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1304 Articles
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JNCI Vol. 99, Issue 17
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September 5, 2007
Minor surgical procedures are regularly performed with adju-
vant injections of local anesthetic agents combined with sys-
temic sedative and analgesic medications. Although modern
drug regimens are effective in eliminating pain and improving
tolerability of procedures, surgery continues to be associated
with clinically significant side effects, including postsurgical
pain, nausea, and fatigue ( 1 – 3 ). These complications frequently
prolong recovery room stay, delay discharge, lead to unantici-
pated readmission, and require additional pharmacotherapeutic
Affiliations of authors: Department of Oncological Sciences (GHM, DHB,
JBS), Department of Surgery (AG, CRW), and Department of Anesthesiology
ARTICLE
A Randomized Clinical Trial of a Brief Hypnosis
Intervention to Control Side Effects in Breast
Surgery Patients
Guy H . Montgomery , Dana H . Bovbjerg , Julie B . Schnur , Daniel David , Alisan Goldfarb , Christina R. Weltz ,
Clyde Schechter , Joshua Graff-Zivin , Kristin Tatrow , Donald D . Price , Jeffrey H. Silverstein
Background Breast cancer surgery is associated with side effects, including postsurgical pain, nausea, and fatigue. We
carried out a randomized clinical trial to test the hypotheses that a brief presurgery hypnosis intervention
would decrease intraoperative anesthesia and analgesic use and side effects associated with breast cancer
surgery and that it would be cost effective.
Methods We randomly assigned 200 patients who were scheduled to undergo excisional breast biopsy or lumpec-
tomy (mean age 48.5 years) to a 15-minute presurgery hypnosis session conducted by a psychologist or
nondirective empathic listening (attention control). Patients were not blinded to group assignment.
Intraoperative anesthesia use (i.e., of the analgesics lidocaine and fentanyl and the sedatives propofol and
midazolam) was assessed. Patient-reported pain and other side effects as measured on a visual analog
scale (0 – 100) were assessed at discharge, as was use of analgesics in the recovery room. Institutional
costs and time in the operating room were assessed via chart review.
Results Patients in the hypnosis group required less propofol (means = 64.01 versus 96.64 µ g; difference = 32.63;
95% confidence interval [CI] = 3.95 to 61.30) and lidocaine (means = 24.23 versus 31.09 mL; difference =
6.86; 95% CI = 3.05 to 10.68) than patients in the control group. Patients in the hypnosis group also
reported less pain intensity (means = 22.43 versus 47.83; difference = 25.40; 95% CI = 17.56 to 33.25), pain
unpleasantness (means = 21.19 versus 39.05; difference = 17.86; 95% CI = 9.92 to 25.80), nausea (means =
6.57 versus 25.49; difference = 18.92; 95% CI = 12.98 to 24.87), fatigue (means = 29.47 versus 54.20; differ-
ence = 24.73; 95% CI = 16.64 to 32.83), discomfort (means = 23.01 versus 43.20; difference = 20.19; 95%
CI = 12.36 to 28.02), and emotional upset (means = 8.67 versus 33.46; difference = 24.79; 95% CI = 18.56 to
31.03). No statistically significant differences were seen in the use of fentanyl, midazolam, or recovery
room analgesics. Institutional costs for surgical breast cancer procedures were $8561 per patient at Mount
Sinai School of Medicine. Patients in the hypnosis group cost the institution $772.71 less per patient than
those in the control group (95% CI = 75.10 to 1469.89), mainly due to reduced surgical time.
Conclusions Hypnosis was superior to attention control regarding propofol and lidocaine use; pain, nausea, fatigue,
discomfort, and emotional upset at discharge; and institutional cost. Overall, the present data support the
use of hypnosis with breast cancer surgery patients.
J Natl Cancer Inst 2007;99: 1304 – 12
Sciences (JHS), Mount Sinai School of Medicine, New York, NY; Department
of Clinical Psychology and Psychotherapy, Babes-Bolyai University, Cluj-
Napoca, Romania (DD); Department of Family and Social Medicine, Albert
Einstein College of Medicine, Bronx, NY (CS); Department of Health Policy
and Management, Columbia University, New York, NY (JGZ); Department of
Psychology, Good Shepherd Rehabilitation Hospital, Allentown, PA (KT);
Departments of Oral and Maxillofacial Surgery and Neuroscience, University
of Florida, Gainesville, FL (DDP) .
Correspondence to: Guy H. Montgomery, PhD, Department of Oncological
Sciences, Mount Sinai School of Medicine, Box 1130, 1 Gustave L. Levy
Place, New York, NY 10029-6574 (e-mail: guy.montgomery@mssm.edu ).
See “Funding” and “Notes” following “References.”
DOI: 10.1093/jnci/djm106
© The Author 2007. Published by Oxford University Press. All rights reserved.
For Permissions, please e-mail: journals.permissions@oxfordjournals.org.
JNCI Journal of the National Cancer Institute Advance Access published August 28, 2007
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intervention ( 2 , 4 , 5 ), all of which are associated with increased
costs.
