Critical Care Medicine

Journal of Pharmacy Practice

24(1) 7-16
Mechanical Ventilation: Introduction ª The Author(s) 2011
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for the Pharmacy Practitioner DOI: 10.1177/0897190010388145
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Michael J. Cawley, PharmD, RRT, CPFT1

Abstract
Mechanical ventilation is a common therapeutic modality required for the management of patients unable to maintain adequate
intrinsic ventilation and oxygenation. Mechanical ventilators can be found within various hospital and nonhospital environments
(ie, nursing homes, skilled nursing facilities, and patient’s home residence), but these devices generally require the skill of a
multidisciplinary health care team to optimize therapeutic outcomes. Unfortunately, pharmacists have been excluded in the
discussion of mechanical ventilation since this therapeutic modality may be perceived as irrelevant to drug utilization and the
usual scope of practice of a hospital pharmacist. However, the pharmacist provides a crucial role as a member of the
multidisciplinary team in the management of the mechanically ventilated patient by verifying accuracy of prescribed
medications, providing recommendations of alternative drug selections, monitoring for drug and disease interactions, assisting
in the development of institutional weaning protocols, and providing quality assessment of drug utilization. Pharmacists may
be intimidated by the introduction of advanced ventilator microprocessor technology, but understanding and integrating
ventilator management with the pharmacotherapeutic needs of the patient will ultimately help the pharmacist be a better
qualified and respected practitioner. The goal of this article is to assist the pharmacy practitioner with a better understanding
of mechanical ventilation and to apply this information to improve delivery of pharmaceutical care.

