Symptom Update Masterclass: Delirium Jason Boland Senior Clinical Lecturer and Honorary Consultant in Palliative Medicine Wolfson Centre for Palliative Care Research Hull York Medical School University Of Hull, UK Approach Assessment (Hx, Ex, Ix) o Diagnose delirium o Find the cause o Impact on patient/family/staff Explanation (patient/family) Treat the cause Non-Pharmacological Drugs Delirium What is it How common is it What causes it Diagnosis Management o Reverse cause o Non-drug o Drug Overview Overview o Drugs Drugs Delirium What is it How common is it What causes it Diagnosis Management Drug trials 2012 Cochrane review of drug therapy for delirium in terminally ill patients found a paucity of trials comparing different management options Agar et al, RCT JAMA Intern Med. 2017;177(1):34-42. Efficacy of Oral Risperidone, Haloperidol, or Placebo for Symptoms of Delirium Among Patients in Palliative Care Double-blind, parallel-arm, dose-titrated RCT 11 Australian inpatient hospice or hospital palliative care services Adults receiving palliative care, with: life-limiting illness delirium (DSM-IV, MDAS score >6) delirium symptoms score (sum of NuDESC: behavioural, communication, and perceptual) of 1 or more 1
Dose a priori outcomes Dosing based on prior controlled trials <65 years: 1mg first dose, then 0.5mg bd o Doses titrated by 0.25mg on day 1 and by 0.5 mg thereafter to a maximum dose of 4mg/d >65 years: half loading, initial, maximum doses o Alongside management of delirium precipitants and non-pharmacological strategies Primary: average of 2 delirium symptom scores on day 3 Secondary: daily MDAS score lowest delirium symptoms score midazolam use extrapyramidal symptoms, sedation Han CS, Kim YK. A double-blind trial of risperidone and haloperidol for the treatment of delirium. Psychosomatics. 2004;45(4):297-301. Results n=247: 82 risperidone; 81 haloperidol; 84 placebo No significant differences in baseline characteristics Delirium symptom scores higher in patients taking haloperidol or risperidone P < 0.001 vs. placebo P = 0.002 More extrapyramidal effects with risperidone and haloperidol vs placebo o None serious More sedation, especially with haloperidol Median survival o 26 days placebo o 17 days risperidone o 16 days haloperidol Haloperidol 73% more likely to die vs placebo (P = 0.003) Low doses used 2
Conclusion Less Midazolam used in placebo compared with risperidone and haloperidol (P = 0.007 0.02) For those who needed midazolam, no difference in the median dosage o median (IQR) dosage: 2.5 mg (2.5-5.0 mg) for placebo and risperidone 4 mg (2.5-5.0 mg) for haloperidol Individualized management of delirium precipitants and non-pharmacological strategies results in better control of delirium symptoms than with the addition of risperidone or haloperidol Other drug studies In cancer or palliative care: no placebo Other adequately powered RCTs: in ITU no differences in days without delirium meta-analysis of antipsychotics for the treatment or prevention of delirium in hospital and ITU: no effect in reducing the severity or duration of delirium Neufeld Kj et al. J Am Geriatr Soc. 2016;64(4):705-714. Page VJ, et al. Lancet Respir Med. 2013;1(7):515-523. Prophylactic haloperidol (2mg) did not affect 28 day survival in 1789 critically ill adults in ICU vs placebo No difference in all 15 secondary outcomes Antipsychotics? Some psychiatrists say role for (e.g. hallucinations, illusions), no matter the severity of the delirium, if not managed with nonpharmacological strategies Pharmacological Interventions Only use medication if: Non-pharmacological interventions not successful The patient is a danger to themselves or others Low dose Haloperidol, Risperidone or Olanzapine o Quetiapine in Parkinson s or Lewy Body Benzodiazepines o alcohol or benzodiazepine withdrawal o add on (esp: sleep wake disturbance, agitation) Meagher, Agar, Teodorczuk. 2017 http://www.ccsmh.ca/en/projects/deliriumguidelineadaptgroup.cfm 3
What to do??? Individualized management identify delirium and precipitants early treat underlying cause(s) non-pharmacological strategies family drugs SR in Palliative care inpatients 8 studies, 1079 participants, advanced cancer 8 different screening/assessment tools Prevalence: 13-42% at admission 26-62% during admission 59-88% near death With DSM4: Higher prevalence (42-88%) If daily screening: 33-45% 68-86% Hypoactive delirium Hosie 2013, Delirium prevalence, incidence, and implications for screening in specialist palliative care inpatient settings: a systematic review Assessment Clinical notes and patient review o Consciousness, somnolence, behavior, cooperativeness, concentration, mood lability, executive function, short term memory o Time course Collateral information o Staff, family/friends baseline function, personality, psych history Medication review o PRNs, recent meds discontinued or started o Substance dependence (?withdrawal - inc. alcohol) Recent medical illness and interventions Examination, investigations Trigger Questions identify delirium Acute change in 1. Behaviour 2. Function 3. Cognition 4. Sleep wake cycle Fluctuates Testing Serial 7 s spelling WORLD backwards months of the year backward counting down from 20 Mini mental status exam (MMSE) o not sensitive in identifying delirium o repeated can reveal fluctuant course Orientation/concentration Confusion Assessment Method Requirement for delirium = 1, 2 AND either 3 OR 4 1. Abrupt change? 2. Inattention, can t focus? 3. Disorganized thinking? Incoherent, rambling, illogical? 4. Altered level of consciousness? (Hyper-alert to stupor?) Sensitivity (94 to 100%), specificity (90 to 95%) AND 4
Memorial Delirium Assessment Scale 1. Reduced level of awareness 2. Disorientation 3. Short-term memory impairment 4. Impaired digit span 5. Reduced ability to maintain and shift attention 6. Disorganized thinking 7. Perceptual disturbance 8. Delusions 9. Decreased or increased psychomotor activity 10. Sleep-wake cycle disturbance What to reverse? Dehydration Electrolytes (Calcium, sodium) Lungs, liver, heart, kidney, brain (failure) Infection Rx (especially medications) Opioids, benzodiazepines, steroids, SSRIs Injury, illness, surgery Unfamiliar environment Metabolic / Substance abuse Şenel 2015, Delirium Frequency and Risk Factors Among Patients With Cancer in Palliative Care Unit. Non-Pharmacological Interventions Environmental interventions o Frequent orientation (clock, family pictures, windows) o family or friends visit frequently; introduce themselves o minimize staff switching If appropriate o Initiate toileting routines o Move/mobilize ASAP o Quiet room, soothing music Close observation (esp. hyperactive) o Unpredictable Ensure in Care Plan Inform family Treatment - Education o including that delirium fluctuates and can last for weeks Once the patient starts to improve explain to them o what delirium is o how common it is and the usual course It is very frightening for them and may fear they have a psychiatric illness Family Information verbal and written o What it is o Causes o Presentation o Management o Communication o Care o Support https://www.bruyere.org/en/delirium Summary Sudden change in mental status, decreased attention, fluctuating Common Assess aetiology and reverse o dehydration, infection, metabolic, drugs intoxication/withdrawal - combination Non-Pharmacological Interventions Drugs o Need further drug trials 5
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