Nonpharmacotherapeutic manipulations of physiologic pro-
cesses have achieved success in mitigating pain and anxiety in many
contexts ( 6 , 7 ). One such technique is hypnosis, a brief cognitive –
behavioral technique with no specifi c side effects ( 8 , 9 ). Clinical
research with at least 20 different surgical populations has in -
dicated that hypnosis can reduce the need for medication, reduce
postsurgical symptoms, or enhance recovery (e.g., by reducing
pain, nausea, and length of hospital stay) ( 7 ).
Breast cancer surgery patients represent the largest cohort of
female cancer patients treated surgically in the United States each
year ( 10 ). Therefore, the development of nonpharmacologic inter-
ventions that can reduce the need for medication and provide
symptom relief for these patients could have a large impact. A
single small study has provided evidence of the treatment effi cacy
of hypnosis with breast cancer surgical patients ( 11 ). In addition,
meta-analyses ( 7 , 12 ), narrative reviews ( 13 , 14 ), and randomized
clinical studies ( 15 – 18 ) all support the potential clinical utility of
hypnosis with surgical breast cancer patients.
Breast cancer surgery thus represents an opportunity to exam-
ine the clinical benefi ts of presurgery hypnosis. Based on the
literature reviewed above, we designed a randomized clinical trial
of a brief presurgery hypnosis intervention compared with an
atten tion control condition in breast cancer surgery patients. Our
primary hypothesis was that a brief presurgery hypnosis inter-
vention would decrease use of perioperative pharmacotherapeutic
agents and would decrease pain, nausea, fatigue, discomfort, and
emotional upset following breast cancer surgery. Our secondary
hypothesis was that brief presurgery hypnosis would reduce costs
associated with surgical and medical procedures (e.g., use of medi-
cations, time spent in clinical areas).
Patients and Methods
Participants
Women scheduled for breast cancer surgery were recruited from
two Mount Sinai Medical Center (MSMC) surgical practices
(C. Weltz and A. G oldfarb). Patients who were scheduled to
undergo excisional breast biopsy or lumpectomy, with or without
limited axillary node dissection (including sentinel lymph node
biopsy), were eligible. The surgical procedures differed in that a
greater surgical margin was taken with lumpectomy to ensure full
resection of malignant tissue ( 19 ). Eligibility criteria also included
the ability to speak and read English (because the intervention and
study forms were in English) and willingness to be randomly
assigned to study treatment condition. Patients were ineligible if
they were scheduled for mastectomy or lumpectomy with full axil-
lary dissection or if they had any uncontrolled major comorbid
mental or physical illness. Patient hypnotizability was not assessed
because previous data indicate that approximately 89% of patients
would be responsive to the hypnosis intervention ( 7 ) and because
prescreening for hypnotizability with “gold standard” measures
would take longer than the intervention itself ( 20 ). The study
was approved by the Mount Sinai School of Medicine Institu -
tional Review Board, and all patients provided written informed
consent. Participants were randomly assigned to the hypnosis or
attention control group using computer-generated random positive
integers ( 21 ). Both the hypnosis and attention control conditions
are described below. Randomization was allocated by surgery type
(lumpectomy or excisional breast biopsy). That is, separate random-
ization allocations were used for each surgery type to ensure roughly
equivalent distributions of surgical patients across study groups
(it should be noted that the randomization allocations resulted in
unequal numbers in the intervention groups). To reduce potential
bias, blinding procedures were followed for assessment personnel,
anesthesiologists, and surgeons. Although blinding to group assign-
ment was not formally assessed, the following precautions were
followed: 1) the hypnosis intervention took place in a private room
away from clinical staff (anesthesiologists, surgeons); 2) anesthesia
data were recorded from computer records; no outcome data were
collected by clinical staff; 3) the same interventionists (PhD-level
clinical psychologists) met with all patients (hypnosis and attention
control), so the study assessment staff were not cued to group
assignment by the presence of an interventionist; and 4) the inter-
ventionists collected no outcome data. Interventionists were given
each patient ’ s randomization assignment on the morning of surgery.
Eligibility was confirmed before group assignment ( Fig. 1 ).
The hypnosis intervention was provided in a 15-minute session
on the morning of surgery, within 1 hour before surgery. The
postsurgical assessment was conducted at the end of the surgical
treatment day, before hospital discharge. Because patients received
CONTEXT AND CAVEATS
Prior knowledge
Hypnosis has been shown to reduce the need for medication and
postsurgical symptoms in some surgical populations, but its effec-
tiveness in breast cancer patients undergoing surgery was not
known.
Study design
Randomized trial in which use of anesthesia during surgery and
patient-reported postsurgical pain and other side effects were
compared in women who were randomly assigned to a brief
psychologist-conducted hypnosis intervention before excisional
tumor biopsy or lumpectomy or to a control (nondirected listening)
session with a psychologist. Institutional costs of surgery were also
compared between the groups.
Contribution
Patients in the hypnosis group required less of the analgesic lido-
caine and the sedative propofol during surgery than patients in the
control group; they also reported less postsurgical pain and other
side effects and spent less time in surgery. Surgical costs were also
lower in the hypnosis group.
Implications
The hypnosis intervention not only reduced use of anesthesia and
self-reported pain but also reduced institutional costs for surgery,
mainly by reducing time in the operating room.
Limitations
Patients were not blinded to their group assignment, and the ef -
fectiveness of blinding of the research and clinical staff was not
formally assessed. Whether the hypnosis intervention would be
effective if administered by nonpsychologists was not evaluated.
