Trial Outcomes & Findings for The Influence of Postoperative Analgesia on Systemic Inflammatory Response and POCD After Femoral Fractures Surgery (NCT NCT02848599)
NCT ID: NCT02848599
Last Updated: 2020-09-01
Results Overview
Measurement will be done before and 24 and 72 hours after the surgery.
Recruitment status
COMPLETED
Study phase
PHASE2
Target enrollment
86 participants
Primary outcome timeframe
Before, 24 and 72 hours after the surgery
Results posted on
2020-09-01
Participant Flow
From July 2016 to September 2017, 86 patients were included in the study in accordance with the inclusion criteria and 70 of them completed the study. The study design was a prospective, randomized, controlled trial. It was conducted at the University Hospital Osijek (Croatia).
No patients were excluded from the study before assignment to groups.
Participant milestones
| Measure |
Morphine
The patient-controlled intravenous analgesia with morphine (basal flow of 0.5-2 mg / h, bolus dose of 0.5 mg, lockout interval of 20 minutes, hour limit of 3 doses), which will be carried out 72 hours after the surgery
morphine
|
Levobupivacaine
Upon completion of the operation for a period of 72 hours will be implemented continuous epidural local anesthetic through the Patient Controlled Analgesia (PCA) pump (Levobupivacaine 0.125%, basal flow of 6 ml / hour, a bolus dose of 2 ml, lockout interval of 20 minutes, hour limit of 3 doses).
levobupivacaine
|
|---|---|---|
|
Overall Study
STARTED
|
42
|
44
|
|
Overall Study
COMPLETED
|
35
|
35
|
|
Overall Study
NOT COMPLETED
|
7
|
9
|
Reasons for withdrawal
| Measure |
Morphine
The patient-controlled intravenous analgesia with morphine (basal flow of 0.5-2 mg / h, bolus dose of 0.5 mg, lockout interval of 20 minutes, hour limit of 3 doses), which will be carried out 72 hours after the surgery
morphine
|
Levobupivacaine
Upon completion of the operation for a period of 72 hours will be implemented continuous epidural local anesthetic through the Patient Controlled Analgesia (PCA) pump (Levobupivacaine 0.125%, basal flow of 6 ml / hour, a bolus dose of 2 ml, lockout interval of 20 minutes, hour limit of 3 doses).
levobupivacaine
|
|---|---|---|
|
Overall Study
Protocol Violation
|
7
|
9
|
Baseline Characteristics
Race and Ethnicity were not collected from any participant.
Baseline characteristics by cohort
| Measure |
Morphine
n=35 Participants
The patient-controlled intravenous analgesia with morphine (basal flow of 0.5-2 mg / h, bolus dose of 0.5 mg, lockout interval of 20 minutes, hour limit of 3 doses), which will be carried out 72 hours after the surgery
morphine
|
Levobupivacaine
n=35 Participants
Upon completion of the operation for a period of 72 hours will be implemented continuous epidural local anesthetic through the Patient Controlled Analgesia (PCA) pump (Levobupivacaine 0.125%, basal flow of 6 ml / hour, a bolus dose of 2 ml, lockout interval of 20 minutes, hour limit of 3 doses).
levobupivacaine
|
Total
n=70 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=35 Participants
|
0 Participants
n=35 Participants
|
0 Participants
n=70 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
0 Participants
n=35 Participants
|
0 Participants
n=35 Participants
|
0 Participants
n=70 Participants
|
|
Age, Categorical
>=65 years
|
35 Participants
n=35 Participants
|
35 Participants
n=35 Participants
|
70 Participants
n=70 Participants
|
|
Sex: Female, Male
Female
|
34 Participants
n=35 Participants
|
32 Participants
n=35 Participants
|
66 Participants
n=70 Participants
|
|
Sex: Female, Male
Male
|
1 Participants
n=35 Participants
|
3 Participants
n=35 Participants
|
4 Participants
n=70 Participants
|
|
Race and Ethnicity Not Collected
|
—
|
—
|
0 Participants
Race and Ethnicity were not collected from any participant.
