Intra-Articular Morphine versus Dexmedetomedine for Knee Arthroscopy under Local Anesthesia.

BACKGROUND: Knee arthroscopy has both diagnostic and therapeutic applications which can be performed under general, regional, or local anesthesia. Morphine is used as an additive to local anesthetics. Dexmedetomedine, the highly selective alpha-2 (α2)-adrenoceptor agonist with the sedative and analgesic effect can be used also to augment local anesthetic effect. PATIENTS AND METHODS: Sixty patients submitted for elective knee arthroscopy whose age between 25 and 45 years, of either sex, the American society of anethesiologists physical status Classes I and II at a university hospital were enrolled in this study. Patients were classified into two groups. Morphine Group (M) (n = 30): Patients received 20 ml of 0.5% bupivacaine plus 5 ml of 0.2% lidocaine with epinephrine 1:200,000 plus 1 mg morphine. Dexmedetomedine Group (D) (n = 30): Patients received 20 ml of 0.5% bupivacaine plus 5 ml of 0.2% lidocaine with epinephrine 1:200,000 plus 1 μg/kg dexmedetomedine.
RESULTS: Demographic data of patients showed no significant difference among the studied groups. Heart rate (HR) was significantly lower in (D) Group compared to that of (M) Group 5 min from the start of procedure to immediately postoperatively. Moreover, (D) Group showed a significant decrease in HR 10 min up to 35 min intraoperatively compared to the basal value. Furthermore, mean arterial blood pressure (MBP) was significantly lower in (D) Group compared to that of (M) Group 15 min from the start of surgery up to 1 h postoperatively. Furthermore, (D) Group showed a significant decrease in MBP 15 min intraoperative up to 2 h postoperatively compared to the basal value. While there was no significant difference in (visual analogue score [VAS], onset and total consumption of ketorolac, surgeon and patients' satisfaction, side effects in (D) Group compared to (M) Group, respectively.
CONCLUSION: Addition of either morphine or dexmedetomidine to bupivacaine intraarticularly improved both intraoperative anesthesia and postoperative analgesia with minimal side effects or complications in knee arthroscopy, with superiority of dexmedetomidine compared to morphine on hemodynamic stability.

INTRODUCTION

One of the most common orthopedic procedures is knee arthroscopy; it has both diagnostic and therapeutic applications. Knee arthroscopy has become the gold standard for the diagnosis and management of meniscal and ligamentous injuries.[1]

General, regional, or local anesthesia could be performed for knee arthroscopy. However, to provide faster discharge times, epidural anesthesia, and peripheral nerve block both had provided more rapid discharge than general anesthesia in previous reports, spinal anesthesia also has shown rapid discharge when compared to general anesthesia.[2]

The use of local anesthesia started to be mentioning over the past few decades,[3] but still considered inferior to other forms of anesthesia, may be due to the fear of insufficient anesthesia or because of a bad patient experience.[4] In fact it prevents any pain sensation during knee surgery, the patient is conscious throughout the procedure and discharged soon.[5] It also gives the advantage of postoperative analgesia, increased blood flow to extremities, there is also theoretical decrease in reflex sympathetic dystrophy, decreased the common side effects of analgesics as nausea, vomiting, drowsiness, and urine retention.[6]

The intra-articular (IA) opioids as a therapeutic option arose when experimental studies identified mobilization of opioid receptors in peripheral tissues induced by inflammatory stimuli, whose effects are reversible by the administration of the specific opioid antagonist. Anti-inflammatory effects on the synovial tissue, producing analgesia similar to that of dexamethasone, as well as the reduction in the number of leukocytes in the chronically inflamed joint, were also observed.[7]

Dexmedetomedine, the potent and highly selective alpha-2 (α2)-adrenoceptor agonist, also has sympatholytic, sedative, amnesic, and analgesic properties.[8] The mechanism by which dexmedetomedine mediates IA analgesia is not clearly defined. However, it might be similar to those suggested for IA clonidine.[9] Clonidine may act on α2-adrenergic presynaptic receptors and inhibit the release of norepinephrine at peripheral afferent nociceptors. It can provide local anesthetic effects by inhibiting the conduction of nerve signals through C and Ad fibers and may stimulate the release of enkephalin-like substances at peripheral sites. Furthermore, the analgesic effect of clonidine could be mediated through the modulation of the opioid-analgesic pathway.[10]

We hypothesize that IA morphine may be more effective than dexmedetomedine as an adjuvant to local anesthesia during knee arthroscopy.