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the brief intervention before their surgery and were assessed for
outcome variables before discharge that same day, no patients were
lost to follow-up (see Fig. 1 ). Patients were enrolled from February
2000 to February 2006.
Treatment Conditions
Both the hypnosis and attention control sessions were delivered
to patients individually by interventionists according to the study
protocol manual and were standardized to last 15 minutes. The
protocol manual was developed in an initial preliminary study with
breast cancer surgical patients ( 11 ) (details of the intervention can
be obtained from G. H. Montgomery).
The hypnosis intervention was based on previously published
work ( 11 , 22 ). The scripted hypnosis session included a relaxation-
based induction (including imagery for muscle relaxation), sug-
gestions for pleasant visual imagery, suggestions to experience
relaxation and peace, specifi c symptom-focused suggestions (i.e.,
to experience reduced pain, nausea, and fatigue), a deepening pro-
cedure, and instructions for how patients could use hypnosis on
their own following the intervention session.
The attention control procedure was based on a published
attention control paradigm that has been used with interven-
tional radiology patients ( 23 – 25 ). Patients in the attention con-
trol group spent identical amounts of time with interventionists
as did patients in the hypnosis group, to control for professional
attention. Attention control sessions were led by the same
interventionists who led the hypnosis sessions. However, the
interventionists did not lead the attention control patients
in imagery, relaxation, or even simple discussion. Rather, the
interventionists allowed patients to direct the fl ow of the con-
versation and provided supportive/empathic comments ac -
cording to standardized procedures ( 23 ). The interventionists
matched verbal and nonverbal communication patterns, lis-
tened attentively, avoided the use of prejudicial or negatively
valued language, and used emotionally neutral descriptors in
conversation ( 23 ).
All four interventionists were PhD-level clinical psychologists
with advanced training in the use of hypnosis in a medical setting.
All interventionists went through didactic and practical training
and completed at least fi ve practice interventions with healthy
volunteers under the direct supervision of G. H. Montgomery.
Patient permission was obtained to audiotape all sessions, and 20%
of audiotapes were randomly reviewed by G. H. Montgomery to
ensure treatment fi delity.
The interventionists did not participate in data collection, and
each interventionist worked with an equal number of hypnosis and
control patients. There were no statistically signifi cant effects of
interventionist on any outcome variable (all P values > .43).
Operative procedures (surgical and anesthetic) followed uni-
form institutional guidelines. Anesthesia was administered by
Department of Anesthesiology faculty and by residents and fellows
under their supervision. All patients were treated with the same
monitored anesthesia care protocol that included propofol, mid-
azolam, fentanyl, and lidocaine. The procedure involved a combi-
nation of analgesics (lidocaine [2% with 1 : 100 000 epinephrine])
and fentanyl) with anesthesia (conscious to deep sedation achieved
with midazolam and propofol). Dosage of sedatives was titrated by
anesthesiologists who were blinded to patient intervention group
assignment. Doses of lidocaine were administered as determined
by the anesthesiologist in response to patient agitation. Local
anesthesia was supplemented with an intravenous sedation regimen
to achieve an Observer’s Assessment of Alertness/Sedation score of
2 – 4 ( 26 ). Monitored anesthesia care involved combinations of
short-acting narcotic agents (fentanyl 0.5 – 2 µ g/kg infusion)
and sedative agents (midazolam 0.01 – 0.1 mg/kg and/or propofol
0 – 50 µ g/kg). Patients were also given acetaminophen and acet-
aminophen/oxycodone hydrochloride in the postanesthesia care
unit as needed based on their reports of pain.
Fig. 1 . Trial fl ow diagram. Randomization
allocations resulted in unequal numbers in
the groups.
356 Assessed for Eligibility
156 Excluded
42 Not Meeting Inclusion Criteria
51 Refused to Participate
42 Unable to contact
200 Randomized
95 Assigned to Receive Attention Control
95 Received Attention Control
0 Lost to Follow-Up at Discharge
0 Discontinued Attention Control
95 Included in Analysis
0 Excluded from Analysis
105 Assigned to Receive Hypnosis
105 Received Hypnosis
0 Lost to Follow-Up at Discharge
0 Discontinued Hypnosis
105 Included in Analysis
0 Excluded From Analysis
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Outcome Measures
Demographic information (e.g., age, education, marital status) was
collected from patients using mailed questionnaires. Medical charts
were reviewed and abstracted for apposite medical and surgical data
(e.g., anesthesia and operative records). After patients reached
standardized hospital criteria for discharge ( 27 ), their subjective
experiences of pain intensity, pain unpleasantness, fatigue, nausea,
physical discomfort, and emotional upset were assessed by BA- and
MA-level research assistants using 10-cm visual analog scales
(VASs) ( 11 , 28 – 36 ). Both intensity (i.e., amount) and unpleasantness
( 30 – 32 ) of pain were assessed to capture its sensory and affective
dimensions ( 37 ). The scores for each VAS ranged from 0 to 100.
Because all patients underwent ambulatory surgical procedures, all
VAS outcome assessments took place on the same day as surgery.
