Prevention of laparoscopic surgery induced hypothermia with warmed humidified insufflation: Is the experimental combination of a warming blanket synergistic?
Prevention of laparoscopic surgery induced hypothermia with warmed humidified insufflation: Is the experimental combination of a warming blanket synergistic?
Eric Noll 0 1
Sophie Diemunsch 0 1
Julien Pottecher 0 1
Jean-Pierre Rameaux 0 1
Michele Diana 1
Eric Sauleau 1
Kurt Ruetzler 1
Pierre Diemunsch 0 1
0 Service d'Anesth eÂsie ReÂ animation Chirurgicale, HoÃ pitaux Universitaires, Strasbourg, France, 2 Institut Hospitalo-Universitaire de Strasbourg, Strasbourg, France , 3 DeÂ partement de Bio statistique, CHU Strasbourg, Strasbourg , France , 4 Department of Outcomes Research, Anesthesiology Institute, Cleveland Clinic , Cleveland , United States of America
1 Editor: Iratxe Puebla, Public Library of Science , UNITED KINGDOM
Maintaining normothermia during anesthesia is imperative to provide quality patient care and to prevent adverse outcomes. Prolonged laparoscopic procedures have been identified as a potential risk factor for hypothermia, due to continuous insufflation of cold and dry carbon dioxide. Perioperative hypothermia is associated with increased hospital cost and many complications including; impaired drug metabolism, impaired immune function, cardiac morbidity, shivering, coagulopathy. In this experimental study, four pigs underwent four interventions each, resulting in 16 total trials. Using standardized general anesthesia in a randomized Latin-square sequence the four interventions include: 1. Control group without an administered pneumoperitoneum, 2. Administered standard pneumoperitoneum using 21ÊC insufflated gas and under-body forced-air warming, 3. Administered pneumoperitoneum with insufflation of warmed/humidified carbon dioxide, 4. Administered pneumoperitoneum with insufflation of warmed/humidified carbon dioxide and under-body forced-air warming. The primary outcome was distal esophageal temperature change 4 hours after trocar insertion.
Data Availability Statement: All relevant data are
within the paper and its Supporting Information
Funding: Laparoscopic Humigard insufflators were
provided for free by Fisher & Paykel HealthCare.
Pierre Diemunsch reported his participation in a
research meeting sponsored by Fisher & Paykel in
2013. The specific role of this author is articulated
in the `author contributions' section. The funders
had no role in study design, data collection and
Four hours after trocar insertion, pigs in the control group lost 2.1 ± 0.4ÊC; pigs with warmed
and humidified insufflation lost 1.8 ± 0.4ÊC; pigs with forced-air warming group lost 1.3 ±
0.9ÊC; and pigs exposed to a combination of warmed and humidified insufflation with
forcedair warming increased by 0.3 ± 0.2ÊC.
analysis, decision to publish, or preparation of the
Competing interests: Laparoscopic Humigard
insufflators were provided for free by Fisher &
Paykel HealthCare. Pierre Diemunsch reported his
participation in a research meeting sponsored by
Fisher & Paykel in 2013. This does not alter our
adherence to PLOS ONE policies on sharing data
This experimental animal study provides evidence that a combination of warmed and
humidified insufflation of carbon dioxide (CO2) in conjunction with forced-air warming is an
effective strategy in the prevention of perioperative hypothermia. Further clinical trials
investigating humans are therefore indicated.
Perioperative hypothermia is associated with adverse outcomes including impaired drug
metabolism, impaired immune function, cardiac morbidity, shivering, coagulopathy, and
increased use of hospital resources [1±5]. Several methods have been developed for
maintaining normothermia during surgery. A few normothermia methods include warming patients
before the induction of anesthesia [6±8]; conductive warming by circulating water garments
or water mattresses; covering the patient's back and/or other parts of the body [
efficient ªenergy transferº pads [
]; and convective warming from forced-air blanket
Convective (forced-air) warming is the most common intraoperative warming strategy
since it is safe, easy to use, and has the potential to transfer a considerable amount of heat to
the anterior surface of patients. There are limitations to the use of forced-air warming
however. Forced-air warming is relatively inefficient on a surface-area to volume basis and it is
often not possible, or practical, for warming patients having large open-procedures. It is
known that single forced-air warming does not reliably prevent perioperative hypothermia
]. Due to forced-air strategy inadequacy, additional (re)-warming strategies are indicated to
Laparoscopic procedures are another risk factor for developing perioperative hypothermia
due to prolonged surgical time and increased heat loss via exposure to cold/dry CO2
insufflation during pneumoperitoneum [15±17]. Insufflated CO2 is typically administered with a
temperature of 21ÊC, which is significantly colder than the patient's normal temperature range of
Prior experiments indicate that heating and humidification of insufflated carbon dioxide
may be beneficial in preventing perioperative hypothermia [
]. Furthermore, the interaction
between the temperature of insufflated air and forced air warming has yet to be quantified.
