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Page 1
Crit Care Nurs Q
Vol. 44, No. 1, pp. 33-48
Copyright (c) 2021 Wolters Kluwer Health, Inc. All rights reserved.
Smoking Addiction and
Strategies for Cessation
Briana DiSilvio, MD; Mohammad Baqdunes, MD;
Ahmad Alhajhusain, MD; Tariq Cheema, MD, FCCP, MMM
Cigarette smoking is the leading cause of chronic obstructive pulmonary disease (COPD) world
wide. Smoking cessation is thus integral to the treatment of COPD. Nicotine addiction is a disease
dependent on the complex interactions of neurotransmitter pathways, conditioned behaviors, en
vironmental cues, genetic predisposition, and personal life circumstances, which render some
more susceptible to tobacco abuse than others. The most successful smoking cessation programs
are individualized, comprehensive, and utilize combinations of clinician counseling, behavioral
reinforcement, community resources, advanced technology support (eg, smartphone apps, and
Internet Web sites), and pharmacotherapy (both nicotine-based and nonnicotine medications).
E-cigarettes were introduced to the US market in 2006 and touted as a safer alternative to to
bacco cigarette smoking. Unfortunately, over the last 5 to 10 years, recreational e-cigarette use, or
"vaping," has increased in popularity, especially among adolescents. This has introduced nicotine
addiction to an entire generation of nonsmokers and resulted in numerous cases of acute lung
disease, now known as e-cigarette or vape product use-associated lung injury (EVALI). In light of
these adverse events, e-cigarettes and vape products are not currently recommended as a smoking
cessation aid. Key words: nicotine addiction, nicotine replacement therapy, smoking cessation,
stages of change, vaping
T
OBACCO use is the leading cause of
preventable disease, disability, and death
in the United States.1 In 2018, the Centers
for Disease Control and Prevention (CDC)
estimated that 13.7% of US adults 18 years
and older  currently smoked cigarettes.  This
number has decreased compared with 2005
when 20.9% of US adults smoked cigarettes.2
Although this downtrend in tobacco use is en
couraging, greater than 34 million adults are
Author Affiliation: Division of Pulmonary Critical
Care Medicine, Allegheny Health Network, Allegheny
General Hospital, Pittsburgh, Pennsylvania.
Dr Cheema serves on the speaker's bureau for
Boehringer Ingelheim and GSK. Consultant for Noveme
Biotherapeutics Inc.
The authors have disclosed that they have no signif
icant relationships with, or fnancial interest in, any
commercial companies pertaining to this article.
Correspondence: Tariq Cheema, MD, FCCP, MMM, Di
vision of Pulmonary Critical Care Medicine, Allegheny
General Hospital, 320 East North Ave, Pulmonary Lab,
Pittsburgh, PA 15212 (Tariq.cheema@ahn.org).
DOI: 10.1097/CNQ.0000000000000338
still actively smoking, with roughly 480 000
deaths every year attributed to cigarette
use.2,3 More than 16 million Americans suffer
from a smoking-related disease, predomi
nantly chronic obstructive pulmonary disease
(COPD).3 Despite the detrimental health ef
fects, 38% of patients with COPD still smoke
cigarettes.4 Smoking cessation slows the pro
gression of lung disease, reduces mortality,
and is an essential component of COPD
treatment.5-7 In this article, we discuss the
pathophysiology of nicotine addiction, the
clinician approach to addressing tobacco de
pendence, pharmacologic treatment to aid
cessation, and behavioral therapy interven
tions.  Lastly, we examine  the role of e
cigarettes in smoking cessation and their con
tribution to the alarming rise of recreational
vaping and emergence of vaping-related lung
injury.
NICOTINE ADDICTION
Approximately 70% of smokers desire to
quit; however, less than 10% are able to do
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33

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CRITICAL CARE NURSING QUARTERLY/JANUARY-MARCH 2021
so successfully each year.8,9 It is the effects of
nicotine that drive addiction to tobacco prod
ucts and make sustained smoking cessation
a challenge. Tobacco addiction is complex
and is dependent on the interplay of pharma
cology, learned and conditioned behaviors,
social and environmental cues, and genetic
makeup.10
Pharmacology of addiction and
tolerance
Inhalation of smoke particles from a
cigarette results in transmission of nicotine di
rectly to the lung alveoli. Once in the lungs,
nicotine can be rapidly absorbed into the
pulmonary venous circulation. Nicotine sub
sequently enters the arterial circulation and
is quickly transported to the brain where it
binds to nicotinic cholinergic receptors.10,11
Activation of these receptors triggers the re
lease of a variety of neurotransmitters in the
brain, among which is dopamine. Dopamine
plays a critical role in reward-motivated be
havior and the sensation of pleasure.10,12 In
addition to nicotine, inhaled cigarette smoke
contains substances that block the enzymatic
breakdown of dopamine in the body. The in
hibition of the enzymes, monoamine oxidase
type A and type B, thus increases dopamine
levels in the brain, further adding to the
addictiveness of smoking.13,14
With repeated cigarette smoke expo
sure, tolerance (also known as neuroadap
tation) develops to some of the effects of
nicotine.10,15 Desensitization occurs when
nicotine receptors close and become unre
sponsive to prolonged nicotine stimulation.15
Consequently there is a reduction in the pri
mary rewarding and reinforcing effects of
nicotine, which leads individuals to smoke
more to achieve the same pleasurable effect
as before.16 Desensitization is followed by
upregulation of nicotinic cholinergic recep
tors in the brain.17 The symptoms of craving
and withdrawal occur when desensitized re
ceptors become responsive during periods of
smoking abstinence, such as nighttime sleep
or attempts to quit. Smoking alleviates crav
ing and withdrawal by providing the nicotine
needed to activate nicotinic cholinergic re
ceptors in the brain, propagating a viscous
cycle of physical dependence.18
Conditioned behavior
Nicotine reduces stress levels and anxiety
in smokers. Daily smokers become depen
dent on cigarettes to enhance their mood, im
prove concentration, optimize performance
of various tasks, and decrease appetite.10,19
Cessation of smoking has the opposite ef
fect, causing irritability, depression, anger,
restlessness, anxiety, and weight gain.20 Even
when the physical symptoms of withdrawal
have diminished, the urge to resume smok
ing frequently persists, at this point having
more to do with conditioned behaviors and
smoking-related environmental cues. Smok
ers often associate cigarette use with breaks
from work, alcoholic beverages with friends,
coffee consumption, driving in the car, and
relief from stressful states.21,22 The antici
pated soothing and pleasurable effects of
nicotine in such situations are powerful cues
that sustain smoking in active users, and
trigger relapse in those who have recently
quit.
