Abstract
Maintenance of airway secretion clearance, or airway hygiene, is important for the preservation of airway patency and the prevention of respiratory tract infection. Impaired airway clearance often prompts admission to the intensive care unit (ICU) and can be a cause and/or contributor to acute respiratory failure. Physical methods to augment airway clearance are often used in the ICU but few are substantiated by clinical data. This review focuses on the impact of oral hygiene, tracheal suctioning, bronchoscopy, mucus-controlling agents, and kinetic therapy on the incidence of hospital-acquired respiratory infections, length of stay in the hospital and the ICU, and mortality in critically ill patients. Available data are distilled into recommendations for the maintenance of airway hygiene in ICU patients.
Introduction
Clearance of airway secretions, or airway hygiene, is a normal physiological process needed for the preservation of airway patency and the prevention of respiratory tract infection. Impaired clearance of airway secretions can result in atelectasis and pneumonia, and may contribute to respiratory failure prompting admission to an intensive care unit (ICU).
Physical methods to augment the clearance of secretions are often used in the ICU. This review focuses on mechanical methods and pharmacological agents commonly used to maintain airway hygiene in the ICU, and their effect on clinical outcomes of critically ill patients. The impact of oral hygiene, tracheal suctioning, bronchoscopy, mucus-controlling agents, and kinetic therapy on the incidence of nosocomial respiratory infections, length of stay in the hospital and the ICU, and mortality will be discussed. Where possible, we have distilled available data into recommendations for airway hygiene in ICU patients.
Methods
Literature for this article was identified by searching the PubMed database (1966 to present). English-language articles of relevance were selected and reviewed. Additional resources were obtained through the bibliographies of reviewed articles. The following search terms were used: airway hygiene, oral hygiene, mucociliary clearance, tracheal suctioning, bronchoscopy, mucolytics, chest physiotherapy, kinetic therapy, continuous lateral rotational therapy, selective digestive decontamination, nosocomial pneumonia, hospital-acquired pneumonia, ventilator-associated pneumonia, and pneumonia.
A summary of recommendations and associated strength of supporting evidence for strategies used in the reduction of nosocomial pneumonia is shown in Table 1. The following grading system described by Kollef [1] was used to assess strength of evidence: A, supported by at least two randomized, controlled investigations; B, supported by at least one randomized, controlled investigation; C, supported by nonrandomized, concurrent-cohort investigations, historical-cohort investigations, or case series; U, undetermined or not yet studied in clinical investigations.
Table 1.
Strategies | Recommended for clinical use | Grade | Reduction in HCAP | Reduction in mortality | Refs |
Effective strategies | |||||
Chlorhexidine gluconate oral rinse | Yes | A | Yes | No | 11–14 |
Endotracheal suctioning on 'as needed' basis (compared with routine suctioning) | Yes | A | No increased incidence of HCAP | No | 45,57,58 |
Kinetic therapy | Yesa | A | Inconclusive | No | 105–111 |
Ineffective strategies | |||||
Selective digestive decontamination | No | A | Inconclusive | No | 15–33 |
Oral topical iseganan | No | B | No | No | 35 |
Aerosolized mucus-controlling agents | No | U | N/A | N/A | 85–88 |
Endotracheal instillation of saline | No | C | N/A | N/A | 52,53 |
Chest physiotherapy | No | A | Inconclusive | No | 114, 117–125 |
Strategies of equivocal or undetermined effectiveness | |||||
Continuous subglottic suctioning | Yesb | A | Yes | No | 70–75 |
Bronchoscopy | Yesc | B | N/A | N/A | 114 |
Closed (in-line) endotracheal suctioning (compared with open suctioning) | Yesd | A | Inconclusive | No | 59–68 |
The grading scheme used is as follows: A, supported by at least two randomized, controlled investigations; B, supported by at least one randomized, controlled investigation; C, supported by nonrandomized, concurrent-cohort investigations, historical-cohort investigations, or case series; U, undetermined or not yet studied in clinical investigations. HCAP, healthcare-associated pneumonia; N/A, not applicable. aThe increased cost of kinetic beds is offset by the decreased length of stay; bthis strategy is recommended for patients expected to require more than 72 hours of mechanical ventilation; cthis strategy is recommended for patients with acute atelectasis involving more than a single lung segment in the absence of air bronchograms who remain symptomatic after 24 hours of chest physiotherapy; dthis strategy is recommended for patients requiring mechanical ventilation for more than four days.
Oral/pharyngeal hygiene
A general tenet of hospital-acquired pneumonia and ventilator-associated pneumonia (VAP) is that infections of the lower respiratory tract are preceded by colonization or infection of the upper airway. Thus, most hospital-acquired pneumonias stem from micro- or macro-aspiration of infected secretions from the upper airway. Methods that reduce oropharyngeal colonization have been postulated to reduce infections of the lower respiratory tract in the critically ill. Surprisingly, nasopharyngeal and oropharyngeal hygiene often receives little attention from intensivists.
Many risk factors have been linked to airway colonization, including severity of illness, length of hospitalization, prior or concomitant antibiotic use, malnutrition, endotracheal intubation, azotemia, underlying pulmonary disease, inadequate oral hygiene, substandard infection control practises during bathing, tracheal suctioning, enteral feeding, and endotracheal tube manipulation. Furthermore, critical illness is associated with alterations in oral mucosal-cell-surface fibronectin and carbohydrate expression patterns, disruption of the mucosa by endotracheal tubes and suction catheters, and increased secretion of mucus, all of which provide binding sites for pathogenic bacteria [2-5]. Gram-negative bacteria and Staphylococcus aureus replace the normal upper-airway flora of patients hospitalized for more than 5 days [6]. Not surprisingly, many patients (50%) have pathogenic bacteria in their oropharynx on admission to the ICU [7]. The periodontal areas, oropharynx, sinuses, stomach, and trachea are colonized by the end of the first week in most mechanically ventilated patients [7-9]. Tracheal and oropharyngeal colonization is associated with VAP, whereas gastric colonization in the setting of acid suppression therapy may not be [7,8,10].
Oral antiseptic rinses such as chlorhexidine gluconate reduce the rate of nosocomial pneumonia in critically ill patients [11-13]. The twice-daily use of chlorhexidine gluconate 0.12% oral rinse reduced respiratory tract infections by 69% and antibiotic use by 43% in cardiac surgical patients postoperatively without affecting antibiotic resistance patterns [11]. The impact was greatest in patients intubated for more than 24 hours and who had the highest degree of bacterial colonization [13]. The cost of nursing care did not significantly increase with the use of chlorhexidine oral rinse, and the liquid form was easier and quicker to apply than an antibiotic paste [11,13]. Despite the reduction in bacterial colonization and/or nosocomial pneumonia, the use of oral antiseptic rinses has not been shown to affect the duration of mechanical ventilation or survival, although it may modestly reduce the length of stay in the hospital [12,14].
Selective decontamination of the oropharynx, and gastric and subglottic area, or selective digestive tract decontamination (SDD) with several different regimens have been proposed as a method for decreasing VAP. These SDD regimens have included one or more of the following antibiotics: polymixin, tobramycin/gentamycin, vancomycin, and amphotericin B suspension. More than 50 randomized controlled trials and 12 meta-analyses evaluating the SDD prophylaxis have been published [15-29]. These trials were conducted in unselected medical and surgical patients who required 2 days or more of mechanical ventilation and in selected patients including liver transplant, cardiac surgical, and burn patients. Most randomized control trials found a beneficial effect in reduction of bacterial colonization and/or VAP; however, effects on length of stay in the ICU and mortality are inconsistent. Although some analyses suggest a reduction in mortality in selected patients [24,27], others have demonstrated only a modest effect with the use of combined (topical and systemic) SDD therapy [18,19,23]. Survival advantage seems to be limited to surgical ICU patients treated with a combination of parenteral and topical prophylactic antibiotics [18,24,30]. A modified SDD regimen that includes oral vancomycin reduces the rate at which isolates of methicillin-resistant Staphylococcus aureus are found [31,32]. The impact of this regimen on the incidence of nosocomial pneumonia is less clear [31,32]. Furthermore, a transient increase in isolation of vancomycin-resistant Enterococcus has been observed with this regimen [32]. Failure of SDD strategies to reduce morbidity and mortality consistently in critically ill patients may be related to suboptimal study design, the emergence of antibiotic-resistant bacteria, and an alteration in hosts' normal bacteriologic flora [33]. Additional toxicity and increased healthcare costs related to SDD [17,27,34] have further dampened the enthusiasm for this preventive strategy. On the basis of available evidence, SDD with topical antibiotics should not be routinely used in the ICU. If combined parenteral and topical SDD is used in surgical/trauma patients, clinicians should be vigilant in monitoring for the emergence of new multidrug-resistant organisms.
