Haloperidol for the Treatment of Delirium in ICU Patients.

BACKGROUND: Haloperidol is frequently used to treat delirium in patients in the intensive care unit (ICU), but evidence of its effect is limited. METHODS: In this multicenter, blinded, placebo-controlled trial, we randomly assigned adult patients with delirium who had been admitted to the ICU for an acute condition to receive intravenous haloperidol (2.5 mg 3 times daily plus 2.5 mg as needed up to a total maximum daily dose of 20 mg) or placebo. Haloperidol or placebo was administered in the ICU for as long as delirium continued and as needed for recurrences. The primary outcome was the number of days alive and out of the hospital at 90 days after randomization. RESULTS: A total of 1000 patients underwent randomization; 510 were assigned to the haloperidol group and 490 to the placebo group. Among these patients, 987 (98.7%) were included in the final analyses (501 in the haloperidol group and 486 in the placebo group). Primary outcome data were available for 963 patients (97.6%). At 90 days, the mean number of days alive and out of the hospital was 35.8 (95% confidence interval [CI], 32.9 to 38.6) in the haloperidol group and 32.9 (95% CI, 29.9 to 35.8) in the placebo group, with an adjusted mean difference of 2.9 days (95% CI, -1.2 to 7.0) (P = 0.22). Mortality at 90 days was 36.3% in the haloperidol group and 43.3% in the placebo group (adjusted absolute difference, -6.9 percentage points [95% CI, -13.0 to -0.6]). Serious adverse reactions occurred in 11 patients in the haloperidol group and in 9 patients in the placebo group. CONCLUSIONS: Among patients in the ICU with delirium, treatment with haloperidol did not lead to a significantly greater number of days alive and out of the hospital at 90 days than placebo. (Funded by Innovation Fund Denmark and others; AID-ICU ClinicalTrials.gov number, NCT03392376; EudraCT number, 2017-003829-15.).

Nitrous oxide analgesia for bone marrow aspiration and biopsy - A randomized, controlled and patient blinded study.

Background and aims Bone marrow aspiration and/or biopsy (BMAB), performed under local anaesthesia in adults, is a common and often painful procedure. Anxiety is known to intensify pain during the procedure. Nitrous oxide (N2O), known for its sedative and analgesic benefit in various short medical procedures and labour pain, could be advantageous also for pain relief during bone marrow examination. N2O acts rapidly and is eliminated in a couple of minutes once the inhalation is stopped, and occasional side effects (e.g. dizziness and nausea) are mild. The aim of this study was to compare the analgesic effects of inhaled 50% mixture of nitrous oxide and oxygen to 50% oxygen during bone marrow examination. Methods In this randomized, controlled, patient and observer blinded study patients received either 50% mixture of nitrous oxide and oxygen or 50% mixture of oxygen in air during bone marrow examination, in addition to local analgesia. Both patient groups comprised 35 adult patients. Pre-procedural anxiety and procedural pain were rated on the Numeral Rating Scale (NRS 0‒10). Cognitive function was measured before and 30 min after the procedure. Possible side effects were recorded. A telephone interview was performed 24 h later. Results There were no statistically significant differences in pain scores of the procedural steps (median NRS ranging 3.0‒4.0) between the study groups. High pain scores of 8‒10 comprised 0% vs. 8.6% of the scores during infiltration, 2.9% vs. 5.7% during puncture, 11.4% vs. 14.3% during aspiration and 2.9% vs. 2.9% during biopsy in N2O and 50% O2 groups, respectively (NS). Pre-procedural anxiety (median NRS 3.5 in both groups), measured in the outpatient clinic just prior to procedure, correlated with pain intensity during bone marrow aspiration (P = 0.045). There were no significant differences between side effects. During the BMAB four patients (3 in N2O group, 1 in 50% O2 group) reported dizziness and one patient in the N2O group reported nausea. Gas inhalation did not affect the cognitive function of the participants. In both groups the majority (>80%) of the patients was satisfied with the inhalation technique. During the 24 h interview, most of the participants were pain free and they did not report any serious adverse effects. Conclusions In spite of similar moderate to strong procedural pain in both groups and no benefit of N2O, most patients were satisfied with the inhalational techniques. We assume that the bedside presence of an anaesthesiologist and the distraction caused by the inhalational arrangements introduced positive context-sensitive therapeutic effect independent of the gas used. Pre-procedural anxiety predicted pain associated with bone marrow aspiration. Implications Inhaled 50% nitrous oxide was not an effective analgesic during bone marrow examination in our unselected outpatient population. Further studies should concentrate on its use with patients predicted to be at increased risk of suffering intense pain during the procedure, such as very anxious patients or those who have a painful history of previous bone marrow examinations.

Warmed and buffered lidocaine for pain relief during bone marrow aspiration and biopsy. A randomized and controlled trial.

