Prospective, Comparative Study of the On-Q s PainBuster s Postoperative Pain Relief System and Thoracic Epidural Analgesia After Thoracic Surgery Michael Ried, MD,* Christian Schilling,* Tobias Potzger,* Karl-Peter Ittner, MD,† Andrea Rupp, MD,‡ Tamas Szöke, MD,§ Hans-Stefan Hofmann, MD,*§ and Claudius Diez, MD* Objective: Pain after thoracotomy is associated with intense discomfort leading to impaired pulmonary function. Design: Prospective, non-randomized trial from April 2009 to September 2011. Setting: Department of Thoracic Surgery, single-center. Participants: Thoracic surgical patients. Interventions: Comparison of thoracic epidural analgesia (TEA) with the On-Qs PainBusters system after thoracotomy. Measurements and Main Results: The TEA group (n ¼ 30) received TEA with continuous 0.2% ropivacaine at 4 mL-to-8 mL/h, whereas Painbusters patients (n ¼ 32) received 0.75% ropivacaine at 5 mL/h until postoperative day 4 (POD4). Basic and on-demand analgesia were identical in both groups. Pain was measured daily on a numeric analog scale from 0 (no pain) to 10 (worst pain) at rest and at exercise. There were no significant differences regarding demographic and preoperative data between the groups, but PainBusters patients had a slightly lower relative forced
expiratory volume in 1 second (FEV1) (71 ⫾ 20% versus 86 ⫾ 21%; p ¼ 0.01). Most common surgical procedures were lobectomies (38.8%) and atypical resections (28.3%) via anterolateral thoracotomy. Most common primary diagnoses were lung cancer (48.3%) and tumor of unknown origin (30%). At POD1, median postoperative pain at rest was 2.1 (1; 2.8) in the TEA group and 2 (1.5; 3.8; p ¼ 0.62) in the PainBusters group. At exercise, median pain was 4.3 (3.5; 3.8) in the TEA group compared to 5.0 (4.0; 6.5; p ¼ 0.07). Until POD 5 there were decreases in pain at rest and exercise but without significant differences between the groups. Conclusions: Sufficient analgesia after thoracotomy can be achieved with the intercostal PainBusters system in patients, who cannot receive TEA. & 2014 Elsevier Inc. All rights reserved.
T
is placed intraoperatively in the intercostal space at the site of the surgical incision. The PainBusters system has proven its efficacy in obstetric, orthopedic and cardiac surgery for pain control but has not been examined in detail after thoracic surgery.5–7 Safety and performance data are still lacking. Therefore, the authors conducted this pilot study with the objective of determining if postoperative analgesia with the PainBusters system is an efficient, safe, and reliable alternative to patient-controlled TEA after thoracic surgery.
HORACIC SURGERY with thoracotomy has been reported to be among the most intense clinical postoperative pain experiences known.1 The sources of pain not only arise from surgical incisions but also from disrupted intercostal nerves, retracted ribs, chest wall inflammation adjacent to the incision, injured pulmonary parenchyma, and from the placement of chest tubes.2 Nociceptive pathways after thoracic surgery are poorly understood, but it is believed that noxious input is conveyed to the central nervous system along the intercostal, vagus, and phrenic nerves. The shoulder pain that frequently accompanies thoracic procedures seems to derive from afferent phrenic activity.3 In addition, the need for constant respiratory effort and enhanced respiratory toilette produces an intense and relentless barrage of noxious input. Control of postoperative pain is important and might help to avoid chronic thoracic pain syndromes. Thoracic epidural analgesia (TEA) is currently the standard for analgesia after thoracic surgery with anterolateral thoracotomy and usually all patients, in the absence of contraindications, receive an epidural catheter for major thoracic procedures.4 It combines a local anesthetic and a lipophilic opioid for initial and maintenance analgesia. The placement of the catheter depends on what incision is planned (eg, anterolateral/posterolateral, median sternotomy). Judicious fluid and pressor administration avoids the large fluid shifts that could adversely affect physiology, particularly in patients with limited cardiac or pulmonary reserve.2 However, TEA cannot be used in all patients due to technical, medical, or other reasons. Apart from patientcontrolled intravenous analgesia (PCA), the On-Qs PainBusters system is a closed, patient-independent system for local continuous delivery of a local anesthetic via a Soaker™ catheter with multiple lateral openings for widespread infiltration of wounds (I-Flow Corp., Lake Forest, CA). This catheter
KEY WORDS: thoracotomy, thoracic surgery, thoracic epidural analgesia, PainBusters, postpoerative pain
METHODS The study was designed as a prospective but not randomized pilot trial from April 2009 to September 2011 at the Departments for Thoracic Surgery, University Medical Center Regensburg and Hospital Barmherzige Brüder Regensburg. The authors tested the hypothesis of whether or not postoperative analgesia with the On-Qs PainBusters postoperative pain relief system (I-Flow Corp., LLC, Lake Forest, CA) is an efficient, safe, and reliable alternative in pain reduction compared to patient-controlled TEA in patients after open thoracic surgery who are not suitable for TEA. This study was approved by the local ethics committee of the University Medical Center Regensburg, and individual consent was obtained from each patient. Patients 418 years with open lung
From the Departments of *Thoracic Surgery and †Anesthesiology, University Medical Center Regensburg and the Departments of ‡Anaesthesiology and §Thoracic Surgery, Hospital Barmherzige Brüder Regensburg, Regensburg, Germany. Send reprint requests to Michael Ried, MD, University Medical Center Regensburg, Department of Thoracic Surgery, Franz-JosefStrauß-Allee 11, 93053 Regensburg, Germany. E-mail: micha. [email protected] © 2014 Elsevier Inc. All rights reserved. 1053-0770/2601-0001$36.00/0 http://dx.doi.org/10.1053/j.jvca.2013.12.028
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Table 1. Basic and On-demand Analgesia PainBusters (N ¼ 32)
TEA (N ¼ 30)
Basic analgesia Day of operation POD 1 to 3 On-demand analgesia Day of operation POD 1 to 3
metamizol, 1g IV (maximum 5g IV daily), or paracetamol, 1g IV (maximum 4g IV daily) ibuprofen, 400 mg po q 8 h, or metamizol, 1g IV or po (maximum 5g daily) piritramide paracetamol, 1g IV (maximum 4g daily), or morphine, 10 mg po q 4 h, or oxycodone, 10 mg or 20 mg every 8 h
Abbreviations: IV, intravenous; po, perioral; POD, postoperative day.
