Comparison of articaine and lidocaine for infiltration anaesthesia in patients undergoing bone marrow aspiration and biopsy

2.1. Local anaesthetics 

Patients were randomized to three different groups: lidocaine 20mg/ml (Lidocain®, Orion Pharma, Finland), articaine 20mg/ml (Ultracain®, Sanofi-Aventis comp., France) and articaine 40mg/ml. Adrenaline 5μg/ml was added to the local anaesthetic solutions before use. The physician performing the aspiration and / or biopsy was blinded to the solution used.

2.2. Local anaesthetic infiltration and punctures 

Before the procedure, the skin, the subcutaneous tissue and the periosteum of the bone were anaesthetized by infiltrating anaesthetic solution with a 21G needle using a third of the scheduled volume into each compartment. The volume of the solution was 6ml for bone marrow aspiration at the sternal manubrium, 8ml for aspiration of the sternal body and 10ml for aspiration and/or biopsy of the iliac crest. Two minutes after infiltration of the local anaesthetic drug, a 14–16G bone marrow aspiration needle was inserted into the marrow. If the patient was also scheduled for biopsy, this was always performed as the last step. The bone marrow biopsy was taken from the iliac crest, near the site of the preceding aspiration, using an 8G needle (Angiotech, T-lock™, Gainesville, FL, USA). If anaesthesia was not adequate for the insertion of the aspiration needle, half the initially used amount was administered for the second infiltration.

2.3. Tests for anxiety and pain 

Before the bone marrow procedure the anxiety level of the patient was evaluated on a verbal scale 0–4, where 0=no anxiety, 4=very anxious. Emotions such as nervousness, fear, tension and stress were not separated in the pre-procedural examination and, thus, they were covered under the “anxiety” score. The patients received sedative premedication (diazepam orally) by request.

During the procedure the effectiveness of anaesthesia was evaluated at predetermined times using the numeral rating scale (NRS) (0=no pain, 10=worst pain imaginable). The analgesic effect was evaluated during application of the local anaesthetic, during puncture, during bone marrow aspiration, during bone marrow biopsy and immediately after the procedure. Also the grade of subjective unpleasantness during puncture and aspiration was registered on the scale 0–4 (0=no feeling at all, 4=very unpleasant experience).

2.4. Post-intervention interviews 

Thirty minutes after the bone marrow aspiration and/or biopsy the patients were interviewed. The interviewer was blinded to the used local anaesthetic solution. The patients’ present general condition and the pain score were recorded. They were also asked if the pain during injection was stronger or milder than expected.

After 24h the patient was interviewed by telephone by a blinded member of the study group. Structured questions about general condition, haematomas or bleeding at the puncture site, the grade of pain and the need for medicines were asked. The patient was also asked to compare the painfulness of the procedure to that of the previous bone marrow samplings. The patient was once more contacted after 2 weeks and again the general condition, and grade and location of the possible pain were evaluated.

2.5. Statistics 

The demographic data was analyzed using ANOVA and non-parametric data with non-parametric tests including Kruskal–Wallis and Mann–Whitney U. Spearman Rank correlation was used with parametric data.

3.1. Anxiety 

Prior to the procedure, the patients expressed varying level of anxiety on the scale 0–4 (median 1.00, mean 1.28, SD 1.43, range 0–4) without difference between the groups. Sixty-eight patients (45.3%) were not anxious at all (score 0), while 16 patients (10.7%) were very anxious (score 4). Six patients received diazepam 5–10mg orally prior to the procedure. In comparison with those patients having had previous experience from the procedure, the level of anxiety was higher (P<0.01) in patients having their first BMAB.

3.2. Pain experience 

The median pain score on the NRS at the injection of the local anaesthetic was 3 (mean 3.5, range 0–10), the first-timers reporting higher scores than the others (P<0.05). In eight patients (four patients in the lidocaine 20mg/ml group and four patients in the articaine 20mg/ml group), a second local anaesthetic infiltration was made because of inadequate anaesthesia as tested by pricking with the bone marrow aspiration needle.