|
|
Education
No school
|
1 Participants
n=35 Participants
|
1 Participants
n=35 Participants
|
2 Participants
n=70 Participants
|
|
Education
Less than high school
|
31 Participants
n=35 Participants
|
29 Participants
n=35 Participants
|
60 Participants
n=70 Participants
|
|
Education
High school
|
3 Participants
n=35 Participants
|
5 Participants
n=35 Participants
|
8 Participants
n=70 Participants
|
|
ASA (American Society of Anesthesiologist physical status)
ASA II
|
3 Participants
n=35 Participants
|
3 Participants
n=35 Participants
|
6 Participants
n=70 Participants
|
|
ASA (American Society of Anesthesiologist physical status)
ASA III
|
32 Participants
n=35 Participants
|
32 Participants
n=35 Participants
|
64 Participants
n=70 Participants
|
|
Duration of surgery
|
49 minutes
n=35 Participants
|
52 minutes
n=35 Participants
|
52 minutes
n=70 Participants
|
|
BMI
|
24.8 kg/m^2
n=35 Participants
|
23.9 kg/m^2
n=35 Participants
|
24.4 kg/m^2
n=70 Participants
|
|
Perioperative transfusion
|
2 Units of PRBC (packed red blood cells)
n=35 Participants
|
2 Units of PRBC (packed red blood cells)
n=35 Participants
|
2 Units of PRBC (packed red blood cells)
n=70 Participants
|
PRIMARY outcome
Timeframe: Before, 24 and 72 hours after the surgeryMeasurement will be done before and 24 and 72 hours after the surgery.
Outcome measures
| Measure |
Morphine
n=35 Participants
The patient-controlled intravenous analgesia with morphine (basal flow of 0.5-2 mg / h, bolus dose of 0.5 mg, lockout interval of 20 minutes, hour limit of 3 doses), which will be carried out 72 hours after the surgery
morphine
|
Levobupivacaine
n=35 Participants
Upon completion of the operation for a period of 72 hours will be implemented continuous epidural local anesthetic through the Patient Controlled Analgesia (PCA) pump (Levobupivacaine 0.125%, basal flow of 6 ml / hour, a bolus dose of 2 ml, lockout interval of 20 minutes, hour limit of 3 doses).
levobupivacaine
|
|---|---|---|
|
Interleukin-6 Concentration in Peripheral Blood.
Before surgery
|
27.2 pg/ml
Interval 17.8 to 46.8
|
26.6 pg/ml
Interval 19.7 to 38.0
|
|
Interleukin-6 Concentration in Peripheral Blood.
24h after surgery
|
104 pg/ml
Interval 73.0 to 156.8
|
97.7 pg/ml
Interval 65.9 to 119.1
|
|
Interleukin-6 Concentration in Peripheral Blood.
72h after surgery
|
50 pg/ml
Interval 30.2 to 97.5
|
30.5 pg/ml
Interval 23.1 to 52.4
|
PRIMARY outcome
Timeframe: Before, 24,48,72,96 and 120 hours after the surgeryAssessment of cognitive function will be done using the Mini-mental state examination (MMSE) rating scales before and 24,48,72,96 and 120 hours after the surgery at the same time every morning. Mini-Mental State Examination Scale: minimum score is 0 and maximum score is 30; the severity of cognitive impairment: no cognitive impairment=25-30; mild cognitive impairment=19-24; moderate cognitive impairment=10-18; and severe cognitive impairment\<9. Higher scores mean a better and lower scores mean a worse outcome.