Risk factors for smoking dependence
Tobacco use typically begins during ado
lescence. Routine exposure to nicotine at
a young age increases the risk of smoking
dependence and addiction.3,23 The CDC re
ports that 90% of adult tobacco users began
smoking by the age of 18 years.3 Risk fac
tors for smoking in childhood or adolescence
include exposure from parents, peer pres
sure, poor academic performance, behavioral
issues (impulsivity, defance), mood disor
ders (anxiety, depression), low self-esteem,
and genetic infuences (Table 1).24-26 Ani
mal studies support the vulnerability of our
youth to addiction by demonstrating that
nicotine exposure in developing rat brains
can lead to permanent changes. Adolescent
rats exposed to nicotine have higher rates of
nicotine self-administration as adults, fndings
that are consistent with trends seen in human
populations.10,27,28
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Smoking Addiction and Strategies for Cessation
35
Table 1. Risk Factors for Smoking Addiction
Onset of tobacco smoking during
childhood or adolescence (<18 y)
Parental exposure
Peer pressure
Poor academic performance
Behavioral issues (ie, impulsivity, defance)
Mood disorders (ie, anxiety, depression)
Low self-esteem
Mental illness
Substance abuse
Lower socioeconomic status
Genetic predisposition
Additional risk factors for smoking addic
tion include mental illness, substance abuse,
and lower socioeconomic status. In a 2016
national survey, 32% of adults with mental
illness reported current use of tobacco com
pared with 23% of adults without mental
illness. In that same survey, 64% of adult
cigarette smokers reported co-use of alco
hol compared with 53% of adult nonsmokers.
Twenty-fve percent of cigarette smokers
reported co-use of illicit drugs (marijuana, co
caine, heroin, inhalants, and hallucinogens)
compared with 7% of nonsmokers.29 Smok
ing is also more prevalent among adults with
a GED certifcate only compared with adults
with graduate degrees (36% vs 3.7%), and
among adults with an annual household in
come less than $35 000 compared with those
with an annual household income more than
$100 000 (31% vs. 7.3%).2
Genetic influences
There is increasing evidence that genetics
play a role in susceptibility to nicotine ad
diction. Numerous studies exploring smoking
patterns and related behaviors among fam
ily members, adopted relatives, and twins
have found consistent heritability suggest
ing a substantial genetic contribution. As
one such example, nicotine is metabolized
primarily by the liver enzyme CYP2A6. In
dividuals with a genetic variant of CYP2A6
have reduced enzyme activity and metabolize
cigarettes slower. Slow metabolizers smoke
fewer cigarettes daily and are more likely
to successfully quit compared with rapid
metabolizers who experience more severe
withdrawal symptoms.30
CLINICIAN APPROACH TO SMOKING
CESSATION
Health care providers play a pivotal role
in identifying patients with cigarette addic
tion and providing them with the support
and tools needed to effectively quit smoking.
