Abstract
The aim of the present study is to evaluate the analgesic activity, patient satisfaction, and side effect profile of different concentrations of levobupivacaine plus fentanyl administered through thoracic epidural patient-controlled analgesia in patients undergoing thoracotomy. The study included 60 patients who were randomly divided into three groups. At the end of the surgery, group I (n = 20) received 0.125% levobupivacaine plus 3 mg fentanyl, group II received 0.1% levobupivacaine plus 3 mg fentanyl, and group III received 0.05% levobupivacaine plus 3 mg fentanyl via an epidural catheter placed at the level of T10-11 or T11-12. For all groups, the patient-controlled analgesia device was programmed to deliver a loading dose of 14 mL at an infusion rate of 4 mL/h, and a bolus dose of 2 mL/h, with a locked out interval of 15 minutes and 60 mL of a 4-hour limit. The following parameters were evaluated at 5, 10, 15, 20, 30, and 40 minutes and at 1, 2, 4, 8, 16, and 24 hours after admission to the intensive care unit, at which nausea and vomiting scales, Visual Analog Scale I-II, Ramsay sedation scale, Bromage scale, pupil diameter, arterial blood pressure, heart rate, respiratory rate, and SpO2 were measured and recorded. Any side effect was also documented. As the result of the evaluation, visual Analog Scale I-II scores, patient satisfaction scores, mean arterial blood pressure, and heart rate significantly differed in group I as compared with groups II and III. No side effects were encountered except mild nausea, which was seen in group III and did not require treatment. Motor blockage, pupil size, respiratory rate, and SpO2 were not monitored in any of the patients in all groups. In conclusion, our study suggested that the use of 0.125% levobupivacaine, together with 3 mg/mL fentanyl, constitutes a good combination, and can be used safely without causing hemodynamic change and motor block
Keywords
analgesia, epidural: thoracic; analgesia, patient-controlled; pain, postoperative; thoracotomy;
1. Introduction
Inadequate pain management after thoracotomy causes complications such as incapability of deep breathing, difficulties in coughing up secretions, bronchospasm, atelectasia, pneumonia, hypoxemia, respiratory failure, and prolongation of mechanical ventilation.1, 2 The purpose of pain management in the postoperative period is to provide pain control, prevent respiratory and gastrointestinal system dysfunctions, and facilitate early mobilization.3 A related report in literature indicated that epidural analgesia as the gold standard management for pain in the post-thoracotomy period.4 Compared with other methods, epidural analgesia plays an important role in reducing pulmonary complications, such as atelectasia, pneumonia, and respiratory deficiency.5
To our knowledge, the use of epidural levobupivacaine plus fentanyl as post-thoracotomy analgesia has not yet been investigated. In addition, the debate relative to the effects of volume and concentration of the local anesthetic solution for epidural analgesia remains unresolved.6 In our study, we ventured to determine the minimally effective concentration of levobupivacaine in patients undergoing thoracotomy by comparing different concentrations of levobupivacaine plus fentanyl for thoracic epidural patient-controlled analgesia method.
2. Methods
The ethics committee of the university hospital approved the study, and the tenets of the Declaration of Helsinki were strictly observed. A total of 60 patients (50 men and 10 women) between 20 and 80 years of age, who were undergoing elective posterolateral or lateral thoracotomy at Pamukkale University Medical School Hospital from July 2007 to February 2008, were included in the study. Patients were divided randomly into three groups, with a closed envelope system. Group I (n = 20) received 0.125% levobupivacaine + 3 μg/mL fentanyl, group II (n = 20) received 0.1% levobupivacaine + 3 μg/mL fentanyl, and group III (n = 20) received 0.05% levobupivacaine + 3 μg/mL fentanyl. Written informed consent was obtained from all participants. Patients with ASA (American Society of Anesthesiologists) classification of I–III were included in the study. Exclusion criteria were as follows: allergies to any of the medicines used in the study; serious cardiac, renal, or liver diseases; morbid obesity (body mass index >40); history of bleeding disorders; and contraindications for epidural anesthesia.
One hour before anesthesia, patients were premedicated with midazolam 2 mg i.v. and atropine 0.01 mg/kg i.v. The epidural catheter was inserted between T10 and T11 using a loss of resistance technique for confirmation, and the tip of the catheter was directed upward for 5 cm. A loading dose of 14 mL was given, and an infusion at 4 mL/h was started following attachment of the patient-controlled analgesia device to the epidural catheter when the closure of skin was started. The locked out interval was set at 15 minutes, and each bolus dose was set at 2 mL.
After patients' admission to the post-operative intensive care unit, the following clinical manifestations were scaled: satisfaction scoring (0, severe pain; 1, pain with narcotic; 2, slightly uncomfortable with no narcotic; 3, no discomfort), motor function by Bromage scale (0, no motor block; 1, inability to raise the extended legs; 2, inability to flex knees; 3, inability to flex ankle joints), sedation level by Ramsay scale (1, anxious, agitated, or restless; 2, cooperative, oriented, tranquil; 3, responding to commands only; 4, brisk response to slight glabellar tap; 5, sluggish response to slight glabellar tap; 6, no response to slight glabellar tap), nausea by 4-point nausea vomiting scale (0, no nausea or vomiting; 1, mild nausea; 2, severe nausea; 3, retching or vomiting), pain by Visual Analog Scale (VAS) (I—pain during normal breathing; II—pain occurring with deep breathing and coughing). Assessment of pupils (due to narcotic use), arterial blood pressure; heart rate (HR), respiration rate; SpO2 values and side effects were also recorded by an anesthesiologist ignorant of the study. Intramuscular injection of 1 mg kg−1 pethidine HCl was given for rescue analgesia when a score of VAS was over 3. Intravenous metoclopramide 10 mg was given for nausea and vomiting. If the sedation score was 5 or higher, the epidural infusion was stopped and the head level was raised.
