BJA Advance Access originally published online on June 23, 2006
British Journal of Anaesthesia 2006 97(3):393-400; doi:10.1093/bja/ael147
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Continuous spinal microcatheter (28 gauge) technique for arterial bypass surgery of the lower extremities and comparison of ropivacaine with or without morphine for postoperative analgesia
Department of Anaesthesiology and Intensive Care Medicine, Helsinki University Central Hospital PB 340, FIN 00029 Helsinki, Finland
*Corresponding author. E-mail: johannes.forster{at}fimnet.fi
Accepted for publication April 15, 2006.
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Abstract |
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Background. The aim of this study was to evaluate a microcatheter technique for continuous spinal anaesthesia (CSA) and continuous spinal postoperative analgesia (CSPA) in vascular surgery.
Methods. A total of 47 patients (range 51–95 yr, ASA II–IV) undergoing peripheral bypass surgery of the lower extremities received a spinal microcatheter (28 gauge) at L3–L4 or L2–L3. For CSA, ropivacaine 7.5 mg ml–1 was given in small increments. Central venous pressure was maintained 
3 mm Hg. Of 47 patients, 44 received CSPA, either using ropivacaine alone 2 mg h–1 (group R, n=22) or ropivacaine 1 mg h–1 with morphine 8 µg h–1 (group RM, n=22) for 24 h after surgery (randomized, double-blinded).
Results. Intraoperative haemodynamic control was good; during the initial 60 min only four patients received phenylephrine i.v. for hypotension. Up to 30% of the patients felt mild pain at incision but surgery [mean duration 173 min (range 66–327)] was successfully completed under CSA in 45 patients. In four instances of acute revision surgery, a new block was administered utilizing the spinal catheter in place. Postoperative pain relief was comparably adequate in both groups with no difference in rescue pain medication. Four patients (three in R, one in RM) had weak motor blockade in the first postoperative morning.
Conclusions. The described CSA technique offered good haemodynamic control, ease of maintaining spinal anaesthesia, and ease of providing a new spinal block for revision. The combination of low-dose ropivacaine and morphine for CSPA did not offer any benefit compared with the higher ropivacaine dose alone.
Keywords: anaesthetic techniques, spinal, continuous; anaesthetics local, ropivacaine; analgesia, postoperative, continuous; analgesics opioid, morphine; surgery, vascular
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Introduction |
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The continuous spinal anaesthesia (CSA) technique offers several advantages over single-shot spinal anaesthesia making the CSA technique potentially attractive in patients undergoing extensive surgery of the lower part of the body.1 2 By intermittent administration of small doses of a local anaesthetic through the spinal catheter, the spread of the block can be better regulated and the risk of abrupt decreases in arterial pressure can be reduced compared with single-shot spinal anaesthesia or epidural anaesthesia.1 Also, an adequate level of anaesthesia can be maintained in prolonged surgery. Finally, the spinal catheter can be utilized for continuous spinal postoperative analgesia (CSPA).
The CSA technique with macrocatheters (22 gauge or thicker) has been used successfully in patients undergoing vascular surgery.3 4 However, with such relatively thick needles and catheters increased numbers of erythrocytes have been detected in the cerebrospinal fluid to a disturbing degree.4 Therefore, thinner catheters designed specifically for CSA should probably be used, particularly in patients who are on low-molecular-weight heparin (LMWH) and receive intraoperative heparin.
CSPA has been found to provide good analgesia after major orthopaedic surgery of the lower extremities,5–7 but recurrence of motor blockade in the postoperative period was a problem in studies using continuous infusion of bupivacaine.6 7
In this study, we evaluated the feasibility of a CSA microcatheter (28 gauge) technique in elderly patients undergoing arterial bypass surgery of the lower extremities. Ropivacaine was chosen as the spinal anaesthetic as we expected it to cause less motor blockade than bupivacaine,8 9 the local anaesthetic favoured so far in CSA by us6 7 and others.5 10 With regard to CSPA, we hypothesized that the combination of low-dose ropivacaine (maximum dose 1 mg h–1) and morphine (maximum dose 8 µg h–1) would cause less motor blockade than ropivacaine alone (maximum dose 2 mg h–1).
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Methods |
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This prospective, randomized, controlled and double-blinded study was approved by the local Institutional Ethics Committee and by the National Agency for Medicines. Written informed consent was obtained from all patients before surgery.
