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Clinical Practice Guideline Clinical Practice Guideline: Non-Invasive Mechanical Ventilation as Treatment of Acute Respiratory Failure 1Krankenhaus Oststadt-Heidehaus, Abteilung Pneumologie und internistische Intensivmedizin, Klinikum Region Hannover 2Klinik für Intensivmedizin, Helios Klinikum, Berlin Buch 3Abteilung für Klinische Anästhesiologie und Operative Intensivmedizin, Evangelisches Krankenhaus Göttingen-Weende 4Lungen Klinik Herner 5Institut für theoretische Chirurgie, Phillips-Universität, Marburg *Abteilung für Pneumologie und internistische Intensivmedizin, Krankenhaus Oststadt – Heidehaus, Klinikum Region Hannover GmbH, Podbielskistr. 380, 30659 Hannover, Germany, Email: Bernd.Schoenhofer/at/t-online.de Received March 10, 2008; Accepted May 5, 2008. See "Clinical Practice Guidelines in Deutsches Ärzteblatt International" on page 423.Abstract Introduction Non-invasive mechanical ventilation (NIV) has been used to treat acute respiratory failure (ARF) for approximately 20 years. This guideline addresses the indications for, and limitations of, NIV as treatment for ARF according to evidence-based criteria. Methods A panel of experts from 12 scientific medical societies reviewed circa 2900 publications. The panel judged the clinical relevance of these studies and assessed the evidence presented in each, then held two interdisciplinary consensus conferences to formulate guideline recommendations and algorithms. Results Whenever possible, NIV should be preferred to invasive mechanical ventilation, in order to avoid the risk of ventilator and tube-associated complications such as nosocomial pneumonia (grade of recommendation A). Particularly in patients with hypercapnic ARF, NIV reduces the rate of hospital-acquired pneumonia, the length of hospital stay and mortality in the intensive care unit and in the hospital (grade of recommendation A). NIV (or continuous positive airway pressure) is also recommended in cardiogenic pulmonary edema (grade of recommendation A), as treatment for ARF in immunocompromised patients (grade of recommendation A), to prevent postextubation failure, to facilitate weaning in patients with hypercapnic ARF (grade of recommendation A), and to improve dyspnea in palliative care (grade of recommendation C). NIV is not generally recommended in patients with hypoxic ARF because of its high failure rate of 30% to over 50% in such patients. Discussion Although evidence indicates that NIV can be used as the treatment of first choice for several indications, it is still underutilized in the acute setting. These guidelines provide evidence-based information about the indications for, and limitations of, NIV in the treatment of ARF. Keywords: non-invasive positive pressure ventilation, evidence-based medicine, therapy, acute respiratory distress syndrome, respiratory insufficiency Introduction When treating acute respiratory failure, physicians must ask what form of ventilation is best for the individual patient, i.e., what form of ventilation provides the greatest benefit with the lowest risk. In past decades, mechanical ventilation by way of an invasive access route – an endotracheal tube or tracheostomy – became established as life-saving treatment for acute respiratory failure (ARF). Over the last 20 years, however, a great deal of clinical research has shown that non-invasive ventilation (NIV), too, is a valuable form of treatment for ARF (table 1). NIV is not yet firmly established in acute care in all institutions. According to an international study, 4.9% of 5183 ventilated patients in intensive care units were treated with NIV (1). The NIV rate was only 16.9% among patients who were ventilated because of exacerbations of chronic obstructive pulmonary disease (COPD), despite the fact that good evidence supporting the use of NIV for this indication has been available for several years (2). The utility of NIV is still variably assessed depending on the indication (2, 3).
On this background, 12 scientific medical societies in Germany have now formulated a guideline for the use of NIV in the treatment of ARF. The leading role was played by the German Society for Pulmonology and Respiratory Medicine (Deutsche Gesellschaft für Pneumologie und Beatmungsmedizin, DGP) under the aegis of the Association of the Scientific Medical Societies in Germany (Arbeitsgemeinschaft der Wissenschaftlichen Medizinischen Fachgesellschaften e.V., AWMF). This class S3 guideline is based on a systematic analysis of the literature and an interdisciplinary consensus process (e1). This guideline contains verified indications, contraindications, and criteria for the monitoring and termination of NIV, as well as the advantages and disadvantages of NIV compared with invasive ventilation. The main goal of this guideline is to encourage broader use of this form of treatment in acute care medicine on the basis of the scientific evidence. In this article, the method of guideline development is briefly described and the core recommendations are stated. The full-length version of the guideline can be viewed online at the AWMF website (http://awmf.org) and will be published in August 2008 in the German-language medical journal Pneumologie (the official journal of the DGP). Methods This guideline was developed over a period of three years, from early 2005 to late 2007. A total of 28 experts representing 12 medical specialty societies (box 1) formed six working groups, each of which was devoted to a different indication for NIV.
