Comparison of the Effect of Intra-articular Administration of 0.2% Ropivacaine vs. 0.75% Ropivacaine as an Analgesic in the Immediate Postoperative Period of Knee Arthroscopy in Acute Injuries at the ABC Medical Center
Phase: PHASE4
Conditions: Knee Arthroscopy, Acute Pain
Sponsor: Paola M Zamora Munoz

 
 
 
The American British Cowdray Medical Center 
 
 
Date: March 26, 2020 
 
NCT05807945 
 
 
Comparison of Intra-articular 0.2% Ropivacaine vs 0.75% Ropivacaine in 
Postoperative Knee Arthroscopy 
 
 
 
 
 
Abstract: 
 
 
All patients with acute lesions assistant to the orthopedic and trauma center of the ABC 
medical center will be invited to participate in the study. Those that meet the inclusion 
criteria and later sign an informed consent will be randomized to receive 10 ml of a solution 
with ropivacaine at 0.75% and 0.2% intraarticular for the first 5 minutes after the end of 
surgery (closing of surgical wounds). Both the patient, the physician who applies it and the 
evaluator of outcomes remain blinded to the dose of ropivacaine the patient receives. 
 
Two hours after the end of the surgery, while the patient is in his room, the presence of pain 
will be evaluated by a visual analog scale (EVA), while the patient is asked to flex and extend 
his knee. The result will be quantified continuously, to later categorize the pain in none to 
slight pain (0-3 points) and moderate-severe pain (4-10 points). All the information will be 
recorded on established forms in the clinical file (general data), that includes the variables of 
interest for the study, and is reported by the physicians after standardization of all those 
encharged with collecting information to comply with the conceptual and operative 

operationalization of the variables described in the research protocol. In addition to the 
evaluation of pain, the administration of opiodes to patients for necessary reasons (presence 
of pain) by the physicians in charge is recorded. 
 
It is hoped that, in patients with knee arthroscopy for acute lesion, there is a difference in 
the frequency of moderate-severe pain of 30% in the post-operative (frequency of 37.5% in 
patients with ropivacaine at 2% and frequency of 7.5% in patients with ropivacaine at 
7.5%). 

Background 
Knee arthroscopy is a minor outpatient orthopedic procedure, used primarily to remove 
loose bodies, for debridement of meniscal tears, debridement and remodeling of cartilage 
lesions, ligament reconstruction, meniscus transplants, and arthroscopically assisted 
synovectomy[1]. 
Estimates made in the United States of America indicated that in 2006, 6.3 million 
orthopedic surgical procedures were performed in an outpatient context[1], of which 
984,999 (95% CI: 895,999 to 1,073,215) corresponded to knee arthroscopies[1 ]. In 
Sweden it is estimated that a team consisting of an average of 7 surgeons (from teaching, 
general and local hospitals) performs 330 (110-2,600) arthroscopies annually[2]. 
Post-surgical pain after performing knee arthroscopies has been described in 62.5% of 
patients acutely (4 days after the operation), and in 76.9% of subjects chronically (1 year 
after surgery). surgery)[3]. In patients with moderate-severe preoperative pain (4-10 points 
according to the visual analogue scale (VAS)), the presence of acute and chronic pain 
occurs in 45.6% and 42.7%, respectively, while in those with pain between 0 -3 points, 
acute and chronic pain occurred in 17.2% and 6.9%, respectively[3]. 
Global Surgical Recovery has been investigated using the Global Surgical Recovery Index 
after knee arthroscopy, the evaluation tool consisted of a question “Yes, 100% recovery 
means that your health “You have returned to the same level you had before the surgery, 
what percentage of recovery do you have now?” (“if 100% recovery means your health is 
back to the same level as it was before the surgery, what percentage of recovery are you 
now?”), with 88.5% of participants responding with values ≤80% in a period of 4 days after 
surgery and 50.0% values ≤80% one year after surgery[3]. 
Currently there is no guideline or consensus for the treatment of elective knee 
arthroscopies[2], [4]. However, when analyzing the responses of a questionnaire sent to 
various orthopedic units members of the “Swedish Arthroscopy Society”, it was reported 
that the most common anesthesia technique corresponded to 1) general (83%), 2) local 
anesthesia without or with minimal sedation was used in 13% of patients, 3) while spinal 
anesthesia was performed in 4% of patients[2]. In the postoperative period, 1/37 (2.70%) of 
the units interviewed did not use local intra-articular anesthesia for the treatment of pain, 
8/37 (21.62%) used short-term lidocaine or prilocaine (with or without adrenaline), in 20 

