Although paravertebral block (PVB) is basically easy to perform, its success rate in breast cancer surgery varies according to the extent of surgery, e.g., whether dissection of the axilla is performed. When PVB supplemented with IV sedation was used in breast surgery with axillary dissection, the incidence of inadequate block with the multiinjection technique (C7 to T6) was 15% (1) and with the single-injection (T4) technique was 19% (2). However, an important advantage of PVB with bupivacaine in patients undergoing breast surgery is the long-lasting postoperative analgesia (2–4).
Patients receiving PVB in addition to general anesthesia, or PVB supplemented with IV sedation only, seem to have shorter recovery times (2), experience less postoperative pain (2,3), require fewer analgesics (1,2), and experience less postoperative nausea and vomiting (PONV) (2,3) than breast surgery patients operated on under general anesthesia without regional block. None of the randomized studies on PVB in breast surgery has been placebo controlled; thus, the patients given PVB probably have expected effective postoperative analgesia. To exclude this bias, we planned a study in which all patients were given general anesthesia for breast cancer surgery. In addition, before the induction of general anesthesia, a PVB with bupivacaine or a sham block with saline was performed in a randomized and blinded manner.
The study was approved by the Institutional Ethics Committee and the National Agency for Medicines. Written, informed consent was obtained from all patients. We studied 60 ASA status I–III patients scheduled to undergo elective breast tumor resection or mastectomy with radioisotope-guided (sentinel) lymph node biopsy and general anesthesia. The exclusion criteria included bleeding disorders, contraindications to nonsteroidal antiinflammatory drugs (NSAIDs), allergy to amide-type local anesthetics or NSAIDs, infection at the thoracic paravertebral injection site, pregnancy or breast-feeding, severe obesity (body mass index >35 kg/m2), and Parkinson’s disease. At the preoperative visit, the patients were instructed by one of the investigators how to use visual analog scale (VAS; 0–10 cm) and numerical rating scale (NRS; 0–10).
The patients were premedicated with oral diazepam 0.1–0.12 mg/kg 1–2 h before anesthesia. Clinical monitoring included electrocardiography, pulse oximetry, noninvasive arterial blood pressure, and bispectral index (BIS). They were randomly assigned to receive an ipsilateral PVB at T3 with either bupivacaine HCl 5 mg/mL (Bicain®; Orion Pharma, Espoo, Finland) or saline. A staff anesthesiologist, not participating in study assessment, performed the procedure behind a drape curtain so that the patient, her attending anesthesiologist, and the nursing staff were blinded to the study drug. The patient was in the lateral position with the side to be blocked and operated upward. A 25-gauge needle was inserted 2.5 cm lateral from the cephalad edge of the third thoracic vertebral spinal process, and the skin, subcutaneous tissue, and periosteum of the transverse process were anesthetized with 2–5 mL of lidocaine 10 mg/mL. The PVB was performed with an 18-gauge Tuohy needle and the loss-of-resistance technique, seeking contact with the lateral process of the third thoracic vertebra as a landmark before advancing the needle into the paravertebral space. The bupivacaine dose (0.3 mL/kg) was injected into the paravertebral space in small aliquots with repeated aspiration tests. In another 30 patients after similar infiltration anesthesia with lidocaine, a subcutaneous saline injection of 2 mL was given with a Tuohy needle after first having contacted the lateral process of the third thoracic vertebra and then withdrawing the needle tip to the subcutaneous layer. The patients and all other staff involved in patient management and data collection, including the patient’s anesthesiologist giving the general anesthesia, were unaware of the group assignment.