Guidelines from the United States Preventive
Services Task Force (USPSTF) recommend
clinicians use a 5-step guide, known as the "5
As" approach, when counseling on smoking
cessation.31
Ask
First step is to ask about tobacco use and
smoking habits, past and present. This al
lows clinicians to identify at-risk persons,
including both active smokers and those who
have recently quit but may be vulnerable to
relapse.31 It is crucial to inquire about all
forms of tobacco and nicotine use such as
cigars, pipes, chewing tobacco, hookahs, and
e-cigarettes/vape devices. Nineteen percent
of tobacco users cite use of 2 or more tobacco
products.32 Additional questions should per
tain to frequency of tobacco use, number of
cigarettes (eg, cigars and vapes) smoked daily,
history of quit attempts, withdraw symptoms,
and willingness to cease tobacco use at this
time.33
Advise
Second step is to advise your patient to
quit smoking in a clear, strong, and personal
ized manner.34,35 Several studies have shown
that any face-to-face counseling, even when
brief (<10 minutes), can effectively help
patients quit tobacco smoking and remain ab
stinent for 1 year.31,36 There does, however,
appear to be a dose-response relationship
between intensity/duration of counseling
and quit rates.34 Administering advice that
encourages smoking cessation should not be
restricted to physicians and can be provided
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CRITICAL CARE NURSING QUARTERLY/JANUARY-MARCH 2021
by nurses, social workers, case managers, and
psychologists.37
Assess
Third step is to assess readiness to quit
smoking.34 This can be challenging as many
tobacco users are simply not interested in
smoking cessation. Clinicians may fear iso
lating patients by repeatedly inquiring about
their willingness to stop tobacco use. Fun
damental to the third step is understanding
that a smoker's inclination toward cessa
tion is dynamic and their decision to quit
usually a gradual one.35 Providers may fnd
patients in any 1 of the following 5 "stages
of change": precontemplation (not interested
in quitting), contemplation (self-refection on
tobacco use, weighing pros/cons of quitting),
preparation (commitment made to quit, has
begun developing a plan), action (actively en
gaging in cessation plan), and maintenance
(abstinence from smoking at least 6 months)
(Table 2).38,39
For those contemplating quitting, assis
tance should be provided (see the "Assist"
subsection). For those in the precontem
plative
stage,
motivational
interviewing
techniques may be useful and can help clin
icians more effectively explore the smoker's
own perception of their addiction. Examples
of such techniques include using empathic
and refective listening with regard to the
patient's reasons for not quitting, acknowl
edging
personal
barriers
to
cessation,
Table 2. Five Stages of Behavior Change
highlighting patient values and goals that
confict with smoking, discussing risks asso
ciated with ongoing tobacco use, building
on past cessation success, providing patients
with choices and control over how to pro
ceed, and leaving the door open to future
conversations.34,35
Assist
Fourth step is to assist smokers who are
ready to quit.34 Clinicians should support quit
attempts via a combination of cessation coun
seling, pharmacotherapy, and community re
sources (see the "Pharmacologic Treatments"
and "Behavioral Interventions and Resources"
sections). Past quit attempts should be re
viewed to identify methods that were suc
cessful and the factors that contributed to
relapse. A quit date should be set within 2
weeks and tobacco products should be re
moved from all environments (home, work,
car, etc). It is benefcial for family, friends, and
coworkers to be informed of the quit attempt,
as their encouragement can promote success.
Anticipating temptations, triggers, cravings,
and withdrawal symptoms allows patients to
formulate a plan to overcome the urge to
return to smoking.34,35
Arrange
Fifth step is to arrange follow-up. This
can be done in person or via phone call.
Follow-up should occur within 1 to 2 weeks
with the intention of providing ongoing
Stage
Description
Precontemplation
Not interested in quitting; may be unaware of need to change;
overestimates cost of change; underestimates beneft
Contemplation
Self-refection on tobacco use; weighing pros/cons of quitting; may
consider change within the next 6 mo
Preparation
Commitment made to quit; has begun developing a plan; will take action in
the next month
Action
Actively engaging in cessation plan; has quit within the last 6 mo; needs
encouragement to remain tobacco-free; at high risk of relapse
Maintenance
Abstinence from smoking at least 6 mo; living a smoke-free lifestyle; may
beneft from reminders about high-risk situations
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Smoking Addiction and Strategies for Cessation
37
support, to monitor impact of both pharma
cologic and behavioral treatments, to address
adverse side effects and to discuss barriers to
success the patient may be experiencing.34,35
While total abstinence from smoking is the
ultimate goal, it is realistic to recognize that
many smokers will experience a relapse dur
ing their quit attempt. Up to 50% of smokers
40,41
relapse in the frst year.
On average,
smokers make between 8 and 11 quit at
tempts before successfully quitting.42 Patients
who have failed a quit attempt should be
encouraged to try again, and to smoke as
little as possible during periods of relapse.
Reduced smoking has been associated with
subsequent cessation.35
PHARMACOLOGIC TREATMENTS
Food and Drug Administration (FDA)
approved pharmacotherapy for smoking ces
sation consists of short-acting nicotine re
placement products (gum, lozenge, nasal
spray, and inhaler), long-acting nicotine re
placement therapy (transdermal patch), and
the nonnicotine medications, varenicline, and
sustained-release bupropion (Table 3). Nor
triptyline is an alternative non-FDA-approved
medication for smoking cessation.7
Nicotine gum
Nicotine gum is one of the more commonly
used nicotine replacement therapies (NRTs)
for smoking cessation. It has been shown to
have higher smoking success rates at 1 year
compared with placebo gum (23% vs 13%).63
To achieve optimal effect, a special technique
is required, which consists of slow chewing
alternating with parking the gum between
the cheek and the gums of the mouth. Rec
ommended duration of nicotine gum use is
up to 3 months.43
Advantages to nicotine gum include over
the-counter (OTC) availability, fexible dos
ing, and fast delivery of nicotine for quick
relief of cravings. Furthermore, the habit of
gum chewing can be likened to the habit
of smoking, but with far less toxic effects.50
Disadvantages include the inability to eat
or drink 15 to 30 minutes prior to use,
frequent dosing, jaw fatigue and soreness,
50,51
gastric distention, hiccups, and nausea.
