Pain, PostoperativePredictPainNCT05063227
Prediction of Postoperative Pain by Nociception Monitoring
An observational study of Pain, Postoperative and Analgesia, run by Universitätsklinikum Hamburg-Eppendorf at 1 site in Germany.
Trial summary
General anesthesia is a combination of hypnotic drugs and opioid analgesics. Modern general anesthesia aims to treat nociception induced by surgical stimulation while avoiding an overdose of opioid analgesics and reducing side-effects of opioid administration. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Pain, Postoperative, Analgesia, Anesthesia Recovery Period
- What is being tested?
- Observational: analgesia monitoring indices and changes in heart rate
- How many people
- 60 participants
- Where
- 1 siteGermany
- Study dates
- 6 Oct 2021to 4 Jan 2023
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: This study includes all patients with elective trauma surgery and orthopedic surgery scheduled on a weekday Monday to Friday in the operation theater where the study is conducted,which do not present with an exclusion criterion. There is no further eligibility criteria and thusly, this is a non-sepcified study on all patients that meet the requirements for the three analgesia monitoring devices.
Who may be able to join
- Patients with elective trauma surgery and orthopedic surgery scheduled on a weekday Monday to Friday in the operation theater where the study is conducted
Who cannot join
- Beta blocker, digitalis or cardiac pacemaker therapy
- Higher degrees of cardiac arrhythmias, e.g. atrial fibrillation and atrio-ventricular block >1st degree
- Severe peripheral or cardiac neuropathy
- Eye disease with affection of pupil reactivity
- Intraoperative treatment with ketamine, beta-receptor blockers, beta-receptor agonists or clonidine and treatment with vasoactive medication within 10 min before and during data acquisition period
- Inability to adequately specify postoperative pain level
- Postoperative care in the intensive care unit (ICU) or postanesthesia care unit with planned overnight stay (PACU24, intermediate care unit IMC)
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Predictive Value of Different Nociception Monitoring Systems for the Prediction of Moderate to Severe Postoperative Pain After General Anesthesia
General anesthesia is a combination of hypnotic drugs and opioid analgesics. Modern general anesthesia aims to treat nociception induced by surgical stimulation while avoiding an overdose of opioid analgesics and reducing side-effects of opioid administration. Quality and safety of general anesthesia are of major clinical importance and can be improved by adjusting the opioid analgesics to the optimal individual dose needed. In the current clinical practice, the opioid dosage is usually chosen by clinical judgment, though recently different monitoring devices estimating the effect of nociception during unconsciousness have become commercially available. Nevertheless, the impact of nociception-monitor-guided opioid administration on the administered amount of opioid, postoperative short-term recovery, and long-term outcome is inconclusive. This study aims to investigate the predictive power of different nociception monitoring systems for the prediction of moderate to severe immediate postoperative pain from nociception indices measured before awakening from general anesthesia.
Read the detailed description
General anesthesia is a combination of hypnotic drugs and opioid analgesics. Modern general anesthesia aims to treat nociception induced by surgical stimulation while avoiding an overdose of opioid analgesics and reducing side-effects of opioid administration. Underdosing of opioids during surgery can lead to nociception with increased sympathetic tone, elevated levels of stress hormones, unintended patient movement due to nociception as well as increased postoperative pain. On the other hand, overdosing of opioids can lead to negative side effects such as nausea and vomiting, arterial hypotension, immunosuppression, prolonged recovery times, postoperative delirium 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 adjusting the opioid analgesics to the optimal individual dose needed. In the current clinical practice, the opioid dosage is chosen by clinical judgment of the attending anesthesiologist based on changes in the heart rate, blood pressure, pupil size, lacrimation and sweating of the patient. In recent years, different monitoring devices estimating the effect of nociception during unconsciousness have become commercially available. These monitoring devices use several different mechanisms, such as heart rate (HR) variability, pulse wave photoplethysmography, pupil reflex dilation, and skin conductance measurement, and based on these signals index the nociception/analgesia balance. Such monitoring devices should help physicians choose the right dose of opioid analgesics during general anesthesia. Nevertheless, the impact of nociception-monitor-guided opioid administration on the administered amount of opioid, postoperative short-term recovery, and long-term outcome is inconclusive.
Current literature is inconclusive if the nociception monitoring devices have predictive power to predict immediate postoperative pain after awakening from general anesthesia already before awakening from general anesthesia.
In this prospective, double-blinded, observational clinical study the investigators aim to evaluate the predictive power of different nociception monitoring systems for the prediction of moderate to severe immediate postoperative pain from nociception indices measured before awakening from general anesthesia. The nociception monitoring systems included in the study are the Surgical Pleth Index (SPI), the Pupillary Pain Index (PPI) and the Nociception Level (NOL) and heart rate changes as a variable used in current clinical practice to choose the opioid dosage during general anesthesia.