resections were included. Patients with the following criteria were excluded from this study sample: Age o18 years, previous thoracic surgery, degenerative vertebral disease, chronic pain syndromes, rheumatic disease, chronic steroid or analgesic drug use, and patients with impaired compliance. Minimally invasive procedures, eg, videoassisted thoracoscopic surgery, were not used in these patients. Preoperatively, TEA was planned for all patients in this study. Patients with contraindications for TEA or who refused TEA were treated with the PainBusters system. This included patients who had evidence of an infection, who had an elevated bleeding risk due to inhibitors of platelet aggregation or other anticoagulation, or patients in whom preoperative placement of an epidural catheter technically was not possible. The primary endpoint was the analysis of the postoperative pain within the first 5 postoperative days, whereas secondary endpoints included postoperative complications, eg, pneumonia, length of hospital stay, and the amount of analgesic drugs used after surgery. Data were collected in patient records and specific pain sheets and then were transferred onto a spreadsheet. Postoperative pain was measured with a numeric scale from 0 (no pain) to 10 (worst pain) and was assessed at least 2 times a day at rest and during exercise (mobilization) in the first 5 postoperative days. Glomerular filtration rate (GFR) was estimated with the abbreviated modification in diet in renal disease (MDRD) equation and was calculated as follows: eGFR (mL min1 1.73m2) = 186.3 SCr1.154 Age0.203 0.74 (if female).8 Chronic obstructive lung disease was defined according to the GOLD classification with at least an FEV1/FVC o0.70 (stage I) or lower.9 Ventilation time was defined as duration of postoperative mechanical ventilation in the intensive care unit. Postoperative extubation in the operating room was preferred in all patients immediately after finishing the surgical procedure. Prerequisites were stable hemodynamic conditions and sufficient oxygenation. All patients received total intravenous anesthesia (TIVA) with propofol and remifentanil. Anesthesia was induced with 100 mg-to200 mg of fentanyl. The epidural catheter was inserted at T6-T7 before surgery and before induction of general anesthesia by an experienced anesthesiologist. During surgery, the authors used bupivacaine and then postoperatively switched to ropivacaine. Bupivacaine 0.25% was initially instilled followed by 10 mg of sufentanil (patients 470 years received 5 mg). Bupivacaine was started at infusion rates from 4 mL/hto-8 mL/h. Thirty minutes before finishing the surgery, patients in both groups received a single intravenous dose of paracetamol (acetaminophen: 1g) or metamizol (1g). TEA used ropivacaine 0.2% at patientcontrolled infusion rates from 4 mL/h-to-8 mL/h. It was continued until all thoracotomy tubes were removed (usually POD 4). The PainBusters intercostal catheter was implanted in all patients by the thoracic surgeon at the end of the surgery before the final wound closure. The catheter can be placed directly under the surgeon’s view. The PainBusters elastomeric pump contained 600 mL of 0.75% ropivacaine and released it at 5 mL/h. The PainBusters was removed at POD 4. In addition to TEA and intercostal analgesia, all patients received a basic and an on-demand postoperative analgesia based on specific pain protocols (Table 1).
Statistical analysis was done with Stata 10.1 SE (StataCorp., College Station, TX). Continuous variables first were tested on normality with Q-Q plots and the Shapiro-Wilk test. If normally distributed, these data are shown as mean ⫾ standard deviation and if non-normally distributed as median with 25th and 75th percentiles. Comparison of 2 continuous normally distributed variables was done with Student’s t-test or with Wilcoxon’s rank sum test if non-normally distributed. Intragroup differences of continuous normally distributed variables were analyzed with 1-way analysis of variance followed by Bonferroni’s post hoc test or if non-normally distributed with Friedman’s test. Categorical data were shown as absolute values and frequencies. Comparison of 2 categorical variables in a 2 2 contingency table was performed with Fisher’s exact test and data in a 2 k table with Pearson’s chi-square test. All tests were 2-sided. A p value o 0.05 was considered significant. RESULTS
The authors have summarized the demographic data of all 62 patients in Table 2. Apart from the FEV1, there were no significant differences between the groups. Patients with the PainBusters had a significantly lower FEV1 than patients with EA (71% ⫾ 3.9 v 86% ⫾ 4.3; p ¼ 0.01). Lobectomy was the
Table 2. Preoperative Characteristics TEA Variable
Age (years) Female gender (%) Body mass index (kg m-2) Hypertension (%) Coronary artery disease (%) Chronic kidney disease (%) Diabetes mellitus (insulindependent) (%) Lipid disorder (%) Chronic obstructive lung disease (%) Lung emphysema (%) Peripheral vascular disease (%) Thyroid gland disorder (%) Hemoglobin (g/dL) Creatinine (mg/dL) Prothrombin time (s) GFR (mL/min/1.72 m2) GFR o60 mL/min/1.72 m2 Relative FEV1 (%) FEV1/FVC
PainBusters
N ¼ 30
N ¼ 32
p value
62 ⫾ 9 30 26 ⫾ 3.7 43 10 0 3
63 ⫾ 10 41 27 ⫾ 5 56 3 6 6
0.68 0.43 0.38 0.44 0.34 0.49 1.00
10 33
22 35
0.30 1.00
7 3
16 10
0.42 0.61
20 31 14 (12.3; 14.8) 14 (11.7; 14.4) 0.8 (0.7; 0.9) 0.8 (0.6; 1.0) 29 (28; 32) 30 (28; 33) 91 (82; 120) 96 (80; 115) 0 3 86 ⫾ 21 71 ⫾ 20 73 ⫾ 14 75 ⫾ 13
0.24 0.33 0.93 0.33 0.56 0.24 0.01 0.77
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Table 3. Operative Procedures TEA Type of surgery
Enucleation [%] Atypical resection [%] Segmental resection [%] Lobectomy [%] Extended lobectomy [%] Pneumonectomy [%] Extended pneumonectomy [%]
Table 4. Postoperative Data s
PainBuster
N ¼ 30
N ¼ 32
14 21 10.5 41 10 0 3.5
6.5 35.5 3 35.5 13 3 0 p ¼ 0.50
most common procedure in both groups (TEA: 41% and PainBuster: 35.5%, respectively) followed by atypical lung resection (21% and 35.5%). Overall, there was no further significant difference between the groups (Table 3). Primary lung cancer was the most common diagnosis in both groups followed by tumor of unknown etiology (Fig 1). Preoperative insertion of an epidural catheter required a median time of 15 minutes (10; 20) in patients who received this type of perioperative analgesia. Postoperative Data Twenty percent in the TEA group and 31% in the PainBusters group required postoperative care at the intensive care unit with a median stay of 2.5 days and 2 days respectively. Patients in the PainBusters group had a significantly lower postoperative ventilation time than patients with TEA (3.0 ⫾ 0.9 v 3.5 ⫾ 1.0 hours; p ¼ 0.04), whereas other postoperative variables such as postoperative stay, frequency of respiratory infection, or frequency of rhythm disturbances remained insignificant (Table 4). There was no episode of hypotension in the TEA group, and only 3% of patients