An additional drawback is that some smokers
have reported becoming addicted to nico
tine gum.59 Nicotine gum is contraindicated
in patients with dental problems (ie, loose
teeth, dentures), temporomandibular joint
syndrome, and in the 2 to 4 weeks following
myocardial infarction, uncontrolled arrhyth
mias, and unstable angina. It should be noted
that these cardiovascular precautions apply to
all nicotine products.39,51 Nicotine gum is a
US FDA pregnancy category C drug.39
Nicotine lozenges
Nicotine lozenges are administered orally
and contain 25% more nicotine than gum.61
They have a 6-month success rate of 24%
compared with 14% for placebo.52 Lozenges
should be sucked slowly until the taste be
comes strong and occasionally moved from
one side of the mouth to the other. It is
normal for a warm or tingling sensation to
be felt in the mouth. Lozenges should not
be chewed or swallowed.44 Recommended
duration of lozenge use is 3 to 6 months.35,44
Advantages to lozenges include OTC avail
ability, fexible dosing, ability to be used by
denture wearers, and fast onset of effect to
produce prompt relief of cravings.51,52 Stud
ies have shown delayed weight gain with
lozenge use compared with unassisted smok
ing cessation.52 Lozenges possess many of the
same disadvantages as nicotine gum: inabil
ity to eat or drink 15 to 30 minutes prior
to use, hiccups, mouth and throat irritation,
belching, nausea, and vomiting.35,39,51 Other
side effects include headache, dizziness, di
arrhea, anorexia, and sweating.60 Because of
the potency of nicotine lozenges, there is
a risk of overdose, especially if taken with
some other form of nicotine.61,60 As with all
nicotine replacement products, lozenges are
contraindications in acute cardiovascular dis
ease. It is a US FDA pregnancy category D
drug.51
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CRITICAL CARE NURSING QUARTERLY/JANUARY-MARCH 2021
Table 3. FDA-Approved Pharmacotherapy for Smoking Cessation
Medications
Dose/Instructions
Advantages
Disadvantages
Nicotine gum
Use 4-mg gum if frst
cigarette <30 min after
waking; use 2 mg if
frst cigarette >30 min
after waking. Chew 1
piece every 1-2 h, then
taper; chew up to 24
pieces a day; use gum
for up to 3 mo43
OTC availability, fexible
dosing, fast delivery of
nicotine for quick relief
of cravings; habit of
gum chewing can be
likened to the habit of
smoking50
Cannot eat or drink
15-30 min prior to use,
frequent dosing,; may
cause jaw
fatigue/soreness,
gastric distention,
hiccups, and
nausea50,51; potential
for addiction59; c/i  if
dental problems, TMJ
syndrome; CV
precautions39,51
Nicotine
Use 4-mg lozenge if frst
OTC availability, fexible
Cannot eat or drink 15-30
lozenges
cigarette <30 min after
dosing, can be used by
min prior to use; may
waking; use 2 mg if
frst cigarette >30 min
denture wearers, fast
onset of effect51,52;
cause hiccups, mouth
and throat irritation,
after waking. Start with
delayed weight gain
belching, nausea,
1 lozenge every 1-2 h,
with lozenge use
vomiting, headache,
then taper. Do not use
compared with
dizziness, diarrhea,
>20 lozenges in a
35
day44; use  for 3-6  mo
unassisted smoking
cessation52
anorexia,
sweating35,39,51,60;
overdose concern
because of high
potency61,60; CV
precautions39
Nicotine
1 dose is equal to 1 spray
Control over dosing; fast
Requires a prescription
nasal spray
in each nostril; use 1-2
delivery of nicotine
due to highly addictive
doses every hour, up to
provides immediate
potential51; frequently
40 doses per day; use
rewarding effects35
causes nasal irritation
45
spray for up to 3 mo
(which lasts several
weeks into treatment),
runny nose, sneezing,
throat irritation,
coughing, and watery
45,53; CV
eyes
precautions39
Nicotine
Use 6-16 cartridges per
Control over dosing;
Visible use of device; may
inhaler
day; each cartridge
mimics the
cause mouth and throat
delivers 80 inhalations.
hand-to-mouth motion
irritation, coughing,
Use inhaler for an
of smoking a cigarette53
rhinitis46; requires a
initial 12-wk period,
prescription; CV
followed by a gradual
precautions39
taper over 12 wk46
(continues)
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Smoking Addiction and Strategies for Cessation
39
Table 3. FDA-Approved Pharmacotherapy for Smoking Cessation (Continued)
Medications
Dose/Instructions
Advantages
Disadvantages
Nicotine
If >10 cigarettes per day,
OTC availability, once
Less fexible dosing
patch
use 21-mg patch daily
daily application,
schedule; may cause
for 6 wk, then 14-mg
discreteness, reliable
skin irritation, insomnia
patch daily for 2 wk,
nicotine levels, low risk
if worn at night,
then 7-mg patch daily
of habituation50,51
tachycardia, nausea,
for 2 wk. If <10
vomiting, dizziness35,62;
cigarettes per day, use
slow release of nicotine
14-mg patch daily for
does not suppress
6 wk, then 7-mg
acute cravings; CV
patch daily for
precautions39
2 wk47
Sustained-
Take 150-mg by mouth in
Low potential for abuse;
May cause insomnia, vivid
release
the morning for 3 d,
decreases
dreams, dry mouth,
bupro
then increase to
cessation-related
rhinitis, headaches,
prion
150 mg twice a day;
weight gain compared
nausea, and anxiety;
consider dose
with placebo and NRT;
lowers seizure
reduction in renal and
safer than NRT among
threshold; may cause
hepatic impairment.