A recent randomized controlled trial of oral topical iseganan, an antimicrobial peptide with a broad in vitro activity against aerobic and anaerobic Gram-positive and Gram-negative bacteria and yeasts, was stopped early because of a higher, although not statistically significant, rate of VAP and death among mechanically ventilated ICU patients in the iseganan arm [35]. The widespread use of biocides such as chlorhexidine in hospital, domiciliary, industrial, and other settings raises concern for the development of antibiotic-resistant infection. Fortunately, no clinically significant alteration of antibiotic resistance patterns has been noted in epidemiologic studies [36,37]. Therefore, chlorhexidine gluconate oral rinse, an inexpensive and easily applied agent, should be a routine aspect of care of the critically ill patient.
Tracheal suctioning
Airway hygiene is impaired in critically ill patients as a result of depressed cough reflex and ineffective mucociliary clearance from sedation, high inspired oxygen concentrations, elevated endotracheal tube cuff pressure, and tracheal mucosal inflammation and damage [38-40]. Accordingly, care of intubated patients includes tracheal suctioning to facilitate the removal of airway secretions. Routine suctioning via endotracheal tubes is often performed on the basis of the assumption that it maintains airway patency and prevents pulmonary infection. However, tracheal suctioning induces mucosal injury, exposing the basement membrane and thereby facilitating bacterial adhesion in vitro [41] and in low-birthweight babies [42]. Suctioning has also been associated with many deleterious effects including decreased arterial oxygen tension (12 to 20 mmHg) [43-45], which may be more pronounced in cardiac surgical patients [43] and in patients with hypoxemic respiratory failure requiring high levels of positive end-expiratory pressure [46], in patients with cardiac arrhythmias (7 to 81%) [45,47], and in cardiac arrest in patients with acute spinal cord injury [48]. These detrimental effects of tracheal suctioning, however, may be mimimized through the use of manual hyperinflation, preoxygenation, sedation, and optimal suctioning technique [49-51]. Normal saline is frequently instilled into the trachea before endotracheal suctioning under the assumption that it may help dislodge secretions and facilitate airway clearance. However, Ackerman and colleagues have shown that intratracheal instillation of 5 ml of normal saline adversely effects oxygen hemoglobin saturation and has no effect on the clearance of secretions [52,53]. In addition, a 5 ml saline instillation dislodges fivefold more viable bacterial colonies from the endotracheal tube than does the insertion of a tracheal suction catheter alone [54] and is associated with prolonged deoxygenation [55,56]. Limiting the frequency and duration of tracheal suctioning and limiting the use of saline instillation may prevent its adverse effects without affecting the duration of mechanical ventilation, length of stay in the ICU, mortality in the ICU, and incidence of pulmonary infection [45,57,58]. Thus, tracheal suctioning of intubated patients should be performed on an as-needed basis that is defined by the quantity of secretions obtained, not at prescribed, set intervals.
Closed (in-line), repeated-use endotracheal suction devices have become commonplace in ICUs. These devices eliminate the need for disconnection from mechanical ventilation and do not require single-hand sterile technique of open suction methods. Available data on the effect of these catheters on tracheal colonization are conflicting [59,60]. A single study has reported that in-line suction systems are associated with a reduction in the incidence of VAP [61], but most studies and a recent meta-analysis find no beneficial effect on nosocomial pneumonia [59,62-64]. Their cost-effectiveness, however, is questionable, with some studies demonstrating cost savings [65,66] and others suggesting higher costs associated with closed systems [62,63,67,68]. Despite the failure of closed endotracheal suctioning systems to reduce VAP or mortality, these devices may be preferable because of their efficiency and smaller number of suction-induced complications [65] and cost-effectiveness among patients requiring more than 4 days of mechanical ventilation [66]. Routine changes of these devices are not required [69].
A more recent development is the use of endotracheal tubes with a dorsal suction channel that opens immediately before the inflatable cuff in the subglottic area. Suction can be applied via this port continuously or intermittently for purposes of removing secretions from the subglottic space. A recent meta-analysis reported that these endotracheal tubes reduce early-onset VAP in patients expected to require more than 72 hours of mechanical ventilation. Early-onset VAP was defined as pneumonia occurring 5 to 7 days after intubation. Duration of mechanical ventilation, the length of ICU stay, and mortality were not different when intention-to-treat data were summarized [70]. However, subglottic suctioning does not alter oropharyngeal or tracheal bacterial loads [71], nor does it significantly reduce the duration of mechanical ventilation, length of ICU stay, or mortality [70,72-75]. Furthermore, continuous aspiration of subglottic secretions can cause severe tracheal mucosal damage [76]. Endotracheal tubes with a dorsal suction channel are significantly more expensive than standard endotracheal tubes, increase nursing workload, and therefore have the potential to increase ICU costs [77]. A case cost analysis model suggests a potential cost-saving associated with the use of subglottic suctioning primarily if these tubes decrease the length of the ICU stay [77], which has not been observed [72-75]. The use of endotracheal tubes that allow subglottic suctioning outside populations with a high incidence of early-onset VAP cannot be recommended at present.
Mucus-controlling agents
Distilled water, normal saline, hypertonic and hypotonic saline have long been used to 'loosen' thick airway secretions and promote airway hygiene. However, formed mucus does not readily incorporate topically applied water [78]. Increased sputum production and clearance attributed to bland aerosols, especially hypertonic saline, may be due to the irritant nature of the aerosol, which may cause bronchoconstriction rather than mucolysis [79-81].
N-Acetylcysteine (NAC) is a mucolytic agent that breaks disulfide bonds of mucus, reducing its viscosity and elasticity, and has anti-inflammatory properties in experimental models [79,82]. As a result of its mucolytic properties, many practioners advocate its use in the ICU for assistance in the clearance of airway secretions. Although there are limited data on the use of NAC in ICU patients, it is important for clinicians to recognize the potential deleterious effects of this practice. In vitro, NAC may antagonize aminoglycoside and β-lactam antibiotics [83,84]. Additionally, NAC at concentrations less than 10% inhibits the growth of Pseudomonas strains in vitro [84], potentially causing false-negative sputum cultures. Delivery via aerosol thins airway secretions but does not change pulmonary function or sputum volume in patients with stable chronic bronchitis [85,86]. Furthermore, aerosolized NAC can cause bronchoconstriction and inhibit ciliary function [87,88]. Concomitant administration of a bronchodilator partly ameliorates NAC-induced bronchospasm [89]. Gas exchange may worsen acutely after NAC administration, possibly because liquefied secretions gravitate into smaller airways [90]. Tracheal instillation of NAC through an endotracheal tube or bronchoscope may induce the rapid accumulation of liquefied secretions that must be suctioned immediately to prevent asphyxia [91]. Direct tracheal instillation of NAC is more effective than aerosol inhalation in the treatment of atelectasis caused by mucoid impaction [92,93]; however, it remains unclear whether undirected instillation of NAC results in delivery to areas of mucus accumulation. Thus, despite its widespread use, few data are available to support NAC as a mucolytic agent. Dornase alfa (recombinant human DNase) is used as a mucolytic in cystic fibrosis and other bronchiectatic conditions [94,95]. Case reports of its use in status asthmaticus [96], acute respiratory distress syndrome [97], and mechanically ventilated pediatric patients [94,98] have been published but no prospective efficacy studies are available to support its use in adult ICU patients for airway hygiene.
β2-Adrenergic agonists increase ciliary beat frequency in experimental models, raising the possibility that they may be useful for airway hygiene [99]. Salbutamol increases large-airway mucociliary clearance, both in stable patients with chronic obstructive pulmonary disease and in healthy subjects [100], although this may not be true for smaller airways [101]. There are no data from ICU patients. Thus, despite the simplicity and attractiveness of this approach, there are no data to support the use of inhaled β2-adrenergic agonists as adjuncts for airway hygiene in ICU patients.
Kinetic therapy
Immobility impairs cough and mucociliary clearance in patients receiving mechanical ventilation, thereby promoting retention of secretions [102,103]. Kinetic therapy with beds that intermittently or continuously rotate patients along their longitudinal axis by 40° or more have gained acceptance in the care of the critically ill patients [104].
