A Prospective Randomized Clinical Trial Evaluating the Effect of Convective Pre-warming on Intra-operative Thermoregulatory Capabilities in Patients Enrolled in the TIGER Anesthesia Perioperative Protocol
Phase: NA
Conditions: Temperature Change, Body
Sponsor: University of Missouri-Columbia

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A prospective randomized clinical trial evaluating the effect of convective
pre-warming on intra-operative thermoregulatory capabilities in patients
enrolled in the TIGER anesthesia perioperative protocol
PI: Claire Spradling, BS1
Medical Student
Co-PI: Terri Monk, MD2
Professor
Co-I: Kristen Richter, CRNA2
Co-I: Kay Smith, RN2
Co-I: Adam Zino, MPH2
1University of Missouri School of Medicine
2Department of Anesthesiology and Perioperative Medicine
University of Missouri
Columbia, MO 65201
NCT03876808
Contact: Claire Spradling, BS
University of Missouri School of Medicine
1001 University Ave Apt 102
Columbia, MO 65201
Telephone: (314) 541-7858
Email: cssqn8@health.missouri.edu
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Summary
This prospective randomized clinical trial will assess the effect of pre-operative
convective warming on intra-operative thermoregulation in patients undergoing
gastrointestinal or genitourinary surgical procedures with the TIGER* anesthesia
perioperative protocol.
*See addendum 1
Objectives:
Primary Endpoint:
1. Change in core temperature between induction of anesthesia and end of
skin preparation (but before turning on the operating room forced-air
warmer) as measured by a temperature-sensing Foley catheter
Secondary Endpoints:
1. Change in skin temperature between arrival to the holding area and
departure to the operating room
2. Intraoperative temperatures
3. Skin temperature on arrival to the PACU (post-anesthesia care unit)
4. Differences in temperature changes between elderly (≥ 65 years) and
younger patients
Clinical Hypotheses:
Primary Hypothesis:
We hypothesize that patients who are convectively warmed at 43°C for at least
60 minutes pre-operatively will have a higher core body temperature during the
intraoperative period as measured by a temperature-sensing Foley catheter
Exploratory Hypothesis:
Patients who are convectively warmed prior to surgery will have
1. Temperatures that are significantly increased
a. At departure from the preoperative holding area
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b. In the OR after surgical preparation
c. On arrival to the PACU
2. Older (age ≥ 65 years) patients will demonstrate a greater change in mean
intraoperative temperature compared to younger patients
Background & Rationale:
By the year 2030 the geriatric presence in the United States, defined as any adult
>65 years of age, is estimated to reach around 20% of the entire population.1
Thus, understanding medical concepts as they relate to the elderly is becoming
increasingly important. One such concept is that of hypothermia - a core body
temperature < 36°C - for which age >65 has been found to be an independent
risk factor.2 This complication is especially prevalent intra-operatively due to use
of general anesthetics, cool ambient operating room (OR) temperatures, and
impaired thermal regulation in the elderly.3
The human body employs numerous mechanisms to maintain thermal
homeostasis including: behavioral means of thermoregulation, sweating, pre-
capillary vasodilation, non-shivering and shivering means of heat production, and
arteriovenous shunt vasoconstriction.4 The first, and arguably most important,
regulatory response to occur is that of vasoconstriction, which normally results in
redistribution of blood from the relatively cool periphery to the warmer core
compartment in order to confine metabolic heat to the central tissues.2,5 Patients
undergoing general anesthesia experience reduced vasoconstriction due to
decreased cold response thresholds while patients undergoing epidural
anesthesia experience sympathetic blocks resulting in blunted vasoconstrictive
responses.2,5 All patients experience the afore mentioned side effects of
anesthetics, however it has been proven that the elderly are more susceptible to
hypothermia due to lower vasoconstriction thresholds - determined by a
temperature gradient of 4°C between the periphery and core.
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First explored by Kurz et al.6 in 1993, it was found that use of nitrous oxide and
isoflurane anesthesia lead to an approximately 1.2°C lower vasoconstriction
threshold of 33.9±0.6 in the elderly versus 35.1±0.3 in the young (p < .01). This
subject was again looked at in a 1997 study wherein the vasoconstriction
threshold during nitrous oxide and sevoflurane was observed to be decreased by
approximately 0.8°C in the elderly at 35.0±0.8 versus 35.8±0.3 in the young (p <
.01).7 This is relevant because intraoperative hypothermia has long been known
to lead to adverse outcomes such as increased incidence of myocardial
ischemia, arrhythmias, coagulopathic states, and wound infections.4 In a 2014
retrospective cohort study by Billeter et al.2 patients experiencing core
temperatures <35°C had a four times increase in mortality with complication rates
increasing two fold and incidence of stroke increasing six fold. To counter this
thermoregulatory failure in patients, numerous methods of warming have been
practiced over time to augment the normal body response.