pregnant/lactating
serious
Begin therapy 1-2 wk
before the quit date,
women and patients
with CV disease54,55;
neuropsychiatric
symptoms including
and continue for
48
3-6 mo
bupropion can be
combined with
nicotine patch to
increase effcacy36
depression, psychosis,
suicidal
thoughts/attempts48;
c/i in those with eating
disorders, recent head
trauma, and those
taking MAOIs35,39
Varenicline
0.5 mg by mouth once
Very effective
May cause headache,
daily for 3 d, then
monotherapy for
nausea, insomnia,
0.5 mg twice a day for
smoking cessation
abnormal/vivid dreams,
4 d, then 1 mg  twice a
(increases quit rates by
fatulence, new or
day; reduce dose in
patients with renal
2-3 times compared
with placebo)56,57;
worsening seizures,
increased rates of
impairment and on
varenicline can be
accidental injury;
dialysis. Begin therapy
combined with
neuropsychiatric
1 wk before quit date
nicotine patch to
symptoms have been
and continue for 3-6
49
mo
further increase
effcacy58
reported; there may be
an increased risk of CV
events in patients with
underlying CV
disease49
Abbreviations: c/i, contraindicated; CV, cardiovascular; MAOI, monoamine oxidase inhibitor; NRT, nicotine replacement
therapy; OTC, over-the-counter; TMJ, temporomandibular joint.
Nicotine nasal spray
highest levels of nicotine.64 Despite this,
Of all the nicotine replacement products,
they do not provide nearly the amount of
nasal sprays provide the fastest delivery and
nicotine that cigarettes do.65 Nicotine nasal
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CRITICAL CARE NURSING QUARTERLY/JANUARY-MARCH 2021
spray has a 6-month success rate of 31% com
pared with 14%  for placebo.66 Recommended
treatment duration is 3 months.45
Advantages of nicotine nasal spray include
control over dosing and fast delivery of nico
tine, which provides immediate rewarding
effects similar to that of smoking.35 Disad
vantages include its highly addictive potential
and thus a prescription requirement for
purchase.51 Additional side effects include
nasal irritation, runny nose, sneezing, throat
45,53
irritation, coughing, and watery eyes.
While the severity of nasal irritation declines
with continued use of nicotine nasal spray,
the majority of patients (81%) still report mild
to moderate symptoms after several weeks of
treatment.45 Nicotine nasal spray is a US FDA
pregnancy category D drug.39
Nicotine inhaler
Nicotine inhalers consist of a nicotine-flled
cartridge attached to a plastic mouthpiece.51
The majority of nicotine (>95%) is absorbed
in the mouth rather than in the airways of the
lungs46 Nicotine inhaler use has been shown
to double cessation rates at 6 months when
compared with placebo (23% vs 11%).66 Use
is recommended for an initial 12 weeks' pe
riod, followed by a gradual taper over 12
weeks.46
The advantage of the nicotine inhaler is
that it mimics the hand-to-mouth motion of
smoking a cigarette, which may attenuate
some of the behavioral challenges associ
ated with cessation.53 Disadvantages include
conspicuous use, mouth and throat irri
tation, coughing, rhinitis, and prescription
requirement.46 Nicotine inhalers differ from
vape devices and e-cigarettes in that they are
FDA approved, available via prescription only,
have an exact and stated amount of nicotine,
and do not involve a heating element. Addi
tionally, nicotine inhalers deposit most of the
nicotine in the mouth as opposed to trans
porting it to the lungs as occurs in vaping.67
Vaping has been discussed in more detail in
an upcoming section. Nicotine inhaler is a US
FDA pregnancy category D medication.39
Nicotine transdermal patch
When applied to a dry and hairless area
daily, nicotine transdermal patches release
nicotine in a steady fashion over several
hours.47 Patches have been shown to increase
cessation rates by 1.5 to 2 times when com
pared with placebo.68-70 Nicotine patches are
available in 3 strengths: 7, 14, and 21 mg
per 24 hours.47 Selection of patch strength
and treatment duration depend on how many
cigarettes are smoked daily (refer to Table 1).
The nicotine patch should not be placed on
the same area again for at least 1 week.