A modest body of data regarding the effect of kinetic beds for continuous lateral rotation therapy (CLRT) to facilitate airway hygiene is available. Some of these studies found that CLRT reduced the incidence of pneumonia and decreased the length of stay in the ICU in heterogeneous groups of critically ill patients receiving mechanical ventilation [105-109]. Conversely, other studies detected no meaningful effect on measures of care in the ICU [110,111]. Differences in diagnostic criteria for nosocomial pneumonia and variable use of broad-spectrum antibiotics in treatment and control groups may be responsible for the diametrically opposed results of these studies. Importantly, three of the five studies demonstrating benefit from CLRT were supported by kinetic bed manufacturers [105-107]. Data from these studies support the use of CLRT in critically ill patients. The increased cost of CLRT is offset by reduced nosocomial pneumonia and antibiotic use and a decreased length of stay in the hospital and the ICU [106,108,109,112].
Chest physiotherapy
Chest physiotherapy, including gravity-assisted drainage, chest wall percussion, chest wall vibrations, and manual lung hyperinflation, aids in the re-expansion of atelectatic lung [113-115] and increases peak expiratory flow rates [116]. Chest physiotherapy treatment is as effective as early bronchoscopy in patients with acute atelectasis [114]. A single study examined the role of chest physiotherapy in patients at high risk for post-operative respiratory failure. Hall and colleagues randomized 301 spontaneously breathing patients at high risk for respiratory complications to receive incentive spirometry (IS) or IS plus chest physiotherapy after abdominal surgery [117]. The incidence of respiratory complications was not significantly different between two study groups. The inclusion of physiotherapy, however, required 30 minutes of staff time per patient. A recent meta-analysis examined the role of various chest physiotherapy techniques including IS, deep breathing exercise, chest physical therapy (cough, postural drainage, percussion/vibration, suction, and ambulation), intermittent positive-pressure breathing, and continuous positive airway pressure (CPAP) [118]. In patients who underwent abdominal surgery, any type of lung expansion technique was better than no intervention in the prevention of pulmonary complications. Although no particular intervention seemed superior, IS may require the least staff time, while CPAP may be particularly beneficial in patients who have limited ability to participate with other physiotherapy techniques [118]. In contrast, others reported poor adherence to an independent use of IS among patients recovering from surgery and superiority of encouragement by hospital personnel to the use of IS [119,120]. Current evidence does not support the use of IS in the prevention of complications after cardiac or abdominal surgery [121,122]. When nosocomial pneumonia is used as a specific endpoint, only one study showed the beneficial effect of physiotherapy [123]. Routine chest physiotherapy therefore cannot be recommended for prophylaxis against respiratory complications in spontaneously breathing patients.
There are mixed data about chest physiotherapy in mechanically ventilated patients. A single study of patients receiving mechanical ventilation for 48 hours or more showed a reduced incidence of VAP [124], whereas a second trial in trauma patients was unable to detect an effect on nosocomial pneumonia rates [125]. Furthermore, chest physiotherapy may cause cardiac arrhythmias, bronchospasm, and transient hypoxemia, and may prolong the duration of mechanical ventilation [126-128]. These complications, as well as increased staff use and cost, combined with a paucity of data regarding beneficial effects on the prevention of nosocomial pneumonia, should limit the use of chest physiotherapy to the ICU patients with acute atelectasis, exacerbations of bronchiectasis, and conditions that are characterized by excessive sputum production and impaired cough.
Limited data are available about flutter valves, cornet type devices, or intrapulmonary percussive ventilation in ICU patients. Cough assist devices, which generate a strong expiratory flow through the application of positive pressure followed by the application of negative pressure, have been shown to aid in the removal of secretions [129,130] and may avoid intubation in patients with neuromuscular disease [131]. However, the long-term benefit of these devices in other ICU populations is unclear. A small study of pneumatic high-frequency chest compression in long-term mechanically ventilated patients found it to be just as efficacious as percussion and postural drainage [132], and another study of patients immediately after cardiopulmonary bypass surgery reported reduced sternotomy pain with cough [133].
Bronchoscopy for atelectasis
Atelectasis occurs when alveolar closing volume rises above functional residual capacity and is rarely due to proximal airway obstruction by mucus. Critically ill patients have elevated closing volumes as a result of increased lung water, advanced age, and low functional residual capacity due to respiratory muscle weakness, sedation, and supine positioning [134]. Fiberoptic bronchoscopy is frequently requested and often performed for 'pulmonary toilet' or treatment of atelectasis in critically ill patients; however, its utility in improving gas exchange and preventing nosocomial pneumonia is limited. Only one randomized study compared the efficacy of fiberoptic bronchoscopy with chest physiotherapy for the treatment of acute atelectasis [114]. Thirtyone consecutive patients with acute lobar atelectasis were randomly assigned to receive immediate fiberoptic bronchoscopy with airway lavage followed by chest physiotherapy every 4 hours for 48 hours or to receive chest physiotherapy alone. Patients who were assigned to chest physiotherapy alone underwent 'delayed fiberoptic bronchoscopy' if their atelectasis persisted at 24 hours. Radiographic resolution of lung volume loss with bronchoscopy was similar to that after the first chest physiotherapy treatment in the control group (38% versus 37%). Although half of the patients who were randomized to chest physiotherapy alone underwent 'delayed' bronchoscopy, this study provided the impetus for teaching pulmonologists-in-training that there is rarely a role for bronchoscopy for atelectasis. In addition, bronchoscopy in patients with acute or incipient respiratory failure is not without adverse effects. Deterioration of gas exchange, barotrauma from elevated airway pressures, increased myocardial oxygen demand, and intracranial pressure have been reported [135-138]. Nevertheless, subgroup analysis [114], case series [137,139-143], and clinical experience support a role for bronchoscopy for some patients with atelectasis: specifically, critically ill patients with acute wholelung, lobar, or segmental atelectasis without air bronchograms [114] who are unable to maintain airway hygiene independently and remain symptomatic after 24 hours of aggressive chest physiotherapy (every 4 hours). Clinical experience indicates that atelectasis recurs frequently after bronchoscopy because the cause of compromised airway hygiene continues. Thus, failure to resolve the primary problem should not be an indication for repeated invasive intervention in the airways. There is no role for empiric 'cleaning of the airways' with a bronchoscope.
Conclusion
The rationale for airway hygiene is the prevention of pneumonia and respiratory failure. Current practice reflects clinical experience and expert opinion and not the results of controlled clinical trials. Several evidence-based recommendations can now be made about airway hygiene in critically ill patients. First, oropharyngeal decontamination with oral biocide rinses reduces the incidence of nosocomial pneumonia and should be part of the routine care of the mechanically ventilated patient. Careful monitoring of antibiotic resistance patterns after the initiation of routine biocide use is prudent at this time. Second, tracheal suctioning should be performed only on an 'as needed' basis. Closed (in-line) suction catheter devices should be used and routine changes of these devices are not necessary. Third, aerosolized mucus-controlling agents, such as NAC, and routine instillation of saline have no demonstrable effect on the clearance of airway secretions and should not be routinely used in critically ill patients. Fourth, kinetic therapy decreases the rate of nosocomial pneumonia, and may reduce the length of stay in the ICU and the hospital. The high cost of kinetic beds may be offset by a shortening of stay and a decreased use of systemic antibiotics. Fifth, chest physiotherapy should be limited to patients with acute atelectasis and/or excessive sputum production who are unable to conduct airway hygiene independently. Sixth, the therapeutic role of bronchoscopy in acute atelectasis is limited and transient, and should be reserved primarily for patients with acute atelectasis involving more than a single lung segment in the absence of air bronchograms who remain symptomatic after 24 hours of chest physiotherapy.
Abbreviations
CLRT = continuous lateral rotation therapy; CPAP = continuous positive airway pressure; ICU = intensive care unit; IS = incentive spirometry; NAC = N-acetylcysteine; SDD = selective digestive decontamination; VAP = ventilator-associated pneumonia.
Competing interests
The authors declare that they have no competing interests.
Authors' contributions
All authors participated in literature review and manuscript preparation.