TEA Variable
Surgical time (min) Ventilation time (h) Postoperative care at ICU (%) ICU stay (days) Postoperative stay (days) Respiratory infection (%)* Rhythm disturbances (%)† Bladder dysfunction (%) Intestinal dysfunction (%) Surgical revision (%) Wound infection (%) Respiratory failure with re-intubation (%)
PainBusters
N ¼ 30
N ¼ 32
p value
135 ⫾ 59 3.5 ⫾ 1.0 20 2.5 (1; 4.5) 12 (9; 14) 20 3 3 3 3 24 3.6
114 ⫾ 56 3.0 ⫾ 0.9 31 2 (1; 4) 11 (9; 14) 12.5 13 3 3 3 16 6.3
0.16 0.04 0.39 0.77 0.50 0.35 1.00 1.00 1.00 0.52 1.00
*Radiologic evidence of atelectasis or pneumonia in the routine chest x-ray and concomitant elevated inflammation parameters in the laboratory investigations. †Supraventricular tachycardia or atrial fibrillation.
experienced bladder dysfunction, ie, urinary retention or intestinal dysfunction. Hospital and postoperative stays did not differ between the groups. The authors have summarized frequencies of drugs, number of drug combinations and drug combinations in the anesthetic recovery room and on the ward in Figure 2. The most frequently used drugs in both groups were metamizol (TEA: 73% v PainBusters: 81%; p ¼ 0.15) and piritramide (TEA: 80% v PainBusters: 84%; p ¼ 0.85). On the ward, ibuprofen, metamizol and piritramide were used with similar frequency and without statistical significance (Table 5). A double drug combination was used most frequently for pain control in the anesthetic recovery room, whereas double and triple combinations were used with similar frequencies on the ward. The most common combination was metamizol and piritramide in the anesthetic recovery room and ibuprofen/metamizol and metamizol/piritramide on the ward. Metamizol/piritramide was significantly more frequently used in the PainBusters group in the anesthetic recovery room compared to the TEA group (p ¼ 0.02). Median pain at rest (TEA: 2.1 [1; 2.8] versus PainBusters 2 [1.5; 3.8]; p ¼ 0.62) and at exercise (TEA: 4.3 [3.5; 4.8] versus PainBusters 5 [4; 6.5]; p ¼ 0.07) did not differ between the groups. There was a decrease of pain at rest and at exercise until POD4 without significant differences between the groups (Fig 3). After removal of the PainBusters and TEA catheter at POD4, there was a slight but insignificant increase in median pain from POD4 to POD5. In addition, there were 2 significant intragroup differences. In the TEA group, there was a significant reduction of pain at exercise between POD2 and POD4 (p ¼ 0.004). In the PainBusters group, pain after exercise significantly decreased from POD1 to POD3 (p ¼ 0.001), indicating an earlier reduction of pain at exercise in the PainBusters group compared to the TEA group. DISCUSSION
Fig 1. Bar graph showing the primary diagnoses in both study groups. There was no statistical significance between the groups.
Proper pain management remains essential after thoracic surgery not only because of prevention of serious pulmonary complications but also for preventing chronic post-thoracotomy
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Fig 2. Upper panel: Frequency of analgesic drugs in the anesthetic recovery room and on the ward. Middle panel: Number of drug combinations in the TEA and the PainBusters group. Lower panel: Drug combinations in the anesthetic recovery room and on the ward.
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Table 5. Total Postoperative Doses of On-demand Analgesia
Drug
Anesthetic recovery room Piritramide (mg) Paracetamol (mg) On the ward Ibuprofen (mg) Metamizol (mg) Piritramide (mg) Oxycodone (mg)
TEA
PainBusters
N ¼ 30
N ¼ 32
25.3 ⫾ 15 1454 ⫾ 522 12 32 49 360
(8; 16) (15; 42) (15; 98) (240; 540)
30.5 ⫾ 19 1200 ⫾ 447 16 21 37 290
(9; 18) (15; 31) (7; 82) (165; 440)
p value
0.29 0.36 0.18 0.32 0.64 0.25
pain syndrome.10 Acute and chronic pain after thoracotomy still remain a challenge to clinicians.11 Although epidural analgesia has been shown to be the method of choice, it was not useful in patients with contraindications such as degenerative vertebral disease. The major finding of the authors’ prospective study was that the PainBusters system provided similar postoperative pain control compared to TEA in addition to comparable basic and on-demand analgesia. In fact, there were no significant differences between the groups from POD1 to POD5 after major thoracic surgery with anterolateral thoracotomy. Several studies have shown the effectiveness of TEA for perioperative pain control after thoracic surgery, and the authors could confirm this finding.12,13 TEA provides better postoperative analgesia compared with parenteral opioids.14 However, TEA might be contraindicated in certain patients, and other alternatives for post-thoracotomy pain relief are needed.15 Continuous thoracic paravertebral analgesia seems to be as effective as TEA in controlling post-thoracotomy pain.16–18 It also has the potential to reduce the risk of postoperative complications and to improve the surgical outcome with respect to the length of hospital stay and pulmonary function.19,20 On the other hand, studies have described TEA as being more efficient than paravertebral continuous block at reducing pain after thoracic surgery.21 In summary, both techniques can be recommended, but further investigations are required.22 In a systematic review of the literature, continuous wound catheters were associated with improved analgesia, reduced opioid use, and increased patient satisfaction after a wide range of surgical procedures.23 Furthermore, these innovative techniques may contribute to the reduction of long-term care costs during hospitalization.24 To the authors’ knowledge, there are only little data in the literature regarding the PainBusters system for treatment of post-thoracotomy pain. The use of the PainBusters system seems to decrease the narcotic use and results in low pain scores when compared with continuous epidural infusion.25 Potential disadvantages of the PainBusters system, as a special form of intercostal catheter, are the less reliable spread of local anesthetic and the rapid absorption.26 Thus, some studies demonstrated less effective analgesia than TEA.27,28 However, the authors could not affirm this finding. Compared with another study,29 overall pain scores and differences in pain at rest and exercise in the authors’ study were quite moderate on POD1 to POD5, indicating efficient basic and on-demand analgesia. Other postoperative variables such
Fig 3. Direct comparison of median pain at rest (Upper panel: Resting pain score) and during exercise (Lower panel: Activity pain score) during the first 5 postoperative days is shown. There was no significant difference between the TEA and PainBusters groups. The black arrow indicates the removal of the TEA or PainBusters catheter. The asterisk (*) refers to a significant intragroup difference in the TEA group between POD2 and POD4 and the number sign (#) to a significant intragroup difference in the PainBusters group between POD1 and POD3.