Advantages to nicotine patch use include
OTC availability, once daily application, dis
creteness, reliable nicotine levels, and low
risk of habituation.50,51 Disadvantages in
clude less fexible dosing schedule, skin
irritation, insomnia if worn at night, tachy
cardia, nausea, vomiting, and dizziness.35,62
Unfortunately, the slow release of nicotine
does not suppress acute nicotine cravings. It
is a US FDA pregnancy category D drug.51
Sustained-release bupropion
Bupropion is an atypical antidepressant
that inhibits the reuptake of dopamine and
noradrenaline in the central nervous system
and is a noncompetitive nicotine recep
tor antagonist. The antismoking effect of
bupropion is likely secondary to attenua
tion of nicotine withdrawal symptoms after
cessation.71 In several studies, sustained-
release bupropion demonstrated 6-month
success rates ranging from 21% to 30% com
pared with 10% to 19% for placebo.72-75 A
Cochrane database review of 44 trials re
vealed that when bupropion was used as
sole pharmacotherapy, it increased long-term
cessation rates by 1.6 times.76 Bupropion
therapy should be started 1 to 2 weeks be
fore the quit date, and continued for 3 to 6
months after cessation.48
Bupropion has low potential for abuse,
and is observed to have decreased cessation-
related weight gain compared with placebo
and NRT. It is also felt to be safer than
nicotine among pregnant/lactating women
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Smoking Addiction and Strategies for Cessation
41
and patients with cardiovascular disease.54,55
Commonly experienced adverse effects are
insomnia, vivid dreams, dry mouth, rhini
tis, headaches, nausea, and anxiety. Serious
neuropsychiatric symptoms have been re
ported and include depression, mania, psy
chosis, hostility, agitation, paranoia, homici
dal ideation, suicidal thoughts and behavior,
and attempted suicide. There is a boxed
warning for increased suicidal thoughts and
behaviors in children, adolescents, and young
adults aged 18 to 24 years.48 Bupropion is
contraindicated in patients with eating disor
ders, recent head trauma, and those already
taking monoamine oxidase inhibitors.35,39
The medication should also be avoided in
smokers with a seizure history, and in com
bination with drugs that lower the seizure
threshold. Extreme caution should be taken
in those who concomitantly use alcohol, ben
zodiazepines, barbiturates, and antiepileptics,
as abrupt discontinuation of these substances
can precipitate seizures.48 Bupropion is a US
FDA pregnancy category C drug.39
Varenicline
Varenicline is a selective nicotine recep
tor partial agonist. It reduces cravings and
withdrawal symptoms through partial activa
tion of the receptor, while limiting nicotine's
ability activate the mesolimbic dopamine
system. This attenuates the reinforcing and
rewarding effects that lead to dependence.77
Several studies demonstrate that varenicline
increases the chance of a successful quit at
tempt two- to threefold compared with no
pharmacologic assistance.56,57 In one ran
domized controlled trial (RCT), using vareni
cline 1.0-mg dose increased abstinence rates
at 52 weeks by 5 times when compared
with placebo (22.4% vs 3.9%).78 Pooled re
sults from 4 trials comparing bupropion with
varenicline show a 32% higher quit rate
when varenicline is used.76 The medication
should be started 1 week before quit date and
continued for 3 to 6 months.49
Disadvantages to varenicline use include
headache, nausea, insomnia, abnormal/vivid
dreams, fatulence, the development of new
or worsening seizures, and increased rates
of accidental injury. Like bupropion, post-
marketing neuropsychiatric symptoms have
been reported and include behavioral change,
hostility, agitation, depressed mood, suicidal
thoughts, and attempted suicide. Surprisingly
however, the boxed warning for neuropsy
chiatric symptoms was removed from vareni
cline in 2016 by the FDA after a study
indicated these events occurred only rarely in
those with preexisting psychiatric disease.49
In the past there have been conficting
data regarding varenicline's association with
adverse cardiovascular events.79 More re
cently, a 2016 meta-analysis of 38 RCTs with
over 12 000 patients showed no evidence
that varenicline increases the rate of serious
cardiovascular events, including myocardial
infarction, unstable angina, coronary artery
disease, arrhythmias, congestive heart fail
ure, transient ischemic attack, stroke, sudden
death, and/or cardiovascular-related death.80
The FDA is somewhat ambiguous in their
position on this stating that patients with
underlying cardiovascular disease may be at
increased risk for cardiovascular events but
these concerns need to be balanced with
health benefts of smoking cessation. Vareni
cline is a US FDA pregnancy category C
medication.49
Nortriptyline
Nortriptyline is a non-FDA-approved med
ication for smoking cessation. It is primar
ily prescribed as an antidepressant.34 The
mechanism through which it aids smok
ing cessation is unclear but may relate to
dopaminergic and adrenergic activity.81 Re
search has demonstrated that, when com
pared with placebo, nortriptyline can double
abstinence rates.76 It is available by prescrip
tion in oral form. Recommended dosing is
25 mg once daily begun 10 to 28 days
prior to quit date. Dose can be titrated
to 75 to 100 mg/day as needed. Therapy
should be continued for 12 to 24 weeks
after quit day.34 Nortriptyline use is limited
by an extensive side effect profle, which in
cludes anticholinergic properties (dry mouth,
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CRITICAL CARE NURSING QUARTERLY/JANUARY-MARCH 2021
blurred vision, and urinary retention), psychi
atric manifestations (hallucination, disorien
tation, delusions, and insomnia), neurologic
