JOHTOPUUDUTUKSET PARANTUMATONTA SYÖPÄÄ SAIRASTAVIEN POTILAIDEN KIVUN HOIDOSSA

Transkriptio

1 Erika Rouhento JOHTOPUUDUTUKSET PARANTUMATONTA SYÖPÄÄ SAIRASTAVIEN POTILAIDEN KIVUN HOIDOSSA Lääketieteen ja terveysteknologian tiedekunta Syventävä opinnäytetyö Joulukuu 2021

2 TIIVISTELMÄ Erika Rouhento: Johtopuudutukset parantumatonta syöpää sairastavien potilaiden kivun hoidossa Syventävä opinnäytetyö Tampereen yliopisto Lääketieteen lisensiaatin tutkinto-ohjelma Joulukuu 2021 Syöpäpotilaat kärsivät usein voimakkaista kivuista, jotka eivät lievity tarpeeksi systeemisillä kipulääkkeillä, jolloin tarvitaan muita hoitovaihtoehtoja. Tampereen yliopistollisessa sairaalassa on jo muutaman vuoden ajan käytetty onnistuneesti ultraääniavusteisesti johtopuudutuksia kivun hoidossa. Johtopuudutteiden käyttäminen syöpäpotilaiden kivun lievityksessä on kuitenkin vielä vähäistä ja aiheesta on julkaistu vain muutamia artikkeleita. Tutkimuksessa tarkastellaan johtopuudutuksia syöpäpotilaiden kivunhoitovaihtoehtona opioidien rinnalla ja niiden vaikutusta potilaiden opioidimääriin Tähän retrospektiiviseen tutkimukseen valittiin parantumatonta syöpää sairastavat potilaat, jotka saivat johtopuudutuksen kivunhoitona Tampereen yliopistollisessa sairaalassa tammikuu 2015 ja joulukuu 2018 välisenä aikana. Potilaista kerättiin demografiset perustiedot (sukupuoli, syntymäaika, kuolinaika), diagnoosit, mahdolliset metastaasit, kivun paikantuminen ja voimakkuus, käytössä olevat kipulääkkeet (morfiiniekvivalenttina), saatu puudutus, puudutusaine, puudutuksen kesto ja komplikaatiot. Johtopuudutuksen vaikutusta arvioitiin keräämällä tiedot potilaan kokemasta kivun lievityksestä sairaanhoitajien merkinnöistä 72 tunnin ajan puudutuksen jälkeen. Huomattavan suurelta osalta potilaista puuttui numeerinen arviointi kivusta (NRS), joten tästä ei tehty erillistä selvitystä. Lisäksi laskettiin potilaiden käyttämät opioidit 24 tuntia ennen ja jälkeen puudutuksen ja muutimme ne morfiiniekvivalenteiksi arvioidaksemme puudutuksen vaikutusta opioidien tarpeeseen. 16 potilasta 17:stä koki subjektiivisesti kivunlievitystä johtopuudutuksesta. 12 potilaalla opioidien määrät laskivat, mediaanimuutos päivittäisessä morfiiniekvivalentissa oli -20 mg (IQR: ). Tutkimuksessamme tuli esiin yksi puudutuskatetri-infektio ja kaksi muuta ohimenevää komplikaatiota, mutta yksikään niistä ei ollut vakava tai kuolemaan johtava komplikaatio. Tutkimuksen perusteella voidaan päätellä, että johtopuudutukset ovat turvallisia ja tarjoavat varteenotettavan vaihtoehdon kivunlievitykselle ja vähentävät opioidien tarvetta potilailla keillä on pitkälle edennyt parantumaton syöpä. Avainsanat: syöpäkipu johtopuudutus palliatiivinen hoito 2

3 Sisällysluettelo 1 Introduction Methods statistics ethical considerations Results benefits of nerve blocks complications of the nerve blocks Discussion limitations and strengths of the study Conclusions References

