Large Doses of Methylprednisolone Combined With Gabapentin in Total Knee Arthroplasty

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Arthroplasty Complications, Knee Osteoarthritis, Pain, Postoperative, Perioperative Complication

Intervention / Treatment
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* Drug: Gabapentin 300mg
* Drug: Methylprednisolone 125 mg
* Drug: Tablet
* Drug: Normal Saline 10 mL Injection


Participation Criteria
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Eligibility Criteria
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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,

Ages Eligible for Study
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Minimum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: two groups: the study and controls
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Study Group<br>The study group will receive as pre-emptive analgesia a single dose of 300 mg oral gabapentin and 125 mg intravenous methylprednisolone. | Drug: Gabapentin 300mg<br>* The study group will receive as pre-emptive analgesia a single dose of 300 mg oral gabapentin and 125 mg intravenous methylprednisolone.<br>Drug: Methylprednisolone 125 mg<br>* The study group will receive as pre-emptive analgesia a single dose of 300 mg oral gabapentin and 125 mg intravenous methylprednisolone.<br>|
| Placebo Comparator: Controls group<br>The controls group will receive placebo orally - a tablet without any pharmacological properties, intravenously - saline solution. | Drug: Tablet<br>* The controls group will receive placebo orally - a tablet without any pharmacological properties, intravenously - normal saline solution<br>Drug: Normal Saline 10 mL Injection<br>* The controls group will receive placebo orally - a tablet without any pharmacological properties, intravenously - normal saline solution<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pain intensity assessed by NRS | The level of postoperative pain measured in the numerical rating scale (NRS) at rest (minimum 0 - no pain, maximum 10 - the maximum of pain). | change in every 6 hours on day 0 | 
| the dose of parenteral analgesics agents | Dose of oxycodone hydrochloride in mg/kg body weight, paracetamol in mg/kg body weight, metamizole in g/kg body weight | 24 hours | 
| C-reactive protein (CRP) level | C-reactive protein (CRP) level measured in mg/l | change in 0,1,2,3 days after surgery | 
| Leukocytosis level | Leukocytosis level measured in µL | change in 0,1,2,3 days after surgery | 
| Adverse effects | The occurrence of adverse effects that would delay early rehabilitation, possible complication development, perioperative mortality to the POSSUM scale, comorbidities | 0 day after surgery | 
| Adverse effects | The occurrence of adverse effects that would delay early rehabilitation, possible complication development, perioperative mortality to the POSSUM scale, comorbidities | 1 day after surgery | 
| Adverse effects | The occurrence of adverse effects that would delay early rehabilitation, possible complication development, perioperative mortality to the POSSUM scale, comorbidities | 2 day after surgery | 
| Adverse effects | The occurrence of adverse effects that would delay early rehabilitation, possible complication development, perioperative mortality to the POSSUM scale, comorbidities | 3 day after surgery | 
| Adverse effects | The occurrence of adverse effects that would delay early rehabilitation, possible complication development, perioperative mortality to the POSSUM scale, comorbidities | 14 day after surgery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Duration of femoral nerve blockade | The time of femoral nerve block | on the day of surgery | 
| Blood glucose level | The level of glucose in blood in mmol/l | change in 0,1,2,3 days after surgery | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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total knee arthroplasty, pre-emptive analgesia, methylprednisolone, gabapentin, opioid dose, pain intensity, infection rate