The postoperative pain level will be assessed from anesthesia nurses using the Numerical Rating Scale (NRS) who are blinded to the nociception indices measured before awakening.
For SPI monitoring there are findings suggesting that an SPI > 30 could be the 'best-fit' optimal threshold with the highest sum of sensitivity and specificity to detect moderate to severe pain. Nevertheless, positive and negative predictive value of SPI were still rather low.
For PPI monitoring there are data demonstrating a moderate correlation between PPI values before tracheal extubation and postoperative pain. Another study with pupil dilatation reflex threshold showed only a minor correlation between pupil dilatation reflex threshold and the intensity of immediate postoperative pain.
For NOL monitoring, on the one hand, there are data suggesting that a threshold of > 20 after knife to skin incision has predictive power to predict moderate to severe postoperative pain. On the other hand, the highest combined sensitivity and specificity were still rather low. While a NOL < 10 after skin incision excluded moderate-severe postoperative pain with a negative predictive value of 83%, the NOL during surgery and at the end of surgery did not allow the exclusion or the prediction of moderate-severe postoperative pain.
- Conditions
- Pain, Postoperative, Analgesia, Anesthesia Recovery Period, Opioid Use
- Being tested
- Observational: analgesia monitoring indices and changes in heart rate
- Keywords
- Analgesia Monitoring, General anesthesia
- Medical subject headings
- Pain, Postoperative, Agnosia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Observational: analgesia monitoring indices and changes in heart rateDiagnostic test
After the end of surgery (defined as the time of skin closure or wound dressing), but before awakening (BIS will still be < 60), SPI, PPI and NOL are recorded in a quiet setting without any other stimulation. Within the five minutes data acquisition period nociception indices are recorded every minute (T0, T1, T2, T3, T4, T5). The highest SPI, PPI and NOL are used for further analysis.
| Study group | Role | What they receive |
|---|---|---|
| Study group | As this is a single-group, observational study all patients will be monitored with all three nociception monitoring systems (the Surgical Pleth Index (SPI), the Pupillary Pain Index (PPI) and the Nociception Level (NOL)) and data on heart rate changes as a variable used in current clinical practice to choose the opioid dosage during general anesthesia will be obtained additionally. Receives: Diagnostic Test: Observational: analgesia monitoring indices and changes in heart rate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Primary endpoint will be the diagnostic accuracy (ROC analysis) of the nociception indices after the end of surgery to predict moderate to severe immediate postoperative pain
Numerical Rating Scale (NRS) Scale 4-10 NRS has a minimal value of 0 and a maximal value of 10, higher scores mean a worse outcome (higher pain level).
Measured: Once immediately after arrival in the post-anesthesia care unit (PACU)
Secondary outcomes (5)
The correlation between the nociception indices after the end of surgery and immediate postoperative pain measured with the NRS on a scale of 0 - 10
Numerical Rating Scale (NRS) NRS has a minimal value of 0 and a maximal value of 10, higher scores mean a worse outcome (higher pain level).
Measured: Once immediately after arrival in the post-anesthesia care unit (PACU)
The correlation between the nociception indices after the end of surgery and postoperative pain measured with the NRS on a scale of 0 - 10 after 60 minutes in PACU
Numerical Rating Scale (NRS) NRS has a minimal value of 0 and a maximal value of 10, higher scores mean a worse outcome (higher pain level).
Measured: First 60 minutes after arrival in the PACU
Correlation between the nociception indices and the highest postoperative NRS
Numerical Rating Scale (NRS) NRS has a minimal value of 0 and a maximal value of 10, higher scores mean a worse outcome (higher pain level).
Measured: Once in the first 2 hours during the PACU stay
The correlation between the nociception indices after the end of surgery and the amount of opioids in the first 30 minutes after surgery
Cumulative amount of opioids in morphine equivalents
Measured: Time period of first 30 minutes during the PACU stay
The correlation between the nociception indices after the end of surgery and the amount of opioids in up to 2 hours after surgery
Cumulative amount of opioids in morphine equivalents
Measured: Time period of first 2 hours during the PACU stay
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Oct 2021
- Study start6 Oct 2021
- Primary completion2 Dec 2021
- Study completion4 Jan 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Pain, PostoperativeStudies of the same condition, open and under way.
- More trials run by Universitätsklinikum Hamburg-EppendorfThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case only
- Time perspective
- Prospective
- Enrolment
- 60 participants (actual)
Sponsor and investigators
- Lead sponsor
- Universitätsklinikum Hamburg-Eppendorf
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Rainer Nitzschke, MD, Principal investigator, Center for Anesthesiology and Intensive Care Medicine, University Medical Center Hamburg-Eppendorf
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05063227
- Sponsor's protocol ID
- 2021-06
- Acronym
- PredictPain
- Status last verified
- Jul 2023
- First submitted
- 10 Jul 2021
- Last updated
- 5 Jul 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided: Anonymized data on request only.
