Hyperalgesia, Inflammatory Response, Pain
Conditions
Keywords
Remifentanil, Hyperalgesia, Ketamine, Von Frey's filament, Algometer, Interleukines, Opioid-induced hyperalgesia
Brief summary
The aim of this study was to determine if the addition of ketamine reduces remifentanil-induced hyperalgesia, improves its analgesic effect, inhibits IL(interleukin)-6 and IL-8 (inflammatory cytokines), and stimulates IL-10 (an anti-inflammatory cytokine).
Detailed description
Opioids are very effective in pain relief, but they might lower pain threshold, making the patient more sensitive to a pain stimulus, a condition known as hyperalgesia \[Angst; Clarck, 2006\]. Opioid-induced hyperalgesia (OIH) is usually defined as a reduction in nociceptive thresholds in the peripheral field of the sensitized fibers \[Koppert et al., 2003\], and it is associated with increased pain and higher demand for postoperative analgesia \[Guignard et al., 2000\]. This phenomenon adversely impacts pain control, and has been suggested to occur in the peri-operative context, especially associated with the use of remifentanil, a short-acting opioid \[Guignard et al., 2000\]. Several mechanisms have been proposed to explain the hyperalgesia phenomenon, but the most important seems to be the activation of N-methyl-D-aspartate (NMDA) receptors \[Célèrier et al., 2000\]. Ketamine is a NMDA receptor antagonist that has been shown to reduce postoperative pain and the need for postoperative anesthetics and analgesics. Therefore, it is proposed that ketamine could prevent hyperalgesia, resulting in more effective and long-lasting postsurgical analgesia \[Célèrier et al. 2000\]. The results of studies of low dose of ketamine in the prevention of remifentanil-induced hyperalgesia are controversial. Joly et al. \[2005\] demonstrated a reduction in the consumption of opioids and in hyperalgesia assessed with monofilaments. However, Engelhardt et al \[2008\] showed no differences in pain scores or in postoperative opioid consumption. In addition, some authors observed higher levels of proinflammatory cytokines, associated with increased pain in mice receiving chronic opioid (morphine) infusion \[Johnston et al., 2004; Liang et al., 2008\]. Also, administration of proinflammatory cytokine inhibitors reduced phosphorylation of NMDA receptors \[Zhang et al., 2008\]. However, no study has examined the relationship between the use of remifentanil, the most frequently implicated opioid in OIH \[Guignard et al., 2000\], ketamine (drug capable of inhibiting NMDA-receptors and cytokines) \[Dale et al., 2012\], and the inflammatory response. The aim of this study was to determine if the addition of ketamine reduces remifentanil-induced hyperalgesia, improves its analgesic effect, inhibits IL-6 and IL-8 (inflammatory cytokines), and stimulates IL-10 (an anti-inflammatory cytokine) in patients submitted to laparoscopic cholecystectomy, a procedure with an usually neglected potential for postoperative pain and that has been poorly investigated in association with OIH.
Interventions
DRUGKetamine
Patients in group ketamine was administrated ketamine (5mcg/kg/min) during the surgery.
DRUGSaline
Patients in group N (placebo) was administrated saline during surgery.
Sponsors
Fundação de Amparo à Pesquisa do Estado de São Paulo
Federal University of São Paulo
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 78 Years
Healthy volunteers
No
Inclusion criteria
* ≥ 18 years old * both sexes * ASA physical status I or II * undergoing laparoscopic cholecystectomy
Exclusion criteria
* chronic users of analgesics or had used opioids within 12 h of surgery * history of drug or alcohol abuse or psychiatric disorder * contraindications to self-administration of opioids (ie, unable to understand the patient-controlled analgesia \[PCA\] device) * contraindication for the use of ketamine, such as a psychiatric disorder, acute cardiovascular disorder, or unstable hypertension
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Pain 30 Minutes | 30 minutes | The scale measure pain after 30 minutes (0 - without pain and 10 worst pain possible). The individual can choose any number between 0 - 10. |
| Pain 60 Minutes | 60 minutes | The scale measure pain after 60 minutes (0 - without pain and 10 worst pain possible). The individual can choose any number between 0 - 10. |
| Pain 90 Minutes | 90 minutes | The scale measure pain after 90 minutes (0 - without pain and 10 worst pain possible). The individual can choose any number between 0 - 10. |
| Pain 120 Minutes | 120 minutes | The scale measure pain after 120 minutes (0 - without pain and 10 worst pain possible). The individual can choose any number between 0 - 10. |
| Pain 150 Minutes | 150 minutes | The scale measure pain after 150 minutes (0 - without pain and 10 worst pain possible). The individual can choose any number between 0 - 10. |
| Pain 180 Minutes | 180 minutes | The scale measure pain after 180 minutes (0 - without pain and 10 worst pain possible). The individual can choose any number between 0 - 10. |
| Pain 210 Minutes | 210 minutes | The scale measure pain after 210 minutes (0 - without pain and 10 worst pain possible). The individual can choose any number between 0 - 10. |
