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  • Acute and Chronic Post-Thoracotomy Neuropathic Pain: At-Risk Populations, Prevention, and Treatment

    Authors: Laura Garcia Ramirez SRNA, BSN, CCRN, TCRN; Greta Mitzova-Vladinov, DNP, APRN, CRNA, CHSE
    Central Message: With adequate identification of the population at risk of neuropathic pain after thoracotomies, preventative strategies can be successfully implemented along with treatment options.
    Perspective Statement: Thoracic surgery patients have many comorbidities making it hard to institute analgesia regimens. Anesthesia providers working alongside surgeons can identify patients at risk for acute and chronic neuropathic pain preoperatively. Preventative strategies and early treatment can be instituted. Each patient is unique thus no single preventative strategy is
    recommended but rather a multimodal approach.


    Abstract

    Objectives: Thoracotomies can cause both acute and chronic neuropathic pain even with less invasive approaches. Up to 38% of the patients undergoing video-assisted thoracic surgery still develop chronic post-thoracotomy pain syndrome. It is critical to identify the population at risk prior to surgery to instill preventative measures intraoperatively and be prepared for treatment options immediately postoperatively.

    Methods: CINAHL and Pubmed databases were searched for peer-reviewed articles on patients at risk for neuropathic pain after thoracotomies, prevention, and treatment options.

    Results: In total, 18 articles were identified and reviewed. It was found that populations at risk for acute neuropathic pain included those with cancer diagnosis, preoperative pain history, and previous use of hypnotic medications. Young age and female gender add to the additional risk factors for chronic neuropathic pain. Several preventative strategies have been identified that can be used during the intraoperative and postoperative periods. Treatment options exist for acute neuropathic pain management but much less for chronic pain management.

    Conclusion: With adequate identification of the population at risk of neuropathic pain after thoracotomies, preventative strategies can be successfully implemented along with treatment options.

    Key Words: Post-thoracotomy pain, thoracic surgery, acute pain, chronic pain, pain management


    Introduction

    Thoracotomies can cause long term pain with prevalence as high as 91%.1 Severe post-operative pain known to be caused by thoracic surgeries can lead to an array of complications such as atelectasis and hypoxemia.2 Even with the use of video-assisted approaches, 38% of patients still suffer from chronic post-thoracotomy pain syndrome.3 This syndrome is defined as pain that lasts longer than two months after surgery.4

    Intercostal nerve damage has long been implicated in the development of symptoms of both acute and chronic neuropathic pain.5 Aside from the actual incision, insertion of trocars, chest tubes and drains have been related to causing this nerve damage.6 Symptoms include burning, shooting, and aching sensations.5 Chronic pain can also cause insomnia, loss of appetite, and incapacitate patients, which could make daily activities unbearable.5

    Material and Methods

    CINAHL and Pubmed databases were searched for peer reviewed articles on patients at risk for neuropathic pain after thoracotomies, prevention and treatment options. Terms used included neuropathic pain with thoracotomies, post-thoracotomy, open thoracotomy and video assisted thoracic surgery (VATS). Inclusion criteria were of peer reviewed publications in English from 2010 to 2020.

    Results

    Acute Neuropathic Pain
    Predisposing factors. At-risk populations for acute neuropathic pain included those with a diagnosis of cancer, previous pain, and preoperative use of hypnotic medication.5, 7 Procedural risk factors include open thoracotomy approach, duration of surgery greater than 2.5 hours with open approach, lobectomy and pneumonectomy.5, 8

    Prevention. As described in Table 1, modalities for prevention of acute pain development include paravertebral block (PVB) with 0.5% bupivacaine 0.3mL/kg and dexmedetomidine 1mcg/kg after anesthesia induction.3 A loading dose of magnesium sulfate during induction of anesthesia at 40 mg/kg over 10 minutes followed by an infusion at 10mg/kg/hr for 24 hours has successfully been used to reduce post-operative pain.9 Intraoperative infusions of ketamine, intravenous (IV) or epidurally, has been effective in several studies with dose ranges for IV use of 0.05mg/kg/hr to 1mg/kg/hr.10 Pregabalin 25mg twice per day starting on post-operative day 2 along with a non-steroidal anti-inflammatory medication for 3 months can also prevent both acute and chronic neuropathic pain.5