4 1 Introduction Among patients with advanced cancer, pain is one of the most common and severe symptoms with an increasing severity towards end of life.(1) Although opioids and other analgesics are the cornerstone of cancer pain management, about 10% of patients are still estimated to experience inadequate pain relief, necessitating further treatment options.(2) Peripheral nerve blocks have long been used for perioperative pain (3) but there have only been anecdotal reports of their benefit in patients with advanced cancer. Peripheral anesthetic techniques may alleviate severe cancer pain and diminish the need for opioids, and thus lower the severity of their undesired side effects. (4,5) In our hospital, anesthesiologists have managed cancer pain by using ultrasound-guided peripheral nerve blocks for a few years now, although there is only scarce evidence on the benefits of these blocks in palliative care. This study therefore aims to investigate whether peripheral nerve blocks are feasible and can reduce the need for opioids in patients with incurable cancer who suffer from severe pain. 2 Methods In this retrospective study, we evaluated all patients with incurable cancer who were treated with a peripheral nerve block due to severe cancer pain at the University Hospital of Tampere from January 2015 to December The patients were identified from the hospital s patient database by ICD-codes for cancer diagnoses (C00-99) and procedure codes for local anesthesia. The CAREreporting guidelines and checklist were used for reporting. (6) A review of all the medical records was performed. The patients demographic characteristics, cancer diagnoses, location of metastases, pain medication, date of death, and recorded occurrence, location, and intensity of pain were collected. In addition, data on the type of peripheral nerve block, the date of the procedure, duration of the block, complications of the procedure, and recorded pain relief were obtained. 4

5 The most common peripheral nerve blocks are summarized in Figure 1. Figure 1. Locoregional illustration of the most common peripheral analgesic blocks. Dark grey: plexus brachialis block, Light grey: serratus plane block, Black dots: Transversus abdominis plane block, Diagonal stripes: musculus quadratus fascial plane block, Checkers: femoral nerve block, Grid: popliteal nerve block, and Black: saphenous nerve block. All the blocks in this study were performed with ultrasound guidance by an experienced anesthesiologist and the placement was confirmed with either tape or a combination of tape and tissue glue. The effect of the peripheral nerve block was estimated from the patient s experienced pain relief immediately after the procedure and for 72 hours thereafter. Pain relief was defined by a decreased score in numeric rating scale when available, but the verbal descriptions of 5

6 pain relief found in medical records were also accepted. Change in the 24-hour opioid dosing before vs. after the nerve block was calculated, and all opioids were converted into a daily morphine equivalent. Perioperative and postoperative complications associated with the anesthetic block were recorded until discharge from the hospital. 2.1 statistics Data were analyzed by using descriptive statistical methods. Analyses were performed with IBM SPSS Statistics version (IBM Corp, Armonk, NY). 2.2 ethical considerations This was a retrospective study of medical records. Therefore, approval from an ethical committee was not required according to Finnish ethical regulations. Approval was, however, obtained from the University Hospital of Tampere for access to the patient database. 3 Results We found 2009 patients with a cancer diagnosis from the hospital database. A total of 17 patients with incurable and metastatic or locally advanced cancer received a peripheral nerve block and were included in the study. Median age of the patients was 59 years (range: 21-97) and median survival after the procedure was 51 days (IQR: 21-97). All patients were on opioids. Additionally, 12 of the patients were taking NSAIDs or paracetamol, and 10 were on pregabalin or antidepressants. Four patients received opioids through a subcutaneous or intravenous patient-controlled anesthesia (PCA) device. Characteristics of the peripheral blocks are presented in Table 1. Five patients received a single shot of local anesthetic before continuous block. One patient had the nerve block until death. The exact duration of nerve block could not be calculated from three patients; two were transferred to another hospital district, and one was still alive with a continuous block during the data collection. 6

