Respiratory Gas Conditioning and Humidification: Andreas Schulze, MD
Respiratory Gas Conditioning and Humidification: Andreas Schulze, MD
Respiratory Gas Conditioning and Humidification: Andreas Schulze, MD
Although there have been great advances in our understanding of pulmonary pathophysiology in the management of neonatal lung disorders, the
proper humidication and conditioning of delivered gas remains a mystery
to most clinicians managing these devices. This article attempts to unravel
the mystery and describe the physiologic bases for humidication and gas
conditioning.
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40
50
44 mg/L
37
40
35
30 mg/L
30
30
25
20
10
Temperature (centigrade)
60
0
65
75
85
Relative Humidity (
95
Fig. 1. The relative humidity of a gas depends on its absolute water content and gas temperature. At 37 C and 100% relative humidity, the respiratory gas has 44 mg/L absolute water content. If the gas is saturated (100% relative humidity) at 30 C, its water content is only 30 mg/L.
When the gas is then warmed to 37 C, its relative humidity falls to less than 70%.
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minimal acceptable level of temperature and humidity has not been clearly
established by clinical studies. International and United States standards
recommend an absolute humidity level of inspired gas greater than 33 mg/L
in patients whose supraglottic airway is bypassed [1820]. There is no
doubt that inadequate humidication may lead to progressive airway dysfunction and systemic eects, depending on the degree of under-humidication and coolness, the exposure time, and the underlying disease.
The mucociliary transport system is probably the most sensitive respiratory function to changes in inspired gas humidity and temperature [21].
Transport velocity depends on mucus rheology, the depth of the aqueous
airway lining layer, and cilia beat frequency. Dry inspired gas changes the
viscosity gradient of the airway lining. Dehydrated mucus slows the transport rate and cilia beat frequency. Thinning of the aqueous layer impairs
the recovery stroke of cilia [22,23]. The mucociliary machinery may recover
with rehumidication after short periods of desiccation. Cessation of cilia
activity for 3 hours is irreversible, however, and is followed by inammation
and sloughing of the mucosa [24]. Such damage deprives the upper airway of
its function as a heat and moisture exchanger. Subsequently, the isothermic
saturation boundary retreats into smaller airways and the area of damaged
mucosa progressively extends into the periphery of the lung.
Because the depth of the airway lining uid is only about 7 to 12 mm [25],
water loss by evaporation may increase the osmolarity. This increase may
induce bronchial smooth muscle contraction in patients who have exercise-induced asthma independently of the inhaled air temperature [2629].
The mechanism by which a change in the osmotic environment can lead
to bronchoconstriction is unknown. Airway irritant receptors have been implemented as possible mediators. It is also unknown whether a critical
threshold of respiratory water loss exists to induce a stimulus for bronchoconstriction, or whether this mechanism occurs in preterm infants who have
chronic lung disease.
In a retrospective study, mechanically ventilated infants weighing less
than 1500 g at birth had signicantly more air leaks and more severe chronic
lung disease if exposed during their rst 4 days of life to inspired gas less
than 36.6 C and with less than 37 mg H2O/L [30]. This association could
not be corroborated for more mature infants, suggesting that the resistance
to poor inspiratory gas conditioning might be a function of gestational age.
The cause of necrotizing tracheobronchitis in mechanically ventilated infants and adults has not been fully elucidated, but it is rational to assume
that inadequate humidication is a signicant contributor [3133].
The mucociliary elevator moves secretions up to the tip of the endotracheal tube. This material accumulates and resides there for a variable period
of time awaiting removal by suctioning. It is subjected to desiccation by any
inspiratory gas leaving the endotracheal tube with a capacity to accommodate more water vapor. Inspissation is faster the lower the humidity and the
higher the airow at the endotracheal tube outlet. High minute ventilation
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and an endotracheal tube leak hasten this process. It has been suggested that
humidity levels below a critical threshold of 31 mg H2O/L are associated
with a high risk for endotracheal tube plugging in infants [34]. At least theoretically, however, this does not imply that any humidity level above this
threshold and below full saturation at core body temperature is safe in
regard to upper airway obstruction by inspissated secretions.
