Analgesic Effects of Intraarticular Sufentanil and Sufentanil Plus Methylprednisolone After Arthroscopic Knee Surgery

Abstract

We studied the effect of intraarticular saline, sufentanil, or sufentanil plus methylprednisolone after knee arthroscopic meniscectomy. In a double-blind randomized study, 60 patients undergoing knee arthroscopic meniscectomy were allocated to groups receiving intraarticular saline, intraarticular sufentanil 10 μg, or sufentanil 10 μg plus methylprednisolone 40 mg at the end of arthroscopy during general anesthesia. Postoperatively, pain levels at rest and during movement (i.e., active flexion of the knee) were measured by a visual analog scale and were significantly decreased in the sufentanil and sufentanil plus methylprednisolone groups compared with the control group. Moreover, we found that there was a significant reduction in intraarticular sufentanil and sufentanil plus methylprednisolone in the postoperative consumption of analgesics. We also found that the use of intraarticular sufentanil or sufentanil plus methylprednisolone after knee arthroscopic meniscectomy decreases the amount of supplementary analgesic needed for pain relief during the early postoperative period. In addition, we detected that sufentanil provided prolonged pain relief up to 24 h when compared with control, whereas when we combined sufentanil plus methylprednisolone, we found that it further reduced pain and use of analgesics when compared with sufentanil.

In Brief

IMPLICATIONS: The combined use of intraarticular sufentanil (10 μg) and methylprednisolone (40 mg) in arthroscopic meniscectomy surgery reduced both postoperative pain scores and the use of additional analgesics.

Knee arthroscopy is a very common procedure. Many different methods have been used in an effort to provide adequate analgesia after knee surgery ^(1–4). The degree of postoperative pain varies, and in an effort to find the ideal regime for sufficient postoperative analgesia of long duration with no side effects many clinical studies have been published on intraarticular administration of different drugs in various doses, volumes, and combinations ^(1–6). The question of peripheral opioid receptors has been raised in the context of intraarticular administration of opioids ^(1,7,8).

Opioids administered intraarticularly have been studied with regard to their analgesic efficacy ⁽⁹⁾. Some reports showed intraarticular opioids to be ineffective ^(9,10); others reported a significant positive effect on postoperative analgesia ⁽²⁾. We chose sufentanil because of its greater lipophilic characteristics, which should provide a faster onset of analgesia than morphine ⁽¹¹⁾. Intraarticular glucocorticoid may improve pain relief after meniscectomy ⁽¹²⁾.

The aim of this study was to assess the effect of sufentanil or sufentanil plus methylprednisolone on the postoperative pain and analgesic requirements after arthroscopic meniscectomy.

Methods

After approval by the local ethical committee, informed patient consent was obtained from all study patients. Sixty ASA physical status I–II patients scheduled for knee arthroscopic meniscectomy were included in this study.

The exclusion criteria included daily intake of steroids, nonsteroidal antiinflammatory drugs (NSAIDs) or opioids, relevant drug allergy, and the need for postoperative intraarticular drainage.

All operations were performed under general anesthesia, which was induced with fentanyl 1–1.5 μg · kg⁻¹ and propofol 2.0 mg · kg⁻¹ IV. Tracheal intubation was facilitated with vecuronium 0.1 mg · kg⁻¹, and anesthesia was continued with propofol and breathed N₂O 70% and O₂ 30% by means of the endotracheal tube. After 10 min the dose of propofol was 10 mg · kg⁻¹ · h⁻¹, then 8 mg · kg⁻¹ · h⁻¹ for 10 min, then reduced to 6 mg · kg⁻¹ · h⁻¹ for the rest of the procedure. A thigh pneumatic tourniquet was applied during surgery and until 10 min after the intraarticular injection of the tested drug into the knee joint at the end of the procedure.

Before the arthroscope was removed, patients were randomly assigned to 3 groups for double-blind administration of the tested drug. Group A (n = 20), the control group, received 20 mL isotonic saline intraarticularly and 10 μg sufentanil in 5 mL of isotonic saline IV, Group B (n = 20) received sufentanil 10 μg in 20 mL of isotonic saline intraarticularly and 5 mL isotonic saline IV, and Group C (n = 20) received sufentanil 10 μg plus methylprednisolone 40 mg ⁽¹³⁾ in 20 mL of isotonic saline intraarticularly and 5 mL isotonic saline IV.

The test drug was given to the surgeon who performed the injection through the arthroscope at the end of the procedure (without knowing the contents) to ensure that the drug would be delivered into the joint.

All patients were instructed preoperatively in the use of the 10-cm Visual Analogue Scale (VAS) for pain (0 = no pain to 10 = the worst pain) ⁽¹⁴⁾. Pain levels at rest and during movement (active flexion of the knee) were evaluated.

VAS scores were recorded preoperatively (T0), and at 30 min (T1), 90 min (T2), 180 min (T3), and 24 h (T4) after the intraarticular injection.

Supplementary analgesia—paracetamol 500 mg tablets orally—was given at patient request, and the time of administration was recorded. The occurrence of side effects such as nausea, vomiting, sedation, or pruritus was noted for each patient.

Statistical analysis was performed by the Mann-Whitney U-test, Wilcoxon’s test, LSD post hoc test, and the χ² test as appropriate. In all cases, P < 0.05 was considered to be significant. All data are presented as mean ± sd.

