Intrathecal ropivacaine for total hip arthroplasty: double-blind comparative study with isobaric 7.5 mg ml–1 and 10 mg ml–1 solutions

D. A. McNamee*,1, L. Parks1, A. M. McClelland1, S. Scott2, K. R. Milligan2, K. Ahlén3 and U. Gustafsson3

1Department of Anaesthetics and Intensive Care Medicine, The Queen’s University of Belfast, Whitla Medical Building, 97 Lisburn Road, Belfast BT9 7BL, UK. 2Department of Anaesthetics, Musgrave Park Hospital, Stockmans Lane, Belfast, UK. 3AstraZeneca R&D, Sodertalje, Sweden*Corresponding author

Accepted for publication: June 12, 2001


    Abstract
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 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 
This study was designed to evaluate the efficacy and safety of two concentrations of intrathecal ropivacaine, 7.5 and 10 mg ml–1, in patients undergoing total hip arthroplasty. One hundred and four patients, ASA I–III, were randomized to receive an intrathecal injection of one of two concentrations of isobaric ropivacaine. Group 1 (n=51) received 2.5 ml of 7.5 mg ml–1 ropivacaine (18.75 mg). Group 2 (n=53) received 2.5 ml of 10 mg ml–1 ropivacaine (25 mg). The onset and offset of sensory block at dermatome level T10, maximum upper and lower spread of sensory block and the onset, intensity and duration of motor block were recorded, as were safety data. Onset of motor and sensory block was rapid with no significant differences between the two groups. The median time of onset of sensory block at the T10 dermatome was 2 min (range 1–25 min) in Group 1 and 2 min (range 1–21 min) in Group 2. The median duration of sensory block at the T10 dermatome was 3.0 h (range 0.5–4.2 h) in Group 1 and 3.4 h (1.1–5.9 h) in Group 2 (P=0.002). The median duration of complete motor block was significantly prolonged (P<0.05) in Group 2 compared with Group 1 (1.9 vs 1.2 h, respectively). Anaesthetic conditions were excellent in all but one patient. Intrathecal ropivacaine, in doses of 18.75 and 25 mg, was well tolerated and provided effective anaesthesia for total hip arthroplasty.

Br J Anaesth 2001; 87: 743–7

Keywords: anaesthetic techniques, regional; anaesthetic techniques, spinal; anaesthetics, local; ropivacaine; total hip replacement


    Introduction
 Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 
Ropivacaine, a relatively new amide local anaesthetic with similar local anaesthetic properties as bupivacaine,1 2 is the first single-enantiomer local anaesthetic to be produced commercially. Although a large number of studies have now been performed using ropivacaine for local infiltration, epidural and peripheral nerve block, clinical data concerning the characteristics of ropivacaine following intrathecal injection are limited. Animal studies have demonstrated that intrathecal ropivacaine has little effect on spinal cord blood flow3 and that it produces similar sensory block to that of an equivalent dose of bupivacaine, with a reduced degree of motor block.4

Although several studies have examined the effects of intrathecal ropivacaine in both labouring women5 and patients undergoing minor surgery,6 no studies have evaluated its use in anaesthesia for major surgery. This study was designed to investigate the safety and efficacy of two concentrations of intrathecal isobaric ropivacaine (7.5 and 10 mg ml–1) in patients undergoing primary total hip arthroplasty.


    Methods
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 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 
A Clinical Trials Exemption Certificate was obtained from the Medicines Control Agency and approval for this randomized, double-blind study was granted by the Research Ethics Committee of the Queen’s University of Belfast. Written informed consent was obtained from 104 patients who fulfilled the following inclusion criteria: undergoing primary unilateral total hip arthroplasty (cemented prosthesis) under intrathecal anaesthesia, ASA I–III, age 18–80 yr, height >=150 cm and weight 50–100 kg. Patients who had contraindications to spinal anaesthesia, allergy to amide local anaesthetics, a significant history of substance abuse, who had participated in clinical trials in the preceding 3 months or had previously been enrolled in this study, had significant derangement of laboratory values and women of child bearing potential were excluded.

