Monitor-Guided Analgesia During General Anesthesia - Part II (MOGADA-II)

• ClinicalTrials.gov Identifier: NCT03380949
• Recruitment Status: Completed
• First Posted: December 21, 2017
• Last Update Posted: April 30, 2019
• Sponsor: Universitätsklinikum Hamburg-Eppendorf
• Information provided by (Responsible Party): Universitätsklinikum Hamburg-Eppendorf

Study Description

Brief Summary:

This prospective randomized clinical trial evaluates the effects of a monitor-guided opioid analgesia during general anesthesia. To date no standard-monitoring device exists to specifically reflect the analgesic component of general anesthesia. Quality and safety of general anesthesia are of major clinical importance and should be improved by limiting the opioid analgesic's dosage to the minimum amount needed. The study compares the effects of monitoring nociception during general anesthesia with different innovative techniques in comparison to routine clinical practice.

Condition or disease	Intervention/treatment	Phase
Pain, Postoperative; Pain; Nociceptive Pain; Opioid Use; Analgesia	Procedure: Opioid administration (remifentanil) in intervention group; Procedure: Opioid administration (remifentanil) in control group	Not Applicable

Detailed Description:

This prospective randomized clinical study aims to investigate the effects of a monitor-guided opioid analgesia during general anesthesia by different monitoring systems in comparison to routine clinical practice. Many surgical procedures require general anesthesia. The main components of general anesthesia are hypnosis and analgesia, and anesthesiologists usually combine a hypnotic drug with an opioid analgesic.

Until today, however, there is no standard-monitoring of nociception to specifically reflect the analgesic component of general anesthesia. In clinical practice the opioid dosage is chosen by clinical judgment of the attending anesthesiologist based upon changes of heart rate, blood pressure, pupil size, lacrimation and sweating of the patient.

On the one hand, underdosage of opioids can cause nociception leading to an increased sympathetic tone, increase of plasma levels of stress hormones, nociceptive movements as well as increase postoperative pain. On the other hand, overdosage of opioids can lead to drug side effects such as nausea and vomiting, hemodynamic instability, an increase in recovery times, immunosuppression and an increase in postoperative pain by opioid-induced-hyperalgesia. Quality and safety of general anesthesia are of major clinical importance and can be improved by limiting the administration of opioid analgesics to the optimal individual dose needed. In the last years, different analgesia monitoring devices have been developed for monitoring nociception. The present study evaluates the effects of the administration of opioids during general anesthesia guided by three different monitoring systems in comparison to routine clinical practice. All patients will receive general anesthesia with propofol guided by bispectral index (BIS) with a target of BIS values between 40 and 60. Opioid administration will be guided by one of three analgesic monitoring devices or the interpretation of clinical signs by the attending anesthesiologist in the control group. After institutional approval by the Ethics committee of the Medical Board of the City of Hamburg, Germany and obtaining patients' written informed consent we randomize elective patients with major abdominal surgery for open radical prostatectomy into one of four treatment groups.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 96 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Intervention Model Description: Participants are assigned to intervention groups by chance
• Masking: Double (Participant, Outcomes Assessor)
• Masking Description: Participants are not informed about the group assignement (intervention takes place in general anesthesia). Outcome assessors are persons without knowledge on former treatment in intervention/control group.
• Primary Purpose: Treatment
• Official Title: Investigation of the Effect of Opioid Titration Guided by Analgesia Indices During Total Intravenous Anesthesia
• Actual Study Start Date: December 8, 2017
• Actual Primary Completion Date: April 18, 2018
• Actual Study Completion Date: June 7, 2018