as the length of hospital stay, frequency of respiratory infection or frequency of rhythm disturbances remained insignificant between the groups in the authors’ study. Epidural and PainBusters catheters usually could be taken out at POD4 after all chest tubes had been removed. The limitations of the study arose primarily from its non-randomized design, which implies that conclusions were necessarily limited in their application and causality could not be determined. In addition, the authors have used a variety of analgesic drugs. Metamizol is not widely available and has
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been banned in some countries. However, all of the mentioned drugs are standard analgesic drugs in the authors’ country and, therefore, routinely used. In conclusion, sufficient analgesia after anterolateral thoracotomy can be achieved with the intercostal On-Qs PainBusters
system. The PainBusters can be used as an alternative local pain catheter in patients who cannot receive TEA. The implantation of the catheter is feasible and effective. Further prospective and randomized studies are warranted to confirm these findings in thoracic surgical patients.
REFERENCES 1. Furrer M, Rechsteiner R, Eigenmann V, et al: Thoracotomy and thoracoscopy: Postoperative pulmonary function, pain and chest wall complaints. Eur J Cardiothorac Surg 12:82-87, 1997 2. Gottschalk A, Cohen SP, Yang S, et al: Preventing and treating pain after thoracic surgery. Anesthesiology 104:594-600, 2006 3. Scawn ND, Pennefather SH, Soorae A, et al: Ipsilateral shoulder pain after thoracotomy with epidural analgesia: The influence of phrenic nerve infiltration with lidocaine. Anesth Analg 93:260-264, 2001 4. Wenk M, Schug SA: Perioperative pain management after thoracotomy. Curr Opin Anaesthesiol 24:8-12, 2011 5. Koukis I, Argiriou M, Dimakopoulou A, et al: Use of continuous subcutaneous anesthetic infusion in cardiac surgical patients after median sternotomy. J Cardiothorac Surg 3:2, 2008 6. Magnani E, Corosu R, Mancino P, et al: Postoperative analgesia after cesarean section by continued administration of levobupivacaine with the On-Q Painbuster system over the fascia vs ketorolac þ morphine i.v. Clin Exp Obstet Gynecol 33:223-225, 2006 7. Rampersad SE, Rowell JC, Chang BM: Comparison of the On-Q Painbuster Post-Op Pain Relief System to a thoracic epidural for control of postoperative thoracotomy pain in a child. Paediatr Anaesth 19:1025-1026, 2009 8. Levey AS, Bosch JP, Lewis JB, et al: A more accurate method to estimate glomerular filtration rate from serum creatinine: A new prediction equation. Modification of Diet in Renal Disease Study Group. Ann Intern Med 130:461-470, 1999 9. Kohler D, Fischer J, Raschke F, et al: Usefulness of GOLD classification of COPD severity. Thorax 58:825, 2003 10. Wildgaard K, Ravn J, Kehlet H: Chronic post-thoracotomy pain: A critical review of pathogenic mechanisms and strategies for prevention. Eur J Cardiothorac Surg 36:170-180, 2009 11. Soto RG, Fu ES: Acute pain management for patients undergoing thoracotomy. Ann Thorac Surg 75:1349-1357, 2003 12. Senturk M, Ozcan PE, Talu GK, et al: The effects of three different analgesia techniques on long-term postthoracotomy pain. Anesth Analg 94:11-15, 2002 13. Kotze A, Scally A, Howell S: Efficacy and safety of different techniques of paravertebral block for analgesia after thoracotomy: A systematic review and metaregression. Br J Anaesth 103:626-636, 2009 14. Block BM, Liu SS, Rowlingson AJ, et al: Efficacy of postoperative epidural analgesia: A meta-analysis. JAMA 290:2455-2463, 2003 15. Helms O, Mariano J, Hentz JG, et al: Intra-operative paravertebral block for postoperative analgesia in thoracotomy patients: A randomized, double-blind, placebo-controlled study. Eur J Cardiothorac Surg 40:902-906, 2011
16. Marret E, Bazelly B, Taylor G, et al: Paravertebral block with ropivacaine 0.5% versus systemic analgesia for pain relief after thoracotomy. Ann Thorac Surg 79:2109-2113, 2005 17. Casati A, Alessandrini P, Nuzzi M, et al: A prospective, randomized, blinded comparison between continuous thoracic paravertebral and epidural infusion of 0.2% ropivacaine after lung resection surgery. Eur J Anaesthesiol 23:999-1004, 2006 18. Fortier S, Hanna HA, Bernard A, et al: Comparison between systemic analgesia, continuous wound catheter analgesia and continuous thoracic paravertebral block: A randomised, controlled trial of postthoracotomy pain management. Eur J Anaesthesiol 29:524-530, 2012 19. Elsayed H, McKevith J, McShane J, et al: Thoracic epidural or paravertebral catheter for analgesia after lung resection: Is the outcome different? J Cardiothorac Vasc Anesth 26:78-82, 2012 20. Esme H, Apiliogullari B, Duran FM, et al: Comparison between intermittent intravenous analgesia and intermittent paravertebral subpleural analgesia for pain relief after thoracotomy. Eur J Cardiothorac Surg 41:10-13, 2012 21. Messina M, Boroli F, Landoni G, et al: A comparison of epidural vs. paravertebral blockade in thoracic surgery. Minerva Anestesiol 75: 616-621, 2009 22. Joshi GP, Bonnet F, Shah R, et al: A systematic review of randomized trials evaluating regional techniques for postthoracotomy analgesia. Anesth Analg 107:1026-1040, 2008 23. Liu SS, Richman JM, Thirlby RC, et al: Efficacy of Continuous Wound Catheters Delivering Local Anaesthetic for Postoperative Analgesia: A Quantitative and Qualitative Systematic Review of Randomized Controlled Trials. JACS 203:914-932, 2006 24. Zimberg SE: Reducing pain and costs with innovative postoperative pain management. Managed Care Quarterly 11:34-36, 2003 25. Wheatley GH 3rd, Rosenbaum DH, Paul MC, et al: Improved pain management outcomes with continuous infusion of a local anesthetic after thoracotomy. J Thorac Cardiovasc Surg 130:464-468, 2005 26. Silomon M, Claus T, Huwer H, et al: Interpleural analgesia does not influence postthoracotomy pain. Anesth Analg 91:44-50, 2000 27. Scheinin B, Lindgren L, Rosenberg PH: Treatment of postthoracotomy pain with intermittent instillations of intrapleural bupivacaine. Acta Anaesthesiol Scand 33:156-159, 1989 28. Kambam JR, Hammon J, Parris WC, et al: Intrapleural analgesia for post-thoracotomy pain and blood levels of bupivacaine following intrapleural injection. Can J Anaesth 36:106-109, 1989 29. Yildirim V, Akay HT, Bingol H, et al: Interpleural versus epidural analgesia with ropivacaine for postthoracotomy pain and respiratory function. J Clin Anesth 19:506-511, 2007
