Prolonged weaning: From the intensive care unit to home

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Navalesi, P. Frigerio, A. Patzlaff, S. Häußermann, P. Henseke, M. Kubitschek" "autores" => array:6 [ 0 => array:3 [ "nombre" => "P." "apellidos" => "Navalesi" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "a" "identificador" => "aff0005" ] ] ] 1 => array:3 [ "nombre" => "P." "apellidos" => "Frigerio" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "b" "identificador" => "aff0010" ] ] ] 2 => array:3 [ "nombre" => "A." "apellidos" => "Patzlaff" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "c" "identificador" => "aff0015" ] ] ] 3 => array:3 [ "nombre" => "S." "apellidos" => "Häußermann" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "c" "identificador" => "aff0015" ] ] ] 4 => array:3 [ "nombre" => "P." "apellidos" => "Henseke" "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "d" "identificador" => "aff0020" ] ] ] 5 => array:4 [ "nombre" => "M." "apellidos" => "Kubitschek" "email" => array:1 [ 0 => "martin.kubitschek@linde-gas.com" ] "referencia" => array:2 [ 0 => array:2 [ "etiqueta" => "d" "identificador" => "aff0020" ] 1 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] ] "afiliaciones" => array:4 [ 0 => array:3 [ "entidad" => "Department of Translational Medicine, Eastern Piedmont University, Novara Anesthesia and Intensive Care, Sant’Andrea Hospital, Vercelli, CRRF Mons. L. Novarese, Moncrivello, VC, Italy" "etiqueta" => "a" "identificador" => "aff0005" ] 1 => array:3 [ "entidad" => "Spinal Cord Unit, Niguarda-Ca’ Granda Hospital, Milano, Italy" "etiqueta" => "b" "identificador" => "aff0010" ] 2 => array:3 [ "entidad" => "Inamed GmbH, Robert-Koch-Allee 29, 82131 Gauting, Germany" "etiqueta" => "c" "identificador" => "aff0015" ] 3 => array:3 [ "entidad" => "GBU Healthcare, Linde Gas Headquarters, Seitnerstrasse 70, 82049 Pullach, Germany" "etiqueta" => "d" "identificador" => "aff0020" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "pt" => array:1 [ "titulo" => "Desmame prolongado: da unidade de cuidados intensivos para o domicílio" ] ] "textoCompleto" => "IntroductionGenerally speaking, weaning is the process of withdrawing ventilator support. Some use the term to intend a gradual reduction of ventilator assistance, while others believe that weaning covers the entire process of liberating the patient from both ventilator and endotracheal tube. A uniform and broadly accepted definition of the term weaning is crucial to avoid confusion and is an essential prerequisite for interpreting the results of the studies, and guiding clinical decisions, including site of care and management of difficult patients.<a class="elsevierStyleCrossRef" href="#bib0005">1</a>It is commonly accepted that weaning starts with the first spontaneous breathing trial (SBT), during which the patient is allowed to breath for a relatively brief period of time (30–120min) through a T-tube, or with low levels of either CPAP (2–5cmH2O) or pressure support (≤8cmH2O). When the SBT is successful, the patient is considered weaned and ready to be extubated provided that the natural airway is not at risk of obstruction.<a class="elsevierStyleCrossRef" href="#bib0010">2</a> A recently proposed and largely accepted classification based on difficulty and duration of the weaning process includes: (1) simple weaning, i.e., the patients passes the initial SBT and is successfully extubated at the first attempt; (2) difficult weaning, i.e., up to three SBT or 7 days from the first SBT are necessary to withdraw mechanical ventilation and extubate the patient; (3) prolonged weaning, i.e., more than three SBTs or 7 days from the first SBT are required.<a class="elsevierStyleCrossRef" href="#bib0010">2</a>Because the process of weaning implies two separate, though closely related, aspects, the withdrawal of ventilator assistance and extubation, its complete success is achieved when the patient is able to maintain spontaneous unassisted breathing after extubation. Weaning failure may occur when the patient fails to breathe soon after withdrawal of the ventilator support, as defined by the incapacity to successfully pass the SBT. Rates of weaning failure after a single SBT of between 26 and 42% have been reported by different studies.<a class="elsevierStyleCrossRef" href="#bib0010">2</a> Weaning failure, however, is also the need for re-intubation, conventionally within 48–72h after extubation, so-called extubation failure.<a class="elsevierStyleCrossRefs" href="#bib0015">3,4</a> Extubation failure can be the consequence of the inability, after removal of the endotracheal tube, either to sustain spontaneous unassisted breathing over time, or to maintain a patent upper airway or to clear tracheobronchial secretions.There are situations, however, in which weaning can only be partially accomplished and it remains work in progress.<a class="elsevierStyleCrossRef" href="#bib0010">2</a> On the one hand, mechanical ventilation can be applied through a noninvasive interface, commonly a mask covering nose and mouth, referred to as noninvasive ventilation, which allows extubation while continuing to provide ventilator assistance.<a class="elsevierStyleCrossRef" href="#bib0010">2</a> On the other hand, though successfully disconnected from the ventilator, a patient may still be unable to get the artificial airway removed because of inability to clear secretions or maintain patent the upper airway.<a class="elsevierStyleCrossRef" href="#bib0010">2</a> The rates of mechanical ventilated patients undergoing a tracheotomy vary among studies and may reach values as high as 25%.<a class="elsevierStyleCrossRefs" href="#bib0025">5–7</a>Finally, we lack a clear definition of the ventilator-dependent patient. The ninth revision of the International Classification of Diseases defines long-term ventilated patients as those who have received five or more days of ventilation. Some studies use a time limit as short as 48h, while others as long as 40 days.<a class="elsevierStyleCrossRef" href="#bib0040">8</a> A limit of two weeks has been adopted by most authors to define the threshold for ventilator dependency and the Health Care Financing Administration has expanded this limit to 21 days of mechanical ventilation for at least 6h a day.<a class="elsevierStyleCrossRef" href="#bib0040">8</a> A definition based only on time, however, has limitations because it does not consider type and characteristics of the underlying disease, comorbidities, reversal of the cause responsible for acute respiratory failure, and the overall prognosis, which, for instance, makes the definition of patients who are indicated for transfer from the Intensive Care Unit (ICU) to a specialized weaning unit problematic.Epidemiology and outcome of weaning in ICUWhile for about 70% of patients, the weaning process is simple and successful, for the remaining 30% the initial attempt fails, making the weaning difficult and worsening the prognosis, ICU mortality being reported as high as 25 percent; of these patients, about half progress to prolonged weaning.<a class="elsevierStyleCrossRefs" href="#bib0020">4,9</a> Two studies report that up to 20% of medical ICU patients remain dependent on ventilator after 21 days.<a class="elsevierStyleCrossRefs" href="#bib0020">4,9</a>The longer the duration of mechanical ventilation, the higher the mortality rate; this depends, at least in part, on the complications and side effects of this procedure such as the so-called ventilator-associated pneumonia.<a class="elsevierStyleCrossRef" href="#bib0035">7</a> If on the one hand speeding up the process of weaning may be of benefit, on the other hand, however, it may lead to undue anticipation of extubation and need for reintubation, which has been shown to be associated with a 4.5-fold increased risk of nosocomial pneumonia.<a class="elsevierStyleCrossRef" href="#bib0050">10</a>The time spent in the weaning process may represent a substantial fraction of the overall duration of mechanical ventilation and, depending on the patient population, can be as high as 50%.<a class="elsevierStyleCrossRef" href="#bib0010">2</a> Patients with prolonged weaning account for 6% of all ventilated patients but consume 37% of ICU resources.<a class="elsevierStyleCrossRef" href="#bib0055">11</a>Therefore, prolonged weaning is not only a medical, but also a social and economic problem. US costs for mechanical ventilation are estimated to be 27 billion dollars, corresponding to more than 10% of all hospital costs. Each year about 300,000 people receive prolonged mechanical ventilation in ICU in the US, and this number might double within a decade, with costs increasing up 50 billion dollars.<a class="elsevierStyleCrossRef" href="#bib0060">12</a>Pathophysiology of difficult and prolonged weaningAny patient who does not manage simple weaning should be carefully evaluated for potentially reversible underlying disorders. The success of weaning depends primarily on the ability of the respiratory muscle pump to cope with the load placed upon it. Although neuromuscular capability can be impaired because of pre-existing neurological and neuromuscular underlying disorders, more frequently it is altered as a consequence of Critical Illness Neuro-muscular Abnormalities (CINMA), which combine in a single definition Critical Illness Polyneuropathy and Myopathy. CINMA may intervene and complicate the ICU stay in up to 25% of ICU patients undergoing mechanical ventilation for one week or more.<a class="elsevierStyleCrossRef" href="#bib0065">13</a> CINMA affects predominantly septic patients with multiple organ failure, although drugs such as steroids, aminoglycosides, and neuromuscular blocking agents may also contribute to its occurrence. Avoidance of hyperglycaemia and early rehabilitation have been suggested to reduce CINMA severity and facilitate recovery.<a class="elsevierStyleCrossRef" href="#bib0070">14</a> CINMA may cause, in the context of a generalized weakness, a critical reduction of the force-generating capacity of the respiratory muscles.In humans, diaphragm atrophy and injury may occur after relatively few hours. In a group of brain-death donors, 18–69h of mechanical ventilation and complete diaphragm inactivity resulted in marked atrophy of the diaphragm fibers.<a class="elsevierStyleCrossRef" href="#bib0075">15</a> In addition, the force-generating capacity of the diaphragm is reduced by one-third in ICU patients after 6 days of controlled mechanical ventilation.<a class="elsevierStyleCrossRef" href="#bib0080">16</a> Nutritional state, metabolic and endocrine factors should be also considered as potential causes of reduced force generation capacity of the respiratory muscles.<a class="elsevierStyleCrossRefs" href="#bib0010">2,17,18</a>The inability of the patient to generate a maximal inspiratory pressure of at least 20–25cmH2O is considered a predictive index of unsuccessful weaning.<a class="elsevierStyleCrossRef" href="#bib0095">19</a> Higher values, however, can also be insufficient when the load imposed on the respiratory muscles is increased.The respiratory load depends on the elastic and resistive properties of the respiratory system. An additional threshold load may substantially add to the overall respiratory load when there is dynamic hyperinflation which causes intrinsic positive end-expiratory pressure (PEEPi). The elastic load increases when the compliance of the respiratory system decreases, which may be due to either lung (pneumonia, pulmonary edema of different etiologies, or fibrosis) or chest wall (obesity, pleural thickening or abdominal distension of different etiologies) restriction, or both. Any condition determining airway bronchoconstriction leads to an increased resistive load. The additional resistance imposed by the endotracheal tube also adds to the resistive load, which may be particularly relevant when the internal size of the tube is small or reduced by concrete secretions, frequently as a consequence of inadequate air humidification. In addition, patients who successfully passed the SBT may develop post-extubation respiratory failure because the resistive load increases as a consequence of glottis edema or inability to effectively clear tracheobronchial secretions.The heart-lung interaction may affect the respiratory load. In fact, excessive inspiratory negative intrathoracic pressure swings increase cardiac preload and afterload, which determines in turn lung congestion and edema of the bronchial wall.<a class="elsevierStyleCrossRefs" href="#bib0100">20,21</a> This may be particularly important in patients with cardiac dysfunction, sometimes latent or unrecognized, undergoing a SBT that exposes them to an increased inspiratory effort following the interruption of mechanical ventilation.The load can be further increased because of inappropriate ventilator settings, such as inadequate inspiratory flow rate, excessive time lag between onset of inspiratory effort and the onset of ventilator assistance delivery, ineffective triggering, double triggering, expiratory effort prior to switchover from mechanical inflation to exhalation, causing patient-ventilator dyssynchrony.