Keywords
mechanical ventilation, pharmacist

Introduction pharmacological agent delivery including appropriate drug

selection, accurate dose and dose titration, and monitoring of
Mechanical ventilators are medical devices that provide an arti-
agents that may impede ventilator weaning outcomes.
ficial means of ventilatory support. They are routinely used in
This article will assist the pharmacy practitioner with a
various health care settings including hospitals, long-term care
better understanding to integrate and apply basic principles
facilities, ambulance, and mobile intensive care units (ICUs), of mechanical ventilation with pharmaceutical care delivery for
life flight, and helicopter transport. Also their routine use main-
the mechanically ventilated patient.
tains patient independence during wheelchair ambulation and
within home environments suitable for patients with chronic
respiratory diseases. The technology of these medical devices History of Mechanical Ventilation
has progressed from rudimentary electronic controls to inte-
The history of mechanical ventilation can be traced back to the
grated microprocessor-controlled devices that respond and
term ‘‘artificial respiration’’ identified in Biblical, Egyptian
adapt to patient ventilatory needs to optimize gas exchange.
and Greek references. Artificial respiration continued to be
Education of mechanical ventilation primarily occurs from
experimented with throughout history until the early 19th cen-
health care providers intimately involved with the bedside care
tury, with the development of the ‘‘iron lung.’’ The iron lung
of the patient including pulmonary critical care physicians/
was the first practical mechanical ventilator device that
intensivists and other multidisciplinary team members includ-
ing respiratory therapists and critical care nurses. Pharmacists
routinely encounter patients on mechanical ventilation and 1
Philadelphia College of Pharmacy, University of the Sciences in Philadelphia,
require a better understanding of the terminology and funda- Philadelphia, PA, USA
mentals of ventilator settings, which may ultimately effect drug
therapy utilization. Limited data have been published in the Corresponding Author:
Michael J. Cawley, Department of Pharmacy Practice and Pharmacy
pharmacy literature discussing mechanical ventilation.1-3 The Administration, Philadelphia College of Pharmacy, University of the Sciences
inclusion of pharmacists during the discussion of the ventilator in Philadelphia, 600 South 43rd Street, Philadelphia, PA 19104, USA
plan of the patient provides expert knowledge of Email: m.cawley@usp.edu
8 Journal of Pharmacy Practice 24(1)
improved patient outcomes including patient survival during
the poliomyelitis epidemics in the mid-1950s.4,5 This device
was a airtight metal cylindrical tank that required the patient
to be placed inside in the supine position. The patient’s head
was exposed out of the device. Negative pressure then was gen-
erated with a mechanical pump to make the patient’s chest rise.
Although this device was lifesaving for many patients, it was
very clumsy and impractical based upon its crude mechanical
design. Other devices then spawned from this method of venti-
lation included cuirass devices which required the patient upper
torso to be encased into a crude shell or compartment that also
worked based upon the negative-pressure model. These devices
had limited utility but some models are still utilized around the
world for patients with neuromuscular diseases who require
ventilatory support.
In the 1970s, respiratory critical care medicine changed with
the advent of rudimentary computer microprocessor positive-
pressure ventilators. These devices including the Bennett
MA-I (Puritan-Bennett Corp., Kansas City, Missouri) and the
Ohio 560 (Ohio Medical Products, Madison, Wisconsin)
offered many advantages including ventilator mode selection,
fraction of inspired oxygen (FIO2) adjustment setting, intermit-
tent physiological ‘‘sigh’’ breath to limit atelectasis, positive
end-expiratory pressure (PEEP), inspiratory humidification,
and multiple alarm systems. These devices had the ability for
the medical professional to change multiple ventilator para-
meters and interface with patient ventilatory requirements.
In the 20th century, mechanical ventilators are now
equipped with more advanced microprocessor controls which
augment pressure and flow waveforms to interface and syn-
chronize with patient ventilatory requirements. These devices
will continue to evolve to provide the most advanced technol-
ogy in the modern age of respiratory medicine.
Indications for Mechanical Ventilation
Mechanical ventilation is primarily required for patients unable
to maintain adequate alveolar ventilation, resulting in respira-
tory failure. Respiratory failure can be categorized as hypoxic
or hypercapnic. Hypoxic respiratory failure is inability of the
patient to maintain adequate oxygenation which is measured
by both the partial pressure of oxygen in the arterial blood
(PaO2) and the saturation of oxygen in arterial blood (SaO2).
Inability to correct tissue hypoxemia with the highest amounts
of FIO2 (100%) requires the need for positive pressure ventilation.
Hypercapnic respiratory failure is defined as the inability to
maintain adequate ventilation, or as an increased partial pressure
of carbon dioxide in the arterial blood (PaCO2). Increases in PaCO2
result in progressive respiratory acidosis, also require the need
for positive pressure ventilation. Other pulmonary parameters
for assessing the need for mechanical ventilation have been
published but are beyond the scope of this article.6,7
Mechanical ventilation may be administered by either an
invasive or a noninvasive delivery method. Invasive methods
are required for emergent situations in which airway access and
stabilization is required and for patients unable to maintain
adequate airway protection. Invasive delivery methods require
the introduction of an artificial device to be placed into the
upper airway (ie, endotracheal [ET], nasotracheal, or tracheost-
omy tube). Once the artificial airway is properly placed and
location verified by radiographic evidence, the patient may
now be initiated on mechanical ventilation.
Basics of Mechanical Ventilation
Pharmacists must first become familiar with common terminol-
ogy and basic mechanical functioning associated with the use
of mechanical ventilators. Appendix A provides a summary
of mechanical ventilation terminology including abbreviations,
meanings, and definitions associated with the use of mechani-
cal ventilators. Mechanical ventilator breaths are delivered to
the patient by an integration of both triggering (what initiates
the ventilator support breath) and cycling (what ends the venti-
lator support breath). Ventilator breaths are traditionally classi-
fied as volume, pressure, or time cycled. These forms of
cycling all occur when the inspiratory phase begins and gas
flows through the ventilator circuit into the patient’s lungs.
Volume cycling ends when a predetermined volume is deliv-
ered, pressure cycling ends when a predetermined pressure-
sensing mechanism in the ventilator reaches a preset level, and
time-cycling ends when a timing mechanism in the ventilator
reaches a preset duration. The final result is a ventilator breath
that is delivered with either volume or pressure. A more
