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Midazolam in conjunction with local anaesthesia is superior to Entonox in providing pain relief during bone marrow aspirate and trephine biopsy
  1. G Chakupurakal,
  2. J Delgado,
  3. E Nikolousis,
  4. S Pitchapillai,
  5. D Allotey,
  6. K Holder,
  7. L Bratby,
  8. J de la Rue,
  9. D W Milligan
  1. Department of Haematology, Heart of England Hospital, Birmingham, UK
  1. Dr D W Milligan, Department of Haematology, Birmingham Heartlands Hospital, Birmingham B9 5SS, UK; d.w.milligan{at}


Aim: To compare intravenous titrated midazolam 5–10 mg and inhaled Entonox in addition to local anaesthesia in order to identify which agent provides optimum pain relief.

Methods: Randomised, controlled trial. 49 patients were recruited, of which 46 were evaluable. 24 and 22 patients were recruited into the Entonox and midazolam arms, respectively. Patient experiences as well as staff observations were recorded with questionnaires after recovery from the procedure and 24 hours later.

Results: 45% and 59% of the patients in the midazolam arm could recollect the procedure after 15 minutes and 24 hours, respectively, compared to 96% and 88% who received Entonox. Midazolam provided a more comfortable experience (p<0.01) and improved pain relief (p = 0.01) compared to Entonox immediately after the procedure; this further improved when recalled 24 hours later. Nausea, dizziness and hallucinations were observed with both treatments, but dizziness was significantly more frequent with Entonox (p = 0.048). Clinically relevant respiratory depression (O2 saturation <90%) occurred in 19% of patients in the midazolam arm; sedation was reversed with flumazenil.

Conclusion: Midazolam in conjunction with local anaesthesia provides rapid and reversible sedation as well as effective pain relief during bone marrow biopsy, and is superior to Entonox; however, care must be taken to monitor respiratory function.

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  • Competing interests: None.

  • Ethics approval: The Northern Ireland Multi Ethics Research Committee and MHRA (Medicine and Health products Regulatory Agency) approved the trial protocol.