    Treatment. Treatment of acute pain includes use of standardized analgesia regimen such as fentanyl infusion IV 0.01-0.04mg/hr (can be started intraoperatively) and/or non-steroidal anti-inflammatory drugs beginning on post-operative day (POD) 1 (loxoprofen 180mg/day or acetaminophen 1200mg/day with glomerular filtration rates <50).5

    Chronic Neuropathic Pain
    Predisposing factors. Post-thoracotomy pain syndrome risk factors include patients with a low American Society of Anesthesiologist (ASA) score, cancer recurrence, female gender, young age (average of 45), high number of drains, scar length, length of hospital stay, high average pain score during the first 5 post-operative days at rest and on coughing, moderate pain at discharge, post-operative pain lasting six weeks, pre-operative pain in any location but more so in the thoracic region, brush allodynia, and sensory loss distal to the surgical scar.8, 11-14

    Prevention. Prevention of chronic pain, as seen in Table 1, can be achieved with an intraoperative IV dexmedetomidine infusion of 0.7mcg/kg/hour, total intravenous anesthesia (TIVA), pregabalin and magnesium sulfate intervention described previously.3, 5, 9, 15-16

    Treatment. Options for treatment in patients suffering from post-thoracotomy neuropathic pain syndrome include surgical intercostal neurolysis, spinal cord stimulation system, and subcutaneous injections of botulinum toxin.4, 6, 17

    Discussion

    Regional Anesthesia
    Thoracic epidural blocks (TEB) have long been the preferred method for regional anesthesia. However, the TEBs are associated with some minor complications such as low blood pressure, nausea, and vomiting, itching and urinary retention when compared to PVB. Yeung and colleagues after reviewing 14 studies of patients undergoing thoracotomies concluded that PVB are as effective as TEB for postoperative pain control and with less complications.18

    Postoperative pain at rest, while coughing, or with movement was significantly lower for up to 90 minutes with the use of a PVB with 0.5% bupivacaine and dexmedetomidine at 1mcg/kg after induction of general anesthesia. Time needed for a rescue analgesic was much longer with the dexmedetomidine adjunct (5.11-10.19 hours) versus the PVB with 0.5% bupivacaine alone (2.37- 5.89 hours). Administration of ketorolac was lower as well with dexmedetomidine adjunct, 10 ± 14.6 mg versus 32 ± 21.1 mg with 0.5% bupivacaine. The authors found no complications related to dexmedetomidine use.3

    Alpha-2 Receptor Agonist
    Centrally acting alpha-2 receptor agonists such as dexmedetomidine has shown to have a role in the descending inhibitory pain pathways.16 Alpha-2 agonists display both opioid-sparing and analgesic properties.16 This could be why dexmedetomidine has shown to have positive effects when used as an adjuvant to PVB in the prevention of acute pain and as an intraoperative intravenous drip to prevent chronic pain.3, 16

    An intraoperative dexmedetomidine drip at 0.7mcg/kg/hr starting from induction of anesthesia and followed in the intensive care unit has shown promising results. Pain persisted for more than 3 months in only 18% of patients that received the dexmedetomidine drip versus 35% in those who did not. While patients were in the intensive care unit (ICU), average morphine use was significantly reduced, 4mg in the dexmedetomidine group versus 14mg in the standard group. Fentanyl consumption was also significant with 0-4mcg in the dexmedetomidine group versus 0-245mcg in the standard group.16

    N-Methyl-D-Aspartate (NDMA) Receptor Antagonists
    The NMDA receptor is involved in the development of sensitization, wind-up, expansion of receptive fields, and neuroplastic changes in the central nervous system.9 As a long-term effect, it has been shown that magnesium, as physiological blocker of the NMDA calcium channel, suppresses neuropathic pain, enhances morphine analgesia, and attenuates morphine tolerance, respectively.19

    Magnesium is currently being used as part of many enhanced recovery after surgery (ERAS) protocols. Patients given magnesium sulfate 40mg/kg over 10 minutes during induction of anesthesia followed by an infusion at 10mg/kg/hr for 24 hours needed significantly less morphine on POD 5 and 30 as well as lower use on days 6,7,8 and 90. Numerical rating scale pain scores were significantly lower on POD 1 to 8 and with coughing on days 4,7,8 and 30. Less patients had a numerical pain rating of greater than or equal to 4 on POD 4,7 and 30. Patients had a significant numerical pain rating of 0 on POD 1 to 8. There was significantly less neuropathic pain on POD 30 and 90 with no patient reporting neuropathic pain on POD 90.9