| Pain 240 Minutes | 240 minutes | The scale measure pain after 240 minutes (0 - without pain and 10 worst pain possible). The individual can choose any number between 0 - 10. |
| Pain 6 Hours | 6 hours | The scale measure pain after 6 hours (0 - without pain and 10 worst pain possible). The individual can choose any number between 0 - 10. |
| Pain 12 Hours | 12 hours | The scale measure pain after 12 hours (0 - without pain and 10 worst pain possible). The individual can choose any number between 0 - 10. |
| Pain 18 Hours | 18 hours | The scale measure pain after 18 hours (0 - without pain and 10 worst pain possible). The individual can choose any number between 0 - 10. |
| Pain 24 Hours | 24 hours | The scale measure pain after 24 hours (0 - without pain and 10 worst pain possible). The individual can choose any number between 0 - 10. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Allodynia as Detected With a Soft Brush in the Periumbilical Region 24 h After the Procedure | 24 h after the procedure | The evaluations using the soft brush were performed 2-3 cm from the incision in the periumbilical region (where the large trocar was placed) 24 h after the procedure |
| Allodynia as Detected With a Soft Brush in the Thenar Eminence Before the Procedure | Before the procedure (Baseline) | The evaluations using the soft brush were performed in the thenar eminence of the nondominant hand before the procedure |
| Allodynia as Detected With a Soft Brush in the Thenar Eminence 24 h After the Procedure | 24 h after the procedure | The evaluations using the soft brush were performed in the thenar eminence of the non dominant hand 24 h after the procedure |
| Serum Level of Interleukin (IL)-6 Before the Procedure | Baseline (Before the procedure) | Blood samples were drawn in ethylenediaminetetraacetic acid (EDTA) tubes before the surgery. The blood was centrifuged to separate the plasma and was stored at -70°C. IL-6 was analyzed using the enzyme-linked immunosorbent assay (ELISA) methodology. |
| Serum Level of Interleukin (IL)-6 5 h After the Procedure | 5 h after the procedure | Blood samples were drawn in ethylenediaminetetraacetic acid (EDTA) tubes 5 h after the surgery. The blood was centrifuged to separate the plasma and was stored at -70°C. IL-6 was analyzed using the enzyme-linked immunosorbent assay (ELISA) methodology. |
| Serum Level of Interleukin (IL)-6 24 h After the Procedure | 24 h after the procedure | Blood samples were drawn in ethylenediaminetetraacetic acid (EDTA) tubes 24 h after the surgery. The blood was centrifuged to separate the plasma and was stored at -70°C. IL-6 was analyzed using the enzyme-linked immunosorbent assay (ELISA) methodology. |
| Time to First Morphine Supplementation | 24 hours | — |
| Serum Level of Interleukin (IL)-8 5 h After the Procedure | 5 h after the procedure | Blood samples were drawn in ethylenediaminetetraacetic acid (EDTA) tubes 5 h after the surgery. The blood was centrifuged to separate the plasma and was stored at -70°C. IL-8 was analyzed using the enzyme-linked immunosorbent assay (ELISA) methodology. |
| Serum Level of Interleukin (IL)-8 24 h After the Procedure | 24 h after the procedure | Blood samples were drawn in ethylenediaminetetraacetic acid (EDTA) tubes 24 h after the surgery. The blood was centrifuged to separate the plasma and was stored at -70°C. IL-8 was analyzed using the enzyme-linked immunosorbent assay (ELISA) methodology. |
| Serum Level of Interleukin (IL)-10 Before the Procedure | Baseline (Before the procedure) | Blood samples were drawn in ethylenediaminetetraacetic acid (EDTA) tubes before the surgery. The blood was centrifuged to separate the plasma and was stored at -70°C. IL-6 was analyzed using the enzyme-linked immunosorbent assay (ELISA) methodology. |
| Serum Level of Interleukin (IL)-10 5h After the Procedure | 5h after the procedure | Blood samples were drawn in ethylenediaminetetraacetic acid (EDTA) tubes 5 h after the surgery. The blood was centrifuged to separate the plasma and was stored at -70°C. IL-10 was analyzed using the enzyme-linked immunosorbent assay (ELISA) methodology. |
| Serum Level of Interleukin (IL)-10 24 h After the Procedure | 24 h after the procedure | Blood samples were drawn in ethylenediaminetetraacetic acid (EDTA) tubes 24 h after the surgery. The blood was centrifuged to separate the plasma and was stored at -70°C. IL-6 was analyzed using the enzyme-linked immunosorbent assay (ELISA) methodology. |
| Serum Level of Interleukin (IL)-8 Before the Procedure | Baseline (Before the procedure) | Blood samples were drawn in ethylenediaminetetraacetic acid (EDTA) tubes before the surgery. The blood was centrifuged to separate the plasma and was stored at -70°C. IL-8 was analyzed using the enzyme-linked immunosorbent assay (ELISA) methodology. |
| Morphine Consumption Within 24 h | 24 hours | — |