Data on intraoperative and postoperative anesthesia and analgesia
use were collected from Department of Anesthesiology operative
records within 1 month of surgery. The surgery time variable rep-
resents the time spent by the patient in the operating room, starting
when the surgical team was ready to begin. Surgical time includes
preparation time but does not include time unrelated to the proce-
dure (e.g., tardiness of any individual on the operating team that
prevented the procedure from taking place on schedule). Surgery
time ended when anesthesia was discontinued (as indicated in the
medical records). The recovery (i.e., postanesthesia care unit) time
variable represents time spent in clinical areas in the hospital fol-
lowing surgery before discharge. At MSMC, patients who recover
quickly may be sent directly to administrative areas and therefore
may spend no time in the postanesthesia care unit.
Institutional Cost Data
Data concerning costs of procedures, medications, and staff were
based specifically on financial data from MSMC. Dollar values for
salaries, medication costs, and time spent in clinical areas were
obtained from Mount Sinai Pharmacy, the Department of Surgery,
and the Department of Anesthesiology. To provide a context for
the cost-effectiveness of the intervention, baseline costs were estab-
lished using the overall diagnostic-related group reimbursement
rate for procedures. Threshold analyses were conducted to deter-
mine the monetary break-even points (amount of dollars that could
be spent on a dedicated interventionist without increasing institu-
tional costs) for surgical practices having 100, 200, 300, and 400
breast cancer surgical patients annually. Finally, sensitivity analyses
were conducted to investigate the potential generalizability of the
findings. Because costs may vary widely between institutions, we
calculated cost-effectiveness for hypothetical institutions that have
cost structures of 20%, 30%, or 40% higher or lower than the
MSMC institutional cost structures presented here.
Statistical Analyses
The trial was designed to have a minimum of 80% power with
alpha of .05 to detect a small to medium effect size for clinical out-
comes allowing for the inclusion of up to six potential covariates
(statistically controlling for any possible failures of randomization
on relevant patient factors [age, ethnicity, education, surgery type,
surgeon, marital status]). This approach yielded a projected sample
size of 200 participants. Intent-to-treat procedures were followed
( 38 ). Pretreatment comparisons of demographic and medical
factors ( Table 1 ) were conducted using analysis of variance (ANOVA)
and chi-square tests (using the Mantel – Haenszel test for trend with
ordered variables ( 39 ). All tests of statistical significance were two-
sided. Multivariate analysis of variance (MANOVA) and ANOVA
tests were used because the outcome variables are continuous and
the focus of the hypotheses is on changes in amount and severity of
outcomes, not incidence. Transforming continuous data to categor-
ical data would be inappropriate ( 40 ). For outcome variables, an
effect size “ d ” was calculated (with 95% confidence intervals [CIs])
to provide an estimate of magnitude of intervention effects that can
be compared across studies. d , which is calculated by subtracting the
means of treatment and control groups and dividing by the standard
deviation of the control group ( 41 ), provides a standardized estimate
of effect that can be used to assess clinical meaningfulness and to
compare study results across outcomes and across studies that may
use different outcome assessment methods. By convention ( 42 ), a d
of 0.2 is considered small, of 0.5 is considered medium, and of 0.8 is
considered large. The literature has indicated that an effect size ( d )
of 0.2 or greater is clinically meaningful ( 43 , 44 ).
To establish the cost effects of the hypnosis intervention, con-
sistent with published approaches to cost-effectiveness analyses
( 45 ), dollar values were assigned only to those outcome variables
that statistically differed between groups ( P <.05).
Before calculating inferential statistics, we checked the distribu-
tions of key demographic and medical factors between the treat-
ment and control groups for potential failures of randomization
( Table 1 ). None of the variables showed a statistically signifi cant
difference in distribution between the groups. Therefore, none of
these factors were included as potential covariates in subsequent
analyses. Next, distributions of the primary outcome variables were
examined. There were no gross violations of normality (all skew-
ness and kurtosis values were within ±3) ( 46 ). However, descriptive
analyses indicated that the propofol values contained an outlier:
one value for total amount of propofol was greater than two stan-
dard deviations higher than the next highest value. Winsorizing, a
standard statistical procedure for removing the biasing effects of
outliers ( 47 ), was used for this value. The descriptive analyses also
indicated that two values for time spent in clinical areas were outli-
ers, and these were winsorized as well. Following these data
screening and cleaning procedures, ANOVA statistical procedures
as implemented in SAS ( 21 ) were used to analyze the clinical effec-
tiveness of the intervention. Additional exploratory analyses were
performed to report costs from the institutional perspective as a
function of group assignment ( 45 ). Because some of the clinical
outcomes were under the control of the anesthesiologists (n = 58)
caring for patients in the study, anesthesiologist as a variable was
examined for a possible relationship to study group assignment,
and no relationship between anesthesiologist and study group
assignment was found (Wald = 0.19, P >.66). In addition, including
anesthesiologist as a covariate in preliminary analyses yielded a
pattern of results identical to the original results. Therefore, anes-
thesiologist was not included in the models presented.
