Inhalation and Humidification

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Indian Journal of Anaesthesia, October 2008(P.G.Issue)

Inhalation therapy and Humidification

V Saraswat

Summary

Inhalation therapy is a preferred mode of drug delivery as it provides rapid onset of action, increased bioavailability,

low gastrointestinal side effects and user-friendly environment with better patient compliance. A variety of drugs are

in use and more drugs formulations are being investigated, consequently leading to development of compatible inhal-

ers, which necessitates good understanding of drug formulations and functioning of inhalers. There is no significant

difference between various inhaler devices in their efficacy outcome, however most are drug specific depending on

drug formulations. Multi-drug inhalers are in developmental phase and may be available in future. Oxygen therapy

being the mainstay of inhalation therapy needs special emphasis especially with regards to delivery devices. Climatisation

of inspired gases, both in terms of humidification and temperature maintenance, is the integral part of inhalation

therapy especially so if upper airway is bypassed by intubation or tracheostomy. The problem is compounded incritically ill patients on long-term ventilation. Both active and passive humidifiers are in use, heated humidifiers (HH)

and Heat and moisture exchanger (HME), being most common in use at present. Both, HH and HME, have proved

their efficacy in varying patient requirements, however their use may be guided more by clinical and cost consider-

ations. Use of microbial filters in humidifiers, in some studies, have shown a significant reduction in ventilator-

associated pneumonia (VAP).

Key words Nebulizer, Metered dose inhaler (MDI), Dry powder inhaler (DPI), Oxygen delivery

devices, Heated humidifier (HH), Heat and moisture exchanger (HME),

ventilator-associated pneumonia (VAP)

1.DPMO (A), HQ, WAC, Correspondence to: V Saraswat Subroto Park, New Delhi 110010,

Email: [email protected], [email protected]

Introduction

Inhalation therapy is a term used for a variety of

treatment techniques, including drugs administered via

inhalation. It aims at targeting lung tissue, airway secre-

tion and microorganisms in upper, central and/or pe-

ripheral airways. However, drugs targeting systemic

effects are used aiming at deposition in the alveoli where

it can be rapidly absorbed and distributed.1

Benefits of inhalation therapy

1. A principal benefit of inhalation therapy is the

rapid onset of action, compared to peroral medication

from large absorption area of the lung. Locally acting

drugs have immediate onset of action whereas, sys-

temically active reach the blood stream within seconds.

It is important in rescue medications, pain medication

and time-sensitive therapies, such as insulin.

2. Inhaled drugs avoid GI tract and are not sub-jected to the first-pass metabolism that reduces

bioavailability, avoid undesirable GIT side effects and

are better tolerated.

3. Injected drugs also avoid the problems asso-

ciated with the GI tract, but needles are invasive and

socially uncomfortable to effect self injection. Inhaled

drugs are more user-friendly and result in better patient

compliance.

Drugs used in inhalation therapy

1. Oxygen therapy - The most common form of

inhalation therapy is the provision of oxygen. There are

a multitude of reasons for administering oxygen, rang-

ing from minor to very serious breathing problems like

decreased lung function and systemic organ failures.

The treatments range from at-home oxygen therapy for

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patients with chronic obstructive pulmonary disease

(COPD) to mechanical ventilation for patients with res-

piratory failure.

2. Anaesthetic agents - Anaesthetic agents have

been used by inhalation since the beginning of practice

of anaesthesia. The anaesthetic gases from nitrous ox-

ide to inert gases like helium have been used. Other

agents used by this route in ICU are nitric oxide and

surfactant. In addition, in absence of venous access,

most of the life saving drugs required for immediate

effect may be given endotracheally in ICU.

3. Beta2 agonists - Beta2 agonists arebronchodilators, extensively used in treatment of asthma.

Albuterol, is short-acting and used for acute exacerba-

tions. It relaxes smooth muscle and increases airflow

within 5 minutes and last 3-6 hours. Salmeterol is a

long-acting with slower onset (15-30 minutes), but

longer duration of action (over 12 hours). Inhalers are

colour coded and deliver fixed dose at actuation.

4. Glucocorticoids - Inhaled glucocorticoids are

the most potent inhaled anti-inflammatory drugs cur-

rently available. Early intervention improves asthma

control, normalizes lung function and prevents irrevers-

ible airway damage. Improvement can occur within 24

hours, although maximum benefit may take 1 to 2

weeks. The risks of systemic side effects, such as sup-

pression of the hypothalamic-pituitary axis, are less than

with oral glucocorticoids. Inhaled glucocorticoids in-

clude fluticasone, beclomethasone, budesonide, and

triamcinolone.