| Hyperalgesia in the Preoperative Period as Measured With Monofilaments in Thenar Eminence | Before the procedure (Baseline) | The pain threshold was assessed using six von Frey monofilaments (0,05 g; 0,2 g; 2 g; 4 g; 10 g e 300 g) in thenar eminence in the preoperative period. The use of different von Frey monofilaments, starting with the lightest and ending with the heaviest, was separated by at least 30 seconds to reduce any anticipated responses due to a new stimulation that was performed too soon after the preceding stimulation. Three assessments were made for each monofilament, and this was considered positive when the patient responded to two of the determinations for each monofilament. |
| Hyperalgesia in the Postoperative Period as Measured With Monofilaments in Thenar Eminence | 24 hours after procedure | The pain threshold was assessed using six von Frey monofilaments (0,05 g; 0,2 g; 2 g; 4 g; 10 g e 300 g) in thenar eminence in the postoperative period (24 hours after procedure). The use of different von Frey monofilaments, starting with the lightest and ending with the heaviest, was separated by at least 30 seconds to reduce any anticipated responses due to a new stimulation that was performed too soon after the preceding stimulation. Three assessments were made for each monofilament, and this was considered positive when the patient responded to two of the determinations for each monofilament. |
| Hyperalgesia in the Preoperative Period as Measured With Monofilaments in the Periumbilical Region | Before the procedure (Baseline) | The pain threshold was assessed using six von Frey monofilaments (0,05 g; 0,2 g; 2 g; 4 g; 10 g e 300 g) in the periumbilical region in the preoperative period. The use of different von Frey monofilaments, starting with the lightest and ending with the heaviest, was separated by at least 30 seconds to reduce any anticipated responses due to a new stimulation that was performed too soon after the preceding stimulation. Three assessments were made for each monofilament, and this was considered positive when the patient responded to two of the determinations for each monofilament. |
| Hyperalgesia in the Postoperative Period as Measured With Monofilaments in the Periumbilical Region | 24h after the procedure | The pain threshold was assessed using six von Frey monofilaments (0,05 g; 0,2 g; 2 g; 4 g; 10 g e 300 g) in the periumbilical region in the postoperative period (24h after the procedure). The use of different von Frey monofilaments, starting with the lightest and ending with the heaviest, was separated by at least 30 seconds to reduce any anticipated responses due to a new stimulation that was performed too soon after the preceding stimulation. Three assessments were made for each monofilament, and this was considered positive when the patient responded to two of the determinations for each monofilament. |
| Hyperalgesia in the Preoperative Period as Measured With Algometer in Thenar Eminence | Baseline (before the procedure) | The mechanical pain threshold was evaluated using an algometer. The pressure was increased by 0.1 kgf/second until the patient complained of pain. The mean of three determinations was calculated. |
| Hyperalgesia in the Postoperative Period as Measured With Algometer in Thenar Eminence | 24 h after the procedure | The mechanical pain threshold was evaluated using an algometer. The pressure was increased by 0.1 kgf/second until the patient complained of pain. The mean of three determinations was calculated. |
| Hyperalgesia in the Preoperative Period as Measured With Algometer in the Periumbilical Region | Baseline (before the surgery) | The mechanical pain threshold was evaluated using an algometer. The pressure was increased by 0.1 kgf/second until the patient complained of pain. The mean of three determinations was calculated. |
| Hyperalgesia in the Postoperative Period as Measured With Algometer in the Periumbilical Region | 24 h after the procedure | The mechanical pain threshold was evaluated using an algometer. The pressure was increased by 0.1 kgf/second until the patient complained of pain. The mean of three determinations was calculated. |
| Extension of Hyperalgesia | 24 hours after the procedure | The 300-g filament was used 24 hours after the operation to induce a stimulus and delineate the extent of hyperalgesia from the periumbilical region. The stimulus was started outside the periumbilical region, where no pain sensation was reported, and continued every 0.5 cm until the 4 points of the periumbilical scar were reached (top, right side, left side, and bottom). The first point where the patient complained of pain was marked. If no pain sensation was reported, the stimulus was terminated 0.5 cm from the incision. The distance of each point from the surgical incision was measured, and the sum of the distances of the points was determined. |
| Allodynia as Detected With a Soft Brush in the Periumbilical Region Before the Procedure | Before the procedure (Baseline) | The evaluations using the soft brush were performed 2-3 cm from the incision in the periumbilical region (where the large trocar was placed) before the procedure |
Countries
Brazil
Participant flow
Recruitment details
Inclusion criteria were: ≥18 years of age, any gender, classified as American Society of Anesthesiologists (ASA) Physical Status I or II, and undergoing laparoscopic cholecystectomy at Hospital São Paulo/Federal University of São Paulo, from September 2010 to September 2012.
