Effects of Warmed, Humidified CO2 Insufflation on Body Core Temperature and Cytokine Response

• Sponsor: Azienda Ospedaliera Città della Salute e della Scienza di Torino (Other)
• Overall Status: Completed
• CT.gov ID: NCT02586974
• Collaborator: IRCAD - EITS (Other)
• Enrollment: 64
• Location: 1
• Arms: 2
• Actual Duration (Months): 11
• Patients Per Site Per Month: 5.8

Study Details

Study Description

Brief Summary

The aim of this study is to assess if the conditioning of the insufflation carbon dioxide (CO2) allows for an additional benefit in terms of prevention of the heat loss, when compared with the usual prevention with a forced warm air blanket alone, in the setting of robot-assisted radical prostatectomy (RARP).

Condition or Disease	Intervention/Treatment	Phase
Hypothermia	Device: Humigard	N/A

Detailed Description

Among the possible consequences of cool and dry gas insufflation during laparoscopic procedures are hypothermia and cytokine response, which might cause significant perioperative morbidity. More in detail, body core temperature decrease during laparoscopic surgery has been calculated in humans as 0.3 °C for every 50 L of cold and dry insufflation gas. The reported temperature drop is caused by redistribution of heat and heat loss, both non-specific (due to anaesthesia and environmental patient exposure) and specific (due to peritoneal dry and cool insufflations). The resulting hypothermia can be severe, particularly after prolonged surgery. As for cytokine response, an increase of several pro-inflammatory cytokines has been described following the irritating effect of peritoneal CO2 insufflation.

That said, various devices of conditioning of the insufflating gas have been investigated to reduce the specific heat losses resulting from peritoneal insufflations, as well as to evaluate the inflammatory response. Previous studies conducted on animal models and clinical settings have suggested that warmed and humidified insufflation allows for an improved maintenance of body core temperature, a reduction in the degree of inflammatory response and an improved quality of postoperative course, compared with standard insufflating gas. These findings, however, are still not conclusive as they have not been confirmed by adequate randomized, controlled trials. Furthermore, no device providing warming and humidification has demonstrated a conclusive advantage over standard cold dry gas in terms of prevention of hypothermia during laparoscopy in man.

On the basis of the current available studies favouring warmed and humidified insufflation, the investigators hypothesize that a new device providing warmed and humidified insufflation (Humigard® Fisher and Paykel Healthcare®) might achieve significant benefits over standard insufflation in terms of body core temperature maintenance. The investigators also expect to document a decrease of pro-inflammatory cytokines, as a response to a diminished peritoneal irritation.

Study Design

• Study Type: Interventional
• Actual Enrollment: 64 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Participant)
• Primary Purpose: Supportive Care
• Official Title: Effects of Warmed, Humidified CO2 Insufflation on Body Core Temperature and Cytokine Response: Head-to-head Randomized Comparison Versus Standard Insufflation During Robot Assisted Radical Prostatectomy
• Actual Study Start Date: Sep 1, 2015
• Actual Primary Completion Date: Jun 1, 2016
• Actual Study Completion Date: Aug 1, 2016

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Group H+WB 32 patients will receive warmed, humidified CO2 insufflation with the Humigard® device, along with the hot air warming blanket used as a routine in our institution (forced air warming blanket at 38°C : Bear Hugger®)	Device: Humigard; warmed and humidified CO2 insufflation
No Intervention: Group WB 32 patients will receive standard CO2 insufflation, along with the hot air warming blanket used as a routine in our institution (forced air warming blanket at 38°C : Bear Hugger® and a standard insufflation with non-humidified, non-heated CO2)

Outcome Measures

Primary Outcome Measures

1. Intraoperative Change in Body Core Temperature [Intraoperative at hourly intervals]

   body core temperature of patients undergoing robot-assisted radical prostatectomy (RARP), measured with a disposable esophageal probe

Secondary Outcome Measures

1. Cytokine Interleukin-6 (IL-6) [changes in cytokine levels measured just before induction of anesthesia, after 2 h of pneumoperitoneum, 2 h from exsufflation, and 24 h after surgery]

   mean levels of the pro-inflammatory cytokine interleukin-6 (IL-6) in patients undergoing robot-assisted radical prostatectomy (RARP), measured just before induction of anesthesia, after 2 h of pneumoperitoneum, 2 h from exsufflation, and 24 h after surgery

2. Cytokine Tumor Necrosis Factor (TNF)-Beta [changes in cytokine levels just before induction of anesthesia, after 2 h of pneumoperitoneum, 2 h from exsufflation, and 24 h after surgery]

   mean levels of the pro-inflammatory cytokine tumor necrosis factor (TNF)-beta in patients undergoing robot-assisted radical prostatectomy (RARP), measured just before induction of anesthesia, after 2 h of pneumoperitoneum, 2 h from exsufflation, and 24 h after surgery