    Ketamine is a phencyclidine derivative and binds to NMDA receptor in a non-competitive manner to modulate the central sensory pain processing. Ketamine with its ability to interrupt peripheral and central transmission of pain signaling may be a promising alternative to opioids for post thoracotomy pain.20 Either intravenous (IV) or epidural (EP) ketamine use intraoperatively has shown lower post-thoracotomy pain ratings while coughing at 24 hours (IV) and 72 hours (EP). Ketamine use had significantly less post-operative nausea and vomiting when compared to an opioid-only control group. Many studies found better pain relief at rest and with movement during the first 48 hours with the use of ketamine. One study found greater cessation of patient-controlled analgesia. It has also been found that ketamine use helped respiratory physiotherapy and improved outcomes by preventing atelectasis and pneumonia postoperatively.10

    Gabapentins
    Pregabalin 25mg twice per day starting on post-operative day 2 along with a non-steroidal anti-inflammatory (NSAID) for 3 months showed significantly lower post-operative neuropathic pain (41.3% vs 19.6%) when compared to patients who only received an NSAID. Length of neuropathic pain was significantly shorter in patients that received pregabalin (30 days) versus those who did not (90 days). Those who did experience neuropathic pain had the same time of onset at POD 6. Patient’s pain scores were significantly lower on POD 3 with the use of pregabalin.5

    Choice of Inhalational vs. Intravenous anesthesia
    As we know, general anesthesia is routinely used in thoracic surgery. Current literature suggests that propofol can improve postoperative analgesia compared with inhalational anesthesia in cardiac and thoracic surgeries.15, 21, 22 Total intravenous anesthesia showed a significant decrease in occurrence of chronic neuropathic pain after thoracotomies of 38.2% versus 56.5% with inhaled anesthesia at 3 months and 33.5% versus 50.6% at 6 months. New development of pain at 6 months was significantly less with TIVA at 29.3% versus 48.8% with inhaled anesthesia. During the 3-month follow up, 36% of patients reported constant pain with TIVA versus 40.1% with inhaled anesthesia. At 6 months, 32.8% of patients in the TIVA group reported constant pain versus 44.2% with inhaled anesthesia. Pain was reported to be mostly in the thoracotomy area at both the 3 and 6-month follow up.15

    Conclusion

    Thoracic surgery patients are fragile and older with many comorbidities which make it hard to institute standard analgesia regimens.2 Anesthesia providers working alongside surgeons can help identify patients before surgery that are high risk for chronic neuropathic pain. If these patients can be identified prior to surgery, then preventative strategies can be instituted as described previously. Adequate identification of the population at risk of neuropathic pain with thoracic surgeries, along with preventative strategies and early treatment can prevent and/or decrease acute and chronic neuropathic pain. Each patient is unique and have different comorbidities which is why no single preventative strategy is recommended but rather a multimodal approach.


    Table 1
    Strategies of acute and chronic post-thoracotomy pain prevention.

    AUTHORS STUDY DESIGN SAMPLE SIZE STRATEGY CONCLUSION
    ABD-ELSHAFY ET AL3 Double blind random control trial (RCT) N=60 Group I received thoracic paravertebral block (PVB) with bupivacaine 0.5% (0.3 mL/
    kg) and Group II received PVB with bupivacaine 0.5% (0.3 mL/kg) and dexmedetomidine
    (1 mcg/kg) after induction of general anesthesia.
    Dexmedetomidine as an adjuvant to bupivacaine PVB offers better pain relief
    during the early postoperative hours, and has a favorable effect on chronic postoperative
    pain.
    HOMMA ET AL5 RCT N=92 Patients were randomly assigned to the treatment (pregabalin; initial dose, 50 mg/day) or control (non- steroidal anti-inflammatory drugs) group. Pregabalin patients received non-steroidal anti-inflammatory drugs and pregabalin (25 mg, twice daily) from the second postoperative day.

     

    Pregabalin (50 mg/day) had a significant preventive effect on postoperative neuropathic pain after thoracic surgery, without side effects. Early postoperative administration of pregabalin would help prevent neuropathic pain.