Publications
Koschmieder KC, Funcke S, Shadloo M, Pinnschmidt HO, Greiwe G, Fischer M, Nitzschke R. Validation of three nociception indices to predict immediate postoperative pain before emergence from general anaesthesia: a prospective double-blind, observational study. Br J Anaesth. 2023 Apr;130(4):477-484. doi: 10.1016/j.bja.2022.11.024. Epub 2023 Jan 4.
PubMed 36609057
Study at a glance
From the registry record, last updated by the sponsor on 5 Jul 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Predictive Value of Different Nociception Monitoring Systems for the Prediction of Moderate to Severe Postoperative Pain After General Anesthesia
- ClinicalTrials.gov ID
- NCT05063227
- Acronym / sponsor ID
- PredictPain / 2021-06
- Conditions
- Pain, Postoperative, Analgesia, Anesthesia Recovery Period, Opioid Use
- Keywords
- Analgesia Monitoring, General anesthesia
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 60 participants (actual)
- Lead sponsor
- Universitätsklinikum Hamburg-EppendorfUniversity, hospital or other
- Study start
- 6 Oct 2021 (actual)
- Primary completion
- 2 Dec 2021 (actual)
- Study completion
- 4 Jan 2023 (actual)
- First posted
- 1 Oct 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
General anesthesia is a combination of hypnotic drugs and opioid analgesics. Modern general anesthesia aims to treat nociception induced by surgical stimulation while avoiding an overdose of opioid analgesics and reducing side-effects of opioid administration. Quality and safety of general anesthesia are of major clinical importance and can be improved by adjusting the opioid analgesics to the optimal individual dose needed. In the current clinical practice, the opioid dosage is usually chosen by clinical judgment, though recently different monitoring devices estimating the effect of nociception during unconsciousness have become commercially available. Nevertheless, the impact of nociception-monitor-guided opioid administration on the administered amount of opioid, postoperative short-term recovery, and long-term outcome is inconclusive. This study aims to investigate the predictive power of different nociception monitoring systems for the prediction of moderate to severe immediate postoperative pain from nociception indices measured before awakening from general anesthesia.
Detailed description
General anesthesia is a combination of hypnotic drugs and opioid analgesics. Modern general anesthesia aims to treat nociception induced by surgical stimulation while avoiding an overdose of opioid analgesics and reducing side-effects of opioid administration. Underdosing of opioids during surgery can lead to nociception with increased sympathetic tone, elevated levels of stress hormones, unintended patient movement due to nociception as well as increased postoperative pain. On the other hand, overdosing of opioids can lead to negative side effects such as nausea and vomiting, arterial hypotension, immunosuppression, prolonged recovery times, postoperative delirium 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 adjusting the opioid analgesics to the optimal individual dose needed. In the current clinical practice, the opioid dosage is chosen by clinical judgment of the attending anesthesiologist based on changes in the heart rate, blood pressure, pupil size, lacrimation and sweating of the patient. In recent years, different monitoring devices estimating the effect of nociception during unconsciousness have become commercially available. These monitoring devices use several different mechanisms, such as heart rate (HR) variability, pulse wave photoplethysmography, pupil reflex dilation, and skin conductance measurement, and based on these signals index the nociception/analgesia balance. Such monitoring devices should help physicians choose the right dose of opioid analgesics during general anesthesia. Nevertheless, the impact of nociception-monitor-guided opioid administration on the administered amount of opioid, postoperative short-term recovery, and long-term outcome is inconclusive.
Current literature is inconclusive if the nociception monitoring devices have predictive power to predict immediate postoperative pain after awakening from general anesthesia already before awakening from general anesthesia.
In this prospective, double-blinded, observational clinical study the investigators aim to evaluate the predictive power of different nociception monitoring systems for the prediction of moderate to severe immediate postoperative pain from nociception indices measured before awakening from general anesthesia. The nociception monitoring systems included in the study are the Surgical Pleth Index (SPI), the Pupillary Pain Index (PPI) and the Nociception Level (NOL) and heart rate changes as a variable used in current clinical practice to choose the opioid dosage during general anesthesia.
The postoperative pain level will be assessed from anesthesia nurses using the Numerical Rating Scale (NRS) who are blinded to the nociception indices measured before awakening.
For SPI monitoring there are findings suggesting that an SPI > 30 could be the 'best-fit' optimal threshold with the highest sum of sensitivity and specificity to detect moderate to severe pain. Nevertheless, positive and negative predictive value of SPI were still rather low.
For PPI monitoring there are data demonstrating a moderate correlation between PPI values before tracheal extubation and postoperative pain. Another study with pupil dilatation reflex threshold showed only a minor correlation between pupil dilatation reflex threshold and the intensity of immediate postoperative pain.