/37 (54.05%) used long-acting intra-articular bupivacaine, 5/37 (13.51%) used morphine 
and 3/37 (8.10%) NSAIDs[2]. 
After the use of the different anesthesia methods, the adverse effect on the articular 
cartilage has been evaluated, in addition to the favorable analgesia effects for pain 
management, showing no difference in the harmful effect between the use of general, spinal 
and analgesia. local[5]. 
The effect of the use of various analgesics on pain control in procedures similar to knee 
arthroscopy has previously been studied[6-10]. 
 
After arthroscopy that does not include a procedure such as anterior cruciate ligament, tibial 
tuberosity osteotomy, medial patellofemoral ligament or meniscus surgery, a median opioid 
consumption corresponding to 11.3 (0-52) pills has been reported[11]. 
 
Acute pain (Outcome) 
Pain has been defined as an unpleasant emotional experience associated with tissue 
damage, not just a primary sensation; and like any emotional experience, it is 
subjective[12], [13]. Only the patient himself knows his pain and how much it hurts, 
therefore any assessment of pain must include the report of the subject suffering from the 
pain [13]. The evaluation of acute pain, being a time-limited, unidimensional and short 
event, is easier to measure, is easily reproducible and is not significantly affected by other 
variables[13]. 
It is not possible to extrapolate experimentally produced pain to situations where the pain is 
caused by a pathological process in the patient, because the patient's psychological state, 
associated with the pathology, is present[13]. 
 
Pain assessment 
Subjective measurement is the most frequently used way to measure pain; Unidimensional 
methods only assess intensity and treat pain as a single or simple dimension[13]. 
In order to standardize the evaluation of outcomes of experimental studies and the choice of 
optimal measurement instruments within different contexts of clinical epidemiology, 
initiatives have emerged, such as the COMET initiative[14], from the English “Core 

Outcome Measures in Effectiveness Trials”. ” and COSMIN (COnsensus-based Standards 
for the selection of health Measurement INstruments)[15]. After a search to identify the 
best tool for the evaluation of pain in the present study in the different bases of the 
standardization initiatives for evaluating outcomes, first in the database of the COMET 
initiative[16], no results were seen. of valid measurement instruments when performing a 
general search with the terms “Pain” and Knee (knee), or when searching for the terms 
“Anesthesia and pain control”[17]. However, in the COSMIN initiative's database of 
measurement instruments for patient-reported outcomes, a search with the term “knee” 
(Patient-reported outcome measures for the knee)[18] returned a search result, which 
describes measurement properties of various instruments used in patients with various knee 
procedures or conditions[19], including the VAS. 
 
Visual analogue scale 
The visual analogue scale (VAS) was described and devised in 1976. It consists of a 10 cm 
line that continuously represents the pain spectrum[13]. The line can be displayed 
horizontally or vertically, with right-angled endings at the ends, where the descriptions “No 
pain” and “The worst pain imaginable” appear (Figure 1) [13]. The patient is free to 
indicate the intensity of his or her pain sensation on the continuous line, which constitutes 
the main advantage of the measurement method[13]. In the evaluation of patellofemoral 
pain, the reliability of the VAS is 0.95-0.96, measuring the ability to identify the change in 
pain intensity in various periods of time (test-retest)[19]. 
No Pai 
The worst 
imaginable 
pain 
 
Figure 1. EVisual Analogue Scale (VAS) 
Ropivacaine 
Ropivacaine is a long-acting amide local anesthetic that began clinical use in 1996.[20] 
Structurally, it is chemically similar to bupivacaine and mepivacaine, because they are 
derivatives of “pipecoloxylidide” (name not defined in Spanish), however, ropivacaine, 

being the agent with the lowest lipophilic behavior of its peers, is characterized by lower 
toxicity. systemic when compared with bupivacaine and levobupivacaine[21]–[23]. 
The possible benefits of ropivacaine have been studied in different contexts: 1) in 
infiltration anesthesia[20], 2) in peripheral neural blockade (sciatic and femoral 
nerves)[24], [25]; 3)continuous postoperative analgesia[26]–[29]; 4) intra-articular 
application[30], [31]. 
 