expiratory volume in 1 second (FEV1) (71 ⫾ 20% versus 86 ⫾ 21%; p ¼ 0.01). Most common surgical procedures were lobectomies (38.8%) and atypical resections (28.3%) via anterolateral thoracotomy. Most common primary diagnoses were lung cancer (48.3%) and tumor of unknown origin (30%). At POD1, median postoperative pain at rest was 2.1 (1; 2.8) in the TEA group and 2 (1.5; 3.8; p ¼ 0.62) in the PainBusters group. At exercise, median pain was 4.3 (3.5; 3.8) in the TEA group compared to 5.0 (4.0; 6.5; p ¼ 0.07). Until POD 5 there were decreases in pain at rest and exercise but without significant differences between the groups. Conclusions: Sufficient analgesia after thoracotomy can be achieved with the intercostal PainBusters system in patients, who cannot receive TEA. & 2014 Elsevier Inc. All rights reserved.
T
is placed intraoperatively in the intercostal space at the site of the surgical incision. The PainBusters system has proven its efficacy in obstetric, orthopedic and cardiac surgery for pain control but has not been examined in detail after thoracic surgery.5–7 Safety and performance data are still lacking. Therefore, the authors conducted this pilot study with the objective of determining if postoperative analgesia with the PainBusters system is an efficient, safe, and reliable alternative to patient-controlled TEA after thoracic surgery.
HORACIC SURGERY with thoracotomy has been reported to be among the most intense clinical postoperative pain experiences known.1 The sources of pain not only arise from surgical incisions but also from disrupted intercostal nerves, retracted ribs, chest wall inflammation adjacent to the incision, injured pulmonary parenchyma, and from the placement of chest tubes.2 Nociceptive pathways after thoracic surgery are poorly understood, but it is believed that noxious input is conveyed to the central nervous system along the intercostal, vagus, and phrenic nerves. The shoulder pain that frequently accompanies thoracic procedures seems to derive from afferent phrenic activity.3 In addition, the need for constant respiratory effort and enhanced respiratory toilette produces an intense and relentless barrage of noxious input. Control of postoperative pain is important and might help to avoid chronic thoracic pain syndromes. Thoracic epidural analgesia (TEA) is currently the standard for analgesia after thoracic surgery with anterolateral thoracotomy and usually all patients, in the absence of contraindications, receive an epidural catheter for major thoracic procedures.4 It combines a local anesthetic and a lipophilic opioid for initial and maintenance analgesia. The placement of the catheter depends on what incision is planned (eg, anterolateral/posterolateral, median sternotomy). Judicious fluid and pressor administration avoids the large fluid shifts that could adversely affect physiology, particularly in patients with limited cardiac or pulmonary reserve.2 However, TEA cannot be used in all patients due to technical, medical, or other reasons. Apart from patientcontrolled intravenous analgesia (PCA), the On-Qs PainBusters system is a closed, patient-independent system for local continuous delivery of a local anesthetic via a Soaker™ catheter with multiple lateral openings for widespread infiltration of wounds (I-Flow Corp., Lake Forest, CA). This catheter
KEY WORDS: thoracotomy, thoracic surgery, thoracic epidural analgesia, PainBusters, postpoerative pain
METHODS The study was designed as a prospective but not randomized pilot trial from April 2009 to September 2011 at the Departments for Thoracic Surgery, University Medical Center Regensburg and Hospital Barmherzige Brüder Regensburg. The authors tested the hypothesis of whether or not postoperative analgesia with the On-Qs PainBusters postoperative pain relief system (I-Flow Corp., LLC, Lake Forest, CA) is an efficient, safe, and reliable alternative in pain reduction compared to patient-controlled TEA in patients after open thoracic surgery who are not suitable for TEA. This study was approved by the local ethics committee of the University Medical Center Regensburg, and individual consent was obtained from each patient. Patients 418 years with open lung
From the Departments of *Thoracic Surgery and †Anesthesiology, University Medical Center Regensburg and the Departments of ‡Anaesthesiology and §Thoracic Surgery, Hospital Barmherzige Brüder Regensburg, Regensburg, Germany. Send reprint requests to Michael Ried, MD, University Medical Center Regensburg, Department of Thoracic Surgery, Franz-JosefStrauß-Allee 11, 93053 Regensburg, Germany. E-mail: micha. [email protected] © 2014 Elsevier Inc. All rights reserved. 1053-0770/2601-0001$36.00/0 http://dx.doi.org/10.1053/j.jvca.2013.12.028
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Table 1. Basic and On-demand Analgesia PainBusters (N ¼ 32)
TEA (N ¼ 30)
Basic analgesia Day of operation POD 1 to 3 On-demand analgesia Day of operation POD 1 to 3
metamizol, 1g IV (maximum 5g IV daily), or paracetamol, 1g IV (maximum 4g IV daily) ibuprofen, 400 mg po q 8 h, or metamizol, 1g IV or po (maximum 5g daily) piritramide paracetamol, 1g IV (maximum 4g daily), or morphine, 10 mg po q 4 h, or oxycodone, 10 mg or 20 mg every 8 h
Abbreviations: IV, intravenous; po, perioral; POD, postoperative day.