A central coordinating group carried out the literature searches and provided logistical aid with the analysis of the literature. A search on the terms listed in box 2 in the Medline and Cochrane databases, performed in September 2005, yielded 2425 hits. This catalogue of the relevant literature was updated multiple times up to June 2007, resulting in the addition of 476 further references for a total of about 2900 (figure 1)
With the aid of electronic evaluation tables, more than 90% of the abstracts were accessible over Medline through hyperlinks. This manner of working reduced the need for individual searching and paperwork. Further support from the coordinating group consisted of the administration and distribution of meta-information about the literature search and general instructions about the evaluation of scientific evidence. All participants were informed about the current state of the project in a newsletter that was sent a total of 16 times. Assessment of relevance and qualitative evaluation of scientific evidence The goal of the initial selection procedure was the identification of publications that would be relevant to the development of the guideline from among the 2900 publications that were revealed by the search. In this phase, all publications were assessed according to criteria of clinical relevance. Publications were excluded if
The latter aspect will be discussed more fully in what follows. In general, publications in English or in German were considered. Every article was evaluated by two experts. Differing judgments over inclusion versus exclusion were resolved internally in each working group. The percentage of publications selected as sources for evaluation of the scientific evidence varied from 15% to 25% among the working groups. Even in this initial phase, account had to be taken of the fact that the use of NIV for different indications is supported by different levels of evidence. For some indications, the use of NIV has already been shown to be beneficial by randomized studies with large numbers of patients. Thus, for these indications, observational studies and other publications with similar results could be excluded from the further analysis. Systematic review articles, i.e., review articles with a documented search and meta-analysis of original publications, were accepted for further analysis as long as the data from the publications cited in them were homogeneous. Non-systematic review articles, on the other hand, were classified as expert opinions, and only the original publications that they cited were accepted for further analysis. Evaluation of scientific evidence The quantitative evaluation of the scientific evidence provided by each publication was performed by two experts according to the recommendations of the Oxford Centre of Evidence-Based Medicine (CEBM) (4). The classification system used, based on study design and the quality of execution of each study, is shown in table 2. Uniformity of criteria was ensured by the use of standardized checklists (one for original articles and one for systematic reviews). The guideline cited a total of 243 publications (figure 1)
Two interdisciplinary consensus conferences were held in July 2006 and April 2007 under the auspices of the AWMF. Representatives of the nursing professions and of manufacturers of ventilation apparatus also participated (the latter without vote). The first conference established the central recommendations and algorithms of the guideline; in the second conference, the recommendations were cast in their final wording and the strength of the recommendations was established on the basis of the state of the evidence for each. Results Invasive and non-invasive ventilation There is no doubt that invasive mechanical ventilation is often an indispensable life-saving measure, but it is also associated with the risk of endotracheal tube or ventilator associated pneumonia, leading to high mortality as well as to markedly elevated costs (e2). Invasive ventilation should be avoided in favor of NIV or early extubation whenever possible so that this serious complication can be avoided (grade A recommendation) (e3). NIV has major advantages over invasive ventilation with respect to both respiratory mechanics and infectious disease (table 3).
One advantage of invasive mechanical ventilation in respiratory failure, and particularly in acute respiratory distress syndrome (ARDS), is the greater constancy of pressure, because the lung can collapse if the positive airway pressure is interrupted even for a very short time (e4, 5). NIV, therefore, should not be used if there are important clinical reasons to ventilate invasively (grade B recommendation). NIV is absolutely contraindicated (grade D recommendation) in the following situations:
If a relative contraindication is present (box 3), a trial of NIV can be considered in individual cases, as long as the patient is meticulously observed at close intervals and can be intubated without delay if necessary.