PATIENTS AND METHODS

After obtaining approval of the Institutional Review Board (IRB) of anesthesia and surgical Intensive Care Department, Faculty of Medicine (IRB number R/16674), a written informed consent was obtained from all patients before enrollment in this study. This randomized this prospective, double-blind, randomized controlled study was conducted during the period between June and September 2016 on 60 patients submitted for elective therapeutic knee arthroscopy whose age between 25 and 45 years, of either sex, the American society of anethesiologists (ASA) physical status Classes I and II. This randomized controlled trial was based on the revised CONSORT statement.[11] Randomization was achieved through sealed opaque envelops to avoid bias.

This study aimed to compare the effect of adding dexmedetomidineor or morphine to an infiltration mixture of (bupivacaine, lidocaine, and epinephrine) local anesthesia for knee arthroscopy. The primary outcome measure was the total consumption of intravenous ketorolac given during the first 24 h after surgery. The secondary outcome measures were time to first request of intravenous ketorolac, intensity of pain during rest and activity, side-effects, time for hospital discharge.

Inclusion criteria

Adult patients of the ASA physical Status I and II aged 20–45 years of either sex who were submitted for elective therapeutic knee arthroscopy were included in the study.

Exclusion criteria

Patient refusal, allergy to the used drugs, psychological problems, any previous surgery to the knee, Patients with chronic extensive synovitis or on continuous treatment for pain control, infection at the portal sites of injection. Furthermore, patients with bleeding diathesis or coagulopathy were excluded from the study.

Preoperative assessment

Preoperative assessment included medical history, clinical examination, laboratory investigations, including complete blood count, bleeding profile, blood glucose level, liver and renal function tests, and electrocardiogram (ECG). The procedure was explained to the patient together with the visual analog scale (VAS) where 0 represents no pain and 10 represents the worst pain imaginable.

Sample size

Using G * Power software version 3.1.9.2 (Christian-Albrechts-Universität, Kiel, Germany), adopting a 40% decrease in the requiring postoperative analgesia as an accepted effect size, it was found that a sample size of 51 patients was required to achieve a power of 80% and alpha error of 0.05. Additional nine patients were added to compensate for dropouts making total sample size of 60 patients, 30 patients per each group.

Methods

Eligible patients were randomly allocated into two groups by a closed envelope technique using a computer generated block randomization method in blocks of 10. The computer randomization was performed and the allocation resulted in individual numbered and sealed envelopes before the study.

Morphine Group (M) (n = 30): Patients received a volume 20 ml of 0.5% bupivacaine plus 5 ml of 0.2% lidocaine with epinephrine 1:200,000 plus 1 mg morphine

Dexmedetomedine Group (D) (n = 30): Patients received a volume 20 ml of 0.5% bupivacaine plus 5 ml of 0.2% lidocaine with epinephrine 1:200,000 plus 1 μg/kg dexmedetomedine (Emcure Pharmaceuticals, India).

In the operating room, patient had an intravenous line in a suitable peripheral vein. Patient was monitored by 3-lead ECG, oximetry and noninvasive blood pressure every 10 min.

All the baseline parameters, including mean blood pressures (MBP), heart rate (HR), and peripheral arterial oxygen saturation (SpO2) were observed and recorded.

The anesthetic technique was standardized for all patients. All surgical procedures were done by the same surgeon. The IA local anesthesia was prepared by an individual not involved in the study and injected by the surgeon without knowing the contents.

