Pain, PostoperativePhase 4NCT02241278
Preoperative Ketamine Has no Preemptive Analgesic Effect in Patients Undergoing Colon Surgery.
A Phase 4 study testing Ketamine in people with Pain, Postoperative, run by Hospital Arquitecto Marcide at 1 site in Spain.
Trial summary
The analgesic properties of ketamine are associated with its non-competitive antagonism of the N-methyl-D-aspartate receptor; these receptors exhibit an excitatory function on pain transmission and this binding seems to inhibit or reverse the central sensitization of pain. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Pain, Postoperative
- What is being tested?
- Ketamine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 48 participants
- Where
- 1 siteSpain
- Study dates
- Sep 2001to Jun 2002
- Phase
- Phase 4
- 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 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- age between 18 and 75 years
- normal Body Mass Index (18.5 - 24.9)
- American Society of Anesthesiologists (ASA) class I, II or III
- elective surgery
- surgery time between 60-150 min
- understanding of the Visual Analog Scale (VAS)
- lack of allergies or intolerance to anesthetics
- absence of psychiatric illness
Who cannot join
- cognitive deterioration
- inability to use the Patient-Controlled-Analgesia (PCA) device
- history of chronic pain syndromes
- chronic use of analgesics, sedatives, opioids or steroids
- liver or hematologic disease,
- history of drug or alcohol abuse
- intolerance to ketamine or Paracetamol.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Preoperative Low-dose Ketamine Has no Preemptive Analgesic Effect in Opioid-naïve Patients Undergoing Colon Surgery When Nitrous Oxide is Used
The analgesic properties of ketamine are associated with its non-competitive antagonism of the N-methyl-D-aspartate receptor; these receptors exhibit an excitatory function on pain transmission and this binding seems to inhibit or reverse the central sensitization of pain. In the literature, the value of this anesthetic for preemptive analgesia in the control of postoperative pain is uncertain. The objective of this study was to ascertain whether preoperative low-dose ketamine reduces postoperative pain and morphine consumption in adults undergoing colon surgery.
In a double-blind, randomized trial, 48 patients were studied. Patients in the ketamine group received 0.5 mg/kg intravenous ketamine before surgical incision, while the control group received normal saline. The postoperative analgesia was achieved with a continuous infusion of morphine at 0.015 mg∙kgˉ¹∙hˉ¹ with the possibility of 0.02 mg/kg bolus every 10 min. Pain was assessed using the Visual Analog Scale (VAS), morphine consumption, and hemodynamic parameters at 0, 1, 2, 4, 8, 12, 16, and 24 hours postoperatively. We quantified times to rescue analgesic (Paracetamol), adverse effects and patient satisfaction.
Read the detailed description
In spite of the techniques we have at our disposal and the elementary nature of incisional pain, optimal pain management remains a challenge. Because the severity of early postoperative pain relates to residual pain after some types of surgery, perioperative pain management can considerably influence the long-term quality of life in patients.
Woolf, in 1983, first introduced the theory of preemptive analgesia to attenuate postoperative pain, confirming the presence of a central factor of post-injury pain hypersensitivity in experimental research. After this, experimental studies showed that various anti-nociceptive methods applied before injuries were more effective in reducing post-injury central sensitization in contrast to administration after injury.
After activation of C-fibers by noxious stimuli, sensory neurons become more sensitive to peripheral inputs, a process called central sensitization. 'Wind up, another mechanism activating spinal sensory neurons, is seen after reiterated stimulation of C-fibers. These sensitizations produce c-fos expression in sensory neurons, and are related to the activation of N-methyl-D-aspartic acid (NMDA) and neurokinin receptors. These genes produce long-lasting changes in the pain-processing system, resulting in hyperexcitation. According to Wall, protection of sensory neurons against central sensitization may provide relief from pain after surgery. Based on this assumption, preemptive analgesia has been recommended as an effective aid to control postsurgical pain. NMDA antagonists have been demonstrated to block the induction of central sensitization and revoke the hypersensitivity once it is established.
Ketamine is an old drug that is increasingly being considered for the treatment of acute and chronic pain. Its pharmacology and mechanism of action as an NMDA receptor antagonist are adequately known, but in clinical practice it presents irregular results. Since ketamine is an NMDA-receptor antagonist, it is supposed to avoid or revoke central sensitization, and thus to attenuate postoperative pain.
