The levels of humidification delivered to the mechanically ventilated patient will help prevent airway complications and optimize mucosal performance. Guidelines help determine these levels and how to achieve them.

 Temperature and humidity are added to normally inspired gas through the action of the nose and upper airway, so that gas reaches the lower airway at body temperature and saturated with water vapor. The aim of artificially humidifying the gas delivered to mechanically ventilated patients is twofold: to prevent desiccation of the airway and related complications and to optimize mucosal performance, thus preventing secretion retention. The airway mucosa consists of the layer of cells lining the airway. Blood flowing to the cells transfers body heat to the inspired gas, while the periciliary fluid and mucus provide a moist surface capable of humidifying the gas. Liquid water contained within the mucus and periciliary fluid is converted to water vapor as gas passes over the mucosal surface until equilibrium is achieved and the gas has reached body temperature and is saturated with water vapor. This energy loss means that the mucosal surface is relatively cool prior to exhalation. As exhaled gas passes over this surface, its temperature falls below the dew point, causing approximately 25% of the water vapor in the exhaled gas to condense on the mucosal surface. Hence, there is a net loss of heat and moisture to the environment after each breath; the deficit must be replaced by the body’s systemic reserves.

Conditioning of the gas as it moves down the airway toward the lungs is a gradual process. During normal, quiet breathing, inspired gas is warmed and humidified to 30°C, 95% relative humidity, and 29 mg of water per liter of gas in the upper trachea, and to 34°C, 100% relative humidity, and 38 mg of water per liter of gas in the lower trachea.1,2 The majority of heat and moisture is added in the nasopharynx, but the gas does not achieve body temperature and saturation with water vapor until it reaches the fourth or fifth generation of the bronchi.1 When a patient is intubated, dry medical gases can be delivered to the airway proximal to the carina. Under these conditions, the position in the airway where body temperature and saturation of the gas are achieved shifts distally from the tip of the endotracheal tube, resulting in severe losses of heat and moisture from the main and subsegmental bronchi and in damage to the airway mucosa.3,4

To prevent humidity-related complications, minimum levels of temperature and humidity have been stipulated in guidelines published by various international respiratory organizations. Such complications have still been observed when these guidelines are followed, however, suggesting that higher levels of temperature and humidity are required.5,6 Improving the level of humidity after complications have occurred may not prevent additional microscopic damage to the mucosal surface.

 Figure 1. Schematic of airway mucosa. Reprinted with permission from Crit Care Med.9

Mucociliary Transport System
The mucociliary transport system (Figure 1) lines almost the entire airway surface, from the nose down to the 15th or 16th generation of the airway.7 It is made up of ciliated epithelial cells, each containing 200 to 400 cilia, 5 to 8 mm long, that beat rhythmically at 10 to 30 Hz in a metachronal wave pattern.8

In a recent review, Williams et al9 proposed a model that describes the relationship between the mucociliary transport system’s performance and the humidity of the inspired gas. At any given level of temperature and humidity, mucosal dysfunction was predicted to deteriorate sequentially through four steps: thickened mucus (or thinned mucus, in the case of overhydration); slowed mucociliary transport; mucociliary stasis; and cell damage. The rate of deterioration through these steps was predicted to be related to the magnitude of the humidity deficit. In addition, the model suggests that humidity-related mucosal dysfunction may be further compromised by the presence of lung disease. A meta-analysis of the relevant literature broadly supported the model, showing that mucosal dysfunction (and, potentially, cell damage) could occur within 24 hours of exposure to gas conditioned to approximately 30 mg of water per liter of gas (Figure 2, page 38).9 This analysis also showed that when gas was conditioned to body temperature and saturated with water vapor, no mucosal dysfunction was apparent. Several studies support this hypothesis. King et al10,11 monitored airway epithelial function in anesthetized dogs as core temperature fell after the administration of pentobarbital. The mucociliary transport system was maintained at normal rates if the humidification system was adjusted to deliver gas at close to body temperature and 100% relative humidity. Similarly, if core temperature was maintained at 37°C by use of a hot water blanket, then inspired gas conditioned to 37°C and 100% relative humidity maintained or optimized performance of the mucociliary transport system.

Figure 2. Delivered humidity versus exposure time. Each data point represents a single measurement from studies examined by Williams et al.9 Closed diamonds represent no dysfunction; open circles represent a combination of thick mucus, stopped mucociliary transport, and stopped cilia; and crosses represent cell damage. The dashed trend lines separating no dysfunction, mucociliary dysfunction, and cell damage were determined using linear discriminant analysis. The further the delivered gas deviates from body temperature and saturation with water vapor, the greater and more rapid the mucosal damage. Adapted with permission from Crit Care Med.9

General markers of airway health also support the delivery of gas at body temperature and saturated with water vapor as optimal. The physical properties of airway mucus are optimized,12 and mucus transport velocity is maximal, when the inspired gas is at 37°C and 100% relative humidity.10,12 Cilial beat frequency deteriorates when cilia are exposed to gas at less than core temperature and less than ideal saturation,4,13,14 and the risk of ciliastasis is minimized when heat and moisture are applied to the airway.13 In patients with airway disease, Chalon15 demonstrated that only those patients receiving body-temperature, saturated gas maintained normal epithelial-cell morphology over 3 hours’ exposure to various inspired-gas conditions.