symptoms (paresthesia, ataxia, tremors, and
seizures), cardiovascular disease (myocardial
infarction, stroke, and arrhythmias), hemato
logic dyscrasias (bone marrow suppression),
endocrine abnormalities (gynecomastia, hy
perglycemia, and impotence), and gastroin
testinal disturbance (nausea, vomiting, ab
dominal pain, and diarrhea).82 It is a US FDA
pregnancy category C medication.83
Combination pharmacotherapy
Combining the nicotine patch with a more
rapidly absorbed form of NRT (gum, lozenge,
inhaler, and nasal spray) is more effective
than using a single nicotine product alone
for smoking cessation.34,84-86 As such, com
bination therapy should be offered as initial
treatment over monotherapy when NRT is
chosen.87 This combined regimen is con
sidered safe because patients are still ex
posed to less nicotine overall than smoking
cigarettes.34
Multiple studies have demonstrated that
combination NRT has similar abstinence rates
compared with use of varenicline alone, mak
ing either of these 2 approaches a frst-line
recommendation for smoking cessation.88,89
For those using varenicline monotherapy
who have cut back on smoking but are unable
to quit completely, adding a nicotine patch
increases the likelihood of cessation.58
Bupropion appears to be less effective than
combination NRT or varenicline and as such
should be considered second-line or alterna
tive therapy.87 In patients prescribed bupro
pion who fail to achieve complete tobacco
abstinence, adding a nicotine patch increases
effcacy over bupropion monotherapy.36 The
combination of bupropion and NRT does
not appear to be more effective for smoking
cessation than NRT alone.76
BEHAVIORAL INTERVENTIONS AND
RESOURCES
Nonpharmacologic treatment of tobacco
dependence is integral to successfully achiev
ing smoking cessation. Personalized counsel
ing, behavioral skills training, and motiva
tional interviewing occur at various points
throughout a patient's journey to smoking
abstinence.36 Some of these interventions oc
cur during the initial stages of assessing one's
readiness to quit tobacco and were discussed
previously in the section "Clinician Approach
to Smoking Cessation."
In-person counseling
There are several behavioral therapy modal
ities and counseling formats that can be
employed when assisting a patient in their at
tempt to quit smoking. Strategies should be
tailored to patient interest and availability.87
Brief counseling sessions as part of rou
tine offce visits are what commonly occur
for busy clinicians and patients with lim
ited time. Counseling lasting less than 10
minutes can still increase the proportion of
patients that quit and remain smoke free
at 1 year.34 More formal individual counsel
ing consists of multiple one-on-one clinician
visits dedicated to patient motivation and
reinforcement of behavior change that be
gin even prior to the patient's quit date.87
Patients should receive at least 4 in-person
counseling sessions.34 Group counseling in
volves participants meeting regularly with a
facilitator who is trained in smoking cessation
counseling. The strength of this approach
is that patients can increase their support
ive social network, model behavior discussed
by other group members, get peer feedback
and encouragement on their personal experi
ences, and reduce the cost as associated with
treatment.90
Telephone counseling and text
message/app support
Not all therapy and support must be
provided in person. Telephone counseling in
terventions have been proven effective if pa
tients are provided with at least 3 telephone
calls by professionals trained to offer cessa
tion advice and guidance over the phone.36
Proactive, prearranged calling by a coun
selor is likely more effcacious than reactive
patient-initiated calling.91 In the Unites States,
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Smoking Addiction and Strategies for Cessation
43
patients have additional access to free tele
phone coaching by calling 1-800-QUIT-NOW.
Patients can also register through the CDC
to have free quit help and encouragement
texted to their phone.92 Individuals interested
in more interactive technology can download
free smartphone apps (ie, quitStart) that mon
itor smoking behavior, provide reminders for
taking medication, and offer tailored tips and
inspiration.87,92
Web site resources
Several Internet Web sites are available to
aid smoking cessation efforts. These Web
sites provide information on smoking addic
tion and its harms, tools on how to quit,
and links to other treatment resources. Exam
ples include www.smokefree.gov, www.quit.
com, and www.lung.org/stop-smoking.93-95
These sites should be used as an adjunct
to other treatment approaches, as there is
limited evidence that online resources as
a stand-alone intervention are effective in
increasing cessation rates.87 The most suc
cessful Internet-based interventions involve
Web sites that are interactive and specifcally
tailored to individuals.96
Unproven therapies
Exercise, acupuncture, and hypnotherapy
have all been explored as alternative ther
apies to aid smoking cessation. Systematic
reviews have demonstrated a lack of evidence
that these treatment modalities are benefcial
to improving quit rates.97-99
E-CIGARETTES AND VAPING
Electronic
nicotine
delivery
systems
(ENDS)
are
non-FDA-approved
devices
that
include
e-cigarettes
and
other
vape products. While variations of the
e-cigarette can be traced back to the 1960s,
the modern e-cigarette was developed in
2003 by a Chinese pharmacist, Hon Lik. In
2006, e-cigarettes were frst introduced in the
United States for commercial sale and were
marketed as a safer alternative to smoking
cigarettes.100 The emergence of e-cigarette
or vaping product use-associated lung injury
(EVALI) has certainly challenged that claim.