detailed review of mechanical ventilation focused as a tutorial
for pharmacists can provide additional information.1
Traditionally, the first parameter that must be chosen for ini-
tial implementation of mechanical ventilation is the mode of
ventilation. Despite this fact, other basic parameters must be
clarified before explaining how the mode of ventilation is inte-
grated with the following ventilator parameters.
Tidal Volume
The tidal volume is the volume of air inhaled then passively
exhaled in a normal respiratory cycle.8 The tidal volume breath
is set based upon the patient’s ideal body weight and has
traditionally ranged from 4 to 12 mL/kg.9 Data have also
recommended tidal volume variations including lower volumes
of 4 to 8 mL/kg for patients with restrictive lung disease to limit
peak alveolar pressures and 8 to 10 mL/kg for patients with
obstructive lung disease to limit air trapping.9 Lower tidal
volumes are also proposed for acute lung injury (ALI) and adult
respiratory distress syndrome (ARDS) to limit its effects in
causing barotrauma or volutrauma to alveoli.10 Despite contro-
versy in determining the most optimum tidal volume setting,
most clinicians select an initial tidal volume of 5 to 10 mL/kg.
Respiratory Rate
The respiratory rate is the number of preset tidal volume
breaths the patient will receive per minute. Traditionally,
mechanical ventilator respiratory rates may range from 0 to
Cawley
60 breaths/min. Clinicians initiating mechanical ventilation
may arbitrarily start the initial respiratory rate between 10 and
20 breaths/min. After approximately 20 to 30 minutes, an arter-
ial blood gas sample would then be drawn from the patient. The
resulted PaCO2 and pH would require a change in the ventilator
respiratory rate. If the patient is experiencing hyperventilation
(# PaCO2), a decrease in the preset respiratory rate would be
warranted to raise the PaCO2; if hypoventilation is occurring
(" PaCO2), an increase in the preset respiratory rate would be
warranted to decrease the PaCO2.
Flow Rate
The inspiratory flow rate is the volume of gas that is delivered to
the patients lungs per unit of time. Inspiratory flow rate is
expressed in liters/minute and the setting can ultimately deter-
mine the inspiratory/expiratory (I:E) ratio of the respiratory cycle.
The normal I:E is 1:2, but patients with severe pulmonary
critical care illness (eg, ARDS) may require an inverse I:E of
2:1 or 4:1. A longer inspiratory time may be required to recruit
damaged or compromised pulmonary alveoli to improve
oxygenation and alveolar ventilation. The inspiratory flow rate
is traditionally started at 40 to 60 L/min but may require an
increase or decrease to achieve an optimal I:E ratio based upon
the patient’s pulmonary condition.
Fraction of Inspired Oxygen
The FIO2 is the percentage of oxygen that can be delivered to
the patient during a mechanical ventilator breath or patient
breath. The FIO2 can range from 21% (environmental or room
air) to 100%. During initial implementation of mechanical ven-
tilation, the FIO2 is traditionally initiated at 100% if the
patient’s oxygenation status is unknown. Arterial blood gas
analysis is performed 20 to 30 minutes after the FIO2 change.
Repeated arterial blood gases would only be required to mon-
itor the arterial PaCO2 and pH since these ventilation parameters
may be affected by changes in the respiratory rate. If the clin-
ician is only concerned about the degree of hypoxemia, then
subsequent oxygenation monitoring can be done using a pulse
oximeter to measure the SaO2 in a noninvasive method. A dis-
advantage of this device is it may produce inconsistent results
in patients with compromised peripheral perfusion.
A common concern of oxygen therapy is the potential for
oxygen toxicity. Oxygen has shown to cause the formation of
oxygen metabolites and reactive mediators. Oxygen exposure
to an FIO2 of 40% or higher for up to 30 days is associated with
fibrinitic changes to the pulmonary system.11 Although data
has demonstrated that oxygen has some degree of inflicting
pulmonary changes, the use should not be discouraged for
patients who require treatment of arterial hypoxemia.
Positive End-Expiratory Pressure
PEEP refers to positive pressure that is maintained within the
lungs after the exhalation phase of a mechanical ventilator
9
breath. The primary role for PEEP is to increase the functional
residual capacity (FRC) of the alveoli. Increasing the FRC
increases the surface area of the alveoli, allowing greater sur-
face area for oxygen to transfer into the pulmonary circulation.
The result is increasing oxygenation including improvements
in PaO2 and SaO2. PEEP is traditionally added for patients
unable to attain adequate PaO2 or SaO2 values on FIO2 concen-
trations greater than 50%. The value of adding PEEP is an
oxygen-sparing effect where the potential of oxygen toxicity
is decreased with the need of lower FIO2 requirements. PEEP
is usually begun at 5 cm H2O pressure and is increased in
2.5 cm H2O increments to achieve the optimum PaO2 goal.
PEEP levels usually range from 5 to 10 cm H2O but may
exceed greater than 20 cm H2O (super PEEP) for the most
critically ill patients.
PEEP improves oxygenation delivery but also has negative
adverse effects including potential for pneumothorax and
hemodynamic instability. Pneumothorax may develop due to
excessive intrathoracic pressure. Hemodynamic instability is
induced due to decreased cardiac venous return. Patients may
require greater pharmacological support to optimize hemody-
namics during PEEP including aggressive fluid resuscitation
and/or vasopressor initiation.
Traditional Modes of Mechanical Ventilation
Despite the availability of several advanced modes of ventilator
support, there are still fundamental modes that all ventilators
have in common. The focus of this review is to focus on these
fundamental modes including assist-control ventilation (A/C),
synchronized intermittent mandatory ventilation (SIMV),
pressure-control ventilation (PCV), pressure-support ventila-
tion (PSV), and continuous positive airway pressure (CPAP).
Noninvasive ventilation will discuss CPAP and bilevel positive
airway pressure (BiPAP). Figures 1 and 2 provide a basic
understanding of airway pressure waveforms created during
traditional modes of invasive and noninvasive mechanical
ventilation.
Assist-Control Ventilation
Assist-control (A/C) is one of the most common volume-cycled
modes selected for patients requiring invasive mechanical ven-
tilation. During A/C, the clinician sets a predetermined tidal
volume and respiratory rate but the patient is able to self-
initiate additional tidal volume breaths. The self-initiated
breath occurs due to the negative pressure generated by the
patient within the ventilator tubing. To receive this self-
initiated breath, the clinician must set a triggering threshold
or sensitivity. The sensitivity is traditional set at 2 cm H2O
pressure. Once the patient inhales and reaches this preset sen-
sitivity value, the ventilator will deliver the preset tidal volume
breath. If the patient is unable to generate a self-initiated breath
due to excessive pharmacological sedation or other physiologi-
cal processes inhibiting or ceasing respiration, the patient is
guaranteed to receive the preset tidal volume and respiratory
10 Journal of Pharmacy Practice 24(1)