<a class="elsevierStyleCrossRefs" href="#bib0110">22–25</a>Recent work has shown that neuro-psychological disorders such as delirium, anxiety and depression may also substantially contribute to weaning failure.<a class="elsevierStyleCrossRefs" href="#bib0010">2,25</a> Poor sleep, excessive noise, lack of darkness during nighttime, and an overall unfriendly environment, as the ICU is generally perceived by the patient, may substantially contribute to these neuro-psychological disorders.ICU management of prolonged weaningBecause the pathophysiology of prolonged weaning is complex and often multifactorial, the clinical approach must include either a meaningful evaluation of the specific causes for that specific patient and applying proper interventions. As a rule of thumb, considering that an unfavorable balance between respiratory muscles force and imposed load is the chief cause of weaning failure, any treatment effective in either reducing load and/or augmenting muscle force is beneficial.<a class="elsevierStyleCrossRefs" href="#bib0010">2,26</a>Reduction of the respiratory loadTo reduce an excessive elastic load secondary to a decreased lung compliance, it is crucial to consider any possible cause of acute lung volume restriction that can be reverted by specific therapies, such as diuretics to decrease lung congestion in cardiac or renal failure and other conditions of fluid overload, antibiotics to treat pneumonia, chest physiotherapy for treatment (and prevention) of atelectasis. Causes of abdominal distensions determining chest wall restriction should be also evaluated and eliminated whenever possible, for instance by treating stipsis, abdominal gas distension, and large pleural effusions and ascites.A significant reduction in airway resistance can be achieved by medical therapies, such as bronchodilators to treat bronchoconstriction, steroids and antibiotics to control bronchial inflammation and infections, diuretics to contain bronchial wall edema due to lung congestion.Chest physiotherapy may also help decreasing the respiratory load by removing bronchial secretions, which reduces airway resistance<a class="elsevierStyleCrossRef" href="#bib0135">27</a> and prevents atelectasis.<a class="elsevierStyleCrossRefs" href="#bib0140">28,29</a> Chest physiotherapy includes interventions such as patient positioning and mobilization, breathing exercises, incentive spirometry, manual or mechanical insufflation, aimed at increasing lung volume, regional ventilation and pulmonary compliance, and maneuvers aimed at reducing airway resistance and increasing expiratory flow during forced expiration either with an open (huff) or closed glottis (cough). In spite of a robust physiological background,<a class="elsevierStyleCrossRef" href="#bib0150">30</a> however, the evidence supporting this form of treatment is so far very limited; on the one hand, trials evaluating the impact of chest physiotherapy on the outcome of lack of weaning, on the other hand the contemporary association of different treatments makes a proper evaluation of the physiotherapic techniques problematic.<a class="elsevierStyleCrossRef" href="#bib0155">31</a>While tracheal stenosis, granuloma and tracheomalacia can complicate prolonged endotracheal intubation with a cuffed tube,<a class="elsevierStyleCrossRef" href="#bib0160">32</a> some unrecognized abnormalities, glottis inflammation and edema being the most common, determining increased upper-airway resistance may lead to extubation failure, often irrespective of the duration of intubation. Some advise routine endoscopic evaluation before decannulation.<a class="elsevierStyleCrossRef" href="#bib0165">33</a> A more practical bedside procedure is the so-called “cuff leaked test”, which consists of the evaluation of the amount of leaked volume during volume-targeted mechanical ventilation with uncuffed tube. The preset (insufflated) and the exhaled volume are measured and the percentage of leaked volume is calculated. Leaks ≤12% identifies patients at high risk of developing post-extubation stridor and then failing extubation.<a class="elsevierStyleCrossRef" href="#bib0170">34</a>Medical therapies aimed at reducing airway resistance may also help to decrease PEEPi. Inappropriate ventilator settings, such as those determining hyperventilation or patient-ventilator dyssinchrony, may consistently add to the occurrence and extent of PEEPi and must be, accordingly carefully avoided.<a class="elsevierStyleCrossRef" href="#bib0115">23</a>Improvement of neuromuscular capabilityA tight control of sepsis and hyperglycaemia, and avoidance of neuromuscular blocking agents, aminoglycosides and steroids, may help to decrease the risk of developing CINMA.<a class="elsevierStyleCrossRef" href="#bib0175">35</a> It is important to reduce the time spent on full mechanical support as much as possible, i.e., controlled mechanical ventilation, to avert the risk of diaphragm injury and atrophy.<a class="elsevierStyleCrossRef" href="#bib0080">16</a> Considering and correcting poor nutritional status, electrolyte disturbances and hormone deficiency states, such as hypothyroidism, which may all play a role in decreasing muscle force.<a class="elsevierStyleCrossRef" href="#bib0010">2</a>Lessening dynamic hyperinflation and PEEPi in patients with Chronic Obstructive Pulmonary Disease (COPD) also improves diaphragm force-generating capacity. In fact, when hyperinflation occurs, diaphragm myofibers are shortened at end expiration and their force–length relationship is impaired.<a class="elsevierStyleCrossRef" href="#bib0180">36</a> Unnecessarily high levels of external PEEP and ventilator settings determining iatrogenic hyperinflation should, accordingly, also be carefully avoided.Early whole-body physiotherapy has been shown effective in improving ICU and hospital outcomes, including the duration of mechanical ventilation, primarily by averting the side effects of prolonged immobilization.<a class="elsevierStyleCrossRef" href="#bib0185">37</a> Since inactivity weakens the respiratory muscles too,<a class="elsevierStyleCrossRefs" href="#bib0075">15,38</a> inspiratory muscle training, as obtained by intermittent loading of the respiratory muscles, has been proposed to attenuate respiratory muscle deconditioning.<a class="elsevierStyleCrossRefs" href="#bib0195">39,40</a> A recent randomized trial comparing inspiratory muscle training at moderate intensity, i.e., about 50% of the maximal inspiratory pressure generated by the patient, with Sham training in patients with weaning failure showed that a significantly higher proportion (76%) of patients in the treatment group was weaned, as opposed to those (35%) included in the Sham group.<a class="elsevierStyleCrossRef" href="#bib0205">41</a> These findings were subsequently confirmed in a case-series of ventilator-dependent patients.<a class="elsevierStyleCrossRef" href="#bib0210">42</a> Two evaluations of an early use of inspiratory muscle training in acute critically ill patients from the onset of mechanical ventilation produced contrasting results. While one randomized trial did not report any physiologic or clinical benefit in a group of patients undergoing two daily sessions of inspiratory muscle training, as opposed to controls,<a class="elsevierStyleCrossRef" href="#bib0215">43</a> another one reported reduction of the weaning time (3.6 vs. 5.3 days) in the group of patients going through twice-daily 5-min inspiratory muscle training sessions of moderate intensity, compared to a control group.<a class="elsevierStyleCrossRef" href="#bib0220">44</a> Indeed, the rationale for inspiratory muscle training exists for only a limited number of the patients with reversible diaphragm weakness. In addition, there is a definite lack of a standardized technique to re-train the respiratory muscles. Therefore, further studies are necessary before such an approach can be suggested for clinical use.Poor cough strength leading to ineffective clearing of tracheobronchial secretions may cause extubation failure in patients who successfully completed a SBT. In patients with an artificial airway, a peak expiratory flow while coughing through the tube ≤60L/min has been shown to be correlated with a five-fold increase in the incidence of extubation failure.<a class="elsevierStyleCrossRef" href="#bib0225">45</a>TracheotomyTracheostomy is the most commonly performed procedure in the critically ill, approaching 10% of all intubated patients.<a class="elsevierStyleCrossRef" href="#bib0230">46</a> However, a tracheotomy rate as high as 25% was reported by a 1-d point-prevalence study performed in 412 medical-surgical ICUs from North America, South America, Portugal, and Spain.<a class="elsevierStyleCrossRef" href="#bib0025">5</a> The incidence of tracheotomy varied with the underlying disease, it was 39% in neuromuscular patients, 28% in COPD, and 20% in patients with de novo acute respiratory failure.<a class="elsevierStyleCrossRef" href="#bib0025">5</a> The decision to perform a tracheotomy is predominantly based on the anticipated duration of mechanical ventilation.<a class="elsevierStyleCrossRefs" href="#bib0025">5,46</a> The timing of tracheotomy varies between 3 days and 21 days in the different studies. The routine use of bedside percutaneous techniques is likely to have contributed to anticipating the timing of tracheotomy. In fact, while perioperative complications are quite rare (<2%) with both percutaneous and surgical techniques,<a class="elsevierStyleCrossRef" href="#bib0235">47</a> percutaneous, as opposed to surgical tracheotomy, reduces costs, would-be infections, unfavorable scarring, and overall complications.<a class="elsevierStyleCrossRef" href="#bib0240">48</a> An expected intubation for more than 14 days is nowadays considered as reasonable deadline for considering tracheotomy. Poor airway protective reflexes and severe upper-airway obstructions are additional reasons for tracheotomy.<a class="elsevierStyleCrossRef" href="#bib0230">46</a>Though never proved by large randomized controlled studies, the benefits ascribed to tracheotomy vs. prolonged translaryngeal intubation include improved patient comfort determining less need for sedatives, ease of airway suctioning, enhanced mobility and speech, which may all potentially contribute to facilitating the process of weaning from mechanical ventilation. Whether this translates into an increased ability to transfer ventilator-dependent patients from the ICU is not clear and might actually vary from hospital to hospital. As a matter of fact, not infrequently, the point in time at which tracheotomy is first considered corresponds or just slightly anticipates the decision to discharge the patient from the ICU.Management of prolonged weaning beyond ICUIn principle, when the acute disorder which led to admission to ICU is reversed and clinical stability is achieved, the patient may be considered ready for ICU discharge. At that point, while most ICU patients may be transferred to a hospital ward, some of them who are experiencing prolonged weaning may still be dependent on the ventilator, the tracheotomy, or both. In fact, some patients, though successfully extubated, still need NIV for several hours a day; for others, though successfully weaned off the ventilator, the tracheotomy cannot be concomitantly removed; in the worst scenario, invasive mechanical ventilation may still be necessary for several hours a day.Patients dependent on non-invasive ventilationNoninvasive ventilation is increasingly used especially, though not exclusively, in patients with acute or chronic respiratory failure, in order to reduce the need for intubation and invasive ventilation.<a class="elsevierStyleCrossRef" href="#bib0245">49</a> Some studies have repeatedly shown that noninvasive ventilation can also facilitate the process of weaning in patients with underlying chronic respiratory disease and particularly those with COPD.<a class="elsevierStyleCrossRefs" href="#bib0250">50–53</a> While most of these patients undergoing noninvasive ventilation are successfully weaned off the ventilator, some may need to keep on non-invasive ventilation for some hours/day for weeks<a class="elsevierStyleCrossRef" href="#bib0270">54</a> or on a long-term basis<a class="elsevierStyleCrossRef" href="#bib0275">55</a> to guarantee acceptable values of arterial blood gases and avoid repeated hospital readmission.<a class="elsevierStyleCrossRef" href="#bib0280">56</a>Patients dependent on tracheotomyFor patients who have regained respiratory autonomy and resumed overall clinical stability, the removal of tracheotomy represents a major objective, for reasons related to both clinical, i.e., increased risk of infections and long term complications, and social, i.e., negative impact on daily life activities and relationships. In spite of these considerations, the few recommendations currently available are still largely based on subjective criteria rather than on standardized protocols.