     

    GHEZEL-AHMADI ET AL9 Observational Study N=100 The study group received magnesium sulfate (40 mg/kg over 10 minutes) during induction of anesthesia followed by an infusion over 24 hours (10 mg/kg/h). The presence and severity of pain were assessed before surgery, on postsurgical days 1–8, 30 and 90, respectively.

     

    Magnesium sulfate administration reduces postoperative pain at rest according to the NRS pain scores and is effective in preventing chronic neuropathic post-thoracotomy pain.
    MOYSE ET AL10 Systematic Literature Review Each study was scored on 3 items, 1 – 5 quality scoring scale. A point was given if randomization was described and an additional point was given if the design of the study included a “double” blind approach.

     

    Perioperative ketamine has beneficial acute analgesic effects in the perioperative period, especially when combined with aggressive multimodal analgesia. RCTs showed lower pain scores in the immediate perioperative period.

     

    SONG ET AL15 RCT N=366 Two groups: Group I (n = 173) received total intravenous anesthesia (TIVA) with propofol + remifentanil. Group II (n = 170) received inhalation anesthesia with sevoflurane. Assessed prevalence of Chronic Post-Thoracotomy Syndrome (CPTS) at 3 and 6 months using a numerical rating scale. The incidence of chronic pain was significantly reduced in months 3 and 6 in the TIVA group.
    LEE ET AL16 Observational Study N=133 Dexmedetomidine was given IV at induction of anesthesia (0.7mcg/kg/hour) and continued in the intensive care unit as clinically appropriate.   Pain was assessed 3 months after surgery.

     

    Dexmedetomidine IV significantly reduced postoperative IV opioid requirements and reduced pain 3 months after cardiac surgery.

     

     

     

     