Techniques of non-invasive ventilation Negative and positive pressure ventilation – The favored mode of ventilation for the treatment of ARF is positive pressure ventilation with inspiratory pressure support (assisted mode). This is often combined with positive end-expiratory pressure (PEEP). A minimum respiratory frequency must be set to protect the patient against apnea, and oxygen should be given in whatever amount necessary to ensure a saturation of 85% to 90% (grade D recommendation) (2). Inspiratory pressure support with a mask or helmet (e5) reduces the patient’s work of breathing; furthermore, the application of positive pressure raises transpulmonary pressure and thereby enlarges the end-expiratory lung volume. This effect prevents alveolar closure and promotes the recruitment of alveolar volume (atelectases). Negative pressure respiration, e.g., with a "tank," is only rarely used at present (e6). Interface – There is a broad spectrum of ventilation interfaces in the area of the face, including nose masks, full face masks, and total face masks (illustration a–c)
Ventilation apparatus and modes of ventilation – The spectrum of ventilation apparatus ranges from easy-to-use portable equipment to technically demanding intensive-care ventilators (e9). Unlike patients treated with at-home ventilation because of chronic ventilatory insufficiency, patients with ARF are often markedly agitated and have a pronounced respiratory drive; thus, they are only rarely treated with controlled (i.e., time-based) ventilation and much more often with ventilation that is triggered by the patient’s own respiratory efforts (e9). Important practical considerations for NIV The manner in which NIV is used to treat ARF is largely independent of the specific indication and is presented in figure 2
The most important parameters for monitoring the course of the adaptation phase are the arterial blood gases, the respiratory rate, the patient’s subjective experience of dyspnea, and the patient’s level of alertness (grade C recommendation) (2, e11–e13). In case NIV fails, it should be terminated immediately and the patient should be intubated without delay (grade C recommendation). In the initial phase of the treatment of ARF with NIV, the personnel-to-patient ratio is relatively high at 1:1. Over the further course of treatment, NIV results in a saving of time and effort on the part of the treatment personnel (e14–e17). NIV for the treatment of ARF should preferably be performed in an intensive care unit (grade D recommendation). In cases of isolated respiratory failure (single-organ failure), NIV can also be provided in an intermediate care (step-down) unit. Depending on the local circumstances and resources, NIV might also be provided, in individual cases, on a specialized normal patient ward (e18–e22). The spectrum of indications The guideline provides recommendations for the following groups of indications:
Hypercapnic ARF – The most common cause of hypercapnic ARF, defined as pH <7.35 and PaCO2 >45 mmHg, is an acute exacerbation of COPD (AE-COPD). The elevated airway resistance, dynamic overexpansion of the lungs, and consequent flattening of the diaphragm put excessive demands on the respiratory muscles, leading to imminent exhaustion (e23, e24). In "mild to moderately severe AE-COPD," with a pH of 7.30 to 7.35, NIV should be applied early (grade A recommendation) (8). When used in combination with standard therapy, NIV already lowers the PaCO2, improves the pH, and lowers the respiratory rate within one hour of the initiation of treatment. NIV reduces the frequency of intubation and lessens both the duration of hospital stay and mortality (9, 10, e25). The effectiveness of NIV has also been demonstrated for AE-COPD with pH in the broader range of 7.20 to 7.35 (8, e26). The clinical algorithm for the use of NIV in hypercapnic ARF is shown in figure 3
Hypoxemic ARF – The data are less clear regarding the value of NIV in hypoxemic, rather than hypercapnic, ARF. An experienced team of researchers has shown that NIV in patients with purely hypoxemic ARF significantly lowers the frequency of intubation, the rate of septic shock, and the 90-day mortality compared to standard therapy (11). NIV has also been used with success to treat mixed hypercapnic and hypoxemic ARF, e.g., in COPD patients with pneumonia (e16, e27–e29). The use of continuous positive airway pressure (CPAP) and NIV is recommended for immunosuppressed patients with (hemato-)oncological disorders, as well as for patients with AIDS and Pneumocystis jirovecii pneumonia, also known as Pneumocystis carinii pneumonia (grade A recommendation) (12, 13, e30). NIV should only be used to treat ARDS if the patient is closely monitored in a specialized treatment center (grade D recommendation). The NIV failure rate in a mixed group of patients with hypoxemic ARF was quite high: 30% in patients with community-acquired pneumonia and 50% in patients with ARDS (9, 14). The main causes of NIV failure are to be sought in the complex pathophysiology of hypoxemic forms of ARF and the inadequate constancy of pressure provided by NIV, particularly in the expiratory phase. Cardiogenic pulmonary edema – There is now clear evidence demonstrating the utility of NIV and CPAP, alongside standard medical therapy, in the treatment of cardiogenic pulmonary edema (15, e31). Patients with hypoxemic ARF due to cardiogenic pulmonary edema should first be given oxygen by the nasal route and should then be treated primarily with CPAP (grade A recommendation). The indicated pharmacotherapy and necessary cardiological interventions, such as catheterization, must also be performed without delay (grade D recommendation) (e32–e34). In this situation, CPAP reduced cardiac preload and afterload, reduces the work of breathing, improves coronary perfusion, and normalizes the ventilation-perfusion ratio. If cardiogenic pulmonary edema is associated not only with hypoxemia, but also with hypercapnia, then CPAP should be provided in combination with inspiratory pressure support, i.e., it should be provided as NIV (e35-e39). ARF in the perioperative phase – The reduced functional residual capacity in mechanical ventilation (e40) leads to the end-expiratory closure of smaller airways and the formation of atelectases (figure 4)