+30

Note negative inspiratory(I) pressure to “trigger”

A/C 0 the assist-control breath.
I I
–5

+30
E E E Note spontaneous breathing
(I -inspiration + E -expiration) between SIMV
SIMV 0 breaths. Note negative pressure deflection
“triggered”by the patient, which initiates the
SIMV SIMV breath.
I SIMV SIMV I
–5 I

+30

Note regular time intervals of machine pressure

PCV 0 control breaths.
–5

+30
Note negative inspiratory pressure (I) initiating the
PSV breath. Downward arrow indicates the pressure
PSV 0 plateau of a PSV breath. Upward arrow indicates the
termination of the PSV breath.
I I I
–5

Figure 1. Pressure waveforms of traditional modes of invasive positive pressure ventilation. A/C indicates assist-control ventilation; SIMV,
synchronized intermittent mandatory ventilation; PCV, pressure control ventilation; PSV, pressure support ventilation. Modified from reference 1.

+15

+5
Note CPAP (+5) is maintained during spontaneous
*CPAP 0 breathing.

–5

IPAP IPAP IPAP

+15
+5 Note IPAP (+15) is the PSV value and EPAP (+5) is
EPAP EPAP EPAP
the CPAP value.
BiPAP 0

–5

Figure 2. Pressure waveforms of traditional modes of noninvasive positive pressure ventilation. CPAP indicates continuous positive airway
pressure; BiPAP, bilevel positive airway pressure; IPAP, inspiratory positive airway pressure; EPAP, expiratory positive airway pressure; PSV,
pressure support ventilation; *CPAP is also used during invasive positive pressure ventilation as a ventilator weaning mode.

