疫功能抑制患者具有很高的风险;这些患者经常需要很高的呼吸支持水平(即呼气末正压[PEEP]及吸入氧浓度[FiO2])。气管插管患者常常需要使用镇静药物和(或)镇痛药物,容易发生很多ICU并发症,如呼吸机相关肺炎、ICU获得性肌无力[2]、静脉血栓栓塞[3]、谵妄及认知功能障碍[4]。因此,这些患者病死率很高,估计约为50% [5]。

Therefore, in modern ICU care, noninvasive ventilation is used frequently for the care of patients with acute respiratory failure. Specifically, this intervention can improve gas exchange and reduce the work of breathing without requiring an artificial airway. Consequently, patients treated with noninvasive ventilation may avoid some of the adverse consequences of invasive mechanical ventilation. The most compelling evidence for the benefits of noninvasive ventilation is from studies involving patients with exacerbations of chronic obstructive pulmonary disease6 and acute cardiogenic pulmonary edema.7 The benefits of noninvasive ventilation in hypoxemic immunocompromised patients are less compelling. Two small, randomized clinical trials demonstrated that use of noninvasive ventilation was associated with a substantial decrease in rates of endotracheal intubation, ICU complications, and mortality.5,8 However, these studies are old, and other studies that involved a heterogeneous population of patients with acute hypoxemic respiratory failure demonstrated high rates of treatment failure with noninvasive ventilation.9,10


Over the last 2 decades, the technology of noninvasive ventilation has changed substantially. The ventilators used in the 1990s delivered pressure through the ventilator circuit with room air as the source of fresh gas flow,6 with flow rates that were relatively low (ie, 10 to 35 L/min). These flow rates could be supplemented by oxygen delivered via a side port tubing connection. However, given that room air was the source of most of the fresh gas flow through the ventilator, the highest Fio2 that could be delivered was typically limited to 30% to 40%. Such ventilators were of limited utility in the care of patients requiring higher Fio2 levels. In addition, the ventilator interface was a rubber face mask that was often prone to air leakage when high pressures were needed.6 In contrast, modern noninvasive ventilation involves use of a ventilator with the fresh gas flow source coming directly from the medical oxygen and medical air sources. These connections allow for high pressure and flow and an Fio2 that can be titrated from 21% to 100% as needed. Furthermore, the interfaces now available for noninvasive ventilation administration include more compliant masks of various sizes; these tend to be much more comfortable, particularly for patients with acute hypoxemic respiratory failure, who often require higher levels of PEEP, higher driving pressures, or both.

在过去20年间,无创通气技术发生了显著改变。90年代使用的呼吸机采用空气作为新鲜气流来源,经呼吸机管路产生压力[6],气流流量相对较低(即10-35 L/min)。同时,经侧孔通过连接管路给与氧气。然而,如果将空气作为呼吸机新鲜气流来源,通常情况下可以提供的最高FiO2仅为30-40%。这样的呼吸机在需要较高FiO2的患者治疗中用处有限。另外,呼吸机使用的橡胶面罩在需要较高压力时容易发生漏气[6]。相反,现代无创呼吸机的新鲜气流直接来源于医用氧气和医用空气。这使得无创呼吸机能够产生较高压力,FiO2也能根据需要在21%至100%之间调节。而且,无创通气目前可以使用多种不同型号的面罩;其舒适性更佳,尤其对于急性低氧性呼吸衰竭患者而言,这些患者常常需要较高的PEEP和(或)较高的驱动压力。

Not only has noninvasive ventilation changed, but the case mix and care of critically ill patients with immunocompromise has also changed considerably over the last 20 years. Together, these issues have fueled controversy over the role of noninvasive ventilation for acute hypoxemic respiratory failure in this patient population. Therefore, Lemiale and colleagues11 tested the efficacy of noninvasive ventilation in immunocompromised patients in a multicenter randomized clinical trial, the results of which are published in this issue of JAMA. This study has many strengths. The investigators are an experienced group with a high level of expertise in the use of noninvasive ventilation for respiratory failure. The study was carefully designed, with excellent adherence to the protocol and 100% long-term follow-up. Even though it was impossible to blind the study groups, the end points of 28-day mortality and need for endotracheal intubation are objective and are subject to very low risk for bias affecting the outcome.