5. Anticholinergic drugs - Ipratropium bromide(Atrovent) is a quaternary derivative of atropine that

lacks its adverse side effects. It is used as an additional

reliever medication when short-acting beta2agonists do

not give enough relief. Its anticholinergic action also

decreases mucous secretions.

6. Other drugs Antibiotics, insulin, contracep-

tives and analgesics have been tried and some are in

developmental stage.

DEVICES FOR INHALATION THERAPY

1. Oxygen delivery devices

A wide variety of oxygen delivery systems are

available. (Fig-1) The mask and valve design and oxy-

gen flow rate allows delivery of inspired oxygen of 24-

90% (FiO20.26-0.90). The concentration of oxygen

depends on the ventilatory minute volume (MV) and

the flow rate of oxygen, greater the ventilation, the lower

the FiO2for a given flow rate of oxygen. It is impos-

sible to provide a fixed FiO2to a patient with a varying

ventilatory requirement unless the total MV is provided

at the required FiO2.2 There are two basic types of

oxygen mask which deliver either the entire (high flow

mask) or a proportion (low flow mask) of the ventila-

tory requirement.

Fig 1 Oxygen mask and nasal canula

Nasal prongs are simple, convenient to use and

can provide 24-40% oxygen with flow rates up to 6 L/

min in adults. The FiO2depends on the flow rate of

oxygen (1-6L/min) and varies according to MV. At anoxygen flow rate of 2L/min the oxygen concentration

in the hypopharynx is 25-30%. Nasal prongs prevent

rebreathing, are comfortable for long periods, and al-

low oxygen to be continued during talking and eating.

Local irritation and dermatitis may occur with high flow

rates. Nasal prongs are less prone to complications,

and oxygenation in children is equally effective.3 Neo-

nates and small babies can be given oxygen by a tent

or oxygen hood.

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Low flow masks Simple oxygen masks can

provide 35-50% FiO2, depending on fit, at flow rates

from 5-10 L/min. Flow rates should be maintained at 5L/min or more in order to avoid rebreathing exhaled

CO2that can be retained in the mask. A concentration

of up to 60% can be achieved with addition of reser-

voir bag, and are used mainly in type I respiratory fail-

ure. These masks are generally not suitable for patients

with type II respiratory failure.

High flow, jet mixing masksdeliver about 40L/min of gas through the mask, sufficient to meet the total

respiratory demand unaffected by the pattern of venti-

lation and avoid rebreathing as mask is flushed by thehigh flow rates. The masks contain venturi valves, which

use the principle of jet mixing (Bernoulli effect). When

oxygen passes through a narrow orifice it produces a

high velocity stream that draws a constant proportion

of room air through the base of the venturi valve. Air

entrainment depends on the velocity of the jet (the size

of orifice and oxygen flow rate) and the size of the valve

ports. It can be controlled to give inspired oxygen lev-

els of 24-60%. In COPD and type II respiratory fail-

ure patients, these masks reduce the risk of carbon di-oxide retention while improving hypoxemia. Jet-mixing

masks rated at 35% or higher usually do not deliver

flow rates adequate to meet the inspiratory flow rates

of adults in respiratory distress. They are loose fitting

and comfortable to wear. The OxyMask, a new face

mask for oxygen delivery that uses a small diffuser to

concentrate and direct oxygen toward the mouth and

nose delivers oxygen more efficiently than a Venturi

mask.4 Aerosol masks, tracheostomy collars, T-tube

adapters, and face tents can be used with high-flow

supplemental oxygen systems.

Rebreathing and anaesthetic type oxygen

masksPartial rebreathing masks incorporating non-

rebreathing valves and reservoir bags can provide con-

centrations 40-70% at flow rates of 6-10 L/min. Oxy-

gen flow should always be supplied to maintain the res-

ervoir bag at least one third to one half full on inspira-

tion. In cardiac or respiratory arrest, tight fitting anaes-

thetic-type masks can achieve 100% oxygen. The non-

rebreathing mask is similar to the partial rebreathing

mask except it has a series of one-way valves. One

valve is placed between the bag and the mask to pre-vent exhaled air from returning to the bag. There should

be a minimum flow of 10 L/min to deliver FiO2of 60-

80%.