Participants by arm
| Arm | Count |
|---|---|
| Ketamine A cardioscope, a capnograph, a pulse oximeter, and a noninvasive blood pressure meter were used to monitor the patients. Propofol (2-4 mg/kg), 1 μg/kg remifentanil, and atracurium (0.5 mg/kg) were administered for intubation. Atracurium was titrated to maintain muscle relaxation. Anesthesia was maintained with remifentanil, 0.8% isoflurane, and 50% oxygen without nitrous oxide. Infusion of the solutions was continued until skin closure. The patients in group 1 (G1) received remifentanil (0.4 μg/kg/min) and ketamine (5 μg/kg/min).
Ketamine : Patients in group ketamine will receive ketamine (5mcg/kg/min) during the surgery. | 30 |
| Saline A cardioscope, a capnograph, a pulse oximeter, and a noninvasive blood pressure meter were used to monitor the patients. Propofol (2-4 mg/kg), 1 μg/kg remifentanil, and atracurium (0.5 mg/kg) were administered for intubation. Atracurium was titrated to maintain muscle relaxation. Anesthesia was maintained with remifentanil, 0.8% isoflurane, and 50% oxygen without nitrous oxide. Infusion of the solutions was continued until skin closure. Patients in group 2 (G2) received remifentanil (0.4 μg/kg/min) and saline solution.
Saline : Patients in group N (placebo)will receive saline during surgery. | 30 |
| Total | 60 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 2 | 2 |
Baseline characteristics
| Characteristic | Saline | Ketamine | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 2 Participants | 1 Participants | 3 Participants |
| Age, Categorical Between 18 and 65 years | 28 Participants | 29 Participants | 57 Participants |
| Age, Continuous | 43.40 years STANDARD_DEVIATION 15.9 | 45.80 years STANDARD_DEVIATION 13.1 | 44.60 years STANDARD_DEVIATION 14.5 |
| Region of Enrollment Brazil | 30 participants | 30 participants | 60 participants |
| Sex: Female, Male Female | 24 Participants | 25 Participants | 49 Participants |
| Sex: Female, Male Male | 6 Participants | 5 Participants | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 16 / 28 | 8 / 28 |
| serious Total, serious adverse events | 0 / 28 | 0 / 28 |
Outcome results
Primary
Pain 120 Minutes
The scale measure pain after 120 minutes (0 - without pain and 10 worst pain possible). The individual can choose any number between 0 - 10.
Time frame: 120 minutes
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ketamine | Pain 120 Minutes | 2.2 units on a scale | Standard Deviation 2.1 |
| Saline | Pain 120 Minutes | 2.0 units on a scale | Standard Deviation 1.8 |
p-value: 0.737t-test, 2 sided
Primary
Pain 12 Hours
The scale measure pain after 12 hours (0 - without pain and 10 worst pain possible). The individual can choose any number between 0 - 10.
Time frame: 12 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ketamine | Pain 12 Hours | 1.6 units on a scale | Standard Deviation 1.8 |
| Saline | Pain 12 Hours | 1.4 units on a scale | Standard Deviation 2 |
p-value: 0.673t-test, 2 sided
Primary
Pain 150 Minutes
The scale measure pain after 150 minutes (0 - without pain and 10 worst pain possible). The individual can choose any number between 0 - 10.
Time frame: 150 minutes
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ketamine | Pain 150 Minutes | 1.4 units on a scale | Standard Deviation 1.7 |
| Saline | Pain 150 Minutes | 1.4 units on a scale | Standard Deviation 1.6 |
p-value: <0.872t-test, 2 sided
Primary
Pain 180 Minutes
The scale measure pain after 180 minutes (0 - without pain and 10 worst pain possible). The individual can choose any number between 0 - 10.
Time frame: 180 minutes
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ketamine | Pain 180 Minutes | 1.1 units on a scale | Standard Deviation 1.5 |
| Saline | Pain 180 Minutes | 1.3 units on a scale | Standard Deviation 1.5 |
p-value: 0.598t-test, 2 sided
Primary
Pain 18 Hours
The scale measure pain after 18 hours (0 - without pain and 10 worst pain possible). The individual can choose any number between 0 - 10.
Time frame: 18 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ketamine | Pain 18 Hours | 1.5 units on a scale | Standard Deviation 1.8 |
| Saline | Pain 18 Hours | 1.3 units on a scale | Standard Deviation 1.6 |
p-value: 0.586t-test, 2 sided
Primary
Pain 210 Minutes
The scale measure pain after 210 minutes (0 - without pain and 10 worst pain possible). The individual can choose any number between 0 - 10.
Time frame: 210 minutes
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ketamine | Pain 210 Minutes | 0.9 units on a scale | Standard Deviation 1.6 |
| Saline | Pain 210 Minutes | 1.2 units on a scale | Standard Deviation 1.5 |
p-value: 0.485t-test, 2 sided
Primary
Pain 240 Minutes
The scale measure pain after 240 minutes (0 - without pain and 10 worst pain possible). The individual can choose any number between 0 - 10.
