Original Article Pain and Anxiety During Bone Marrow Biopsy Betty Tanasale, RN, MANP,* Jenne Kits, MA,† Philip M. Kluin, MD, PhD,‡ Albert Trip, PhD,§ and Hanneke C. Kluin-Nelemans, MD, PhD*
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From the *Department of Hematology; †Outpatient Clinic; ‡ Department of Pathology and Laboratory Medicine; § Support staff, University Medical Center Groningen, Groningen, The Netherlands. Address correspondence to Betty Tanasale, RN, MANP, Dept. of Hematology, University Medical Centre Groningen, University of Groningen, Hanzeplein 1, 9700 RB Groningen, The Netherlands. E-mail: [email protected] Received March 14, 2011; Revised June 24, 2011; Accepted June 28, 2011. 1524-9042/$36.00 Ó 2013 by the American Society for Pain Management Nursing doi:10.1016/j.pmn.2011.06.007
ABSTRACT:
A bone marrow biopsy is considered to be painful, often causing anxiety. We observed large differences between patients and wondered which factors cause pain and anxiety. In a prospective study, 202 patients were analyzed. Experienced hematologists and fellows in training (17% of biopsies) performed bone marrow aspirates and biopsies from the posterior iliac crest. Demographics, disease category, performance score, source of information, number of previous biopsies, experience of the hematologist, and length and quality of the biopsy were recorded. Pain and anxiety were measured using a visual analog scale and verbal rating score. Data were subjected to univariate and multivariate regression. The median pain score was 1.9 (range 0-10); 21% did not experience any pain. Anxiety scored 1.8 (range 0-10), and correlated positively with pain (p ¼ .000). By univariate analysis, young age, poor performance, the physician as source of information, and prolonged procedures were associated with more pain. In multivariate analysis, anxiety, information from the physician, and a prolonged procedure persisted. Length or artifacts of the core biopsy did not correlate with pain. In conclusion, bone marrow biopsies performed in an optimal setting by experienced hematologists cause only mild pain, with, however, some patients experienced serious problems. To reduce pain, not only careful local anesthesia, but also the addition of systemic analgesics and especially anxiety reduction seems to be useful. Ó 2013 by the American Society for Pain Management Nursing
A bone marrow biopsy is a frequently performed procedure to diagnose and evaluate hematologic diseases. Many patients undergo this procedure more than once. Although local anesthesia is applied, patients often regard the procedure as very painful (Kuball, Sch€ utz, Gamm, & Weber, 2004; Vanhelleputte, Nijs, Delforge, Evers, & Vanderschueren, 2003). To find predictors of pain, both Vanhelleputte et al. (2003) and Kuball et al. (2004) investigated patient-related and procedure-related variables. Regarding the patient, data were inconsistent or did not contribute as far as age, gender, body mass index, or disease category were concerned. Kuball et al. (2004) suggested that it would be important to measure patient anxiety, because this characteristic might be a strong predictor of pain. Regarding the procedure, it appeared that the duration of the procedure Pain Management Nursing, Vol 14, No 4 (December), 2013: pp 310-317
Bone Marrow Biopsy and Pain
was related to both increased pain (Mueller et al, 2000) and to inexperience of the physician performing the biopsy. In our department, we have observed large differences between patients regarding both anxiety and pain. Therefore, we initiated a prospective study to analyze which factors might contribute both to pain and anxiety to predict which patients might benefit from preventive measures. We focused not only on the patient- and procedure-related factors, but we also related our findings to the procedure and quality of the biopsy itself.
METHODS Patients and Setting Yearly, 1,100 biopsies are performed in the Groningen University Medical Center. All bone marrow biopsies and aspirates are performed by a small group of experienced hematologists and internists in training for hematology. One single person (J.K.) assists and is responsible for preparation of biopsy material, local anesthesia, sampling tubes, and caring for the patient during the procedure. In his absence, a few selected nurses replace him. The procedures are performed daily between 8 a.m. and 9 a.m. at the outpatient clinic. Patients are placed on a bed, in a right or left decubitus position with knees flexed. They do not receive any premedication. The posterior iliac crest is located; skin, subcutaneous tissues, and the periosteum are infiltrated with buffered lidocaine (2%). Anesthesia efficacy is controlled by tapping the periosteum with the needle used to administer the local anesthetic. Usually 10 mL of lidocaine is injected. A small skin incision precedes the introduction of the biopsy needle. Bone marrow biopsies are performed using a T-LokTM bone marrow biopsy needle (8 gauge 4 inches; Angiotech, Gainesville, FL, USA). This biopsy needle system enables the removal of the biopsy specimen with the T-LokTM extraction cannula while the outer needle remains in situ, after which bone marrow can be aspirated in small volumes (1-4 mL) for collection of material for smears, flow cytometry, cytogenetics, and molecular biology. When only an aspirate is needed, a bone marrow aspiration needle (16 gauge 2.7 inches; Angiotech) is used, without preceding skin incision. Local anesthesia procedures are identical. For the present study, all adult patients, hospitalized as well as outpatients, who had to undergo a bone marrow biopsy and/or aspirate between November 2008 and April 2009 were invited to participate by presenting them with a cover letter on their arrival at the outpatient clinic. After giving informed