See related letter by Wise et al., http://ccforum.com/content/12/3/419
References
- Kollef MH. The prevention of ventilator-associated pneumonia. New Engl J Med. 1999;340:627–634. doi: 10.1056/NEJM199902253400807. [DOI] [PubMed] [Google Scholar]
- Levine SA, Niederman MS. The impact of tracheal intubation on host defenses and risks for nosocomial pneumonia. Clin Chest Med. 1991;12:523–543. [PubMed] [Google Scholar]
- Weinmeister KD, Dal Nogare AR. Buccal cell carbohydrates are altered during critical illness. Am J Respir Crit Care Med. 1994;150:131–134. doi: 10.1164/ajrccm.150.1.8025738. [DOI] [PubMed] [Google Scholar]
- Woods DE, Straus DC, Johanson WG, Jr, Bass JA. Role of fibronectin in the prevention of adherence of Pseudomonas aeruginosa to buccal cells. J Infect Dis. 1981;143:784–790. doi: 10.1093/infdis/143.6.784. [DOI] [PubMed] [Google Scholar]
- Woods DE, Straus DC, Johanson WG, Brass JA. Role of salivary protease activity in adherence of gram-negative bacilli to mammalian buccal epithelial cells in vivo. J Clin Invest. 1981;68:1435–1440. doi: 10.1172/JCI110395. [DOI] [PMC free article] [PubMed] [Google Scholar]
- American Thoracic Society Hospital-acquired pneumonia in adults: diagnosis, assessment of severity, initial antimicrobial therapy, and preventive strategies. A consensus statement, November 1995. Am J Respir Crit Care Med. 1996;153:1711–1725. doi: 10.1164/ajrccm.153.5.8630626. [DOI] [PubMed] [Google Scholar]
- Garrouste-Orgeas M, Chevret S, Arlet G, Marie O, Rouveau M, Popoff N, Schlemmer B. Oropharyngeal or gastric colonization and nosocomial pneumonia in adult intensive care unit patients. Am J Respir Crit Care Med. 1997;156:1647–1655. doi: 10.1164/ajrccm.156.5.96-04076. [DOI] [PubMed] [Google Scholar]
- Bonten MJ, Gaillard CA, vanTiel FH, Smeets HG, vanderGeest S, Stobberingh EE. The stomach is not a source for colonization of the upper respiratory tract and pneumonia in ICU patients. Chest. 1994;105:878–884. doi: 10.1378/chest.105.3.878. [DOI] [PubMed] [Google Scholar]
- Cardenosa Cendrero JA, Sole-Violan J, Bordes Benitez A, Noguera Catalan J, Arroyo Fernandez J, Saavedra Santana P, Rodriguez de Castro F. Role of different routes of tracheal colonization in the development of pneumonia in patients receiving mechanical ventilation. Chest. 1999;116:462–470. doi: 10.1378/chest.116.2.462. [DOI] [PubMed] [Google Scholar]
- Bonten MJ, Bergmans DC, Ambergen AW, deLeeuw PW, van-derGeest S, Stobberingh EE, Gaillard CA. Risk factors for pneumonia, and colonization of respiratory tract and stomach in mechanically ventilated ICU patients. Am J Respir Crit Care Med. 1996;154:1339–1346. doi: 10.1164/ajrccm.154.5.8912745. [DOI] [PubMed] [Google Scholar]
- DeRiso AJ, Ladowski JS, Dillon TA, Justice JW, Peterson AC. Chlorhexidine gluconate 0.12% oral rinse reduces the incidence of total nosocomial respiratory infection and nonprophylactic systemic antibiotic use in patients undergoing heart surgery. Chest. 1996;109:1556–1561. doi: 10.1378/chest.109.6.1556. [DOI] [PubMed] [Google Scholar]
- Genuit T, Bochicchio G, Napolitano LM, McCarter RJ, Roghman MC. Prophylactic chlorhexidine oral rinse decreases ventilator-associated pneumonia in surgical ICU patients. Surg Infect (larch mt) 2001;2(1):5–18. doi: 10.1089/109629601750185316. [DOI] [PubMed] [Google Scholar]
- Houston S, Hougland P, Anderson JJ, LaRocco M, Kennedy V, Gentry LO. Effectiveness of 0.12% chlorhexidine gluconate oral rinse in reducing prevalence of nosocomial pneumonia in patients undergoing heart surgery. Am J Crit Care. 2002;11:567–570. [PubMed] [Google Scholar]
- Segers P, Speekenbrink RG, Ubbink DT, van Ogtrop ML, de Mol BA. Prevention of nosocomial infection in cardiac surgery by decontamination of the nasopharynx and oropharynx with chlorhexidine gluconate: a randomized controlled trial. JAMA. 2006;296:2460–2466. doi: 10.1001/jama.296.20.2460. [DOI] [PubMed] [Google Scholar]
- Bergmans DC, Bonten MJ, Gaillard CA, Paling JC, vanderGeest S, vanTiel FH, Beysens AJ, deLeeuw PW, Stobberingh EE. Prevention of ventilator-associated pneumonia by oral decontamination. A prospective, randomized, double-blind, placebo-controlled study. Am J Respir Crit Care Med. 2001;164:382–388. doi: 10.1164/ajrccm.164.3.2005003. [DOI] [PubMed] [Google Scholar]
- Pugin J, Auckenthaler R, Lew DP, Suter PM. Oropharyngeal decontamination decreases incidence of ventilator-associated pneumonia. A randomized, placebo-controlled, double-blind clinical trial. JAMA. 1991;265:2704–2710. doi: 10.1001/jama.265.20.2704. [DOI] [PubMed] [Google Scholar]
- Gastinne H, Wolff M, Delatour F, Faurisson F, Chevret S. A controlled trial in intensive care units of selective decontamination of the digestive tract with nonabsorbable antibiotics. New Engl J Med. 1992;326:594–599. doi: 10.1056/NEJM199202273260903. [DOI] [PubMed] [Google Scholar]
- Selective Decontamination of the Digestive Tract Trialists' Collaborative Group Meta-analysis of randomised controlled trials of selective decontamination of the digestive tract. BMJ. 1993;307:525–532. doi: 10.1136/bmj.307.6903.525. [DOI] [PMC free article] [PubMed] [Google Scholar]
- D'Amico R, Pifferi S, Leonetti C, Torri V, Tinazzi A, Liberati A. Effectiveness of antibiotic prophylaxis in critically ill adult patients: systematic review of randomised controlled trials. BMJ. 1998;316:1275–1285. doi: 10.1136/bmj.316.7140.1275. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Heyland DK, Cook DJ, Jaeschke R, Griffith L, Lee HN, Guyatt GH. Selective decontamination of the digestive tract. An overview. Chest. 1994;105:1221–1229. doi: 10.1378/chest.105.4.1221. [DOI] [PubMed] [Google Scholar]
- Hurley JC. Prophylaxis with enteral antibiotics in ventilated patients: selective decontamination or selective cross-infection? Antimicrob Agents Chemother. 1995;39:941–947. doi: 10.1128/aac.39.4.941. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kollef MH. The role of selective digestive tract decontamination on mortality and respiratory tract infections. A meta-analysis. Chest. 1994;105:1101–1108. doi: 10.1378/chest.105.4.1101. [DOI] [PubMed] [Google Scholar]
- Liberati A, D'Amico R, Pifferi , Torri V, Brazzi L. Antibiotic prophylaxis to reduce respiratory tract infections and mortality in adults receiving intensive care. Cochrane Database Syst Rev. 2004;(1):CD000022. doi: 10.1002/14651858.CD000022.pub2. [DOI] [PubMed] [Google Scholar]
- Nathens AB, Marshall JC. Selective decontamination of the digestive tract in surgical patients: a systematic review of the evidence. Arch Surg. 1999;134:170–176. doi: 10.1001/archsurg.134.2.170. [DOI] [PubMed] [Google Scholar]
- Safdar N, Said A, Lucey MR. The role of selective digestive decontamination for reducing infection in patients undergoing liver transplantation: a systematic review and meta-analysis. Liver Transpl. 2004;10:817–827. doi: 10.1002/lt.20108. [DOI] [PubMed] [Google Scholar]
- Sun X, Wagner DP, Knaus WA. Does selective decontamination of the digestive tract reduce mortality for severely ill patients? Crit Care Med. 1996;24:753–755. doi: 10.1097/00003246-199605000-00005. [DOI] [PubMed] [Google Scholar]