The patient was then turned supine and given glycopyrrolate 0.2 mg IV and fentanyl 1–2 μg/kg IV. General anesthesia was induced with propofol 2–3 mg/kg followed by rocuronium 0.5–0.8 mg/kg to facilitate endotracheal intubation. Anesthesia was maintained with sevoflurane in 40% oxygen in air, keeping the BIS at 40–60 (BIS 2000 monitor, Version 3.3; Aspect Medical Systems, Natick, MA). Heart rate and mean arterial blood pressure (MAP) were maintained within ±20% of the preoperative baseline by giving IV bolus doses of fentanyl approximately 1 μg/kg if the MAP or heart rate increased more than 20% from the baseline. Ephedrine 10 mg was given IV as needed to keep MAP more than 65 mm Hg. All patients were tracheally intubated and mechanically ventilated by using volume-controlled positive-pressure ventilation. Inhaled oxygen, end-tidal sevoflurane, and carbon dioxide concentrations were monitored with a Datex-Ohmeda ADU/AS3 anesthesia delivery unit (Datex-Ohmeda Division, Instrumentarium AB, Bromma, Sweden), which also recorded the consumed volume of liquid sevoflurane. Fresh gas flow was set at 3 L/min.
After emerging from anesthesia, the patients were transferred to the postanesthesia care unit (PACU) for a 2-h observation period. Analgesia in the PACU was provided by oxycodone IV in increments of 2–3 mg (0.04 mg/kg) every 5 min until pain VAS and NRS scores were <3. In the surgical ward, the patients were given oxycodone 0.1 mg/kg IM as needed. Antiemetics were administered if VAS or NRS scores for PONV were >3 or if the patient complained of feeling nausea. First-line medication was metoclopramide 10 mg IV followed as needed by tropisetron 2 mg IV. Droperidol 0.75 mg IV was given in case of persistent PONV. No acetaminophen or NSAIDs were given until the postoperative evening. All patients were given acetaminophen 1 g 3 times daily and ibuprofen approximately 10 mg/kg 3 times daily PO in the surgical ward beginning on the postoperative evening. Analgesia with oral ibuprofen and acetaminophen continued at home, as needed.
The consumption of propofol, sevoflurane, rocuronium, ephedrine, and fentanyl during anesthesia was registered. Recovery from anesthesia and tracheal extubation was assessed by testing the patient’s ability to open the eyes and squeeze hands on verbal command and by asking the patient to tell her birthday and orientation to time and location. In addition, we performed the digit symbol substitution test (DSST) (5) and the Maddox Wing (6) tests every 30 min in the PACU. The DSST is an eye and hand coordination test in which one marks symbols in a chart according to a model, substituting numbers with symbols such as O and X. The subject is given 60 s for the test, and after which the number of correctly marked symbols is counted. The Maddox Wing is an ophthalmological instrument that has been used to detect exophoria and esophoria. The patient sees an arrow with the right eye and a target scale with the left eye. When seen with both eyes, the arrow seems to move and settle down at some point in the target scale. The larger the number, the more exophoria experienced.
Pain intensity on the VAS and NRS (at rest and in motion), time to first analgesia, and consumption of IV oxycodone were recorded by the investigators or a trained nurse in the PACU. PONV and the degree of sedation were assessed on a VAS (0–10 cm) every 30 min for 2 h. In the ward, the patients filled in a questionnaire on the severity of pain, PONV, sedation, quality of sleep, consumption of analgesics, consumption of antiemetics, and ability to move the arm of the side of surgery, as well as any other problems or complications, 6, 12, and 24 h after surgery. The doses of all drugs and their times of administration were checked from the patients’ charts. The patients were interviewed by a study nurse on the first postoperative day. They were also asked about their overall satisfaction with the postoperative analgesia technique by using the NRS scale (0 = dissatisfied; 10 = most satisfied).
Venous blood samples were collected from all patients 0, 5, 10, 20, 30, 45, 60, and 90 min after the completion of the injection of the study drug for assessment of total bupivacaine concentrations. The blood samples were centrifuged, and the plasma was stored at −70°C until analysis of the total plasma concentrations of bupivacaine by high-performance liquid chromatography with a Chiral AGP Column (7).