<a class="elsevierStyleCrossRef" href="#bib0285">57</a> Only one study systematically addressed the problem of weaning from tracheotomy in patients with different underlying disorders, such as COPD, post-surgical complications, hypoxemic respiratory failure, neuromuscular diseases, by means of a relatively simple decisional flowchart.<a class="elsevierStyleCrossRef" href="#bib0290">58</a> This was based on a few parameters aimed at assessing swallowing function and patient ability to spontaneously clear secretions, after determining patient capability of maintaining spontaneous unassisted breathing.<a class="elsevierStyleCrossRef" href="#bib0290">58</a> By using this simple decisional flowchart, it was possible to remove the tracheotomy in almost 80% of the patients with spontaneous breathing autonomy.<a class="elsevierStyleCrossRef" href="#bib0290">58</a> A lower rate of successful decannulation was observed in patients affected by chronic respiratory diseases, and in particular in those with neuromuscular disorders, for whom a more sophisticated approach is likely to be necessary.<a class="elsevierStyleCrossRef" href="#bib0295">59</a>Patient dependent on tracheotomy and mechanical ventilationObservational studies indicate that 34–60% of patients in specialized weaning unit can be weaned successfully from the ventilator support.<a class="elsevierStyleCrossRef" href="#bib0010">2</a> These studies also suggest that successful weaning can occur up to 3 months after admission to these units and that the transfer to a specialized unit does not adversely affect long-term mortality.<a class="elsevierStyleCrossRefs" href="#bib0300">60,61</a> The clinical outcome of patients requiring prolonged mechanical ventilation is largely influenced by the underlying disease, the chances to be completely weaned off both ventilator assistance and tracheotomy approaching 60% in patients with post-operative (58%) and de novo respiratory failure (57%), and slightly exceeding 20% in patients with COPD or neuromuscular disease.<a class="elsevierStyleCrossRef" href="#bib0310">62</a> Also, the long-term survival rate after successful weaning is worse in COPD than in non-COPD patients.<a class="elsevierStyleCrossRefs" href="#bib0010">2,63</a>In patients with neuromuscular disorder, it is crucial to assess the ability to clear secretions. Bach et al.<a class="elsevierStyleCrossRef" href="#bib0295">59</a> showed that peak expiratory flow during cough, so-called peak cough expiratory flow (PCEF) is a better predictor of the likelihood of being weaned from tracheotomy. A variety of cough-augmentation physical therapies, alone or in combination, can be used to increase PCEF and enhance cough efficacy. While the patients with weak expiratory muscle strength, but relatively well preserved inspiratory strength, may benefit from the abdominal-thrust maneuver, also termed “quad cough” or “manually assisted cough,” which replaces or enhances abdominal muscle contraction, those who combine weakness of both the inspiratory and expiratory muscles necessitate, in addition to manually assisted cough, manual or mechanical forms of inspiratory assistance (i.e., insufflation, air staking, glosso-pharyngeal breathing, etc.) to increase the pre-tussive volume.An increasing number of devices specifically designed to assist an insufficient cough have been introduced for clinical use in recent years, which apply to the airway opening positive pressure during the inspiratory phase and negative (sub-atmospheric) pressure during forced expiration.<a class="elsevierStyleCrossRef" href="#bib0320">64</a> These techniques of mechanical cough-augmentation can be successfully used with neuromuscular patients through an artificial airway, but an intact glottis function is required for those breathing through the native airway at which cough assistance is applied by means of an oro-nasal mask. A program including periodic evaluation of cough strength and timely initiation of effective cough-augmentation therapy may dramatically improve the possibility of weaning neuromuscular patients from tracheotomy.<a class="elsevierStyleCrossRef" href="#bib0325">65</a>Although the combination of invasive mechanical ventilation and tracheal suctioning can be successfully used when ventilator assistance is also necessary, in neuromuscular patients this approach has been shown to be associated with increased morbidity.<a class="elsevierStyleCrossRef" href="#bib0320">64</a> The advent of non-invasive ventilation NIV as a means of supporting chronic neuromuscular respiratory insufficiency has spurred on the development of noninvasive cough-augmentation therapies to favor airway clearance. Unfortunately, the need to support cough clearance has not been properly addressed; indeed, guidelines for the management of a weak cough did not exist until relatively recently.<a class="elsevierStyleCrossRef" href="#bib0320">64</a>Specialized weaning unitsDefinitionThere is no uniform, widely recognized definition for “specialized weaning units”, and confusion can arise, as for the term “weaning”, from imprecise language. Generally speaking, these units are protected environments for the treatment of patients requiring prolonged mechanical ventilation. As mentioned by Nava & Vitacca in a dedicated book chapter, several terms are used to characterize these units, such as long-term acute-care facilities, respiratory special care units, chronic ventilator-dependent units, regional weaning centers, ventilator-dependent rehabilitation hospitals, prolonged respiratory-care units, non-invasive respiratory-care units, high-dependency units, and respiratory intensive-care units.<a class="elsevierStyleCrossRef" href="#bib0040">8</a> Beyond the terminology, remarkable differences exist among units, which are primarily, though not exclusively, a consequence of the different healthcare systems and reimbursements, varying not only from country to country, but also often from region to region, and not infrequently from town to town.<a class="elsevierStyleCrossRefs" href="#bib0010">2,8</a> A helpful approach to this problem has been provided by Nava & Vitacca who classified, depending on the type of location, weaning units into two categories, step-down units sited within acute care hospitals, and Weaning Centers serving different acute care hospitals in dedicated areas.<a class="elsevierStyleCrossRef" href="#bib0040">8</a> While the former, with organization and staffing closer to ICUs may often result in not being able to meet the needs of these patients beyond their clinical problems, the latter require a proper environment and a dedicated and composite organization.<a class="elsevierStyleCrossRef" href="#bib0125">25</a>RationaleWeaning from prolonged mechanical ventilation is a complex and time-consuming process covering several procedures. Quick patient turnover, high workloads for the staff, need for continuous monitoring and treatment, and, in some countries, paucity of ICU beds, make ICUs in appropriate for managing patients with prolonged weaning, requiring care with dedicated personnel, which is often not available in the ICU.<a class="elsevierStyleCrossRef" href="#bib0330">66</a> In addition, prolonging the ICU stay may have detrimental consequences on the psychological and cognitive function, which may further complicate and protract the weaning process and affect patient outcomes.<a class="elsevierStyleCrossRefs" href="#bib0335">67,68</a>It has been shown that a substantial proportion of patients, not ready to be separated from the ventilator at ICU discharge can be weaned off the ventilator soon after admission to a specialized weaning unit, which suggests that discontinuation of mechanical ventilation was not a priority for the referring ICUs.<a class="elsevierStyleCrossRefs" href="#bib0345">69,70</a>In a retrospective study including more than 400 ICU patients who had undergone tracheostomy and prolonged mechanical ventilation following an episode of acute respiratory failure, the rate of survivors successfully weaned at the time of ICU discharge was less than 60%.<a class="elsevierStyleCrossRef" href="#bib0355">71</a> The patients who were weaned off both ventilator and tracheotomy had better survival rates than those who did not. This improved survival, however, came at higher hospital costs secondary to longer ICU stay, which indicates that the balance between outcome and economic burden represents a major problem when treating patients with prolonged weaning exclusively in ICU.<a class="elsevierStyleCrossRef" href="#bib0355">71</a> One controlled study compared outcomes and costs of patients with prolonged weaning assigned to either ICU or weaning unit. The rates of mortality were no different between the two groups, but readmissions were fewer, hospital lengths of stay shorter, and costs lower for the patients weaned in the specialized unit.<a class="elsevierStyleCrossRef" href="#bib0300">60</a>In point of fact, patients who are no longer in the acute phase, but are not fully weaned, may benefit from the discharge to specialized units. These units offer several advantages, including an environment with reduced noise and night-time light favoring the return to more physiological circadian rhythms and better sleep, open visiting hours to allow unrestricted visits by relatives and friends, easier access to personal belongings, such as books, computers, tablets, TV, music players, and so on.<a class="elsevierStyleCrossRefs" href="#bib0360">72,73</a> The management of these individuals generally involves more than just expertise in mechanical ventilation, but rather an integrated approach with harmonized procedures conducted by a multidisciplinary team.Beside any other consideration, a weaning unit should also represent a cost-effective alternative to the ICU for the management of patients with prolonged weaning.<a class="elsevierStyleCrossRef" href="#bib0125">25</a>StaffingThe components of this team should be physicians, nurses and respiratory therapists or physiotherapists capable of providing comprehensive respiratory care. While one physician should be present around the clock, the therapists need not be present overnight. The nurse–patient ratio should range between 1:4 and 1:8 depending on the time of the day. Overall, the skills must encompass invasive and noninvasive mechanical ventilation, suctioning, tracheotomy management, and chest physiotherapy including cough assistance techniques. Physical therapists, occupational therapists, for daily living activities, speech therapists, for evaluation and treatment of swallowing dysfunctions, and nutritionists, to optimize calories and proteins administration, should also be part of the team. Psychology and social services should be also available for patient and family evaluation, education and counseling.Understaffing is one of the major determinants of a suboptimal or ineffective or even harmful weaning unit, and should definitely be avoided when building up an accredited effective unit.<a class="elsevierStyleCrossRef" href="#bib0125">25</a>Admission and discharge criteriaAlthough it is advisable for a weaning unit to define and apply admission criteria, these cannot be generalized and depend on the characteristics of each specific unit. While, the possibility of promptly assessing arterial blood gases and having daily access to chest X-ray and routine blood examination represent the minimum standard for a specialized unit, other facilities may enhance the possibility of accepting patients with higher levels of clinical complexity. Most weaning units that are located outside acute-care hospitals, however, clearly cannot offer sophisticated diagnostic procedures and treatments.The patients admitted should obviously be dependent on ventilator assistance, or need an artificial airway, or both.<a class="elsevierStyleCrossRef" href="#bib0370">74</a> It is worth remembering that prolonged weaning is defined by more than three previously failed SBTs or at least 7 days from the first attempt of SBT.<a class="elsevierStyleCrossRef" href="#bib0010">2</a> Several units include in the admission criteria for invasively ventilated patients the presence of a tracheotomy, to avoid the risk of emergency maneuvers consequent to the need to change an obstructed endotracheal tube. Some units require the proposing physician to provide a written statement that the patient has the potential to be weaned from the ventilator or to return to her/his community under ventilator assistance.<a class="elsevierStyleCrossRef" href="#bib0375">75</a>The team should work with the patient and the family to define short and long term goals leading to final discharge home.