After cleaning the skin with a sterilizing solution, the skin and the subcutaneous tissues at antero-medial and antero-lateral portal sites were anesthetized with local anesthesia formed of a mixture of 5 ml 2% lidocaine with 1:200,000 epinephrine at each portal site. The spread of IA solution is encouraged by flexion and extension of the knee joint several times. Then, 20 min are allowed for anesthesia to take effect. The time corresponding to the end of this 20 min will be recorded as baseline for the time interval. Adrenaline could be mixed into the irrigation fluid (10 ml of 1:10,000 adrenaline into 3 l of irrigation fluid) to help in hemostasis.[12]

In the postanesthesia care unit; cardiorespiratory values are monitored ECG, SpO2, MBP, and respiratory rate.

Intraoperative

MBP, HR and peripheral SpO2 were recorded every 10 min till the end of surgery

Intra-operative side effects such as nausea, vomiting, bradycardia, and hypotension also were recorded.

Postoperative

Duration of surgery

HR and MBP were recorded 15 and 30 min and 1, 2, 4, 6, and 12-h postoperative

Any postoperative side effects or complications

Visual analog scale (VAS) on 0–10 cm scale at 1, 2, 4, 6, 12, and 24 h, where a score of 0 represents no pain and 10 is the worst pain imaginable[13]

Total analgesic consumption and the onset of first intravenous analgesia (30-mg ketorolac) required if visual analog Scale score is ≥4 or the patient requests analgesia in the first 24 h

Surgeon satisfaction score (satisfaction visual analogue score) from 0 (not satisfied) to 100 (entirely satisfied) at 24 h[14]

Patients’ satisfaction which is measured by asking them to describe the level of pain control during surgery and whether or not they would like to have any future arthroscopic knee procedures performed by this way (patients’ satisfaction score 1 = very satisfied, 4 = very unsatisfied.[15] Little irritability managed by assurance and sedating dose of propofol (0.05 mg/kg), but sever irritability that obstacles the surgical maneuver and means failed technique, turned to general anesthesia.

Statistical analysis

The statistical analysis of data was performed using Excel program for Figures and SPSS (for IBM) Program the Statistical Package for the Social Science version 21 (IBM Corp, Armonk, NY, USA). The description of the data was done in the form of frequency and proportion for qualitative data and mean ± standard deviation for quantitative data. The normality of distribution was tested by the Kolmogorov–Smirnov test and Shapiro–Wilk test. The analysis of the data was performed to test statistical significant difference between groups. For nonparametric data, the Mann–Whitney test was used to compare between two groups. For quantitative parametric data, independent ttest was used to compare between two groups, and Chi-square test was used for qualitative variable or odds ratio and 95% confidence interval were calculated. P is considered as statistically significant if ≤0.05 at confidence interval 95%.

RESULTS

After statistical analysis of the collected data the results demonstrated that the demographic data of patients showed no significant difference among the studied groups, regarding age, sex, body weight, height, ASA and duration of the procedure, [Table 1].

Table 1

Demographic data of the studied groups

Items	M Group (n=30)	D Group (n=30)	P
Age (years)	26.23±11.45	28.73±14.28	0.45
Sex, n (%)
Male	19 (63)	17 (57)	0.52
Female	11 (37)	13 (43)
Weight (kg)	78.36±21.03	74.03±32.36	0.54
Height (cm)	171.77±26.52	165.87±35.44	0.46
ASA I, n (%)	24 (80)	27 (90)	0.12
ASA II, n (%)	6 (20)	3 (10)	0.65
Duration of surgery (min)	23±8	25±10	0.75

Data are presented as mean±SD. SD=Standard deviation, ASA=American society of anethesiologist, M Group=Morphine group, D Group=Dexmedetomedine group

HR in [Figure 1] was significantly lower in (D) Group compared to (M) Group 5 min after starting the procedure till immediately postoperatively with P = 0.03. Moreover Group (D) showed a significant decrease in HR 10 min from starting surgery up to 35 min intra-operatively compared to the basal value, with P ≤ 0.05.