Time frame: 240 minutes
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ketamine | Pain 240 Minutes | 1.0 units on a scale | Standard Deviation 1.7 |
| Saline | Pain 240 Minutes | 1.1 units on a scale | Standard Deviation 1.5 |
p-value: 0.744t-test, 2 sided
Primary
Pain 24 Hours
The scale measure pain after 24 hours (0 - without pain and 10 worst pain possible). The individual can choose any number between 0 - 10.
Time frame: 24 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ketamine | Pain 24 Hours | 1.4 units on a scale | Standard Deviation 1.5 |
| Saline | Pain 24 Hours | 0.8 units on a scale | Standard Deviation 1 |
p-value: 0.077t-test, 2 sided
Primary
Pain 30 Minutes
The scale measure pain after 30 minutes (0 - without pain and 10 worst pain possible). The individual can choose any number between 0 - 10.
Time frame: 30 minutes
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ketamine | Pain 30 Minutes | 5.5 units on a scale | Standard Deviation 3.5 |
| Saline | Pain 30 Minutes | 6.2 units on a scale | Standard Deviation 2.6 |
p-value: 0.386t-test, 2 sided
Primary
Pain 60 Minutes
The scale measure pain after 60 minutes (0 - without pain and 10 worst pain possible). The individual can choose any number between 0 - 10.
Time frame: 60 minutes
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ketamine | Pain 60 Minutes | 4.6 units on a scale | Standard Deviation 3 |
| Saline | Pain 60 Minutes | 5.1 units on a scale | Standard Deviation 2.5 |
p-value: 0.499t-test, 1 sided
Primary
Pain 6 Hours
The scale measure pain after 6 hours (0 - without pain and 10 worst pain possible). The individual can choose any number between 0 - 10.
Time frame: 6 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ketamine | Pain 6 Hours | 0.9 units on a scale | Standard Deviation 1.2 |
| Saline | Pain 6 Hours | 0.7 units on a scale | Standard Deviation 1 |
p-value: 0.54t-test, 2 sided
Primary
Pain 90 Minutes
The scale measure pain after 90 minutes (0 - without pain and 10 worst pain possible). The individual can choose any number between 0 - 10.
Time frame: 90 minutes
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ketamine | Pain 90 Minutes | 3.4 units on a scale | Standard Deviation 2.4 |
| Saline | Pain 90 Minutes | 3.4 units on a scale | Standard Deviation 2.3 |
p-value: 0.909t-test, 2 sided
Secondary
Allodynia as Detected With a Soft Brush in the Periumbilical Region 24 h After the Procedure
The evaluations using the soft brush were performed 2-3 cm from the incision in the periumbilical region (where the large trocar was placed) 24 h after the procedure
Time frame: 24 h after the procedure
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ketamine | Allodynia as Detected With a Soft Brush in the Periumbilical Region 24 h After the Procedure | 1 participants |
| Saline | Allodynia as Detected With a Soft Brush in the Periumbilical Region 24 h After the Procedure | 0 participants |
p-value: 0.313Chi-squared
Secondary
Allodynia as Detected With a Soft Brush in the Periumbilical Region Before the Procedure
The evaluations using the soft brush were performed 2-3 cm from the incision in the periumbilical region (where the large trocar was placed) before the procedure
Time frame: Before the procedure (Baseline)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ketamine | Allodynia as Detected With a Soft Brush in the Periumbilical Region Before the Procedure | 1 participants |
| Saline | Allodynia as Detected With a Soft Brush in the Periumbilical Region Before the Procedure | 0 participants |
p-value: 0.313Chi-squared
Secondary
Allodynia as Detected With a Soft Brush in the Thenar Eminence 24 h After the Procedure
The evaluations using the soft brush were performed in the thenar eminence of the non dominant hand 24 h after the procedure
Time frame: 24 h after the procedure
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ketamine | Allodynia as Detected With a Soft Brush in the Thenar Eminence 24 h After the Procedure | 1 participants |
| Saline | Allodynia as Detected With a Soft Brush in the Thenar Eminence 24 h After the Procedure | 3 participants |
p-value: 0.611Chi-squared
Secondary
Allodynia as Detected With a Soft Brush in the Thenar Eminence Before the Procedure
The evaluations using the soft brush were performed in the thenar eminence of the nondominant hand before the procedure
Time frame: Before the procedure (Baseline)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Ketamine | Allodynia as Detected With a Soft Brush in the Thenar Eminence Before the Procedure | 1 participants |
| Saline | Allodynia as Detected With a Soft Brush in the Thenar Eminence Before the Procedure | 0 participants |
p-value: 0.313Chi-squared
Secondary
Extension of Hyperalgesia
The 300-g filament was used 24 hours after the operation to induce a stimulus and delineate the extent of hyperalgesia from the periumbilical region. The stimulus was started outside the periumbilical region, where no pain sensation was reported, and continued every 0.5 cm until the 4 points of the periumbilical scar were reached (top, right side, left side, and bottom). The first point where the patient complained of pain was marked. If no pain sensation was reported, the stimulus was terminated 0.5 cm from the incision. The distance of each point from the surgical incision was measured, and the sum of the distances of the points was determined.