- van Saene HK, Stoutenbeek CP, Hart CA. Selective decontamination of the digestive tract (SDD) in intensive care patients: a critical evaluation of the clinical, bacteriological and epidemiological benefits. J Hosp Infect. 1991;18:261–277. doi: 10.1016/0195-6701(91)90184-A. [DOI] [PubMed] [Google Scholar]
- Vandenbroucke-Grauls CM, Vandenbroucke JP. Effect of selective decontamination of the digestive tract on respiratory tract infections and mortality in the intensive care unit. Lancet. 1991;338:859–862. doi: 10.1016/0140-6736(91)91510-2. [DOI] [PubMed] [Google Scholar]
- vanNieuwenhoven CA, Buskens E, Bergmans DC, vanTiel FH, Ramsay G, Bonten MJ. Oral decontamination is cost-saving in the prevention of ventilator-associated pneumonia in intensive care units. Crit Care Med. 2004;32:126–130. doi: 10.1097/01.CCM.0000104111.61317.4B. [DOI] [PubMed] [Google Scholar]
- Krueger WA, Lenhart FP, Neeser G, Ruckdeschel G, Schreck-hase H, Eissner HJ, Forst H, Eckart J, Peter K, Unertl KE. Influence of combined intravenous and topical antibiotic prophylaxis on the incidence of infections, organ dysfunctions, and mortality in critically ill surgical patients: a prospective, stratified, randomized, double-blind, placebo-controlled clinical trial. Am J Respir Crit Care Med. 2002;166:1029–1037. doi: 10.1164/rccm.2105141. [DOI] [PubMed] [Google Scholar]
- Cerda E, Abella A, de la Cal MA, Lorente JA, Garcia-Hierro P, van Saene HK, Alia I, Aranguren A. Enteral vancomycin controls methicillin-resistant Staphylococcus aureus endemicity in an intensive care burn unit: a 9-year prospective study. Ann Surg. 2007;245:397–407. doi: 10.1097/01.sla.0000250418.14359.31. [DOI] [PMC free article] [PubMed] [Google Scholar]
- de la Cal MA, Cerda E, van Saene HK, Garcia-Hierro P, Negro E, Parra ML, Arias S, Ballesteros D. Effectiveness and safety of enteral vancomycin to control endemicity of methicillin-resistant Staphylococcus aureus in a medical/surgical intensive care unit. J Hosp Infect. 2004;56:175–183. doi: 10.1016/j.jhin.2003.09.021. [DOI] [PubMed] [Google Scholar]
- Kollef MH. Selective digestive decontamination should not be routinely employed. Chest. 2003;123:464S–468S. doi: 10.1378/chest.123.5_suppl.464S. [DOI] [PubMed] [Google Scholar]
- Tablan OC, Anderson LJ, Arden NH, Breiman RF, Butler JC, McNeil MM. Guideline for prevention of nosocomial pneumonia. The Hospital Infection Control Practices Advisory Committee, Centers for Disease Control and Prevention. Infect Control Hosp Epidemiol. 1994;15:587–627. doi: 10.1086/646989. [DOI] [PubMed] [Google Scholar]
- Kollef M, Pittet D, Sánchez García M, Chastre J, Fagon JY, Bonten M, Hyzy R, Fleming TR, Fuchs H, Bellm L, Mercat A, Mañez R, Martínez A, Eggimann P, Daguerre M, Luyt CE, Prevention of Pneumonia Study (POPS-1) Trial Group A randomized double-blind trial of iseganan in prevention of ventilator-associated pneumonia. Am J Respir Crit Care Med. 2006;173:91–97. doi: 10.1164/rccm.200504-656OC. [DOI] [PubMed] [Google Scholar]
- Higgins CS, Murtough SM, Williamson E, Hiom SJ, Payne DJ, Russell AD, Walsh TR. Resistance to antibiotics and biocides among non-fermenting Gram-negative bacteria. Clin Microbiol Infect. 2001;7:308–315. doi: 10.1046/j.1198-743x.2001.00253.x. [DOI] [PubMed] [Google Scholar]
- Russell AD. Biocide use and antibiotic resistance: the relevance of laboratory findings to clinical and environmental situations. Lancet Infect Dis. 2003;3:794–803. doi: 10.1016/S1473-3099(03)00833-8. [DOI] [PubMed] [Google Scholar]
- Keller C, Brimacombe J. Bronchial mucus transport velocity in paralyzed anesthetized patients: a comparison of the laryngeal mask airway and cuffed tracheal tube. Anesth Analg. 1998;86:1280–1282. doi: 10.1097/00000539-199806000-00028. [DOI] [PubMed] [Google Scholar]
- Konrad F, Schiener R, Marx T, Georgieff M. Ultrastructure and mucociliary transport of bronchial respiratory epithelium in intubated patients. Intensive Care Med. 1995;21:482–489. doi: 10.1007/BF01706201. [DOI] [PubMed] [Google Scholar]
- Sackner MA, Hirsch JA, Epstein S, Rywlin AM. Effect of oxygen in graded concentrations upon tracheal mucous velocity. A study in anesthetized dogs. Chest. 1976;69:164–167. doi: 10.1378/chest.69.2.164. [DOI] [PubMed] [Google Scholar]
- Hornick DB, Allen BL, Horn MA, Clegg S. Adherence to respiratory epithelia by recombinant Escherichia coli expressing Klebsiella pneumoniae type 3 fimbrial gene products. Infect Immun. 1992;60:1577–1588. doi: 10.1128/iai.60.4.1577-1588.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Brodsky L, Reidy M, Stanievich JF. The effects of suctioning techniques on the distal tracheal mucosa in intubated low birth weight infants. Int J Pediatr Otorhinolaryngol. 1987;14:1–14. doi: 10.1016/0165-5876(87)90044-9. [DOI] [PubMed] [Google Scholar]
- Adlkofer RM, Powaser MM. The effect of endotracheal suctioning on arterial blood gases in patients after cardiac surgery. Heart Lung. 1978;7:1011–1014. [PubMed] [Google Scholar]
- Brown SE, Stansbury DW, Merrill EJ, Linden GS, Light RW. Prevention of suctioning-related arterial oxygen desaturation. Comparison of off-ventilator and on-ventilator suctioning. Chest. 1983;83:621–627. doi: 10.1378/chest.83.4.621. [DOI] [PubMed] [Google Scholar]
- Van de Leur JP, Zwaveling JH, Loef BG, Van der Schans CP. Endotracheal suctioning versus minimally invasive airway suctioning in intubated patients: a prospective randomised controlled trial. Intensive Care Med. 2003;29:426–432. doi: 10.1007/s00134-003-1639-9. [DOI] [PubMed] [Google Scholar]
- Maggiore SM, Lellouche F, Pigeot J, Taille S, Deye N, Durrmeyer X, Richard JC, Mancebo J, Lemaire F, Brochard L. Prevention of endotracheal suctioning-induced alveolar derecruitment in acute lung injury. Am J Respir Crit Care Med. 2003;167:1215–1224. doi: 10.1164/rccm.200203-195OC. [DOI] [PubMed] [Google Scholar]
- Shim C, Fine N, Fernandez R, Williams MH., Jr Cardiac arrhythmias resulting from tracheal suctioning. Ann Intern Med. 1969;71:1149–1153. doi: 10.7326/0003-4819-71-6-1149. [DOI] [PubMed] [Google Scholar]
- Piepmeier JM, Lehmann KB, Lane JG. Cardiovascular instability following acute cervical spinal cord trauma. Cent Nerv Syst Trauma. 1985;2:153–160. doi: 10.1089/cns.1985.2.153. [DOI] [PubMed] [Google Scholar]
- Choi JS, Jones AY. Effects of manual hyperinflation and suctioning in respiratory mechanics in mechanically ventilated patients with ventilator-associated pneumonia. Aust J Physiother. 2005;51:25–30. doi: 10.1016/s0004-9514(05)70050-7. [DOI] [PubMed] [Google Scholar]
- Mancinelli-Van Atta J, Beck SL. Preventing hypoxemia and hemodynamic compromise related to endotracheal suctioning. Am J Crit Care. 1992;1:62–79. [PubMed] [Google Scholar]
- Stiller K. Physiotherapy in intensive care: towards an evidence-based practice. Chest. 2000;118:1801–1813. doi: 10.1378/chest.118.6.1801. [DOI] [PubMed] [Google Scholar]
- Ackerman MH. The effect of saline lavage prior to suctioning. Am J Crit Care. 1993;2:326–330. [PubMed] [Google Scholar]
- Ackerman MH, Mick DJ. Instillation of normal saline before suctioning in patients with pulmonary infections: a prospective randomized controlled trial. Am J Crit Care. 1998;7:261–266. [PubMed] [Google Scholar]