The median NRS pain score at the insertion of the aspiration needle was 2 (mean 2.1, range 0–8), and at aspiration 3.5 (mean 3.9, range 0–10). The bone marrow biopsy was performed to 48 patients and the median NRS score at these biopsies was 3.0 (mean 3.5, range 0–10). Thirty patients (20.0%) reported 4, or higher pain scores on the NRS during the puncture with the aspiration needle (Table 2), with no significant difference between the groups. A still larger proportion of the patients (49.3% and 47.9%, respectively) found the BMAB to be painful (NRS score⩾4).

Table 2. Number of patients with pain score ⩾4, or <4, on the Numeral Rating Scale (NRS, 0=no pain, 10=worst imaginable pain) at different steps of bone marrow aspiration or biopsy. There were no statistically significant differences between the groups.

		Lidocaine 20mg/ml (N=51)		Articaine 20mg/ml (N=50)		Articaine 40mg/ml (N=49)		Tot. (150 patients)
		NRS<4	NRS⩾4	NRS<4	NRS⩾4	NRS<4	NRS⩾4	NRS<4	NRS⩾4
	Puncture, no. of patients	39 (76.5%)	12 (23.5%)	38 (76.0%)	12 (24.0%)	43 (87.8%)	6 (12.2%)	120 (80.0%)	30 (20.0%)
	Aspiration, no. of patients	22 (43.1%)	29 (56.9%)	28 (56.0%)	22 (44.0%)	26 (53.1%)	23 (46.9%)	76 (50, 7%)	74 (49, 3%)
	Biopsy, no. of patients	6 (50.0%)	6 (50.0%)	9 (45.0%)	11 (55.0%)	10 (62.5%)	6 (37.5%)	25 (52.1%)	23 (47.9%)

In the articaine 40mg/ml group there was a smaller proportion of patients who experienced a considerable degree of pain (NRS score⩾4) at the puncture with the aspiration needle and at the biopsy in comparison with the other two groups (Table 2), but this, as well the pain experiences associated with the other procedural steps in the three local anaesthetic groups were not statistically significantly different.

3.3. Post-intervention interviews 

In the 24-h telephone interview, 12 patients (8.0%) reported that there was a small haematoma at the puncture site and two patients reported the occurrence of a small haemorrhage at the puncture site. Median NRS of all patients at this time was 0.0 (mean 0.65, range 0–7). After the bone marrow examination 42 patients started to feel pain at the puncture site in 6.2h, on average, with a median NRS score of 2.0 (mean 2.9, range 1–7). Fifteen of these patients needed pain-medication within 24h from the procedure, mostly oral paracetamol or ibuprofen. Seventy-three patients (48.7%) reported that the injection of the anaesthetic solution had been less painful than expected. Ninety-five patients (63.3%) told that the procedure had been less painful and after-pain experience had been less uncomfortable in 62 patients (41.3%) than expected. Sixteen patients (10.6%) thought that the procedure was more painful and 15 patients (10.0%) experienced more pain afterwards than they had expected. There were no significant differences between the local anaesthetic groups, but both the pain during the aspiration procedure (P<0.05) and the post-procedural recollection of pain (P<0.01) correlated significantly with pre-procedural anxiety. After 2 weeks, 143 patients (95.3%) reported good general condition, median NRS was 0.0 (mean 0.15, range 0–7.5) and 139 patients (92.6%) scored 0.

4.1. Limitations 

BMABs performed by senior haematologists are usually less painful than those performed by trainees (Vanhelleputte et al., 2003). Since only 40 of the bone marrow examination procedures in our study were performed by non-specialist haematologists (not randomized), no detailed subgroup analysis regarding a possible relationship between the doctors’ procedural experience and patients’ pain and anxiety was made. The local anaesthetic infiltration and the latency until the start of the bone marrow puncture were standardized and timed using a stopwatch by a research assistant, which means that the experience (specialist vs. trainee) should not have any significant confounding impact at least on the quality of infiltration anaesthesia and on bone puncture-related pain results.

Rating the degree of anxiety on a verbal zero-to-four point scale was probably too simplified because we did not score separately all emotional and somatic signs and symptoms associated with anxiety, as recommended e.g., by Spielberger and Vagg (1984). However, despite this simplification we were probably successful in rating the general emotional state of the patients immediately before BMAB.