Randomized, Controlled Study of Long-Acting Local Anesthetic (levobupivacaine) in Femoral Artery Sheath Management during and af

Percutaneous coronary intervention (PCI) is central to the management of patients with coronary artery disease. Vascular access is most commonly achieved via the femoral artery by inserting a vascular access sheath. To reduce the risk of acute stent thrombosis, patients receive heparin. However, anticoagulation increases the risk of significant bleeding and hematoma formation at the time of sheath removal,¹ and therefore either sheath removal is delayed for ~4 hours until the anticoagulant effects of heparin have worn off, or a vascular closure device is used. Vascular closure devices can be costly, thus delayed sheath removal is the preferred option in most centers. Lidocaine is the most commonly used local anesthetic for sheath insertion. It has a rapid onset of action, but the duration of action is short.² Sheath removal is usually performed by the nursing staff during the evening. If further analgesia is required at this point, intravenous (IV) opiate is administered, as nurses are generally not permitted to administer further doses of lidocaine. However, there are several deleterious side effects of opiates such as hypotension, respiratory depression, nausea and vomiting, all of which can occur with therapeutic doses. The aim of this current study was to assess the effect of the long-acting local anesthetic agent levobupivacaine used in addition to lidocaine for the management of femoral artery sheaths during and after PCI. Materials and Methods Ethics. The study was undertaken with the approval of the local research ethics committee and in accordance with the Declaration of Helsinki. Written informed consent was obtained from each subject before entry into the study. Patients. Sixty patients undergoing PCI via the femoral artery approach were enrolled. Patients were included if it was intended that the sheath be removed in the cardiology ward 4 hours after the procedure. Patients were excluded if PCI was performed via the radial artery, if they had received analgesia that day, or if they had a history of any adverse reaction to morphine or local anesthetic agents. Study design. This was a randomized, controlled clinical study. Measurements. A visual analogue pain score (0–10) was used to assess patients’ pain. Blood pressure and heart rate were measured invasively during the PCI procedure via the cardiac catheter. Before and after the procedure, blood pressure and heart rate were measured non-invasively using a standard clinical blood pressure measuring device. Study drugs. A dose of 10 ml of 0.5% levobupivacaine (Abbott Laboratories, United Kingdom) was administered subcutaneously around the femoral sheath at the end of the PCI in those patients randomized to the active group. Study protocol. Patients underwent standard preparation for PCI. Patients had a light breakfast prior to being admitted to the cardiology ward. All patients had a venous cannula inserted into a left arm vein. All patients were pre-treated with aspirin (300 mg) and clopidogrel (300 mg) if not already taking these medications regularly. If patients were particularly anxious, they received 5–10 mg of diazepam orally. All patients had subcutaneous lidocaine 1% administered prior to femoral artery sheath insertion. At this stage, both patient and operator were blinded as to which study group the patient was in. All patients underwent coronary angiography to verify that PCI was still indicated. Following PCI, patients who had already given informed written consent were then randomized to either usual care or the administration of 10 ml subcutaneous levobupivacaine (0.5%) via a 19 gauge needle to the area surrounding the femoral artery sheath. A “sticker” was then put on the leg and in the clinical notes of patients who had received levobupivacaine, informing the nurses that the patient had received the long-acting local anesthetic levobupivacaine and may not require additional morphine. Nurses were informed that IV morphine and anti-emetic (metoclopramide 10 mg) could still be given if it was felt that the patient required this. Patients randomized to the control group underwent standard treatment. All patients returned to the cardiology ward after the procedure where the femoral sheath was removed approximately 4 hours later. Nurses on the ward were unaware that the control patients were in the study. Thus, these patients received standard care, which may or may not have involved IV opiate and anti-emetic prior to sheath removal. The following morning, the patients were interviewed and their pain scores recorded for 3 time points: 1) sheath insertion, 2) waiting for sheath removal, and 3) sheath removal. This was done the next morning to avoid interviewing while patients might be experiencing the effects of the IV opiate. The time of sheath removal and the blood pressure and heart rate before and after sheath removal were recorded. Any drowsiness, nausea or vomiting after sheath removal was recorded. Data handling and statistical analysis. Data were entered into a spreadsheet and analyzed using Excel 2002 (Microsoft Inc.) on a laptop computer. Data are presented as average values ± SEM or range, as appropriate. Statistical analysis was performed using the Student’s unpaired two-tailed t-test on continuous data with a normal distribution, and using the Chi-squared or Mann-Whitney test on categorical data. Results Sixty patients took part in the study, 30 of whom received additional levobupivacaine (0.5%) and 30 who received normal standard care. There was no significant difference between the groups in terms of baseline