Patients and pre-anaesthetic considerations
A total of 47 patients (ASA class II–IV) undergoing peripheral arterial bypass surgery of the lower extremities were enrolled. Of these 47 patients, 44 entered the CSPA part of the study (see Results). Exclusion criteria were contraindications to insertion of a spinal catheter (haemostatic abnormalities and/or therapeutic anticoagulation, infection at the puncture site, or anatomical spine abnormalities), mental illness, lack of cooperation and renal insufficiency requiring haemodialysis.
Before surgery, all patients received their normal morning medication, except angiotensin-converting enzyme inhibitors, diuretics, acetylsalicylic acid and diabetes mellitus medication. If a patient was on LMWH, anaesthesia was not initiated until at least 10 h had elapsed from the last dose of LMWH. Medication with an adenosine diphosphate receptor antagonist, an inhibitor of the platelet receptor GPIIb/IIIa, or fondaparinux was an exclusion criterion unless the drug under consideration had been stopped well in advance according to present recommendations.11 Pre-medication consisted of oral diazepam 5–10 mg. Intraoperative monitoring included pulse oximetry, ECG, invasive arterial pressure, hourly urine output and body temperature measurement. A central venous catheter (internal jugular or subclavian vein) was placed in all patients and Ringer's acetate i.v. 5–10 ml kg–1 was administered in order to achieve a central venous pressure (CVP) of 3 mm Hg before the initiation of the spinal anaesthesia.
Spinal anaesthesia
With the patients in the lateral decubitus position the intrathecal space was punctured with a 22 gauge Quincke needle at the L3–L4 or L2–L3 interspace. The bevel of the needle was facing laterally during puncture, and when free backflow of cerebrospinal fluid occurred, the bevel was turned cephalad. A 28 gauge spinal catheter was advanced through the spinal needle 3–4 cm into the subarachnoid space. We used the CoSpan® set for CSA (Kendall, Neustadt, Germany). The Tuohy-Borst® catheter adapter and the filter belonging to the set were attached.
After the placement of the spinal catheter, the patients were turned to the supine position. Initially, 1.0 ml of ropivacaine 7.5 mg ml–1 was administered intrathecally (Naropin®, AstraZeneca). Spinal anaesthesia was titrated with incremental boluses (0.5 ml) of the same ropivacaine solution, until sensory block had reached at least dermatome T10 (loss of cold sensation). The time between two boluses was at least 3 min. Additional boluses of ropivacaine were given during surgery as needed. If required, the patients received i.v. midazolam and fentanyl as additional pre-medication, or for sedation or pain during the operation (e.g. position-related discomfort, or pain at the site of surgery).
Intraoperative phase
After the initial spinal dose of ropivacaine, arterial pressure, CVP and heart rate were recorded every 3 min for 15 min, and, after that, every 5 min for the next 45 min. Sensory block (hypoaesthesia to cold, swab of cotton soaked with alcohol) and motor blockade were tested every 5 min. Motor blockade was assessed using a modified Bromage scale (0=full flexion of knee and foot, 1=just able to move knee, 2=able to move foot only, 3=unable to move foot or knee).12 The i.v. infusion therapy regime was adjusted according to urine output, and blood loss and with the aim of maintaining a CVP of at least 3 mm Hg. The fluids administered included Ringer's acetate 5–10 ml kg–1 h–1, hydroxyethyl starch 60 mg ml–1, and blood component transfusion. The doses of any drugs needed to treat hypotension and bradycardia were recorded. The patients received heparin 100 IU kg–1 i.v. before clamping of the artery. The need for additional heparin doses was evaluated according to intraoperative monitoring of the activated clotting time. Protamine i.v. and intra-arterial papaverine were given at the discretion of the surgeon. At the end of surgery, the surgeon was asked whether he had been satisfied with the motor block during surgery (complete motor block—minor movements, manageable—movements to a disturbing degree).