- Hagler DA, Traver GA. Endotracheal saline and suction catheters: sources of lower airway contamination. Am J Crit Care. 1994;3:444–447. [PubMed] [Google Scholar]
- Akgul S, Akyolcu N. Effects of normal saline on endotracheal suctioning. J Clin Nurs. 2002;11:826–830. doi: 10.1046/j.1365-2702.2002.00655.x. [DOI] [PubMed] [Google Scholar]
- Kinloch D. Instillation of normal saline during endotracheal suctioning: effects on mixed venous oxygen saturation. Am J Crit Care. 1999;8:231–240. [PubMed] [Google Scholar]
- Cordero L, Sananes M, Ayers LW. A comparison of two airway suctioning frequencies in mechanically ventilated, very-low-birthweight infants. Respir Care. 2001;46:783–788. [PubMed] [Google Scholar]
- Wood CJ. Can nurses safely assess the need for endotracheal suction in short-term ventilated patients, instead of using routine techniques? Intensive Crit Care Nurs. 1998;14:170–178. doi: 10.1016/S0964-3397(98)80486-2. [DOI] [PubMed] [Google Scholar]
- Deppe SA, Kelly JW, Thoi LL, Chudy JH, Longfield RN, Ducey JP, Truwit CL, Antopol MR. Incidence of colonization, nosocomial pneumonia, and mortality in critically ill patients using a Trach Care closed-suction system versus an open-suction system: prospective, randomized study. Crit Care Med. 1990;18:1389–1393. doi: 10.1097/00003246-199012000-00016. [DOI] [PubMed] [Google Scholar]
- Rabitsch W, Kostler WJ, Fiebiger W, Dielacher C, Losert H, Sherif C, Staudinger T, Seper E, Koller W, Daxbock F, Schuster E, Knobl P, Burgmann H, Frass M. Closed suctioning system reduces cross-contamination between bronchial system and gastric juices. Anesth Analg. 2004;99:886–892. doi: 10.1213/01.ANE.0000143353.85428.39. [DOI] [PubMed] [Google Scholar]
- Combes P, Fauvage B, Oleyer C. Nosocomial pneumonia in mechanically ventilated patients, a prospective randomised evaluation of the Stericath closed suctioning system. Intensive Care Med. 2000;26:878–882. doi: 10.1007/s001340051276. [DOI] [PubMed] [Google Scholar]
- Jongerden IP, Rovers MM, Grypdonck MH, Bonten MJ. Open and closed endotracheal suction systems in mechanically ventilated intensive care patients: a meta-analysis. Crit Care Med. 2007;35:260–270. doi: 10.1097/01.CCM.0000251126.45980.E8. [DOI] [PubMed] [Google Scholar]
- Lorente L, Lecuona M, Martin MM, Garcia C, Mora ML, Sierra A. Ventilator-associated pneumonia using a closed versus an open tracheal suction system. Crit Care Med. 2005;33:115–119. doi: 10.1097/01.CCM.0000150267.40396.90. [DOI] [PubMed] [Google Scholar]
- Zeitoun SS, de Barros AL, Diccini S. A prospective, randomized study of ventilator-associated pneumonia in patients using a closed vs. open suction system. J Clin Nurs. 2003;12:484–489. doi: 10.1046/j.1365-2702.2003.00749.x. [DOI] [PubMed] [Google Scholar]
- Johnson KL, Kearney PA, Johnson SB, Niblett JB, MacMillan NL, McClain RE. Closed versus open endotracheal suctioning: costs and physiologic consequences. Crit Care Med. 1994;22:658–666. doi: 10.1097/00003246-199404000-00023. [DOI] [PubMed] [Google Scholar]
- Lorente L, Lecuona M, Jimenez A, Mora ML, Sierra A. Tracheal suction by closed system without daily change versus open system. Intensive Care Med. 2006;32:538–544. doi: 10.1007/s00134-005-0057-6. [DOI] [PubMed] [Google Scholar]
- Adams DH, Hughes M, Elliott TS. Microbial colonization of closed-system suction catheters used in liver transplant patients. Intensive Crit Care Nurs. 1997;13:72–76. doi: 10.1016/S0964-3397(97)80135-8. [DOI] [PubMed] [Google Scholar]
- Zielmann S, Grote R, Sydow M, Radke J, Burchardi H. Endotracheal suctioning using a 24-hour continuous system. Can costs and waste products be reduced? Anaesthesist. 1992;41:494–498. [PubMed] [Google Scholar]
- Kollef MH, Prentice D, Shapiro SD, Fraser VJ, Silver P, Trovillion E, Weilitz P, von Harz B, St John R. Mechanical ventilation with or without daily changes of in-line suction catheters. Am J Respir Crit Care Med. 1997;156:466–472. doi: 10.1164/ajrccm.156.2.9612083. [DOI] [PubMed] [Google Scholar]
- Dezfulian C, Shojania K, Collard HR, Kim HM, Matthay MA, Saint S. Subglottic secretion drainage for preventing ventilator-associated pneumonia: a meta-analysis. Am J Med. 2005;118:11–18. doi: 10.1016/j.amjmed.2004.07.051. [DOI] [PubMed] [Google Scholar]
- Girou E, Buu-Hoi A, Stephan F, Novara A, Gutmann L, Safar M, Fagon JY. Airway colonisation in long-term mechanically ventilated patients. Effect of semi-recumbent position and continuous subglottic suctioning. Intensive Care Med. 2004;30:225–233. doi: 10.1007/s00134-003-2077-4. [DOI] [PubMed] [Google Scholar]
- Kollef MH, Skubas NJ, Sundt TM. A randomized clinical trial of continuous aspiration of subglottic secretions in cardiac surgery patients. Chest. 1999;116:1339–1346. doi: 10.1378/chest.116.5.1339. [DOI] [PubMed] [Google Scholar]
- Mahul P, Auboyer C, Jospe R, Ros A, Guerin C, el Khouri Z, Galliez M, Dumont A, Gaudin O. Prevention of nosocomial pneumonia in intubated patients: respective role of mechanical subglottic secretions drainage and stress ulcer prophylaxis. Intensive Care Med. 1992;18:20–25. doi: 10.1007/BF01706421. [DOI] [PubMed] [Google Scholar]
- Smulders K, vanderHoeven H, Weers-Pothoff I, Vandenbroucke-Grauls C. A randomized clinical trial of intermittent subglottic secretion drainage in patients receiving mechanical ventilation. Chest. 2002;121:858–862. doi: 10.1378/chest.121.3.858. [DOI] [PubMed] [Google Scholar]
- Valles J, Artigas A, Rello J, Bonsoms N, Fontanals D, Blanch L, Fernandez R, Baigorri F. Continuous aspiration of subglottic secretions in preventing ventilator-associated pneumonia. Ann Intern Med. 1995;122:179–186. doi: 10.7326/0003-4819-122-3-199502010-00004. [DOI] [PubMed] [Google Scholar]
- Berra L, Panigada M, De Marchi L, Greco G, Z-Xi Y, Baccarelli A, Pohlmann J, Costello KF, Appleton J, Mahar R, Lewandowski R, Ravitz L, Kolobow T. New approaches for the prevention of airway infection in ventilated patients. Lessons learned from laboratory animal studies at the National Institutes of Health. Minerva Anestesiol. 2003;69:342–347. [PubMed] [Google Scholar]
- Shorr AF, O'Malley PG. Continuous subglottic suctioning for the prevention of ventilator-associated pneumonia. Potential economic implications. Chest. 2001;119:228–235. doi: 10.1378/chest.119.1.228. [DOI] [PubMed] [Google Scholar]
- Rau JL. Mucus-controlling agents. In: Rau JL, editor. Respiratory Care Pharmacology. St Louis: Mosby; 1994. pp. 195–222. [Google Scholar]
- Ackerman MH. The use of bolus normal saline instillations in artifical airways: is it useful or necessary? Heart Lung. 1985;14:505–506. [PubMed] [Google Scholar]
- Bostick J, Wendelgass ST. Normal saline instillation as part of the suctioning procedure: effects on PaO2 and amount of secretions. Heart Lung. 1987;16:532–537. [PubMed] [Google Scholar]
- Smith CM, Anderson SD. A comparison between the airway response to isocapnic hyperventilation and hypertonic saline in subjects with asthma. Eur Respir J. 1989;2:36–43. [PubMed] [Google Scholar]