Oral pre-medication consisted of diazepam 10 mg and ranitidine 150 mg. Following arrival in the anaesthetic room, i.v. access was established, full non-invasive monitoring applied and the patient placed in the lateral position with the affected hip uppermost. Following skin infiltration with 1% lignocaine, a 20-gauge introducer needle was inserted at the L2/3 or the L3/4 interspace through which a 25-gauge pencil-point needle with its opening uppermost was passed. Correct needle placement was identified by free flow of cerebrospinal fluid and 2.5 ml of study drug was injected. The spinal needle was removed and the patient placed supine to perform the initial assessments. Following completion of the initial assessments and before the commencement of surgery, patients were returned to the lateral position and a continuous i.v. infusion of 1% propofol commenced. The rate of this infusion was adjusted to render the patients drowsy but rousable. Surgery was commenced within 45 min of the administration of the study drug.

The upper and lower spread of sensory block was determined bilaterally using loss of cold sensation to ice. The dermatomes were identified by reference to a standard diagram. Sensory block was assessed at 2 and 5 min post-injection and at 5-min intervals thereafter until two consecutive levels of sensory block were identical. Assessments were continued at 30-min intervals following the completion of surgery until normal sensation returned. The degree of motor block in the non-operative leg was assessed at the same time points as sensory block using a modified Bromage scale (0=no motor block, 1=inability to raise extended legs, 2=inability to flex knees, 3=inability to flex ankle joints). Assessment of motor block ceased once normal motor function returned. Heart rate and arterial pressure were recorded using standard non-invasive techniques/monitors before intrathecal injection and thereafter at 5, 10, 15, 20, 25, 30, 45, and 60 min, then hourly until 8 h post-injection.

The quality of anaesthesia (judged by the anaesthetist), the quality of muscle relaxation (opinion of the surgeon) and the degree of intraoperative comfort (judged by the patient) were recorded as excellent, satisfactory or unsatisfactory. Intraoperative blood loss, the time to first request for post-operative analgesia and the total morphine consumption in the first 24 h following surgery were also noted. Patients were followed up daily for adverse events (defined as any unintended or unfavourable sign, symptom, or disease temporally associated with the use of intrathecal ropivacaine) and serious adverse events (defined as any adverse event which requires a prolonged hospital stay, results in permanent disability or incapacity, is life-threatening or results in death) for the duration of their hospital stay and again by telephone 14–21 days post-surgery.

A difference of 45 min in the duration of sensory block at T10 was taken to be clinically significant. An estimated 22 patients per group were necessary to detect a 45 min difference in the duration of sensory block at T10 with an 80% power, based on a simple unstratified two-sample 95% t-based confidence interval for group comparison, under normality assumptions. The Stratified Wilcoxon (mid) rank sum test was used for comparison between the two groups. A P value of less than 0.05 was considered statistically significant.


    Results
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 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 
The characteristics of the two groups were comparable in terms of age, height, weight, gender, and ASA classification. There was no significant difference in the duration of surgery (Table 1). Three patients in the ropivacaine 7.5 mg ml–1 group were excluded from the clinical efficacy analysis (one with low serum sodium, one with low serum potassium, one inadequate sensory block). The two patients excluded because of abnormal plasma electrolytes had previously had normal values recorded at the pre-operative assessment clinic and results from samples taken on the day of surgery were unavailable at the time of surgery. One patient in the ropivacaine 10 mg ml–1 group was also excluded from the clinical efficacy analysis because of chest pain immediately before surgery. All four patients were included in the safety analysis. All patients were able to co-operate fully with the subsequent assessments.


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Table 1 Patient characteristics and duration of surgery (median (range)). No significant differences
 
The median time of onset of sensory block at the T10 dermatome was 2 min (range 2–25 min) in the 7.5 mg ml–1 group and 2 min (range 2–21 min) in the 10 mg ml–1 group. The median duration of sensory block at the T10 dermatome was 3.0 h (range 0.5–4.2 h) in the 7.5 mg ml–1 group and 3.4 h (1.1–5.9 h) in the 10 mg ml–1 group (P=0.002).