rate. If the patient is unable to generate an A/C breath, then the deliver the same tidal volume and respiratory rate, but CMV
mode would be referred to as control-mode ventilation (CMV). does not allow the patient to self-initiate a breath.
CMV (eg, machine controlled) and A/C (eg spontaneous sup- A/C mode is often started as the initial mechanical ventilator
port) are technical variations of each other. CMV and A/C mode due to simplicity and familiarity by clinicians. This mode
Cawley
is very effective but it does come with limitations in its use
including the potential for hyperventilation, resulting in
excessive minute ventilation. A preset tidal volume (mL) 
respiratory rate (breaths/minute or bpm) equals minute
ventilation (eg, 0.7 L  14 bpm ¼ 9.8 L/min). If the patient
begins to self-initiate additional tidal volume breaths due to
experiencing pain, anxiety, or other etiologies, the result
may be hyperventilation and respiratory alkalosis (eg, 0.7 L
 25 bpm ¼ 17.5 L/min). Clinicians that prefer limiting
pharmacological interventions to decrease respiratory drive
may consider changing the ventilator mode to SIMV.
Synchronized Intermittent Mandatory Ventilation
SIMV is another common volume-cycled mode of mechanical
ventilation. SIMV is similar to A/C in that the patient receives a
preset tidal volume and respiratory rate, but the key difference
is the patient’s own respiratory rate is synchronized with the
SIMV ventilator rate. As the patient receives the preset tidal
volume and respiratory rate, the patient is able to breathe at
their own tidal volume between each preset ventilator breath.
The result is the patient can spontaneously breathe between
each of the preset tidal volume supported breaths. Some clini-
cians prefer this mode since the ventilator not only delivers pre-
set tidal volume breaths but allows the patient to contribute to
their own respiratory effort. Allowing the patient to contribute
to their own respiratory effort improves respiratory muscle
exercise and conditioning.12 A potential disadvantage of SIMV
is when the patient respiratory muscle conditioning is exceed-
ing above and beyond what is capable for the patient. This will
lead to increased work of breathing, respiratory fatigue, and
ultimately respiratory failure, inhibiting weaning from
mechanical ventilation. Either limiting the patient’s time on
SIMV or adding PSV to SIMV may limit respiratory fatigue
and improve ventilator weaning outcomes.
Before the introduction of SIMV, IMV (Intermittent Manda-
tory Ventilation) was the primary mode of choice. IMV and
SIMV again are technical variations of each other. The only
difference between IMV and SIMV is that SIMV allows the
patients spontaneous breathing pattern to be synchronized with
the SIMV rate. Due to this advancement, SIMV has replaced
IMV in modern mechanical ventilators.
Pressure-Control Ventilation
PCV is a time-cycled pressure-cycled mode that provides a
constant pressure throughout the inspiratory phase. PCV is
often required for patients unable to maintain adequate oxyge-
nation or ventilation goals during volume-controlled ventila-
tion (A/C or SIMV) or may also be initiated in patients
experiencing increased peak airway pressures during volume-
controlled ventilation. The most critically ill pulmonary
patients including ARDS and ALI may require PCV to achieve
oxygenation and ventilatory goals. A major limitation of this
form of ventilation is it requires excessive sedation, and possi-
ble pharmacological paralysis, to optimize oxygenation and
11
ventilation. Also, there is always the potential for pulmonary
complications including pneumothorax due to excessive intra-
pulmonary pressures.
Pressure Support Ventilation
PSV provides a preset pressure assistance that is delivered
during each spontaneous patient breath. The primary purpose
of this mode of ventilation is to overcome airway resistance
of the ET tube and to decrease ventilator tubing dead space.
Both airway resistance and ventilator tubing dead space are
primary etiologies that lead to an increase in the work of
breathing. As a result, failure to wean from mechanical ven-
tilation is increased. PSV can be used alone for weaning from
mechanical ventilation or it can be used in combination with
other modes (SIMV) to assist the patient during periods of
spontaneous breathing. If used alone, PSV is delivered with
each spontaneous patient breath. If used with SIMV, PSV
is only applied during spontaneous breaths taken between
ventilator-mandated breaths. Clinicians initially set the pres-
sure support by increasing the pressure until the patient
achieves the desired expired tidal volume. If the patient
requires initial higher pressure support levels (eg, 20 cm
H2O), then progressive weaning of pressure support will be
required for removal of mechanical ventilation. Extubation
and removal of mechanical ventilation will be considered
once the patient is breathing comfortably and has reached a
final PSV level of 6 to 8 cm H2O.13
Continuous Positive Airway Pressure
CPAP is a preset pressure level that is maintained within the
pulmonary system throughout the respiratory cycle. CPAP
requires a patient to provide and maintain a continuous respira-
tory effort. This mode may be initiated in different ways based
upon the ventilator manufacturer but traditionally the ventilator
respiratory rate is set to 0 to prevent any controlled ventilator
breaths from being initiated. Once the respiratory rate is set
to 0 then CPAP is added. Levels of 5 cm H2O are traditionally
started to maintain physiological pulmonary pressure above
atmospheric pressure. CPAP can be either administered alone
or combined with PSV (eg, CPAP 5cm H2O þ PSV 10 cm
H2O). During spontaneous ventilation, the patient will receive
CPAP to maintain continuous airway pressure to optimize
alveolar ventilation and PSV to provide a present pressure level
during each spontaneous patient breath to decrease the work of
breathing. CPAP alone or with PSV are the primary ventilator
modes used to promote ventilator weaning and mechanical
ventilation discontinuation.
Advanced Modes of Mechanical
Ventilation
Mechanical ventilators have evolved to integrate both com-
puter microprocessor technologies with ventilatory require-
ments for the patient. Many ventilator manufacturers have
12
incorporated new forms of advanced modes of mechanical
ventilation for their products. Unfortunately, there is limited
scientific data to support the routine use of these advanced
modes in daily clinical practice. Examples of advanced modes
of ventilation include biphasic intermittent positive airway
pressure, mandatory minute ventilation, proportional assist
ventilation, adaptive support ventilation, pressure regulated
volume control, high-frequency oscillatory ventilation, and
airway pressure release ventilation. Until more scientific data
are published in regard to the efficacy of one advanced mode
over another, these modes will continue to be used as rescue
therapy or when other traditional ventilator modes fail.
Modes of Noninvasive Mechanical