In contrast to studies from more than a decade prior, the investigators in the current trial were unable to demonstrate a mortality benefit, with 24.1% mortality in the group with early use of noninvasive ventilation (46 deaths among 191 patients) vs 27.3% mortality in the group receiving oxygen alone (50 deaths among 183 patients) (P = .47). Furthermore, intubation rates were not different between the groups (38.2% in the noninvasive ventilation group vs 44.8% in the oxygen alone group, P = .20).

与10多年前的研究不同,研究者并未发现无创通气能够改善病死率,早期使用无创通气组病死率24.1%(191名患者中46名死亡),仅接受氧疗组病死率27.3%(183名患者中50名死亡)(p = .47)。而且,两组间气管插管比例也没有差异(无创通气组38.2%,单纯氧疗组44.8%,p = .20)

However, before the use of noninvasive ventilation in immunocompromised patients is abandoned, these findings should be contextualized by advances in ICU care in the past 15 years, since publication of the seminal articles on this intervention in this type of patient population.5,8


First, overall mortality in the immunocompromised critically ill population has declined with advances in targeted chemotherapy, prophylactic use of antibiotics, and improved supportive care.12 In their study, Lemiale et al anticipated a higher baseline mortality of 35%, which limited their power to detect a mortality difference. Second, the patients enrolled in the earlier trials by Hilbert et al8 and Antonelli et al5 had greater degrees of tachypnea compared with patients in the current study (upper respiratory rate, 35-38/min vs 25/min), suggesting a greater severity of respiratory failure in the previous trials. However, unlike the earlier studies of noninvasive ventilation in acute hypoxemic respiratory failure,5,8 Lemiale et al did not report a severity of illness score (eg, Simplified Acute Physiology Score).13 Given the much higher respiratory rates and higher mortality in the earlier trials, it may be that the patients in this current trial had lower acuity of illness. Third, in the study by Lemiale et al, a greater proportion of patients in the oxygen alone group than in the noninvasive ventilation group received high-flow oxygen via nasal cannula. Given the recent findings of improved mortality with high-flow nasal cannula compared with noninvasive ventilation,14 perhaps the benefits from noninvasive ventilation were diluted with the use of this therapy. As the authors suggest, a comparison of high-flow oxygen and noninvasive ventilation for the management of acute hypoxemic respiratory failure in immunocompromised patients warrants further study. Therefore, all of these factors may have contributed to regression to the mean for the clinical outcomes in this negative trial.

首先,随着针对性化疗、预防性抗生素以及支持治疗的进步,免疫功能抑制的危重病患者病死率降低[12]。Lemiale等人在研究中预计基线病死率高达35%,这限制了此项研究检测病死率差异的效力。其次,与此项研究相比,Hilbert等 [8]和 Antonelli等 [5]的较早研究中入选患者呼吸频数的程度更重(呼吸频率上限35-38 bpm vs. 25 bpm),提示既往研究中患者呼吸衰竭更为严重。然而,与既往无创通气治疗急性低氧性呼吸衰竭的研究不同[5,8],Lemiale等并未报告疾病严重程度评分(如简化急性生理评分)[13]。根据早期研究中呼吸频率更快及病死率更高的情况,此项研究中的患者很可能病情较轻。第三,在Lemiale等人的研究中,单纯氧疗组有更多患者接受经鼻导管高流量氧疗。鉴于近期研究发现高流量鼻导管氧疗较无创通气改善病死率[14],使用高流量鼻导管氧疗可能会减弱无创通气的益处。正如作者所指出的,比较高流量氧疗与无创通气治疗免疫功能抑制患者的急性低氧性呼吸衰竭还需要进一步的研究。因而,所有这些因素均可能导致这一研究中临床预后的阴性结果。

The physiologic goals of noninvasive ventilation in the treatment of acute hypoxemic respiratory failure are to recruit lung with the proper use of PEEP and unload the respiratory muscles with the addition of pressure support ventilation. Physiologic studies examining use of noninvasive ventilation in acute lung injury have suggested that a PEEP of at least 10 cm H2O is required to significantly improve Pao2:Fio2 ratio with therapy.15 Furthermore, titration of PEEP and pressure support ventilation titration can be limited by the face mask leak and poor patient tolerance, even with modern ventilators and face mask interfaces, thus decreasing the efficacy of noninvasive ventilation delivered via face mask. With additional efforts to continue to reduce the percentage of critically ill patients who require invasive mechanical ventilation, alternative strategies for noninvasive ventilation that minimize face mask leak, improve oxygenation, and decrease work of breathing with alternative interfaces such as high-flow nasal cannula will need further investigation.

