Corley Amanda, Rickard Claire M, Aitken Leanne M, Johnston Amy, Barnett Adrian, Fraser John F, Lewis Sharon R, Smith Andrew F
Critical Care Research Group, The Prince Charles Hospital and University of Queensland, Level 5, CSB, Rode Rd, Chermside, Queensland, Australia, 4032.
National Centre of Research Excellence in Nursing, Menzies Health Institute Queensland, Griffith University, Brisbane, Australia.
Cochrane Database Syst Rev. 2017 May 30;5(5):CD010172. doi: 10.1002/14651858.CD010172.pub2.
High-flow nasal cannulae (HFNC) deliver high flows of blended humidified air and oxygen via wide-bore nasal cannulae and may be useful in providing respiratory support for adult patients experiencing acute respiratory failure in the intensive care unit (ICU).
We evaluated studies that included participants 16 years of age and older who were admitted to the ICU and required treatment with HFNC. We assessed the safety and efficacy of HFNC compared with comparator interventions in terms of treatment failure, mortality, adverse events, duration of respiratory support, hospital and ICU length of stay, respiratory effects, patient-reported outcomes, and costs of treatment.
We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2016, Issue 3), MEDLINE, the Cumulative Index to Nursing and Allied Health Literature (CINAHL), Embase, Web of Science, proceedings from four conferences, and clinical trials registries; and we handsearched reference lists of relevant studies. We conducted searches from January 2000 to March 2016 and reran the searches in December 2016. We added four new studies of potential interest to a list of 'Studies awaiting classification' and will incorporate them into formal review findings during the review update.
We included randomized controlled studies with a parallel or cross-over design comparing HFNC use in adult ICU patients versus other forms of non-invasive respiratory support (low-flow oxygen via nasal cannulae or mask, continuous positive airway pressure (CPAP), and bilevel positive airway pressure (BiPAP)).
Two review authors independently assessed studies for inclusion, extracted data, and assessed risk of bias.
We included 11 studies with 1972 participants. Participants in six studies had respiratory failure, and in five studies required oxygen therapy after extubation. Ten studies compared HFNC versus low-flow oxygen devices; one of these also compared HFNC versus CPAP, and another compared HFNC versus BiPAP alone. Most studies reported randomization and allocation concealment inadequately and provided inconsistent details of outcome assessor blinding. We did not combine data for CPAP and BiPAP comparisons with data for low-flow oxygen devices; study data were insufficient for separate analysis of CPAP and BiPAP for most outcomes. For the primary outcomes of treatment failure (1066 participants; six studies) and mortality (755 participants; three studies), investigators found no differences between HFNC and low-flow oxygen therapies (risk ratio (RR), Mantel-Haenszel (MH), random-effects 0.79, 95% confidence interval (CI) 0.49 to 1.27; and RR, MH, random-effects 0.63, 95% CI 0.38 to 1.06, respectively). We used