NIV can be used to improve ventilation and oxygenation during bronchoscopy (e47–e50) (grade C recommendation). Because of the paucity of clinical data, no general recommendation can be given regarding the use of NIV in the preparatory phase before surgery. Weaning from the ventilator and the post-extubation phase – Invasively ventilated patients with COPD should be extubated as early as possible and switched to NIV (grade A recommendation). In such patients, extubation followed by NIV was shown to improve the success rate of weaning to a statistically significant extent as compared with continued invasive ventilation in a control group. It also lowered mortality and the rates of reintubation, tracheotomy, and other complications. The utility of NIV in difficult weaning due to hypoxemic (as opposed to hypercapnic) respiratory failure is still being debated. Above all in elderly COPD patients with chronic heart failure and hypersecretion, who are at high risk of developing hypercapnic ARF after extubation, the early application of NIV lowers the rates of reintubation and death (e51, e52, 17, 18). Data from randomized controlled studies do not support the use of NIV in patients with hypoxemic ARF after extubation (3, e53). The only positive results to date from the use of NIV in cases of difficult weaning due to hypoxic respiratory failure are derived from small, single-center studies (e54). NIV in pediatrics – No randomized studies have been published that demonstrate any advantage of NIV over invasive ventilation in children and adolescents, except in the neonatal period. Consequently, the guideline recommendations in this area are based on observational studies. ARF in children and adolescents can be effectively treated with NIV (grade C recommendation). In ARF due to cystic fibrosis, a trial of NIV should be performed in preference to invasive ventilation, as long as NIV is not contraindicated (grade C recommendation). The same holds for children with neuromuscular disorders (grade C recommendation) and for immunosuppressed children (grade C recommendation). NIV to treat ARF in children should always be performed in an intensive care unit (grade C recommendation). NIV in palliative care – NIV can be used palliatively to relieve dyspnea and improve the quality of life (grade C recommendation) (e55, e56, 19). Even if a patient has issued an advance directive that he or she should not be intubated, NIV can still be initiated after the patient has been comprehensively informed about it, as long as there is no objection to mechanical ventilation as such (grade B recommendation) (e55, 19, e57, e58, e59, 20, e60). A recent study revealed that about 30% of patients who died in an intermediate-care unit were treated with NIV (19). While being treated with NIV, patients continue to possess a certain degree of autonomy. In such situations, physicians must monitor the treatment with all due care to ensure that the effect of NIV is not merely to prolong the patient’s suffering and/or the dying process (e61). Discussion The currently available scientific evidence shows that NIV is markedly superior to invasive ventilation for the treatment of hypercapnic ARF (box 4) and cardiogenic pulmonary edema, as well as hypoxemic ARF in immunosuppressed patients. Further indications are the postoperative prophylaxis against reintubation and difficult weaning after prolonged invasive ventilation for hypercapnic respiratory failure. The high failure rate of NIV (30% to over 50%) in patients with hypoxemic ARF argues against the routine use of NIV for this indication.
Despite the good evidence that is available for the above indications, NIV is still underused in the everyday practice of intensive care medicine. This guideline is intended to help NIV become more firmly established in practice. Limitations and weaknesses of this guideline The recommendations of evidence-based medicine are usually derived from studies that were performed under controlled conditions on selected groups of patients, often in a single institution, by teams with extensive clinical experience. Thus, the generalization of study results to everyday clinical practice is not justified without further qualification. Furthermore, a lack of experience, staff, and equipment often stand in the way of the successful use of NIV (e62), particularly when it is used for indications in which its efficacy is less well documented. Finally, a guideline is in any case no more than a snapshot of the current state of scientific knowledge. This guideline is only valid until three years after publication; an update will be needed then, at the latest.
Acknowledgments The authors thank the German Society of Pulmonology and Respiratory Medicine (Deutsche Gesellschaft für Pneumologie und Beatmungsmedizin, DGP) for financing a position for a scientific assistant as well as the consensus conferences. We also thank the AG Pneumologischer Kliniken, the AG Heimbeatmung und Respiratorentwöhnung, and the German Society of Anesthesiology and Intensive Care Medicine (Deutsche Gesellschaft für Anästhesiologie und Intensivmedizin, DGAI) for their co-financing of the position for a scientific assistant. Translated from the original German by Ethan Taub, M.D. Footnotes Conflict of interest statement Prof. Schönhofer has received lecture honoraria from the ResMed and Heinen & Löwenstein companies. Prof. Kuhlen has received lecture honoraria from the ResMed, Dräger, Tyco, Viasys, and Maquet companies. Prof. Neumann has received lecture fees from the manufacturers Dräger and B+P Beatmungsprodukte GmbH. Dr. Westhoff, Dipl.-Ing. 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