Ventilation
Noninvasive mechanical ventilation or noninvasive positive
pressure ventilation (NIPPV) is a form of ventilation initiated
for patients who require assistance in optimizing pulmonary
gas exchange including patient with obstructive sleep apnea,
respiratory failure induced by acute exacerbations of chronic
obstructive pulmonary disease (COPD), and acute respiratory
failure caused by acute pulmonary edema.14,15 NIPPV has the
advantages to avoid many of the complications of ET intuba-
tion including oversedation, airway trauma, and ventilator-
associated pneumonia.16,17 The primary form of NIPPV is
BiPAP because of its ability to integrate both inspiratory and
expiratory positive airway pressures to optimize pulmonary gas
exchange. A secondary NIPPV mode is CPAP. Both forms of
NIPPV require the patient to wear an anatomically appropriate
mask or nasal device. Patients require the skill of a respiratory
therapist to select and custom fit the best device to achieve and
maintain optimum performance and patient comfort.
Bilevel Positive Airway Pressure
BiPAP is a form of NIPPV that utilizes and cycles both inspira-
tory (I) and expiratory (E) pressure to achieve optimum venti-
latory outcomes. The inspiratory pressure is considered the
PSV, and the expiratory pressure is the CPAP level. BiPAP
is clinically indicated for patients with chronic stable or pro-
gressive respiratory failure (preventing the need for ET intuba-
tion), which may include patients with COPD exacerbations,
acute pulmonary edema, asthma, pneumonia, or for patients
who refuse ET intubation.
Physician prescribing BiPAP may transcribe the written
orders with the following abbreviation format: BiPAP I10/E4.
The designation I10 refers to the inspiratory pressure (pressure
support) level of 10 cm H2O and E4 refers to the expiratory pres-
sure (CPAP) level of 4 cm H2O. To begin BiPAP, the patient is
placed in a sitting position and inclined at approximately 45 . As
the inspiratory and expiratory pressures are initiated, the mask is
then gently placed over the patient’s nose or mouth and fitted for
comfort. Patients are usually started at an inspiratory pressure of
8 to 10 cm H2O and expiratory pressure of 4 to 6 cm H2O. The
BiPAP device can also be set for a backup mandatory ventilator
Journal of Pharmacy Practice 24(1)
respiratory rate (4-12 bpm) for patients who may experience
apnea. Oxygen can be titrated into the BiPAP circuit between
0.5 and 6 L/min for patients requiring supplemental treatment for
tissue hypoxia.
Continuous Positive Airway Pressure
As previously discussed, CPAP is primarily used as a weaning
mode for patients during invasive mechanical ventilation but
can also be used as a very effective NIPPV strategy. CPAP tra-
ditionally has been implemented for common BiPAP pulmon-
ary indications but is more commonly used for adult patients
with a diagnosis of moderate-to-severe obstructive sleep
apnea.18 Obstructive sleep apnea is primarily diagnosed with
nocturnal sleep study testing. The optimum CPAP pressure is
selected based upon the results of the sleep study test results,
which may have included periods of oxygen desaturation or
increased apnea periods. After the patient is custom fitted for
the appropriate mask or nasal device, the CPAP level is usually
initiated at 2.5 to 15 cm H2O. Oxygen may be titrated into the
CPAP circuit between 0.5 and 6 L/min for patients requiring
supplemental treatment for tissue hypoxia.
Both CPAP and BiPAP devices, although very effective, are
not without their limitations. The primary limitation of CPAP
devices is compliance with their use. Patients may discontinue
or abandon the use of their CPAP devices due to discomfort,
noise level, or potential discouragement of intimacy with a
sleeping partner. Compliance rates for utilizing nocturnal pos-
itive airway pressure vary throughout the literature based upon
the definition of adequate adherence. A comprehensive review
of CPAP literature published prior to 2003 found noncompli-
ance rates to vary from 5% to 50%, with an average of 20%.19
Humidification
Inspired air enters through the nostrils and passes over the
warm ciliated mucous layer before passing into the nasophar-
ynx. This process maintains a hydroscopic foundation to main-
tain mucous viscosity and assistance to transport foreign
inhaled material. During mechanical ventilation, patients may
require oxygen or other compressed air source gases. Since
these compressed gas sources are dry, they require humidifica-
tion before delivery to the patient. Humidification is accom-
plished utilizing heated systems such as a heated pass over
humidification source or nonheated source such as a
heatmoisture exchange system. Both systems provide advan-
tages and disadvantages. Heated pass over systems may poten-
tially harbor and colonize bacterial organisms and require
frequent sterilization. Heatmoisture exchange systems which
are connected at the end of the ventilator tubing to the ET tube
may become occluded with pulmonary secretions, thus
resulting in increased airway pressures and work of breathing.
Alarms
Mechanical ventilators require safeguards to prevent malfunc-
tion and potential harm to the patient. These machines are
Cawley
equipped with a multitude of electronic alarms that must be set,
checked visually, and checked for auditory sound and docu-
mented. Respiratory care departments have specific protocols
to provide this safeguard. Alarms include low/high pressure,
apnea, patient disconnect, low/high FIO2, low/high respiratory
rate, and low/high minute volume.
Complications of Invasive and
Noninvasive Mechanical Ventilation
Invasive mechanical ventilation may be associated with numer-
ous complications including mechanical, physiologic, and oper-
ator error. Mechanical complications include simple
malfunction of the device or improper setting of alarms. Physio-
logic complications include lung overinflation (volutrauma or
barotraumas), leading to pneumothorax, oxygen toxicity, health
care-associated pneumonia (hospital and ventilator), sinusitis,
gastrointestinal complications, neuromuscular weakness, delir-
ium, and cardiovascular instability.1 Also, complications of the
artificial airway including hard and soft palate injuries, vocal
cord dysfunction or paralysis, soft tissue injury to the oral cavity,
tracheal stenosis, and self-extubation.20 Many of these compli-
cations are primarily caused by the inflatable cuff located at the
distal portion of the ET or tracheostomy tube. The ET cuff is a
low-pressure cuff device that is required to maintain an airtight
seal between the ET or tracheostomy tube and the tracheal soft
tissue. The cuff is inflated to a pressure range of 10 to 20 cm
H2O. Overinflation of this cuff or maintaining exceedingly high
pressures can cause increased pressure on tracheal capillaries
leading to ischemia and potentially tracheal stenosis or rupturing
of the cuff. ET or tracheostomy cuff rupture requires immediate
intervention for replacement. ET and tracheostomy tubes should
be checked periodically for proper function which includes