Outcome measures
| Measure |
Morphine
n=35 Participants
The patient-controlled intravenous analgesia with morphine (basal flow of 0.5-2 mg / h, bolus dose of 0.5 mg, lockout interval of 20 minutes, hour limit of 3 doses), which will be carried out 72 hours after the surgery
morphine
|
Levobupivacaine
n=35 Participants
Upon completion of the operation for a period of 72 hours will be implemented continuous epidural local anesthetic through the Patient Controlled Analgesia (PCA) pump (Levobupivacaine 0.125%, basal flow of 6 ml / hour, a bolus dose of 2 ml, lockout interval of 20 minutes, hour limit of 3 doses).
levobupivacaine
|
|---|---|---|
|
Changes in Cognitive Function
Before surgery
|
21 score on a scale
Interval 19.0 to 23.0
|
22 score on a scale
Interval 20.0 to 25.0
|
|
Changes in Cognitive Function
24 h after surgery
|
20 score on a scale
Interval 18.0 to 23.0
|
22 score on a scale
Interval 20.0 to 25.0
|
|
Changes in Cognitive Function
48 h after surgery
|
20 score on a scale
Interval 18.0 to 23.0
|
21 score on a scale
Interval 20.0 to 24.0
|
|
Changes in Cognitive Function
72 h after surgery
|
20 score on a scale
Interval 17.0 to 23.0
|
21 score on a scale
Interval 20.0 to 25.0
|
|
Changes in Cognitive Function
96 h after surgery
|
20 score on a scale
Interval 15.0 to 23.0
|
21 score on a scale
Interval 20.0 to 25.0
|
|
Changes in Cognitive Function
120 h after surgery
|
20 score on a scale
Interval 17.0 to 23.0
|
22 score on a scale
Interval 20.0 to 25.0
|
SECONDARY outcome
Timeframe: Before, 24,72 and 120 hours after the surgeryMeasurement will be done before and 24,72 and 120 hours after the surgery.
Outcome measures
| Measure |
Morphine
n=35 Participants
The patient-controlled intravenous analgesia with morphine (basal flow of 0.5-2 mg / h, bolus dose of 0.5 mg, lockout interval of 20 minutes, hour limit of 3 doses), which will be carried out 72 hours after the surgery
morphine
|
Levobupivacaine
n=35 Participants
Upon completion of the operation for a period of 72 hours will be implemented continuous epidural local anesthetic through the Patient Controlled Analgesia (PCA) pump (Levobupivacaine 0.125%, basal flow of 6 ml / hour, a bolus dose of 2 ml, lockout interval of 20 minutes, hour limit of 3 doses).
levobupivacaine
|
|---|---|---|
|
Changes in C-reactive Protein (CRP) Levels
120 h after surgery
|
66.9 mg/L
Interval 40.6 to 98.2
|
54.6 mg/L
Interval 30.7 to 70.0
|
|
Changes in C-reactive Protein (CRP) Levels
Before surgery
|
57.2 mg/L
Interval 10.0 to 90.3
|
57.8 mg/L
Interval 36.7 to 70.2
|
|
Changes in C-reactive Protein (CRP) Levels
24 h after surgery
|
106.2 mg/L
Interval 74.1 to 145.0
|
98.1 mg/L
Interval 77.1 to 116.8
|
|
Changes in C-reactive Protein (CRP) Levels
72 h after surgery
|
118.5 mg/L
Interval 82.9 to 149.9
|
95 mg/L
Interval 71.2 to 117.9
|
SECONDARY outcome
Timeframe: Before, 24,72 and 120 hours after the surgeryMeasurement will be done before and 24,72 and 120 hours after the surgery.