This antihyperalgesic action can be achieved by smaller doses than those required for anesthesia. Small-dose ketamine has been specified as not more than 1 mg/kg when given as an iv bolus, and not higher than 20 µg∙kgˉ¹∙minˉ¹ when given as a constant infusion.
Low-doses preemptive ketamine administered iv seem to reduce postoperative pain and/or analgesic consumption. According to one study, a single dose of ketamine 1 mg/kg, when administered in conjunction with local anesthetics, opioids or other anesthetics, provides good postoperative pain control.
Regardless of the overwhelming effectiveness of preemptive ketamine in animal experiments, clinical reports are mixed; some authors have described positive effects while others have not.
While early reviews of clinical findings were mostly contradictory, there is still conviction in the effectiveness of preemptive analgesia.
To our knowledge, no prior controlled study has determined the effectiveness of preoperative low-dose iv ketamine as contrasted with placebo in adults after open colon surgery. Thus, this clinical trial was designed to examine the postoperative analgesic effectiveness and opioid-sparing effect of single low-dose iv ketamine in contrast with placebo administered preoperatively.
- Conditions
- Pain, Postoperative
- Being tested
- Ketamine
- Keywords
- colon surgery, ketamine, patient-controlled-analgesia, preemptive analgesia
- Medical subject headings
- Pain, Postoperative
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
KetamineDrug
Also called ketamine chlorhydrate
In the operating room, the anesthesiologist administered 0.5 mg/kg of ketamine chlorhydrate in 50 mL of 0.9 % saline intravenously to patients in the ketamine group 30 minutes before surgical incision (a single dose).
| Study group | Role | What they receive |
|---|---|---|
| Control | Placebo comparator | In the operating room, the anesthesiologist administered 50 mL of 0.9% saline intravenously to patients in the control group 30 minutes before surgical incision. |
| Ketamine | Experimental | In the operating room, the anesthesiologist administered 0.5 mg/kg of ketamine chlorhydrate in 50 mL of 0.9 % saline intravenously to patients in the ketamine group 30 minutes before surgical incision. (a single dose). Receives: Drug: Ketamine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Visual Analog Scale (VAS) score
The VAS represents a scale with the lowest value as 0 (no pain) and the highest value as 10 (worst imaginable pain).
Measured: at 0 hours postoperatively (arrival at recovery room)
Visual Analog Scale (VAS) score
The VAS represents a scale with the lowest value as 0 (no pain) and the highest value as 10 (worst imaginable pain).
Measured: at 1 hour postoperatively
Visual Analog Scale (VAS) score
The VAS represents a scale with the lowest value as 0 (no pain) and the highest value as 10 (worst imaginable pain).
Measured: at 2 hours postoperatively
Visual Analog Scale (VAS) score
The VAS represents a scale with the lowest value as 0 (no pain) and the highest value as 10 (worst imaginable pain).
Measured: at 4 hours postoperatively
Visual Analog Scale (VAS) score
The VAS represents a scale with the lowest value as 0 (no pain) and the highest value as 10 (worst imaginable pain).
Measured: at 8 hours postoperatively
Visual Analog Scale (VAS) score
The VAS represents a scale with the lowest value as 0 (no pain) and the highest value as 10 (worst imaginable pain).
Measured: at 12 hours postoperatively
Visual Analog Scale (VAS) score
The VAS represents a scale with the lowest value as 0 (no pain) and the highest value as 10 (worst imaginable pain).
Measured: at 16 hours postoperatively
Visual Analog Scale (VAS) score
The VAS represents a scale with the lowest value as 0 (no pain) and the highest value as 10 (worst imaginable pain).
Measured: at 24 hours postoperatively
Secondary outcomes (1)
morphine consumption
The cumulative amounts of morphine (mg) administered through the Patient-Controlled-Analgesia (PCA) device as a basal infusion and the incremental supplemental bolus required by the patient were documented at these time points.
Measured: at 0, 1, 2, 4, 8, 12, 16, and 24 hours postoperatively
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Sep 2014 (estimated)
- Study startSep 2001
- Primary completionJun 2002
- Study completionJun 2002
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Pain, PostoperativeStudies of the same condition, open and under way.