Continuous spinal analgesia and the postoperative phase
After surgery, the patients were transferred to the recovery room and allocated to one of the two study groups for CSPA. Allocation was done by block randomization with block sizes of 20, 20 and 6 (closed envelope method). Randomization was performed by a third party not involved in the study. All patients and all physicians and nurses involved in the treatment of the patients were blinded throughout the whole study. For group R (n=22) a 5.0 mg ml–1 solution was prepared by mixing 20 ml of ropivacaine 7.5 mg ml–1 and 10 ml of NaCl 0.9%. For group RM (n=22), 10 ml of ropivacaine 7.5 mg ml–1 were mixed with 20 ml of NaCl 0.9% and 0.3 ml of morphine 2 mg ml–1 (Morphine® Inj., Leiras), resulting in concentrations of 2.48 mg ml–1 and 19.8 µg ml–1 for ropivacaine and morphine, respectively. The spinal infusion was started when first voluntary contractions of thigh muscles were seen. The infusion was scheduled for 24 h. The initial syringe pump (Top 5200®, Terumo) rate was 0.4 ml h–1 in both groups, that is ropivacaine 2 mg h–1 in R, and ropivacaine 1 mg h–1 plus morphine 8 µg h–1 in RM. As needed, the rate of the infusion was adjusted in steps of 0.1 ml h–1 downwards (hypotension, pronounced motor block) or upwards (pain at the site of surgery); however, not exceeding 0.4 ml h–1. The display of the pump was marked with alerting red tapes and a warning text that the infusion speed must not exceed 0.4 ml h–1.
After surgery, the patients were kept either in the recovery room overnight (depending on space and staff) or for 4–8 h, as needed, after which they were transferred to the surgical ward. The arterial line was removed before the patient's transfer to the surgical ward. For postoperative thromboprophylaxis, the surgeon prescribed s.c. dalteparin (Fragmin®, Pharmacia/Pfizer), 2500–5000 IU twice a day. The removal of the spinal catheter was timed in relation to the administration of the LMWH, that is 10 h after the previous and 2 h before the next LMWH dose.11
Postoperative study parameters
Study parameters were measured 4 and 8 h after the start of the spinal infusion, between 08:00 and 10:00 on the first postoperative day (POD), and, finally, later on during day time when the spinal infusion was stopped. At these predetermined times the following parameters were recorded: blood pressure, heart rate, ventilatory frequency, SpO2, degree of sedation, degree of motor blockade and pain at rest and during moderate flexion of the operated leg. Sedation was evaluated on a five-step scale (sleep=sound sleep at night, but easily rousable, 0=awake, 1=the patient snoozes but is easily rousable, 2=the patient is drowsy, 3=the patient sleeps and is difficult to rouse). Pain intensity was evaluated on a 50 cm long visual analogue scale (VAS) graded from 0 (no pain) to 10 (worst pain imaginable).13 Patients were asked whether they had suffered from postoperative nausea and vomiting (PONV) or from pruritus at any time point between the previous and the present interview. PONV was recorded on a three-step scale (no—feeling nauseated—retching or vomiting), as was pruritus (no—slight to moderate—strong itching). Additionally, in each interview, patients were asked to judge their satisfaction concerning the pain management regimen on a four-step scale (0=not satisfied with the pain management regime, 1=insufficient pain relief and bothersome side-effects, 2=sufficient pain relief and few side-effects, 3=excellent pain relief and no side-effects). Finally, on the second POD, we visited the patients in order to detect any problems or complaints possibly related to the spinal-catheter technique.
Supplemental analgesics and other drugs
All patients received 1 g acetaminophen i.v. (Perfalgan®, Bristol-Myers Squibb) every 8 h during the spinal infusion, and thereafter, acetaminophen 1 g orally every 8 h. Rescue pain medication was oxycodone 2–3 mg i.v. in the recovery room, and 5–10 mg i.m. or 10–20 mg orally after transfer to the surgical ward. The oxycodone requirements on the first and second POD were recorded. PONV was treated with tropisetron (Navobane®, Novartis) 2 mg i.v. or metoclopramide 10 mg i.v. Severe pruritus was treated with hydroxyzine (Atarax®, UCB) 25 mg orally, if required.
Statistical analyses
As appropriate, groups were compared with the 
2-test or Fisher's exact test for categorical data, with t-tests or with repeated-measures ANOVA for continuous data, and with the Mann–Whitney U-test for non-parametric data. A P-value <0.05 was considered statistically significant. A total of 20 patients per group were considered necessary to detect statistical significance (
=0.05, one sided, power=80%) based on our previous experience with bupivacaine (mean difference between the groups 23% when comparing CSPA with bupivacaine 2 mg h–1 alone vs bupivacaine 1 mg h–1 and morphine 8 µg h–1 with respect to the number of patients scoring a modified Bromage score of 2 or 3).7 The latter study was used as a basis for the power analysis because there were no published comparative data for ropivacaine with CSPA. To allow for possible drop-outs, we decided to allocate 23 patients to each group. All statistical calculations were performed using the StatView® for Windows® Version 5.0.1. computer program (SAS Institute Inc., Cary, NC, USA).