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written consent, they received a first questionnaire addressing anxiety to be filled in 5 minutes before the procedure. Within 5 minutes after the procedure, they received a second questionnaire addressing pain. Each patient was included only once. Patients were excluded who could not complete the questionnaires (e.g., cognitive disabilities, language problems, emotional disturbance) or who refused to participate. Patients who received analgesics solely because of the bone marrow biopsy were also excluded. Out of 276 patients, 202 patients met the inclusion criteria for the study. The study was approved by the Medical Ethics Committee of the University Medical Center Groningen and was performed according to the Declaration of Helsinki. Variables The following patient-related variables were collected: age, gender, disease category, indication for the bone marrow procedure (diagnosis, staging, and response evaluation), performance status (Eastern Cooperative Oncology Group; Naumann et al, 2004 [ECOG] 0-4), number of previous bone marrow biopsies or aspirates, and the hospital where the procedure had been performed. To assess fear of pain during the biopsy (procedure-related anxiety) and fear for the final result (outcome-related anxiety), we used a visual analog scale (VAS) (Gift, 1989 & Keogh & Cochrane, 2002). In our questionnaire we presented a horizontal line, 100 mm in length, anchored on the left-hand side by the description ‘‘no anxiety at all’’ and on the on the right-hand side by ‘‘the worst imaginable anxiety.’’ The patients marked on the line the point that they felt represented their perception of their current state. We determined the VAS score by measuring in millimeters from the left-hand end of the line to the crossmark (Oken et al, 1982: Wewers & Lowe, 1990: Herr, Spratt, Garand, & Li (2007). Outcome-related anxiety was scored after the question whether the patient was worried about the final outcome, i.e., the diagnosis based on the bone marrow examination. Pain was assessed using two methods: first, the VAS, with the descriptions ‘‘no pain at all’’ on the left and ‘‘the worst imaginable pain’’ on the right, and second, a verbal rating score system (VRS) with five categories: absent, mild, moderate, severe, and very severe pain. Patients were informed about the procedure of a bone marrow puncture (e.g., preparation of the patient, local analgesia, duration, postpuncture care, and differences between aspiration and biopsy. The sources of the information obtained, physician, nurse, relatives, brochure, website (http://www.hematologi egroningen.nl/patienten/content/2beenmergonderzoe
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k.htm), or other, were recorded for each individual patient (more than one answer could be given). The procedure-related variables were recorded by the assistant (J.K.) during the procedure: name of the physician, name of the assistant, and experience of the physician expressed as the number of previously performed bone marrow biopsies: 1,000. When a procedure was prolonged, the causes were recorded: dry tap, anatomy-related, patient-related, and/or technical problems. The quality of the bone marrow core was scored independently of the other variables by the pathologist (P.M.K.) as follows: length in mm (measured from the microscopic preparations on the microscopic glass slides), tangentially taken specimens, or other features, such as the presence of multiple periosteal planes (Wilkins & Clark, 2009). To correct for confounding sources of pain, we documented simultaneous use of analgesics, sedating drugs, and anticoagulants. We divided analgesics into two categories: opioid and nonopioid. Sedating drugs were categorized into benzodiazepines and antidepressants. Anticoagulants were classified as acetylsalicylic acid, vitamin K antagonists, and low-molecularweight heparin. Data Analysis The dependent variable for this analysis was pain. Possible predictors of pain were first analyzed separately, using analysis of variance on categoric variables and linear regression on the continuous factors as appropriate. In all cases p values of 1,000 biopsies, and only 17% of the procedures were performed by fellows in training. We observed a trend toward a relationship between experience of the hematologist and the VAS score. The lack of significance (p ¼ .22) seems to be due to the small number of data in the group of doctors with the lowest experience. Despite our expectations, a patient’s previous experience of undergoing a bone marrow procedure in our hospital or in other hospitals did not influence the pain or anxiety levels. Almost all respondents (n ¼ 194) had received previous information about the procedure. Nine patients answered ‘‘no’’ when asked if they had received information before the procedure. Five of those patients had previously undergone a bone marrow biopsy. The most recorded source of information was the brochure (in 86 cases). Patients who received information from a physician (among others) had higher pain levels than those informed by others. In contrast, no such relation was found between the source of information and anxiety levels (p ¼ .12-.56). No correlation was seen between the length of the biopsy core and pain. The median length of the biopsy was 20 mm (range 1-44 mm) Even biopsies with
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Bone Marrow Biopsy and Pain
TABLE 1. Patient-Related Possible Determinants of Pain Variable Age, y
Gender Disease category
Indication Procedure Information source*
Previous biopsies or aspirates Use of analgesics Use of sedatives Use of anticoagulants
Subgroup
n
(%)
18-30 31-50 51-65 >65 Female Male Acute leukemia Chronic lymphocytic leukemia Chronic myeloid leukemia Malignant lymphoma Multiple myeloma Myelodysplastic syndrome Mastocytosis Other Diagnostic/staging Remission status Aspirate only Biopsy and aspirate Physician Nurse Relative Brochure Website of the department Other sources None† 0 1 2 Opioid Nonopioid Unknown Antidepressives Benzodiazepines Unknown Acetylsalicyl acid Low-molecular-weight heparin Vitamin K antagonists Unknown
12 42 96 52 89 113 36 8 9 39 37 41 4 28 70 132 78 123 70 57 13 86 14 62 9 63 40 99 15 14 6 2 12 1 16 14 11 9
(6) (21) (48) (26) (44) (56) (18) (4) (5) (19) (18) (20) (2) (14) (35) (65) (39) (61) (34) (28) (6) (43) (7) (31) (4) (31) (20) (49) (17) (8) (25)
*Since multiple sources were applicable the total percentage is >100%. † Nine patients received no information; five of them had previously undergone one or more similar procedures.
a length of $3 cm fell in all VAS scores (Fig. 2). Neither could a relation be found between the presence of tangential or multiple periosteal planes and pain (Table 3). In a multivariate analysis, only the factors anxiety, source of previous information, and prolonged procedure persisted.
DISCUSSION A bone marrow puncture is an important tool in the evaluation of hematologic diseases (Bain, Clark, Lampert & Wilkins, 2001). We performed a prospective study on a wide range of possible predictors of pain during a bone marrow biopsy and/or aspiration
procedure. The VAS median pain levels, scored by 197 patients, were low (1.9) though with a wide range. A considerable number of patients (21%) underwent the procedure without any pain at all, but almost one-half of the patients rated the pain as moderate or more on a VRS. Patients with high anxiety levels experienced more pain. Other predictors for high pain levels were a younger age, a poor performance score, and a prolonged procedure. Remarkably, physicians appeared to be poor information givers, because patients who received information from the physician (among other sources), experienced significantly more pain than when they had been informed by nurses or others.