7 Table 1. Patient characteristics Gender (Age) Cancer type Location of pain Block Pain relief reported Change in daily MoEkv Duration of block, days F (49) Breast Shoulder, arm BPB c Yes -6 mg 10 d M (50) Esophageal Abdomen, QLB c Yes -330 mg 12 d side/flank F (26) Gynaecologic Liver (liver QLB b,c Yes -210 mg 21 d al capsule) F (59) Gynecological Pelvis, lower QLB b,c No +36 mg 2 6 d abdomen F (74) Gynecological Pelvis, leg FNB c Yes -270 mg 2 > 65 d F (51) Gynecological Thigh FNB c Yes +20 mg 46 d M (52) Lung Shoulder, arm BPB ss,c Yes -20 mg 54 d F (84) Lung Upper chest, SPB ss,c Yes -15 mg 19 d side/flank M (62) Melanoma Shoulder BPB c Yes -260 mg > 7 d M (59) Oral Arm BPB c Yes +18 mg 36 d M (46) Pancreatic Upper QLB b,ss,c Yes -30 mg 2 > 23 d 1 abdomen F (44) Pancreatic Upper QLBb ss Yes +24,5 mg 2 1 d abdomen M (66) Pleura Lower chest, QLB ss,c Yes -150 mg 9 d side/flank M (80) Prostatic Side/Flank, SPBb c Yes d costa/rib F (73) Rectal Lower QLB c Yes -44,5 mg 7 d abdomen M (33) Rectal Upper chest, SPBb ss,c Yes -100 mg 111 d shoulder blade M (62) Ventricular Side/Flank QLB ss Yes -12,5 mg 2 d F, Female; M, Male; QLB, quadratus lumborum block; BPB, brachial plexus block; SPB, serratus plane block; FNB, femoral nerve block; MoEkv, morphine equivalent; ss, single shot; c, continuous b, bilateral; >, at least (whole duration unknown) 1 Patient still alive at the time; 2 Continuos opioid infusion (PCA); 3 Intravenous bolus injections of oxycodone 7

8 3.1 benefits of nerve blocks All except one patient felt pain relief through the nerve block. This one patient suffered from peritoneal pain due to cervical cancer and received a QLB instead of epidural anesthesia because of suspected systemic infection. The pain was initially relieved but again worsened during the next four days. It was then noticed that the catheter had been ignored on the ward. The QLB catheter was replaced with epidural and finally with intrathecal analgesia, which controlled the pain thereafter. Median daily opioid doses converted to morphine equivalent before and after the peripheral nerve block were 183 mg (IQR ) and 150 mg (IQR ), respectively. Twelve (71%) patients were able to diminish their daily opioid dose, while the median change in daily opioid dose was - 20 mg (IQR: ). Additional doses taken as needed by the patients with PCA were not available from the medical records. 3.2 complications of the nerve blocks Three patients presented with complication of the nerve block, but none were fatal. One patient with a brachial plexus block had numbness in the face and shortness of breath. The symptoms disappeared after the dose was reduced. Another patient experienced abnormal sweating with an increasing twitch after a single shot QLB with clonidine. The symptoms subsided and did not return when the patient received a continuous QLB (ropivacaine + clonidine) after two days. In addition, one patient had an infection at the catheter insertion site that was managed with antibiotics and by removing the catheter. 4 Discussion According to this analysis, peripheral blocks seem feasible and beneficial for patients with incurable cancer who suffer from severe pain. The complications are scarce and less harmful than those previously reported with central nerve blocks. In a multicenter study from 30 palliative care centers, the second most intensive symptom in cancer patients was pain, the intensity of which also increased towards end of life.(1) All 8

9 of the 17 patients with a median survival of under two months included in our study suffered from severe pain. They either received high doses of opioids or augmenting opioid doses did not bring any additional pain relief. Sixteen out of the seventeen patients reported pain relief from the block. They did not receive any other type of palliative interventions that could have had an influence on pain during the study period. In 4 patients, increased morphine doses were needed within the 24-hour timeline after placing the block. According to the findings of the narrative reviews of Klepstad and Kurita (7) the success rates of the blocks and the incidence of complications were of a similar magnitude to those in our study. Altogether, 79 cancer pain patients were dispersed among 16 studies in these reviews. Two of the studies contained 25 patients and the remaining 14 were case reports ranging from 1 to 7 patients. Of the two largest studies, one was of intercostal blocks (8), not included in our study, and the local anesthetic used in the other study was butamben, which is no longer in use due to its harmful side effects.(9) The small number of patients and the different methods used in the previous and present study limit the conclusions that can be drawn about the overall effectiveness of peripheral blocks on cancer pain. The reported overall risk of adverse events of peripheral nerve blocks in different indications is about 0-16/ (8) Although the rate of infection in peripheral catheters is low with a minimal morbidity, even fatal infections may occur.(10) One of our patients had a local infection that was treated with antibiotics. The use of peripheral catheters therefore warrants better education of personnel on the technical details and the amount of analgesic, rate of dosing, and the mode of dosage (bolus or infusion) of the analgesic. This education was insufficient in one of our cases and led to a lack of pain relief. Since the peripheral nerve blocks seem feasible and the possible risks are less harmful than with neuraxial anesthesia techniques, we recommend using ultrasound-guided peripheral nerve blocks as a safe and effective option for cancer patients in the alleviation of pain towards the end of life. 9