Outcome measures
| Measure |
Morphine
n=35 Participants
The patient-controlled intravenous analgesia with morphine (basal flow of 0.5-2 mg / h, bolus dose of 0.5 mg, lockout interval of 20 minutes, hour limit of 3 doses), which will be carried out 72 hours after the surgery
morphine
|
Levobupivacaine
n=35 Participants
Upon completion of the operation for a period of 72 hours will be implemented continuous epidural local anesthetic through the Patient Controlled Analgesia (PCA) pump (Levobupivacaine 0.125%, basal flow of 6 ml / hour, a bolus dose of 2 ml, lockout interval of 20 minutes, hour limit of 3 doses).
levobupivacaine
|
|---|---|---|
|
Changes in Fibrinogen Concentrations in Peripheral Blood
Before surgery
|
5.5 g/L
Interval 4.8 to 6.1
|
4.5 g/L
Interval 3.8 to 5.3
|
|
Changes in Fibrinogen Concentrations in Peripheral Blood
24 h after surgery
|
5.3 g/L
Interval 4.8 to 5.6
|
4.7 g/L
Interval 3.9 to 5.2
|
|
Changes in Fibrinogen Concentrations in Peripheral Blood
72 h after surgery
|
5.7 g/L
Interval 5.4 to 6.4
|
5.2 g/L
Interval 4.4 to 6.2
|
|
Changes in Fibrinogen Concentrations in Peripheral Blood
120 h after surgery
|
5.4 g/L
Interval 4.7 to 6.0
|
5 g/L
Interval 4.2 to 5.4
|
SECONDARY outcome
Timeframe: During the first 72 hours after the surgery assessment will be done every 3 hours, after that assessment will be done 3 times daily until dischargeAssessment will be done using Numeric Rating Scale (NRS). During the first 72 hours after the surgery assessment will be done every 3 hours, after that assessment will be done 3 times daily. Median of 8 time points measurements during the first 24, 48 and 72 hours after the surgery will be reported. After that, median of 3 time points will be reported from the 4. to 6. postoperative day and on the day of discharge. Minimum score 0 and maximum score 10 ( 0-No Pain; 1-3 Mild Pain; 4-6 Moderate Pain; 7-10 Severe Pain ). Higher scores mean a worse and lower scores mean a better outcome.
Outcome measures
| Measure |
Morphine
n=35 Participants
The patient-controlled intravenous analgesia with morphine (basal flow of 0.5-2 mg / h, bolus dose of 0.5 mg, lockout interval of 20 minutes, hour limit of 3 doses), which will be carried out 72 hours after the surgery
morphine
|
Levobupivacaine
n=35 Participants
Upon completion of the operation for a period of 72 hours will be implemented continuous epidural local anesthetic through the Patient Controlled Analgesia (PCA) pump (Levobupivacaine 0.125%, basal flow of 6 ml / hour, a bolus dose of 2 ml, lockout interval of 20 minutes, hour limit of 3 doses).
levobupivacaine
|
|---|---|---|
|
Changes in Pain Intensity
3,6,9,12,15,18,21 and 24h after surgery
|
1.4 score on a scale
Interval 0.6 to 2.9
|
0.6 score on a scale
Interval 0.3 to 0.9
|
|
Changes in Pain Intensity
27,30,33,36,39,42,45 and 48h after surgery
|
1.5 score on a scale
Interval 0.8 to 2.3
|
0.5 score on a scale
Interval 0.3 to 0.9
|
|
Changes in Pain Intensity
51,54,57,60,63,66,69 and 72h after surgery
|
1.4 score on a scale
Interval 0.9 to 1.9
|
0.5 score on a scale
Interval 0.1 to 0.8
|
|
Changes in Pain Intensity
4. postoperative day (every 8 hours)
|
1.4 score on a scale
Interval 0.8 to 1.9
|
0.3 score on a scale
Interval 0.0 to 0.8
|
|
Changes in Pain Intensity
5. postoperative day (every 8 hours)
|
1.4 score on a scale
Interval 1.0 to 2.0
|
0 score on a scale
Interval 0.0 to 1.0
|
|
Changes in Pain Intensity
6. postoperative day (every 8 hours)
|
1.3 score on a scale
Interval 0.7 to 2.3
|
0 score on a scale
Interval 0.0 to 0.7
|
|
Changes in Pain Intensity
Day of discharge
|
1 score on a scale
Interval 0.0 to 1.0
|
0 score on a scale
Interval 0.0 to 0.0
|
SECONDARY outcome
Timeframe: 14 daysPopulation: The reasons for exclusion of 16 patients were: inability to perform combined spinal-epidural anaesthesia (5 patients), technical problems with PCA pump (4 patients), withdrawal of epidural catheter (2 patients), postoperative delirium and use of antipsychotics (3 patients) and fever and use of antipyretics (2 patients).