Arms and Interventions

Arm	Intervention/treatment
Experimental: PPI (Pain Pupillary Index); Opioid administration (remifentanil) in intervention group is guided by PPI derived from video-pupillometry performed with the AlgiScan™ by IDMed, Marseille, France. The device measures the degree of pupillary reflex dilation (PRD) following a nociceptive stimulation. It automatically increases the intensity of the electric stimulation from 10 to 60 mA and displays the PPI as numerical index between 0 and 10. A low PPI score indicates deep, a high score light analgesia. A PPI score of 2-3 is supposed to represent an optimal level of analgesia. A remifentanil bolus of 30 µg will be administered and the infusion rate of remifentanil will be increased by 0.03 µg/kg/min if PPI score is calculated more than 3. Remifentanil infusion will be decreased by 0.03 µg/kg/min if PPI score is <1.	Procedure: Opioid administration (remifentanil) in intervention group; Elective surgery in radical open abdominal prostatectomy. Opioid titration (remifentanil) is guided by analgesia indices during general anesthesia in the experimental arms.
Experimental: SPI (Surgical Pleth Index); Opioid administration (remifentanil) in intervention group is guided by SPI derived from photoplethysmography performed by the device CARESCAPE™ B650 Patient Monitor by GE Healthcare, Helsinki, Finland. Included in the monitoring system is a software that continuously calculates the SPI from normalized heart rate and pulse wave amplitude derived from finger plethysmography. The numerical index ranges between 0 (low sympathetic tone) and 100 (high sympathetic tone). A SPI score between 20 and 50 has been proposed as the target range. A remifentanil bolus of 30 µg will be administered and the infusion rate of remifentanil will be increased by 0.03 µg/kg/min if SPI score is calculated more than 50. Remifentanil infusion will be decreased by 0.03 µg/kg/min if PPI score is calculated below 20.	Procedure: Opioid administration (remifentanil) in intervention group; Elective surgery in radical open abdominal prostatectomy. Opioid titration (remifentanil) is guided by analgesia indices during general anesthesia in the experimental arms.
Experimental: NOL (Nociception Level); Opioid administration (remifentanil) in intervention group is guided by NOL derived from finger photoplethysmography performed with the device PMD200™ manufactured by Medasense, Ramat Gan, Israel. The device continuously calculates the NOL with a multi-parametric approach from pulse rate, pulse rate variability, pulse wave amplitude, skin conductance level and fluctuations, skin temperature and finger motion. It is presented on a scale from 0 (no pain) to 100 (extreme pain). A NOL score between 10 and 25 has been proposed as the target range. A remifentanil bolus of 30 µg will be administered and the infusion rate will be increased by 0.03 µg/kg/min if NOL score is calculated more than 25. Remifentanil infusion will be decreased by 0.03 µg/kg/min if PPI score is calculated below 10.	Procedure: Opioid administration (remifentanil) in intervention group; Elective surgery in radical open abdominal prostatectomy. Opioid titration (remifentanil) is guided by analgesia indices during general anesthesia in the experimental arms.
Active Comparator: Control; Opioid administration (remifentanil) in control group is guided according to standard clinical practice of the attending anesthesiologist based upon changes of heart rate, blood pressure, lacrimation and sweating of the patient.	Procedure: Opioid administration (remifentanil) in control group; Elective surgery in radical open abdominal prostatectomy. Opioid titration (remifentanil) is guided by clinical signs in the control group.

Outcome Measures

Primary Outcome Measures :

1. Intraoperative opioid consumption [ Time Frame: 1 day ]
   Compares the amount of intraoperative opioid administration (remifentanil) per minute of general anesthesia and per kg bodyweight between groups.

Secondary Outcome Measures :

1. Time to extubation [ Time Frame: 1 day ]
   Postoperative recovery time: Time interval between end of operation and tracheal extubation of the patient.
2. Time to Fit-for-discharge [ Time Frame: 1 day ]

   Postoperative recovery time: Time interval between postoperative tracheal extubation and the patient reaching fit-for-discharge criteria.

   criteria from the PACU to the ward.

3. Postoperative pain level [ Time Frame: 1 day ]
   Postoperative pain level measured with the highest score in numeric pain rating scale (NRS).
4. Postoperative opioid administration [ Time Frame: 1 day ]
   Amount of postoperative opioid administration (piritramid) in the postanesthesia care unit (PACU). Piritramid is given if NRS score is > 3.
5. Patient satisfaction [ Time Frame: 2-21 days ]
   Patient satisfaction with the general anesthesia and pain management evaluated by a numeric rating scale.
6. Release of stress hormones [ Time Frame: 1 day ]
   Amount of perioperative plasma level of cortisol and ACTH.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• Radical open abdominal prostatectomy scheduled in the operation theater where the study is conducted
• > 18 years

Exclusion Criteria:

• Chronic opioid therapy
• Beta blocker and digitalis therapy
• Eye disease with affection of pupil reactivity
• Pacemaker therapy
• Higher degrees of cardiac arrhythmias, e.g. atrial fibrillation
• Pre-operative medication with steroids

Contacts and Locations

Locations

Germany

Department of Anesthesiology; Center of Anesthesiology and Intensive Care Medicine, Hamburg Eppendorf University Medical Center

Hamburg, Germany, 20246

Sponsors and Collaborators

Universitätsklinikum Hamburg-Eppendorf

Investigators

• Principal Investigator: Rainer Nitzschke, MD; Department of Anesthesiology, Hamburg Eppendorf University Medical Center
• Principal Investigator: Sandra Funcke, MD; Department of Anesthesiology, Hamburg Eppendorf University Medical Center

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Funcke S, Pinnschmidt HO, Brinkmann C, Wesseler S, Beyer B, Fischer M, Nitzschke R. Nociception level-guided opioid administration in radical retropubic prostatectomy: a randomised controlled trial. Br J Anaesth. 2021 Feb;126(2):516-524. doi: 10.1016/j.bja.2020.09.051. Epub 2020 Nov 20.

• Responsible Party: Universitätsklinikum Hamburg-Eppendorf
• ClinicalTrials.gov Identifier: NCT03380949
• Other Study ID Numbers: 20171120
• First Posted: December 21, 2017
• Last Update Posted: April 30, 2019
• Last Verified: April 2019

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No
• Plan Description: All data will be anonymized before publication.

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Universitätsklinikum Hamburg-Eppendorf:

Analgesia; Monitoring; Opioid; Sufentanil; Sevoflurane

Additional relevant MeSH terms:

Pain, Postoperative; Nociceptive Pain; Neurologic Manifestations; Postoperative Complications; Pathologic Processes; Pain; Remifentanil; Analgesics, Opioid; Narcotics; Central Nervous System Depressants; Physiological Effects of Drugs; Analgesics; Sensory System Agents; Peripheral Nervous System Agents