Results
Comparisons of pretreatment demographic and medical factors
( Table 1 ) indicate that there were no statistically significant
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between-group differences in these factors. Intraoperative use of
analgesics for pain control (fentanyl and lidocaine) and of seda-
tives (midazolam and propofol), as well as postoperative use of
acetaminophen and acetaminophen/oxycodone hydrochloride for
pain control, were compared between the hypnosis and attention
control groups ( Table 2 ) using MANOVA. There was an overall
Table 1 . Pretreatment comparisons of treatment groups *
Characteristic
Hypnosis intervention group
(N = 105)
Attention control group
(N = 95)
F or
2
value P value †
Age (y), mean (SD)
48.73 (12.88) 48.25 (13.30) F = 0.07 .80
Ethnicity
White 71 (67%) 55 (58%)
2
= 2.91 .41
Hispanic 13 (12%) 17 (18%)
African American 11 (11%) 15 (16%)
Other 10 (10%) 8 (8%)
Marital status
Currently married 53 (50%) 45 (47%)
2
= 0.19 .66
Education
2
= 0.07 .78
≤ 12 y 13 (12%) 12 (13%)
Partial college 26 (25%) 22 (23%)
4-y college graduate 39 (37%) 34 (36%)
Postgraduate 27 (26%) 27 (28%)
Weight (kg), mean (SD)
66.30 (14.42) 65.59 (14.97) F = 0.09 .81
Scheduled surgery
Lumpectomy 29 (28%) 22 (23%)
2
= 0.52 .47
Excisional biopsy 76 (72%) 73 (77%)
Postsurgery diagnosis
Cancer positive 37 (35%) 26 (27%)
2
= 1.43 .24
Needle localization procedure
Yes 57 (54%) 54 (57%)
2
= 0.13 .72
Axillary node dissection ‡
Yes 19 (18%) 12 (13%)
2
= 1.14 .29
* SD = standard deviation.
† The Mantel – Haenszel test for trend is reported for the education variable. Other P values are from analysis of variance and chi-square tests. All P values are
two-sided.
‡ Includes patients undergoing sentinel lymph node biopsy.
Table 2 . Perioperative anesthesia use by intervention group *
Type of anesthesia
Hypnosis group (N = 105)
Attention control group
(N = 95)
Mean
difference
(95% CI) F value P value † d ‡ (95% CI) Mean (SD)
Median
(range) Mean (SD)
Median
(range)
Intraoperative analgesics
Fentanyl ( µ g) 0.14
(0.22)
0.50
(0.10 – 1.50)
0.15
(0.25)
1.09
(0.10 – 1.53)
0.01
( − 0.05 to 0.08)
0.19 .67 0.04
( − 0.24 to 0.32)
Lidocaine (mL) 24.23
(12.25)
20.00
(2.00 – 100.00)
31.09
(15.05)
30.00
(3.00 – 80.00)
6.86
(3.05 to 10.68)
12.62 <.001 0.46
(0.18 to 0.74)
Intraoperative sedatives
Midazolam (mg) 2.07
(1.41)
2.00
(2.00 – 6.00)
2.23
(1.56)
2.00
(2.00 – 6.00)
0.16
( − 0.26 to 0.57)
0.54 .46 0.10
( − 0.18 to 0.38)
Propofol ( µ g) 64.01
(92.23)
0.08
(0.00 – 370.00)
96.64
(113.14)
70.00
(0.00 – 600.00)
32.63
(3.95 to 61.30)
5.03 .03 0.29
(0.01 to 0.57)
Postoperative analgesics
Acetaminophen (mg) 49.05
(171.63)
0
(0 – 650)
56.84
(192.36)
0
(0 – 1000)
7.79
( − 24.13 to 31.90)
0.09 .76 0.04
( − 0.24 to 0.32)
Acetaminophen/oxycodone
hydrochloride (mg) §
0.30
(1.31)
0
(0 – 10)
0.54
(1.71)
0
(0 – 10)
0.24
( − 0.18 to 0.66)
1.27 .26 0.14
( − 0.14 to 0.42)
* SD = standard deviation; CI = confidence interval.
† P values are from analysis of variance tests. All P values are two-sided.
‡ d represents the standardized effect size for intervention group effects on outcome variables. An effect size ( d ) of 0.2 or greater is considered to be clinically
meaningful ( 43 ).
§ For patients who received acetaminophen/oxycodone hydrochloride, acetaminophen dose remained constant (325 mg), and only oxycodone dose is shown.
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group difference in intraoperative medication use [ F (4, 195) =
3.91, P <.005], with patients in the hypnosis group receiving less
medication than patients in the control group. Regarding specific
medications, one-way ANOVAs revealed that use of lidocaine and
propofol was statistically significantly lower in patients in the
hypnosis group. For lidocaine, the mean difference (control
minus hypnosis group) was 6.86 mL (95% CI = 3.05 to 10.68),
and for propofol, the mean difference was 32.63 µ g (95%
CI = 3.95 to 61.30). Fentanyl and midazolam use, however, did
not differ statistically significantly between the two groups. There
was no effect of the intervention on postanesthesia care unit anal-
gesic use (acetaminophen or acetaminophen/oxycodone hydro-
chloride) ( P values > .20).