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TABLE 2. Determinants of Pain: Scores and Correlations (n ¼ 197*) No. with VAS Pain Score Subgroup
#1
>1-#5
>5-10
Median
Range
Total1
18-50 >50 Female Male No Yes Acute leukemias, MDS‡ CLL§ CML{ Multiple myeloma Malignant lymphoma Other 0-2 3-4 Aspirate and biopsy Aspirate only Diagnostic Remission status 1,000 No Yes Dry tap Anatomy-related Patient-related Technical problems Unknown 1 $2 Less than expected The same as expected More than expected Yes No Yes No Yes No Yes No Yes No Yes No Yes No
8 63 32 39 47 24 28 3 1 12 16 11 68 3 45 26 26 45 7 21 43 57 14 5 4 1 3 1 34 37 42 26 2 69 2 19 50 20 49 5 64 29 40 3 66 22 47
20 63 30 53 61 22 26 4 8 17 14 14 77 6 44 39 26 57 18 19 46 66 17 5 1 5 7
18 25 25 18 28 15 22 1 0 5 8 7 38 5 33 10 17 26 7 15 21 25 18 3 5 5 4
2.7 1.7 2.5 1.8 1.9 2.0 2.2 1.9 1.7 2.2 1.7 1.9 1.9 3.8 2.3 1.7 1.8 2.0 2.8 1.7 1.7 1.8 2.7 2.5 3.5 5.0 2.7
0-10 0-10 0-10 0-10 0-10 1-10 0-10 0.4-7.6 0-4.8 0-7.2 0-10 0-7.9 0-10 0-10 0-10 0-10 0-10 0-10 0-10 0-10 0-10 0-10 0-10 0-7 0-10 0-9 0-10
38 45 42 32 9 77 6 25 52 21 56 7 70 36 41 8 69 25 52
22 21 12 18 12 42 1 24 18 15 27 1 41 20 22 3 39 13 29
1.8 2.3 1.7 1.8 5.4 2.0 2.6 2.6 1.8 2.0 1.9 1.9 2.0 2.5 1.7 3.2 1.9 1.8 2.0
0-10 0-10 0-7.4 0-10 0-10 0-10 0-10 0-10 0-10 0-8.4 0-10 0-8.8 0-10 0-10 0-10 0-7.1 0-10 0-10 0-10
46 151 87 110 136 61 76 8 9 34 38 32 183 14 122 75 69 128 33 55 110 148 49 13 10 11 14 1 94 103 96 76 23 188 9 68 120 56 132 13 175 85 103 14 174 60 128
Variable Age, y Gender Previous biopsy Diagnosis
Performance score Type of puncture Indication Physician experience, no. of procedures Prolonged procedure Cause of prolonged procedure
No. of aspirations Expected pain Information before procedure Information by physician Information by nurse Information by relative Information by brochure Information by website Information by other sources
VAS
*Five patients did not record pain VAS. † Significant (p < .05). ‡ Myelodysplastic syndrome. § Chronic lymphocytic leukemia. { Chronic myeloid leukemia.
p Value .02† .09 .74
.03† .32 .54 .22 .01†
.54
.01† .81 .72 . 89 .90 .88
Bone Marrow Biopsy and Pain
FIGURE 1.
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Pain scores: verbal rating score (VRS).
Although not verified, it might well be that physicians trivialize the procedure, whereas nurses tend to aggravate the potential pain. This fits with the observation by Kuball et al. (2004) that physicians, compared with nurses and patients, tend to underestimate pain experiences related to bone marrow punctures. Our data are in line with Vanhelleputte et al. (2003) and Kuball et al. (2004) regarding pain scores. However, the pain scores of our patients were far below those of Swords et al. (2010), who reported mean scores varying between 3.8 and 4.1. Whereas Kuball et al. (2004) could not confirm the results of Vanhelleputte et al. (2003) on the role of age, we did: young age was a predictor for a high pain experience. However, in a multivariate analysis it appeared that young patients are more afraid than elderly ones,
FIGURE 2. - Pain and length of biopsy. The y axis shows the visual analog scale (VAS) score for pain and the x axis the total length of the biopsy (mm) as measured from the microscopic preparations on the microscopic glass slides.