We therefore conducted a randomized crossover animal trial to test the applicability and
efficacy of using heated/humidified carbon dioxide that is insufflated during abdominal
pneumoperitoneum for normothermia maintenance. The primary analysis was to determine if
insufflating heated/humidified carbon dioxide combined with underbody forced-air warming
is advantageous in maintaining normothermia during pneumoperitoneum when compared to
the use of either warming strategy alone.
After the institutional animal ethics committee approval (Ircad Committee of Ethics: ICO
METH, President Prof. Didier Mutter, approval NÊ 38.2012.01.041), four large white pigs aged between 2 and 3 months were included in a randomized, crossover study. All animals used in the study were managed in accordance with the French laws for animal use and care. The
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method of care was also in compliance with the directives of the European Community
Council (2010/63/EU) with respect to the principles of 3R (Replacement, Reduction, Refinement).
Each of the four treatment days were separated by eight resting (non-intervention) days.
On each study day, the four pigs were randomly assigned to one of the four interventions.
Each animal underwent all of the following treatments one time:
1. General anesthesia without administered pneumoperitoneum (control group)
2. Under-body forced air warming blanket at 38ÊC (Bair Hugger) and a standard insufflation
with non-humidified, non-heated CO2 (forced air group)
3. Insufflation with humidified and heated CO2 using the Humigard device (Fisher and Paykel
Healthcare) without warming blanket (warmed insufflation group)
4. Combination of an under-body forced air warming blanket and insufflation of humidified and heated carbon dioxide using the Humigard device (combination group)
Based on the experimental approach and lack of available data from previous studies, we
decided to include four pigs undergoing four interventions each, resulting in 16 interventions
total. This cross-over study design is appropriate in order to demonstrate feasibility and
practical implementation of the study setting. This trial may provide appropriate evidence for
subsequent clinical trials.
Four large, male, white pigs aged between 2 and 3 months were provided by a local farming company (Copvial, Brumath, France). The pigs were housed in individual stable boxes under the supervision of an animal keeper.
The pigs were given a three day habituation period at the research facility with ad libitum
access to food and water. On the intervention days, each of the four pigs was sedated using
intramuscular administration of ketamine (20 mg/kg) and azaperone (2 mg/kg) [
weighing the pigs and placing them in the supine position on the operating table, an IV
catheter (22 Gauge) was inserted into the auricular vein and a crystalloid infusion was administered
at a rate of 4 ml/kg/h. General anesthesia was induced with 3mg/kg propofol and 0.6 mg/kg
rocuronium intravenously. After tracheal intubation (Portex Blue Line 6-mm), anesthesia was
maintained with 1% end-tidal concentration of isoflurane combined with 60% nitrous oxide
in oxygen. Mechanical ventilation using a semi-closed circle system (Aysis Carestation, GE
Healthcare, United Kingdom or Datex Ohmeda Aespire, GE Healthcare, United Kingdom)
was adjusted to maintain end-tidal PCO2 between 35 and 40 mmHg. Gas flow was maintained
at a total of 1 Liter per hour. A temperature probe (Odam Physiogard SM 785TM) was inserted
into the distal esophagus. The ambient temperature of the room was maintained near 20ÊC.
With the exception of the control group, a pneumoperitoneum was created by the surgeon
using a Veress needle. The pigs were inflated with CO2 prior to the insertion of two separate
laparoscopic trocars. A camera was introduced via one trocar, while the other was used to
create a controlled gas leakage at 120 L/h. The treatment groups underwent a 4-hour intervention
with continuous CO2 insufflation to maintain an intra-abdominal pressure of 10 mmHg
(Thermoflator, Karl Storz, TuÈbingen, Germany). In the warmed insufflation group and in the
combination group, the insufflated CO2 was humidified to saturation and heated to 37ÊC
using a Humigard device (Fisher and Paykel Healthcare, New Zealand).