Non-invasive assisted ventilationSupplemental

oxygen may be provided through tight fitting nasal or

full-face masks during nasal intermittent positive pres-

sure ventilation and continuous positive airways pres-

sure. (Fig-2) It is used to support ventilation in sleep-

associated hypoventilation, during weaning from me-

chanical ventilation, and in respiratory failure associ-ated with COPD. The technique improves oxygenation

by recruiting under ventilated alveoli. As intubation is

avoided the risks of nosocomial pneumonia are re-

duced. The CPAP mask often becomes uncomfortable

and gastric distension may occur, hence patients must

be cooperative, able to protect their airway, have the

strength to breathe spontaneously and cough effectively,

failing which mechanical ventilation can be instituted.

The type of interface affects the NIMV outcome more

than the ventilatory mode.5

Fig 2 Mask for noninvasive ventilation (NIV)

Hyperbaric oxygen therapy (HBO), delivers pure

oxygen under pressure equal to two to three times nor-

mal atmospheric pressure. At a pressure of 300 kPa

the small quantity of oxygen in solution in the blood can

be increased by up to 300% and diffusion through tis-

sues may be improved.2 This treatment has been espe-

cially effective in high altitude pulmonary edema and


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scuba divers. The patient enters the chamber and oxy-

gen is delivered under forced pressure. The therapy

usually lasts one hour, although it can take up to fivehours in serious decompression cases. Before exiting

the chamber, the pressure will eventually be lowered to

normal atmospheric level.

2.Devices for inhaled medications

There are four different kinds of inhalation de-

vices:

(a)Nebulizer systems - Nebulizer changes liq-

uid medicine into fine droplets (aerosol or mist) thatare inhaled through a mouthpiece or mask. (Fig-3) It

can be used to deliver saline, distilled water or medi-

cines in liquid formulation. It is based on one of three

different techniques - jet, ultrasonic and vibrating mem-

brane. The device may be heated or unheated. Choos-

ing the optimal device for a patient is essential to en-

sure the effectiveness of the therapy. However, the

choice is dependent on several different factors and

there is no single device that is best for all patients in all

situations. Inhalation technique and handling of the de-vice is essential for the effective treatment.

age group. Spacers decrease the amount of drug de-

posited in the oropharynx (up to 80% of the actuated

dose with the MDI alone), thereby reducing systemicand other side effects. The drugs currently available in

MDI formulations include beta agonists, glucocorticoids,

ipratropium bromide, cromolyn sodium, and nedo-

cromil. Each product delivers a set amount of drug-

per actuation (puff). In the United States, MDIs are

labeled according to the amount of drug delivered at

the mouthpiece, whereas in Canada and the European

Union, they are labeled according to the amount of drug

delivered from the valve.

MDIs use chlorofluorocarbons (CFCs) as thepropellant. New devices, propelled by Hydrof-

luoroalkane (HFA) have been developed and are cur-

rently available with different medicines. The Clean Air

Act and an international environmental treaty have led

to the phase out of CFC-propelled inhalers by De-

cember 31, 2008 as they deplete the ozone layer.

(c) Dry powder inhaler (DPI) - Special inhaler

are in use to deliver the dry powder medicines. (Fig-4)

When inhaled fast enough the medicine is released. DPIwhen compared with MDI are as efficient and may be

superior delivery device for some drugs.6

Fig 3 Nebulizer

(b) Metered dose inhaler (MDI) - It consists

of a pressurized canister of medication in a plastic case

with a mouthpiece. Pressing the MDI releases a mist of

medication. It is portable, efficient and convenient and

are designed for actuation during a slow, deep inhala-

tion for optimal lung delivery. The addition of a spacer

improves drug delivery and can be used in paediatric

Fig 4 Dry powder inhaler (DPI)

(d) Monodispersed aerosols with a very nar-

row range of smaller particle sizes target drug delivery

to specific areas of the lung where it is most effective.

However, as smaller particles are more easily absorbed

into the pulmonary circulation they may be associated

with a higher incidence of systemic side effects. The

optimal particle size required to maximize the thera-

peutic ratio of a molecule may be different for a 2-

agonist and inhaled corticosteroid.



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Effect of particle size

The destination of aerosol particles is critical to

the efficacy of inhalation therapy. For locally-acting

drugs, the particles need to be deposited in the area of

the respiratory tract requiring treatment. For systemi-

cally-acting drugs, particles need to reach the alveoli

for absorption.