We then compared the hypnosis and attention control groups
on patient-reported pain intensity, pain unpleasantness, nausea,
fatigue, discomfort, and emotional upset. These outcomes were
analyzed as continuous variables ( Table 3 ). A MANOVA analysis
of the six outcomes (as assessed by VAS) indicated that there was
an overall effect of intervention group on these outcomes collec-
tively [ F (6, 193) = 15.73, P <.0001]. One-way ANOVAs of the
effects of intervention group on VAS outcomes revealed that each
outcome was statistically signifi cantly lower in patients randomly
assigned to the hypnosis group compared with those in the control
group: pain intensity (mean difference between control and hyp-
nosis group = 25.40, 95% CI = 17.56 to 33.25), pain unpleasant-
ness (mean difference = 17.86, 95% CI = 9.92 to 25.80), nausea
(mean difference = 18.92, 95% CI = 12.98 to 24.87), fatigue (mean
difference = 24.73, 95% CI = 16.64 to 32.83), discomfort (mean
difference = 20.19, 95% CI = 12.36 to 28.02), and emotional upset
(mean difference = 24.79, 95% CI = 18.56 to 31.03). In all cases,
mean differences were clinically meaningful. That is, the effect size
( d ) for each of the VAS outcomes was larger than the 0.2 minimum
guideline for clinical meaningfulness (43). Indeed, all of the effect
sizes fell in the medium or large range (VAS outcome effect sizes
ranged from d = 0.57 to d = 0.91).
Consistent with our interest in cost-effectiveness, we also inves-
tigated the possibility that the hypnosis intervention would reduce
time spent in clinical areas relative to attention control patients.
Analyses of clinical time revealed a statistically signifi cant effect of
group on surgery time but not on recovery time ( Table 4 ). Patients
in the hypnosis group spent 10.60 fewer minutes (95% CI = 0.92
to 20.27) in surgery than those in the control group.
To analyze the potential cost savings associated with adjunctive
hypnosis from the perspective of the institution, dollar values were
obtained from MSMC records for factors on which the groups
differed statistically signifi cantly (surgery time, propofol, lido-
caine), consistent with standard procedures in the literature (45)
( Table 5 ). Cost savings can also be placed in the context of the
procedure cost. Surgical breast procedures cost our institution
$8561 per patient. The hypnosis intervention reduced institutional
Table 3 . Postsurgical scores on patient symptoms and group effect *
Visual analog scale
outcome data †
Hypnosis group
(N = 105)
Attention control group
(N = 95)
Mean difference
(95% CI) F value P value ‡ d § (95% CI) Mean (SD)
Median
(range) Mean (SD)
Median
(range)
Pain intensity 22.43 (25.37) 15 (0 – 100) 47.83 (30.82) 46 (0 – 100) 25.40 (17.56 to 33.25) 40.79 <.001 0.82 (0.53 to 1.11)
Pain unpleasantness 21.19 (25.41) 11 (0 – 100) 39.05 (31.43) 35 (0 – 100) 17.86 (9.92 to 25.80) 19.69 <.001 0.57 (0.28 to 0.85)
Nausea 6.57 (18.01) 0 (0 – 100) 25.49 (24.41) 13 (3 – 100) 18.92 (12.98 to 24.87) 39.41 <.001 0.78 (0.49 to 1.07)
Fatigue 29.47 (28.40) 20 (0 – 100) 54.20 (29.61) 55 (5 – 100) 24.73 (16.64 to 32.83) 36.32 <.001 0.84 (0.55 to 1.13)
Discomfort 23.01 (23.58) 18 (0 – 80) 43.20 (32.26) 42 (4 – 100) 20.19 (12.36 to 28.02) 25.87 <.001 0.63 (0.35 to 0.91)
Emotional upset 8.67 (16.62) 0 (0 – 100) 33.46 (27.30) 19 (4 – 100) 24.79 (18.56 to 31.03) 61.48 <.001 0.91 (0.62 to 1.20)
* SD = standard deviation; CI = confidence interval.
† Scores on all scales range from 0 to 100.
‡ P values are from analysis of variance tests. All P values are two-sided.
§ d represents the standardized effect size for intervention group effects on outcome variables. An effect size ( d ) of 0.2 or greater is considered to be clinically
meaningful ( 43 ).
Table 4 . Mean clinical care times (in minutes) by group *
Clinical area
Hypnosis group
(N = 105)
Attention control group
(N = 95)
Mean difference
(95% CI) F value P value † d ‡ (95% CI) Mean (SD)
Median
(range) Mean (SD)
Median
(range)
Surgery 43.37 (38.68) 37 (9 – 171) 53.97 (29.56) 49 (8 – 163) 10.60 (0.92 to 20.27) 4.66 .04 0.36 (0.08 to 0.64)
Postanesthesia
care unit
76.33 (41.44) 79 (0 – 217) 88.76 (56.09) 90 (0 – 275) 12.42 ( – 1.24 to 26.09) 3.21 .08 0.22 ( – 0.06 to 0.50)
* SD = standard deviation; CI = confidence interval.
† P values are from analysis of variance tests. All P values are two-sided.
‡ d represents the standardized effect size for intervention group effects on outcome variables. An effect size ( d ) of 0.2 or greater is considered to be clinically
meaningful (43).
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costs on average by $772.71 per patient (95% CI = $75.10 to
$1469.89; Table 5 ). It should be noted that the cost savings is
largely accounted for by reduced surgery time and that MSMC
surgery costs incorporated personnel (e.g., nurses) as well as
equipment (e.g., surgical tables) unless otherwise indicated. This
between-group difference was statistically signifi cant [ F (1, 198) =
4.77, P <.03].