An under-body warming blanket was positioned under the pigs for the forced air and combination groups. The forced-air blower was set to 38ÊC, and activated immediately after tracheal intubation.
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At the end of the four hour study period, the pneumoperitoneum was exsufflated and each
abdominal access port was infiltrated with 5mL of 2% lidocaine (Lidocaine B. Braun,
Germany). Once adequate spontaneous breathing was established, the pigs were extubated and
returned to the care of the animal keeper at a facility with ad libitum access to food and water.
At the end of the fourth intervention day, data collection was complete and the animals
were euthanized using deep anesthesia for 15 minutes (isoflurane 5 vol % in O2/N2O: 40%/
60%) followed by a 20 mL IV injection of a saturated solution of potassium chloride.
Demographic and morphometric characteristics of the pigs were recorded. Time recording
started after complete trocar insertion. Distal esophageal temperature and total volume of
insufflated CO2 was recorded in fifteen minutes intervals.
The temperature values are presented as mean ± standard error. Linear mixed models were
used to compare the temperature for each of the 15 minutes intervals for the four intervention
groups. A random subject effect was systematically included as a normal distribution with zero
mean and little variance. For time effect, we used dummy variables or linear slope. For
multiple comparisons adjustment, we the controlled family-wise error rate simultaneous inference,
with a global 5% alpha error risk.[
] All raw data are publicly accessible in S1 Appendix
temperatures per pig and intervention.
All four pigs underwent and survived each of the four interventions. The mean body weight
was 20.9 ± 0.6 kg. The mean ambient temperature in the operating room was 20.6 ± 0.4Ê C.
Initial group mean temperature did not statistically differ between groups (control: 36.5 ±
0.3ÊC; warmed insufflation: 37.1 ± 0.8ÊC; forced air: 36.9 ± 0.4ÊC; combination: 37.4 ± 0.5ÊC).
Four hours after each intervention, the mean distal esophageal temperature dropped 2.1 ± 0.4ÊC in the control group, dropped 1.3 ± 0.9ÊC in the forced air group, dropped 1.8 ± 0.4ÊC in the warming insufflation group, and raised 0.3 ± 0.2ÊC in the combination group (S1
Appendix temperatures per pig and intervention). Variation in distal esophageal
temperature over the course of the procedure for each group is represented in Fig 1. Considering the
entire experimental time course, the slope in core temperature is not statistically significant in
the warming insufflation plus forced-air group (combination group). The observed decrease
in distal esophageal temperature was statistically significant in the control group when
compared to the combination group. Moreover, statistically significant differences time slope
differences were noted between the control group and the combination group, as well as between
the warmed insufflation and combination group.
When the core temperature was divided into categorical values with time, the difference in core temperature between the control and combination group was found to be statistically significant with 210 min of insufflation.
This study demonstrates the potential advantage of using a forced-air warming blanket in
combination with insufflating heated/humidified CO2 for normothermia maintenance in pigs
undergoing pneumoperitoneum in comparison to prior techniques.
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Fig 1. Changes in core temperatures during the study period in each group. Circle blue line: control group (no insufflation); Square green line: warmed
insufflation group (heating and humidification of the insufflation CO2); Triangle orange line: forced air group (standard insufflation with lower-body warming
blanket); Triangle red line: combination group (heating and humidification of the insufflation CO2 in association with underbody warming blanket).Red Star
stands at time after which the difference in temperature becomes significant across groups control group versus combination group i.e. 210 min.
Hypothermia during anesthesia is common among surgical patients, thus warming is
necessary. Even with current warming application, the core temperature typically drops during
the first 60 to 90 minutes of surgery. This drop in temperature is mainly attributed to the initial
core heat redistribution to the peripheries [
]. After the redistribution period, general
anesthesia causes a further decrease in temperature due to peripheral vasodilatation and
increased peripheral blood flow [
]. Similar to the clinical setting, the pigs core
temperature dropped over the time, as demonstrated in our control group.
Forced-air warming is intended to prevent heat loss by covering the maximum amount of skin-surface area . While normothermia was better maintained by forced-air warming compared to the control group, it still eventually failed in the prevention of inadvertent perioperative hypothermia.