<a class="elsevierStyleCrossRef" href="#bib0125">25</a> If, based on objective data, the whole team consider additional weaning attempts to be worthless, these should be interrupted to avoid further frustration, anxiety and depression, and patient and family promptly and clearly informed. When everyone involved in the process, i.e., the team, the patient and the family, agree on the futility of pursuing the weaning efforts, the primary goal becomes the setting up of the best possible discharge program, in which complexity will clearly depend on the level of patient dependence. Of course, it is much more complex to discharge a tracheotomized patient on full ventilator support around the clock, rather than a patient on nocturnal noninvasive ventilation. Once it has been established that the patient's clinical condition, motivation and home environment are suitable for undertaking a long-term domiciliary ventilation program, several logistical aspects remain to be carefully considered and addressed with respect to both the care givers and the equipment.<a class="elsevierStyleCrossRefs" href="#bib0125">25,74</a>SummaryWeaning failure is commonly understood to be an incapacity to successfully pass the SBT, while extubation failure is the inability to sustain spontaneous breathing after removal of the endotracheal tube. Whereas the process of weaning is simple and completely successful for most of the patients who are able to maintain spontaneous unassisted breathing after extubation, some experience difficult or prolonged weaning. For these patients it is crucial to properly assess the underlying causes of failure in order to facilitate the process of discontinuation of mechanical ventilation. A few patients, however, experience prolonged weaning and undergo tracheotomy, requiring a more gradual reduction in ventilator support and lengthening of spontaneous breathing periods. Patients who are no longer in the acute phase, but are not fully weaned, may benefit from being discharged to specialized units that must be characterized by a proper environment and a dedicated and composite organization. Location, staffing, admission and discharging criteria are key issues for these units and need to be further evaluated by future well-designed studies.Ethical disclosuresProtection of human and animal subjectsThe authors declare that no experiments were performed on humans or animals for this study.Confidentiality of dataThe authors declare that no patient data appear in this article.Right to privacy and informed consentThe authors declare that no patient data appear in this article.Conflicts of interestInamed GmbH is a Contract Research Organization specialized in the respiratory area and has been commissioned by Linde AG to provide consulting for the REMEO® development project. P. Navalesi worked as consultant for Inamed GmbH on this project, A. Patzlaff and S. Häußermann are employees of Inamed GmbH, P. Henseke and M. Kubitschek are employees of Linde AG. There is no other conflict of interest in connection with this paper." "textoCompletoSecciones" => array:1 [ "secciones" => array:14 [ 0 => array:3 [ "identificador" => "xres548428" "titulo" => "Abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0005" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec566245" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres548429" "titulo" => "Resumo" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0010" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec566244" "titulo" => "Palavras-chave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Introduction" ] 5 => array:2 [ "identificador" => "sec0010" "titulo" => "Epidemiology and outcome of weaning in ICU" ] 6 => array:2 [ "identificador" => "sec0015" "titulo" => "Pathophysiology of difficult and prolonged weaning" ] 7 => array:3 [ "identificador" => "sec0020" "titulo" => "ICU management of prolonged weaning" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0025" "titulo" => "Reduction of the respiratory load" ] 1 => array:2 [ "identificador" => "sec0030" "titulo" => "Improvement of neuromuscular capability" ] 2 => array:2 [ "identificador" => "sec0035" "titulo" => "Tracheotomy" ] ] ] 8 => array:3 [ "identificador" => "sec0040" "titulo" => "Management of prolonged weaning beyond ICU" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0045" "titulo" => "Patients dependent on non-invasive ventilation" ] 1 => array:2 [ "identificador" => "sec0050" "titulo" => "Patients dependent on tracheotomy" ] 2 => array:2 [ "identificador" => "sec0055" "titulo" => "Patient dependent on tracheotomy and mechanical ventilation" ] ] ] 9 => array:3 [ "identificador" => "sec0060" "titulo" => "Specialized weaning units" "secciones" => array:4 [ 0 => array:2 [ "identificador" => "sec0065" "titulo" => "Definition" ] 1 => array:2 [ "identificador" => "sec0070" "titulo" => "Rationale" ] 2 => array:2 [ "identificador" => "sec0075" "titulo" => "Staffing" ] 3 => array:2 [ "identificador" => "sec0080" "titulo" => "Admission and discharge criteria" ] ] ] 10 => array:2 [ "identificador" => "sec0085" "titulo" => "Summary" ] 11 => array:3 [ "identificador" => "sec0090" "titulo" => "Ethical disclosures" "secciones" => array:3 [ 0 => array:2 [ "identificador" => "sec0095" "titulo" => "Protection of human and animal subjects" ] 1 => array:2 [ "identificador" => "sec0100" "titulo" => "Confidentiality of data" ] 2 => array:2 [ "identificador" => "sec0105" "titulo" => "Right to privacy and informed consent" ] ] ] 12 => array:2 [ "identificador" => "sec0110" "titulo" => "Conflicts of interest" ] 13 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "fechaRecibido" => "2014-03-13" "fechaAceptado" => "2014-04-29" "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec566245" "palabras" => array:3 [ 0 => "Mechanical ventilation" 1 => "Weaning" 2 => "Specialized weaning unit (SWU)" ] ] ] "pt" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palavras-chave" "identificador" => "xpalclavsec566244" "palabras" => array:3 [ 0 => "Ventilação Mecânica" 1 => "Desmame" 2 => "Unidade Especializada em Desmame (SWU)" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "Weaning is the process of withdrawing mechanical ventilation which starts with the first spontaneous breathing trial (SBT). Based on the degree of difficulty and duration, weaning is classified as simple, difficult and prolonged. Prolonged weaning, which includes patients who fail 3 SBTs or are still on mechanical ventilation 7 days after the first SBT, affects a relatively small fraction of mechanically ventilated ICU patients but these, however, requires disproportionate resources. There are several potential causes which can lead to prolonged weaning. It is nonetheless important to understand the problem from the point of view of each individual patient in order to adopt appropriate treatment and define precise prognosis. An otherwise stable patient who remains on mechanical ventilation will be considered for transfer to a specialized weaning unit (SWU). Though there is not a precise definition, SWU can be considered as highly specialized and protected environments for patients requiring mechanical ventilation despite resolution of the acute disorder. Proper staffing, well defined short-term and long-term goals, attention to psychological and social problems represent key determinants of SWU success. Some patients cannot be weaned, either partly or entirely, and may require long-term home mechanical ventilation. In these cases the logistics relating to caregivers and the equipment must be carefully considered and addressed." ] "pt" => array:2 [ "titulo" => "Resumo" "resumen" => "O desmame ventilatório é o processo de retirar a ventilação mecânica, que se inicia com o primeiro teste de respiração espontânea (SBT). Baseado no grau de dificuldade e duração, o desmame é classificado como simples, difícil ou prolongado. O desmame prolongado, que inclui doentes que falharam 3 SBTs ou que ainda estão sob ventilação mecânica, 7 dias após o primeiro SBT, afecta um fracção relativamente pequena dos doentes sob ventilação mecânica na UCI mas estes, no entanto, precisam de recursos desproporcionados. Existem diversas causas potenciais que podem levar ao desmame prolongado. No entanto é importante compreender o problema do ponto de vista individual de cada doente, de forma a adoptar o tratamento adequado e definir um prognóstico preciso. Um doente de outra forma estável, que continue em ventilação mecânica, será considerado para transferência para uma unidade especializada em desmame (SWU). Apesar de não existir uma definição precisa, a SWU pode ser considerada como um ambiente altamente especializado e protegido para doentes que necessitam de ventilação mecânica apesar da resolução da doença aguda. Recursos apropriados, objectivos bem definidos a curto e longo prazo, atenção aos problemas psicológicos e sociais são os principais factores determinantes do sucesso de uma SWU. Não é possível obter o desmame ventilatório em alguns doentes,, seja parcial ou totalmente, podendo estes necessitar de ventilação de longo prazo, no domicílio. Nestes casos, a logística relacionada com os prestadores de cuidados e o equipamento deve ser cuidadosamente considerada e satisfeita." ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "This article is part of the REMEO® development project and has been commissioned by Linde AG, Linde Gas Headquarters, Seitnerstrasse 70, 82049 Pullach, Germany." ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:75 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "Weaning from mechanical ventilation" "autores" => array:1 [ 0 => array:2 [ "etal" => false "autores" => array:2 [ 0 => "M.J. Tobin" 1 => "A. 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Prolonged weaning: From the intensive care unit to home

Desmame prolongado: da unidade de cuidados intensivos para o domicílio

P. Navalesia, P. Frigeriob, A. Patzlaffc, S. Häußermannc, P. Henseked, M. Kubitschekd,

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martin.kubitschek@linde-gas.com

Corresponding author.

a Department of Translational Medicine, Eastern Piedmont University, Novara Anesthesia and Intensive Care, Sant’Andrea Hospital, Vercelli, CRRF Mons. L. Novarese, Moncrivello, VC, Italy

b Spinal Cord Unit, Niguarda-Ca’ Granda Hospital, Milano, Italy

c Inamed GmbH, Robert-Koch-Allee 29, 82131 Gauting, Germany

d GBU Healthcare, Linde Gas Headquarters, Seitnerstrasse 70, 82049 Pullach, Germany

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during which the patient is allowed to breath for a relatively brief period of time &#40;30&#8211;120<span class="elsevierStyleHsp" style=""></span>min&#41; through a T-tube&#44; or with low levels of either CPAP &#40;2&#8211;5<span class="elsevierStyleHsp" style=""></span>cmH<span class="elsevierStyleInf">2</span>O&#41; or pressure support &#40;&#8804;8<span class="elsevierStyleHsp" style=""></span>cmH<span class="elsevierStyleInf">2</span>O&#41;&#46; When the SBT is successful&#44; the patient is considered weaned and ready to be extubated provided that the natural airway is not at risk of obstruction&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> A recently proposed and largely accepted classification based on difficulty and duration of the weaning process includes&#58; &#40;1&#41; simple weaning&#44; i&#46;e&#46;&#44; the patients passes the initial SBT and is successfully extubated at the first attempt&#59; &#40;2&#41; difficult weaning&#44; i&#46;e&#46;&#44; up to three SBT or 7 days from the first SBT are necessary to withdraw mechanical ventilation and extubate the patient&#59; &#40;3&#41; prolonged weaning&#44; i&#46;e&#46;&#44; more than three SBTs or 7 days from the first SBT are required&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a></p><p id="par0015" class="elsevierStylePara elsevierViewall">Because the process of weaning implies two separate&#44; though closely related&#44; aspects&#44; the withdrawal of ventilator assistance and extubation&#44; its complete success is achieved when the patient is able to maintain spontaneous unassisted breathing after extubation&#46; Weaning failure may occur when the patient fails to breathe soon after withdrawal of the ventilator support&#44; as defined by the incapacity to successfully pass the SBT&#46; Rates of weaning failure after a single SBT of between 26 and 42&#37; have been reported by different studies&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> Weaning failure&#44; however&#44; is also the need for re-intubation&#44; conventionally within 48&#8211;72<span class="elsevierStyleHsp" style=""></span>h after extubation&#44; so-called extubation failure&#46;<a class="elsevierStyleCrossRefs" href="#bib0015"><span class="elsevierStyleSup">3&#44;4</span></a> Extubation failure can be the consequence of the inability&#44; after removal of the endotracheal tube&#44; either to sustain spontaneous unassisted breathing over time&#44; or to maintain a patent upper airway or to clear tracheobronchial secretions&#46;</p><p id="par0020" class="elsevierStylePara elsevierViewall">There are situations&#44; however&#44; in which weaning can only be partially accomplished and it remains work in progress&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> On the one hand&#44; mechanical ventilation can be applied through a noninvasive interface&#44; commonly a mask covering nose and mouth&#44; referred to as noninvasive ventilation&#44; which allows extubation while continuing to provide ventilator assistance&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> On