Time frame: 24 hours after the procedure
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ketamine | Extension of Hyperalgesia | 10.61 centimeter | Standard Deviation 8.63 |
| Saline | Extension of Hyperalgesia | 11.82 centimeter | Standard Deviation 8.36 |
p-value: 0.593t-test, 2 sided
Secondary
Hyperalgesia in the Postoperative Period as Measured With Algometer in Thenar Eminence
The mechanical pain threshold was evaluated using an algometer. The pressure was increased by 0.1 kgf/second until the patient complained of pain. The mean of three determinations was calculated.
Time frame: 24 h after the procedure
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ketamine | Hyperalgesia in the Postoperative Period as Measured With Algometer in Thenar Eminence | 0.56 kilogram force/second | Standard Deviation 0.44 |
| Saline | Hyperalgesia in the Postoperative Period as Measured With Algometer in Thenar Eminence | 0.51 kilogram force/second | Standard Deviation 0.44 |
p-value: 0.677t-test, 2 sided
Secondary
Hyperalgesia in the Postoperative Period as Measured With Algometer in the Periumbilical Region
The mechanical pain threshold was evaluated using an algometer. The pressure was increased by 0.1 kgf/second until the patient complained of pain. The mean of three determinations was calculated.
Time frame: 24 h after the procedure
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ketamine | Hyperalgesia in the Postoperative Period as Measured With Algometer in the Periumbilical Region | 3.5 kilogram force/second | Standard Deviation 1.6 |
| Saline | Hyperalgesia in the Postoperative Period as Measured With Algometer in the Periumbilical Region | 3.7 kilogram force/second | Standard Deviation 1.7 |
p-value: 0.65t-test, 2 sided
Secondary
Hyperalgesia in the Postoperative Period as Measured With Monofilaments in Thenar Eminence
The pain threshold was assessed using six von Frey monofilaments (0,05 g; 0,2 g; 2 g; 4 g; 10 g e 300 g) in thenar eminence in the postoperative period (24 hours after procedure). The use of different von Frey monofilaments, starting with the lightest and ending with the heaviest, was separated by at least 30 seconds to reduce any anticipated responses due to a new stimulation that was performed too soon after the preceding stimulation. Three assessments were made for each monofilament, and this was considered positive when the patient responded to two of the determinations for each monofilament.
Time frame: 24 hours after procedure
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ketamine | Hyperalgesia in the Postoperative Period as Measured With Monofilaments in Thenar Eminence | 290 gram | Standard Deviation 54.8 |
| Saline | Hyperalgesia in the Postoperative Period as Measured With Monofilaments in Thenar Eminence | 247 gram | Standard Deviation 115 |
p-value: 0.019t-test, 2 sided
Secondary
Hyperalgesia in the Postoperative Period as Measured With Monofilaments in the Periumbilical Region
The pain threshold was assessed using six von Frey monofilaments (0,05 g; 0,2 g; 2 g; 4 g; 10 g e 300 g) in the periumbilical region in the postoperative period (24h after the procedure). The use of different von Frey monofilaments, starting with the lightest and ending with the heaviest, was separated by at least 30 seconds to reduce any anticipated responses due to a new stimulation that was performed too soon after the preceding stimulation. Three assessments were made for each monofilament, and this was considered positive when the patient responded to two of the determinations for each monofilament.
Time frame: 24h after the procedure
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ketamine | Hyperalgesia in the Postoperative Period as Measured With Monofilaments in the Periumbilical Region | 248 gram | Standard Deviation 114 |
| Saline | Hyperalgesia in the Postoperative Period as Measured With Monofilaments in the Periumbilical Region | 205 gram | Standard Deviation 140 |
p-value: 0.221t-test, 2 sided
Secondary
Hyperalgesia in the Preoperative Period as Measured With Algometer in Thenar Eminence
The mechanical pain threshold was evaluated using an algometer. The pressure was increased by 0.1 kgf/second until the patient complained of pain. The mean of three determinations was calculated.
Time frame: Baseline (before the procedure)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ketamine | Hyperalgesia in the Preoperative Period as Measured With Algometer in Thenar Eminence | 2.51 kilogram force/second | Standard Deviation 1.43 |
| Saline | Hyperalgesia in the Preoperative Period as Measured With Algometer in Thenar Eminence | 2.19 kilogram force/second | Standard Deviation 0.92 |
p-value: 0.325t-test, 2 sided
Secondary
Hyperalgesia in the Preoperative Period as Measured With Algometer in the Periumbilical Region
The mechanical pain threshold was evaluated using an algometer. The pressure was increased by 0.1 kgf/second until the patient complained of pain. The mean of three determinations was calculated.