One method used to decrease intraoperative hypothermia is warming patients
before surgery via skin surface warmers. Numerous studies have found that even
brief periods of pre-warming can improve intraoperative temperatures
significantly for as long as 75-90 minutes after induction.8,9 In procedures lasting
less than 90 minutes, Horn et al.10 found that as little as 10 minutes of pre-
warming decreased incidence of intraoperative hypothermia from 69% to just
13% while Torossian et al.11 decreased the incidence from 60% to 38% in his
study using a self-warming blanket for 30 minutes pre-operatively. Studies have
also shown that longer pre-warming of 45-60 minutes can prevent hypothermia
for up to 2 hours after induction.12
While significant research has been performed on the effects of warming patients
before they undergo surgical procedures, scant evidence demonstrates the effect
of pre-warming in the elderly. In one article specifically looking at pre-warming in
the elderly (mean age ~72-73) it was found that, after pre-warming for 20
minutes, there was no significant change in incidence of hypothermia but there
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was a significant difference in severity of hypothermia when it did occur.13 This
study focused only on men undergoing transurethral resection of the prostate
however, and suffers from lack of generalizability. With the proportion of the
geriatric population continuing to expand, and the potential adverse effects
resulting from their increased susceptibility to intraoperative hypothermia, it is of
the utmost importance to look into methods to counter this dilemma and expand
the database on the topic.
Study Design:
This will be a prospective randomized clinical trial performed at a single
academic hospital. Due to the nature of the trial, the anesthesiologists and
subjects will not be blinded to their group assignment, but the postoperative
assessments will be. All subjects will receive standardized pre-operative
preparations, induction, and intraoperative infusions, as dictated by the TIGER
anesthesia perioperative protocol.
In addition to these measures, one group will undergo convective warming during
the preoperative preparations, completed for a minimum of 60 minutes prior to
entering the operating room, while the other group will undergo standard of care,
which includes providing each patient with a warming gown that is not turned on
as well as blankets and sheets with more blankets provided on patient request.
40 patients undergoing GI or
GU surgery enrolled in the
TIGER anesthesia
perioperative protocol
20 patients
Pre-warmed
with convection
20 patients
No additional
pre-warming
beyond
standard of
care
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Study Procedures:
I.
Patient population: 40 patients undergoing gastrointestinal or genitourinary
surgeries, who are enrolled in the TIGER anesthesia perioperative
protocol
II.
Inclusion criteria:
a. ASA I-IV
b. Other inclusion criteria as delineated in the TIGER anesthesia
perioperative protocol
III.
Exclusion criteria:
a. Inability to obtain written informed consent
b. Inability to obtain Foley catheter temperature recordings
c. Family history of malignant hyperthermia
d. Preoperative temperature > 38° C
e. Other exclusion criteria as delineated in the TIGER anesthesia
perioperative protocol
IV.
Randomization: On the day of surgery, patients will be randomized to one
of two groups:
1. Warming group: This group will undergo pre-warming at a
temperature of 43° C or a minimum of 60 minutes beginning upon
arrival to the pre-operative room continuing until they are taken to
the operating room. This will be achieved with blankets as well as
the use of a Bair Hugger® heating gown.
2. Standard of care group: this group will receive the standard of care
during the preoperative period, which includes providing the patient
with blankets and sheets, as well as additional blankets upon
request. They will also wear a Bair Hugger® heating gown, but it
will not be used for preheating prior to surgery.
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V.
Randomization will be stratified for the type of surgery (gastrointestinal
versus genitourinary) in an effort to reduce confounding.
VI.
Blinding: Due to the nature of this study, the anesthesiologist, nursing
staff, operating room staff, and the subject will know to which group the
subject has been assigned.
VII.
Anesthetic management as outlined in the enhanced recovery protocol.
VIII.
Postoperative pain management as outlined in the enhanced recovery
protocol.
IX.