Large particles (5-10 m) do not follow changes

in the direction of airflow and are deposited by inertial

impact in the upper airways. Particles deposited in the

mouth and throat can be swallowed and lead to local

or systemic side effects. Intermediate-sized particles(3-5 m) can be carried further, into smaller airways of

the bronchi and bronchioles. Small particles (


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America, oxygen is not humidified as long as flow is

less than 4L/min, as per guidelines for oxygen therapy

announced by the ACCP-NHLBI in 1984 and revisedby AARC in 2002. The oxygen received through a

nasal cannula at 0.5-4 L/min or through a Venturi mask

at 24-40% constitutes only a small percentage of the

patients inspiratory tidal volume compared with the

water content delivered from the airway. Increasing the

relative humidity of the room air easily compensates

this humidity deficit, hence routine humidification of low-

flow oxygen or low-concentration oxygen is not justifi-

able.15

Noninvasive positive-pressure ventilation deliversair at a high flow, with a low relative humidity, at high

inspiratory pressure. Addition of a heated humidifier

increases the relative and absolute humidity to levels

acceptable for nonintubated patients, with minimal ef-

fect on delivered pressure.16 Heated humidifiers have

been found to be more effective than helmet17 and oily

nose drops while delivering CPAP18 and improves ab-

solute humidity in nasal CPAP therapy with nasal mask

leak making it more acceptable.19

Ventilation with endotracheal intubation bypasses

the upper airway and the normal heat and moisture

exchanging process of inspired gases. A continuous loss

of moisture and heat occurs and predisposes patients

to serious airway damage. Ventilation with dry and cold

gases leads to epithelial cell disorders, increased mu-

cus viscosity and restriction of the mucociliary function

resulting in hypothermia, atelectasis and hypoxaemia.

On the other hand, over-humidification or ventilation

with hyperthermic gases may lead to tracheal burning,

alteration in surfactant and epithelial cell disorders lead-

ing to hyperthermia, hyponatraemia, atelectasis and

hypoxaemia. Thus, it is of crucial importance to moni-

tor ventilatory gas conditioning closely, especially in ICU

patients subjected to prolonged mechanical ventilation.

Currently heated humidifying systems (HH) (ac-

tive) (Fig-5) and heat and moisture exchange filter

(HMEF) (passive) (Fig-6) are in common use in ana-

esthesia and intensive care units (ICU).

Fig 5 Heated humidifier (HH)

Fig 6 Heat and moisture exchanger filter (HMEF)

During general anaesthesia gas climate is signifi-

cantly improved by low flow techniques with fresh gas

flows equal or less than 1 L/min. With higher FGF ratesthe humidity decreases markedly while high gas tem-

peratures are maintained. Gas climatisation is also in-

fluenced by the temperature loss and water condensa-

tion within the hoses, factors that are related to the tech-

nical design and material of the patient hose system. In

routine clinical practice conventional and coaxial hose

systems are similar in respect to the climatisation of

breathing gases and acceptable, but not optimal. The

coaxial hose system lead to improved climatisation in

long lasting procedures only. Whereas, heated breath-

ing hoses perform markedly better and sufficient mois-

ture and temperature values can be achieved.20 The

HMEs improve the inspiratory AH, RH and tempera-

ture of the anaesthetic gases during different FGFs but

do not prevent drop in body temperature.21Unheated

wire circuits perform better than heated circuits in terms

of delivered relative humidity.22

Heated humidifier (HH) Vs heat and

moisture exchanger (HME)



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HH are considered better in terms of preserva-

tion of relative humidity and temperature than HME,23

however, modern HMEs are able to maintain physi-ological air-conditioning even in long-term ventilated

patients with less labour and costs per day.24 In spon-

taneously breathing, tracheostomized ICU patients also

both, HH and HMEs perform satisfactorily in preser-

vation of heat and humidity of inspired gases.25 HMEs

of different manufacturers may differ in their perfor-

mance,26 but different composition of condensation

surface or filter membrane does not seem to have much

effect on their performance.27 The use of HMEs in neo-

nates can achieve an absolute humidity of 28 mgH2

O/L

and atemperature of 30 C or more, but higher values

are achieved using aHH.28

There does not seem to have a consensus on how

frequently HME filters should be changed. Since using

the HME for a longer time may have effect on its per-

formance as well as colonization of bacteria, changing

the HME every 24 hours has been advocated. Earlier

studies suggested that changing HME filters after 48

hours did not affect its performance and maintained heat

and humidity.29,30

Other studies reported satisfactoryperformance after three days to one week31-33 How-

ever, all these studies reported some indirect evidence

of very little, if any, change in HME resistance.