Threshold analyses were conducted to determine the break-
even point at which the hypnosis intervention would no longer
yield cost savings from an institutional perspective. As an exam-
ple, based on the cost savings presented in Table 5 , if a surgical
practice included 100 breast cancer surgical patients annually, the
practice could devote $77 271 of resources to compensating a
psychologist before the fi nancial break-even point is reached. In
other words, the intervention is cost saving or cost neutral if the
annual total compensation package of the psychologist is less
than or equal to $77 271. Similarly, compensation packages of
$154 542, $231 813, or $309 084 could be devoted to paying psy-
chologists in surgical practices of 200, 300, and 400 patients,
respectively, before the break-even points would be reached.
These threshold analyses do not assume other duties of a psy-
chologist and represent only 25, 50, 75, and 100 hours, respec-
tively, of providing the hypnosis intervention annually by the
psychologist.
Our cost-effectiveness results are based specifi cally on MSMC
cost data. To gauge the generalizability of the results, we con-
ducted a sensitivity analysis. Sensitivity analysis addresses the
possibility that cost structures will differ at different institutions
(e.g., the cost per minute of surgery may be higher or lower at
other institutions due to variance in salaries). Sensitivity analyses
indicate that if cost structures were 20%, 30%, or 40% greater
than MSMC costs, the intervention would reduce institutional
costs by $927, $1004, and $1082, respectively. If cost structures
were 20%, 30%, or 40% less than MSMC costs, the intervention
would reduce institutional costs by $618, $541, and $464
respectively.
Discussion
The present randomized controlled trial demonstrated that a brief
hypnosis intervention before breast cancer surgery statistically
significantly reduced intraoperative use of the analgesic lidocaine
and the sedative propofol. The hypnosis intervention also reduced
patient-reported postsurgical pain (intensity and unpleasantness),
nausea, fatigue, discomfort, and emotional upset to an extent that
was consistent with benchmarks for clinically meaningful differ-
ences ( 43 ) as well as with effect sizes in the surgical hypnosis litera-
ture (7). Analyses of pretreatment demographic and medical factors
indicated that the between-group differences were not attributable
to failures of randomization.
The impact of the hypnosis intervention on medication use
should be considered in the context of current medical practice at
our institution (MSMC). Most patients presenting for breast can-
cer surgery typically receive a standard dose of fentanyl and/or
midazolam before the onset of the procedure and titrated doses of
lidocaine and propofol as judged necessary by the anesthesiologist
based on patient agitation. Thus, based on clinical practice at
MSMC, it is not surprising that the hypnosis intervention affected
the use of lidocaine and propofol specifi cally because those are the
two agents that are typically titrated to individual patient responses.
The titration of lidocaine and propofol is consistent with anesthe-
siology practice at other institutions (e.g., 48).
The effectiveness of hypnosis for controlling side effects of
other types of surgery [e.g., breast reduction ( 16 ), gynecologic
surgery ( 49 ), coronary artery bypass ( 50 )] has been established in
the broader literature (7); however, this study is, to our knowl-
edge, the fi rst randomized trial with breast cancer surgical patients
that was suffi ciently powered to demonstrate these benefi cial
effects as well as to demonstrate cost-effectiveness. Some earlier
studies have failed to fi nd effects of hypnosis with surgical
patients. For example, one study provided hypnosis in the surgical
suite after the initiation of general anesthesia ( 51 ) and found no
effect of hypnosis. However, it is unclear whether these patients
had the necessary cognitive capacity following the onset of gen-
eral anesthesia to participate in, or even to perceive, the hypnotic
suggestions. Overall, our results support the present hypnosis
intervention as a brief, clinically effective means for controlling
patients’ pain, nausea, fatigue, discomfort, and emotional upset
following breast cancer surgery beyond traditional pharmaco-
therapeutic approaches.
Cost-effectiveness analyses provided strong evidence that hyp-
nosis reduced costs from an institutional perspective. On average,
each patient in the hypnosis group reduced costs to the institution
by $772.71 relative to a patient in the control condition. These
cost savings were due primarily to reduced time in surgery in the
hypnosis group. It is possible that the shorter procedure times in
the hypnosis group were due to the patients being easier to prepare
for surgery and to sedate or due to less time having been spent
administering medications to patients. However, we did not in -
vestigate these mechanisms, and therefore, these possibilities are
highly speculative. Overall, our results are consistent with studies
Table 5 . Hypnosis intervention effects on institutional costs *
Clinical factors and costs
Hypnosis group
(N = 105)
Attention control
group (N = 95)
Surgery-related costs
OR time (mean) 43.37 min 53.97 min
OR room cost † $67.50/min $67.50/min
Surgeon cost ‡ $2.26/min $2.26/min
Anesthesiologist cost § $1.96/min $1.96/min
Average sedative or
analgesic cost
Propofol $23.81/patient $35.94/patient
Lidocaine $1.24/patient $1.59/patient
Interventionist cost || $0.75/min $0.75/min
Mean total cost
$3146.80 $3919.51
* OR = operating room. Variables included in this table are those that differed
statistically significantly by group. Cost-effectiveness analyses conform to
standard practice in economic evaluations of medical technologies ( 45 ). It
may take institutions time to adjust OR scheduling to maximize the savings,
but the underlying presumption is that in the long run, scheduling will adjust.