the other hand&#44; though successfully disconnected from the ventilator&#44; a patient may still be unable to get the artificial airway removed because of inability to clear secretions or maintain patent the upper airway&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> The rates of mechanical ventilated patients undergoing a tracheotomy vary among studies and may reach values as high as 25&#37;&#46;<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5&#8211;7</span></a></p><p id="par0025" class="elsevierStylePara elsevierViewall">Finally&#44; we lack a clear definition of the ventilator-dependent patient&#46; The ninth revision of the International Classification of Diseases defines long-term ventilated patients as those who have received five or more days of ventilation&#46; Some studies use a time limit as short as 48<span class="elsevierStyleHsp" style=""></span>h&#44; while others as long as 40 days&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> A limit of two weeks has been adopted by most authors to define the threshold for ventilator dependency and the Health Care Financing Administration has expanded this limit to 21 days of mechanical ventilation for at least 6<span class="elsevierStyleHsp" style=""></span>h a day&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> A definition based only on time&#44; however&#44; has limitations because it does not consider type and characteristics of the underlying disease&#44; comorbidities&#44; reversal of the cause responsible for acute respiratory failure&#44; and the overall prognosis&#44; which&#44; for instance&#44; makes the definition of patients who are indicated for transfer from the Intensive Care Unit &#40;ICU&#41; to a specialized weaning unit problematic&#46;</p></span><span id="sec0010" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0030">Epidemiology and outcome of weaning in ICU</span><p id="par0030" class="elsevierStylePara elsevierViewall">While for about 70&#37; of patients&#44; the weaning process is simple and successful&#44; for the remaining 30&#37; the initial attempt fails&#44; making the weaning difficult and worsening the prognosis&#44; ICU mortality being reported as high as 25 percent&#59; of these patients&#44; about half progress to prolonged weaning&#46;<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4&#44;9</span></a> Two studies report that up to 20&#37; of medical ICU patients remain dependent on ventilator after 21 days&#46;<a class="elsevierStyleCrossRefs" href="#bib0020"><span class="elsevierStyleSup">4&#44;9</span></a></p><p id="par0035" class="elsevierStylePara elsevierViewall">The longer the duration of mechanical ventilation&#44; the higher the mortality rate&#59; this depends&#44; at least in part&#44; on the complications and side effects of this procedure such as the so-called ventilator-associated pneumonia&#46;<a class="elsevierStyleCrossRef" href="#bib0035"><span class="elsevierStyleSup">7</span></a> If on the one hand speeding up the process of weaning may be of benefit&#44; on the other hand&#44; however&#44; it may lead to undue anticipation of extubation and need for reintubation&#44; which has been shown to be associated with a 4&#46;5-fold increased risk of nosocomial pneumonia&#46;<a class="elsevierStyleCrossRef" href="#bib0050"><span class="elsevierStyleSup">10</span></a></p><p id="par0040" class="elsevierStylePara elsevierViewall">The time spent in the weaning process may represent a substantial fraction of the overall duration of mechanical ventilation and&#44; depending on the patient population&#44; can be as high as 50&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> Patients with prolonged weaning account for 6&#37; of all ventilated patients but consume 37&#37; of ICU resources&#46;<a class="elsevierStyleCrossRef" href="#bib0055"><span class="elsevierStyleSup">11</span></a></p><p id="par0045" class="elsevierStylePara elsevierViewall">Therefore&#44; prolonged weaning is not only a medical&#44; but also a social and economic problem&#46; US costs for mechanical ventilation are estimated to be 27 billion dollars&#44; corresponding to more than 10&#37; of all hospital costs&#46; Each year about 300&#44;000 people receive prolonged mechanical ventilation in ICU in the US&#44; and this number might double within a decade&#44; with costs increasing up 50 billion dollars&#46;<a class="elsevierStyleCrossRef" href="#bib0060"><span class="elsevierStyleSup">12</span></a></p></span><span id="sec0015" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0035">Pathophysiology of difficult and prolonged weaning</span><p id="par0050" class="elsevierStylePara elsevierViewall">Any patient who does not manage simple weaning should be carefully evaluated for potentially reversible underlying disorders&#46; 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in the context of a generalized weakness&#44; a critical reduction of the force-generating capacity of the respiratory muscles&#46;</p><p id="par0055" class="elsevierStylePara elsevierViewall">In humans&#44; diaphragm atrophy and injury may occur after relatively few hours&#46; In a group of brain-death donors&#44; 18&#8211;69<span class="elsevierStyleHsp" style=""></span>h of mechanical ventilation and complete diaphragm inactivity resulted in marked atrophy of the diaphragm fibers&#46;<a class="elsevierStyleCrossRef" href="#bib0075"><span class="elsevierStyleSup">15</span></a> In addition&#44; the force-generating capacity of the diaphragm is reduced by one-third in ICU patients after 6 days of controlled mechanical ventilation&#46;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> Nutritional state&#44; metabolic and endocrine factors should be also considered as potential causes of reduced force generation capacity of the respiratory muscles&#46;<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2&#44;17&#44;18</span></a></p><p id="par0060" class="elsevierStylePara elsevierViewall">The inability of the patient to generate a maximal inspiratory pressure of at least 20&#8211;25<span class="elsevierStyleHsp" style=""></span>cmH<span class="elsevierStyleInf">2</span>O is considered a predictive index of unsuccessful weaning&#46;<a class="elsevierStyleCrossRef" href="#bib0095"><span class="elsevierStyleSup">19</span></a> Higher values&#44; however&#44; can also be insufficient when the load imposed on the respiratory muscles is increased&#46;</p><p id="par0065" class="elsevierStylePara elsevierViewall">The respiratory load depends on the elastic and resistive properties of the respiratory system&#46; An additional threshold load may substantially add to the overall respiratory load when there is dynamic hyperinflation which causes intrinsic positive end-expiratory pressure &#40;PEEPi&#41;&#46; The elastic load increases when the compliance of the respiratory system decreases&#44; which may be due to either lung &#40;pneumonia&#44; pulmonary edema of different etiologies&#44; or fibrosis&#41; or chest wall &#40;obesity&#44; pleural thickening or abdominal distension of different etiologies&#41; restriction&#44; or both&#46; Any condition determining airway bronchoconstriction leads to an increased resistive load&#46; The additional resistance imposed by the endotracheal tube also adds to the resistive load&#44; which may be particularly relevant when the internal size of the tube is small or reduced by concrete secretions&#44; frequently as a consequence of inadequate air humidification&#46; In addition&#44; patients who successfully passed the SBT may develop post-extubation respiratory failure because the resistive load increases as a consequence of glottis edema or inability to effectively clear tracheobronchial secretions&#46;</p><p id="par0070" class="elsevierStylePara elsevierViewall">The heart-lung interaction may affect the respiratory load&#46; In fact&#44; excessive inspiratory negative intrathoracic pressure swings increase cardiac preload and afterload&#44; which determines in turn lung congestion and edema of the bronchial wall&#46;<a class="elsevierStyleCrossRefs" href="#bib0100"><span class="elsevierStyleSup">20&#44;21</span></a> This may be particularly important in patients with cardiac dysfunction&#44; sometimes latent or unrecognized&#44; undergoing a SBT that exposes them to an increased inspiratory effort following the interruption of mechanical ventilation&#46;</p><p id="par0075" class="elsevierStylePara elsevierViewall">The load can be further increased because of inappropriate ventilator settings&#44; such as inadequate inspiratory flow rate&#44; excessive time lag between onset of inspiratory effort and the onset of ventilator assistance delivery&#44; ineffective triggering&#44; double triggering&#44; expiratory effort prior to switchover from mechanical inflation to exhalation&#44; causing patient-ventilator dyssynchrony&#46;<a class="elsevierStyleCrossRefs" href="#bib0110"><span class="elsevierStyleSup">22&#8211;25</span></a></p><p id="par0080" class="elsevierStylePara elsevierViewall">Recent work has shown that neuro-psychological disorders such as delirium&#44; anxiety and depression may also substantially contribute to weaning failure&#46;<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2&#44;25</span></a> Poor sleep&#44; excessive noise&#44; lack of darkness during nighttime&#44; and an overall unfriendly environment&#44; as the ICU is generally perceived by the patient&#44; may substantially contribute to these neuro-psychological disorders&#46;</p></span><span id="sec0020" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0040">ICU management of prolonged weaning</span><p id="par0085" class="elsevierStylePara elsevierViewall">Because the pathophysiology of prolonged weaning is complex and often multifactorial&#44; the clinical approach must include either a meaningful evaluation of the specific causes for that specific patient and applying proper interventions&#46; As a rule of thumb&#44; considering that an unfavorable balance between respiratory muscles force and imposed load is the chief cause of weaning failure&#44; any treatment effective in either reducing load and&#47;or augmenting muscle force is beneficial&#46;<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2&#44;26</span></a></p><span id="sec0025" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0045">Reduction of the respiratory load</span><p id="par0090" class="elsevierStylePara elsevierViewall">To reduce an excessive elastic load secondary to a decreased lung compliance&#44; it is crucial to consider any possible cause of acute lung volume restriction that can be reverted by specific therapies&#44; such as diuretics to decrease lung congestion in cardiac or renal failure and other conditions of fluid overload&#44; antibiotics to treat pneumonia&#44; chest physiotherapy for treatment &#40;and prevention&#41; of atelectasis&#46; Causes of abdominal distensions determining chest wall restriction should be also evaluated and eliminated whenever possible&#44; for instance by treating stipsis&#44; abdominal gas distension&#44; and large pleural effusions and ascites&#46;</p><p id="par0095" class="elsevierStylePara elsevierViewall">A significant reduction in airway resistance can be achieved by medical therapies&#44; such as bronchodilators to treat bronchoconstriction&#44; steroids and antibiotics to control bronchial inflammation and infections&#44; diuretics to contain bronchial wall edema due to lung congestion&#46;</p><p id="par0100" class="elsevierStylePara elsevierViewall">Chest physiotherapy may also help decreasing the respiratory load by removing bronchial secretions&#44; which reduces airway resistance<a class="elsevierStyleCrossRef" href="#bib0135"><span class="elsevierStyleSup">27</span></a> and prevents atelectasis&#46;<a class="elsevierStyleCrossRefs" href="#bib0140"><span class="elsevierStyleSup">28&#44;29</span></a> Chest physiotherapy includes interventions such as patient positioning and mobilization&#44; breathing exercises&#44; incentive spirometry&#44; manual or mechanical insufflation&#44; aimed at increasing lung volume&#44; regional ventilation and pulmonary compliance&#44; and maneuvers aimed at reducing airway resistance and increasing expiratory flow during forced expiration either with an open &#40;huff&#41; or closed glottis &#40;cough&#41;&#46; In spite of a robust physiological background&#44;<a class="elsevierStyleCrossRef" href="#bib0150"><span class="elsevierStyleSup">30</span></a> however&#44; the evidence supporting this form of treatment is so far very limited&#59; on the one hand&#44; trials evaluating the impact of chest physiotherapy on the outcome of lack of weaning&#44; on the other hand the contemporary association of different treatments makes a proper evaluation of the physiotherapic techniques problematic&#46;<a class="elsevierStyleCrossRef" href="#bib0155"><span class="elsevierStyleSup">31</span></a></p><p id="par0105" class="elsevierStylePara elsevierViewall">While tracheal stenosis&#44; granuloma and tracheomalacia can complicate prolonged endotracheal intubation with a cuffed tube&#44;<a