Results

Demographic data, duration of anesthesia, and tourniquet time are summarized in Table 1. With regard to demographic data, duration of anesthesia and tourniquet time, significant differences were not observed among Groups A, B, and C. No side effects were noted after the administration of intraarticular sufentanil and sufentanil plus methylprednisolone. No patient developed a postoperative infection.

Table 1: Patient Demographics and Duration of Anesthesia and Tourniquet Time

Difference of VAS scores at rest and during movement among Groups A, B, and C at each measuring time are shown in Figure 1 (at rest) and Figure 2 (during movement).

Figure 1.: Visual analog scale pain scores (median and range) at rest of each time period: T0 (preoperative), T1 (30 min), T2 (90 min), T3 (180 min), T4 (24 h). *P < 0.05, control compared with sufentanil; **P < 0.05, sufentanil compared with sufentanil plus methylprednisolone.

Figure 2.: Visual analog scale pain scores (median and range) during movement of each time period: T0 (preoperative), T1 (30 min), T2 (90 min), T3 (180 min), T4 (24 h). *P < 0.05, control compared with sufentanil; **P < 0.05, sufentanil compared with sufentanil plus methylprednisolone.

Postoperatively, pain scores during rest and movement were significantly higher in the control group than in the other two groups (P < 0.05) and the difference between the B and C groups were also significant (P < 0.05). Postoperatively, supplementary analgesic consumption was significantly decreased in the intraarticular sufentanil and sufentanil plus methylprednisolone groups (versus control group) (P < 0.05), and the difference between the B and C groups were also significant (P < 0.05) (Figure 3).

Figure 3.: Oral paracetamol (mg, mean ± sd) given at T1 (30 min), T2 (90 min), T3 (180 min), and T4 (24 h) postoperative periods. *P < 0.05, control compared with other two groups; **P < 0.05, sufentanil compared with sufentanil plus methylprednisolone.

Discussion

After knee arthroscopy, patients often suffer from pain. To reduce pain after arthroscopy NSAIDs ^(15,16), intraarticular bupivacaine and/or intraarticular morphine ⁽¹⁷⁾ have been used.

Opioid analgesia has been associated with the activation of opioid receptors in the central nervous system. Peripheral opioid receptors may be activated only in the presence of tissue inflammation and opioid-binding sites have been identified in synovial tissue, indicating that analgesia is locally mediated ^{(1,2,14,18,19)}.

The analgesic effect of intraarticular opioids after arthroscopy is controversial. Intraarticular administration of opioids such as fentanyl or meperidine did not result in a significant analgesic effect as compared with intraarticular morphine ⁽¹⁸⁾. However, other studies have revealed analgesic efficacy with intraarticular fentanyl ⁽²⁰⁾ as well as with intraarticular meperidine ^(21–23).

In our study, 10 μg sufentanil, another opioid, provided a postoperative analgesic administered intraarticularly. Because sufentanil is a highly lipophilic opioid, the delayed onset of analgesic effect occurring with morphine could theoretically avoided with sufentanil ⁽²⁾. In our study, we detected a fast onset of analgesia with the effect lasting up to 24 h postoperatively. Moreover, the consumption of postoperative analgesia in the sufentanil group was significantly less than in the control group. We detected that VAS scores of the sufentanil group in our measurement points were significantly lower than those of the control group. Giving intraarticular methylprednisolone acetate 40 mg also caused a further reduction of pain and use of supplementary analgesics, because a reduced swelling by administration of methylprednisolone may enhance the analgesic effect of sufentanil ⁽¹³⁾. Similarly, Wang et al. ⁽¹²⁾ found that in patients with osteoarthritis of the knee, 10 mg triamcinolone acetonide relieved pain for 24 hours after arthroscopic debridement and synovectomy. Infection is a potential complication in the use of intraarticular glucocorticoid administration. Montgomery and Campbell ⁽²⁴⁾ reported the incidence of septic arthritis to be 0.2% in patients treated with glucocorticoids. In our study, postoperative infection was not seen in any patient.

Sufentanil, a highly lipophilic drug, possibly enables a rapid penetration through the synovium into the bloodstream ⁽¹¹⁾. Therefore, we hypothesized that the control group should systemically receive the amount of sufentanil that is given for local block. In our study, 10 μg sufentanil was administered IV to the control group. A systemic analgesic effect of intraarticular sufentanil could be excluded because the control group had less pain relief postoperatively.

Volume is also related to intraarticular pressure. Excessive pressure may facilitate systemic absorption once the tourniquet is released ⁽¹⁾. The volume used in our study was the same that was used in previous studies ⁽²⁵⁾.

The application of tourniquet and the time of its removal may be related to the duration of the local action of the tested drug and the rate of opioid absorption from the joint ^(11,26). Thus, in our study, after the administration of the tested drug was completed in all patients, the tourniquet was kept inflated for 10 minutes.

Factors related to the severity of pain after knee surgery are the amount of surgical trauma, the residual effects of perioperative analgesia, and the sensitivity of methods for postoperative pain registration ⁽²⁷⁾. For this reason, all our patients experienced the same surgical trauma (arthroscopic meniscectomy) and surgical time.

To prevent any residual analgesic effects of opioids that were used during induction, we applied the same analgesic technique in all our patients. In addition, to obtain accurate registration of the pain scores and the required supplementary analgesia, our patients stayed at the hospital during the entire period of the study.

We conclude that intraarticular administration of sufentanil alone and the combination of sufentanil and methylprednisolone after knee meniscectomy are effective, reliable, and well-tolerated analgesic techniques. Sufentanil plus methylprednisolone reduced pain and use of supplementary analgesics effectively.