10 5 Limitations and strengths of the study This was a retrospective study with a small patient population. Our results do not, however, differ from other published case series, which have all had the same limitation. Our original plan was to collect the patients quantitative pain ratings before and after the block. However, the pain ratings were missing in approximately 40% of patients and for the four patients on PCA the doses needed in addition to continuous infusions were not marked in the patient charts. Another limitation is that many of the patients were transferred home or to community hospitals after receiving the block -thus the effect of the block was not traceable after that. 6 Conclusions Ultrasound guided peripheral blocks may provide considerable analgesia and decrease the need for opioids without major complications (11) in patients with advanced cancer and severe pain. To confirm these findings, we call for prospective randomized studies, probably requiring a multicenter approach to reach enough patients. 10

11 7 References 1. Verkissen MN, Hjermstad MJ, Van Belle S, Kaasa S, Deliens L, Pardon K. Quality of life and symptom intensity over time in people with cancer receiving palliative care: Results from the international European Palliative Care Cancer Symptom study. PLoS One [Internet]. 2019;14(10):e Available from: 2. Fallon M, Giusti R, Aielli F, Hoskin P, Rolke R, Sharma M, et al. Management of cancer pain in adult patients: ESMO Clinical Practice Guidelines. Ann Oncol [Internet]. 2018;29(July):iv Available from: 3. Murauski JD, Gonzalez KR. Peripheral nerve blocks for postoperative analgesia. Vol. 75, AORN journal p ; quiz Larkin PJ, Cherny NI, La Carpia D, Guglielmo M, Ostgathe C, Scotté F, et al. Diagnosis, assessment and management of constipation in advanced cancer: ESMO Clinical Practice Guidelines. Ann Oncol. 2018;29(July):iv Porreca F, Ossipov MH. Nausea and Vomiting Side Effects with Opioid Analgesics during Treatment of Chronic Pain: Mechanisms, Implications, and Management Options. Pain Med [Internet] May 1 [cited 2020 Jan 22];10(4): Available from: 6. Gagnier JJ, Kienle G, Altman DG, Moher D, Sox H, Riley D; the CARE Group. The CARE Guidelines: Consensus-based Clinical Case Reporting Guideline Development. 7. Klepstad P, Kurita GP, Mercadante SM, Sjøgren P. Evidence of peripheral nerve blocks for cancer-related pain: A systematic review. Minerva Anestesiol. 2015;81(7): Wong FCS, Lee TW, Yuen KK, Lo SH, Sze WK, Tung SY. Intercostal nerve blockade for cancer pain: Effectiveness and selection of patients. Hong Kong Med J. 2007;13(4): Shulman M, Lubenow TR, Nath HA, Blazek W, McCarthy RJ, Ivankovich AD. Nerve blocks with 5% butamben suspension for the treatment of chronic pain syndromes. Reg Anesth Pain Med. 1998;23(4): Nicolotti D, Iotti E, Fanelli G, Compagnone C. Perineural catheter infection: a systematic review of the literature. J Clin Anesth [Internet]. 2016;35: Available from: Bomberg H, Wetjen L, Wagenpfeil S, Schöpe J, Kessler P, Wulf H, et al. Risks and benefits of ultrasound, nerve stimulation, and their combination for guiding peripheral nerve blocks: A retrospective registry analysis. Anesth Analg. 2018;127(4):

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