Mechanical ventilation with dry gas results in a mean decrease in rectal
temperature by 1.4 C within one hour in neonates. Even moderate warming
to 31.5 C and humidifying the inspiratory gas reduces the insensible water
loss in intubated preterm infants signicantly and consistently to levels
below those of extubated infants in room air at 27 C [35].
Severe underhumidication nally leads to impaired surfactant activity,
decreased functional residual capacity, atelectasis, and compromised pulmonary mechanics [36].
5 L/min
Respirator
25
Incubator
5 L/min
5 L/min
= temperature probes
Humidifier
Chamber
Maximum water consumption
5 L/min x 44 mg H2O/L
= 220 mg/min = 13.2 mg/h
= 13.2 mL/h
Fig. 2. Position of three temperature probes of a heated-wire humidication system for infants.
The user sets the target temperature to be reached at the endotracheal tube adaptor. This
temperature is commonly set at or slightly greater than 37 C. The temperature inside the
humidier chamber must be high enough to vaporize an amount of water near the absolute
water content of gas saturated at 37 C (44 mg/L). The water consumption rate of a humidier
chamber required to reach a target respiratory gas humidity can be calculated from the circuit
ow rate. Observation of this water consumption rate can be used as a simple test of the
eciency of a humidier.
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SCHULZE
circuit and lead to loss of gas temperature and rainout. Such a problem may
arise when the incubator temperature is higher than the targeted gas temperature or from a radiation heat source. Insulating the temperature probe by
a light reective patch or other material can improve the performance of the
system. Another way to alleviate this problem is to place the temperature
probe just outside the heated eld and use an unheated extension adaptor
tubing to carry the gas through the heated eld to the infant. The extension
tube does not need to incorporate heated wires because its temperature is
maintained by the heated eld. If cooler incubator temperatures are used
(as usually used for older preterm infants), rainout occurs in the unheated
segment, particularly at low circuit gas ow rates. A circuit should then
be used that is equipped with a heated wire along the entire length of its inspiratory limb. Another suitable type of circuit is that with two temperature
probes, one outside the heated eld and the other close to the wye adaptor.
These circuits can perform well over a range of incubator temperatures both
greater than and less than the target respiratory gas temperature. This is because the heated wire servo-control can be programmed to select the lower
of the two recorded temperatures to drive the power output. The maximum
heat output of any heated wire circuit may not be sucient to meet target
gas temperatures under extremes of room and incubator temperatures.
Also, generic circuits have been on the market that may not be fully compatible with the humidier and its power source. There has been a warning that
covering heated wire circuits with drapes or other material for insulation
may involve a risk for melting or charring of circuit components [37].
Articial noses
Heat and moisture exchangers (HMEs) are designed to recover part of
the heat and moisture contained in the expired air. A sponge material of
low thermal conductivity inside the clear plastic housing of these devices
absorbs heat and condenses water vapor during expiration for subsequent
release during inspiration. HMEs are an attractive alternative to heated humidiers for several reasons, such as simplication of the ventilator circuit,
passive operation without requirement of external energy and water sources,
no ventilator circuit condensate, low risk for circuit contamination [38], and
low expense. Additionally, some HMEs are coated with bacteriostatic substances and equipped with bacterial or viral lters (HMEF). Devices called
hygroscopic condenser humidiers (HCHs) use hygroscopic compounds,
such as CaCl2, MgCl2, LiCl, or others, to increase the water retention capacity. Small HME/HCHs for neonatal applications are commercially available, but data on their use are sparse. Theoretically, an application in
small subjects may be particularly eective because mean delivered inspiratory humidity increases inversely with tidal volume [39]. Also, the HME
membranes may become saturated before a large volume expiration has
been completed, which increases respiratory water loss. A pediatric HME
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maintained an average inspiratory humidity greater than 30 mg/L in a clinical study involving neonates for a test period of 6 hours [40]. Other clinical
studies on pediatric and neonatal application conrmed the ability of HME/
HCHs to conserve heat and to provide humidity levels that are appropriate
for short-term conventional mechanical ventilation [4143]. Bench studies
on high-frequency oscillatory ventilation in a neonatal lung model showed
that a neonatal HME was able to provide more than 35 mg/L of mean humidity at the proximal end of the endotracheal tube adapter. The HME
dampened the oscillatory pressure amplitude less than a neonatal endotracheal tube of 3.5 mm inner diameter [44]. The safety and eectiveness of
HME/HCH for long-term mechanical ventilation is controversial in adults
[4549] and has not been established in infants. Depending on their actual
water load and duration of use, HMEs add a variable resistance and dead
space to the circuit [5052]. A risk for airway occlusion from clogging
with secretions or from a dislodgement of HME internal components [53]
has been reported for infants even during short-term application. Also, an
expiratory air leak impairs the barrier eect against moisture loss [54,55].
