Intrathecal Ropivacaine and Clonidine for Ambulatory Knee Arthroscopy: A Dose–Response Study

The protocol was approved by the Clinical Research Practices Committee of the Cliniques St Anne—St Remi (Brussels, Belgium), and informed consent was obtained from each patient at the preoperative visit. One hundred twenty patients, classified as American Society of Anesthesiologists physical status I, scheduled for knee arthroscopy were enrolled in the study. A power analysis based on our previous study 1for the current protocol showed that 15 patients would provide a power greater than 0.8 (α= 0.05) for detection of differences (30 min) in time to the capacity of ambulation. 1In all of these patients, a tourniquet with a pressure of 400 mmHg was used to provide a bloodless operative field. No premedication was administered the day of surgery. Patients were placed in the lateral position (left or right to maintain the operative site upward), and an intravenous bolus of at least 250 ml lactated Ringer’s solution was administered followed by an infusion of 100 ml/h. Heart rate and blood pressure were measured at 5-min intervals before and during induction, surgery, and recovery using an automated oscillometer. Arterial oxygen saturation was registered continuously by pulse oximetry.

A combined spinal–epidural technique was performed at the L3–L4 interspace using a midline approach. Dural puncture was performed using a 29-gauge pencil-point needle. After a free flow of clear cerebrospinal fluid was obtained, 4 ml of one of the following intrathecal isobaric solutions was injected according to a computer-generated list of random numbers: patients in group 1 (n =30) received 8 mg ropivacaine; patients in group 2 (n =30) received 8 mg ropivacaine plus 15 μg clonidine; patients in group 3 (n =30) received 8 mg ropivacaine plus 45 μg clonidine; patients in group 4 (n =30) received 8 mg ropivacaine plus 75 μg clonidine. All injections were made with the hole of the needle oriented to the upper side. The injection was made with a Luer-Lock syringe (Terumo, Tokyo, Japan), which made it possible to inject the dose in 35 s. The anesthetic solution was injected without barbotage or aspiration at the beginning or at the end of the injection. The study solutions were prepared by a senior anesthesiologist not involved in the patients’ care, and the patient and the anesthesiologist who delivered analgesia were blind to the study solutions. After the time spent in the lateral position for placement of the epidural catheter (approximately 5 min), the patients were turned to the supine position and observed during 30 min in the induction room. If systolic arterial pressure decreased more than 50 mmHg from the initial value or below 70 mmHg, a vasopressor (ephedrine) was administered intravenously. Bradycardia (heart rate < 50 beats/min) was treated with intravenous atropine.

The criteria used to evaluate the quality of anesthesia provided by the different solutions are the same as those used in the previous study. 1The level and duration of sensory anesthesia—defined as the loss of sharp sensation by using a pinprick test (20-gauge hypodermic needle)—were recorded bilaterally at the midclavicular level. This assessment was performed at 6, 8, 10, 12, 14, 16, 18, 20, and 30 min after intrathecal injection and then every 15 min until regression to S2.

Motor block in the lower limb was assessed using a modified Bromage scale (1 = complete motor blockade; 2 = almost complete motor blockade, the patient is able only to move the feet; 3 = partial motor blockade, the patient is able to move the knees; 4 = detectable weakness of hip flexion, the patient is able to raise the leg but is unable to keep it raised; 5 = no detectable weakness of hip flexion, the patient is able to keep the leg raised for 10 s at least; 6 = no weakness at all, the patient is able to perform partial knee bend while lying supine). These measurements were performed at 10, 15, 20 and 30 min before surgery and every 15 min after surgery. When no motor blockade could be detected (modified Bromage scale 6) and when the patients were ready, they were asked to walk. The time elapsed between intrathecal injection and walking and the time elapsed between intrathecal injection and spontaneous micturition were recorded.

During surgery, the surgeon assessed the quality of motor blockade as perfect, adequate, poor, or inadequate. The same surgeon performed all procedures.

The quality of intraoperative analgesia was evaluated by the patient using the following 4-point scale: 1 = perfect analgesia, no sensation at all from the surgical site; 2 = adequate analgesia, sensation of motion only; 3 = inadequate analgesia, discomfort, but the patient declines additional analgesia; 4 =major discomfort, additional analgesics are necessary. In this situation, the patient received either an intravenous bolus of 5 μg sufentanil or 4 ml bupivacaine, 0.5%, via  the epidural catheter when the patient felt pain and the surgeon reported difficult operative conditions (because of the lack of motor blockade). Data collected from the patients after injection of additional epidural bupivacaine were not considered.

Results are expressed as the mean ± SD. The comparison of normally distributed continuous variables between the groups was performed by means of one-way analysis of variance and, if appropriate, followed by a Student-Newman-Keuls multiple comparison test. Nominal categorical data among study groups were compared using the chi-square test. Ordinal categorical variables and nonnormal distribution continuous variables were compared using the Kruskal-Wallis test and, if appropriate, followed by pairwise Wilcoxon rank sum tests for multiple comparisons between the groups. Hemodynamic data were analysed using analysis of variance for repeated measures. P < 0.05 was considered to be significant.

Demographic data did not differ among study groups (table 1). The combined spinal–epidural technique was easy and uneventful in all patients. The relevant aspects of the spinal block are presented in table 2. The duration of sensory and motor block was significantly shorter in patients treated with 8 mg ropivacaine and in patients treated with 8 mg ropivacaine and 15 μg clonidine.

