Midazolam: Significant Pain Reduction in Patients Undergoing Bone Marrow Puncture - a Clinical Trial.

Purpose: Bone marrow puncture with biopsy and aspiration is an everyday routine technique in haematology. The investigation induces substantial pain and fear in many patients. To our knowledge, prospective studies in adults have not yet been published. The aim of our prospective four-arm single-center interventional study was to compare the effect of relaxation (music with facultative instruction on how to relax) with that of an analgetic drug (piritramide), an anxiolytic drug (midazolam) and placebo to reduce pain and anxiety on a double-blind basis.

Methods: 138 patients (60.9% male, 39.1% female, median age 59.5 years, range 21 – 81 years; 26.5% with benign disease, 73.5% with malignant disease) were assigned randomly to one of the four interventional arms taking into consideration the contraindications for piritramide and midazolam before iliac crest puncture. The dose of piritramide administered was 0.05 mg/kg body weight i.v. and that of midazolam 0.035 mg/kg body weight i.v. Local anaesthesia with 1% lidocaine at the puncture site envisaged was administered in each patient. The pain tolerance, pain intensity and fear intensity were measured using visual analogy scales (VAS) from 0 to 10 immediately after puncture (early evaluation) and after two weeks (late evaluation).

Results: 134 patients (97%) could be evaluated. 23% of the patients received relaxation exercise, 26% piritramide, 27% midazolam and 24% placebo. Midazolam was able to increase the pain tolerance and reduce the intensity of pain induced by puncture to a significant extent compared to the other three arms, but there was no difference in the intensity of fear. No differences were found between the early and late evaluation. Subgroup analysis did not show any differences in respect of gender distribution, indication for bone marrow puncture, incidence of complications (e.g. several attempted punctures or wish for a special alleviative treatment).

Conclusions: Midazolam was shown to reduce significantly the pain induced by bone marrow puncture. All subgroups benefited equally from midazolam administration. In accordance with the results of our study, we recommend that midazolam after appropriate information should be offered to every patient before carrying out the bone marrow puncture provided that midazolam is not contraindicated and that there is adequate monitoring of the patients after puncture.