resections were included. Patients with the following criteria were excluded from this study sample: Age o18 years, previous thoracic surgery, degenerative vertebral disease, chronic pain syndromes, rheumatic disease, chronic steroid or analgesic drug use, and patients with impaired compliance. Minimally invasive procedures, eg, videoassisted thoracoscopic surgery, were not used in these patients. Preoperatively, TEA was planned for all patients in this study. Patients with contraindications for TEA or who refused TEA were treated with the PainBusters system. This included patients who had evidence of an infection, who had an elevated bleeding risk due to inhibitors of platelet aggregation or other anticoagulation, or patients in whom preoperative placement of an epidural catheter technically was not possible. The primary endpoint was the analysis of the postoperative pain within the first 5 postoperative days, whereas secondary endpoints included postoperative complications, eg, pneumonia, length of hospital stay, and the amount of analgesic drugs used after surgery. Data were collected in patient records and specific pain sheets and then were transferred onto a spreadsheet. Postoperative pain was measured with a numeric scale from 0 (no pain) to 10 (worst pain) and was assessed at least 2 times a day at rest and during exercise (mobilization) in the first 5 postoperative days. Glomerular filtration rate (GFR) was estimated with the abbreviated modification in diet in renal disease (MDRD) equation and was calculated as follows: eGFR (mL min1 1.73m2) = 186.3 SCr1.154 Age0.203 0.74 (if female).8 Chronic obstructive lung disease was defined according to the GOLD classification with at least an FEV1/FVC o0.70 (stage I) or lower.9 Ventilation time was defined as duration of postoperative mechanical ventilation in the intensive care unit. Postoperative extubation in the operating room was preferred in all patients immediately after finishing the surgical procedure. Prerequisites were stable hemodynamic conditions and sufficient oxygenation. All patients received total intravenous anesthesia (TIVA) with propofol and remifentanil. Anesthesia was induced with 100 mg-to200 mg of fentanyl. The epidural catheter was inserted at T6-T7 before surgery and before induction of general anesthesia by an experienced anesthesiologist. During surgery, the authors used bupivacaine and then postoperatively switched to ropivacaine. Bupivacaine 0.25% was initially instilled followed by 10 mg of sufentanil (patients 470 years received 5 mg). Bupivacaine was started at infusion rates from 4 mL/hto-8 mL/h. Thirty minutes before finishing the surgery, patients in both groups received a single intravenous dose of paracetamol (acetaminophen: 1g) or metamizol (1g). TEA used ropivacaine 0.2% at patientcontrolled infusion rates from 4 mL/h-to-8 mL/h. It was continued until all thoracotomy tubes were removed (usually POD 4). The PainBusters intercostal catheter was implanted in all patients by the thoracic surgeon at the end of the surgery before the final wound closure. The catheter can be placed directly under the surgeon’s view. The PainBusters elastomeric pump contained 600 mL of 0.75% ropivacaine and released it at 5 mL/h. The PainBusters was removed at POD 4. In addition to TEA and intercostal analgesia, all patients received a basic and an on-demand postoperative analgesia based on specific pain protocols (Table 1).
Statistical analysis was done with Stata 10.1 SE (StataCorp., College Station, TX). Continuous variables first were tested on normality with Q-Q plots and the Shapiro-Wilk test. If normally distributed, these data are shown as mean ⫾ standard deviation and if non-normally distributed as median with 25th and 75th percentiles. Comparison of 2 continuous normally distributed variables was done with Student’s t-test or with Wilcoxon’s rank sum test if non-normally distributed. Intragroup differences of continuous normally distributed variables were analyzed with 1-way analysis of variance followed by Bonferroni’s post hoc test or if non-normally distributed with Friedman’s test. Categorical data were shown as absolute values and frequencies. Comparison of 2 categorical variables in a 2 2 contingency table was performed with Fisher’s exact test and data in a 2 k table with Pearson’s chi-square test. All tests were 2-sided. A p value o 0.05 was considered significant. RESULTS
The authors have summarized the demographic data of all 62 patients in Table 2. Apart from the FEV1, there were no significant differences between the groups. Patients with the PainBusters had a significantly lower FEV1 than patients with EA (71% ⫾ 3.9 v 86% ⫾ 4.3; p ¼ 0.01). Lobectomy was the
Table 2. Preoperative Characteristics TEA Variable
Age (years) Female gender (%) Body mass index (kg m-2) Hypertension (%) Coronary artery disease (%) Chronic kidney disease (%) Diabetes mellitus (insulindependent) (%) Lipid disorder (%) Chronic obstructive lung disease (%) Lung emphysema (%) Peripheral vascular disease (%) Thyroid gland disorder (%) Hemoglobin (g/dL) Creatinine (mg/dL) Prothrombin time (s) GFR (mL/min/1.72 m2) GFR o60 mL/min/1.72 m2 Relative FEV1 (%) FEV1/FVC