Composition of e-cigarettes/vape
products
ENDS vary in size, shape, and composi
tion  but in general  have  4 main compo
nents: a reservoir that holds the liquid to
be aerosolized or "vaped" (also known as
e-liquid), an atomizer, which is a heating
element, a battery to power the atom
izer, and a mouthpiece for inhalation.100,101
The primary components of e-liquid consist
of nicotine, synthetic favoring, tetrahydro
cannabinol, cannabidiol, and/or butane hash
oils (dabs). A combination of these sub
stances in varying ratios can be present
in any one given vape product.102 What is
more alarming are the additional chemical
constituents present in ENDS that are unbe
knownst to the consumer. Propylene glycol,
glycerin, polycyclic aromatic hydrocarbons,
formaldehyde, nitrosamines, volatile organic
chemicals, and inorganic toxic metals have
all been detected in vape products.103,104
Compounding matters further, substances
in e-liquid undergo thermal decomposition
by the metallic heating coils to produce
novel toxic compounds.102 Intense heat re
leases heavy metals such as iron, aluminum,
zinc, nickel, tin, and lead into the aerosol.
E-cigarette and vape users are thus potentially
exposed to infnite combinations and permu
tations of inhalants with unknown adverse
effects.100
Targeting youth
While favoring of traditional tobacco
cigarettes is prohibited, the e-liquids in vape
products come in more than 7000 unique
favors, making them particularly appealing
to the nation's youth. Since 2014, ENDS
have been the most commonly used nicotine
product among adolescents.100 From 2017
to 2018, the prevalence of e-cigarette and
vape device use increased from 11.7% to
20.8% among US high school students.105
By 2019, 27.5% of high school students and
10.5% of middle school students endorsed
vaping.106 This amounts to over 5 million
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CRITICAL CARE NURSING QUARTERLY/JANUARY-MARCH 2021
middle and high school students engaged in
current use of e-cigarette/vape products. In
contrast, only 3.2% of US adults reported cur
rent e-cigarette/vape device use in 2018.107
Of substantial concern is that use of ENDS
has introduced nicotine addiction to an entire
generation of nonsmokers and may become a
bridge to future tobacco use.100
E-cigarette or vaping product
use-associated lung injury
Since 2019, the CDC has linked vaping to
the development of a severe form of acute
lung disease, which they named EVALI (e
cigarette or vaping product use-associated
lung injury).108 EVALI is diverse in presenta
tion with the following lung injury patterns
reported: diffuse alveolar hemorrhage, exoge
nous lipoid pneumonia, acute eosinophilic
pneumonia, hypersensitivity pneumonitis,
respiratory bronchiolitis-interstitial lung dis
ease, and organizing pneumonia.102,109 Diag
nosis consists of use of an ENDS within 90
days of symptom onset, pulmonary infltrates
on computed tomography of the chest or
chest roentgenogram, absence of pulmonary
infection on initial workup, and no alternative
plausible diagnosis.102 As of February 2020,
there have been a total of 2807 hospitalized
EVALI cases with 68 deaths.108
The role of e-cigarettes in smoking
cessation
E-cigarettes and vape products are not
currently approved by the FDA as smok
ing cessation aids.107 Results from available
studies regarding effcacy in smoking ces
sation are mixed. Evidence from a 2016
systematic review of 2 RCTs involving 662
participants found that e-cigarettes with nico
tine increased long-term quit rates by twofold
compared with nonnicotine e-cigarettes.110 A
2019 RCT of 889 participants determined that
e-cigarettes were more effective to achieve
smoking abstinence at 1 year than NRT, when
both products were accompanied by behav
ioral support (18% vs 9.9%).111 In contrast, a
CDC online survey of 15 000 smokers found
that most adult e-cigarette users attempting to
quit tobacco actually do not stop smoking tra
ditional cigarettes, and instead become dual
users of both products.112 Despite the poten
tial effcacy of e-cigarettes and vape devices as
quit aids, safety concerns outlined previously
in this article appear to outweigh the benefts
of their use.
The USPSTF has formally concluded that
there is insuffcient evidence to recommend
e-cigarettes for smoking cessation in adults.
The CDC and the FDA recommend that
adults currently using nicotine-containing
e-cigarettes or vaping products as alternatives
to cigarettes should not return to smoking.
Instead, they should consider using FDA-
approved smoking cessation medications. If
patients choose to use e-cigarettes, they
should completely stop use of traditional
cigarettes and not partake in dual use of both
products. ENDS should never be used by
youths, adolescents, young adults, or women
who are pregnant. Adults who do not cur
rently use tobacco products should not start
using e-cigarettes or vaping products.108
CONCLUSIONS
Despite its decline in recent years, to
bacco smoking still continues to be a major
threat to the health of millions of individu
als in this country and even more worldwide.
Nicotine addiction is complex and an under
standing of the pharmacology, conditioned
behaviors, risk factors for abuse, and genetic
contribution is crucial for successful treat
ment. Smoking cessation programs are most
effective when they implore a multimodal ap
proach including clinician counseling, behav
ioral reinforcement, pharmacotherapy, and
even interactive technology. Cessation strate
gies should be tailored to individual interests.
Triumph over smoking is highly dependent
upon maintenance of patient autonomy and
input to this process. While there is some
evidence that e-cigarettes and vape products
may assist the effort to quit, overwhelming
safety concerns render them an unadvised
option at this point.
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Smoking Addiction and Strategies for Cessation
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