Heating and humidification of insufflated carbon dioxide alone was not sufficient for
temperature maintenance as the pigs became hypothermic over time. These findings were not
surprising, as the humidification and heating of insufflated CO2 only compensates for the heat
loss due to using the standard cold and dry CO2 insufflation of the peritoneum. However, this
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method does not prevent other heat loss mechanisms from occurring, such as peripheral
]. Nevertheless, the effect on heat loss prevention was unimpressive when
compared to the control group.
Interestingly, the reduction of core temperature in this group (1.8 ± 0.4ÊC) is similar to that
previously reported in another study (1.9 ± 0.1ÊC), though the insufflation gas flow differed
significantly (180 L/h vs. 120 L/h in the current study) . As a consequence of this,
insufflation gas flow per hour may be important in high-flow settings. The gas flow was sufficient in
preventing specific heat loss induced by peritoneal insufflation, but again was not effective in
stopping heat loss based on peripheral vasodilatation. Therefore, further investigation to
compare moderate to low flow insufflation in a clinical setting is warranted.
Both heating/humidification of insufflated CO2 and forced-air warming techniques failed
to prevent inadvertent perioperative hypothermia when used separately. It seems reasonable
that the combination of the two techniques might be beneficial, as they are acting on different
thermo-physical heat loss pathways in separate anatomical areas. It should be noted that this
combination approach was not able to prevent redistribution, but the effect was advantageous
in comparison to the other groups. This was not surprising since only pre-warming may
This study has several limitations. First, this study intended to provide initial experimental
data and was designed as a pilot study for subsequent clinical trials. Increased heat loss due to
the insufflation of cold CO2 is known, and used as a part of the basis for this trial. Based
on ethical considerations and the aim to reduce the number of animals used, we did not
include a fifth intervention consisting of standard cold insufflation without any warming
strategy applied. While the overall number of animals studied and interventions performed is low,
is was sufficient enough to provide reliable initial data for the indication for future clinical
trials. Administered fluids were not warmed, which is common practice in the clinical setting for
human patients. The capacity of warming fluids prior to administration to increase the core
temperature is limited. An advantage may be the prevention of further decreasing the core
temperature by administering warm fluids rather than cold fluids [
]. Finally, since this study
was performed using animal subjects, our findings cannot be translated directly into daily
clinical practice. The results obtained by this study appear reliable and may serve as a basis for
subsequent trials involving humans.
This experimental study showed that neither the warmed/humidified CO2 insufflation, nor the
forced-air warming blanket alone were effective in the prevention of perioperative
hypothermia. This trial indicated better maintenance of temperature in combining the two approaches
since they act on different anatomical areas and use different thermo-physical concepts. A
human clinic trail evaluating the prevention of inadvertent perioperative hypothermia in long
lasting laparoscopic cases is needed.
S1 Appendix. Temperatures per pig and intervention.
The authors want to thank Logan Glosser, BS for proof-reading the manuscript and the
Groupe Alsacien de Soutien à la Recherche en AnestheÂsie ReÂanimation (GASRAR).
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Conceptualization: Eric Noll, Sophie Diemunsch, Jean-Pierre Rameaux, Kurt Ruetzler, Pierre
Data curation: Sophie Diemunsch, Julien Pottecher, Jean-Pierre Rameaux.
Formal analysis: Eric Sauleau, Pierre Diemunsch.
Funding acquisition: Pierre Diemunsch.
Investigation: Eric Noll, Sophie Diemunsch, Julien Pottecher, Jean-Pierre Rameaux, Michele
Diana, Pierre Diemunsch.
Methodology: Eric Noll, Julien Pottecher, Jean-Pierre Rameaux, Michele Diana.
Project administration: Eric Noll, Sophie Diemunsch, Julien Pottecher, Pierre Diemunsch.
Supervision: Kurt Ruetzler, Pierre Diemunsch.
Validation: Eric Sauleau.
Visualization: Eric Sauleau.
Writing ± original draft: Eric Noll, Sophie Diemunsch, Julien Pottecher, Jean-Pierre
Rameaux, Eric Sauleau, Kurt Ruetzler, Pierre Diemunsch.
Writing ± review & editing: Eric Noll, Kurt Ruetzler, Pierre Diemunsch.
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