PainBusters
N ¼ 30
N ¼ 32
p value
62 ⫾ 9 30 26 ⫾ 3.7 43 10 0 3
63 ⫾ 10 41 27 ⫾ 5 56 3 6 6
0.68 0.43 0.38 0.44 0.34 0.49 1.00
10 33
22 35
0.30 1.00
7 3
16 10
0.42 0.61
20 31 14 (12.3; 14.8) 14 (11.7; 14.4) 0.8 (0.7; 0.9) 0.8 (0.6; 1.0) 29 (28; 32) 30 (28; 33) 91 (82; 120) 96 (80; 115) 0 3 86 ⫾ 21 71 ⫾ 20 73 ⫾ 14 75 ⫾ 13
0.24 0.33 0.93 0.33 0.56 0.24 0.01 0.77
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Table 3. Operative Procedures TEA Type of surgery
Enucleation [%] Atypical resection [%] Segmental resection [%] Lobectomy [%] Extended lobectomy [%] Pneumonectomy [%] Extended pneumonectomy [%]
Table 4. Postoperative Data s
PainBuster
N ¼ 30
N ¼ 32
14 21 10.5 41 10 0 3.5
6.5 35.5 3 35.5 13 3 0 p ¼ 0.50
most common procedure in both groups (TEA: 41% and PainBuster: 35.5%, respectively) followed by atypical lung resection (21% and 35.5%). Overall, there was no further significant difference between the groups (Table 3). Primary lung cancer was the most common diagnosis in both groups followed by tumor of unknown etiology (Fig 1). Preoperative insertion of an epidural catheter required a median time of 15 minutes (10; 20) in patients who received this type of perioperative analgesia. Postoperative Data Twenty percent in the TEA group and 31% in the PainBusters group required postoperative care at the intensive care unit with a median stay of 2.5 days and 2 days respectively. Patients in the PainBusters group had a significantly lower postoperative ventilation time than patients with TEA (3.0 ⫾ 0.9 v 3.5 ⫾ 1.0 hours; p ¼ 0.04), whereas other postoperative variables such as postoperative stay, frequency of respiratory infection, or frequency of rhythm disturbances remained insignificant (Table 4). There was no episode of hypotension in the TEA group, and only 3% of patients
TEA Variable
Surgical time (min) Ventilation time (h) Postoperative care at ICU (%) ICU stay (days) Postoperative stay (days) Respiratory infection (%)* Rhythm disturbances (%)† Bladder dysfunction (%) Intestinal dysfunction (%) Surgical revision (%) Wound infection (%) Respiratory failure with re-intubation (%)
PainBusters
N ¼ 30
N ¼ 32
p value
135 ⫾ 59 3.5 ⫾ 1.0 20 2.5 (1; 4.5) 12 (9; 14) 20 3 3 3 3 24 3.6
114 ⫾ 56 3.0 ⫾ 0.9 31 2 (1; 4) 11 (9; 14) 12.5 13 3 3 3 16 6.3
0.16 0.04 0.39 0.77 0.50 0.35 1.00 1.00 1.00 0.52 1.00
*Radiologic evidence of atelectasis or pneumonia in the routine chest x-ray and concomitant elevated inflammation parameters in the laboratory investigations. †Supraventricular tachycardia or atrial fibrillation.
experienced bladder dysfunction, ie, urinary retention or intestinal dysfunction. Hospital and postoperative stays did not differ between the groups. The authors have summarized frequencies of drugs, number of drug combinations and drug combinations in the anesthetic recovery room and on the ward in Figure 2. The most frequently used drugs in both groups were metamizol (TEA: 73% v PainBusters: 81%; p ¼ 0.15) and piritramide (TEA: 80% v PainBusters: 84%; p ¼ 0.85). On the ward, ibuprofen, metamizol and piritramide were used with similar frequency and without statistical significance (Table 5). A double drug combination was used most frequently for pain control in the anesthetic recovery room, whereas double and triple combinations were used with similar frequencies on the ward. The most common combination was metamizol and piritramide in the anesthetic recovery room and ibuprofen/metamizol and metamizol/piritramide on the ward. Metamizol/piritramide was significantly more frequently used in the PainBusters group in the anesthetic recovery room compared to the TEA group (p ¼ 0.02). Median pain at rest (TEA: 2.1 [1; 2.8] versus PainBusters 2 [1.5; 3.8]; p ¼ 0.62) and at exercise (TEA: 4.3 [3.5; 4.8] versus PainBusters 5 [4; 6.5]; p ¼ 0.07) did not differ between the groups. There was a decrease of pain at rest and at exercise until POD4 without significant differences between the groups (Fig 3). After removal of the PainBusters and TEA catheter at POD4, there was a slight but insignificant increase in median pain from POD4 to POD5. In addition, there were 2 significant intragroup differences. In the TEA group, there was a significant reduction of pain at exercise between POD2 and POD4 (p ¼ 0.004). In the PainBusters group, pain after exercise significantly decreased from POD1 to POD3 (p ¼ 0.001), indicating an earlier reduction of pain at exercise in the PainBusters group compared to the TEA group. DISCUSSION
Fig 1. Bar graph showing the primary diagnoses in both study groups. There was no statistical significance between the groups.
Proper pain management remains essential after thoracic surgery not only because of prevention of serious pulmonary complications but also for preventing chronic post-thoracotomy
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Fig 2. Upper panel: Frequency of analgesic drugs in the anesthetic recovery room and on the ward. Middle panel: Number of drug combinations in the TEA and the PainBusters group. Lower panel: Drug combinations in the anesthetic recovery room and on the ward.