Time frame: Baseline (before the surgery)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ketamine | Hyperalgesia in the Preoperative Period as Measured With Algometer in the Periumbilical Region | 3.6 kilogram force/second | Standard Deviation 1.5 |
| Saline | Hyperalgesia in the Preoperative Period as Measured With Algometer in the Periumbilical Region | 3.9 kilogram force/second | Standard Deviation 1.4 |
p-value: 0.545t-test, 2 sided
Secondary
Hyperalgesia in the Preoperative Period as Measured With Monofilaments in Thenar Eminence
The pain threshold was assessed using six von Frey monofilaments (0,05 g; 0,2 g; 2 g; 4 g; 10 g e 300 g) in thenar eminence in the preoperative period. The use of different von Frey monofilaments, starting with the lightest and ending with the heaviest, was separated by at least 30 seconds to reduce any anticipated responses due to a new stimulation that was performed too soon after the preceding stimulation. Three assessments were made for each monofilament, and this was considered positive when the patient responded to two of the determinations for each monofilament.
Time frame: Before the procedure (Baseline)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ketamine | Hyperalgesia in the Preoperative Period as Measured With Monofilaments in Thenar Eminence | 300 gram | Standard Deviation 0 |
| Saline | Hyperalgesia in the Preoperative Period as Measured With Monofilaments in Thenar Eminence | 300 gram | Standard Deviation 0 |
p-value: 0.999t-test, 2 sided
Secondary
Hyperalgesia in the Preoperative Period as Measured With Monofilaments in the Periumbilical Region
The pain threshold was assessed using six von Frey monofilaments (0,05 g; 0,2 g; 2 g; 4 g; 10 g e 300 g) in the periumbilical region in the preoperative period. The use of different von Frey monofilaments, starting with the lightest and ending with the heaviest, was separated by at least 30 seconds to reduce any anticipated responses due to a new stimulation that was performed too soon after the preceding stimulation. Three assessments were made for each monofilament, and this was considered positive when the patient responded to two of the determinations for each monofilament.
Time frame: Before the procedure (Baseline)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ketamine | Hyperalgesia in the Preoperative Period as Measured With Monofilaments in the Periumbilical Region | 279 gram | Standard Deviation 77.1 |
| Saline | Hyperalgesia in the Preoperative Period as Measured With Monofilaments in the Periumbilical Region | 269 gram | Standard Deviation 92 |
p-value: 0.652t-test, 2 sided
Secondary
Morphine Consumption Within 24 h
Time frame: 24 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ketamine | Morphine Consumption Within 24 h | 27.40 milligram | Standard Deviation 18.3 |
| Saline | Morphine Consumption Within 24 h | 27.70 milligram | Standard Deviation 12.9 |
p-value: 0.946t-test, 2 sided
Secondary
Serum Level of Interleukin (IL)-10 24 h After the Procedure
Blood samples were drawn in ethylenediaminetetraacetic acid (EDTA) tubes 24 h after the surgery. The blood was centrifuged to separate the plasma and was stored at -70°C. IL-6 was analyzed using the enzyme-linked immunosorbent assay (ELISA) methodology.
Time frame: 24 h after the procedure
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ketamine | Serum Level of Interleukin (IL)-10 24 h After the Procedure | 8.6 picogram/milliliter | Standard Deviation 18.5 |
| Saline | Serum Level of Interleukin (IL)-10 24 h After the Procedure | 5.0 picogram/milliliter | Standard Deviation 5.5 |
p-value: 0.557t-test, 2 sided
Secondary
Serum Level of Interleukin (IL)-10 5h After the Procedure
Blood samples were drawn in ethylenediaminetetraacetic acid (EDTA) tubes 5 h after the surgery. The blood was centrifuged to separate the plasma and was stored at -70°C. IL-10 was analyzed using the enzyme-linked immunosorbent assay (ELISA) methodology.
Time frame: 5h after the procedure
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ketamine | Serum Level of Interleukin (IL)-10 5h After the Procedure | 9.1 picogram/milliliter | Standard Deviation 19.1 |
| Saline | Serum Level of Interleukin (IL)-10 5h After the Procedure | 5.5 picogram/milliliter | Standard Deviation 7.9 |
p-value: 0.745t-test, 2 sided
Secondary
Serum Level of Interleukin (IL)-10 Before the Procedure
Blood samples were drawn in ethylenediaminetetraacetic acid (EDTA) tubes before the surgery. The blood was centrifuged to separate the plasma and was stored at -70°C. IL-6 was analyzed using the enzyme-linked immunosorbent assay (ELISA) methodology.
