A pilot phase II randomized, cross-over, double-blinded, controlled efficacy study of octreotide versus hyoscine hydrobromide for control of noisy breathing at the end-of-life. Atropine, hyoscine butylbromide, or scopolamine are equally effective for the treatment of death rattle in terminal care. [Efficacy of glycopyrronium bromide and scopolamine hydrobromide in patients with death rattle: a randomized controlled study].
Noisy breathing at the end of life (noisy breathing ("NB") occurs in up to 90% of people. Interventions have not been systematically evaluated. There has been clinical observation coupled with a proposed mechanism of effect that supports a role for octreotide in management of NB. The aim of this phase II study was to assess ten completed participants for the feasibility of an adequately powered phase III study. This randomized, double-blind, crossover pilot trial recruited participants from an inpatient palliative unit. Participants while well and their proxies simultaneously provided written informed consent. If NB were encountered, people were randomized to 200 mcg octreotide or 400 mcg hyoscine hydrobromide subcutaneously. If subsequent treatment was needed, the other medication was administered. A five point categorical scale documented the nurses' assessment of secretions over six hours. Eighty participants were consented of whom 10 (3 females, 7 males; median age 79, all with advanced cancer) received medication, five in each arm. There was no difference in the median time to administration of the second medication (3 hours). Two participants in each arm had a 2 category reduction of intensity after the second medication. Although feasible to consent and study this population in a way that respects autonomy and dignity even in the terminal hours of life, this pilot study suggests reconsideration of the pharmacological interventions (choice of agents, dosing, timing of dosing and pharmacokinetic profiles), standardizing of non-pharmacological care; and ways to measure directly family distress before further randomized studies for this symptom. Death rattle is a frequent symptom (25%-50%) in the terminal stage of life, but there is neither standardized treatment nor prospective investigation performed on the effectiveness of anticholinergic drugs. The aim of the present study was to investigate the effectiveness of three different anticholinergic drugs in the treatment of death rattle in the terminal stage of life. Terminal patients who developed death rattle were randomly assigned 0.5mg atropine, 20mg hyoscine butylbromide, or 0.25mg scopolamine. Each treatment was initiated with a subcutaneous bolus, which was followed by continuous administration of the same drug. The intensity of death rattle and side effects were prospectively scored at different time points. Three hundred and thirty-three eligible patients were randomized to atropine, hyoscine butylbromide, or scopolamine after informed consent from the patient or the appointed representative. For the three drugs, death rattle decreased to a nondisturbing intensity or disappeared after one hour in 42%, 42%, and 37% of cases, respectively (P=0.72). Further, effectiveness improved over time without significant differences among the treatment groups (effectiveness at 24 hours was 76%, 60%, and 68%, respectively). In an analysis on the three groups together, treatment was more effective when started at a lower initial rattle intensity; median survival after start of therapy was 23.9 hours. These data suggest that there are no significant differences in effectiveness or survival time among atropine, hyoscine butylbromide, and scopolamine in the treatment of death rattle. Death rattle is an extremely distressing symptom for the dying patient and for his environment. The aim of this study was to assess the efficacy of glycopyrronium bromide as compared with scopolamine hydrobromide in alleviating death rattle in terminal cancer patients with cognitive impairment.
                In a randomized, controlled study design patients were allocated in two groups. Group A received scopolamine hydrobromide in a dose of 0.5 mg intravenously every 6 hours for a period of 12 hours, group B received glycopyrronium bromide 0.4 mg every 6 hours for a period of 12 hours. In addition, standardized sedatives were administered as required and the analgesic therapy continued either orally or, if necessary, subcutaneously or intravenously in equipotent doses. Every 2 hours death rattle was assessed and rated on a scale of 1 to 5 (1 = audible breathing noises, 5 = very severe rattling noises). In addition, restlessness and expressions of pain were assessed and rated on a scale of 1 to 3 (1 = mild, 2 = moderate, 3 = severe).
                13 patients were included in the study, 7 patients were allocated to group A and 6 patients to group B. There were no significant differences in demographic data, age, weight and diagnosis distribution between the two groups. Group B demonstrated a significant reduction of death rattle in the first 12 hours (p = 0.029) in comparison to group A. There were no significant differences concerning the side effects (restlessness, expressions of pain) in both groups.
                Glycopyrronium bromide given in a dose of 0,4 mg every six hours demonstrated a significant reduction of death rattle compared to scopolamine hydrobromide. Concerning side effects (restlessness, expressions of pain) there was no difference between both substances.
In our original Cochrane review, we concluded that there was no evidence to show that any intervention, be it pharmacological or non-pharmacological, was superior to placebo in the treatment of noisy breathing. This conclusion has not changed. We acknowledge that in the face of heightened emotions when death is imminent, it is difficult for staff not to intervene. It is therefore likely that the current therapeutic options will continue to be used. However, patients need to be closely monitored for lack of therapeutic benefit and adverse effects while relatives need time, explanation and reassurance to relieve their fears and concerns. There remains a need for well-designed multi-centre studies with objective outcome measures which demonstrates the efficacy of intervention against placebo for this condition.