Clinical trial NCT04653415: Large Doses of Methylprednisolone Combined With Gabapentin in Total Knee Arthroplasty
Official title: The Impact of Pre-emptive Large Doses of Methylprednisolone Combined With Gabapentin on Pain Treatment and Convalescence After Total Knee Arthroplasty in Elderly: A Double-blind Randomized Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Arthroplasty Complications
Knee Osteoarthritis
Pain, Postoperative
Perioperative Complication
Keywords: total knee arthroplasty
pre-emptive analgesia
methylprednisolone
gabapentin
opioid dose
pain intensity
infection rate
Lead sponsor: Jagiellonian University
Sponsor class: OTHER
First posted: 2020-12-04
Enrollment: 160
Sex: ALL
Minimum age (years): 65
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: two groups: the study and controls
Primary purpose: TREATMENT

Brief summary: The aim of the study was to assess whether administration of gabapentin and methylprednisolone as "pre-emptive analgesia" in a group of patients above 65 years of age would be effective in complex pain management therapy following total knee arthroplasty (TKA). For the study investigators will qualify one hundred seventy, above 65 years old patients. The participants will be double-blind randomized into two groups: the study and controls The study group will receive as "pre-emptive" analgesia a single dose of 300 mg oral gabapentin and 125 mg intravenous methylprednisolone, while the others placebo. Perioperatively, all the patients will receive opioid and nonopioid analgesic agents calculated for 1 kg of body weight. Investigators will measure the levels of inflammatory markers (leukocytosis, C-reactive protein - CRP), pain intensity level at rest (numerical rating scale - NRS), the life parameters and all complications.

Detailed description: The aim of the study was to assess whether administration of gabapentin and methylprednisolone as "pre-emptive analgesia" in a group of patients above 65 years of age would be effective in complex pain management therapy following total knee arthroplasty (TKA).170 patients operated on due to unilateral TKA will be double-blinded randomized into two groups: the study and the controls. Exclusion criteria are: clinical situation that 1/ restricted glucocorticoid administration: diabetes type 1 and 2, CRP levels above normal values (≥5 mg/l), chronic steroid treatment, peptic ulcers treated in the past 30 days and 2/and the chronic pain in the course of gonarthrosis, high intensity requiring use opioids.

The participants of the study will be subjected to the standardized procedure of subarachnoid anesthesia with subsequent unilateral femoral nerve block at the operated side, followed by the surgical procedure - unilateral TKA. The study group will receive as "pre-emptive" analgesia a single dose of 300 mg oral gabapentin and 125 mg intravenous methylprednisolone, while the others placebo. Prior to anesthesia induction, the patients receive: anti-infection prophylactics intravenous cephazolin 2.0 g, for hemostasis control - tranexamic acid 1.0 g, an anti-emetic agent - ondansetron 8 mg. Fluid supply (crystalloids) will be standardized: 12 ml/kg in the first hour of surgery and 6 ml/kg in the following hours, packed red blood cells if blood loss exceeded 600 ml and hemoglobin concentration \<10g/l during the time of operation. Pain management will be carried out based on the results of the NRS scales at rest. Every 6 hours NRS will be checked and intravenous PCA (patient-controlled analgesia) oxycodone hydrochloride, if pain was ≥4 points NRS or intravenous paracetamol, metamizole, if the pain was 2 - 4 NRS points will be administered, all pain medications will be calculated for 1 kg of body weight. In keeping with the ERAS (Enhanced Recovery After Surgery) protocol, on the day of surgery the patients will receive orally fluids and meals, will be mobilized and rehabilitated.

The study was approved by the institutional review board (nr 1072.6120.11.2020). Oral and written informed consent to participate in the study will be collected from all participants of the study. The statistical analysis of the groups will be performed to asess the demographic dates, life parameters, general condition in keeping with the ASA (American Society of Anesthesiology), POSSUM (Physiologic and Operative Severity Score for the enUmeration of Mortality and Morbidity) score, total dose of analgesic medications administered parenterally calculated for 1 kg of body mass in response to value of NRS at rest on day 0, time of administration the first dose, and duration of peripheral nerve block. On the day of surgery and on subsequent days, determinations will be made of glycemia levels and inflammatory markers: C-reactive protein (CRP) and leukocytosis levels.

Eligibility criteria: Inclusion Criteria:

* patients over 65 years old operated on unilateral total knee arthroplasty

Exclusion Criteria:

* diabetes type 1 and 2,
* CRP levels above normal values (≥5 mg/l),
* chronic steroid treatment,
* peptic ulcers treated in the past 30 days,
* chronic pain in the course of gonarthrosis,

Primary outcomes:
measure: Pain intensity assessed by NRS
timeFrame: change in every 6 hours on day 0
measure: the dose of parenteral analgesics agents
timeFrame: 24 hours
measure: C-reactive protein (CRP) level
timeFrame: change in 0,1,2,3 days after surgery
measure: Leukocytosis level
timeFrame: change in 0,1,2,3 days after surgery
measure: Adverse effects
timeFrame: 0 day after surgery
measure: Adverse effects
timeFrame: 1 day after surgery
measure: Adverse effects
timeFrame: 2 day after surgery
measure: Adverse effects
timeFrame: 3 day after surgery
measure: Adverse effects
timeFrame: 14 day after surgery
Secondary outcomes:
measure: Duration of femoral nerve blockade
timeFrame: on the day of surgery
measure: Blood glucose level
timeFrame: change in 0,1,2,3 days after surgery
Other outcomes:
measure: Mean age
timeFrame: the day of surgery
measure: Mean hospitalization time
timeFrame: from admission to hospital till 14 days after surgery
measure: Mean postoperative hospitalization time
timeFrame: change from 0 till 14 days after surgery
measure: Postoperative Mean Arterial Pressure (MAP)
timeFrame: change in 0,1,2,3 days after surgery
measure: Postoperative pulse
timeFrame: change in 0,1,2,3 days after surgery
measure: Postoperative saturation (Sp02) of the arterial blood
timeFrame: change in 0,1,2,3 days after surgery
measure: Physiological and Operative Severity Score for the enUmeration of Mortality and morbidity (POSSUM) morbidity
timeFrame: the day of the surgery
measure: Physiological and Operative Severity Score for the enUmeration of Mortality and morbidity (POSSUM) mortality
timeFrame: the day of the surgery
measure: Physiological and Operative Severity Score for the enUmeration of Mortality and morbidity (POSSUM) physiological score
timeFrame: the day of the surgery
measure: American Society of Anesthesiology Score (ASA)
timeFrame: the day of the surgery
Locations:
city: Krakow
country: Poland
facility: University Hospital in Krakow
state: Malopolska
Study officials:
References:
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