Clinical trial NCT02848599
Conditions: Postoperative Cognitive Dysfunction
Keywords: postoperative analgesia postoperative cognitive disfunction
Sponsor: Osijek University Hospital
Start date: 2016-07-01; Completion date: 2017-09-01
Enrollment: 86 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The purpose of this study is to determine whether epidural levobupivacaine applied for the purpose of post-operative analgesia compared to systemic analgesia with morphine leads to better pain control, stronger suppression of the inflammatory response and the production of inflammatory mediators, faster recovery of patients and consequently less incidence of postoperative cognitive dysfunction (POCD) in elderly patients after surgical treatment of femoral fractures.

Detailed description:
The research will be carried out at the Department of Surgery at Clinical Hospital Centre(CHC) Osijek after approval by the Ethics Committee of CHC Osijek and will be organized as a prospective randomized trial. Respecting the including and excluding criteria for participation in the study, the research will include 70 patients aged 65 years and over who are undergoing surgery for proximal femur fractures and will be operated with the same operating technique (osteosynthesis with nail). All participants will receive the same type of anesthesia and one of two forms of post-operative analgesia, so it will be divided into two groups (35 patients) depending on which form of post-operative analgesia receive. Randomization will be performed by drawing an envelope in which the specified one or other form of post-operative analgesia will be written. The study will be stopped in case of serious complications life-threatening (excessive sedation, respiratory insufficiency, hemodynamic instability and profound hypotension, heart rhythm disorders), which could possibly be related to the administration of drugs used for postoperative analgesia.

Arms: arm 1: 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 arm 2: 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).
Interventions: intervention 1: morphine intervention 2: levobupivacaine
Intervention descriptions: intervention 1: None intervention 2: None

Protocol documents:
Prot_000.pdf: 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
NCT02848599 
 
ID: 25-1:6563-3/2014 
    The Influence of 
Postoperative Analgesia 
on Systemic Inflammatory 
Response and POCD 
After Femoral Fractures 
Surgery 
Document Date: May 26, 2017 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


The study was approved by the University Hospital Osijek Ethics Committee 
(Approval number 25-1:6563-3/2014, 19.5.2014.) and written informed consent 
was obtained from all subjects. The study design was a prospective, 
randomized, controlled trial. All patients received spinal anesthesia and one of 
two techniques of postoperative analgesia: intravenous patient-controlled 
analgesia (PCA) with morphine or patient-controlled epidural analgesia 
(PCEA) with 0.125% levobupivacaine. According to technique of postoperative 
analgesia which was applied, patients were allocated into two groups, the 
morphine group and the levobupivacaine group. Randomization was done 
before surgery by pulling out the envelope in which it was written the group 
division. Inclusion criteria were age ≥ 65, American Society of 
Anesthesiologists (ASA) physical status I-III, Mini-Mental State Examination 
(MMSE) score ≥ 17.Exclusion criteria were age < 65, ASA physical status > III, 
MMSE score < 17, history of dementia, schizophrenia, Parkinson's disease 
and cerebrovascular disease, use of opioids and benzodiazepines longer than 
one month before surgery, alcoholism, severe liver disease (class C according 
to Child-Pugh classification), severe kidney disease requiring hemodialysis, 
multiple trauma and the presence of head injury, communication issues such 
as serious hearing or visual impairment, any contraindication for regional 
anesthesia and for the both techniques of postoperative analgesia. Cefazolin 
1g was given to all patients 30 minutes before incision and two other doses 
were given postoperatively. All patients were sedated with midazolam, 2 to 3 
mg intravenously, before induction of anesthesia. In the morphine group spinal 
anesthesia was induced with subarachnoidally injection of 12.5-15 mg 0,5% 
levobupivacaine. In the levobupivacaine group combined spinal-epidural 
anesthesia was performed. First, the epidural space was entered with Tuohy 
epidural needle and the spinal needle was introduced via the lumen of the 
epidural needle into the subarachnoid space through which 12.5-15 mg of 
0.5% levobupivacaine was injected. After that epidural catheter was inserted in 
the epidural space and its position was checked radiologically and confirmed 
with the test dose of 0.5% levobupivacaine after the spinal anesthesia was 
released. During the operation blood pressure was measured non-invasively 
every 5 minutes and its decrease greater than 20% from preoperative values 
was corrected by fluid administration and incremental IV injections of 
vasoconstrictors. The ECG and peripheral oxygen saturation by pulse 
oximeter were continuously monitored. Postoperative analgesia was obtained 
using patient-controlled analgesia (PCA) for the first 72 h. In the morphine 
group intravenous PCA was provided with the following settings: 0.5-2 mg/h 
basal flow, 0.5 mg bolus dose, and a 20-min lockout. Postoperative epidural 
PCA analgesia was obtained with 0.125% levobupivacaine with 6-12 ml/h 
basal flow, 2 ml bolus dose, and a 20-min lockout. Analgesia was assessed by 
Numerical Rating Scale (NRS), from 0 (no pain) to 10 (maximum pain) every 
three hours 72h postoperatively and then 3 times a day until discharge. In all 
patients complete blood count, differential blood count, CRP and fibrinogen 
were calculated 30 min before induction of anesthesia, 24h, 72h and 120h 
postoperatively. Blood glucose level was measured every 4 hours for 72h after 


surgery and further depending on the values. The plasma concentrations of IL-
6 was measured 30 min before induction of anesthesia, 24h and 72h 
postoperatively. Duration of surgery, blood loss, erythrocyte transfusion, body 
temperature and postoperative hospital stay were recorded. Cognitive 
functions were assessed using Mini-Mental State Examination (MMSE) 
preoperatively (baseline) and from the 1stto the5th postoperative day and on the 
day of discharge(the day of surgery was marked as 0 day), once a day 
between 6 and 8 am. Anxiety and depression were assessed using Hospital 
Anxiety and Depression Scale (HADS) preoperatively (baseline) and on the 
1stand 5thpostoperative day and on the day of discharge once a day, at the 
same time when cognitive functions were evaluated. 
 

SAP_001.pdf: 
 
 
 
 
 
 
 
 
NCT02848599 
 
ID: 25-1:6563-3/2014 
    The Influence of 
Postoperative Analgesia 
on Systemic Inflammatory 
Response and POCD 
After Femoral Fractures 
Surgery 
Document Date: May 26, 2017 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


 
Category data were represented by absolute and relative frequencies. 
Variations of category variables were tested by Fisher's exact test. The 
numerical data are described by the median and the limits of the interquartile 
range. The normality of distribution of observed numeric variables was tested 
by the Shapiro -Wilk test. The differences between the normal distribution of 
numeric variables between the two independent groups were tested by Mann-
Whitney's In Test. To determine the difference between the two dependent 
samples, Friedman's test was used. Logistic regression was used to assess 
the influence of several factors on the likelihood that POCD would develop in 
the observed subjects. The receiver operating curve (ROC) analysis was used 
to determine the optimal threshold, area under the curve (AUC), specificity, 
and sensitivity of the tested parameters. All P values were two-tailed. The level 
of significance was set at Alpha = 0.05. The statistical analysis was performed 
using MedCalc Statistical Software version 14.12.0 (MedCalc Software bvba, 
Ostend, Belgium; http://www.medcalc.org; 2014)