characteristics (Table 1). Furthermore, there were no procedural differences between the groups in terms of anticoagulant use, number of vessels stented, length of procedure, or duration of sheath insertion (all p > 0.05). There was no difference between groups in terms of blood pressure or heart rate at baseline during or after the procedure (all p > 0.05). More patients in the control group received intravenous morphine at the time of sheath removal. In the control group, 11 patients received morphine prior to sheath removal compared to 2 patients in the levobupivacaine group. Of the 11 patients in the control group, 3 patients experienced nausea and 2 vomited, compared to 2 patients feeling nauseated and none vomiting in the levobupivacaine group. There was no difference between the control group and levobupivacaine group in pain scores at the time of sheath insertion (2.0 ± 0.4 versus 1.8 ± 0.3; p = 0.80). Both groups recorded low pain scores while waiting for sheath removal, and the score was slightly (but not significantly) lower in the levobupivacaine group (1.3 ± 0.2 versus 0.8 ± 0.2; p = 0.09). Pain scores were significantly lower in the levobupivacaine group during sheath removal 2.2 ± 0.4 versus 1.1 ± 0.2; p = 0.02) (Figure 1). Furthermore, there were no femoral hematomas > 5 cm in either group. One patient (control group) developed a small femoral artery pseudoaneurysm which delayed discharge from the hospital. Discussion This study is the first to investigate the effect of subcutaneous levobupivacaine use in the management of a femoral sheaths during PCI. We have demonstrated that, despite a reduction in the use of an IV opiate, patients receiving levobupivacaine at the time of PCI experienced less pain during sheath removal 4 hours later. Traditionally, IV opiate or repeat subcutaneous lidocaine have been used as analgesics during femoral artery sheath removal. Increasingly, sheath removal is performed by nursing staff who may not be permitted to inject further local anesthetic agents, thus use opiate analgesia. However, opiates have several deleterious side effects even when administered at therapeutic doses. The additional actions of opiates can result in unwanted systemic side effects including hypotension, respiratory depression and vomiting. Systemic hypotension may reduce the coronary blood flow, increasing the risk of acute stent thrombosis. Respiratory depression may result in acidosis and hypoxia, which can have deleterious cardiac effects. Nausea and vomiting have been shown to affect 40% of people who receive IV morphine and can occur despite concomitant administration of anti-emetics. The act of vomiting may induce mechanical strain on the femoral artery sheath entry site and cause re-bleeding, which can ultimately lead to additional discomfort and, if severe, delayed discharge. Notably, these side effects of morphine, which may impede the patient’s recovery, occur at normal analgesic therapeutic levels. Thus, an alternative analgesic which does not have these side effects could be preferable for post-PCI recovery and for patient safety. Furthermore, morphine is a controlled drug, requiring two staff-grade nurses to administer it at our institution at a time of the day when nursing staff numbers may be low. Thus, an alternative to morphine may have practical benefits to nurses on the ward, increasing nursing time for other patients. A longer-acting local anesthetic agent is one approach to avoid the potential problems with IV morphine. Bupivacaine^3–5 has been effectively used in several clinical situations such as labor analgesia via lumbar epidural blockade, post-prostate analgesia and abdominal surgery.^6,7 However, there have been concerns regarding the potential cardiotoxicity of bupivacaine given that it exhibits tight-binding affinity to myocardial sodium channels.^5,8,9 The “L” stereoisomer of levobupivacaine is significantly less potent at blocking sodium channels and therefore less cardiotoxic than bupivacaine,¹⁰ but levobupivacaine has similar analgesic properties.^11,12 Thus, levobupivacaine is potentially safer to use in cardiac patients. In this current study we saw no evidence of myocardial depression in the levobupivacaine group. Both bupivacaine2 and levobupivacaine5 provide longer-lasting analgesia than lidocaine, but their onset of action is delayed, thus we used lidocaine for initial anesthesia in both groups. Levobupivacaine has been evaluated in several clinical settings.¹³ However, there have been no previous studies investigating the use of levobupivacaine in the management of femoral artery sheaths following PCI. This study showed that the additional use of levobupivacaine reduced the pain experienced during removal of the femoral artery sheath compared to lidocaine alone. The pain scores in the levobupivacaine group were, on average, 1 less than the control groups. While this is a statistically significant result, whether this difference is clinically significant is less certain. In general, patients in this study tolerated the presence of the femoral artery sheath well, but there was a trend towards a reduction in pain experienced during the period where patients waited for sheath removal, although this did not reach statistical significance. The perception of pain can vary considerably between patients, however, it is likely that any reduction in discomfort would be welcomed by the patient. In conclusion, the use of levobupivacaine in patients undergoing PCI with delayed sheath removal reduced the need for IV opiate and provided better analgesia and patient comfort than lidocaine alone. Email: s.j.leslie@ed.ac.uk

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