Whilst there was a trend towards a longer duration of sensory block at different dermatome levels in the ropivacaine 10 mg ml–1 group, this difference was not statistically significant. The duration of sensory block in each group is shown in Figure 1. There was no significant difference in either the maximum upper or lower spread of sensory block before or after surgery (Fig. 2). Anaesthesia was judged to be excellent in all patients, except for one in the ropivacaine 7.5 mg ml–1 group who complained of deep wound pain approximately 5 min after skin incision despite a pre-operative sensory block to T10. General anaesthesia was instituted, the patient was pain free post-operatively with a sensory block level at T7 and motor block of 3 on the modified Bromage Scale in the recovery ward. This patient had no recall of any intraoperative pain.



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Fig 1 Regression of upper dermatomal level of sensory block with time (median and range). No significant differences.

 


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Fig 2 Upper extent of levels of analgesia in the individual patients after intrathecal administration of isobaric 7.5 or 10 mg ml–1 ropivacaine. Horizontal bars represent medians. No significant differences

 
All patients achieved motor block of at least 1 on the modified Bromage scale. The onset of motor block was slower than that of sensory block as demonstrated by the increased proportion of patients exhibiting an increased degree of motor block post-operatively compared with the degree of motor block seen pre-operatively. The median duration of complete motor block (modified Bromage Scale 3) was significantly prolonged (P<0.05) in the ropivacaine 10 mg ml–1 group compared with the ropivacaine 7.5 mg ml–1 group (1.9 vs 1.2 h, respectively). There were no other significant differences in the degree or duration of motor block between the two groups. The characteristics of post-operative motor block in each group are displayed in Figure 3.



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Fig 3 Motor block following intrathecal administration of isobaric 7.5 or 10 mg ml–1 ropivacaine. Numbers represent modified Bromage Scale. Duration of grade 3 motor block significantly prolonged in ropivacaine 10 mg ml–1 group (P<0.05).

 
Excellent muscle relaxation was reported in 90% of patients in the ropivacaine 7.5 mg ml–1 group and in 98% of patients in the ropivacaine 10 mg ml–1 group. All patients reported excellent intraoperative analgesia.

The median time to first analgesic request was similar in both groups (7.5 mg ml–1=3.3 h, 10 mg ml–1=3.9 h). Median morphine requirements (7.5 mg ml–1=50 mg (range 0–94 mg), 10 mg ml–1=42 mg (range 17–120 mg)) in the first 24 h following surgery were similar.

Intrathecal ropivacaine produced an initial moderate decrease in arterial pressure. Intraoperative hypotension requiring treatment with i.v. ephedrine occurred in 24% of patients in both the 7.5 and 10 mg ml–1 ropivacaine groups. No patients in the ropivacaine 7.5 mg ml–1 group required treatment for intraoperative bradycardia. Three patients in the ropivacaine 10 mg ml–1 group required i.v. atropine 0.6 mg to correct symptomatic bradycardia in the intraoperative period. The most commonly reported adverse events during the first 24 h were pyrexia, nausea, vomiting, hypotension, and oliguria. These events were similarly distributed between groups. There was no significant difference in the blood loss between the two groups (median 480 ml in the ropivacaine 7.5 mg ml–1 group, median 370 ml in the ropivacaine 10 mg ml–1 group).


