“Painless” Bone Marrow Aspiration by Slow Suctioning Does Not Affect Peripheral Blood Contamination of the Specimen: Randomized Prospective Crossover Trials

Abstract The pain during bone marrow aspiration (BMA) can be best explained by negative pressure inside the bone marrow cavity. Although most standard textbooks recommend rapid suctioning with high negative pressure to minimize peripheral blood contamination, this technique might be associated with more pain. To date, there is no evidence that rapid suctioning can reduce peripheral blood contamination. To find a technique that reduces pain without loss of specimen quality, we conducted two trials. The first was a randomized, crossover trial comparing slow aspiration with low negative pressure (L method) and rapid aspiration with high negative pressure (H method). To evaluate pain during the procedure, 49 patients with hematological malignancy who required BMA more than once were randomly assigned to receive either the first aspiration by the L method and the second by the H method or vice versa. Under local anesthesia, a 16-gauge BMA needle was inserted into the BM cavity. A 1-mL syringe (L method) or a 30-mL syringe (H method) was used to aspirate 0.5 mL of BM fluid. To ensure accuracy of aspiration volume in the H method, an extension tube was connected between the 30-mL syringe and needle, and clamped by forceps when the aspirated volume reached 0.5 mL. Pain during each procedure was evaluated using a visual analog scale (VAS), verbal descriptor scale (VDS), and McGill pain questionnaire (MPQ). In the first trial, repeated measures one-way analysis of variance design was used for serial measurement of pain, and the one-tailed Wilcoxon’s test was used to compare pain between the two groups. The second trial compared aspirate quality between the L and H methods. Sixteen allogeneic transplantation donors (median age, 33.5 years; range, 22 to 62 years), underwent the first puncture of the harvest procedure under general anesthesia. BMA was drawn simultaneously from the right and left posterior iliac crest with a 1-mL and a 30-mL syringe; the aspiration side and syringe size were randomized. Nucleated cell counts (NCC) of the BM specimens were determined by automated hematology analyses. The non-inferiority margin was defined as less than 25% on the basis of the absolute difference of NCC between the L and H methods. In the first trial, 34 of the 49 patients (67%; 21 men and 13 women; median age, 49 years; age range, 17 to 77 years) completed the study and provided VAS, VDS and MPQ score data after two consecutive BMA. Present pain intensity (PPI) score of the MPQ was significantly decreased with L method when compared with H method (median absolute difference 0, P=0.037) (Table 1). VAS score and total pain rating index (PRI) of the MPQ were also lower with the L method (median absolute differences −0.6 and −0.5), although these results did not reach statistical significance. There was no significant ordinal interaction in repeated measurement of any scores except the affective-PRI of the MPQ, which was significantly higher at the first aspiration, regardless of the negative pressure intensity (P=0.024). In the second trial, the geometric mean of NCC with the L method was non-inferior to the mean with the H method (P=0.025) (Table 2). These findings indicated that BMA with low negative pressure tended to be less painful, while maintaining specimen quality. There remains difficulty in evaluating the impact of psychological factors on the results. Nonetheless, on the basis of our results we recommend suctioning slowly with low negative pressure using a small syringe in order to reduce pain during BMA. Table 1 L method H method P-value median (range) median (range) VDS 1 (0 to 3) 1 (0 to 3) 0.212 VAS 2.2 (0 to 8.4) 3.2 (0 to 9.0) 0.055 MPQ PRI-S 3 (0 to 16) 4 (0 to 30) 0.080 PRI-A 0 (0 to 7) 0 (0 to 9) 0.192 PRI-E 0 (0 to 4) 0 (0 to 4) 0.414 F’RI-M 2 (0 to 11) 3 (0 to 11) 0.093 PRI-T 6 (0 to 32) 7.5 (0 to 53) 0.063 PPI 1 (0 to 4) 1 (0 to 5) 0.037 Table 2 L method H method P-value Genomic mean of NCC (×104/μL) (95%IC) 6.6 (4.6–9.5) 7.8 (5.9– 10.4) 0.025

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