Postoperative IV oxycodone consumption was used to calculate the statistical power. A sample size estimate indicated that 24 patients per group would give a power of 80% at a level of 0.05 for detecting a difference of at least 30% in oxycodone consumption. The study size was thus prospectively set to 60 patients, with 30 assigned to each treatment group. Statistical analyses were performed with SPSS for Windows, Release 11.0.1 (SPSS Inc., Chicago, IL). Normally distributed data were analyzed by using unpaired Student’s t-tests or analysis of variance for repeated measurements, whereas for analysis of categorical and skewed data, Mann-Whitney U-tests, χ2 tests, or Kruskal-Wallis tests were used as appropriate. The results are presented as mean ± sd, median (interquartile range), or number of patients. P < 0.05 was considered statistically significant.
The two groups were similar with respect to demographic characteristics (Table 1) and to the duration and extent of surgery (Table 2). Dissection of the axillary lymph nodes was performed in 23 patients (11 in the control group and 12 in the bupivacaine group), prolonging surgery by approximately an hour. One patient in the bupivacaine group developed moderate bilateral convulsions without losing consciousness immediately when the total dose (120 mg) had been injected. The convulsions stopped after the administration of diazepam 5 mg IV. Her general anesthesia and surgery could be performed as scheduled, and her data were included in the study. The bupivacaine plasma concentration in the sample taken at the time of convulsions was 1107 ng/mL. No other complications associated with PVB occurred.
There were no differences in the total doses of fentanyl, propofol, rocuronium, or sevoflurane during the anesthesia. The groups were similar with respect to BIS and end-tidal sevoflurane measured at different time points during the anesthesia (induction, intubation, beginning of surgery, axillary dissection, skin closure, end of surgery, extubation, opening of the eyes on verbal command, hand squeeze on verbal command, recall own date of birth, and orientation to time and place). The intervals from the end of surgery to tracheal extubation, to opening the eyes on verbal command, to recalling own date of birth when asked, and to orientation to time and place were similar in both groups. More ephedrine for treatment of hypotension was required in the bupivacaine group (P = 0.02) (Table 2).
Patients with PVB recovered faster from anesthesia and were more alert in the PACU, as indicated by better performance on the DSST and Maddox Wing tests and by lower sedation scores (Table 3). However, PVB did not alter primary awakening from general anesthesia, as indicated by similar recovery times (responses to commands) in both groups. PVB did not alter ipsilateral shoulder mobility, as indicated by similar flexion and abduction on the preoperative day, in the PACU and on the first postoperative day (Table 3).
PVB given before general anesthesia reduced the severity of postoperative pain and oxycodone consumption after breast tumor resection or mastectomy with radioisotope-guided (sentinel) lymph node biopsy (Table 4). The patients given PVB with bupivacaine had less postoperative pain, as indicated by longer times to first analgesic dose, lower VAS scores, and 40% smaller oxycodone consumption in the PACU. PVB reduced the opioid demand statistically significantly (P < 0.05) in patients who underwent axillary dissection. On the first postoperative day, the number of patients who experienced continuous aching pain and pain at rest was significantly smaller in the PVB group (Table 5). Additionally, the PVB patients had fewer incidents of PONV (P = 0.026) and received fewer doses of antiemetic medication (P = 0.046) than the control group (Table 4). On the whole, the patients were very satisfied with the anesthesia, pain management, and overall anesthetic treatment, as indicated by the NRS scores. The only significant difference between groups was poorer satisfaction scores for treatment of PONV in the PACU in the control group (P = 0.016).
There was great interindividual variation in the total plasma concentrations of bupivacaine. The largest total bupivacaine plasma concentration (750 ng/mL), on average, occurred 20 min after the injection (Fig. 1). The largest individual total bupivacaine concentration (1310 ng/mL) was measured in a 20-min sample.
This study showed that a PVB with bupivacaine 1.5 mg/kg, performed before general anesthesia in patients scheduled for breast surgery, resulted in less need for postoperative opioid analgesics in the first hours after surgery and in less overall intensity of pain on the first postoperative day. The fact that the initial postoperative analgesia was relatively good may have had certain beneficial consequences. For instance, the smaller amount of opioid consumed by the PVB patients, in comparison with control patients, in the PACU was probably an explanation for the rapid psychomotor recovery and the infrequent PONV in the patients given PVB with bupivacaine before surgery.