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confirming that anxiety overrules other predicting factors. We observed a correlation between anxiety levels and pain levels. We recorded two types of anxiety: procedure-related and outcome-related. Although both types of anxiety correlated positively with pain, the procedure-related fear was statistically more important. Exploring the data on anxiety, we analyzed the data with anxiety as the dependent variable to see which factors predict fear. It appeared that women, especially young ones, had significantly higher anxiety levels before a bone marrow biopsy than men. A poor performance score also predicted anxiety. In our hands, the type of bone marrow punctures (aspiration or biopsy) was not related to pain. This contrasts with Vanhelleputte et al. (2003) and Kuball et al. (2004), who both related a biopsy to prolonged procedure and increased pain levels. Our biopsy technique probably explains this difference. We used an extraction cannula, enabling the outer needle to remain in situ, after which bone marrow could be aspirated. This system definitely shortens the procedure when both a biopsy and aspirate are taken. Even with a new rotary powered device, as advocated by Swords (2010), mean pain scores remained higher (2.6-3.2) than reported by us. In addition, we studied whether the length of the biopsy specimen would contribute but could not find any correlation: Longer biopsy specimens are not more painful. Finally, biopsies with artifacts are often caused by specimens taken tangentially and associated with increased periosteal damage. We hypothesized that biopsies associated with increased periosteal damage would correlate with increased pain intensity; however, we could not confirm this, either. Procedure-related complications were important predictors for more pain experience (Vanhelleputte et al., 2003 and Kuball et al., 2004). In our study, a complicated procedure (undoubtedly reflecting a longer procedure duration) significantly increased pain experience. We expected that morbid or severe obesity would hamper the procedure and would increase pain levels. We encountered only seven patients with morbid or severe obesity, of whom the majority had low pain scores (median score 2), which is in line with Vanhelleputte et al. (2003), who made the same remarkable observation that a body mass index >30 kg/m2 was related to less pain. Obviously, a high body mass index does not always predict increased fat tissue above the posterior iliac crest which would make it more difficult to localize and perform the biopsy. In our study, the majority of biopsies were performed by experienced hematologists. The policy in our hospital to restrict the procedure to experienced
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TABLE 3. Bone Marrow Core Versus Pain (n ¼120) VAS Pain
Quality Integrity Tangential periostal plane
Sufficient Insufficient Sufficient Insufficient No Yes Missing
#1
>1-# 5
>5-10
Total
31 13 28 16 31 12
36 10 34 12 28 18
18 12 21 9 18 12
85 35 83 37 77 42 1
operators, i.e., hematologists and hematology fellows, seems to be useful. We could not prove that experience is important, because the percentage of biopsies performed by an inexperienced fellow was too low. We considered it to be unethical to expand our data with more inexperienced physicians outside the group of hematology fellows in training, given our excellent results. It is obvious that preventive measures could reduce pain in some patients. Van Helleputte et al. (2003) showed in a randomized placebo-controlled trial that the oral analgesic tramadol significantly reduced pain (2 50 patients; score 2.9 vs. 1.7) during a bone marrow biopsy. Milligan et al. (1987) focused on anxiolytic treatment with lorazepam and performed a small placebo-controlled study consisting of 46 patients. This group demonstrated an absence of immediate pain reduction but instead a significant pain reduction in a 24-hour recall pain score. Finally, Talamo et al. (2009) used a combination of analgesia and anxiolysis (n ¼ 34) and reported a significant lower pain score compared with patients who received only local anesthesia (n ¼ 50). Unfortunately, that study lacked a randomized comparison and the differences between pain scores were minor. As far as the nursing interventions are concerned, our recommendations (based on best practices) to decrease anxiety are to provide realistic information and
to avoid long waiting time in the waiting room before the procedure. During the procedure it is important that the assisting nurse is not only focused on assisting the physician, but also paying attention to the patient. Partners should be allowed to accompany the patient during the procedure if that contributes to a calm atmosphere. In conclusion, bone marrow biopsies performed in an optimal setting by experienced hematologists were associated with mild pain. Although a small number of patients experienced serious problems, it is suggested that addressing anxiety may be a useful tool in reducing the pain experience. We did not find a single strong predictor of pain; many factors appeared to be important, some stronger than others. This makes it difficult to predict which patient will be at risk and can benefit from prophylactic measures. In any future trial, one should focus on pain and anxiety reduction in a stepwise approach: first, optimal local anesthesia, followed by systemic analgesic drugs, and finally, systematic anxiolytic drugs. Careful stratification for the predictors described in this study will be important.
Acknowledgments The authors thank the patients for their participation and are grateful to the nurses of the outpatient clinic and the hematologists of the Department of Hematology.
REFERENCES Bain, B. J., Clark, D. M., Lampert, I. A., & Wilkins, B. S. (2001). Bone marrow pathology, (3rd ed.) London: Blackwell Science. Gift, A. G. (1989). Visual analogue scales: Measurement of subjective phenomena. Nursing Research, 38, 286–288. Herr, K., Spratt, K. F., Garand, L., & Li, L. (2007). Evaluation of the Iowa Pain Thermometer and other selected pain intensity scales in younger and older adult cohort using controlled clinical pain. Pain Medicine, 8, 585–600.
Keogh, E., & Cochrane, M. (2002). Anxiety sensitivity, cognitive biases, and the experience of pain. Journal of Pain, 3, 320–329. Kuball, J., Sch€ utz, J., Gamm, H., & Weber, M. (2004). Bone marrow punctures and pain. Acute Pain, 6, 9–14. Milligan, D. W., Howard, M. R., & Judd, A. (1987). Premedication with lorazepam before bone marrow biopsy. Journal of Clinical Pathology, 40, 696–698.
Bone Marrow Biopsy and Pain
Mueller, P. R., Biswal, S., Halpern, E. F., Kaufman, J. A., & Lee, M. J. (2000). Interventional radiologic procedures: Patient anxiety, perception of pain, understanding of procedure, and satisfaction with medication—A prospective study. Radiology, 215, 684–688. Naumann, R., K€ ollner, V., Einsle, F., Schneider, E., Ehninger, G., Joraschky, P., & Kugler, J. (2004). Pain perception in patients undergoing bone marrow puncture—A pilot study. Perceptual and Motor Skills, 98, 116–122. Oken, M. M., Creech, R. H., Tormey, D. C., Horton, J., Davis, T. E., McFadden, E. T., & Carbone, P. P. (1982). Toxicity and response criteria of the Eastern Cooperative Oncology Group. American Journal of Clinical Oncology, 5, 649–655. Swords, R. T., Anguita, J., Higgins, R. A., Yunes, A., Naski, M., Padmanabhan, S., Kelly, K. R., Mahalingam, D., Philbeck, T., Miller, L., Giles, F. J., Kinney, M., & Brenner, A. (2010). A new rotary powered device for bone marrow
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aspiration and biopsy yields superior specimens with less pain: Results of a randomised clinical study. Blood, 116, 650– 651, (abst. 1529). Talamo, G., Liao, J., Bayerl, M. G., Claxton, D. F., & Zangari, M. (2009). Oral administration of analgesia and anxiolysis for pain associated with bone marrow biopsy. Support Care Cancer, 18, 301–305. Vanhelleputte, P., Nijs, K., Delforge, M., Evers, G., & Vanderschueren, S. (2003). Pain during bone marrow aspiration: Prevalence and prevention. Journal of Pain Symptom Management, 26, 860–866. Wewers, M. E., & Lowe, N. K. (1990). A critical review of visual analogue scales in the measurement of clinical phenomena. Research in Nursing & Health, 13, 227–236. Wilkins, B. S., & Clark, D. M. (2009). Making the most of bone marrow trephine biopsy. Histopathology, 55, 631–640.