    Discussion
 Top
 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 
Animal studies have shown that intrathecal ropivacaine produced effective local anaesthesia with an equipotent sensory block but shorter duration of motor block than intrathecal bupivacaine,4 and no signs of neurological toxic effects have been seen.3 9 In a study of 40 patients undergoing minor orthopaedic surgery who received 3 ml 0.5% or 0.75% intrathecal ropivacaine, the higher dose was associated with a prolonged duration of analgesia and higher degree of motor block.6 A crossover study in 18 volunteers who did not undergo surgery, estimated hyperbaric ropivacaine to have a potency of approximately half that of bupivacaine. In this study, intrathecal ropivacaine was associated with a high incidence of back pain.7 Furthermore, another recent study of 150 patients comparing equal doses of intrathecal bupivacaine with intrathecal ropivacaine in patients undergoing knee arthroscopy showed a shorter duration of both sensory and motor block with ropivacaine compared with that of bupivacaine. No evidence of post-dural puncture headache or transient radicular irritation was observed in any of the treatment groups.8

To our knowledge, this study is the first study to evaluate intrathecal ropivacaine for use as a sole agent in patients undergoing major surgery. The efficacy and safety of two glucose-free solutions of ropivacaine, 7.5 and 10 mg ml–1, were assessed for intrathecal anaesthesia in patients undergoing total hip replacement. Both solutions produced similar results in terms of onset and spread of analgesia. In a previous study which compared 3.0 ml of 5 and 7.5 mg ml–1 glucose-free ropivacaine in patients undergoing lower limb surgery, only 32% and 50%, respectively, of patients achieved a sensory block of at least T10.6 This contrasts with our study in which virtually all patients achieved adequate sensory block. Furthermore, the upper extent of sensory block was much higher in this study with approximately 10% of patients with sensory anaesthesia in the cervical dermatomes compared with a maximum sensory block at the T4 dermatome in the study carried out by van Cleef and colleagues. This may be because of a difference in the characteristics of the populations studied, the use of a higher dose of ropivacaine, or the difference in the position of the patient during the institution of intrathecal anaesthesia. Furthermore, sensory block in our study was tested using loss of sensation to ice rather than loss of sensation to pinprick, which may produce a significant discrepancy in the assessment of sensory block following intrathecal anaesthesia.10 The subgroup of patients with sensory anaesthesia in the cervical dermatomes did not demonstrate any upper limb motor weakness, respiratory distress, decrease in oxygen saturation, or cardiovascular compromise. This suggests a significant separation in the extent of motor and sensory block when loss of sensation to ice is used.

The one patient in whom a loss of cold sensation to ice at the T10 dermatome did not produce adequate anaesthesia may have had a surgical incision with an upper limit above this level. Furthermore, this patient was pain free in the recovery ward with a sensory level of T7 and motor block of modified Bromage Scale 3 suggesting that the spinal anaesthetic may have had a slow onset.

In common with a previous study,6 an increase in the dose of intrathecal ropivacaine administered led to an increased duration of profound motor block. The variation in spread of sensory block may be attributed to the use of an isobaric solution.

In terms of safety, both doses of intrathecal ropivacaine provided a high degree of cardiovascular stability with a low incidence of bradycardia. The degree of hypotension was as expected for an elderly population undergoing an operative procedure under a combination of spinal anaesthesia and propofol sedation with an ongoing blood loss; the hypotension seen was associated with the commencement of the i.v. infusion of 1% propofol rather than the institution of spinal anaesthesia. The most commonly reported adverse events were those commonly seen in connection to major surgery.

A significant finding was the absence of symptoms of post-dural puncture headache compared with an incidence of 25% in a previous study.6 Although spinal anaesthesia was performed using a larger gauge needle in our study (25-gauge as opposed to 26-gauge), the difference in incidence may be accounted for by the use of a pencil-point needle as opposed to a Quinke needle and again by the difference in the age of the two patient groups. This suggests that intrathecal ropivacaine is not associated with an increased incidence of post-dural puncture headache. No patient reported symptoms of neurological problems post- operatively.


    Acknowledgements
 
We would like to thank Mr D. Beverland and the other consultant orthopaedic surgeons for their patience and assistance with the scheduling of suitable cases and the nursing staff of Musgrave Park Hospital for their help in carrying out the observations. This research was supported by a grant from AstraZeneca Pharmaceuticals Ltd.


    References
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 Abstract
 Introduction
 Methods
 Results
 Discussion
 References
 
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