Until now, the efficacy (comparison against placebo or non-active substance) of 
ropivacaine in the control of pain after knee arthroscopy has not been evaluated. However, 
the results of the efficacy or efficiency of active substances similar to ropivacaine have 
been studies [32-41]. Ropivacaine, such as bupivacaine or levobupivacaine in pain control, 
in different strata of the population that has undergone knee arthroscopy, as well as the 
adverse effects and limitations of studies previously carried out in the population of interest 
for this study. 
 
Research question 
What is the analgesic effect of the intra-articular administration of 0.2% ropivacaine vs 
0.75% ropivacaine in the immediate postoperative period of knee arthroscopy in acute 
injuries? 
 
Justification 
The prevalence of moderate-severe pain in post-knee arthroscopy patients is 71.2%. The 
prevalence of acute postoperative pain is 37.5% and chronic pain is 37.7%, exceeding the 
prevalence compared to that of other surgical procedures of different specialties. 
This study will provide evidence regarding the effect of an anesthetic on postoperative pain 
control, as well as the effects on reducing opioid consumption and patient mobilization. 
The administration of opioids is part of a common practice in pain management, however it 
represents a risk for patients due to their adverse effects and high risk of dependence. It is 
necessary to look for alternatives that reduce opioid consumption in postoperative patients, 
taking care of the cost-benefit for the patient as well as for health institutions. 

The reduction in postoperative pain with the applied strategies that has been observed is up 
to 30% in the immediate postoperative (1st measurement), 20% at 8 hrs (2nd measurement) 
and 10% at 24% (3rd measurement). 
 
Objectives 
General objective: 
- To evaluate the analgesic effect of the intra-articular administration of 0.75% ropivacaine 
in the immediate postoperative period of knee arthroscopy in acute injuries. 
 
Specific objectives: 
- To evaluate the effect of intra-articular administration of 0.75% ropivacaine in reducing 
opioid consumption in the immediate postoperative period of knee arthroscopy in acute 
injuries. 
- To evaluate the effect of intra-articular administration of 7.5% ropivacaine on mobility in 
the immediate postoperative period of knee arthroscopy in acute injuries. 
 
Hypothesis 
The Intraarticular administration of 0.75% ropivacaine reduces acute pain by 30% in 
postoperative knee arthroscopy patients in acute injuries. 
 
Methods 
All patients with acute knee articular cartilage lesions who attend the Orthopaedic and 
Trauma Center of the ABC Medical Center will be invited to participate, under the scrutiny 
of a sole surgical team. 
 
Selection criteria 
-Mental health: healthy (not taking any medication) 
-Articular cartilage lesion Grade I, II or III by Outerbridge 
-Elective knee surgery 
-Patients with any of the following diagnoses: 
-Simple menisc lesion 

-Lesion of a single knee (unilateral) 
 
 
Exclusion criteria 
-Neuromotor diseases (alterations in step, strength or sensitivity) 
-History of knee surgery (orthopedic) 
-Instability that includes knee ligament lesions 
-Addictions 
-Mental diseases in medical treatment 
-Hepatic diseases 
-Allergy to any of the medications used in the study 
-Epidural or peridural anesthesia 
-Chronic pain in treatment 
-Postoperative drain of knee arthroscopy 
-Pregnant or lactating 
 
 
Model description 
After confirming that the patients meet the selection criteria, they will be invited to 
participate in the study. Upon accepting through signed informed consent, the physician in 
charge of randomization (physician 1) will be informed and the surgery scheduled. The day 
of the surgery, the physician in charge of randomization will report the maneuver to be 
received from the anesthesiologist (physician 2) in charge, who will prepare the dose of 
ropivacaine and give it to a physician blinded to the maneuver (physician 3); this physician 
will apply the ropivacaine intraarticular to the patient. The level of pain will be evaluated 
two hours after the end of surgery by a physician blinded to the maneuver the patient has 
received (physician 4), while the patient is in his room, and the presence of acute-moderate- 
severe pain (4-10 points) is evaluated by a visual analog scale (EVA) while the patient is 
requested to flex and extend the knee. 
 