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Patients, surgery and spinal anaesthesia
In one patient, the intrathecal space could not be identified at lumbar puncture. This patient was replaced by the next recruited patient with regard to the randomization envelope which had not been opened yet at the time of drop-out. One patient in the ropivacaine and morphine group withdrew her consent to the study after arrival in the recovery room. One patient (ASA class II, BMI 23.7) randomized to ropivacaine had to be placed in the prone position for popliteal–popliteal reconstruction of an aneurysm of the popliteal artery. Spinal anaesthesia via the intrathecal catheter was given according to the protocol. In spite of i.v. sedation, the patient found it difficult to stay comfortable in the prone position and movements of the upper body disturbed the surgeons. When surgery lasted considerably longer than planned, the patients had to be given general anaesthesia with tracheal intubation in order to assure sufficient ventilation. Because of these drop-outs, only 44 patients entered the postoperative CSPA part of the study.
The R and RM groups were similar with regard to patient characteristics, data related to surgery (Table 1) and fluid therapy (data not presented). Details concerning the spinal anaesthesia of the 44 patients with CSPA are presented in Table 2. Spinal anaesthesia spread slowly. After 20 (range 15–25) min, the median level of sensory block (25th–75th percentile) was T9 (T10–T7) in the R group and T10 (T11–T6) in the RM group. In five instances (three in the R group, twice in the RM group), where onset was particularly slow, slight head-up tilt of the operating table was applied for 10–20 min in order to enhance cranial spread of the local anaesthetic. A total of 13 patients experienced mild pain during skin incision (six in the R group and seven in the RM group). This was treated satisfactorily with fentanyl i.v. (11 patients) and intrathecal top-ups (12 patients), and with local infiltration of the incision area with lidocaine 10 mg ml–1 (4 patients). In three patients, the surgeons found it disturbing that the patients started to move their legs towards the end of surgery with decreased motor blockade despite a still adequate sensory block.
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Revision of the surgical wound because of postoperative haematoma was necessary in four patients (three from the R group and one from the RM group). For these procedures, the anaesthesiologist on call stopped the spinal infusion and gave ropivacaine 7.5 mg ml–1 in doses of 0.5–1.0 ml (total amounts 1–2 ml) through the spinal catheter. This resulted in sufficient sensory anaesthesia for these revisions, which lasted 20–60 min. The spinal infusion was recommenced when voluntary contractions of the thigh muscles were seen.
Technical aspects related to CSA (all 47 patients) and CSPA (44 patients)
The identification of the intrathecal space was unproblematic in 37 patients. In nine patients, three or more punctures were needed and in one patient the identification of the intrathecal space was not possible. In three patients, a bloody tap with the needle occurred. However, the appearance of the cerebrospinal fluid was clear in all patients once free flow was obtained. Threading the catheter into the intrathecal space was easy in all but two patients, in whom insertion of the catheter succeeded only when the spinal needle had been withdrawn 1–2 mm. Short lasting, mild paraesthesia during puncture or catheter advancement was recorded in 11 patients. In four patients, we encountered problems related to the tightness of the seal of the catheter's adapter. In three patients, this problem was overcome by tightening the screw of the adapter and by injecting the local anaesthetic very slowly, but in one instance, these measures were not successful and the adapter had to be replaced. However, we did not encounter any catheter disconnection. In one patient, the spinal infusion pump reported an occlusion alarm. It remained unclear from the record file of the pump whether the patient had received the planned amount of spinal drugs for a period of 3 h before the alarm. In another patient, obvious kinking of the catheter near the adapter occurred, which was detected within an hour and corrected.