The effect of all our PVBs was not comparable, because some of the patients who had received bupivacaine for the PVB needed oxycodone early in the PACU. Because of the variability in the duration of surgery and in the patients’ ability to cooperate, a reliable estimation of the quality of the PVB during surgery was not possible. Although there is evidence of vertical spread of the paravertebrally injected local anesthetic over several adjacent dermatomes (8–10), the interindividual variation in the range of the spread of sensory analgesia, or even radiographic contrast medium, is large. For instance, Cheema et al. (9) noted a unilateral spread of sensory analgesia from one to eight dermatomes after a single injection of 0.5% bupivacaine 15 mL for thoracic PVB. Surgically acceptable conditions for breast surgery, also including occasional axillary dissection, have been accomplished by single-injection PVB (2,11), although a substantial number of patients required additional analgesics, infiltration with a local anesthetic, and deep sedation. Whether a multiinjection PVB (at C7-T6 or C7-T7) (1,4,12) is superior to a single-injection technique for breast resection has not been evaluated. Published results on pain and recovery are quite similar. In our opinion, although the incidences of pneumothorax and intravascular injection in PVBs are small, we find it logical that the risk of complications per patient increases when multiple injections are performed.
In one patient of the PVB group, at least a part of the solution must have been accidentally injected intravascularly, despite repeated negative aspiration tests before the injection. It can be assumed, however, that only a small fraction of the injected bupivacaine entered the blood circulation, because the patient did not lose consciousness and because the convulsions were easily aborted by a small IV dose of diazepam. Unfortunately, we did not measure the free plasma concentrations of bupivacaine; therefore, no conclusions can be drawn regarding the relationship between toxicity and plasma concentrations (13). No other complications possibly associated with PVB—such as interpleural puncture, pneumothorax, or dural puncture (14)—were encountered in our study. Such complications are rare, but serious, and therefore it is advisable to perform the PVB in awake and cooperative patients. If general anesthesia is induced soon after the PVB injection, careful monitoring of respiratory and hemodynamic variables is mandatory.
The incidence of PONV in our patient population was relatively infrequent, considering that the general risk of PONV in women undergoing breast surgery under general anesthesia is high (15). To what extent the use of propofol (16)—for the induction of anesthesia, for avoidance of nitrous oxide (17), and as an active strategy of early treatment of PONV (18)—reduced the occurrence of PONV remains speculative. In any case, the patients who had a PVB with bupivacaine experienced less PONV, and, as mentioned earlier, this may be associated with both the smaller amount of consumed oxycodone and less blurred consciousness in the immediate postanesthetic period. These are factors known to induce nausea (17).
All our patients were given ibuprofen and acetaminophen as soon as they could swallow tablets in the post-PACU period. The opioid consumption and, consequently, the PONV scores were very low in the post-PACU period. The patients with bupivacaine PVB still had significantly lower pain VAS scores at six hours after the operation (P = 0.016). Although the pain VAS scores were low in both groups at 24 hours after the operation, some patients in the placebo group experienced pain at rest and continuous aching pain; few or none did so in the PVB group (P < 0.01). Preoperative bupivacaine PVB seems to have an extended analgesic effect that lasts for at least 24 hours after breast surgery.
The usefulness of a preincisional single-injection PVB at the level of the third thoracic vertebra for postoperative analgesia in women undergoing breast surgery, which also often involves axillary dissection, was substantiated in this randomized and placebo-controlled study. In our study, the analgesic effect was detectable for the entire 24 hours after surgery. Our 60 patients will be assessed regularly for a year to detect any possible development of chronic pain and its relationship to analgesia in the immediate postoperative period (19). The immediate recovery from anesthesia of those of our patients who had received a PVB was qualitatively good, as indicated by more rapid regaining of normal psychomotor function and control of the ocular muscles. The fact that more patients in the placebo group had PONV may be due, primarily, to their larger consumption of IV oxycodone. There are block performance-related risks involved in PVB. The intravascular injection of bupivacaine might have been avoided in our patient if the solution had contained epinephrine. It is also important to realize the risk of tension pneumothorax in patients who receive a thoracic PVB soon followed by general anesthesia with tracheal intubation and mechanical positive-pressure ventilation. We are hopeful that our follow-up of these patients will demonstrate prolonged benefits of using PVB.