3. Postoperative Pain [changes in postoperative pain measured at patient awakening and then every 30 min in the recovery room, until discharge to the ward. Successively, it was measured at 12, 24, and 48 h]

   postoperative pain in patients undergoing robot-assisted radical prostatectomy (RARP) as measured by the Numeric Pain Rating Score (NRS), measured at patient awakening and after 12, 24, and 48 h from surgery. NRS goes from 0 to 10, where 0 means no pain and 10 the maximum pain possible.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 40 Years to 80 Years
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• all patients undergoing RARP, with or without pelvic lymph node dissection, with a CO2 insufflation scheduled to last more than 60 minutes

Exclusion Criteria:

• patients over 80 years old, patients American Society of Anesthesiologist (ASA) status 4 or higher, patients not willing to sign the informed consent, conversions to open surgery

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	A.O.U. San Giovanni Battista Molinette	Torino	TO	Italy	10126

Sponsors and Collaborators

• Azienda Ospedaliera Città della Salute e della Scienza di Torino
• IRCAD - EITS

Investigators

• Principal Investigator: Paolo Gontero, Prof, AOU Città della Salute e della Scienza

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Marco Oderda, PhD fellow, Azienda Ospedaliera Città della Salute e della Scienza di Torino
• ClinicalTrials.gov Identifier: NCT02586974
• Other Study ID Numbers: 0052588
• First Posted: Oct 27, 2015
• Last Update Posted: Feb 12, 2020
• Last Verified: Feb 1, 2020

• Keywords provided by Marco Oderda, PhD fellow, Azienda Ospedaliera Città della Salute e della Scienza di Torino: CO2 insufflation; robot assisted radical prostatectomy; laparoscopy; hypothermia; cytokine response
• Additional relevant MeSH terms: Hypothermia

Study Results

Participant Flow

Recruitment Details	All patients undergoing RARP at Città della Salute e della Scienza Hospital between September 2015 and June 2016 were screened for inclusion.
Pre-assignment Detail	Exclusion criteria were as follows: age >80 years, ASA status >3, allergic status needing corticosteroid premedication, refusal to sign the informed consent, cognitive disability, conversion to open surgery.

Arm/Group Title	Group H+WB	Group WB
Arm/Group Description	32 patients will receive warmed, humidified CO2 insufflation with the Humigard® device, along with the hot air warming blanket used as a routine in our institution (forced air warming blanket at 38°C : Bear Hugger®) Humigard: warmed and humidified CO2 insufflation	32 patients will receive standard CO2 insufflation, along with the hot air warming blanket used as a routine in our institution (forced air warming blanket at 38°C : Bear Hugger® and a standard insufflation with non-humidified, non-heated CO2)
Period Title: Overall Study
STARTED	32	32
COMPLETED	32	32
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Group H+WB	Group WB	Total
Arm/Group Description	32 patients will receive warmed, humidified CO2 insufflation with the Humigard® device, along with the hot air warming blanket used as a routine in our institution (forced air warming blanket at 38°C : Bear Hugger®) Humigard: warmed and humidified CO2 insufflation	32 patients will receive standard CO2 insufflation, along with the hot air warming blanket used as a routine in our institution (forced air warming blanket at 38°C : Bear Hugger® and a standard insufflation with non-humidified, non-heated CO2)	Total of all reporting groups
Overall Participants	32	32	64
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	66.4 (7.0)	64.4 (9.0)	65.4 (8.0)
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%
Male	32 100%	32 100%	64 100%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	0 0%	0 0%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	0 0%	0 0%
White	32 100%	32 100%	64 100%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
Italy	32 100%	32 100%	64 100%

Outcome Measures

1. Primary Outcome

Title	Intraoperative Change in Body Core Temperature
Description	body core temperature of patients undergoing robot-assisted radical prostatectomy (RARP), measured with a disposable esophageal probe
Time Frame	Intraoperative at hourly intervals

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Group Humigard+Warming Blanket (H+WB)	Group Warming Blanket (WB)
Arm/Group Description	32 patients will receive warmed, humidified CO2 insufflation with the Humigard® device, along with the hot air warming blanket used as a routine in our institution (forced air warming blanket at 38°C : Bear Hugger®) Humigard: warmed and humidified CO2 insufflation	32 patients will receive standard CO2 insufflation, along with the hot air warming blanket used as a routine in our institution (forced air warming blanket at 38°C : Bear Hugger® and a standard insufflation with non-humidified, non-heated CO2)
Measure Participants	32	32
start of surgery	35.73 (0.37)	35.70 (0.34)
after 1h	35.78 (0.42)	35.77 (0.37)
after 2h	35.96 (0.53)	35.90 (0.41)
after 3h	36.11 (0.60)	36.07 (0.52)
after 4h	36.34 (0.64)	36.07 (0.55)
end of surgery	36.26 (0.69)	36.06 (0.62)