HME must not be used in conjunction with heated humidiers, nebulizers,
or metered dose inhalers, which may cause a hazardous increase in device
resistance [56] or wash o the hygroscopic coating [57]. Dierent brands
of HME/HCHs may vary widely in their performance characteristics. Their
eectiveness is not reliably reected by indirect clinical measures, such as the
occurrence of nosocomial pneumonia, number of endotracheal tube occlusions, or frequency of tracheal suctioning and instillation [58]. Visual evaluation of the amount of moisture in the adapter segment between the
endotracheal tube and the HME/HCH was found to closely correlate with
objective measurements of the delivered humidity, however [59]. Device performance has improved much during recent years, and further advances can
be expected to facilitate neonatal applications. Microprocessor-controlled
active release of additional external heat and water into the airway between
an HME and the endotracheal tube adapter increased the inspired gas humidity to 100% at 37 C without obvious untoward eects in 24-hour studies
in adults. Such hybrid systems, however, require further study and renement [60].
Aerosol application
Aerosol water particles that range in size from about 1 to 10 mm may deposit on the airway by impaction (larger particles) or sedimentation (smaller
particles). Sedimentation occurs as a gravitational eect when airow velocity declines in the smaller airways. An aerosol cannot contribute to respiratory gas conditioning downstream to the isothermic saturation boundary
because the gas is already fully saturated. For this same reason, aerosol water particles cannot be eliminated in this airway region through evaporation
and exhalation. They therefore become a water burden on the mucosa that
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vapor but also some aerosol capable of dispersing infectious particles. The
colonization risk may be reduced by the use of sterile closed delivery systems
or by maintaining a water reservoir temperature greater than 60 C (pasteurization) [36]. It has been shown in adults, however, that such colonization
usually originates from the patients own respiratory ora and may occur
within a few hours of connecting a sterile circuit [72,73]. It was subsequently
observed that the incidence of nosocomial pneumonia in adults was not increased when ventilator circuits were changed less frequently than every
24 hours or even between patients [50,74,75]. Nevertheless, although these
studies indicate that ventilator circuit changes may be extended to more
than 48 hours, the optimal rate of circuit changes for infants is unknown.
Changing a ventilator circuit is not a benign procedure because it may disrupt ventilation in a potentially dangerous way, and medical personnel may
become a vector for cross-contamination between patients [76]. Arguments
can therefore be made for weekly circuit changes or for no circuit changes at
all, except between patients.
In 2005, a meta-analysis of randomized controlled trials found a protective eect against ventilator-associated pneumonia in adults with the use of
HMEs compared with heated humidiers, particularly in patients ventilated
for 7 days or longer [77]. The size of this eect, however, is likely small; it
could not be corroborated in two more recent studies on a large number
of patients [50,78].
Summary
There is a strong physiologic rationale for delivering the inspiratory gas
at or close to core body temperature and saturated with water vapor to infants who have an articial airway undergoing longer-term mechanical ventilatory assistance. Cascade humidiers with a heated wire ventilatory circuit
may achieve this goal safely. Whenever saturated air leaves the humidier
chamber at 37 C and condensate accumulates in the circuit, the gas loses humidity and acquires the potential to dry airway secretions near the tip of the
endotracheal tube. Heat and moisture exchangers and hygroscopic condenser humidiers with or without bacterial lters have become available
for neonates. They can provide sucient moisture output for short-term
ventilation without excessive additional dead space or ow-resistive loads
for term infants. Their safety and ecacy for very low birthweight infants
and for long-term mechanical ventilation have not been established conclusively. A broader application of these inexpensive and simple devices is
likely to occur with further design improvements. When heated humidiers
are appropriately applied, water or normal saline aerosol application oers
no additional signicant advantage in inspiratory gas conditioning and may
impose a water overload on the airway or even systemically. Although airway irrigation by periodic bolus instillation of normal saline solution before
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