All statistical analyses were carried out using SPSS statistical software (SPSS for windows, version 14.0). Analysis of variance and t-test was used to compare systolic arterial pressure, diastolic arterial pressure, mean arterial pressure (MAP), HR, respiratory rate (RR), SpO2, VAS scores, and body temperature. A repeated-measures analysis of variance test was used for within-group comparisons. The differences were considered significant when p < 0.05.
3. Results
Age, sex, ASA classification, nausea–vomiting, pupil size, MAP, HR, RR, SpO2, patient satisfaction score (PSS), and hemodynamic parameters are shown in Table 1.
When the groups are compared in terms of VAS I, significantly lower scores were seen in group I than for the other groups at all time points (Table 2). Adequate analgesia level after thoracotomy with respect to VAS I was observed within 5 minutes in group I, 30 minutes in group II, and by the 2nd hour in group III. Similarly, VAS II after thoracotomy were significantly lower (p < 0.05) in group I at all time points. Adequate analgesia level with respect to VAS II was observed within 5 minutes in group I, 30 minutes in group II, and by the 2nd hour in group III.
When the groups were compared with respect to PSS, the satisfaction score was significantly higher in group I than in the other groups (p < 0.05).
No difference in the scores by Bromage scale was detected between the groups, and this also applied to pupil assessment. The score by Bromage scale was 3 in all groups, and no motor blocks were observed.
4. Discussion
In the present study, we found differences in MAP, VAS I, VAS II, mean HRs, and PSS following continuous epidural infusion of three different concentrations of levobupivacaine plus fentanyl in patients admitted for thoracic surgery. Our study also confirms that the best quality analgesia for post-thoracotomy patients is to use a continuous epidural infusion of a mixture of 0.125% levobupivacaine + 3 μg fentanyl. To our knowledge, this is the first report to evaluate the minimal effective concentrations of levobupivacaine with fentanyl in post-thoracotomy patients.
De Cosmo et al7 compared the analgesia quality, motor block, and side effects of two different concentrations of levobupivacaine (0.125% vs. 0.0625%) plus sufentanil (1 mg/mL) given in continuous epidural infusion after thoracotomy. They reported that VAS scores were similar for both groups at rest, but better pain control was established in the group using 0.125% levobupivacaine during coughing. Similarly, in the present study, the VAS I and VAS II values were better for the group administered the 0.125% concentration than for the other groups.
Kopacz et al8 reported a superior analgesia with lower VAS score could be obtained with a combination of levobupivacaine (0.125%) and fentanyl (3 μg/mL). The aim of our study was to determine analgesia quality, and pain in normal breathing which was assessed with VAS score I, while pain during coughing was evaluated with VAS score II. Both the VAS I and II scores were significantly lower in group I than in the other groups (p < 0.05). Adequate analgesia levels with respect to VAS I and VAS II scores after epidural infusion were realized by 5 minutes in group I, by 30 minutes in group II, and by the 2nd hour in group III. We observed that in our study the analgesic activity started earlier mainly due to the increased concentration of the local anesthetic used.
In epidural analgesia with local anesthetics, systemic hypotension frequently occurs. Kopacz and coworkers,8 who used a combination of levobupivacaine 0.125% and fentanyl 4 μg/mL, identified the occurrence of hypotension in 44.6% of their patients. Cheng et al9 compared the efficacy of 0.5% bupivacaine with 0.5% levobupivacaine during elective cesarean section and reported that systemic hypotension could occur likewise in both groups. We did not observe any hypotension and bradycardia in our patients. This might be due to the anchorage of the epidural catheter at the level of T8 and development of limited sympathetic blockage of lower extremities with very low volume of loading dose.
Although opioids are the most effective agents for severe pain, the severity of their side effects is dose related. All opioids cause constriction of the pupils. Tolerance does not develop against this effect, and it is the best sign for determining opioid intoxication and the onset of the analgesic effect.10 We measured the pupil diameter in order to assess the systemic effect of fentanyl. We did not notice any systemic effect in any of the groups.
The other side effect of local anesthetics and opioids in epidural analgesia is urinary retention.11 Etches et al12 reported four patients with oliguria after thoracotomy where meperidine and/or bupivacaine were used for analgesia. Unfortunately, we could not evaluate urinary retention as our patients were urinary catheterized.
The most frequently encountered complications of epidural opioid administration are nausea and vomiting,13 with which many patients are very dissatisfied during the post-operative period. When local anesthetics are used as an epidural infusion, they prevent gastrointestinal paralysis, and in turn reduce in nausea and vomiting and visceral reflex activity. In the present study, no nausea was reported group I; mild nausea was reported in two patients in group II and 10 patients in group III, but this did not necessitate intervention. We consider that this nausea may be related to the use of pethidine HCl for pain control.14
In conclusion, our study suggests that the use of 0.125% levobupivacaine combined with 3 μg/mL fentanyl, constitutes a good analgesia; this dose can be used safely without causing hemodynamic change and motor block.