Background and purpose Local infiltration anaesthesia is frequently painful due to low pH of the used anaesthetics, such as lidocaine. Usually pH of the solution is near 4.0, which causes tissue irritation and excitation of the pain mediating nerve endings. Warming and buffering the local anaesthetic solution have been shown to reduce the patient's experience of pain and unpleasantness during infiltration. Buffering reduces the dissociation of the local anaesthetic molecule and may enhance the anaesthetic's entrance into nerve cells. In this randomized placebo-controlled trial warmed and buffered lidocaine with adrenaline was compared to room temperature unbuffered lidocaine with adrenaline infiltrated before bone marrow aspiration and/or biopsy (BMAB). The aim was to find out to what extent warming and buffering would diminish pain during infiltration and whether this would be reflected in less pain also during subsequent steps of the BMAB procedure. Methods One hundred patients scheduled to undergo BMAB were interviewed regarding subjective experiences from previous medical procedures, current chronic and temporary medications, and their present state of anxiety before the BMAB procedure. They received local anaesthetic infiltration of lidocaine prior to BMAB. The solution used was either warmed lidocaine 20 mg/ml with adrenaline buffered with sodium bicarbonate 75 mg/ml (warmed and buffered group, 50 patients, pH approximately 7.3, 32°C) or unbuffered lidocaine 20 mg/ml with adrenaline mixed with NaCl 0.9% solution (control group, 50 patients, pH approximately 3.7, room temperature). The lidocaine concentration was similar in both groups. The bone marrow sampling needle was inserted 2 min after local anaesthetic infiltration. The grade of preprocedural anxiety, and pain sensations during the BMAB, both rated on NRS (numeral rating scale, 0-10) were compared between the groups. Results In comparison with the use of an unbuffered solution at room temperature warmed and buffered lidocaine with adrenaline caused less pain during infiltration (median NRS 4.0 vs. 2.0, P < 0.002) but it did not make performing the other phases of BMAB any less painful. As expected, painful experiences from previous medical, other than BMAB, or dental procedures and anxiety were associated with local anaesthetic infiltration pain during BMAB. Patients' own pain or anxiolytic medication did not lessen pain during BMAB. Conclusions By warming and buffering the lidocaine solution containing adrenaline it is possible to make the pain during infiltration less intense. Unfortunately, such benefit was not detected during the following steps of BMAB, initiated 2 min later. Preprocedural anxiety made procedural pain more intense including that of the local anaesthetic infiltration. Implications Warming and buffering the local anaesthetic prior to its administration is an effective and simple way of diminishing pain during infiltration. This benefit seems to be underutilized in the BMAB procedure. However, warming and buffering are not sufficient enough to diminish pain during bone marrow sampling and thus additional pain alleviating methods should be used, particularly in patients showing preprocedural anxiety.

Anxiety and pain during bone marrow aspiration and biopsy.

Background Previously we found that pre-procedural nervousness and tension (translated into English as "anxiety"), assessed on a non-validated five-point scale, correlated with pain intensity of the various stages of bone marrow aspiration and biopsy (BMAB). The fewer the previous BMAB procedures the stronger the pain from a repeated procedure. The primary purpose of the present observational study is to evaluate the state of anxiety just before BMAB and to find out whether it affects the pain experiences during the various stages of the BMAB procedure. We also examined whether first-timers differ from patients with previous BMAB experience in the degree of anxiety and intensity of BMAB procedural pain. Methods A total of 166 adult outpatients undergoing the BMAB from the Helsinki University Hospital were enrolled, 48 of them being first-timers. The level of anxiety was measured with State-Trait Anxiety Inventory (STAI) and the pain experiences associated with the various stages of the procedure were evaluated on the NRS-scale (Numeral Rating Scale 0-10) and using the Finnish pain vocabulary. BMAB was planned to be performed under lidocaine infiltration anaesthesia but, on request, patients were allowed to receive premedication with diazepam orally or alfentanil i.m. If, in spite of supplemental local anaesthetic the patient still felt pain from the sampling needle tip, i.m. alfentanil was administered. Results There was a clear association between anxiety and pain during all stages of the procedure, except during biopsy. The NRS scores varied from 0 to 10 in all the various stages of BMAB. The first-timers did not differ from the more experienced patients with regard to pain experiences; only the pain felt during the local anaesthetic infiltration was milder (P = 0.007) in first-timers than in the others. Procedural pain in those who were given analgesic or sedative premedication was similar (P < 0.05) to that in the non-premedicated patients. The words characterizing the pain of the various stages belonged to a major extent (76-90%) to the sensory class of words. Conclusion Pre-procedural anxiety had a major impact on the pain ratings. The first-timers and patients with previous experience of BMAB had a similar degree of pre-procedural anxiety, as well as of the intensity of procedural pain, except that infiltration of local anaesthetic was less painful in the first-timers. Implications Identification of anxious (fearful) patients prior to BMAB, and premedicating them individually may improve satisfaction in both patient and caregiver.

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

Infiltration anaesthesia with articaine, a local anaesthetic able to penetrate bone, may relieve procedural pain better than lidocaine in bone marrow aspiration and biopsy. This randomised, double-blind study comprised 150 patients with suspected or known haematologic disease. Either articaine 20mg/ml (50 patients), articaine 40mg/ml (49 patients) or lidocaine 20mg/ml (51 patients), all with adrenaline 5mug/ml, was infiltrated in volume of 6ml (sternal manubrium), 8ml (sternal body) or 10ml (iliac crest) 2min before puncture. Numeral rating scale score (median, range) at injection of local anaesthetic was 3.0 (0-10), at bone puncture 2.0 (0-8), at aspiration 3.5 (0-10) and at biopsy (48 patients) 3.0 (0-10). Pre-procedural anxiety, rated on a verbal scale, correlated significantly with experienced pain (P<0.01). Very anxious patients had fewer previous bone marrow examinations (P<0.01) and they experienced more pain during aspiration (P<0.05). In the post-interview 42 patients reported appearance of pain (median 2.0, range 1-7) after 6.2h, on average, and 15 patients needed oral analgesics. No parameter differed significantly between the groups. In conclusion, the quality of infiltration anaesthesia for bone marrow punctures and aspiration with articaine and lidocaine was similarly poor. Several patients experienced strong pain which correlated with the degree of anxiety.