maintaining adequate cuff pressures.
Noninvasive mechanical ventilation complications may
occur particularly through mechanical or operator error, but
patients are able to respond and simply discontinue the use of
the device (CPAP or BiPAP) until properly serviced. Subtle
physiological complications can occur including drying out
of the nasal mucosa, abdominal distention and flatulence, and
tissue irritation due to improperly fitted mask or nasal device.
Aerosol Therapy
Patients receiving both invasive and noninvasive mechanical
ventilation may require aerosol therapy. Aerosol therapy may
be administered by an aerosol generator such as a jet nebulizer
or metered dose inhaler (MDI). Both aerosol delivery devices
may assist in the delivery of beta agonists, anticholinergics,
antimicrobials, or other pharmacological agents. Despite the
advantages and disadvantages of both devices, there are several
factors that influence drug delivery to the mechanically venti-
lated patient. For an in-depth review, the reader is referred to a
1997 publication by Dhand and Tobin.21
Although all host factors are important, it is unlikely that
they will change for most patients (eg, ET size, tidal volume,
13
pressure waveform, device including MDI or nebulizer). One
exception may include the introduction of humidification into
the ventilator circuit during aerosol administration. Data have
identified that the administration of heated humidified air dur-
ing pharmacological aerosol delivery using a MDI can decrease
the amount of drug delivered to the smaller airways as much as
40%.21 Although significant decrease in the amount of drug
delivered to the smaller airways is evident, experts recommend
not shutting off heated humidification during aerosol MDI
treatment. Rationale includes forgetting to reinitiate the heated
aerosol, thus, potentially leading to pulmonary mucosa water
loss, exacerbating pulmonary mucous retention. Experts agree
that dosing of beta agonists and anticholinergic agents via MDI
should be increased to 4 to 6 puffs every 3 to 6 hours for stable
mechanically ventilated patients and higher doses may be
required for patients experiencing bronchospasm.22
MDI propellants are presently changing from chlorofluoro-
carbon (CFC) to hydrofluoroalkanes (HFA) due to effects of
depleting environmental ozone.23 HFA have demonstrated
similar drug deposition to the bronchi compared to CFC agents.
Optimization of drug delivery to the lower respiratory tract via
MDI is to add a spacer device approximately 15 cm from the
ET tube and coordinate the MDI actuation with the beginning
of ventilator inspiration.24 Connecting a nebulizer approxi-
mately 18 cm from the patient wye (connection from the end
of the ventilator tubing to the ET tube) also optimizes drug
delivery.25 The majority of adult ICUs prefer MDI over jet
nebulizer because of convenience, more consistent dosing, and
reduced chance of bacterial infection.26 In regard to pharma-
coeconomics, older data have suggested MDIs to be more
cost-effective than jet nebulizers; however, this may not be true
in transitioning from CFC-MDIs to HFA-MDIs. Prospective
clinical trials are needed to assess this issue between HFA
MDIs and jet nebulizers in mechanically ventilated patients.
Weaning From Invasive Mechanical
Ventilation
Weaning and discontinuing of invasive mechanical ventilation
is the ultimate goal for the patient. Weaning indicates gradual
cessation of all mandated ventilator support. Traditionally, clin-
icians have chosen one of a variety of techniques either alone or
in combination for weaning a patient from invasive mechanical
ventilation including SIMV or IMV, CPAP, PSV, or a sponta-
neous breathing trial (SBT) administered once per day or inter-
mittently several trials per day.27 SBT can be done by having the
patient breathe via a ‘‘T-piece’’ which allows the patient to be
disconnected from the ventilator and breathing through the ET
tube connected to a humidified oxygen supply. Another popular
SBT method is for the patient to interface with the ventilator
with low levels of PSV and CPAP (eg, PSV 5 cm H2O with
5 cm H2O CPAP). After initiation of a selected weaning method,
the patient is observed for signs and symptoms associated with
failure to wean from mechanical ventilation including increased
shortness of breath, tachycardia, diaphoresis, oxygen desatura-
tion, hypertension, and increased anxiety. A patient who is able
14
to maintain comfort without any obvious signs of respiratory
distress or pulmonary decompensation may be considered a can-
didate for extubation and removal from mechanical ventilation.
Throughout the medical literature, weaning from mechanical
ventilation is discussed in relation to the ventilator mode or
adjusting ventilator parameters to improve chances of disconti-
nuation. Weaning must also include a pharmacological weaning
component that includes discussion of sedatives, narcotic analge-
sics, and neuromuscular blocking agents (NMBAs). No universal
method has been devised to wean narcotic analgesics or sedatives
in patients receiving mechanical ventilation. Based upon the SBT
model, spontaneous awaking trials (SATs) have demonstrated
success as an alternative or adjunctive method for ventilator
weaning. This method discontinues all narcotic and sedative
agents daily to allow the patient to fully recover on their own. If
the patient is calm and comfortable, sedation is discontinued. If
a patient demonstrates respiratory distress, sedation may be rein-
itiated at half the previous dose. This is done daily until the patient
is able to achieve adequate criteria for removal of mechanical
ventilatory support without the need for continued sedative
agents. Recent data have demonstrated that when combining SBT
and SAT patients were 32% less likely to die at any instant during
the year compared to patients weaned with usual care and SBT.28
Other experts agree that the latest generation of weaning protocols
that combine SBT and SATs represent a streamlined, effective,
and safe approach to ventilator weaning and can be used for most
patients in the ICU.29 Although these methods have demonstrated
success, some clinicians may resist implementing these strategies
based upon a number of rationales including familiarity and suc-
cess with previous weaning methods, acute patient agitation due
to sedative discontinuation leading to dysynchrony with mechan-
ical ventilation which may precipitate a decrease in SaO2, hemo-
dynamic instability, and potential patient self-extubation.
A committed ICU team is required if SBT and SAT are to be rou-
tinely utilized within the ICU environment. If the patient demon-
strates improvement in their pulmonary status requiring to
‘‘lighten up’’ the patient’s sedation, the following general rule for
weaning is recommended. Decrease the continuous infusion of
either or both narcotic analgesic or sedative by 10% to 25% per
day, with periodic bolus dosing as needed for breakthrough pain
or agitation.30 This strategy has been recommended but weaning
