When a BMBA is performed in adults, a local anesthetic (LA), usually lidocaine or a similar drug, is used to numb the area of the skin and periosteum at the puncture site before the procedure. Lidocaine can be given along with sodium bicarbonate to reduce the burning pain of the lidocaine solution . In case of an adverse reaction to the medication, an alternative drug, like chloroprocaine or bupivacaine hydrochloride can be used . Articaine, a LA that is able to penetrate the bone, can also be used, however, studies have shown that the drug is not superior to lidocaine, and that patients do not report lower pain scores . Other drugs may be used for local anesthesia such as mepivacain; however, there are very limited data to support the use of one drug over another in bone marrow biopsies.
Intravenous sedation (IVS) with drugs such as lorazepam, midazolam, or diazepam is often administered in addition to LA [10, 15]. Besides reducing anxiety and pain perception, IVS has shown to produce a retrograde amnesia for the procedure in many patients . These drugs are commonly requested by patients that experienced severe pain during their first bone marrow biopsy (which underlines the importance that the first biopsy is as painless as possible). In a different study, a combination of hydromorphone and lorazepam administered 90 min prior to a BMBA showed a lower pain perception and retrograde amnesia in half of the patients . According to several studies, patients receiving IVS tend to be more often willing to undergo a future BMBA, compared to patients receiving only LA . Apart from the favorable effects, IVS administration has serious drawbacks, like prolongation of the hospital stay, requirement of additional staff and equipment, and furthermore, it contributes to an increase in incidence of adverse effects. Before administration, the beneficial effects of IVS need to be balanced against the adverse effects for each given patient. When given the choice between LA only and LA/IVS, patients choosing LA were more satisfied with their choice. However, patients that received IVS alongside LA had a lower pain score compared to patients receiving LA only . We have to remember that many times the patients experiencing severe pain during the first bone marrow biopsy will ask for IVS. Personal experience shows that when biopsy is performed in such patients by an experienced physician that uses only LA, the IVS will not be requested in further biopsies if the patients who felt pain during biopsy are satisfied afterwards.
Since LA does not prevent the transient pain experienced during suction, premedication with a centrally acting opioid analgesic, like tramadol, can be used to reduce the pain intensity significantly, indicating that the pain provoked by vacuum aspiration of bone marrow is opioid-responsive . In comparison to other opioids, tramadol lacks the unwanted effects on the cardiovascular and respiratory system and is therefore better tolerated [12, 37]. With a 50-mg dose used prior to the biopsy, the pain could be reduced, and there were no major side effects reported in the study patients. Another study indicates the use of deep sedation in the form of midazolam, fentanyl, and propofol for pain reduction .
The most recent studies have shown some reduction in pain intensity with the usage of nitrous oxide/oxygen (N2O/O2) or nitrous oxide alone . This gas may be used for pain relief in BMBAs [20, 41]. Patients self-administer the gas a couple of minutes before and during the procedure when discomfort is experienced . The benefits of this approach are the low cost, no hospitalization, and less nursing or medical supervision. In a study, it was shown that 93 % of pediatric patients undergoing various procedures with a nitrous oxide/oxygen mixture, would choose this again, if the procedure had to be repeated in the future . However, adverse effects like diffusion hypoxia have been reported . In a different study , patients were offered a choice between LA alone or LA in combination with N2O/O2. A pain reduction was noted in the LA/N2O/O2 group, but the results were not statistically significant. However, 84 % of the patients using this combination would request it again for a future procedure .
In conclusion, premedication with a LA alone or in combination with IVS did reduce pain but did not prevent unbearable pain . Tramadol can be used to further reduce the intensity of pain, but severe pain may still occur in some patients .
One of the important pain-influencing factors during BMBAs is the patients’ anxiety before the procedure. Establishing trust by being honest, providing accurate information in terms the patient can understand, and ensuring comfort and privacy can lower the patients’ anxiety prior to the procedure. A survey of data clearly indicates the influence of information provided by the physician on pain during a procedure . Often underestimated, good information prior to procedure could be an effective and simple way to reduce pain during examinations, since inadequate information at any time shows a trend towards an association with unbearable pain. Patients who reported to have received information about the procedure or who had previous personal experience with bone marrow examination could arrange a mental strategy and experience unbearable pain less often .
Another approach is the use of different types of biopsy devices. Development of new equipment, such as biopsy needles with internal snares to capture bone marrow, reduces the discomfort experienced by the patient [18, 19] and allows easier biopsy for the physician if used properly. In addition, a new mechanical device, the OnControl Bone Marrow Biopsy System, was introduced recently. The mechanical device was assessed in a small randomized trial, in which it was shown to cause similar pain compared to the conventional biopsy needles, however with possibility of more complications, even though the biopsy done with the powered device took half the time compared to the manual biopsy . The positive effect of automated biopsy needle was a reduction of the residual pain the day after the biopsy. Unfortunately, the data coming from a limited number of patients cannot be well interpreted, as it is impossible to randomize the operator's skills to perform the bone marrow biopsy with a normal device versus a new device that is provided by the sponsor of the trial.
Also, alternative ways of pain reduction were explored in different centers to reduce the discomfort associated with a BMBA. For example, hypnosis has been used as an adjunct to local anesthetics and showed to be beneficial [1, 29]. In one study, hypnosis showed to lower the anxiety during the procedure but did not show any significant decrease in pain . Cognitive behavioral therapy has also been compared to hypnosis but has not been as effective . Other variants are used, such as music therapy or art therapy (like nature screens combined with nature sounds), to provide a distraction for the patient and to decrease the level of anxiety .
Strategy for pain reduction during bone marrow biopsy
So far, there is no formal recommendation on how to effectively reduce pain during the bone marrow biopsy. However, the data collected during different trials and the experience from different centers show that simple conclusions can be drawn. Firstly, the emphasis should be focused on patient information. The doctors should inform the patient about the procedure and provide necessary information on what will be done. Secondly, the first biopsy should preferably be performed by an experienced operator as this is the point where the greatest anxiety is felt, and pain during that first procedure was shown to be connected with pain in the following biopsies. When possible, we would recommend sending psychologically fragile patients undergoing their first BMBA to a physician in a center known to perform the least painful BMBA. Additionally, better pharmacological ways for patient anesthesia and sedation should be explored. The patients should be carefully anesthetized, and the local anesthetic, allowed time for proper infiltration of the puncture site. Insufficient local anesthesia is the most easily avoidable mistake during bone marrow biopsies. Short sedations can be offered to patients preferring pain relief, if the ward has the capacity of providing the possibility for further observation. For patients experiencing severe pain during the marrow suction, tramadol can be given before the procedure, as it was shown to significantly reduce this pain. The patient should be asked when the strongest pain was experienced during the previous procedure, as this provides the operator with information on possible pain-causing factors and allows in many cases the improvement in following biopsies. There is a little chance that formal recommendations for BMBAs will be made at any time soon, as there are very little data arising from trials in this field of medicine. We can just hope that slow progress in this field and implementation of the data already present will lead to less painful biopsies in the future.