† Includes nursing staff, intravenous line setup, monitoring.
‡ $150 000/y, 30% benefits, 45 wk/y, 32 h/wk.
§ $130 000/y, 30% benefits, 45 wk/y, 32 h/wk.
|| $50 000/y, 30% benefits, 45 wk/y, 32 h/wk.
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Articles 1311
demonstrating the ability of hypnosis to be a cost-effective inter-
vention in other clinical contexts (e.g., radiologic procedures)
( 18 , 25 ). In particular, reduced procedure times associated with
hypnosis have been demonstrated in interventional radiology
patients ( 24 ).
The present brief hypnosis intervention appears to be one of
the rare clinical interventions that can simultaneously reduce both
symptom burden and costs. Patients are likely to benefi t from less
time in surgery and reduced use of sedatives because patients
undergoing longer surgical procedures with more sedatives tend to
have greater nausea ( 52 ) and pain (4) following surgery and tend to
recover more slowly ( 53 ).
In this study, it appeared that time in surgery was by far the
largest contributor to cost savings ( Table 5 ). It should be recog-
nized that it may take time for hospital administrators to adjust
operating room scheduling to maximize cost savings. However, the
present approach is consistent with standard practice in economic
evaluations of medical technologies, and cost savings should be
realized in the long run ( 45 ). The present results are limited to
institutional costs, which are a subset of the overall societal costs
associated with breast cancer surgery. Societal costs would also
include costs from the individual’s (patient’s) perspective (e.g.,
missed days of work, medical bills) as well as those of third-party
payers.
No study is without limitations, and the present one is no
exception. One limitation is that patients were not blind to group
assignment. Unfortunately, blinding of the patients to group
assignment in the present behavioral medicine protocol would
have been impossible. Patients in the hypnosis intervention group
must be aware and active participants in the hypnosis intervention
itself. They are told explicitly that they are participating in a hyp-
nosis intervention, that they will experience hypnotic suggestions,
and that they will be able to respond to them. Providing the con-
trol group with a similar set of instructions would be tantamount
to providing them with hypnosis. However, we recognize that
there is a possibility that the lack of patient blinding could have
created demand characteristics for patients that could have
affected self-report outcomes. To reduce this possibility, inter-
ventionists collected no outcome data in this study and had no
contact with patients outside of the intervention session itself,
which occurred before surgery. There is also the possibility that
demand characteristics may have infl uenced the amount of intra-
operative medications used. Patients in the hypnosis condition
may have suppressed their agitation while in surgery; thus, anes-
thesiologists could have used less lidocaine and propofol. However,
this seems unlikely as such a scenario would involve a great deal of
patient will and conscious behavioral control while in surgery.
Furthermore, if the effect were due to demand characteristics, we
would also have anticipated that we would have found between-
group differences on postoperative analgesic use, but we did not.
The possibility that demand characteristics affected procedure
time seems even more unlikely given the large number of factors
that a hypnosis patient would have to control to decrease surgical
procedure time.
A second limitation of this study is that a formal assessment of
the effectiveness of blinding of research or clinical staff was not
conducted. However, as already noted, methodologic precautions
were taken to make it unlikely that either research or clinical staff
were aware of study group assignment. Future research should
include a more formal blinding assessment.
The results of this study suggest at least fi ve future research
directions. First, it will be important to investigate the contribu-
tions of individual components of the intervention (e.g., relax-
ation, specifi c suggestions) to the benefi cial effects of the
intervention. Second, it will be of interest to determine the extent
to which the benefi cial effects reported here extend to longer
term outcomes (e.g., pain 1 month following surgery). Third,
future studies should confi rm the results in other patient and
demographic samples. Fourth, although the threshold and sensi-
tivity analyses suggested that the intervention would continue to
be cost effective under a variety of reasonable circumstances,
future research should investigate these effects at other institu-
tions. Fifth, psychologists may not be available at all institutions,
and therefore, the clinical effi cacy of more readily available per-
sonnel (e.g., anesthesiologists, nurses) needs to be empirically
evaluated.
In conclusion, the present randomized controlled trial demon-
strated that a brief presurgery hypnosis intervention reduces medi-
cation use, pain intensity, pain unpleasantness, nausea, fatigue,
discomfort, and emotional upset in women undergoing breast
cancer surgery. The results are strongly supportive of cost savings
associated with this approach accruing to the institution. Together,
the combination of potential improvements in symptom burden
for the hundreds of thousands of women facing breast cancer sur-
gery each year and the economic benefi t for institutions argues
persuasively for the more widespread application of brief presurgi-
cal hypnosis.
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Funding
National Cancer Institute (CA105222, CA81137); American Cancer
Society (CRTG 00-312, PF-05-098-01-CPPB); Department of Defense
(DAMD17-99-1-9303).
Notes
We are required to indicate that the content of the information contained in
this report does not necessarily refl ect the position or policy of the Department
of Defense. The funding agencies had no role in the design, data collection, or
data analysis of the study or in the writing of this manuscript.
Manuscript received January 5 , 2007 ; revised June 25 , 2007 ; accepted
July 11 , 2007.
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