- Sheffner AL, Medler EM, Jacobs LW, Sarett HP. The in vitro reduction in viscosity of human tracheobronchial secretions by acetylcysteine. Am Rev Respir Dis. 1964;90:721–729. doi: 10.1164/arrd.1964.90.5.721. [DOI] [PubMed] [Google Scholar]
- Lawson D, Saggers BA. N.A.C. and antibiotics in cystic fibrosis. BMJ. 1965;5430:317. doi: 10.1136/bmj.1.5430.317. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Parry MF, Neu HC. Effect of N-acetylcysteine on antibiotic activity and bacterial growth in vitro. J Clin Microbiol. 1977;5:58–61. doi: 10.1128/jcm.5.1.58-61.1977. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Barton AD. Aerosolized detergents and mucolytic agents in the treatment of stable chronic obstructive pulmonary disease. Am Rev Respir Dis. 1974;110:104–110. doi: 10.1164/arrd.1974.110.6P2.104. [DOI] [PubMed] [Google Scholar]
- Dueholm M, Nielsen C, Thorshauge H, Evald T, Hansen NC, Madsen HD, Maltbek N. N-acetylcysteine by metered dose inhaler in the treatment of chronic bronchitis: a multi-centre study. Respir Med. 1992;86:89–92. doi: 10.1016/S0954-6111(06)80220-9. [DOI] [PubMed] [Google Scholar]
- Dorsch W, Auch E, Powerlowicz P. Adverse effects of acetylcysteine on human and guinea pig bronchial asthma in vivo and on human fibroblasts and leukocytes in vitro. Int Arch Allergy Appl Immunol. 1987;82:33–39. doi: 10.1159/000234286. [DOI] [PubMed] [Google Scholar]
- Mant TG, Tempowski JH, Volans GN, Talbot JC. Adverse reactions to acetylcysteine and effects of overdose. Br Med J (Clin Res Ed) 1984;289(6439):217–9. doi: 10.1136/bmj.289.6439.217. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kory RC, Hirsch SR, Giraldo J. Nebulization of N-acetylcysteine combined with a bronchodilator in patients with chronic bronchitis. A controlled study. Dis Chest. 1968;54:504–509. doi: 10.1378/chest.54.6.504. [DOI] [PubMed] [Google Scholar]
- Lourenco RV, Cotromanes E. Clinical aerosols II. Therapeutic aerosols. Arch Intern Med. 1982;142:2299–2308. doi: 10.1001/archinte.142.13.2299. [DOI] [PubMed] [Google Scholar]
- Lieberman J. The appropriate use of mucolytic agents. Am J Med. 1970;49:1–4. doi: 10.1016/S0002-9343(70)80107-3. [DOI] [PubMed] [Google Scholar]
- Irwin RS, Thomas HD. Mucoid inpaction of the bronchus. Diagnosis and treatment. Am Rev Respir Dis. 1973;108:955–959. doi: 10.1164/arrd.1973.108.4.955. [DOI] [PubMed] [Google Scholar]
- Urschel HC, Jr, Paulson DL, Shaw RR. Mucoid impaction of the bronchi. Ann Thorac Surg. 1966;2:1–16. doi: 10.1016/s0003-4975(10)66532-0. [DOI] [PubMed] [Google Scholar]
- Boogaard R, de Jongste JC, Merkus PJ. Pharmacotherapy of impaired mucociliary clearance in non-CF pediatric lung disease. A review of the literature. Pediatr Pulmonol. 2007;42:989–1001. doi: 10.1002/ppul.20693. [DOI] [PubMed] [Google Scholar]
- Flume PA, O'Sullivan BP, Robinson KA, Goss CH, Mogayzel PJ, Jr, Willey-Courand DB, Bujan J, Finder J, Lester M, Quittell L, Rosenblatt R, Vender RL, Hazle L, Sabadosa K, Marshall B, Cystic Fibrosis Foundation, Pulmonary Therapies Committee Cystic fibrosis pulmonary guidelines: chronic medications for maintenance of lung health. Am J Respir Crit Care Med. 2007;176:957–969. doi: 10.1164/rccm.200705-664OC. [DOI] [PubMed] [Google Scholar]
- Greally P. Human recombinant DNase for mucus plugging in status asthmaticus. Lancet. 1995;346:1423–1424. doi: 10.1016/S0140-6736(95)92436-1. [DOI] [PubMed] [Google Scholar]
- Morris C, Mullan B. Use of dornase alfa in the management of ARDS. Anaesthesia. 2004;59:1249. doi: 10.1111/j.1365-2044.2004.04018.x. [DOI] [PubMed] [Google Scholar]
- Riethmueller J, Borth-Bruhns T, Kumpf M, Vonthein R, Wiskirchen J, Stern M, Hofbeck M, Baden W. Recombinant human deoxyribonuclease shortens ventilation time in young, mechanically ventilated children. Pediatr Pulmonol. 2006;41(1):61–6. doi: 10.1002/ppul.20298. [DOI] [PubMed] [Google Scholar]
- Frohock JI, Wijkstrom-Frei C, Salathe M. Effects of albuterol enantiomers on ciliary beat frequency in ovine tracheal epithelial cells. J Appl Physiol. 2002;92:2396–2402. doi: 10.1152/japplphysiol.00755.2001. [DOI] [PubMed] [Google Scholar]
- Lafortuna CL, Fazio F. Acute effect of inhaled salbutamol on mucociliary clearance in health and chronic bronchitis. Respiration. 1984;45:111–123. doi: 10.1159/000194607. [DOI] [PubMed] [Google Scholar]
- Svartengren K, Philipson K, Svartengren M, Camner P. Effect of adrenergic stimulation on clearance from small ciliated airways in healthy subjects. Exp Lung Res. 1998;24:149–158. doi: 10.3109/01902149809099579. [DOI] [PubMed] [Google Scholar]
- Beck-Sague C, Banerjee S, Jarvis WR. Infectious diseases and mortality among US nursing home residents. Am J Public Health. 1993;83:1739–1742. doi: 10.2105/ajph.83.12.1739. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kaneko K, Milic-Emili J, Dolovich MB, Dawson A, Bates DV. Regional distribution of ventilation and perfusion as a function of body position. J Appl Physiol. 1966;21:767–777. doi: 10.1152/jappl.1966.21.3.767. [DOI] [PubMed] [Google Scholar]
- Raoof S, Chowdhrey N, Raoof S, Feuerman M, King A, Sriraman R, Khan FA. Effect of combined kinetic therapy and percussion therapy on the resolution of atelectasis in critically ill patients. Chest. 1999;115:1658–1666. doi: 10.1378/chest.115.6.1658. [DOI] [PubMed] [Google Scholar]
- deBoisblanc BP, Castro M, Everret B, Grender J, Walker CD, Summer WR. Effect of air-supported, continuous, postural oscillation on the risk of early ICU pneumonia in nontraumatic critical illness. Chest. 1993;103:1543–1547. doi: 10.1378/chest.103.5.1543. [DOI] [PubMed] [Google Scholar]
- Fink MP, Helsmoortel CM, Stein KL, Lee PC, Cohn SM. The efficacy of an oscillating bed in the prevention of lower respiratory tract infection in critically ill victims of blunt trauma. A prospective study. Chest. 1990;97:132–137. doi: 10.1378/chest.97.1.132. [DOI] [PubMed] [Google Scholar]
- Kirschenbaum L, Azzi E, Sfeir T, Tietjen P, Astiz M. Effect of continuous lateral rotational therapy on the prevalence of ventilator-associated pneumonia in patients requiring long-term ventilatory care. Crit Care Med. 2002;30:1983–1986. doi: 10.1097/00003246-200209000-00006. [DOI] [PubMed] [Google Scholar]
- Summer WR, Curry P, Haponik EF, Nelson S, Elston R. Continuous mechanical turning of intensive care unit patients shortens length of stay in some diagnostic-related groups. J Crit Care. 1989;4:45–53. doi: 10.1016/0883-9441(89)90091-9. [DOI] [Google Scholar]
- Whiteman K, Nachtmann L, Kramer D, Sereika S, Bierman M. Effects of continuous lateral rotation therapy on pulmonary complications in liver transplant patients. Am J Crit Care. 1995;4:133–139. [PubMed] [Google Scholar]
- Gentilello L, Thompson DA, Tonnesen AS, Hernandez D, Kapadia AS, Allen SJ, Houtchens BA, Miner ME. Effect of a rotating bed on the incidence of pulmonary complications in critically ill patients. Crit Care Med. 1988;16:783–786. doi: 10.1097/00003246-198808000-00010. [DOI] [PubMed] [Google Scholar]
- Traver GA, Tyler ML, Hudson LD, Sherrill DL, Quan SF. Continuous oscillation: outcome in critically ill patients. J Crit Care. 1995;10:97–103. doi: 10.1016/0883-9441(95)90000-4. [DOI] [PubMed] [Google Scholar]