Time frame: Baseline (Before the procedure)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ketamine | Serum Level of Interleukin (IL)-10 Before the Procedure | 7.8 picogram/milliliter | Standard Deviation 20 |
| Saline | Serum Level of Interleukin (IL)-10 Before the Procedure | 1.9 picogram/milliliter | Standard Deviation 3.3 |
p-value: 0.435t-test, 2 sided
Secondary
Serum Level of Interleukin (IL)-6 24 h After the Procedure
Blood samples were drawn in ethylenediaminetetraacetic acid (EDTA) tubes 24 h after the surgery. The blood was centrifuged to separate the plasma and was stored at -70°C. IL-6 was analyzed using the enzyme-linked immunosorbent assay (ELISA) methodology.
Time frame: 24 h after the procedure
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ketamine | Serum Level of Interleukin (IL)-6 24 h After the Procedure | 24.1 picogram/milliliter | Standard Deviation 21.3 |
| Saline | Serum Level of Interleukin (IL)-6 24 h After the Procedure | 24.8 picogram/milliliter | Standard Deviation 31.5 |
p-value: 0.938t-test, 2 sided
Secondary
Serum Level of Interleukin (IL)-6 5 h After the Procedure
Blood samples were drawn in ethylenediaminetetraacetic acid (EDTA) tubes 5 h after the surgery. The blood was centrifuged to separate the plasma and was stored at -70°C. IL-6 was analyzed using the enzyme-linked immunosorbent assay (ELISA) methodology.
Time frame: 5 h after the procedure
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ketamine | Serum Level of Interleukin (IL)-6 5 h After the Procedure | 29.3 picogram/milliliter | Standard Deviation 23.6 |
| Saline | Serum Level of Interleukin (IL)-6 5 h After the Procedure | 34.8 picogram/milliliter | Standard Deviation 48.7 |
p-value: 0.676t-test, 2 sided
Secondary
Serum Level of Interleukin (IL)-6 Before the Procedure
Blood samples were drawn in ethylenediaminetetraacetic acid (EDTA) tubes before the surgery. The blood was centrifuged to separate the plasma and was stored at -70°C. IL-6 was analyzed using the enzyme-linked immunosorbent assay (ELISA) methodology.
Time frame: Baseline (Before the procedure)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ketamine | Serum Level of Interleukin (IL)-6 Before the Procedure | 3.3 picogram/milliliter | Standard Deviation 9.5 |
| Saline | Serum Level of Interleukin (IL)-6 Before the Procedure | 2.1 picogram/milliliter | Standard Deviation 3.4 |
p-value: 0.312t-test, 2 sided
Secondary
Serum Level of Interleukin (IL)-8 24 h After the Procedure
Blood samples were drawn in ethylenediaminetetraacetic acid (EDTA) tubes 24 h after the surgery. The blood was centrifuged to separate the plasma and was stored at -70°C. IL-8 was analyzed using the enzyme-linked immunosorbent assay (ELISA) methodology.
Time frame: 24 h after the procedure
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ketamine | Serum Level of Interleukin (IL)-8 24 h After the Procedure | 6.0 picogram/milliliter | Standard Deviation 7.2 |
| Saline | Serum Level of Interleukin (IL)-8 24 h After the Procedure | 4.5 picogram/milliliter | Standard Deviation 6.1 |
p-value: 0.5t-test, 2 sided
Secondary
Serum Level of Interleukin (IL)-8 5 h After the Procedure
Blood samples were drawn in ethylenediaminetetraacetic acid (EDTA) tubes 5 h after the surgery. The blood was centrifuged to separate the plasma and was stored at -70°C. IL-8 was analyzed using the enzyme-linked immunosorbent assay (ELISA) methodology.
Time frame: 5 h after the procedure
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ketamine | Serum Level of Interleukin (IL)-8 5 h After the Procedure | 8.0 picogram/milliliter | Standard Deviation 6.8 |
| Saline | Serum Level of Interleukin (IL)-8 5 h After the Procedure | 11.3 picogram/milliliter | Standard Deviation 15.1 |
p-value: 0.422t-test, 2 sided
Secondary
Serum Level of Interleukin (IL)-8 Before the Procedure
Blood samples were drawn in ethylenediaminetetraacetic acid (EDTA) tubes before the surgery. The blood was centrifuged to separate the plasma and was stored at -70°C. IL-8 was analyzed using the enzyme-linked immunosorbent assay (ELISA) methodology.
Time frame: Baseline (Before the procedure)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Ketamine | Serum Level of Interleukin (IL)-8 Before the Procedure | 3.3 picogram/milliliter | Standard Deviation 4.1 |
| Saline | Serum Level of Interleukin (IL)-8 Before the Procedure | 2.2 picogram/milliliter | Standard Deviation 3.2 |
p-value: 0.385t-test, 2 sided
Secondary
Time to First Morphine Supplementation
Time frame: 24 hours
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Ketamine | Time to First Morphine Supplementation | 18 minutes |
| Saline | Time to First Morphine Supplementation | 15 minutes |
p-value: 0.113Mann-Whitney