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From the *Department of Hematology; †Outpatient Clinic; ‡ Department of Pathology and Laboratory Medicine; § Support staff, University Medical Center Groningen, Groningen, The Netherlands. Address correspondence to Betty Tanasale, RN, MANP, Dept. of Hematology, University Medical Centre Groningen, University of Groningen, Hanzeplein 1, 9700 RB Groningen, The Netherlands. E-mail: [email protected] Received March 14, 2011; Revised June 24, 2011; Accepted June 28, 2011. 1524-9042/$36.00 Ó 2013 by the American Society for Pain Management Nursing doi:10.1016/j.pmn.2011.06.007
ABSTRACT:
A bone marrow biopsy is considered to be painful, often causing anxiety. We observed large differences between patients and wondered which factors cause pain and anxiety. In a prospective study, 202 patients were analyzed. Experienced hematologists and fellows in training (17% of biopsies) performed bone marrow aspirates and biopsies from the posterior iliac crest. Demographics, disease category, performance score, source of information, number of previous biopsies, experience of the hematologist, and length and quality of the biopsy were recorded. Pain and anxiety were measured using a visual analog scale and verbal rating score. Data were subjected to univariate and multivariate regression. The median pain score was 1.9 (range 0-10); 21% did not experience any pain. Anxiety scored 1.8 (range 0-10), and correlated positively with pain (p ¼ .000). By univariate analysis, young age, poor performance, the physician as source of information, and prolonged procedures were associated with more pain. In multivariate analysis, anxiety, information from the physician, and a prolonged procedure persisted. Length or artifacts of the core biopsy did not correlate with pain. In conclusion, bone marrow biopsies performed in an optimal setting by experienced hematologists cause only mild pain, with, however, some patients experienced serious problems. To reduce pain, not only careful local anesthesia, but also the addition of systemic analgesics and especially anxiety reduction seems to be useful. Ó 2013 by the American Society for Pain Management Nursing
A bone marrow biopsy is a frequently performed procedure to diagnose and evaluate hematologic diseases. Many patients undergo this procedure more than once. Although local anesthesia is applied, patients often regard the procedure as very painful (Kuball, Sch€ utz, Gamm, & Weber, 2004; Vanhelleputte, Nijs, Delforge, Evers, & Vanderschueren, 2003). To find predictors of pain, both Vanhelleputte et al. (2003) and Kuball et al. (2004) investigated patient-related and procedure-related variables. Regarding the patient, data were inconsistent or did not contribute as far as age, gender, body mass index, or disease category were concerned. Kuball et al. (2004) suggested that it would be important to measure patient anxiety, because this characteristic might be a strong predictor of pain. Regarding the procedure, it appeared that the duration of the procedure Pain Management Nursing, Vol 14, No 4 (December), 2013: pp 310-317
Bone Marrow Biopsy and Pain
was related to both increased pain (Mueller et al, 2000) and to inexperience of the physician performing the biopsy. In our department, we have observed large differences between patients regarding both anxiety and pain. Therefore, we initiated a prospective study to analyze which factors might contribute both to pain and anxiety to predict which patients might benefit from preventive measures. We focused not only on the patient- and procedure-related factors, but we also related our findings to the procedure and quality of the biopsy itself.
METHODS Patients and Setting Yearly, 1,100 biopsies are performed in the Groningen University Medical Center. All bone marrow biopsies and aspirates are performed by a small group of experienced hematologists and internists in training for hematology. One single person (J.K.) assists and is responsible for preparation of biopsy material, local anesthesia, sampling tubes, and caring for the patient during the procedure. In his absence, a few selected nurses replace him. The procedures are performed daily between 8 a.m. and 9 a.m. at the outpatient clinic. Patients are placed on a bed, in a right or left decubitus position with knees flexed. They do not receive any premedication. The posterior iliac crest is located; skin, subcutaneous tissues, and the periosteum are infiltrated with buffered lidocaine (2%). Anesthesia efficacy is controlled by tapping the periosteum with the needle used to administer the local anesthetic. Usually 10 mL of lidocaine is injected. A small skin incision precedes the introduction of the biopsy needle. Bone marrow biopsies are performed using a T-LokTM bone marrow biopsy needle (8 gauge 4 inches; Angiotech, Gainesville, FL, USA). This biopsy needle system enables the removal of the biopsy specimen with the T-LokTM extraction cannula while the outer needle remains in situ, after which bone marrow can be aspirated in small volumes (1-4 mL) for collection of material for smears, flow cytometry, cytogenetics, and molecular biology. When only an aspirate is needed, a bone marrow aspiration needle (16 gauge 2.7 inches; Angiotech) is used, without preceding skin incision. Local anesthesia procedures are identical. For the present study, all adult patients, hospitalized as well as outpatients, who had to undergo a bone marrow biopsy and/or aspirate between November 2008 and April 2009 were invited to participate by presenting them with a cover letter on their arrival at the outpatient clinic. After giving informed
311
written consent, they received a first questionnaire addressing anxiety to be filled in 5 minutes before the procedure. Within 5 minutes after the procedure, they received a second questionnaire addressing pain. Each patient was included only once. Patients were excluded who could not complete the questionnaires (e.g., cognitive disabilities, language problems, emotional disturbance) or who refused to participate. Patients who received analgesics solely because of the bone marrow biopsy were also excluded. Out of 276 patients, 202 patients met the inclusion criteria for the study. The study was approved by the Medical Ethics Committee of the University Medical Center Groningen and was performed according to the Declaration of Helsinki. Variables The following patient-related variables were collected: age, gender, disease category, indication for the bone marrow procedure (diagnosis, staging, and response evaluation), performance status (Eastern Cooperative Oncology Group; Naumann et al, 2004 [ECOG] 0-4), number of previous bone marrow biopsies or aspirates, and the hospital where the procedure had been performed. To assess fear of pain during the biopsy (procedure-related anxiety) and fear for the final result (outcome-related anxiety), we used a visual analog scale (VAS) (Gift, 1989 & Keogh & Cochrane, 2002). In our questionnaire we presented a horizontal line, 100 mm in length, anchored on the left-hand side by the description ‘‘no anxiety at all’’ and on the on the right-hand side by ‘‘the worst imaginable anxiety.’’ The patients marked on the line the point that they felt represented their perception of their current state. We determined the VAS score by measuring in millimeters from the left-hand end of the line to the crossmark (Oken et al, 1982: Wewers & Lowe, 1990: Herr, Spratt, Garand, & Li (2007). Outcome-related anxiety was scored after the question whether the patient was worried about the final outcome, i.e., the diagnosis based on the bone marrow examination. Pain was assessed using two methods: first, the VAS, with the descriptions ‘‘no pain at all’’ on the left and ‘‘the worst imaginable pain’’ on the right, and second, a verbal rating score system (VRS) with five categories: absent, mild, moderate, severe, and very severe pain. Patients were informed about the procedure of a bone marrow puncture (e.g., preparation of the patient, local analgesia, duration, postpuncture care, and differences between aspiration and biopsy. The sources of the information obtained, physician, nurse, relatives, brochure, website (http://www.hematologi egroningen.nl/patienten/content/2beenmergonderzoe
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k.htm), or other, were recorded for each individual patient (more than one answer could be given). The procedure-related variables were recorded by the assistant (J.K.) during the procedure: name of the physician, name of the assistant, and experience of the physician expressed as the number of previously performed bone marrow biopsies: 1,000. When a procedure was prolonged, the causes were recorded: dry tap, anatomy-related, patient-related, and/or technical problems. The quality of the bone marrow core was scored independently of the other variables by the pathologist (P.M.K.) as follows: length in mm (measured from the microscopic preparations on the microscopic glass slides), tangentially taken specimens, or other features, such as the presence of multiple periosteal planes (Wilkins & Clark, 2009). To correct for confounding sources of pain, we documented simultaneous use of analgesics, sedating drugs, and anticoagulants. We divided analgesics into two categories: opioid and nonopioid. Sedating drugs were categorized into benzodiazepines and antidepressants. Anticoagulants were classified as acetylsalicylic acid, vitamin K antagonists, and low-molecularweight heparin. Data Analysis The dependent variable for this analysis was pain. Possible predictors of pain were first analyzed separately, using analysis of variance on categoric variables and linear regression on the continuous factors as appropriate. In all cases p values of 1,000 biopsies, and only 17% of the procedures were performed by fellows in training. We observed a trend toward a relationship between experience of the hematologist and the VAS score. The lack of significance (p ¼ .22) seems to be due to the small number of data in the group of doctors with the lowest experience. Despite our expectations, a patient’s previous experience of undergoing a bone marrow procedure in our hospital or in other hospitals did not influence the pain or anxiety levels. Almost all respondents (n ¼ 194) had received previous information about the procedure. Nine patients answered ‘‘no’’ when asked if they had received information before the procedure. Five of those patients had previously undergone a bone marrow biopsy. The most recorded source of information was the brochure (in 86 cases). Patients who received information from a physician (among others) had higher pain levels than those informed by others. In contrast, no such relation was found between the source of information and anxiety levels (p ¼ .12-.56). No correlation was seen between the length of the biopsy core and pain. The median length of the biopsy was 20 mm (range 1-44 mm) Even biopsies with
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Bone Marrow Biopsy and Pain
TABLE 1. Patient-Related Possible Determinants of Pain Variable Age, y
Gender Disease category
Indication Procedure Information source*
Previous biopsies or aspirates Use of analgesics Use of sedatives Use of anticoagulants
Subgroup
n
(%)
18-30 31-50 51-65 >65 Female Male Acute leukemia Chronic lymphocytic leukemia Chronic myeloid leukemia Malignant lymphoma Multiple myeloma Myelodysplastic syndrome Mastocytosis Other Diagnostic/staging Remission status Aspirate only Biopsy and aspirate Physician Nurse Relative Brochure Website of the department Other sources None† 0 1 2 Opioid Nonopioid Unknown Antidepressives Benzodiazepines Unknown Acetylsalicyl acid Low-molecular-weight heparin Vitamin K antagonists Unknown
12 42 96 52 89 113 36 8 9 39 37 41 4 28 70 132 78 123 70 57 13 86 14 62 9 63 40 99 15 14 6 2 12 1 16 14 11 9
(6) (21) (48) (26) (44) (56) (18) (4) (5) (19) (18) (20) (2) (14) (35) (65) (39) (61) (34) (28) (6) (43) (7) (31) (4) (31) (20) (49) (17) (8) (25)
*Since multiple sources were applicable the total percentage is >100%. † Nine patients received no information; five of them had previously undergone one or more similar procedures.
a length of $3 cm fell in all VAS scores (Fig. 2). Neither could a relation be found between the presence of tangential or multiple periosteal planes and pain (Table 3). In a multivariate analysis, only the factors anxiety, source of previous information, and prolonged procedure persisted.
DISCUSSION A bone marrow puncture is an important tool in the evaluation of hematologic diseases (Bain, Clark, Lampert & Wilkins, 2001). We performed a prospective study on a wide range of possible predictors of pain during a bone marrow biopsy and/or aspiration
procedure. The VAS median pain levels, scored by 197 patients, were low (1.9) though with a wide range. A considerable number of patients (21%) underwent the procedure without any pain at all, but almost one-half of the patients rated the pain as moderate or more on a VRS. Patients with high anxiety levels experienced more pain. Other predictors for high pain levels were a younger age, a poor performance score, and a prolonged procedure. Remarkably, physicians appeared to be poor information givers, because patients who received information from the physician (among other sources), experienced significantly more pain than when they had been informed by nurses or others.