2. Secondary Outcome

Title	Cytokine Interleukin-6 (IL-6)
Description	mean levels of the pro-inflammatory cytokine interleukin-6 (IL-6) in patients undergoing robot-assisted radical prostatectomy (RARP), measured just before induction of anesthesia, after 2 h of pneumoperitoneum, 2 h from exsufflation, and 24 h after surgery
Time Frame	changes in cytokine levels measured just before induction of anesthesia, after 2 h of pneumoperitoneum, 2 h from exsufflation, and 24 h after surgery

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Group H+WB	Group WB
Arm/Group Description	32 patients will receive warmed, humidified CO2 insufflation with the Humigard® device, along with the hot air warming blanket used as a routine in our institution (forced air warming blanket at 38°C : Bear Hugger®) Humigard: warmed and humidified CO2 insufflation	32 patients will receive standard CO2 insufflation, along with the hot air warming blanket used as a routine in our institution (forced air warming blanket at 38°C : Bear Hugger® and a standard insufflation with non-humidified, non-heated CO2)
Measure Participants	32	32
start of surgery	2.13 (2.07)	2.20 (2.2)
after 2h	4.61 (5.04)	4.16 (3.5)
2h from exsufflation	29.13 (24.18)	25.91 (22.9)
24h after surgery	27.01 (25.12)	23.67 (25.8)

3. Secondary Outcome

Title	Cytokine Tumor Necrosis Factor (TNF)-Beta
Description	mean levels of the pro-inflammatory cytokine tumor necrosis factor (TNF)-beta in patients undergoing robot-assisted radical prostatectomy (RARP), measured just before induction of anesthesia, after 2 h of pneumoperitoneum, 2 h from exsufflation, and 24 h after surgery
Time Frame	changes in cytokine levels just before induction of anesthesia, after 2 h of pneumoperitoneum, 2 h from exsufflation, and 24 h after surgery

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Group H+WB	Group WB
Arm/Group Description	32 patients will receive warmed, humidified CO2 insufflation with the Humigard® device, along with the hot air warming blanket used as a routine in our institution (forced air warming blanket at 38°C : Bear Hugger®) Humigard: warmed and humidified CO2 insufflation	32 patients will receive standard CO2 insufflation, along with the hot air warming blanket used as a routine in our institution (forced air warming blanket at 38°C : Bear Hugger® and a standard insufflation with non-humidified, non-heated CO2)
Measure Participants	32	32
start of surgery	5.74 (4.8)	6.29 (6.6)
after 2h	5.69 (5.8)	5.20 (4.2)
2h from exsufflation	5.44 (5.3)	4.90 (4.5)
24h after surgery	6.11 (5.7)	7.24 (6.0)

4. Secondary Outcome

Title	Postoperative Pain
Description	postoperative pain in patients undergoing robot-assisted radical prostatectomy (RARP) as measured by the Numeric Pain Rating Score (NRS), measured at patient awakening and after 12, 24, and 48 h from surgery. NRS goes from 0 to 10, where 0 means no pain and 10 the maximum pain possible.
Time Frame	changes in postoperative pain measured at patient awakening and then every 30 min in the recovery room, until discharge to the ward. Successively, it was measured at 12, 24, and 48 h

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Group H+WB	Group WB
Arm/Group Description	32 patients will receive warmed, humidified CO2 insufflation with the Humigard® device, along with the hot air warming blanket used as a routine in our institution (forced air warming blanket at 38°C : Bear Hugger®) Humigard: warmed and humidified CO2 insufflation	32 patients will receive standard CO2 insufflation, along with the hot air warming blanket used as a routine in our institution (forced air warming blanket at 38°C : Bear Hugger® and a standard insufflation with non-humidified, non-heated CO2)
Measure Participants	32	32
Patient awakening	2.5 (2.6)	2.3 (2.8)
At 12 hours	1.6 (1.8)	1.9 (2.2)
At 24 hours	1.3 (1.5)	1.8 (2.1)
At 48 hours	0.6 (1.1)	1.1 (1.9)

Adverse Events

Time Frame	Adverse event data during hospital stay, an average of 4 days
Adverse Event Reporting Description	Adverse events (as per Clavien-Dindo classification) directly linked to the CO2 insufflation during the robot-assisted laparoscopic procedure (standard vs Humigard)
Arm/Group Title	Group H+WB		Group WB
Arm/Group Description	32 patients will receive warmed, humidified CO2 insufflation with the Humigard® device, along with the hot air warming blanket used as a routine in our institution (forced air warming blanket at 38°C : Bear Hugger®) Humigard: warmed and humidified CO2 insufflation		32 patients will receive standard CO2 insufflation, along with the hot air warming blanket used as a routine in our institution (forced air warming blanket at 38°C : Bear Hugger® and a standard insufflation with non-humidified, non-heated CO2)
All Cause Mortality
	Group H+WB		Group WB
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/32 (0%)		0/32 (0%)
Serious Adverse Events
	Group H+WB		Group WB
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/32 (0%)		0/32 (0%)
Other (Not Including Serious) Adverse Events
	Group H+WB		Group WB
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/32 (0%)		0/32 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.