For NOL monitoring, on the one hand, there are data suggesting that a threshold of > 20 after knife to skin incision has predictive power to predict moderate to severe postoperative pain. On the other hand, the highest combined sensitivity and specificity were still rather low. While a NOL < 10 after skin incision excluded moderate-severe postoperative pain with a negative predictive value of 83%, the NOL during surgery and at the end of surgery did not allow the exclusion or the prediction of moderate-severe postoperative pain.
Study design
- Observational model
- Case only
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Study group | – | Diagnostic Test: Observational: analgesia monitoring indices and changes in heart rateAs this is a single-group, observational study all patients will be monitored with all three nociception monitoring systems (the Surgical Pleth Index (SPI), the Pupillary Pain Index (PPI) and the Nociception Level (NOL)) and data on heart rate changes as a variable used in current clinical practice to choose the opioid dosage during general anesthesia will be obtained additionally. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- This study includes all patients with elective trauma surgery and orthopedic surgery scheduled on a weekday Monday to Friday in the operation theater where the study is conducted,which do not present with an exclusion criterion. There is no further eligibility criteria and thusly, this is a non-sepcified study on all patients that meet the requirements for the three analgesia monitoring devices.
Key inclusion criteria (1 listed)
- Patients with elective trauma surgery and orthopedic surgery scheduled on a weekday Monday to Friday in the operation theater where the study is conducted
Key exclusion criteria (7 listed)
- Beta blocker, digitalis or cardiac pacemaker therapy
- Higher degrees of cardiac arrhythmias, e.g. atrial fibrillation and atrio-ventricular block >1st degree
- Severe peripheral or cardiac neuropathy
- Eye disease with affection of pupil reactivity
- Intraoperative treatment with ketamine, beta-receptor blockers, beta-receptor agonists or clonidine and treatment with vasoactive medication within 10 min before and during data acquisition period
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Observational: analgesia monitoring indices and changes in heart rateAfter the end of surgery (defined as the time of skin closure or wound dressing), but before awakening (BIS will still be < 60), SPI, PPI and NOL are recorded in a quiet setting without any other stimulation. Within the five minutes data acquisition period nociception indices are recorded every minute (T0, T1, T2, T3, T4, T5). The highest SPI, PPI and NOL are used for further analysis. | Diagnostic test | Study group |
Primary outcome
Primary endpoint will be the diagnostic accuracy (ROC analysis) of the nociception indices after the end of surgery to predict moderate to severe immediate postoperative pain
Time frame: Once immediately after arrival in the post-anesthesia care unit (PACU)
Numerical Rating Scale (NRS) Scale 4-10 NRS has a minimal value of 0 and a maximal value of 10, higher scores mean a worse outcome (higher pain level).
5 secondary outcomes
The correlation between the nociception indices after the end of surgery and immediate postoperative pain measured with the NRS on a scale of 0 - 10
Time frame: Once immediately after arrival in the post-anesthesia care unit (PACU)
The correlation between the nociception indices after the end of surgery and postoperative pain measured with the NRS on a scale of 0 - 10 after 60 minutes in PACU
Time frame: First 60 minutes after arrival in the PACU
Correlation between the nociception indices and the highest postoperative NRS
Time frame: Once in the first 2 hours during the PACU stay
The correlation between the nociception indices after the end of surgery and the amount of opioids in the first 30 minutes after surgery
Time frame: Time period of first 30 minutes during the PACU stay
The correlation between the nociception indices after the end of surgery and the amount of opioids in up to 2 hours after surgery
Time frame: Time period of first 2 hours during the PACU stay
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Jul 2023.
- Derived from this study: PubMed 36609057Koschmieder KC, Funcke S, Shadloo M, Pinnschmidt HO, Greiwe G, Fischer M, Nitzschke R. Validation of three nociception indices to predict immediate postoperative pain before emergence from general anaesthesia: a prospective double-blind, observational study. Br J Anaesth. 2023 Apr;130(4):477-484. doi: 10.1016/j.bja.2022.11.024. Epub 2023 Jan 4.
- Individual participant dataSharing planned: Undecided. Anonymized data on request only.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Rainer Nitzschke, MD principal investigator
Center for Anesthesiology and Intensive Care Medicine, University Medical Center Hamburg-Eppendorf
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Pain, Postoperative and Analgesia, run by Universitätsklinikum Hamburg-Eppendorf at 1 site in Germany.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 5 Jul 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Germany. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Primary endpoint will be the diagnostic accuracy (ROC analysis) of the nociception indices after the end of surgery to predict moderate to severe immediate postoperative pain (time frame: Once immediately after arrival in the post-anesthesia care unit (PACU)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT05063227, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Jul 2023.