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Table 5. Total Postoperative Doses of On-demand Analgesia
Drug
Anesthetic recovery room Piritramide (mg) Paracetamol (mg) On the ward Ibuprofen (mg) Metamizol (mg) Piritramide (mg) Oxycodone (mg)
TEA
PainBusters
N ¼ 30
N ¼ 32
25.3 ⫾ 15 1454 ⫾ 522 12 32 49 360
(8; 16) (15; 42) (15; 98) (240; 540)
30.5 ⫾ 19 1200 ⫾ 447 16 21 37 290
(9; 18) (15; 31) (7; 82) (165; 440)
p value
0.29 0.36 0.18 0.32 0.64 0.25
pain syndrome.10 Acute and chronic pain after thoracotomy still remain a challenge to clinicians.11 Although epidural analgesia has been shown to be the method of choice, it was not useful in patients with contraindications such as degenerative vertebral disease. The major finding of the authors’ prospective study was that the PainBusters system provided similar postoperative pain control compared to TEA in addition to comparable basic and on-demand analgesia. In fact, there were no significant differences between the groups from POD1 to POD5 after major thoracic surgery with anterolateral thoracotomy. Several studies have shown the effectiveness of TEA for perioperative pain control after thoracic surgery, and the authors could confirm this finding.12,13 TEA provides better postoperative analgesia compared with parenteral opioids.14 However, TEA might be contraindicated in certain patients, and other alternatives for post-thoracotomy pain relief are needed.15 Continuous thoracic paravertebral analgesia seems to be as effective as TEA in controlling post-thoracotomy pain.16–18 It also has the potential to reduce the risk of postoperative complications and to improve the surgical outcome with respect to the length of hospital stay and pulmonary function.19,20 On the other hand, studies have described TEA as being more efficient than paravertebral continuous block at reducing pain after thoracic surgery.21 In summary, both techniques can be recommended, but further investigations are required.22 In a systematic review of the literature, continuous wound catheters were associated with improved analgesia, reduced opioid use, and increased patient satisfaction after a wide range of surgical procedures.23 Furthermore, these innovative techniques may contribute to the reduction of long-term care costs during hospitalization.24 To the authors’ knowledge, there are only little data in the literature regarding the PainBusters system for treatment of post-thoracotomy pain. The use of the PainBusters system seems to decrease the narcotic use and results in low pain scores when compared with continuous epidural infusion.25 Potential disadvantages of the PainBusters system, as a special form of intercostal catheter, are the less reliable spread of local anesthetic and the rapid absorption.26 Thus, some studies demonstrated less effective analgesia than TEA.27,28 However, the authors could not affirm this finding. Compared with another study,29 overall pain scores and differences in pain at rest and exercise in the authors’ study were quite moderate on POD1 to POD5, indicating efficient basic and on-demand analgesia. Other postoperative variables such
Fig 3. Direct comparison of median pain at rest (Upper panel: Resting pain score) and during exercise (Lower panel: Activity pain score) during the first 5 postoperative days is shown. There was no significant difference between the TEA and PainBusters groups. The black arrow indicates the removal of the TEA or PainBusters catheter. The asterisk (*) refers to a significant intragroup difference in the TEA group between POD2 and POD4 and the number sign (#) to a significant intragroup difference in the PainBusters group between POD1 and POD3.
as the length of hospital stay, frequency of respiratory infection or frequency of rhythm disturbances remained insignificant between the groups in the authors’ study. Epidural and PainBusters catheters usually could be taken out at POD4 after all chest tubes had been removed. The limitations of the study arose primarily from its non-randomized design, which implies that conclusions were necessarily limited in their application and causality could not be determined. In addition, the authors have used a variety of analgesic drugs. Metamizol is not widely available and has
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been banned in some countries. However, all of the mentioned drugs are standard analgesic drugs in the authors’ country and, therefore, routinely used. In conclusion, sufficient analgesia after anterolateral thoracotomy can be achieved with the intercostal On-Qs PainBusters
system. The PainBusters can be used as an alternative local pain catheter in patients who cannot receive TEA. The implantation of the catheter is feasible and effective. Further prospective and randomized studies are warranted to confirm these findings in thoracic surgical patients.
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16. Marret E, Bazelly B, Taylor G, et al: Paravertebral block with ropivacaine 0.5% versus systemic analgesia for pain relief after thoracotomy. Ann Thorac Surg 79:2109-2113, 2005 17. Casati A, Alessandrini P, Nuzzi M, et al: A prospective, randomized, blinded comparison between continuous thoracic paravertebral and epidural infusion of 0.2% ropivacaine after lung resection surgery. Eur J Anaesthesiol 23:999-1004, 2006 18. Fortier S, Hanna HA, Bernard A, et al: Comparison between systemic analgesia, continuous wound catheter analgesia and continuous thoracic paravertebral block: A randomised, controlled trial of postthoracotomy pain management. Eur J Anaesthesiol 29:524-530, 2012 19. Elsayed H, McKevith J, McShane J, et al: Thoracic epidural or paravertebral catheter for analgesia after lung resection: Is the outcome different? J Cardiothorac Vasc Anesth 26:78-82, 2012 20. Esme H, Apiliogullari B, Duran FM, et al: Comparison between intermittent intravenous analgesia and intermittent paravertebral subpleural analgesia for pain relief after thoracotomy. Eur J Cardiothorac Surg 41:10-13, 2012 21. Messina M, Boroli F, Landoni G, et al: A comparison of epidural vs. paravertebral blockade in thoracic surgery. Minerva Anestesiol 75: 616-621, 2009 22. Joshi GP, Bonnet F, Shah R, et al: A systematic review of randomized trials evaluating regional techniques for postthoracotomy analgesia. Anesth Analg 107:1026-1040, 2008 23. Liu SS, Richman JM, Thirlby RC, et al: Efficacy of Continuous Wound Catheters Delivering Local Anaesthetic for Postoperative Analgesia: A Quantitative and Qualitative Systematic Review of Randomized Controlled Trials. JACS 203:914-932, 2006 24. Zimberg SE: Reducing pain and costs with innovative postoperative pain management. Managed Care Quarterly 11:34-36, 2003 25. Wheatley GH 3rd, Rosenbaum DH, Paul MC, et al: Improved pain management outcomes with continuous infusion of a local anesthetic after thoracotomy. J Thorac Cardiovasc Surg 130:464-468, 2005 26. Silomon M, Claus T, Huwer H, et al: Interpleural analgesia does not influence postthoracotomy pain. Anesth Analg 91:44-50, 2000 27. Scheinin B, Lindgren L, Rosenberg PH: Treatment of postthoracotomy pain with intermittent instillations of intrapleural bupivacaine. Acta Anaesthesiol Scand 33:156-159, 1989 28. Kambam JR, Hammon J, Parris WC, et al: Intrapleural analgesia for post-thoracotomy pain and blood levels of bupivacaine following intrapleural injection. Can J Anaesth 36:106-109, 1989 29. Yildirim V, Akay HT, Bingol H, et al: Interpleural versus epidural analgesia with ropivacaine for postthoracotomy pain and respiratory function. J Clin Anesth 19:506-511, 2007