class="elsevierStyleCrossRef" href="#bib0160"><span class="elsevierStyleSup">32</span></a> some unrecognized abnormalities&#44; glottis inflammation and edema being the most common&#44; determining increased upper-airway resistance may lead to extubation failure&#44; often irrespective of the duration of intubation&#46; Some advise routine endoscopic evaluation before decannulation&#46;<a class="elsevierStyleCrossRef" href="#bib0165"><span class="elsevierStyleSup">33</span></a> A more practical bedside procedure is the so-called &#8220;cuff leaked test&#8221;&#44; which consists of the evaluation of the amount of leaked volume during volume-targeted mechanical ventilation with uncuffed tube&#46; The preset &#40;insufflated&#41; and the exhaled volume are measured and the percentage of leaked volume is calculated&#46; Leaks &#8804;12&#37; identifies patients at high risk of developing post-extubation stridor and then failing extubation&#46;<a class="elsevierStyleCrossRef" href="#bib0170"><span class="elsevierStyleSup">34</span></a></p><p id="par0110" class="elsevierStylePara elsevierViewall">Medical therapies aimed at reducing airway resistance may also help to decrease PEEPi&#46; Inappropriate ventilator settings&#44; such as those determining hyperventilation or patient-ventilator dyssinchrony&#44; may consistently add to the occurrence and extent of PEEPi and must be&#44; accordingly carefully avoided&#46;<a class="elsevierStyleCrossRef" href="#bib0115"><span class="elsevierStyleSup">23</span></a></p></span><span id="sec0030" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0050">Improvement of neuromuscular capability</span><p id="par0115" class="elsevierStylePara elsevierViewall">A tight control of sepsis and hyperglycaemia&#44; and avoidance of neuromuscular blocking agents&#44; aminoglycosides and steroids&#44; may help to decrease the risk of developing CINMA&#46;<a class="elsevierStyleCrossRef" href="#bib0175"><span class="elsevierStyleSup">35</span></a> It is important to reduce the time spent on full mechanical support as much as possible&#44; i&#46;e&#46;&#44; controlled mechanical ventilation&#44; to avert the risk of diaphragm injury and atrophy&#46;<a class="elsevierStyleCrossRef" href="#bib0080"><span class="elsevierStyleSup">16</span></a> Considering and correcting poor nutritional status&#44; electrolyte disturbances and hormone deficiency states&#44; such as hypothyroidism&#44; which may all play a role in decreasing muscle force&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a></p><p id="par0120" class="elsevierStylePara elsevierViewall">Lessening dynamic hyperinflation and PEEPi in patients with Chronic Obstructive Pulmonary Disease &#40;COPD&#41; also improves diaphragm force-generating capacity&#46; In fact&#44; when hyperinflation occurs&#44; diaphragm myofibers are shortened at end expiration and their force&#8211;length relationship is impaired&#46;<a class="elsevierStyleCrossRef" href="#bib0180"><span class="elsevierStyleSup">36</span></a> Unnecessarily high levels of external PEEP and ventilator settings determining iatrogenic hyperinflation should&#44; accordingly&#44; also be carefully avoided&#46;</p><p id="par0125" class="elsevierStylePara elsevierViewall">Early whole-body physiotherapy has been shown effective in improving ICU and hospital outcomes&#44; including the duration of mechanical ventilation&#44; primarily by averting the side effects of prolonged immobilization&#46;<a class="elsevierStyleCrossRef" href="#bib0185"><span class="elsevierStyleSup">37</span></a> Since inactivity weakens the respiratory muscles too&#44;<a class="elsevierStyleCrossRefs" href="#bib0075"><span class="elsevierStyleSup">15&#44;38</span></a> inspiratory muscle training&#44; as obtained by intermittent loading of the respiratory muscles&#44; has been proposed to attenuate respiratory muscle deconditioning&#46;<a class="elsevierStyleCrossRefs" href="#bib0195"><span class="elsevierStyleSup">39&#44;40</span></a> A recent randomized trial comparing inspiratory muscle training at moderate intensity&#44; i&#46;e&#46;&#44; about 50&#37; of the maximal inspiratory pressure generated by the patient&#44; with Sham training in patients with weaning failure showed that a significantly higher proportion &#40;76&#37;&#41; of patients in the treatment group was weaned&#44; as opposed to those &#40;35&#37;&#41; included in the Sham group&#46;<a class="elsevierStyleCrossRef" href="#bib0205"><span class="elsevierStyleSup">41</span></a> These findings were subsequently confirmed in a case-series of ventilator-dependent patients&#46;<a class="elsevierStyleCrossRef" href="#bib0210"><span class="elsevierStyleSup">42</span></a> Two evaluations of an early use of inspiratory muscle training in acute critically ill patients from the onset of mechanical ventilation produced contrasting results&#46; While one randomized trial did not report any physiologic or clinical benefit in a group of patients undergoing two daily sessions of inspiratory muscle training&#44; as opposed to controls&#44;<a class="elsevierStyleCrossRef" href="#bib0215"><span class="elsevierStyleSup">43</span></a> another one reported reduction of the weaning time &#40;3&#46;6 vs&#46; 5&#46;3 days&#41; in the group of patients going through twice-daily 5-min inspiratory muscle training sessions of moderate intensity&#44; compared to a control group&#46;<a class="elsevierStyleCrossRef" href="#bib0220"><span class="elsevierStyleSup">44</span></a> Indeed&#44; the rationale for inspiratory muscle training exists for only a limited number of the patients with reversible diaphragm weakness&#46; In addition&#44; there is a definite lack of a standardized technique to re-train the respiratory muscles&#46; Therefore&#44; further studies are necessary before such an approach can be suggested for clinical use&#46;</p><p id="par0130" class="elsevierStylePara elsevierViewall">Poor cough strength leading to ineffective clearing of tracheobronchial secretions may cause extubation failure in patients who successfully completed a SBT&#46; In patients with an artificial airway&#44; a peak expiratory flow while coughing through the tube &#8804;60<span class="elsevierStyleHsp" style=""></span>L&#47;min has been shown to be correlated with a five-fold increase in the incidence of extubation failure&#46;<a class="elsevierStyleCrossRef" href="#bib0225"><span class="elsevierStyleSup">45</span></a></p></span><span id="sec0035" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0055">Tracheotomy</span><p id="par0135" class="elsevierStylePara elsevierViewall">Tracheostomy is the most commonly performed procedure in the critically ill&#44; approaching 10&#37; of all intubated patients&#46;<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">46</span></a> However&#44; a tracheotomy rate as high as 25&#37; was reported by a 1-d point-prevalence study performed in 412 medical-surgical ICUs from North America&#44; South America&#44; Portugal&#44; and Spain&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> The incidence of tracheotomy varied with the underlying disease&#44; it was 39&#37; in neuromuscular patients&#44; 28&#37; in COPD&#44; and 20&#37; in patients with de novo acute respiratory failure&#46;<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a> The decision to perform a tracheotomy is predominantly based on the anticipated duration of mechanical ventilation&#46;<a class="elsevierStyleCrossRefs" href="#bib0025"><span class="elsevierStyleSup">5&#44;46</span></a> The timing of tracheotomy varies between 3 days and 21 days in the different studies&#46; The routine use of bedside percutaneous techniques is likely to have contributed to anticipating the timing of tracheotomy&#46; In fact&#44; while perioperative complications are quite rare &#40;&#60;2&#37;&#41; with both percutaneous and surgical techniques&#44;<a class="elsevierStyleCrossRef" href="#bib0235"><span class="elsevierStyleSup">47</span></a> percutaneous&#44; as opposed to surgical tracheotomy&#44; reduces costs&#44; would-be infections&#44; unfavorable scarring&#44; and overall complications&#46;<a class="elsevierStyleCrossRef" href="#bib0240"><span class="elsevierStyleSup">48</span></a> An expected intubation for more than 14 days is nowadays considered as reasonable deadline for considering tracheotomy&#46; Poor airway protective reflexes and severe upper-airway obstructions are additional reasons for tracheotomy&#46;<a class="elsevierStyleCrossRef" href="#bib0230"><span class="elsevierStyleSup">46</span></a></p><p id="par0140" class="elsevierStylePara elsevierViewall">Though never proved by large randomized controlled studies&#44; the benefits ascribed to tracheotomy vs&#46; prolonged translaryngeal intubation include improved patient comfort determining less need for sedatives&#44; ease of airway suctioning&#44; enhanced mobility and speech&#44; which may all potentially contribute to facilitating the process of weaning from mechanical ventilation&#46; Whether this translates into an increased ability to transfer ventilator-dependent patients from the ICU is not clear and might actually vary from hospital to hospital&#46; As a matter of fact&#44; not infrequently&#44; the point in time at which tracheotomy is first considered corresponds or just slightly anticipates the decision to discharge the patient from the ICU&#46;</p></span></span><span id="sec0040" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0060">Management of prolonged weaning beyond ICU</span><p id="par0145" class="elsevierStylePara elsevierViewall">In principle&#44; when the acute disorder which led to admission to ICU is reversed and clinical stability is achieved&#44; the patient may be considered ready for ICU discharge&#46; At that point&#44; while most ICU patients may be transferred to a hospital ward&#44; some of them who are experiencing prolonged weaning may still be dependent on the ventilator&#44; the tracheotomy&#44; or both&#46; In fact&#44; some patients&#44; though successfully extubated&#44; still need NIV for several hours a day&#59; for others&#44; though successfully weaned off the ventilator&#44; the tracheotomy cannot be concomitantly removed&#59; in the worst scenario&#44; invasive mechanical ventilation may still be necessary for several hours a day&#46;</p><span id="sec0045" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0065">Patients dependent on non-invasive ventilation</span><p id="par0150" class="elsevierStylePara elsevierViewall">Noninvasive ventilation is increasingly used especially&#44; though not exclusively&#44; in patients with acute or chronic respiratory failure&#44; in order to reduce the need for intubation and invasive ventilation&#46;<a class="elsevierStyleCrossRef" href="#bib0245"><span class="elsevierStyleSup">49</span></a> Some studies have repeatedly shown that noninvasive ventilation can also facilitate the process of weaning in patients with underlying chronic respiratory disease and particularly those with COPD&#46;<a class="elsevierStyleCrossRefs" href="#bib0250"><span class="elsevierStyleSup">50&#8211;53</span></a> While most of these patients undergoing noninvasive ventilation are successfully weaned off the ventilator&#44; some may need to keep on non-invasive ventilation for some hours&#47;day for weeks<a class="elsevierStyleCrossRef" href="#bib0270"><span class="elsevierStyleSup">54</span></a> or on a long-term basis<a class="elsevierStyleCrossRef" href="#bib0275"><span class="elsevierStyleSup">55</span></a> to guarantee acceptable values of arterial blood gases and avoid repeated hospital readmission&#46;<a class="elsevierStyleCrossRef" href="#bib0280"><span class="elsevierStyleSup">56</span></a></p></span><span id="sec0050" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0070">Patients dependent on tracheotomy</span><p id="par0155" class="elsevierStylePara elsevierViewall">For patients who have regained respiratory autonomy and resumed overall clinical stability&#44; the removal of tracheotomy represents a major objective&#44; for reasons related to both clinical&#44; i&#46;e&#46;&#44; increased risk of infections and long term complications&#44; and social&#44; i&#46;e&#46;&#44; negative impact on daily life activities and relationships&#46; In spite of these considerations&#44; the few recommendations currently available are still largely based on subjective criteria rather than on standardized protocols&#46;<a class="elsevierStyleCrossRef" href="#bib0285"><span class="elsevierStyleSup">57</span></a> Only one study systematically addressed the problem of weaning from tracheotomy in patients with different underlying disorders&#44; such as COPD&#44; post-surgical complications&#44; hypoxemic respiratory failure&#44; neuromuscular diseases&#44; by means of a relatively simple decisional flowchart&#46;<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">58</span></a> This was based on a few parameters aimed at assessing swallowing function and patient ability to spontaneously clear secretions&#44; after determining patient capability of maintaining spontaneous unassisted