Figure 1

Heart rate changes in the studied groups. Significant when (P ≤ 0.05). Significant between the 2 groups. Δ Significant compared to the basal value

Also, arterial MBP was significantly lower in (D) Group compared to (M) Group 15 min after the start of surgery up to 1 h postoperatively with P = 0.002. Also (D) Group showed a significant decrease in MBP 15 min after the procedure up to 2 h postoperatively compared to the basal value (P ≤ 0.05) [Figure 2].

Figure 2

Mean arterial blood pressure of the studied groups. Significant when (P ≤ 0.05). Significant between the 2 groups. Δ Significant compared to the basal value

Figure 3 showed no significant change in VAS values between the studied groups.

Figure 3

Visual Analogue Score of studied groups. Significant when (P ≤ 0.05)

Table 2 showed no significant difference in the onset and the total analgesic consumption of ketorolac in (D) Group compared with (M) Group with P = 0.058 and 0.061 respectively.

Table 2

Onset (h) and total dose analgesia of ketorolac (mg)

	M Group (n=30)	D Group (n=30)	P
Onset of analgesic request (h)	14.31±4.71	11.50±6.42	0.058
Total analgesic consumption (mg)	48.5±17.1	57.4±21.4	0.061

Data are presented as mean±SD. SD=Standard deviation, M Group=Morphine group, D Group=Dexmedetomedine group

Also, Table 3 showed no significant change in both surgeon and patient satisfaction among the studied groups with P = 0.37.

Table 3

Surgeon and patients’ satisfaction score

Items	M Group (n=30)	D Group (n=30)	P
Surgeon satisfaction score (0-100)	70.4±2.6	80.2±1.8	0.17
Patient satisfaction score (1-4)	2.8±1.5	2.3±1.7	0.37

Data are presented as mean±SD. SD=Standard deviation, M Group=Morphine group, D Group=Dexmedetomedine group

And Table 4 showed the incidence of side effects in the studied groups as: nausea, vomiting, bradycardia and hypotension with no significant change.

Table 4

Presence of side effects in the studied groups as: Postoperative nausea and vomiting, bradycardia, and hypotension

Side effects	M Group (n=30), n (%)	D Group (n=30), n (%)	P
PONV	5 (16)	2 (7)	0.92
Hypotension	2 (7)	5 (16)	0.92
Bradycardia	0 (0)	4 (13)	0.73

Data are presented as n (%). PONV=Postoperative nausea and vomiting, M Group=Morphine group, D Group=Dexmedetomedine group

DISCUSSION

General and spinal anesthesia were the preferred method of anesthesia for arthroscopic knee surgery.[3] Recently local anesthesia, has gained acceptance because of its low cost, time saving, and safety.[5]

Our study showed a significant decrease in HR and blood pressure in the D Group compared to the M Group either intra-or postoperatively. A local anesthetic injection has a limited direct effect on hemodynamics. Its indirect effect may be attributed to decreasing pain intensity by analgesic effect caused by adding dexmedetomidine to bupivacaine compared to morphine, This was in agreement with Perritt et al.,[16] who studied the effect of IA α-agonists for arthroscopic knee surgery and found that hypotension and bradycardia are associated with the use of α-2 agonists, given either systemically or peripherally.

VAS showed a no significant changes in D Group compared to M Group either intra-operatively, at closure time or postoperatively. Although morphine either locally or intravenously can reduce pain produced by knee arthroscopy as concluded before by many studies.[7] However, recent studies search for other drugs which may help in this aspect like dexmedetomidine.