In the clinical setting, airway thermodynamics have been suggested as an indicator of the optimal level of humidification. Ryan et al16 found that when the inspired gas was conditioned to less than body temperature and was not saturated with water vapor, the gas warmed as it passed through the endotracheal tube,with no additional moisture being added by the endotracheal tube. This resulted in the delivery of gas of low relative humidity. Miyao et al17 demonstrated that the risk of endotracheal-tube obstruction or partial occlusion is greatly increased if the relative humidity of the inspired gas is less than 100%. Not only is the patency of the endotracheal tube at risk, but any mucus that has collected at the base of the endotracheal tube (due to the action of the mucociliary transport system) may dehydrate before it can be removed via suction.

Delivering low levels of humidity can have serious consequences. Many authors5,18-22 report an increased risk of endotracheal-tube occlusion in mechanically ventilated patients as a result of low-humidity gas delivery. Low humidity is also associated with increased secretion viscosity,5 atelectasis,20 and reduced endotracheal-tube patency.23 Conditioning inhaled gas to close to body temperature and saturating it with water vapor can prevent these complications.24,25

Injury of the mucociliary transport system can result from inhalation of aerosols and noxious gases. Tobacco smoke has been shown to impair mucociliary clearance by a number of authors.26-28 Goodman et al27 measured mucus velocity in young and old subjects, both smokers and nonsmokers. Age and a history of smoking were both associated with significantly slower mucus velocities For example, in subjects whose age ranged from 19 to 28 years, a smoking history (7 to 21 pack-years) reduced mean tracheal mucus velocity from 10.1±3.5 mm per minute (nonsmokers) to 3.4±4 mm per minute (smokers). In contrast, older subjects (40 to 70 years of age) with a smoking history and obstructive chronic bronchitis had a mean tracheal mucus velocity of just 0.8±1.6 mm per minute.27 Several authors have shown that anesthetic agents such as atropine,29,30 pentobarbital,31 and halothane32 impair the performance of the mucociliary transport system. Greater than normal fractions of inspired oxygen33 and dehydration34 have also been demonstrated to slow the mucociliary transport system.

The presence of underlying lung disease or injury influences the performance of the mucociliary transport system. Intubation itself results in impaired mucociliary clearance through injury of the epithelium and reduction in the extent of ciliation of the bronchial epithelium.35 Impaired mucociliary function has also been correlated with longer ventilation time.35 Asthma exacerbation, viral and bacterial acute bronchitis, and chronic bronchitis can have a negative effect on mucociliary clearance.33 Respiratory-tract infection can impair mucociliary clearance through cytotoxic effects on the epithelium or through the production of substances that directly affect the mucociliary transport system.36

The combination of poor humidity delivery and other factors that impair mucosal function will have a cumulative adverse effect on the mucociliary transport system.9 Mucosal dysfunction is likely to occur more rapidly following exposure to a humidity level that might otherwise be considered adequate in a patient having good lung health. Hence, patients with impaired lung function should always receive ventilator gases conditioned to body temperature and saturated with water vapor.

Humidification Systems
The method of humidity generation can be active (using a heated humidifier) or passive (using a heat-and-moisture exchanger or artificial nose) and can employ aerosols (using nebulizers or bubble-through humidifiers) or water vapor (using heated pass-over or wick humidifiers).37 It is generally accepted, however, that humidification devices should generate water vapor only, since there is an increased risk of nosocomial pneumonia if aerosol generators38 and bubble-through humidifiers39 transport bacteria to the patient. There is a trend leading away from delivering aerosols to the airway because this has been shown to increase pulmonary arterial-wall thickness, decrease alveolar space, and increase interstitial and intra-alveolar edema.40

The humidification of inhaled gas is determined by the heat-and-moisture exchanger selected or, for a heated humidifier, the chosen settings. Factors influencing this choice include the need to control condensate generation, infection control issues, and the need for aerosols or water vapor. It is clear that the device employed should provide gases that are as close as possible to body temperature and saturated with water vapor so that mucosal dysfunction and related clinical complications can be prevented. Only a heated humidifier is capable of conditioning gases to body temperature and saturating them with water vapor.41

The humidification of inspired gases is essential for intubated patients. Currently published international standards and institutional guidelines disagree as to the appropriate level of humidity that should be delivered to mechanically ventilated patients. A recent meta-analysis9 offers the possibility of consensus, showing that only gases that are at body temperature and saturated with water vapor optimize mucociliary function, and that the lower the delivered humidity, the more rapidly mucosal dysfunction occurs. In addition, many lung diseases, a history of smoking, hydration status, and interventions such as anesthesia or supplemental oxygen can easily disrupt the mucociliary transport system, putting these patients at greater risk for complications if low humidity is delivered. Therefore, to ensure the best mucosal function and to reduce the risk of mucus thickening or endotracheal-tube occlusion, inspired gases should be conditioned to body temperature and saturated with water vapor.

Stuart N. Ryan, PhD, is a research scientist, Respiratory Humidification Group, Fisher & Paykel Healthcare, Auckland, New Zealand. Bryan D. Peterson is an engineer in Business Development, Respiratory Humidification Group, Fisher & Paykel Healthcare, London.

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