the GRADE approach to downgrade the certainty of this evidence to low because of study risks of bias and different participant indications. Reported adverse events included nosocomial pneumonia, oxygen desaturation, visits to general practitioner for respiratory complications, pneumothorax, acute pseudo-obstruction, cardiac dysrhythmia, septic shock, and cardiorespiratory arrest. However, single studies reported adverse events, and we could not combine these findings; one study reported fewer episodes of oxygen desaturation with HFNC but no differences in all other reported adverse events. We downgraded the certainty of evidence for adverse events to low because of limited data. Researchers noted no differences in ICU length of stay (mean difference (MD), inverse variance (IV), random-effects 0.15, 95% CI -0.03 to 0.34; four studies; 770 participants), and we downgraded quality to low because of study risks of bias and different participant indications. We found no differences in oxygenation variables: partial pressure of arterial oxygen (PaO)/fraction of inspired oxygen (FiO) (MD, IV, random-effects 7.31, 95% CI -23.69 to 41.31; four studies; 510 participants); PaO (MD, IV, random-effects 2.79, 95% CI -5.47 to 11.05; three studies; 355 participants); and oxygen saturation (SpO) up to 24 hours (MD, IV, random-effects 0.72, 95% CI -0.73 to 2.17; four studies; 512 participants). Data from two studies showed that oxygen saturation measured after 24 hours was improved among those treated with HFNC (MD, IV, random-effects 1.28, 95% CI 0.02 to 2.55; 445 participants), but this difference was small and was not clinically significant. Along with concern about risks of bias and differences in participant indications, review authors noted a high level of unexplained statistical heterogeneity in oxygenation effect estimates, and we downgraded the quality of evidence to very low. Meta-analysis of three comparable studies showed no differences in carbon dioxide clearance among those treated with HFNC (MD, IV, random-effects -0.75, 95% CI -2.04 to 0.55; three studies; 590 participants). Two studies reported no differences in atelectasis; we did not combine these findings. Data from six studies (867 participants) comparing HFNC versus low-flow oxygen showed no differences in respiratory rates up to 24 hours according to type of oxygen delivery device (MD, IV, random-effects -1.51, 95% CI -3.36 to 0.35), and no difference after 24 hours (MD, IV, random-effects -2.71, 95% CI -7.12 to 1.70; two studies; 445 participants). Improvement in respiratory rates when HFNC was compared with CPAP or BiPAP was not clinically important (MD, IV, random-effects -0.89, 95% CI -1.74 to -0.05; two studies; 834 participants). Results showed no differences in patient-reported measures of comfort according to oxygen delivery devices in the short term (MD, IV, random-effects 0.14, 95% CI -0.65 to 0.93; three studies; 462 participants) and in the long term (MD, IV, random-effects -0.36, 95% CI -3.70 to 2.98; two studies; 445 participants); we downgraded the certainty of this evidence to low. Six studies measured dyspnoea on incomparable scales, yielding inconsistent study data. No study in this review provided data on positive end-expiratory pressure measured at the pharyngeal level, work of breathing, or cost comparisons of treatment.