Perioperative assessments
a. Duration of pre-warming prior to surgery
b. Temperature change from arrival in the pre-operative holding area
to leaving for the operating room as measured by a skin-
temperature thermometer.
c. Temperature change, as measured by a Foley catheter sensor
inserted, after induction of anesthesia to the end of surgical skin
preparation.
d. Temperature as measured with a Foley catheter sensor
throughout the operative procedure.
e. Temperature change between leaving the operating room and
arrival in the Post Anesthesia Care Unit (PACU).
f. Duration of hospital stay, estimated blood loss, transfusion
requirements, and postoperative complications
X.
Sample size and statistical consideration:
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a. This is a pilot study and, if pre-warming is successful at preventing
intraoperative hypothermia, data from this study will be used to
develop larger studies. We plan to enroll 20 patients per group for
a total sample size of 40 subjects to obtain pilot data.
b. Data will be analyzed using chi-square and t-tests as appropriate
with p < 0.05 considered significant.
Risks:
I.
No adverse effects are currently expected through participation in this
study other than possible sweating and discomfort in patients in the pre-
warming group heated for more than one hour.
a. Patients in the pre-warming group will be warned of the potential for
sweating or discomfort due to warmth during informed consent at
the pre-operative clinic visit. If they feel uncomfortable during the
pre-warming process, staff will turn down the warmers from 43C to
38C; if symptoms persist staff will turn the warmers off.
b. If significant adverse events other than sweating or discomfort
occur, the gown will be turned off, standard of care for the event
provided, and the investigators will be notified
II.
All identifiable information will be kept in a secure location and will not be
given to anyone unaffiliated with the University Hospital except as required
by law.
a. Despite efforts to maintain confidentiality, a small risk associated
with breach of confidentiality is still present
III.
There are no anticipated financial risks to patients.
Benefits:
Direct Benefit -
·
In the pre-warming group, patient's may feel warmer pre- and post-
operatively. Patients may also have higher temperatures throughout the
day of surgery which may contribute to decreased incidence of
hypothermia and it's adverse effects.
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Indirect Benefit -
·
Patients may benefit from taking part in this research to the extent that
they are contributing to medical knowledge. The information learned from
this study may benefit other patients with risk of low body temperatures
during surgery in the future.
Costs:
Patients will be required to pay for any treatment considered standard of care for
the procedure under which they will be going. Bair Hugger® gowns are included
in standard of care measures (each patient is provided with one pre-operatively
whether or not they are used) and thus using them throughout the morning, prior
to surgery, does not increase cost.
Ethical Considerations:
I.
Patient Expectations:
a. This study is not double-blinded and thus patients in the
experimental arm may expect improved outcomes due to
participation.
b. Expectations of improved outcomes will be managed in the pre-
operative clinic setting during the informed consent process.
c. Patients will be explicitly told that this trial measures temperatures
and only a few post-operative clinical outcomes, thus they may not
experience a tangible benefit.
II.
Patient Comfort:
a. Increasing pre-operative temperatures with convective heating
methods may compromise patient comfort and cause sweating to
occur;14 this will be clearly explained to all patients agreeing to
participate in the study during the informed consent process.
i. If patients in the experimental arm begin to feel
uncomfortable, the staff will lower the temperature of the
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heating gown from 43°C to 38°C; if discomfort persists at
38°C, staff can turn the heating gown off
b. Patient comfort may be compromised by use of Foley catheter
temperature sensors; this will be mitigated by insertion of catheters
post-induction.
i. Inserting Foley catheters is routine care for all of the
surgeries studied in this trial and thus should not be
exposing patients to the potential of more harm than is
inherent in the process of surgery
III.
Confidentiality:
a. Investigators will have access to patient information and records.
b. All paper files will be de-identified
c. All computerized information will be de-identified and kept in files
on password-secured computers in the University of Missouri
Department of Anesthesiology
d. A code key with identifiable information will be kept in a separate
secure location
IV.
Informed Consent:
a. Informed consent will be obtained from all participating patients in
the pre-operative clinic setting.
b. This study is excluding vulnerable patients comprising of prisoners,
minors, and those with mental disability in order to maintain the
integrity of the informed consent process.
V.
Managing Adverse Events:
a. No adverse effects are currently expected through participation in
this study other than possible sweating and discomfort in patients
heated more than one hour.14
b. If any adverse events should arise due to pre-warming measures,
they will be documented in the patient’s chart, disclosed to the PI,
and observed in study results.