breathing&#46;<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">58</span></a> By using this simple decisional flowchart&#44; it was possible to remove the tracheotomy in almost 80&#37; of the patients with spontaneous breathing autonomy&#46;<a class="elsevierStyleCrossRef" href="#bib0290"><span class="elsevierStyleSup">58</span></a> A lower rate of successful decannulation was observed in patients affected by chronic respiratory diseases&#44; and in particular in those with neuromuscular disorders&#44; for whom a more sophisticated approach is likely to be necessary&#46;<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">59</span></a></p></span><span id="sec0055" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0075">Patient dependent on tracheotomy and mechanical ventilation</span><p id="par0160" class="elsevierStylePara elsevierViewall">Observational studies indicate that 34&#8211;60&#37; of patients in specialized weaning unit can be weaned successfully from the ventilator support&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> These studies also suggest that successful weaning can occur up to 3 months after admission to these units and that the transfer to a specialized unit does not adversely affect long-term mortality&#46;<a class="elsevierStyleCrossRefs" href="#bib0300"><span class="elsevierStyleSup">60&#44;61</span></a> The clinical outcome of patients requiring prolonged mechanical ventilation is largely influenced by the underlying disease&#44; the chances to be completely weaned off both ventilator assistance and tracheotomy approaching 60&#37; in patients with post-operative &#40;58&#37;&#41; and de novo respiratory failure &#40;57&#37;&#41;&#44; and slightly exceeding 20&#37; in patients with COPD or neuromuscular disease&#46;<a class="elsevierStyleCrossRef" href="#bib0310"><span class="elsevierStyleSup">62</span></a> Also&#44; the long-term survival rate after successful weaning is worse in COPD than in non-COPD patients&#46;<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2&#44;63</span></a></p><p id="par0165" class="elsevierStylePara elsevierViewall">In patients with neuromuscular disorder&#44; it is crucial to assess the ability to clear secretions&#46; Bach et al&#46;<a class="elsevierStyleCrossRef" href="#bib0295"><span class="elsevierStyleSup">59</span></a> showed that peak expiratory flow during cough&#44; so-called peak cough expiratory flow &#40;PCEF&#41; is a better predictor of the likelihood of being weaned from tracheotomy&#46; A variety of cough-augmentation physical therapies&#44; alone or in combination&#44; can be used to increase PCEF and enhance cough efficacy&#46; While the patients with weak expiratory muscle strength&#44; but relatively well preserved inspiratory strength&#44; may benefit from the abdominal-thrust maneuver&#44; also termed &#8220;quad cough&#8221; or &#8220;manually assisted cough&#44;&#8221; which replaces or enhances abdominal muscle contraction&#44; those who combine weakness of both the inspiratory and expiratory muscles necessitate&#44; in addition to manually assisted cough&#44; manual or mechanical forms of inspiratory assistance &#40;i&#46;e&#46;&#44; insufflation&#44; air staking&#44; glosso-pharyngeal breathing&#44; etc&#46;&#41; to increase the pre-tussive volume&#46;</p><p id="par0170" class="elsevierStylePara elsevierViewall">An increasing number of devices specifically designed to assist an insufficient cough have been introduced for clinical use in recent years&#44; which apply to the airway opening positive pressure during the inspiratory phase and negative &#40;sub-atmospheric&#41; pressure during forced expiration&#46;<a class="elsevierStyleCrossRef" href="#bib0320"><span class="elsevierStyleSup">64</span></a> These techniques of mechanical cough-augmentation can be successfully used with neuromuscular patients through an artificial airway&#44; but an intact glottis function is required for those breathing through the native airway at which cough assistance is applied by means of an oro-nasal mask&#46; A program including periodic evaluation of cough strength and timely initiation of effective cough-augmentation therapy may dramatically improve the possibility of weaning neuromuscular patients from tracheotomy&#46;<a class="elsevierStyleCrossRef" href="#bib0325"><span class="elsevierStyleSup">65</span></a></p><p id="par0175" class="elsevierStylePara elsevierViewall">Although the combination of invasive mechanical ventilation and tracheal suctioning can be successfully used when ventilator assistance is also necessary&#44; in neuromuscular patients this approach has been shown to be associated with increased morbidity&#46;<a class="elsevierStyleCrossRef" href="#bib0320"><span class="elsevierStyleSup">64</span></a> The advent of non-invasive ventilation NIV as a means of supporting chronic neuromuscular respiratory insufficiency has spurred on the development of noninvasive cough-augmentation therapies to favor airway clearance&#46; Unfortunately&#44; the need to support cough clearance has not been properly addressed&#59; indeed&#44; guidelines for the management of a weak cough did not exist until relatively recently&#46;<a class="elsevierStyleCrossRef" href="#bib0320"><span class="elsevierStyleSup">64</span></a></p></span></span><span id="sec0060" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0080">Specialized weaning units</span><span id="sec0065" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0085">Definition</span><p id="par0180" class="elsevierStylePara elsevierViewall">There is no uniform&#44; widely recognized definition for &#8220;specialized weaning units&#8221;&#44; and confusion can arise&#44; as for the term &#8220;weaning&#8221;&#44; from imprecise language&#46; Generally speaking&#44; these units are protected environments for the treatment of patients requiring prolonged mechanical ventilation&#46; As mentioned by Nava &#38; Vitacca in a dedicated book chapter&#44; several terms are used to characterize these units&#44; such as long-term acute-care facilities&#44; respiratory special care units&#44; chronic ventilator-dependent units&#44; regional weaning centers&#44; ventilator-dependent rehabilitation hospitals&#44; prolonged respiratory-care units&#44; non-invasive respiratory-care units&#44; high-dependency units&#44; and respiratory intensive-care units&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> Beyond the terminology&#44; remarkable differences exist among units&#44; which are primarily&#44; though not exclusively&#44; a consequence of the different healthcare systems and reimbursements&#44; varying not only from country to country&#44; but also often from region to region&#44; and not infrequently from town to town&#46;<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2&#44;8</span></a> A helpful approach to this problem has been provided by Nava &#38; Vitacca who classified&#44; depending on the type of location&#44; weaning units into two categories&#44; step-down units sited within acute care hospitals&#44; and Weaning Centers serving different acute care hospitals in dedicated areas&#46;<a class="elsevierStyleCrossRef" href="#bib0040"><span class="elsevierStyleSup">8</span></a> While the former&#44; with organization and staffing closer to ICUs may often result in not being able to meet the needs of these patients beyond their clinical problems&#44; the latter require a proper environment and a dedicated and composite organization&#46;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">25</span></a></p></span><span id="sec0070" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0090">Rationale</span><p id="par0185" class="elsevierStylePara elsevierViewall">Weaning from prolonged mechanical ventilation is a complex and time-consuming process covering several procedures&#46; Quick patient turnover&#44; high workloads for the staff&#44; need for continuous monitoring and treatment&#44; and&#44; in some countries&#44; paucity of ICU beds&#44; make ICUs in appropriate for managing patients with prolonged weaning&#44; requiring care with dedicated personnel&#44; which is often not available in the ICU&#46;<a class="elsevierStyleCrossRef" href="#bib0330"><span class="elsevierStyleSup">66</span></a> In addition&#44; prolonging the ICU stay may have detrimental consequences on the psychological and cognitive function&#44; which may further complicate and protract the weaning process and affect patient outcomes&#46;<a class="elsevierStyleCrossRefs" href="#bib0335"><span class="elsevierStyleSup">67&#44;68</span></a></p><p id="par0190" class="elsevierStylePara elsevierViewall">It has been shown that a substantial proportion of patients&#44; not ready to be separated from the ventilator at ICU discharge can be weaned off the ventilator soon after admission to a specialized weaning unit&#44; which suggests that discontinuation of mechanical ventilation was not a priority for the referring ICUs&#46;<a class="elsevierStyleCrossRefs" href="#bib0345"><span class="elsevierStyleSup">69&#44;70</span></a></p><p id="par0195" class="elsevierStylePara elsevierViewall">In a retrospective study including more than 400 ICU patients who had undergone tracheostomy and prolonged mechanical ventilation following an episode of acute respiratory failure&#44; the rate of survivors successfully weaned at the time of ICU discharge was less than 60&#37;&#46;<a class="elsevierStyleCrossRef" href="#bib0355"><span class="elsevierStyleSup">71</span></a> The patients who were weaned off both ventilator and tracheotomy had better survival rates than those who did not&#46; This improved survival&#44; however&#44; came at higher hospital costs secondary to longer ICU stay&#44; which indicates that the balance between outcome and economic burden represents a major problem when treating patients with prolonged weaning exclusively in ICU&#46;<a class="elsevierStyleCrossRef" href="#bib0355"><span class="elsevierStyleSup">71</span></a> One controlled study compared outcomes and costs of patients with prolonged weaning assigned to either ICU or weaning unit&#46; The rates of mortality were no different between the two groups&#44; but readmissions were fewer&#44; hospital lengths of stay shorter&#44; and costs lower for the patients weaned in the specialized unit&#46;<a class="elsevierStyleCrossRef" href="#bib0300"><span class="elsevierStyleSup">60</span></a></p><p id="par0200" class="elsevierStylePara elsevierViewall">In point of fact&#44; patients who are no longer in the acute phase&#44; but are not fully weaned&#44; may benefit from the discharge to specialized units&#46; These units offer several advantages&#44; including an environment with reduced noise and night-time light favoring the return to more physiological circadian rhythms and better sleep&#44; open visiting hours to allow unrestricted visits by relatives and friends&#44; easier access to personal belongings&#44; such as books&#44; computers&#44; tablets&#44; TV&#44; music players&#44; and so on&#46;<a class="elsevierStyleCrossRefs" href="#bib0360"><span class="elsevierStyleSup">72&#44;73</span></a> The management of these individuals generally involves more than just expertise in mechanical ventilation&#44; but rather an integrated approach with harmonized procedures conducted by a multidisciplinary team&#46;</p><p id="par0205" class="elsevierStylePara elsevierViewall">Beside any other consideration&#44; a weaning unit should also represent a cost-effective alternative to the ICU for the management of patients with prolonged weaning&#46;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">25</span></a></p></span><span id="sec0075" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0095">Staffing</span><p id="par0210" class="elsevierStylePara elsevierViewall">The components of this team should be physicians&#44; nurses and respiratory therapists or physiotherapists capable of providing comprehensive respiratory care&#46; While one physician should be present around the clock&#44; the therapists need not be present overnight&#46; The nurse&#8211;patient ratio should range between 1&#58;4 and 1&#58;8 depending on the time of the day&#46; Overall&#44; the skills must encompass invasive and noninvasive mechanical ventilation&#44; suctioning&#44; tracheotomy management&#44; and chest physiotherapy including cough assistance techniques&#46; Physical therapists&#44; occupational therapists&#44; for daily living activities&#44; speech therapists&#44; for evaluation and treatment of swallowing dysfunctions&#44; and nutritionists&#44; to optimize calories and proteins administration&#44; should also be part of the team&#46; Psychology and social services should be also available for patient and family evaluation&#44; education and counseling&#46;</p><p id="par0215" class="elsevierStylePara elsevierViewall">Understaffing is one of the major determinants of a suboptimal or ineffective or even harmful weaning unit&#44; and should definitely be avoided when building up an accredited effective unit&#46;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">25</span></a></p></span><span