In a recently published study, four electrostatic

HMEF were assessed on a bench-test in conformity

with the ISO 9360: 2000 standard. They showed dif-

ferences between the HMEFs for both humidification

and resistance parameters. When compared to the new

version of the standards, HMEFs demonstrated their

reliability, however, evolution of humidification and flow

resistance characteristics over 24h showed a structural

degradation, limiting their use over a longer period.34

The type of humidification device may negatively

influence the mechanical efficacy of ventilation. HMEs

have been noted to have small increase in airway resis-

tance and dead space25,35 that may alter the alveolar

ventilation and may play a crucial role in difficult to wean

patients and unless the pressure support level is con-

siderably increased, the use of a HME should not be

recommended in difficult or potentially difficult to wean

patients with chronic respiratory failure.36

It may alsoprovide some PEEP effect during spontaneous ventila-

tion.35 Some studies have reported endotracheal tube

occlusion caused by inadequate airway humidification

with use of HMEs in ICU patients.11,37-39

There is major concern regarding the type of

humidification system on the rate of ventilator-associ-

ated pneumonia (VAP). Various studies have failed to

record the colonization of HMEs with microbial after

varying period of ventilation nor different kind of HMEs

have shown any change in tracheal colonization orVAP.27,30-32 Two meta-analyses have suggested an as-

sociation between the use of HME and a decreased

VAP rate40,41

There has been equivocal evidence in respect to

choice of humidifiers in relation to reducing the inci-

dence of VAP, some favoring HME42,43 while others

reporting lower incidence from HH in patients requir-

ing long-term respirator therapy.44 Both HHand HMEs

can be used with no

significant impact on the incidenceof VAP and other criteria may justify their choice.45This

was summarized well by Kola et al in a meta-analysis,

who found a significant reduction in the incidence of

VAP in patients humidified with HMEs during MV, par-

ticularly in patients ventilated for 7days or longer. How-

ever, this finding is limited by the exclusion of patients

at high risk for airway occlusion from some of the stud-

ies. Moreover, contraindications (tenacious secretions,

airway obstructive disease, hypothermia) and techni-

cal issues of HMEs must be considered.41

Two mechanisms have been postulated in devel-

opment of VAPs; the inclusion of microbiological gas

filter in the HME, which protects the patient from ex-

ogenous VAP; and reduced contaminated condensate

in the HME circuit. Previous studies evaluating the ef-

fect of gas filtration in anaesthesia machines46,47 and in

ventilators48were unable to demonstrate differences in

the incidence of VAP between the patient groups with

and without filters. The contaminated condensate can


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be reduced by changing HMEs at an interval of 48 hours

or less and improvement of design of HH (servo-con-

trolled with dual-heated circuit and an autofeed cham-ber). Lower incidence of tube occlusion,11,37,38,49 thick

bronchial secretions and atelectasis 11,23,37,50have been

reported with HH than patients with HMEs.

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Election Notification 2008

The following office bearers of ISA HQ are retiring on 30th December 2008:

1. Dr. K. R. N. Tagore - President

2. Dr. B.V.R. Sastry - Vice President

3. Dr. Anjan Datta - Hon. Secretary

4. Dr. Bijendra Kumar Roy - Treasurer5. Dr. Rajib Bhattacharya - Governing Council Member

6. Dr. Rajnish Kumar Jain - Governing Council Member

Therefore Election to the Governing Council ISA 2008 will be held at conference venue

of ISACON 2008 at S N Medical College, Jodhpur. Vacancies open for the year 2008 are as

follows and nominations are hereby invited for:

1. The President

2. The Vice President

3. Hon. Secretary

4. Treasurer

5. Governing Council Members three (3) posts

Rules and regulations regarding eligibility and the election are as par Article VII of the

Memorandum of Association of ISA.

Last Date for receiving nomination at ISAHQ: 28th November08

Last date for withdrawal of nomination: 26th December08 by 12 noon

Publication of Valid Nominations: 27th December08 at 1 PM

Polling: 28th December08 from 9AM till 4 PM

Specimen nomination form is available at our web site. One representative of each candi-

date will be allowed to be present at the designated area at the polling booth for observation. All

candidates seeking election may inform the name of their representative to the Chief ElectionOfficer in writing by 27th December08. Any sort of canvassing inside the polling arena is prohib-

ited. MEMBERS WITH VALID PHOTO ID CARD WITH BARCODE WILL BE ALLOWED

TO CAST THEIR VOTE.

Requests for bar code will be entertain till 15th November 2008 at HQ.

Dr. Anjan Datta

31st August08 Hon. Secretary, ISA (HQ)

Email:[email protected], [email protected]

Inhalation and Humidification

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Transcript of Inhalation and Humidification