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c. If any serious adverse events occur due to pre-warming measures,
that interfere with or require discontinuation of said measures,
patient’s will be treated with the standard of care for the event and it
will be disclosed to the PI immediately for review of safety.
VI.
Retention of Records:
a. Paper patient records will be retained in a locked cabinet for no
more than 7 years after completion of the study.
b. For retention of computerized patient records, within 1 year of
completion of the study they will be printed and held in a locked
cabinet for no more than 7 years after completion of the study.
VII.
Gender Considerations:
a. This intervention is expected to affect both male and female
patients and is not currently intended for use in only one sex.
References:
1. Centers for Disease Control and Prevention. The State of Aging and
Health in America 2013. Atlanta, GA: Centers for Disease Control and
Prevention, US Dept of Health and Human Services; 2013.
2. Billeter, Adrian T., et al. “Unintentional Perioperative Hypothermia Is
Associated with Severe Complications and High Mortality in Elective
Operations.” Surgery, vol. 156, no. 5, 2014, pp. 1245–1252.,
doi:10.1016/j.surg.2014.04.024.
3. Frank SM, Beattie C, Christopherson R, et al. Epidural versus general
anesthesia, ambient operating room temperatire and patient age as
predictors of inadvertent hypothermia. Anesthesiology 1992; 77: 252-257.
4. Sessler, Daniel I. “Chapter 8: Preoperative Thermoregulation.” Geriatric
Anesthesia, 2nd ed., Springer, New York, NY, 2008, pp. 107–118.
5. Glosten B, Hynson J, Sessler DI, McGuire J. Preanesthetic skin-surface
warming reduces redistribution hypothermia caused by epidural block.
Anesth Analg. 1993; 77: 488-93.
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6. Kurz A, Plattner O, Sessler DI, et al. The threshold for thermoregulatory
vasoconstriction during nitrous oxide/isoflurane anesthesia is lower in
elderly than young patients. Anesthesiology 1993; 79: 465-469
7. Ozaki, Makoto, et al. “The Threshold for Thermoregulatory
Vasoconstriction During Nitrous Oxide/Sevoflurane Anesthesia Is
Reduced in the Elderly.” Anesthesia & Analgesia, vol. 84, no. 5, 1997, pp.
1029–1033., doi:10.1213/00000539-199705000-00014.
8. Kim JY, Shinn H, Oh YJ, Hong YW, Kwak HJ, Kwak YL. The effect of skin
surface warming during anesthesia preparation on preventing
redistribution hypothermia in the early operative period of off-pump
coronary artery bypass surgery. Eur J Cardiothoracic Surg. 2006; 29: 343-
7.
9. Perl, T, et al. Efficacy of a Novel Prewiring System in the Prevention of
Preoperative Hypothermia. A Prospective, Randomized, Multi Center
Study. Edizioni Minerva Medica, Apr. 2014,
www.minervamedica.it/en/journals/minerva-
anestesiologica/article.php?cod=R02Y2014N04A0436. Accessed 2 June
2017.
10.Horn EP, Bein B, Bohm R, Steinfath M, Sahili N, Hocker J. The effect of
short time periods of pre-operative warming in the prevention of peri-
operative hypothermia. Anesthesia. 2012; 67: 612-7.
11. Torossian, Alexander, et al. “Active Perioperative Patient Warming Using
a Self-Warming Blanket (BARRIER EasyWarm) Is Superior to Passive
Thermal Insulation: a Multinational, Multicenter, Randomized
Trial.” Journal of Clinical Anesthesia, vol. 34, 2016, pp. 547–554.,
doi:10.1016/j.jclinane.2016.06.030. Accessed 1 June 2017.
12.Vanni, Simone Maria Dâ€™Angelo, et al. “Preoperative Combined with
Intraoperative Skin-Surface Warming Avoids Hypothermia Caused by
General Anesthesia and Surgery.” Journal of Clinical Anesthesia, vol. 15,
no. 2, 2003, pp. 119–125., doi:10.1016/s0952-8180(02)00512-3.
Accessed 1 June 2017.
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13.Jo, Youn Yi, et al. "Effect of preoperative forced-air warming on
hypothermia in elderly patients undergoing transurethral resection of the
prostate." Urology journal 12.5 (2015): 2366-2370.
14.Sessler DI, Schroeder M, Merrifield B, Matsukawa T, Cheng C. Optimal
duration and temperature of pre-warming. Anesthesiology 1995; 82: 674-
81.
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