    Works Cited

    1. Wong J, Cooper J, Thomas R, Langford R, Anwar S. (2019). Persistent postsurgical pain following thoracotomy: A comparison of thoracic epidural and paravertebral blockade as preventive analgesia. Pain Medicine. 2019;20(9):1796–1802. https://doi-org.access.library.miami.edu/10.1093/pm/pny293
    2. Kelsheimer B, Williams C, Kelsheimer, C. New emerging modalities to treat post-thoracotomy pain syndrome: A review. Missouri Medicine. 2019; 116(1), 41–44.
    3. Abd-Elshafy SK, Abdallal F, Kamel EZ, Edwar H, Abd Allah E, Maghraby HH, Sayed JA, Ali MS, Elkhayat H, Mahran GS, Allah EA. Paravertebral dexmedetomidine in video-assisted thoracic surgeries for acute and chronic pain prevention. Pain Physician. 2019;22(3): 271–280.
    4. Fabregat G, Asensio SJM, Palmisani S, Villanueva PVL, De Andrés J. Subcutaneous botulinum toxin for chronic post-thoracotomy pain. Pain Practice. 2013;13(3): 231–234. https://doi-org.access.library.miami.edu/10.1111/j.1533-2500.2012.00569.x
    5. Homma T, Doki Y, Yamamoto Y, Ojima T, Shimada Y, Kitamura N, Yoshimura N. Risk factors of neuropathic pain after thoracic surgery. Journal of Thoracic Disease. 2019;10(5): 2898–2907. https://doi-org.access.library.miami.edu/10.21037/jtd.2018.05.25
    6. Cappellari AM, Tiberio F, Alicandro G, Spagnoli D, Grimoldi N. Intercostal neurolysis for the treatment of postsurgical thoracic pain: A case series. Muscle & Nerve. 2018; 58(5):671–675. https://doi-org.access.library.miami.edu/10.1002/mus.26298
    7. Shanthanna H, Aboutouk D, Poon E, Cheng J, Finley C, Paul J, Thabane L. A retrospective study of open thoracotomies versus thoracoscopic surgeries for persistent postthoracotomy pain. Journal of Clinical Anesthesia. 2016; 35:215–220. https://doi-org.access.library.miami.edu/10.1016/j.jclinane.2016.07.029
    8. Mongardon N, Pinton-Gonnet C, Szekely B, Michel-Cherqui M, Dreyfus JF, Fischler M. Assessment of chronic pain after thoracotomy: A 1-year prevalence study. Clinical Journal of Pain. 2011;27(8):677–681.https://doi-org.access.library.miami.edu/10.1097/AJP.0b013e31821981a3
    9. Ghezel-Ahmadi V, Ghezel-Ahmadi D, Schirren J, Tsapopiorgas C, Beck G, Bölükbas S. Perioperative systemic magnesium sulphate to minimize acute and chronic post-thoracotomy pain: A prospective observational study. Journal of Thoracic Disease. 2019;11(2):418–426. https://doi-org.access.library.miami.edu/10.21037/jtd.2019.01.50
    10. Moyse DW, Kaye AD, Diaz JH, Qadri MY, Lindsay D, Pyati S. Perioperative ketamine administration for thoracotomy pain. Pain Physician. 2017;20(3):173–184.
    11. Dualé C, Guastella V, Morand D, Cardot JM, Aublet-Cuvelier B, Mulliez A, Schoeffler P, Escande G, Dubray C. Characteristics of the neuropathy induced by thoracotomy: A 4-month follow-up study with psychophysical examination. Clinical Journal of Pain. 2011;27(6): 471–480. https://doi-org.access.library.miami.edu/10.1097/AJP.0b013e31820e12d4
    12. Guastella V, Mick G, Soriano C, Vallet L, Escande G, Dubray C, Eschalier A. A prospective study of neuropathic pain induced by thoracotomy: Incidence, clinical description, and diagnosis.  2011;152(1):74–81. https://doi-org.access.library.miami.edu/10.1016/j.pain.2010.09.004
    13. Kampe S, Geismann B, Weinreich G, Stamatis G, Ebmeyer U, Gerbershagen HJ. The influence of type of anesthesia, perioperative pain, and preoperative health status on chronic pain six months after thoracotomy-A prospective cohort study. Pain Medicine. 2017;18(11): 2208–2213. https://doi-org.access.library.miami.edu/10.1093/pm/pnw230
    14. Salvat E, Schweitzer B, Massard G, Meyer N, Blay F, Muller A, Barrot M. Effects of β2 agonists on post-thoracotomy pain incidence. European Journal of Pain. 2015;19(10): 1428–1436. https://doi-org.access.library.miami.edu/10.1002/ejp.673
    15. Song JG, Shin JW, Lee EH, Choi DK, Bang JY, Chin JH, Choi IC. Incidence of post-thoracotomy pain: A comparison between total intravenous anaesthesia and inhalation anaesthesia. Eur J Cardiothorac Surg. 2012;41(5):1078-82. https://doi.org/10.1093/ejcts/ezr133
    16. Lee YC, Li J, Jhee B, Bailey M, Shehabi Y. Peri-operative dexmedetomidine and chronic pain after cardiac surgery. Anesthesia & Analgesia. 2016;123(3S): 406. https://doi.org/10.1213/01.ane.0000492709.33948.24
    17. Wininger KL, Bester ML, Deshpande KK. Spinal cord stimulation to treat postthoracotomy neuralgia: Non–Small-Cell lung cancer: A case report. Pain Management Nursing. 2012;13(1):52–59. https://doi-org.access.library.miami.edu/10.1016/j.pmn.2011.11.001
    18. Yeung JHY, Gates S, Naidu BV, Wilson MJA, Gao Smith F. Paravertebral block versus thoracic epidural for patients undergoing thoracotomy. Cochrane Database of Systematic Reviews. 2016;2. Art. No.: CD009121. https://doi.org/10.1002/14651858.CD009121.pub2
    19. Guo BL, Lin Y, Hu W, et al. Effects of systemic magnesium on post-operative analgesia: Is the current evidence strong enough? Pain Physician 2015; 18:405-18.
    20. Chumbley GM, Thompson L, Swatman JE, Urch C. Ketamine infusion for 96 hr after thoracotomy: Effects on acute and persistent pain. Eur J Pain 2019; 23:985-93.
    21. Peng K, Liu HY, Wu SR, Liu H, Zhang ZC, Ji FH. Does propofol anesthesia lead to less postoperative pain compared with inhalational anesthesia?: A systematic review and meta-analysis. Anesth Analg. 2016;123(4):846–858. https://doi.org/10.1213/ANE.0000000000001504
    22. Qiu Q, Choi SW, Wong SS, Irwin MG, Cheung CW. Effects of intra-operative maintenance of general anaesthesia with propofol on postoperative pain outcomes – A systematic review and meta-analysis. Anaesthesia. 2016;71(10):1222–1233. https://doi.org/10.1111/anae.13578