Intraoperative haemodynamics
Systolic and diastolic arterial pressure, mean arterial pressure (MAP), CVP and heart rate decreased slightly but steadily over time during the first hour of anaesthesia (P<0.0001, repeated-measures ANOVA). For example, the mean (SD) MAP was 106 (16) mm Hg before spinal anaesthesia and 87 (11) mm Hg 60 min after the start of spinal anaesthesia (Fig. 1). Mean (SD) heart rate was 61 (12) beats min–1 before spinal anaesthesia. The greatest change on average in heart rate was observed after 45 min when heart rate was 58 (11) beats min–1. During the initial 60 min, four patients received phenylephrine i.v. for hypotension with total doses of phenylephrine not exceeding 0.2 mg. The amounts of vasoactive drugs given during the whole intraoperative period are presented in Table 2. Mean CVP values remained at a level of 4–7 mm Hg throughout the 60 min observation period.
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Postoperative analgesia and adverse effects
Pain relief was comparable in both groups in terms of VAS scores at rest and in motion (Table 3). The need for rescue pain medication (oxycodone) did not differ statistically between the groups. During the study infusion, 5 patients from the R group and 11 from the RM group did not need any oxycodone (P=0.12,
2 with Yates' continuity correction). During the 24 h after the infusion, three patients from each group did not require oxycodone. The majority of the patients had no measurable motor blockade during the infusion (no inter-group difference) (Fig. 2). In four patients in group R, the infusion rate was reduced because of pronounced motor block, compared with one patient in the RM group. Grade 1 motor blockade was detected in three patients from the R and one from the RM group on the first postoperative morning and in one patient from each group later that day. Results for PONV, headache and other side-effects, and patient satisfaction are reported in Table 4. The pain management regimen was classified as insufficient only once, by a patient in the R group on the morning of the first POD.
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There was no difference between the R and RM groups at the four predetermined interview points with regard to MAP (P=0.67), heart rate (P=0.2), ventilatory frequency (P=0.17) and pulse oximetry (P=0.42). Hypotension was the main reason for reducing the speed of intrathecal infusion. A pulse oximetry value of less than 92% was recorded in three patients, two from the R group and one from the RM group. However, these low pulse oximetry values were not accompanied by any other obvious problematic clinical findings. Sedation scores were one in all but one patient, who had a score of 3. This value was recorded in the recovery room 8 h after the start of the infusion, soon after the patient had received haloperidol 5 mg i.v. because of restlessness and confusion.
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Discussion |
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The spinal catheter technique used here for CSA and CSPA in patients undergoing arterial bypass surgery of the lower extremities provided good intraoperative haemodynamic control and adequate pain relief after surgery with good to excellent patient satisfaction. The study did not support the hypothesis that the mixture of low-dose ropivacaine (maximum 1 mg h–1) and morphine (maximum 8 µg h–1) produces less motor blockade than ropivacaine alone (maximum 2 mg h–1).
Quality of the spinal anaesthesia
All but one of the procedures were finished under CSA. Development of spinal anaesthesia was quite slow in many instances, especially with regard to motor blockade. Although the degree of skin anaesthesia appeared sufficient before the start of surgery (loss of cold sensation up to at least T10), one-third of our patients experienced some pain at skin incision. However, similar observations, that is slow onset of spinal anaesthesia and occurrence of pain during incision, were made by Pitkänen and colleagues14 who used small increments of bupivacaine 5 mg ml–1 for CSA and tested sensory block by pinprick with the aim of achieving a block to T10.
Haemodynamic changes during operation
Our results regarding haemodynamic changes during the initial phase of the spinal anaesthesia correspond to those by Morrison and colleagues15 who found that only 1 of 20 patients undergoing femoro-popliteal grafting needed ephedrine i.v. in the first half-hour after the initial dose of isobaric tetracaine 1% 1.5 ml. However, 63% of the patients in Morrison's study received ephedrine for hypotension at some point during the procedure. The difference between these findings and those in our study (only 25% needed vasopressors during operation) might be explained by the fact that we monitored the CVP invasively and tried to maintain it above a preset level. Lundorff and colleagues16 and Sabaté and co-workers17 found no haemodynamic difference between CSA and single-shot spinal anaesthesia in patients undergoing vascular surgery. In the study by Lundorff and colleagues, ephedrine was given to 50% of the patients in the CSA and to 46% in the single-shot group. To our understanding, they did not monitor CVP invasively and, perhaps more importantly, an initial dose of 1 ml of 0.5% plain bupivacaine was given with the patients still in the sitting position. In our study and that by Morrison and colleagues the initial bolus was given after the patient had been returned to the supine position. A comparison with the Sabaté's study17 is difficult. One hundred and twelve consecutive patients were allocated according to the anticipated duration of surgery into a group who received single-shot spinal anaesthesia if surgery was expected to last less than 3 h (n=42) or a group who received CSA if surgery was expected to last 3 h or more (n=70). As the CSA group included more patients with hypertension or diabetes mellitus, one might argue that, in terms of vasoactive drugs needed, the haemodynamic control in group CSA was at least as good as in the single-shot spinal group.