1. Coveney E, Weltz CR, Greengrass R, et al. Use of paravertebral block anesthesia in the surgical management of breast cancer: experience in 156 cases. Ann Surg 1998;227:496–501.
2. Pusch F, Freitag H, Weinstabl C, et al. Single-injection paravertebral block compared to general anaesthesia in breast surgery. Acta Anaesthesiol Scand 1999;43:770–4.
3. Klein SM, Bergh A, Steele SM, et al. Thoracic paravertebral block for breast surgery. Anesth Analg 2000;90:1402–5.
4. Weltz CR, Greengrass RA, Lyerly HK. Ambulatory surgical management of breast carcinoma using paravertebral block. Ann Surg 1995;222:19–26.
5. Hindmarch I. Psychomotor function and psychoactive drugs. Br J Clin Pharmacol 1980;10:189–209.
6. Hannington-Kiff JG. Measurement of recovery from outpatient general anaesthesia with a simple ocular test. BMJ 1970;3:132–5.
7. Arvidsson T, Bruce HF, Halldin MM. Lack of metabolic racemisation of ropivacaine, determined by liquid chromatography using a chiral AGP column. Chirality 1995;7:272–7.
8. Karmakar MK, Kwok WH, Kew J. Thoracic paravertebral block: radiological evidence of contralateral spread anterior to the vertebral bodies. Br J Anaesth 2000;84:263–5.
9. Cheema SP, Ilsley D, Richardson J, Sabanathan S. A thermographic study of paravertebral analgesia. Anaesthesia 1995;50:118–21.
10. Richardson J, Jones J, Atkinson R. The effect of thoracic paravertebral blockade on intercostal somatosensory evoked potentials. Anesth Analg 1998;87:373–6.
11. Naja MZ, Ziade MF, Lönnqvist PA. Nerve-stimulator guided paravertebral blockade vs. general anaesthesia for breast surgery: a prospective randomized trial. Eur J Anaesthesiol 2003;20:897–903.
12. Greengrass R, O’Brien F, Lyerly K, et al. Paravertebral block for breast cancer surgery. Can J Anaesth 1996;43:858–61.
13. Tucker GT, Mather LE. Pharmacology of local anaesthetic agents: pharmacokinetics of local anaesthetic agents. Br J Anaesth 1975;47(Suppl):213–24.
14. Karmakar MK. Thoracic paravertebral block. Anesthesiology 2001;95:771–80.
15. Hammas B, Thorn SE, Wattwil M. Superior prolonged antiemetic prophylaxis with a four-drug multimodal regimen: comparison with propofol or placebo. Acta Anaesthesiol Scand 2002;46:232–7.
16. Jokela RM, Kangas-Saarela TA, Valanne JV, et al. Postoperative nausea and vomiting after sevoflurane with or without ondansetron compared with propofol in female patients undergoing breast surgery. Anesth Analg 2000;91:1062–5.
17. Gan TJ, Meyer T, Apfel CC, et al. Consensus guidelines for managing postoperative nausea and vomiting. Anesth Analg 2003;97:62–71.
18. Eberhart LH, Mauch M, Morin AM, et al. Impact of a multimodal anti-emetic prophylaxis on patient satisfaction in high-risk patients for postoperative nausea and vomiting. Anaesthesia 2002;57:1022–7.
© 2004 International Anesthesia Research Society
19. Tasmuth T, von Smitten K, Kalso E. Pain and other symptoms during the first year after radical and conservative surgery for breast cancer. Br J Cancer 1996;74:2024–31.