- 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
- Interventional
- Phase
- Phase 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 48 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hospital Arquitecto Marcide
- Sponsor type
- University, hospital or other
- Collaborators
- Complexo Hospitalario Universitario de A Coruña
- Responsible party
- Principal investigator, Beatriz Nistal Nuno, Complexo Hospitalario Universitario de A Coruña
- Investigators
- Manuel Camba Rodriguez, M.D., Study chair, Hospital Arquitecto MarcideBeatriz Nistal Nuno, M.D., Principal investigator, Complexo Hospitalario Universitario A CorunaEnrique Freire-Vila, M.D., Study director, Complexo Hospitalario Universitario A CorunaFrancisco Castro Seoane, M.D., Principal investigator, Hospital Arquitecto Marcide
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02241278
- Sponsor's protocol ID
- MK334037
- Status last verified
- Sep 2014
- First submitted
- 11 Sep 2014
- Last updated
- 16 Sep 2014
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 16 Sep 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Preoperative Low-dose Ketamine Has no Preemptive Analgesic Effect in Opioid-naïve Patients Undergoing Colon Surgery When Nitrous Oxide is Used
- ClinicalTrials.gov ID
- NCT02241278
- Acronym / sponsor ID
- MK334037
- Conditions
- Pain, Postoperative
- Keywords
- colon surgery, ketamine, patient-controlled-analgesia, preemptive analgesia
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 48 participants (actual)
- Lead sponsor
- Hospital Arquitecto MarcideUniversity, hospital or other
- Collaborators
- Complexo Hospitalario Universitario de A Coruña
- Study start
- Sep 2001
- Primary completion
- Jun 2002 (actual)
- Study completion
- Jun 2002 (actual)
- First posted
- 16 Sep 2014 (estimated)
- 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.
The analgesic properties of ketamine are associated with its non-competitive antagonism of the N-methyl-D-aspartate receptor; these receptors exhibit an excitatory function on pain transmission and this binding seems to inhibit or reverse the central sensitization of pain. In the literature, the value of this anesthetic for preemptive analgesia in the control of postoperative pain is uncertain. The objective of this study was to ascertain whether preoperative low-dose ketamine reduces postoperative pain and morphine consumption in adults undergoing colon surgery.
In a double-blind, randomized trial, 48 patients were studied. Patients in the ketamine group received 0.5 mg/kg intravenous ketamine before surgical incision, while the control group received normal saline. The postoperative analgesia was achieved with a continuous infusion of morphine at 0.015 mg∙kgˉ¹∙hˉ¹ with the possibility of 0.02 mg/kg bolus every 10 min. Pain was assessed using the Visual Analog Scale (VAS), morphine consumption, and hemodynamic parameters at 0, 1, 2, 4, 8, 12, 16, and 24 hours postoperatively. We quantified times to rescue analgesic (Paracetamol), adverse effects and patient satisfaction.
Detailed description
In spite of the techniques we have at our disposal and the elementary nature of incisional pain, optimal pain management remains a challenge. Because the severity of early postoperative pain relates to residual pain after some types of surgery, perioperative pain management can considerably influence the long-term quality of life in patients.
Woolf, in 1983, first introduced the theory of preemptive analgesia to attenuate postoperative pain, confirming the presence of a central factor of post-injury pain hypersensitivity in experimental research. After this, experimental studies showed that various anti-nociceptive methods applied before injuries were more effective in reducing post-injury central sensitization in contrast to administration after injury.
After activation of C-fibers by noxious stimuli, sensory neurons become more sensitive to peripheral inputs, a process called central sensitization. 'Wind up, another mechanism activating spinal sensory neurons, is seen after reiterated stimulation of C-fibers. These sensitizations produce c-fos expression in sensory neurons, and are related to the activation of N-methyl-D-aspartic acid (NMDA) and neurokinin receptors. These genes produce long-lasting changes in the pain-processing system, resulting in hyperexcitation. According to Wall, protection of sensory neurons against central sensitization may provide relief from pain after surgery. Based on this assumption, preemptive analgesia has been recommended as an effective aid to control postsurgical pain. NMDA antagonists have been demonstrated to block the induction of central sensitization and revoke the hypersensitivity once it is established.
Ketamine is an old drug that is increasingly being considered for the treatment of acute and chronic pain. Its pharmacology and mechanism of action as an NMDA receptor antagonist are adequately known, but in clinical practice it presents irregular results. Since ketamine is an NMDA-receptor antagonist, it is supposed to avoid or revoke central sensitization, and thus to attenuate postoperative pain.
This antihyperalgesic action can be achieved by smaller doses than those required for anesthesia. Small-dose ketamine has been specified as not more than 1 mg/kg when given as an iv bolus, and not higher than 20 µg∙kgˉ¹∙minˉ¹ when given as a constant infusion.