Duration of postoperative hospital stay in days
Outcome measures
| Measure |
Morphine
n=42 Participants
The patient-controlled intravenous analgesia with morphine (basal flow of 0.5-2 mg / h, bolus dose of 0.5 mg, lockout interval of 20 minutes, hour limit of 3 doses), which will be carried out 72 hours after the surgery
morphine
|
Levobupivacaine
n=44 Participants
Upon completion of the operation for a period of 72 hours will be implemented continuous epidural local anesthetic through the Patient Controlled Analgesia (PCA) pump (Levobupivacaine 0.125%, basal flow of 6 ml / hour, a bolus dose of 2 ml, lockout interval of 20 minutes, hour limit of 3 doses).
levobupivacaine
|
|---|---|---|
|
Postoperative Hospital Stay
|
7 days
Interval 7.0 to 8.0
|
7 days
Interval 7.0 to 8.0
|
Adverse Events
Morphine
Serious events: 0 serious events
Other events: 5 other events
Deaths: 0 deaths
Levobupivacaine
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Morphine
n=35 participants at risk
The patient-controlled intravenous analgesia with morphine (basal flow of 0.5-2 mg / h, bolus dose of 0.5 mg, lockout interval of 20 minutes, hour limit of 3 doses), which will be carried out 72 hours after the surgery
morphine
|
Levobupivacaine
n=35 participants at risk
Upon completion of the operation for a period of 72 hours will be implemented continuous epidural local anesthetic through the Patient Controlled Analgesia (PCA) pump (Levobupivacaine 0.125%, basal flow of 6 ml / hour, a bolus dose of 2 ml, lockout interval of 20 minutes, hour limit of 3 doses).
levobupivacaine
|
|---|---|---|
|
Gastrointestinal disorders
Nausea
|
8.6%
3/35 • Number of events 3 • Adverse event data were collected from end of the surgery until discharge from the hospital or date of death from any cause, whichever came first, assessed up to 10 days.
Gastrointestinal side effects- nausea, constipation, vomiting Neurological side effects- paresthesia
|
0.00%
0/35 • Adverse event data were collected from end of the surgery until discharge from the hospital or date of death from any cause, whichever came first, assessed up to 10 days.
Gastrointestinal side effects- nausea, constipation, vomiting Neurological side effects- paresthesia
|
|
Nervous system disorders
Paresthesia
|
0.00%
0/35 • Adverse event data were collected from end of the surgery until discharge from the hospital or date of death from any cause, whichever came first, assessed up to 10 days.
Gastrointestinal side effects- nausea, constipation, vomiting Neurological side effects- paresthesia
|
5.7%
2/35 • Number of events 2 • Adverse event data were collected from end of the surgery until discharge from the hospital or date of death from any cause, whichever came first, assessed up to 10 days.
Gastrointestinal side effects- nausea, constipation, vomiting Neurological side effects- paresthesia
|
|
Gastrointestinal disorders
Constipation
|
14.3%
5/35 • Number of events 5 • Adverse event data were collected from end of the surgery until discharge from the hospital or date of death from any cause, whichever came first, assessed up to 10 days.
Gastrointestinal side effects- nausea, constipation, vomiting Neurological side effects- paresthesia
|
0.00%
0/35 • Adverse event data were collected from end of the surgery until discharge from the hospital or date of death from any cause, whichever came first, assessed up to 10 days.
Gastrointestinal side effects- nausea, constipation, vomiting Neurological side effects- paresthesia
|
Additional Information
Dr. Gordana Kristek
University Hospital Osijek, Croatia
Phone: +385915115746
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place