AUTHORS' CONCLUSIONS: We were unable to demonstrate whether HFNC was a more effective or safe oxygen delivery device compared with other oxygenation devices in adult ICU patients. Meta-analysis could be performed for few studies for each outcome, and data for comparisons with CPAP or BiPAP were very limited. In addition, we identified some risks of bias among included studies, differences in patient groups, and high levels of statistical heterogeneity for some outcomes, leading to uncertainty regarding the results of our analysis. Consequently, evidence is insufficient to show whether HFNC provides safe and efficacious respiratory support for adult ICU patients.
高流量鼻导管（HFNC）通过宽孔鼻导管输送高流量的混合湿化空气和氧气，可能有助于为重症监护病房（ICU）中出现急性呼吸衰竭的成年患者提供呼吸支持。
我们评估了纳入16岁及以上入住ICU且需要HFNC治疗的参与者的研究。我们比较了HFNC与对照干预措施在治疗失败、死亡率、不良事件、呼吸支持持续时间、住院和ICU住院时间、呼吸效应、患者报告结局以及治疗成本方面的安全性和有效性。
我们检索了Cochrane对照试验中心注册库（CENTRAL；2016年第3期）、MEDLINE、护理学与健康相关文献累积索引（CINAHL）、Embase、科学引文索引、四个会议的论文集以及临床试验注册库；并手工检索了相关研究的参考文献列表。我们在2000年1月至2016年3月期间进行了检索，并于2016年12月重新检索。我们将四项潜在感兴趣的新研究添加到“待分类研究”列表中，并将在更新综述时将它们纳入正式的综述结果中。
我们纳入了采用平行或交叉设计的随机对照研究，比较成人ICU患者使用HFNC与其他形式的无创呼吸支持（通过鼻导管或面罩的低流量氧气、持续气道正压通气（CPAP）和双水平气道正压通气（BiPAP））。
两位综述作者独立评估研究是否纳入、提取数据并评估偏倚风险。
我们纳入了11项研究，共1972名参与者。六项研究中的参与者患有呼吸衰竭，五项研究中的参与者在拔管后需要氧疗。十项研究比较了HFNC与低流量氧气设备；其中一项还比较了HFNC与CPAP，另一项单独比较了HFNC与BiPAP。大多数研究报告随机化和分配隐藏不充分，并且提供的结局评估者盲法细节不一致。我们没有将CPAP和BiPAP比较的数据与低流量氧气设备的数据合并；对于大多数结局，研究数据不足以对CPAP和BiPAP进行单独分析。对于治疗失败（1066名参与者；六项研究）和死亡率（755名参与者；三项研究）的主要结局，研究者发现HFNC与低流量氧气疗法之间没有差异（风险比（RR），Mantel-Haenszel（MH），随机效应0.79，95%置信区间（CI）0.49至1.27；以及RR，MH，随机效应0.63，95%CI 0.38至1.06）。由于研究的偏倚风险和不同的参与者适应症，我们使用GRADE方法将此证据的确定性降至低等级。报告的不良事件包括医院获得性肺炎、氧饱和度下降、因呼吸并发症就诊于全科医生、气胸、急性假性肠梗阻、心律失常、感染性休克和心肺骤停。然而，单项研究报告了不良事件，我们无法合并这些结果；一项研究报告使用HFNC时氧饱和度下降的发作次数较少，但在所有其他报告的不良事件中没有差异。由于数据有限，我们将不良事件证据的确定性降至低等级。研究人员指出ICU住院时间没有差异（平均差（MD），逆方差（IV），随机效应0.15，95%CI -0.03至0.34；四项研究；770名参与者），并且由于研究的偏倚风险和不同的参与者适应症，我们将质量降至低等级。我们发现氧合变量没有差异：动脉血氧分压（PaO）/吸入氧分数（FiO）（MD，IV，随机效应7.31，95%CI -23.69至41.31；四项研究；510名参与者）；PaO（MD，IV，随机效应2.79，95%CI -5.47至11.05；三项研究；355名参与者）；以及长达24小时的氧饱和度（SpO）（MD，IV，随机效应0.72，95%CI -0.73至2.17；四项研究；512名参与者）。两项研究的数据显示，接受HFNC治疗的患者在24小时后测量的氧饱和度有所改善（MD，IV，随机效应1.28，95%CI 0.02至2.55；445名参与者），但这种差异很小且无临床意义。除了对偏倚风险和参与者适应症差异的担忧外，综述作者还指出氧合效应估计中存在高度无法解释的统计异质性，我们将证据质量降至极低等级。对三项可比研究的荟萃分析表明，接受HFNC治疗的患者在二氧化碳清除方面没有差异（MD，IV，随机效应-0.75，95%CI -2.04至0.55；三项研究；590名参与者）。两项研究报告肺不张没有差异；我们没有合并这些结果。六项比较HFNC与低流量氧气的研究（867名参与者）的数据显示，根据氧气输送设备类型，长达24小时的呼吸频率没有差异（MD，IV，随机效应-1.51，95%CI -3.36至0.35），24小时后也没有差异（MD，IV，随机效应-2.71，95%CI -7.12至1.70；两项研究；445名参与者）。将HFNC与CPAP或BiPAP比较时，呼吸频率的改善在临床上并不重要（MD，IV，随机效应-0.89，95%CI -1.74至-0.05；两项研究；834名参与者）。结果显示，根据氧气输送设备，患者报告的短期舒适度测量结果没有差异（MD，IV，随机效应0.14，95%CI -0.65至0.93；三项研究；462名参与者），长期也没有差异（MD，IV，随机效应-0.36，95%CI -3.70至2.98；两项研究；445名参与者）；我们将此证据的确定性降至低等级。六项研究以不可比的量表测量了呼吸困难，得出的数据不一致。本综述中没有研究提供关于咽部水平测量的呼气末正压、呼吸功或治疗成本比较的数据。
我们无法证明与其他氧合设备相比，HFNC在成年ICU患者中是否是一种更有效或更安全的氧气输送设备。对于每个结局，能够进行荟萃分析的研究很少，与CPAP或BiPAP比较的数据非常有限。此外，我们在纳入的研究中发现了一些偏倚风险、患者群体差异以及某些结局的高度统计异质性，导致我们分析结果的不确定性。因此，证据不足以表明HFNC是否为成年ICU患者提供安全有效的呼吸支持。