Low-doses preemptive ketamine administered iv seem to reduce postoperative pain and/or analgesic consumption. According to one study, a single dose of ketamine 1 mg/kg, when administered in conjunction with local anesthetics, opioids or other anesthetics, provides good postoperative pain control.
Regardless of the overwhelming effectiveness of preemptive ketamine in animal experiments, clinical reports are mixed; some authors have described positive effects while others have not.
While early reviews of clinical findings were mostly contradictory, there is still conviction in the effectiveness of preemptive analgesia.
To our knowledge, no prior controlled study has determined the effectiveness of preoperative low-dose iv ketamine as contrasted with placebo in adults after open colon surgery. Thus, this clinical trial was designed to examine the postoperative analgesic effectiveness and opioid-sparing effect of single low-dose iv ketamine in contrast with placebo administered preoperatively.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Control | Placebo comparator | –In the operating room, the anesthesiologist administered 50 mL of 0.9% saline intravenously to patients in the control group 30 minutes before surgical incision. |
| Ketamine | Experimental | Drug: KetamineIn the operating room, the anesthesiologist administered 0.5 mg/kg of ketamine chlorhydrate in 50 mL of 0.9 % saline intravenously to patients in the ketamine group 30 minutes before surgical incision. (a single dose). |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- age between 18 and 75 years
- normal Body Mass Index (18.5 - 24.9)
- American Society of Anesthesiologists (ASA) class I, II or III
- elective surgery
- surgery time between 60-150 min
Key exclusion criteria (7 listed)
- cognitive deterioration
- inability to use the Patient-Controlled-Analgesia (PCA) device
- history of chronic pain syndromes
- chronic use of analgesics, sedatives, opioids or steroids
- liver or hematologic disease,
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 |
|---|---|---|
| KetamineAlso: ketamine chlorhydrateIn the operating room, the anesthesiologist administered 0.5 mg/kg of ketamine chlorhydrate in 50 mL of 0.9 % saline intravenously to patients in the ketamine group 30 minutes before surgical incision (a single dose). | Drug | Ketamine |
Primary outcome
Visual Analog Scale (VAS) score
Time frame: at 0 hours postoperatively (arrival at recovery room)
The VAS represents a scale with the lowest value as 0 (no pain) and the highest value as 10 (worst imaginable pain).
Visual Analog Scale (VAS) score
Time frame: at 1 hour postoperatively
The VAS represents a scale with the lowest value as 0 (no pain) and the highest value as 10 (worst imaginable pain).
Visual Analog Scale (VAS) score
Time frame: at 2 hours postoperatively
The VAS represents a scale with the lowest value as 0 (no pain) and the highest value as 10 (worst imaginable pain).
Visual Analog Scale (VAS) score
Time frame: at 4 hours postoperatively
The VAS represents a scale with the lowest value as 0 (no pain) and the highest value as 10 (worst imaginable pain).
Visual Analog Scale (VAS) score
Time frame: at 8 hours postoperatively
The VAS represents a scale with the lowest value as 0 (no pain) and the highest value as 10 (worst imaginable pain).
Visual Analog Scale (VAS) score
Time frame: at 12 hours postoperatively
The VAS represents a scale with the lowest value as 0 (no pain) and the highest value as 10 (worst imaginable pain).
Visual Analog Scale (VAS) score
Time frame: at 16 hours postoperatively
The VAS represents a scale with the lowest value as 0 (no pain) and the highest value as 10 (worst imaginable pain).
Visual Analog Scale (VAS) score
Time frame: at 24 hours postoperatively
The VAS represents a scale with the lowest value as 0 (no pain) and the highest value as 10 (worst imaginable pain).
1 secondary outcome
morphine consumption
Time frame: at 0, 1, 2, 4, 8, 12, 16, and 24 hours postoperatively
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 16 Sep 2014.
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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.
Manuel Camba Rodriguez, M.D. study chair
Hospital Arquitecto Marcide
Beatriz Nistal Nuno, M.D. principal investigator
Complexo Hospitalario Universitario A Coruna
Enrique Freire-Vila, M.D. study director
Complexo Hospitalario Universitario A Coruna
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Ketamine in people with Pain, Postoperative, run by Hospital Arquitecto Marcide at 1 site in Spain.
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 8 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 16 Sep 2014. 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 Spain. 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. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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?
Visual Analog Scale (VAS) score (time frame: at 0 hours postoperatively (arrival at recovery room)). The study lists 8 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 16 Sep 2014.