Efficacy of the continuous spinal analgesia
Our study is the first one to evaluate CSPA after peripheral arterial surgery and there are no published comparative data of ropivacaine alone or ropivacaine with an opioid for CSPA. The dosages of the drugs were low and were chosen to be similar to those used in earlier studies performed in our department. For example, in the study by Bachmann and colleagues,7 bupivacaine 2 mg h–1 or bupivacaine 1 mg h–1 with morphine 8 µg h–1 were administered for CSPA after hip and knee arthroplasty.7
Analgesia was adequate in both groups with no clinically meaningful difference in amounts of oxycodone rescue medication (Table 3). It is possible, that some patients would have benefited from slightly higher infusion rates with respect to pain relief, but for safety reasons we decided not to exceed the rate of 0.4 ml h–1 in this study. The small dose of intrathecal morphine used in the RM group did not seem to result in smaller oxycodone requirements during the 24 h after the spinal infusion, that is to say there was no carry over effect.
Motor blockade was not recorded in most of the patients at any time during the study infusion. In fact, only four patients (three in the R group and one in the RM group) had grade 1 motor blockade on the first POD. No conclusions can be made about any difference between the R and RM groups, but, from a clinical point of view, we consider it important that motor blockade was less marked in this study using ropivacaine than in the previous study performed in our department in which we used bupivacaine.7 For example, in both groups in this study, slightly more than 10% had a modified Bromage score of 2 after 4 h from the start of the spinal infusion, whereas with bupivacaine 2 mg h–1 or with bupivacaine 1 mg h–1 plus morphine 8 µg h–1 more than 70% of all patients had a score of 2 or 3 measured 3 h after initiation of the infusion.7
Safety and technical considerations
CSA via macrocatheters has been used in vascular surgery.3 4 In the study by Rao and El-Etr,3 CSA was given through a macrocatheter (puncture needle 19 gauge and catheter 22 gauge) to 847 vascular surgery patients with a very low incidence of minor neurological sequelae. In the study by Lindgren and colleagues,4 who used a 19 gauge Tuohy needle and a 22 gauge catheter in both vascular and non-vascular surgical patients, an increased number of erythrocytes (>100x106 litre–1) in the cerebrospinal fluid was found in up to 26% of the patients after the puncture and still later in the postoperative phase with the polyurethane catheter in place. In spite of the haemorrhages detected, which suggest injury to blood vessels by the equipment, no related neurological symptoms or other serious consequences were observed.4 At the present, the benefit of a reduced risk of intrathecal haemorrhage and possible neurological sequelae with a microcatheter technique remains hypothetical.
Earlier, technical problems during CSA have been reported with both micro- and macrocatheters to a similar extent.1 5 18–20 In our study, technical problems and transient paraesthesia on insertion of the catheter occurred with an incidence similar to those in earlier studies describing CSA,10 21 22 continuous epidural analgesia23 and combined spinal–epidural anaesthesia.21 22 We encountered no adapter-catheter disconnections as described by others,5 24 instead, we had problems with the tightness of the seal of the adapter.
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Conclusions |
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The CSA microcatheter technique used here was associated with good haemodynamic control, ease of top-up, and ease of providing a new spinal block for revision surgery. We encountered a relatively large number of technical problems which, fortunately, did not lead to harm in any patient. With regard to CSPA, the addition of morphine (maximum 8 µg h–1) to the low-dose ropivacaine (maximum 1 mg h–1) in RM did not offer any clear benefit in terms of analgesia or side-effects, as compared with the higher ropivacaine dose in R (maximum 2 mg h–1).
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Acknowledgments |
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This work was supported by a research fund granted by the Helsinki University Central Hospital. We are grateful to the colleagues and nursing staff of the Meilahti Hospital, Helsinki University Central Hospital, for valuable assistance throughout the study.
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Footnotes |
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Presented in part at the 28th Congress of the Scandinavian Society of Anaesthesiology and Intensive Care Medicine, Reykjavik, Iceland, June 29–July 3, 2005 
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References |
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