Randomization: 
 
Randomization will be performed by number generator software OxMaR (Oxford 
Minimization and Randomization). 

Blinding: 
 
Blinding will be performed once the patient will agree to participate; the physician in 
charge of randomization will inform the anesthesiologist of the maneuver that corresponds 
to the patient programmed for surgery, who will prepare the dose for the patient and hands 
it to the physician who will apply the maneuver (who is blinded to the maneuver). All 
patients will receive 10 ml of solution with different doses of ropivacaine, the application 
vehicles being equal in physical appearance. The physician who will evaluate the outcome 
will not participate in the randomization, surgery or application of the maneuver, and will 
remain blinded to the dose the patient receives, as does the patient. 
 
Maneuver 
Knee arthroscopy will be carried out by 2 orthopedic surgeons trained in arthroscopic surgery and 
with minimum experience of 10 years. 
 
The application of ropivacaine will be performed at the end of the surgical procedure, once the 
arthroscopic portals are sutured, the main surgeon for the infiltration is given, according to the 
randomization, 10 ml of ropivacaine at 0.2% or 10 ml of ropivacaine at 0.75%, as may be the case, 
which will be administered with the anesthesized patient by intraarticular via in the knee (in the 
anatomical level of the upper pole of the ball joint, under the iliotibial band). Once the infiltration is 
complete, placement of gauze and simple bandage procedes, and once the anesthesiologist indicates, 
the patient is passed to recovery, where the evaluation of outcomes (no-slight pain / moderate severe 
pain) will be performed. 
 
 
Exit from the study: 
-Any transoperative event that requires the suspension of surgery. 
-Any transoperative event that impedes the application of intraarticular ropivacaine. 
 
The patients in both arms receive 10 ml of intraarticular solution in the knee (at the 
anatomical point at the level of the upper pole of the ball joint, under the iliotibial band), 
with different content of ropivacaine; the vehicle for application presents the same physical 
appearance for all patients and is applied by previously standardized treating physicians. 
 
Sample size 
Expecting an absolute difference, an absolute difference of 30% is expected for the presence of 
moderate-severe pain, considering a level of significance=5% and power=80%. Needed are 68 
subjects, 34 for each arm. 
Given that the evaluation of outcome is performed 2 hrs. after the application of the maneuver, and 
due to the low incidence of postoperative anesthetic complications, loss of information is estimated 
at <1%. 
 
Sample size and statistical analysis: Sample size was estimated to establish a difference of 
30% in considering the presence of moderate-severe pain among patients treated with 
different doses of ropivacaine, considering an alpha level of 0.05 and beta of 0.20. Required 

were 68 patients divided into two groups of 34 each. Loss of information was expected at 
<1%, and 2 subjects were added to the sample size, increasing the requirement to 70 subjects 
in total. For statistical analysis, the statistical program SPSS version 27 will be used (IBM 
Armonk, New York). Contrast of the incidence of outcomes between the two groups by 
different doses of ropivacaine will be carried out by X2 or Fisher exact test, when necessary. 
Multivariate analyses will be performed by logistic regression analysis, considering a value 
of p<0.05 as significant, and double gradient differences in exposure to different variables 
between treatment groups were included in multivariate analysis. 
In the intention-to-treat analysis (ITT), the main and secondary outcomes will be contrasted 
between the groups, considering the randomization of the different doses of ropivacaine, and 
in the per-protocol analysis (PP), the results of the incidence of moderate-severe pain will 
be contrasted between groups formed by randomization; however, those that received opioids 
in the first 2 hours post-surgery will be excluded, in order to know the effect of the use of 
ropivacaine at 7.5% without the effect of a conjugate maneuver. 
 