- Kelley RE, Bell LK, Mason RL. Cost analysis of kinetic therapy in the prevention of complications of stroke. South Med J. 1990;83:433–434. doi: 10.1097/00007611-199004000-00018. [DOI] [PubMed] [Google Scholar]
- Mackenzie CF, Shin B. Cardiorespiratory function before and after chest physiotherapy in mechanically ventilated patients with post-traumatic respiratory failure. Crit Care Med. 1985;13:483–486. doi: 10.1097/00003246-198506000-00009. [DOI] [PubMed] [Google Scholar]
- Marini JJ, Pierson DJ, Hudson LD. Acute lobar atelectasis: a prospective comparison of fiberoptic bronchoscopy and respiratory therapy. Am Rev Respir Dis. 1979;119:971–978. doi: 10.1164/arrd.1979.119.6.971. [DOI] [PubMed] [Google Scholar]
- Stiller K, Geake T, Taylor J, Grant R, Hall B. Acute lobar atelectasis. A comparison of two chest physiotherapy regimens. Chest. 1990;98:1336–1340. doi: 10.1378/chest.98.6.1336. [DOI] [PubMed] [Google Scholar]
- MacLean D, Drummond G, Macpherson C, McLaren G, Prescott R. Maximum expiratory airflow during chest physiotherapy on ventilated patients before and after the application of an abdominal binder. Intensive Care Med. 1989;15:396–399. doi: 10.1007/BF00261500. [DOI] [PubMed] [Google Scholar]
- Hall JC, Tarala RA, Tapper J, Hall JL. Prevention of respiratory complications after abdominal surgery: a randomised clinical trial. BMJ. 1996;312:148–152. doi: 10.1136/bmj.312.7024.148. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lawrence VA, Cornell JE, Smetana GW. Strategies to reduce postoperative pulmonary complications after noncardiothoracic surgery: systematic review for the American College of Physicians. Ann Intern Med. 2006;144:596–608. doi: 10.7326/0003-4819-144-8-200604180-00011. [DOI] [PubMed] [Google Scholar]
- Lederer DH, Van de Water JM, Indech RB. Which deep breathing device should the postoperative patient use? Chest. 1980;77:610–613. doi: 10.1378/chest.77.5.610. [DOI] [PubMed] [Google Scholar]
- Van De Water JM. Preoperative and postoperative techniques in the prevention of pulmonary complications. Surg Clin North Am. 1980;60:1339–1348. doi: 10.1016/s0039-6109(16)42282-6. [DOI] [PubMed] [Google Scholar]
- Overend TJ, Anderson CM, Lucy SD, Bhatia C, Jonsson BI, Timmermans C. The effect of incentive spirometry on postoperative pulmonary complications: a systematic review. Chest. 2001;120:971–978. doi: 10.1378/chest.120.3.971. [DOI] [PubMed] [Google Scholar]
- Pasquina P, Tramer MR, Granier JM, Walder B. Respiratory physiotherapy to prevent pulmonary complications after abdominal surgery: a systematic review. Chest. 2006;130:1887–1899. doi: 10.1378/chest.130.6.1887. [DOI] [PubMed] [Google Scholar]
- Morran CG, Finlay IG, Mathieson M, McKay AJ, Wilson N, McArdle CS. Randomized controlled trial of physiotherapy for postoperative pulmonary complications. Br J Anaesth. 1983;55:1113–1117. doi: 10.1093/bja/55.11.1113. [DOI] [PubMed] [Google Scholar]
- Ntoumenopoulos G, J PJ, M> M, Cade JF. Chest physiotherapy for the prevention of ventilator-associated pneumonia. Intensive Care Med. 2002;28:850–856. doi: 10.1007/s00134-002-1342-2. [DOI] [PubMed] [Google Scholar]
- Ntoumenopoulos G, Gild A, Cooper DJ. The effect of manual lung hyperinflation and postural drainage on pulmonary complications in mechanically ventilated trauma patients. Anaesth Intensive Care. 1998;26:492–496. doi: 10.1177/0310057X9802600503. [DOI] [PubMed] [Google Scholar]
- Hammon WE, Connors AF, McCaffree DR. Cardiac arrhythmias during postural drainage and chest percussion of critically ill patients. Chest. 1992;102:1836–1841. doi: 10.1378/chest.102.6.1836. [DOI] [PubMed] [Google Scholar]
- Selsby DS. Chest physiotherapy. BMJ. 1989;298:541–542. doi: 10.1136/bmj.298.6673.541. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Templeton M, Palazzo MG. Chest physiotherapy prolongs duration of ventilation in the critically ill ventilated for more than 48 hours. Intensive Care Med. 2007;33:1938–1945. doi: 10.1007/s00134-007-0762-4. [DOI] [PubMed] [Google Scholar]
- Kang SW, Kang YS, Moon JH, Yoo TW. Assisted cough and pulmonary compliance in patients with Duchenne muscular dystrophy. Yonsei Med J. 2005;46:233–238. doi: 10.3349/ymj.2005.46.2.233. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Newth CJ, Amsler B, Anderson GP, Morley J. The effects of varying inflation and deflation pressures on the maximal expiratory deflation flow-volume relationship in anesthetized rhesus monkeys. Am Rev Respir Dis. 1991;144:807–813. doi: 10.1164/ajrccm/144.4.807. [DOI] [PubMed] [Google Scholar]
- Marchant WA, Fox R. Postoperative use of a cough-assist device in avoiding prolonged intubation. Br J Anaesth. 2002;89:644–647. doi: 10.1093/bja/aef227. [DOI] [PubMed] [Google Scholar]
- Whitman J, VanBeusekom R, Olson S, Worm M, Indihar F. Preliminary evaluation of high-frequency chest compression for secretion clearance in mechanically ventilated patients. Respir Care. 1993;38:1081–1087. [PubMed] [Google Scholar]
- Laurikka JO, Toivio I, Tarkka MR. Effects of a novel pneumatic vest on postoperative pain and lung function after coronary artery bypass grafting. Scand Cardiovasc J. 1998;32:141–144. doi: 10.1080/14017439850140094. [DOI] [PubMed] [Google Scholar]
- Tobin M. Principles and Practices of Mechanical Ventilation. 2. New York: Mc-Graw Hill; 2006. [Google Scholar]
- Kerwin AJ, Croce MA, Timmons SD, Maxwell RA, Malhotra AK, Fabian TC. Effects of fiberoptic bronchoscopy on intracranial pressure in patients with brain injury: a prospective clinical study. J Trauma. 2000;48:878–882. doi: 10.1097/00005373-200005000-00011. [DOI] [PubMed] [Google Scholar]
- Lindholm CE, Ollman B, Snyder JV, Millen EG, Grenvik A. Cardiorespiratory effects of flexible fiberoptic bronchoscopy in critically ill patients. Chest. 1978;74:362–368. doi: 10.1378/chest.74.4.362. [DOI] [PubMed] [Google Scholar]
- Snow N, Lucas AE. Bronchoscopy in the critically ill surgical patient. Am Surg. 1984;50:441–445. [PubMed] [Google Scholar]
- Trouillet JL, Guiguet M, Gibert C, Fagon JY, Dreyfuss D, Blanchet F, Chastre J. Fiberoptic bronchoscopy in ventilated patients. Evaluation of cardiopulmonary risk under midazolam sedation. Chest. 1990;97:927–933. doi: 10.1378/chest.97.4.927. [DOI] [PubMed] [Google Scholar]
- Kreider ME, Lipson DA. Bronchoscopy for atelectasis in the ICU: a case report and review of the literature. Chest. 2003;124:344–350. doi: 10.1378/chest.124.1.344. [DOI] [PubMed] [Google Scholar]
- Lindholm CE, Ollman B, Snyder J, Millen E, Grenvik A. Flexible fiberoptic bronchoscopy in critical care medicine. Diagnosis, therapy and complications. Crit Care Med. 1974;2:250–261. doi: 10.1097/00003246-197409000-00004. [DOI] [PubMed] [Google Scholar]
- Olopade CO, Prakash UB. Bronchoscopy in the critical-care unit. Mayo Clin Proc. 1989;64:1255–1263. doi: 10.1016/s0025-6196(12)61288-9. [DOI] [PubMed] [Google Scholar]
- Stevens RP, Lillington GA, Parsons GH. Fiberoptic bronchoscopy in the intensive care unit. Heart Lung. 1981;10:1037–1045. [PubMed] [Google Scholar]
- Weinstein HJ, Bone RC, Ruth WE. Pulmonary lavage in patients treated with mechanical ventilation. Chest. 1977;72:583–587. doi: 10.1378/chest.72.5.583. [DOI] [PubMed] [Google Scholar]