In agreement with our study. Another research group[17] studied the effect of IA bupivacaine/dexmedetomidine after knee arthroscopy and found it superior to bupivacaine alone with lower VAS scores both at rest and during movement. Moreover, Perritt et al.,[16] concluded that α2 agonists increases the duration of analgesia with reduction in pain intensity as evidenced by low VAS scores up to 24 h after surgery. Another study[18] concluded that IA dexmedetomidine and local anesthetic showed a decrease in opioid use during the first 24 h after the procedure, while the VAS decreased only up to 6 h postoperatively. Another support to our results are two different studies evaluated the efficacy of IA dexmedetomidine and they concluded that IA dexmedetomidine in a dose of 1 μg/kg alleviates postoperative pain, reduces the need for narcotics as analgesics and increases the time to first analgesic request.[1920]

The analgesic requirements displayed a nonsignificant change in D Group compared to M Group in our study. This is in agreement with Ismail et al.[21] who compared intrathecal and IA dexmedetomidine regarding postoperative pain following knee arthroscopy, and they found that IA dexmedetomidine improved the quality and duration of postoperative analgesia and reduced postoperative analgesic consumption. The mechanism is not fully understood, but it might be similar to that suggested for clonidine effect on α 2 adrenergic presynaptic receptor inhibiting the release of norepinephrine at peripheral afferent nociceptors. Dexmedetomidine also has a local anesthetic effect by inhibiting nerve impulses through C and Aδ fibers with an analgesic effect via modulation of opioid analgesic pathway and stimulation of enkephalinlike substance at peripheral sites. Also, different studies found that dexmedetomidine as an additive to local anesthetics, demonstrated a dose dependent prolongation of sensory block, increase in motor block, along with prolongation of the postoperative analgesia, thus allowing for a decrease in the local anesthetic dose in the studied patients.[172223]

Both surgeon and patient satisfaction score demonstrated nonsignificant changes in D Group compared to M Group in our study which agrees with Al-Qtaibi[4] in his study on knee arthroscopy under local anesthesia where he found that arthroscopy under local anesthesia is an effective, safe method for treating selected knee pathologies, with both patient and surgeon satisfaction >90%.

On the other hand, Forssblad and Weidenhielm[24] concluded that 0.9% of primary arthroscopies performed under local anesthesia could not be done safely because of patient discomfort. Nevertheless, they found no difference in the frequency of re-arthroscopy between operations performed under local anesthesia and those under general anesthesia.

Complications as hypertension, nausea, vomiting, sweating, sedation, hypotension, bradycardia or intolerable pain were comparable in both groups. Nausea and vomiting were treated using ondansetron 8 mg intravenously as a single dose. This result was in agreement with Paul et al.[25] where they concluded that no significant side effects were noted with dexmedetomidine.

Regarding the possible side effects Perritt et al.[16] conducted that local anesthetics may have possible side-effects. There have been reports of postoperative chondrolysis after arthroscopic shoulder and ankle surgery. Chondrolysis is a condition in which extensive loss of articular cartilage occurs over a relatively short period of time. The pathogenesis is unclear, and the condition is rare, but a number of experimental studies have suggested that LA may damage articular cartilage. Addition of an α-2 agonist appears to improve postoperative analgesia and thus allows a reduction in concentration of LA to be used. This may reduce the risk of chondro-toxicity, which can be debilitating in young athletes.

Our study have points of strength

First it is comparing efficacy of IA morphine or dexmedetomidine under local anesthesia alone, not spinal or general anesthesia. Also up to our knowledge no comparative study between them was performed in humans but in animals only.[26] Moreover a good sample size was done for our patient with randomization and blinding.

Our study have some limitations

First, there was no control group who received bupivacaine alone. This may be attributed to we want to compare which is a more effective adjuvant, morphine or dexmeditomidine as both of them proved to improve the efficacy of local anesthetics. Also higher doses of both morphine and dexmeditomidine may be added in further studies for a more favourable effects.

CONCLUSION

Addition of either morphine or dexmedetomidine to bupivacaine intra-articularly improve both intraoperative anesthesia and postoperative analgesia with limited side effects or complications in elective knee arthroscopy, with superiority in hemodynamic stability of dexmedetomidine compared to morphine.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.