Combined Oral Fentanyl Citrate and Midazolam as Premedication for Bone Marrow Aspiration and Biopsy in Patients with Hematological Malignancies: A Randomized, Controlled and Patient-Blinded Clinical Trial

Claudio Cerchione,Cristiano Minucci,Maria Benedetta Giannini,Aniello Casoria,Mattia Altini,Ilaria Santoriello,Sonia Ronconi,Giorgia Simonetti,Marco Picardi,Davide Nappi,Vincenzo Martinelli,Ugo De Giorgi,Giovanni Martinelli,Angela Gravetti,Andrea Ghelli Luserna Di Rorà,Fabrizio Pane,Sara Bravaccini,Delia Cangini,Novella Pugliese

doi:10.3390/jcm9020395

Abstract

Bone marrow aspiration and biopsy (BMAB) is a painful procedure, and the routinely used local infiltration anesthesia (LIA) with lidocaine is unable to provide pain relief during the most uncomfortable phases. The primary endpoint of the present randomized, patient-blinded trial was to evaluate the efficacy of an opioid and benzodiazepine combination plus LIA (sedoanalgesia) in patients undergoing BMAB for hematological malignancies. The secondary endpoint was the safety of the procedure in an outpatient setting. Ancillary assessments were anticipatory anxiety related to pain recall in the event of re-biopsy, and adequacy of bone tissue harvested. Patients were randomly assigned to one of 2 arms to receive either sedoanalgesic placebo plus LIA (standard group) or oral fentanyl citrate 200 μg plus oral midazolam 5 mg plus LIA (combo group) during BMAB. Pre-procedural anxiety and procedural pain were assessed according to the Numerical Rating Scale (NRS: 0–10), dividing the time of the procedure into five intervals (T0, T1, T2a, T2b and T3) and evaluating the degree of discomfort at each time (T) in both groups. One hundred and sixteen patients were eligible for the study. At T2b (time of biopsy) and T3 (time after biopsy), a significantly lower perception of pain was registered in the combo group. Moreover, there were no significant sedoanalgesia-related side-effects. Finally, histological specimens were higher in quality in the combo group. Sedoanalgesia was highly effective in reducing pain during biopsy, diminished anticipatory anxiety in patients undergoing re-biopsy and led to fewer non-diagnostic specimens being harvested.

Highlights

Bone marrow aspiration and biopsy (BMAB) is a medical procedure commonly used for the diagnosis and follow-up of several hematological and non-hematological diseases [1,2]
Experience in performing a BMAB is associated with a lower level of pain because a skilled physician can notably reduce the length of the procedure and minimize the need for a repeat biopsy [19]
Anticipatory fear of a painful procedure such as BMAB can substantially increase the perception of pain and play a key role in the discomfort felt by the patient, creating a general state of anxiety that can negatively affect quality of life

Summary

Introduction

Bone marrow aspiration and biopsy (BMAB) is a medical procedure commonly used for the diagnosis and follow-up of several hematological and non-hematological diseases [1,2]. BMAB consists in bone marrow aspiration and bone trephine biopsy, usually performed on the posterior iliac crest to reduce patient discomfort. The pain associated with BMAB is the main issue for patients undergoing this procedure, making its relief an important objective for physicians. Analgesia for BMAB is commonly provided by local infiltration anesthesia (LIA) alone [2]. Given the difficulty in achieving sufficient anesthesia in bone and bone marrow, BMAB is often a painful, uncomfortable and anxiogenic experience for patients. A prospective study by Degen et al reported that patients who had previously experienced a painful BMAB often referred to it as ‘unbearable’ pain [4]

Methods

Results

Discussion

Conclusion