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TABLE 2. Determinants of Pain: Scores and Correlations (n ¼ 197*) No. with VAS Pain Score Subgroup
#1
>1-#5
>5-10
Median
Range
Total1
18-50 >50 Female Male No Yes Acute leukemias, MDS‡ CLL§ CML{ Multiple myeloma Malignant lymphoma Other 0-2 3-4 Aspirate and biopsy Aspirate only Diagnostic Remission status 1,000 No Yes Dry tap Anatomy-related Patient-related Technical problems Unknown 1 $2 Less than expected The same as expected More than expected Yes No Yes No Yes No Yes No Yes No Yes No Yes No
8 63 32 39 47 24 28 3 1 12 16 11 68 3 45 26 26 45 7 21 43 57 14 5 4 1 3 1 34 37 42 26 2 69 2 19 50 20 49 5 64 29 40 3 66 22 47
20 63 30 53 61 22 26 4 8 17 14 14 77 6 44 39 26 57 18 19 46 66 17 5 1 5 7
18 25 25 18 28 15 22 1 0 5 8 7 38 5 33 10 17 26 7 15 21 25 18 3 5 5 4
2.7 1.7 2.5 1.8 1.9 2.0 2.2 1.9 1.7 2.2 1.7 1.9 1.9 3.8 2.3 1.7 1.8 2.0 2.8 1.7 1.7 1.8 2.7 2.5 3.5 5.0 2.7
0-10 0-10 0-10 0-10 0-10 1-10 0-10 0.4-7.6 0-4.8 0-7.2 0-10 0-7.9 0-10 0-10 0-10 0-10 0-10 0-10 0-10 0-10 0-10 0-10 0-10 0-7 0-10 0-9 0-10
38 45 42 32 9 77 6 25 52 21 56 7 70 36 41 8 69 25 52
22 21 12 18 12 42 1 24 18 15 27 1 41 20 22 3 39 13 29
1.8 2.3 1.7 1.8 5.4 2.0 2.6 2.6 1.8 2.0 1.9 1.9 2.0 2.5 1.7 3.2 1.9 1.8 2.0
0-10 0-10 0-7.4 0-10 0-10 0-10 0-10 0-10 0-10 0-8.4 0-10 0-8.8 0-10 0-10 0-10 0-7.1 0-10 0-10 0-10
46 151 87 110 136 61 76 8 9 34 38 32 183 14 122 75 69 128 33 55 110 148 49 13 10 11 14 1 94 103 96 76 23 188 9 68 120 56 132 13 175 85 103 14 174 60 128
Variable Age, y Gender Previous biopsy Diagnosis
Performance score Type of puncture Indication Physician experience, no. of procedures Prolonged procedure Cause of prolonged procedure
No. of aspirations Expected pain Information before procedure Information by physician Information by nurse Information by relative Information by brochure Information by website Information by other sources
VAS
*Five patients did not record pain VAS. † Significant (p < .05). ‡ Myelodysplastic syndrome. § Chronic lymphocytic leukemia. { Chronic myeloid leukemia.
p Value .02† .09 .74
.03† .32 .54 .22 .01†
.54
.01† .81 .72 . 89 .90 .88
Bone Marrow Biopsy and Pain
FIGURE 1.
-
Pain scores: verbal rating score (VRS).
Although not verified, it might well be that physicians trivialize the procedure, whereas nurses tend to aggravate the potential pain. This fits with the observation by Kuball et al. (2004) that physicians, compared with nurses and patients, tend to underestimate pain experiences related to bone marrow punctures. Our data are in line with Vanhelleputte et al. (2003) and Kuball et al. (2004) regarding pain scores. However, the pain scores of our patients were far below those of Swords et al. (2010), who reported mean scores varying between 3.8 and 4.1. Whereas Kuball et al. (2004) could not confirm the results of Vanhelleputte et al. (2003) on the role of age, we did: young age was a predictor for a high pain experience. However, in a multivariate analysis it appeared that young patients are more afraid than elderly ones,
FIGURE 2. - Pain and length of biopsy. The y axis shows the visual analog scale (VAS) score for pain and the x axis the total length of the biopsy (mm) as measured from the microscopic preparations on the microscopic glass slides.