Variables to be evaluated 
 
 
Dependent variable 
Pain (Primary 
outcome) 
Conceptual definition: Sensory and emotional experience associated 
with a present or potential injury or a described one. 
Operational definition: The sensation of painful discomfort at the 
surgical site (Mild, moderate or severe). 
Type of variable: Dichotomous qualitative. 
Measuring instrument: VAS (0-10 points) 
Measurement units: Mild 0-3 points, moderate-severe 4-10 points. 

Opioid use 
Conceptual definition: Drug whose analgesic action is produced 
thanks to the interaction with the opioid receptors of the neurons of the 
central nervous system. 
Operational definition: According to the VAS pain score 
administration of Tradol dose of 50mg IV. 
Type of variable: Qualitative dichotomous 
Measuring instrument: Information extracted from the patient's file. 
Measurement units: Not use / Use. 
Mobility 
Conceptual definition: Amplitude of joint oscillation within natural 
limits. 
Operational definition: The active mobility performed by the patient 
in the postoperative period. 
Variable type: Dichotomous qualitative. 
Measuring instrument: Observation made by the doctor in the 
postoperative period after the indication of flexion and extension of the 
leg, elevation and descent of it actively before the doctor. 
Measurement units: Present / absent. 
Independent variable 
Ropivacaine 
0.75% 
Conceptual definition: Long-lasting amide-type local anesthetic with 
lower lipid solubility. 
Operational definition: IA administration to the knee of 10 ml of 
0.75% ropivacaine. 
Variable type: Dichotomous qualitative. 
Measuring instrument: Experimental maneuver. 

Measurement units: No / Yes 
Ropivacaine 
0.2% 
Conceptual definition: Long-acting amide-type local anesthetic with 
lower lipid solubility 
Operational definition: IA administration to the knee of 10 ml of 0.2% 
ropivacaine. 
Variable type: Dichotomous qualitative. 
Measuring instrument: Experimental maneuver. 
Measurement units: No / Yes 
Peripheral variables/covariates/Probable confounders /Probable interactors 
Sex 
Conceptual definition: Organic condition of the individual. 
Operational definition: Identification of the individual as Male or 
Female. 
Type of variable: Dichotomous qualitative. 
Measurement units: Male / Female. 
Age 
Conceptual definition: Time lived by a person. 
Operational definition: 18-35 years; 36 – 60 years. 
Variable type: qualitative ordinal 
Measurement units: 18-35; 36-60 
BMI 
Conceptual definition: Mathematical reason that associates weight and 
height. 
Operational definition: 1. normal weight BMI<25 vs 2. overweight 
BMI≥25 

Variable type: qualitative ordinal 
Measurement units: kg/m 2 
Time 
of 
evolution 
Conceptual definition: Duration from the onset of symptoms or their 
detection 
Operational definition: 1. <4 weeks and 2. >5 weeks 
Variable type: qualitative ordinal 
Measurement units: number of weeks 
Physical 
activity 
Conceptual definition: Any body movement produced by skeletal 
muscles that requires energy expenditure 
Operational definition: active vs sedentary 
Variable type: dichotomous qualitative 
Measurement units: 0-1 
Etiology 
of 
surgery 
Conceptual definition: Cause of the organism before the disease 
Operational definition: traumatic vs degenerative 
Variable type: dichotomous qualitative 
Measurement units: 0-1 
Duration 
of 
Surgery 
Conceptual definition: Time spent performing interventions inside and 
outside the human body 
Operational definition: 1. <45 min and 2. ≥ 45 min 
Variable type: qualitative ordinal 
Measurement units: minutes 

Type 
of 
articular 
cartilage injury 
Conceptual definition: Description of the different degrees of 
chondropathy 
Operational definition: I: 0mm, II: < 0.5mm and III : >0.5mm 
Variable type: qualitative ordinal 
Measurement units: millimeters 
 
 
 
 
 
 
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