id="sec0080" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0100">Admission and discharge criteria</span><p id="par0220" class="elsevierStylePara elsevierViewall">Although it is advisable for a weaning unit to define and apply admission criteria&#44; these cannot be generalized and depend on the characteristics of each specific unit&#46; While&#44; the possibility of promptly assessing arterial blood gases and having daily access to chest X-ray and routine blood examination represent the minimum standard for a specialized unit&#44; other facilities may enhance the possibility of accepting patients with higher levels of clinical complexity&#46; Most weaning units that are located outside acute-care hospitals&#44; however&#44; clearly cannot offer sophisticated diagnostic procedures and treatments&#46;</p><p id="par0225" class="elsevierStylePara elsevierViewall">The patients admitted should obviously be dependent on ventilator assistance&#44; or need an artificial airway&#44; or both&#46;<a class="elsevierStyleCrossRef" href="#bib0370"><span class="elsevierStyleSup">74</span></a> It is worth remembering that prolonged weaning is defined by more than three previously failed SBTs or at least 7 days from the first attempt of SBT&#46;<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> Several units include in the admission criteria for invasively ventilated patients the presence of a tracheotomy&#44; to avoid the risk of emergency maneuvers consequent to the need to change an obstructed endotracheal tube&#46; Some units require the proposing physician to provide a written statement that the patient has the potential to be weaned from the ventilator or to return to her&#47;his community under ventilator assistance&#46;<a class="elsevierStyleCrossRef" href="#bib0375"><span class="elsevierStyleSup">75</span></a></p><p id="par0230" class="elsevierStylePara elsevierViewall">The team should work with the patient and the family to define short and long term goals leading to final discharge home&#46;<a class="elsevierStyleCrossRef" href="#bib0125"><span class="elsevierStyleSup">25</span></a> If&#44; based on objective data&#44; the whole team consider additional weaning attempts to be worthless&#44; these should be interrupted to avoid further frustration&#44; anxiety and depression&#44; and patient and family promptly and clearly informed&#46; When everyone involved in the process&#44; i&#46;e&#46;&#44; the team&#44; the patient and the family&#44; agree on the futility of pursuing the weaning efforts&#44; the primary goal becomes the setting up of the best possible discharge program&#44; in which complexity will clearly depend on the level of patient dependence&#46; Of course&#44; it is much more complex to discharge a tracheotomized patient on full ventilator support around the clock&#44; rather than a patient on nocturnal noninvasive ventilation&#46; Once it has been established that the patient&#39;s clinical condition&#44; motivation and home environment are suitable for undertaking a long-term domiciliary ventilation program&#44; several logistical aspects remain to be carefully considered and addressed with respect to both the care givers and the equipment&#46;<a class="elsevierStyleCrossRefs" href="#bib0125"><span class="elsevierStyleSup">25&#44;74</span></a></p></span></span><span id="sec0085" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0105">Summary</span><p id="par0235" class="elsevierStylePara elsevierViewall">Weaning failure is commonly understood to be an incapacity to successfully pass the SBT&#44; while extubation failure is the inability to sustain spontaneous breathing after removal of the endotracheal tube&#46; Whereas the process of weaning is simple and completely successful for most of the patients who are able to maintain spontaneous unassisted breathing after extubation&#44; some experience difficult or prolonged weaning&#46; For these patients it is crucial to properly assess the underlying causes of failure in order to facilitate the process of discontinuation of mechanical ventilation&#46; A few patients&#44; however&#44; experience prolonged weaning and undergo tracheotomy&#44; requiring a more gradual reduction in ventilator support and lengthening of spontaneous breathing periods&#46; Patients who are no longer in the acute phase&#44; but are not fully weaned&#44; may benefit from being discharged to specialized units that must be characterized by a proper environment and a dedicated and composite organization&#46; Location&#44; staffing&#44; admission and discharging criteria are key issues for these units and need to be further evaluated by future well-designed studies&#46;</p></span><span id="sec0090" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0110">Ethical disclosures</span><span id="sec0095" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0115">Protection of human and animal subjects</span><p id="par0240" class="elsevierStylePara elsevierViewall">The authors declare that no experiments were performed on humans or animals for this study&#46;</p></span><span id="sec0100" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0120">Confidentiality of data</span><p id="par0245" class="elsevierStylePara elsevierViewall">The authors declare that no patient data appear in this article&#46;</p></span><span id="sec0105" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0125">Right to privacy and informed consent</span><p id="par0250" class="elsevierStylePara elsevierViewall">The authors declare that no patient data appear in this article&#46;</p></span></span><span id="sec0110" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0130">Conflicts of interest</span><p id="par0255" class="elsevierStylePara elsevierViewall">Inamed GmbH is a Contract Research Organization specialized in the respiratory area and has been commissioned by Linde AG to provide consulting for the REMEO<span class="elsevierStyleSup">&#174;</span> development project&#46; P&#46; Navalesi worked as consultant for Inamed GmbH on this project&#44; A&#46; Patzlaff and S&#46; H&#228;u&#223;ermann are employees of Inamed GmbH&#44; P&#46; Henseke and M&#46; Kubitschek are employees of Linde AG&#46; There is no other conflict of interest in connection with this paper&#46;</p></span></span>"
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        "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Weaning is the process of withdrawing mechanical ventilation which starts with the first spontaneous breathing trial &#40;SBT&#41;&#46; Based on the degree of difficulty and duration&#44; weaning is classified as simple&#44; difficult and prolonged&#46; Prolonged weaning&#44; which includes patients who fail 3 SBTs or are still on mechanical ventilation 7 days after the first SBT&#44; affects a relatively small fraction of mechanically ventilated ICU patients but these&#44; however&#44; requires disproportionate resources&#46; There are several potential causes which can lead to prolonged weaning&#46; It is nonetheless important to understand the problem from the point of view of each individual patient in order to adopt appropriate treatment and define precise prognosis&#46; An otherwise stable patient who remains on mechanical ventilation will be considered for transfer to a specialized weaning unit &#40;SWU&#41;&#46; Though there is not a precise definition&#44; SWU can be considered as highly specialized and protected environments for patients requiring mechanical ventilation despite resolution of the acute disorder&#46; Proper staffing&#44; well defined short-term and long-term goals&#44; attention to psychological and social problems represent key determinants of SWU success&#46; Some patients cannot be weaned&#44; either partly or entirely&#44; and may require long-term home mechanical ventilation&#46; In these cases the logistics relating to caregivers and the equipment must be carefully considered and addressed&#46;</p></span>"
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        "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">O desmame ventilat&#243;rio &#233; o processo de retirar a ventila&#231;&#227;o mec&#226;nica&#44; que se inicia com o primeiro teste de respira&#231;&#227;o espont&#226;nea &#40;SBT&#41;&#46; Baseado no grau de dificuldade e dura&#231;&#227;o&#44; o desmame &#233; classificado como simples&#44; dif&#237;cil ou prolongado&#46; O desmame prolongado&#44; que inclui doentes que falharam 3 SBTs ou que ainda est&#227;o sob ventila&#231;&#227;o mec&#226;nica&#44; 7 dias ap&#243;s o primeiro SBT&#44; afecta um frac&#231;&#227;o relativamente pequena dos doentes sob ventila&#231;&#227;o mec&#226;nica na UCI mas estes&#44; no entanto&#44; precisam de recursos desproporcionados&#46; Existem diversas causas potenciais que podem levar ao desmame prolongado&#46; No entanto &#233; importante compreender o problema do ponto de vista individual de cada doente&#44; de forma a adoptar o tratamento adequado e definir um progn&#243;stico preciso&#46; Um doente de outra forma est&#225;vel&#44; que continue em ventila&#231;&#227;o mec&#226;nica&#44; ser&#225; considerado para transfer&#234;ncia para uma unidade especializada em desmame &#40;SWU&#41;&#46; Apesar de n&#227;o existir uma defini&#231;&#227;o precisa&#44; a SWU pode ser considerada como um ambiente altamente especializado e protegido para doentes que necessitam de ventila&#231;&#227;o mec&#226;nica apesar da resolu&#231;&#227;o da doen&#231;a aguda&#46; Recursos apropriados&#44; objectivos bem definidos a curto e longo prazo&#44; aten&#231;&#227;o aos problemas psicol&#243;gicos e sociais s&#227;o os principais factores determinantes do sucesso de uma SWU&#46; N&#227;o &#233; poss&#237;vel obter o desmame ventilat&#243;rio em alguns doentes&#44;&#44; seja parcial ou totalmente&#44; podendo estes necessitar de ventila&#231;&#227;o de longo prazo&#44; no domic&#237;lio&#46; Nestes casos&#44; a log&#237;stica relacionada com os prestadores de cuidados e o equipamento deve ser cuidadosamente considerada e satisfeita&#46;</p></span>"
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Article information

ISSN: 08732159
Original language: English

DOI:10.1016/j.rppneu.2014.04.006

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2024 November	15	5	20
2024 October	187	52	239
2024 September	266	50	316
2024 August	266	57	323
2024 July	296	54	350
2024 June	206	67	273
2024 May	242	116	358
2024 April	177	86	263
2024 March	184	72	256
2024 February	161	67	228
2024 January	264	57	321
2023 December	120	36	156
2023 November	139	73	212
2023 October	131	55	186
2023 September	94	48	142
2023 August	89	37	126
2023 July	92	39	131
2023 June	86	20	106
2023 May	143	55	198
2023 April	92	23	115
2023 March	176	30	206
2023 February	95	38	133
2023 January	84	34	118
2022 December	110	32	142
2022 November	168	62	230
2022 October	174	66	240
2022 September	81	51	132
2022 August	105	45	150
2022 July	121	72	193
2022 June	93	46	139
2022 May	118	56	174
2022 April	103	55	158
2022 March	102	72	174
2022 February	131	58	189
2022 January	175	57	232
2021 December	115	52	167
2021 November	97	45	142
2021 October	136	56	192
2021 September	187	44	231
2021 August	223	53	276
2021 July	136	47	183
2021 June	185	38	223
2021 May	557	58	615
2021 April	725	107	832
2021 March	529	94	623
2021 February	333	57	390
2021 January	277	40	317
2020 December	186	30	216
2020 November	199	44	243
2020 October	149	31	180
2020 September	208	44	252
2020 August	203	58	261
2020 July	226	52	278
2020 June	217	36	253
2020 May	231	47	278
2020 April	277	79	356
2020 March	197	33	230
2020 February	173	43	216
2020 January	196	53	249
2019 December	181	101	282
2019 November	218	60	278
2019 October	208	56	264
2019 September	183	56	239
2019 August	750	44	794
2019 July	882	47	929
2019 June	885	35	920
2019 May	792	41	833
2019 April	761	56	817
2019 March	1040	22	1062
2019 February	875	40	915
2019 January	952	42	994
2018 December	689	12	701
2018 November	237	4	241
2018 October	272	9	281
2018 September	82	7	89
2018 August	99	26	125
2018 July	96	21	117
2018 June	124	21	145
2018 May	201	21	222
2018 April	269	22	291
2018 March	248	34	282
2018 February	28	11	39
2018 January	33	19	52
2017 December	35	15	50
2017 November	39	15	54
2017 October	56	21	77
2017 September	54	21	75
2017 August	61	17	78
2017 July	55	22	77
2017 June	50	15	65
2017 May	62	19	81
2017 April	22	8	30
2017 March	34	9	43
2017 February	82	6	88
2017 January	50	6	56
2016 December	36	5	41
2016 November	54	5	59
2016 October	67	5	72
2016 September	80	22	102
2016 August	80	8	88
2016 July	48	31	79
2016 June	5	8	13
2016 May	5	7	12
2016 April	116	3	119
2016 March	172	43	215
2016 February	154	51	205
2016 January	110	29	139
2015 December	179	43	222
2015 November	118	37	155
2015 October	132	37	169
2015 September	109	31	140
2015 August	102	29	131
2015 July	95	17	112
2015 June	70	11	81
2015 May	133	27	160
2015 April	115	34	149
2015 March	92	15	107
2015 February	74	28	102
2015 January	80	26	106
2014 December	130	51	181
2014 November	156	61	217
2014 October	141	106	247
2014 September	127	71	198
2014 August	59	54	113

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