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confirming that anxiety overrules other predicting factors. We observed a correlation between anxiety levels and pain levels. We recorded two types of anxiety: procedure-related and outcome-related. Although both types of anxiety correlated positively with pain, the procedure-related fear was statistically more important. Exploring the data on anxiety, we analyzed the data with anxiety as the dependent variable to see which factors predict fear. It appeared that women, especially young ones, had significantly higher anxiety levels before a bone marrow biopsy than men. A poor performance score also predicted anxiety. In our hands, the type of bone marrow punctures (aspiration or biopsy) was not related to pain. This contrasts with Vanhelleputte et al. (2003) and Kuball et al. (2004), who both related a biopsy to prolonged procedure and increased pain levels. Our biopsy technique probably explains this difference. We used an extraction cannula, enabling the outer needle to remain in situ, after which bone marrow could be aspirated. This system definitely shortens the procedure when both a biopsy and aspirate are taken. Even with a new rotary powered device, as advocated by Swords (2010), mean pain scores remained higher (2.6-3.2) than reported by us. In addition, we studied whether the length of the biopsy specimen would contribute but could not find any correlation: Longer biopsy specimens are not more painful. Finally, biopsies with artifacts are often caused by specimens taken tangentially and associated with increased periosteal damage. We hypothesized that biopsies associated with increased periosteal damage would correlate with increased pain intensity; however, we could not confirm this, either. Procedure-related complications were important predictors for more pain experience (Vanhelleputte et al., 2003 and Kuball et al., 2004). In our study, a complicated procedure (undoubtedly reflecting a longer procedure duration) significantly increased pain experience. We expected that morbid or severe obesity would hamper the procedure and would increase pain levels. We encountered only seven patients with morbid or severe obesity, of whom the majority had low pain scores (median score 2), which is in line with Vanhelleputte et al. (2003), who made the same remarkable observation that a body mass index >30 kg/m2 was related to less pain. Obviously, a high body mass index does not always predict increased fat tissue above the posterior iliac crest which would make it more difficult to localize and perform the biopsy. In our study, the majority of biopsies were performed by experienced hematologists. The policy in our hospital to restrict the procedure to experienced
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TABLE 3. Bone Marrow Core Versus Pain (n ¼120) VAS Pain
Quality Integrity Tangential periostal plane
Sufficient Insufficient Sufficient Insufficient No Yes Missing
#1
>1-# 5
>5-10
Total
31 13 28 16 31 12
36 10 34 12 28 18
18 12 21 9 18 12
85 35 83 37 77 42 1
operators, i.e., hematologists and hematology fellows, seems to be useful. We could not prove that experience is important, because the percentage of biopsies performed by an inexperienced fellow was too low. We considered it to be unethical to expand our data with more inexperienced physicians outside the group of hematology fellows in training, given our excellent results. It is obvious that preventive measures could reduce pain in some patients. Van Helleputte et al. (2003) showed in a randomized placebo-controlled trial that the oral analgesic tramadol significantly reduced pain (2 50 patients; score 2.9 vs. 1.7) during a bone marrow biopsy. Milligan et al. (1987) focused on anxiolytic treatment with lorazepam and performed a small placebo-controlled study consisting of 46 patients. This group demonstrated an absence of immediate pain reduction but instead a significant pain reduction in a 24-hour recall pain score. Finally, Talamo et al. (2009) used a combination of analgesia and anxiolysis (n ¼ 34) and reported a significant lower pain score compared with patients who received only local anesthesia (n ¼ 50). Unfortunately, that study lacked a randomized comparison and the differences between pain scores were minor. As far as the nursing interventions are concerned, our recommendations (based on best practices) to decrease anxiety are to provide realistic information and
to avoid long waiting time in the waiting room before the procedure. During the procedure it is important that the assisting nurse is not only focused on assisting the physician, but also paying attention to the patient. Partners should be allowed to accompany the patient during the procedure if that contributes to a calm atmosphere. In conclusion, bone marrow biopsies performed in an optimal setting by experienced hematologists were associated with mild pain. Although a small number of patients experienced serious problems, it is suggested that addressing anxiety may be a useful tool in reducing the pain experience. We did not find a single strong predictor of pain; many factors appeared to be important, some stronger than others. This makes it difficult to predict which patient will be at risk and can benefit from prophylactic measures. In any future trial, one should focus on pain and anxiety reduction in a stepwise approach: first, optimal local anesthesia, followed by systemic analgesic drugs, and finally, systematic anxiolytic drugs. Careful stratification for the predictors described in this study will be important.
Acknowledgments The authors thank the patients for their participation and are grateful to the nurses of the outpatient clinic and the hematologists of the Department of Hematology.
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Keogh, E., & Cochrane, M. (2002). Anxiety sensitivity, cognitive biases, and the experience of pain. Journal of Pain, 3, 320–329. Kuball, J., Sch€ utz, J., Gamm, H., & Weber, M. (2004). Bone marrow punctures and pain. Acute Pain, 6, 9–14. Milligan, D. W., Howard, M. R., & Judd, A. (1987). Premedication with lorazepam before bone marrow biopsy. Journal of Clinical Pathology, 40, 696–698.
Bone Marrow Biopsy and Pain
Mueller, P. R., Biswal, S., Halpern, E. F., Kaufman, J. A., & Lee, M. J. (2000). Interventional radiologic procedures: Patient anxiety, perception of pain, understanding of procedure, and satisfaction with medication—A prospective study. Radiology, 215, 684–688. Naumann, R., K€ ollner, V., Einsle, F., Schneider, E., Ehninger, G., Joraschky, P., & Kugler, J. (2004). Pain perception in patients undergoing bone marrow puncture—A pilot study. Perceptual and Motor Skills, 98, 116–122. Oken, M. M., Creech, R. H., Tormey, D. C., Horton, J., Davis, T. E., McFadden, E. T., & Carbone, P. P. (1982). Toxicity and response criteria of the Eastern Cooperative Oncology Group. American Journal of Clinical Oncology, 5, 649–655. Swords, R. T., Anguita, J., Higgins, R. A., Yunes, A., Naski, M., Padmanabhan, S., Kelly, K. R., Mahalingam, D., Philbeck, T., Miller, L., Giles, F. J., Kinney, M., & Brenner, A. (2010). A new rotary powered device for bone marrow
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aspiration and biopsy yields superior specimens with less pain: Results of a randomised clinical study. Blood, 116, 650– 651, (abst. 1529). Talamo, G., Liao, J., Bayerl, M. G., Claxton, D. F., & Zangari, M. (2009). Oral administration of analgesia and anxiolysis for pain associated with bone marrow biopsy. Support Care Cancer, 18, 301–305. Vanhelleputte, P., Nijs, K., Delforge, M., Evers, G., & Vanderschueren, S. (2003). Pain during bone marrow aspiration: Prevalence and prevention. Journal of Pain Symptom Management, 26, 860–866. Wewers, M. E., & Lowe, N. K. (1990). A critical review of visual analogue scales in the measurement of clinical phenomena. Research in Nursing & Health, 13, 227–236. Wilkins, B. S., & Clark, D. M. (2009). Making the most of bone marrow trephine biopsy. Histopathology, 55, 631–640.