The intensity of motor blockade assessed by the modified Bromage scale was significantly inferior in patients in group 1 and significantly superior in patients in group 4 when compared with the two other clonidine groups (table 2). This is in accordance with the intraoperative evaluation performed by the surgeon (table 3). Walking was significantly delayed in patients in group 4. The addition of clonidine significantly delayed postoperative micturition except in patients who received 15 μg clonidine (table 2). The majority of patients (> 90%) in groups 2, 3, and 4 evaluated their intraoperative analgesia as perfect or adequate. One patient in group 1 and one patient in group 2 received supplemental intravenous analgesia.

Heart rate did not vary among the groups during the study period. Mean arterial blood pressure was significantly lower (P < 0.05) in patients in groups 3 and 4 (8 mg ropivacaine and 45 and 75 mg clonidine) (fig. 1). Two patients in group 4, fell asleep during surgery. They were, however, easily aroused by simple verbal command. Postoperative course was uneventful for all patients.

Our results show that 15 μg intrathecal clonidine significantly improves the quality of the anesthesia provided by 8 mg intrathecal ropivacaine in patients undergoing ambulatory knee arthroscopy. This quality is obtained without compromising the benefits of low-dose intrathecal ropivacaine, such as short-lasting motor block, early mobilization and micturition. Moreover, such a low dose of intrathecal clonidine is not associated with detectable systemic side effects, such as bradycardia, hypotension, or sedation. The addition of 45 μg clonidine to 8 mg ropivacaine slightly improves the subjective evaluation of the quality of anesthesia. Nevertheless, it prolongs the duration of sensory block, delays the first micturition, and is associated with a moderate decrease in arterial blood pressure.

In the clinical setting studied, the α²-adrenergic agonist clonidine was chosen as an analgesic adjuvant for the following reasons: Intrathecal clonidine clearly increases both the quality and the duration of the anesthesia provided by local anesthetics. 4,5,7–9. This effect has been reported using doses as high as 1 or 2 μg/kg. At these doses, improved analgesia is associated with systemic side effects, such as sedation, relative bradycardia, and hypotension. Our recent experience with intrathecal clonidine in obstetric patients indicates that improved analgesia could be obtained when using a low dose of this α²-adrenergic agonist. 6. In this study, 30 μg intrathecal clonidine significantly increased the analgesia provided by 2.5 or 5 μg intrathecal sufentanil, without systemic side effects. This last observation may be particularly interesting when ambulatory surgery is considered. Finally, intrathecal clonidine also increases the motor blockade as a result of local anesthetic administration. 4,5,7–9Because inadequate muscular relaxation during surgery was an important problem with 8 mg ropivacaine alone, this was another argument in favor of clonidine.

Clonidine was preferred to the μ-opioid agonist sufentanil. Even when used at a low intrathecal dose, rostral cerebrospinal fluid spread and some degree of opioid-induced respiratory depression was reported. 10Moreover, intrathecal opioids have no effect on motor blockade and may worsen urinary retention.

In the current study, three doses of clonidine were tested: 15, 45, and 75 μg. The dose of 75 μg showed significant effects on the objective parameters of anesthesia, i.e.,  duration of sensory and motor blockade, when compared with ropivacaine alone. This same dose was also associated with detectable systemic side effects, such as relative hypotension and sedation. Mobilization and micturition were delayed. The dose of 45 μg increased the duration of sensory block and had no influence on motor blockade or time to walk but was associated with delayed micturition and relative hypotension. In contrast, the addition of 15 μg clonidine to 8 mg ropivacaine preserves the advantage of this low dose of local anesthetic (short-lasting motor block, early ambulation, and micturition) while improving the quality of anesthesia.

If we account for the results of the current study and the results observed during our previous study, 1, a quantitative idea of ropivacaine potentiation by addition of clonidine is possible. The characteristics of the bloc provided by 8 mg ropivacaine associated with 75 μg clonidine are comparable with those obtained with 8 mg bupivacaine or 12 mg ropivacaine. The addition of 75 μg clonidine seems to increase the potency of ropivacaine by 50%.

It is interesting to note the effect of intrathecal clonidine on motor blockade induced by local anesthetics. Intrathecal clonidine alone, even when the dose is as much as 450 μg, does not induce motor blockade or weaknesses. 11,12In contrast, intrathecal clonidine combined with local anesthetics significantly potentiates the intensity and duration of motor blockade. 4,5,7–9Several explanations can be proposed to explain this phenomenon. First, after intrathecal injection, the concentration of clonidine at its site of action, the spinal cord, is much higher than after epidural administration. 13The enhanced intensity of motor blockade may be ascribed to local anesthetic effects of clonidine itself. 14However, the lack of motor weaknesses after high-dose intrathecal clonidine alone does not support this hypothesis. 11,12Another explanation might be that the α²-adrenoceptor agonists induce cellular modification in the ventral horn of the spinal cord (motoneurons hyperpolarization) and facilitate the local anesthetic action. Clonidine reduces motoneuron excitability in cats with spinal injuries 15and has been successfully used in humans to control spasticity. 16 

In conclusion, the association of low-dose clonidine (15 μg) with 8 mg ropivacaine for ambulatory knee arthroscopy significantly improves the subjective parameters that reflect the quality of intraoperative analgesia, and without compromising early mobilization or inferring systemic side effects. The benefits of this association in cases of ambulatory surgery must be weighed against the potential drawbacks that can result from mixing different drugs for intrathecal administration.