无创通气治疗急性低氧性呼吸功能衰竭的生理目标包括,适当使用PEEP使肺复张,加用压力支持通气减轻呼吸肌肉负荷。验证无创通气用于急性肺损伤的生理学研究提示,至少需要10 cmH2O的PEEP才能显著改善PaO2/FiO2比值[15]。而且,即便使用现代呼吸机及面罩,面罩漏气及患者耐受性不佳等问题也限制了PEEP及压力支持调节的效果,从而影响了经面罩进行无创通气的疗效。随着降低危重病患者对有创机械通气需求的努力,采用高流量鼻导管等其他方式,通过其他无创通气策略减少面罩漏气、改善氧合并降低呼吸做功,尚需要进一步研究。


1. Pingleton SK. Complications of acute respiratory failure. Am Rev Respir Dis. 1988;137(6):1463-1493. PubMed | Link to Article

2. Kress JP, Hall JB. ICU-acquired weakness and recovery from critical illness. N Engl J Med. 2014;370(17):1626-1635. PubMed | Link to Article

3. Fowler RA, Mittmann N, Geerts W, et al; Canadian Critical Care Trials Group; Australia and New Zealand Intensive Care Society Clinical Trials Group. Dalteparin vs unfractionated heparin in critically ill patients. N Engl J Med. 2011;364:1305-1314. PubMed | Link to Article

4. Pandharipande PP, Girard TD, Jackson JC, et al; BRAIN-ICU Study Investigators. Long-term cognitive impairment after critical illness. N Engl J Med. 2013;369(14):1306-1316. PubMed | Link to Article

5. Antonelli M, Conti G, Bufi M, et al. Noninvasive ventilation for treatment of acute respiratory failure in patients undergoing solid organ transplantation: a randomized trial. JAMA. 2000;283(2):235-241. PubMed | Link to Article

6. Brochard L, Mancebo J, Wysocki M, et al. Noninvasive ventilation for acute exacerbations of chronic obstructive pulmonary disease. N Engl J Med. 1995;333(13):817-822. PubMed | Link to Article

7. Masip J, Roque M, Sánchez B, Fernández R, Subirana M, Expósito JA. Noninvasive ventilation in acute cardiogenic pulmonary edema: systematic review and meta-analysis. JAMA. 2005;294(24):3124-3130. PubMed | Link to Article

8. Hilbert G, Gruson D, Vargas F, et al. Noninvasive ventilation in immunosuppressed patients with pulmonary infiltrates, fever, and acute respiratory failure. N Engl J Med. 2001;344(7):481-487. PubMed | Link to Article

9. Delclaux C, L’Her E, Alberti C, et al. Treatment of acute hypoxemic nonhypercapnic respiratory insufficiency with continuous positive airway pressure delivered by a face mask: a randomized controlled trial. JAMA. 2000;284(18):2352-2360. PubMed | Link to Article

10. Wysocki M, Tric L, Wolff MA, Millet H, Herman B. Noninvasive pressure support ventilation in patients with acute respiratory failure: a randomized comparison with conventional therapy. Chest. 1995;107(3):761-768. PubMed | Link to Article

11. Lemiale V, Mokart D, Resche-Rigon M, et al; Groupe de Recherche en Réanimation Respiratoire du patient d’Onco-Hématologie. Effect of noninvasive ventilation vs oxygen therapy on mortality among immunocompromised patients with acute respiratory failure: a randomized clinical trial. JAMA. doi:10.1001/jama.2015.12402.

12. Azoulay E, Soares M, Darmon M, Benoit D, Pastores S, Afessa B. Intensive care of the cancer patient: recent achievements and remaining challenges. Ann Intensive Care. 2011;1(1):5. PubMed | Link to Article

13. Le Gall JR, Lemeshow S, Saulnier F. A new Simplified Acute Physiology Score (SAPS II) based on a European/North American multicenter study. JAMA. 1993;270(24):2957-2963. PubMed | Link to Article

14. Frat JP, Thille AW, Mercat A, et al; FLORALI Study Group; REVA Network. High-flow oxygen through nasal cannula in acute hypoxemic respiratory failure. N Engl J Med. 2015;372(23):2185-2196. PubMed | Link to Article

15. L’Her E, Deye N, Lellouche F, et al. Physiologic effects of noninvasive ventilation during acute lung injury. Am J Respir Crit Care Med. 2005;172(9):1112-1118. PubMed | Link to Article

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