titration or implementing weaning protocols depends upon many
different factors including pharmacokinetic and pharmacody-
namic of individual agents, degree of patient critical illness
including pulmonary, neurological, and nutritional status, and
ventilator plan of the patient. Weaning protocols have shown to
demonstrate superior outcomes compared to physician-directed
weaning.31 Patients entering the ICU requiring short-term intuba-
tion (24-48 hours) with no history of pulmonary disease routinely
are targeted for more aggressive downward titration or
discontinuation of narcotic analgesics and sedative infusions to
expedite extubation and discontinuation of mechanical ventilation.
Overuse or aggressive use of narcotic analgesics and/or seda-
tives can directly affect respiratory drive, leading to failure to
wean from mechanical ventilation. This may result in restarting
full ventilatory support in patients continued to be intubated or
Journal of Pharmacy Practice 24(1)
patients who have been extubated may require reintubation or
initiation of NIPPV to maintain adequate oxygenation and venti-
lation. If patients demonstrate dyssynchrony with mechanical
ventilator support despite no obvious physical or mechanical ven-
tilator dysfunction, then pharmacological agents must be
considered. Sedatives and/or analgesics can be administered
every 2 hours ‘‘as needed’’ to optimize patient comfort and accep-
tance of mechanical ventilation. Patients requiring dosing more
often than every 2 hours should be initiated on continuous infu-
sions of either or both classes of agents.30 Pharmacists must be
vigilant in discussing with the patients nurse to maintain frequent
assessment of degree of agitation or sedation utilizing an appro-
priate sedation scoring system. Sedation scoring systems have
demonstrated that both sedatives and analgesics can be titrated
to predetermined end points.30 No sedation scoring system is
superior to another but one method should be chosen and utilized
in every critical care unit to optimize administration of sedatives.
Patients continuing to demonstrate dyssynchrony with
mechanical ventilation despite no physical or mechanical com-
plications of mechanical ventilation and are receiving continu-
ous infusions of narcotic analgesics and sedatives must be
assessed for delirium. Patients inadvertently treated with benzo-
diazepines for delirium may become more agitated and con-
fused. Delirium can be assessed using the Confusion
Assessment Method (CAM) score. The CAM is a diagnostic tool
to assess delirium and can be utilized by nonpsychiatrists. It is
easy to use and has demonstrated effectiveness in clinical inves-
tigations.32 Although controversial, this tool can be completed at
the bedside by the nurse and can be completed in 2 minutes with
a 98% accuracy rate.30 Appropriate diagnosis of delirium can
then be treated with a typical antipsychotic such as haloperidol.
Haloperidol can be given as a bolus dose of 2 to 10 mg, with
repeated doses every 15 to 20 minutes, followed by 25% of the
loading dose scheduled every 4 to 6 hours.30
Pharmacists who understand and participate as a member of
the medical team in discussing the daily ventilator plan can
assist in assessment and weaning of narcotic analgesics and
sedatives. Pharmacists have a vital role in assisting the medical
team in the development of weaning protocols which include
optimizing drug selection, dose titration, and monitoring for
adverse effects to achieve ventilator weaning outcomes. Close
observation of drug utilization may limit potential adverse
effects including neurological and respiratory depression and
lead to successful mechanical ventilation independence.
Conclusion
Mechanical ventilation is a lifesaving and life-sustaining
modality that will continue to evolve. Pharmacists must be
included as a member of the medical team when discussing a
therapeutic ventilatory plan and in the development of ventilator
weaning protocols. Understanding the basic concepts of mechan-
ical ventilation will assist the pharmacist practitioner when making
pharmacotherapeutic recommendations. As medical technology
evolves, pharmacist will continue to play a vital role in rational
drug management to optimize pharmacotherapeutic outcomes.
Cawley
Appendix A
Table A1. Summary of Mechanical Ventilation Terminology
Abbreviation Meaning Definition
Vt Tidal volume Volume of gas inhaled or exhaled
during a normal respiratory
cycle.
VE Minute ventilation Volume of gas exhaled in 1 minute
and is the product of tidal vol-
ume and respiratory rate.
FIO2 Fraction of inspired Percentage of oxygen that can be
oxygen administered ranging from 21%
to 100%.
CMV Control-mode Time-cycled and volume-cycled
ventilation mode of ventilator support
generating an inspiratory tidal
volume breath independent of
the patient’s respiratory effort.
A/C Assist control Volume-cycled mode of ventilator
support administering a
predetermined tidal volume and
respiratory rate such as control-
mode ventilation, but the patient
may also trigger additional tidal
volume breaths above the
preset ventilator settings.
IMV Intermittent manda- Volume-cycled mode of ventilator
tory ventilation support in which a patient
receives a preset tidal volume
and respiratory rate but allows
the patient to breath sponta-
neously between predeter-
mined ventilatory breaths.
SIMV Synchronized inter- Volume-cycled mode of ventilator
mittent mandatory support similar to IMV but
ventilation prevents ‘‘stacking’’ of inspira-
tory tidal volume breaths.
PCV Pressure control Time-cycled and pressure-cycled
ventilation mode where a constant pres-
sure is maintained throughout
the preset inspiratory time.
PEEP Positive end- Maintains pressure held above
expiratory atmospheric pressure during
pressure the exhalation phase of a
mechanical initiated breath.
CPAP Continuous positive Maintains constant pressure held
airway pressure above atmospheric pressure
throughout the respiratory
cycle.
PSV Pressure support Provides preset inspiratory pres-
ventilation sure assistance during each
spontaneous patient breath.
BiPAP Bilevel positive airway Noninvasive positive pressure
pressure ventilation that provides con-
tinuous positive airway pres-
sures that cycles between a
preset high (inspiratory posi-
tive airway pressure [IPAP])
and low (expiratory positive
airway pressure [EPAP]).
(continued)
15
Table A1 (continued)
Abbreviation Meaning Definition
IPAP Inspiratory positive Amount of inspiratory pressure
airway pressure preset and administered during
noninvasive mechanical venti-
lation. IPAP is equivalent to
PSV.
EPAP Expiratory positive Amount of expiratory pressure
airway pressure preset and administered during
noninvasive mechanical venti-
lation. EPAP is equivalent to
CPAP.
Declaration of Conflicting Interests
The author(s) declared no conflicts of interest with respect to the
authorship and/or publication of this article.
Funding
The author(s) received no financial support for the research and/or
authorship of this article.
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