Example of delirium check-list
High-Alert Medications and Suspected Delirium
Background information and research related to these tables:
• A wide range of medications and medication issues may contribute to delirium
o Inappropriate dosing
▪ Too high- for example: digoxin toxicity
▪ Too low- for example: uncontrolled pain may lead to delirium
o Drug-drug interactions
o Drug-disease interactions[i]
▪ Studies demonstrate increase risk in cancer patients on opioids
▪ Studies demonstrate delirium risk is decreased in post-surgical patients when pain is control
o Inappropriate drug selection
▪ Increased drug sensitivities in the elderly
• Potential pathophysiology of delirium based on specific neurotransmitters[ii]:
▪ Excess of dopamine
▪ Depletion of acetylcholine
▪ GABA, serotonin, endorphins and glutamate also play a role
• Many medications maybe suspect, but few are consistently associated with the development of delirium.[iii]
o According to one critical review, psychoactive medications appear to be involved in delirium cases in 15-75% of cases
o Drugs were considered a definite cause of delirium in only 2-14% of cases
o Those cited in the critical review include:
▪ Opioids
▪ Corticosteroids
▪ Benzodiazepines
o Other medications mentioned but not consistently cited include:
▪ Anticholinergics
▪ NSAIDs
▪ Chemotherapeutic agents
o There are not many well designed studies examining drug-induced delirium
▪ The studies have conflicting results
▪ The studies vary in regards to design and analysis
▪ Benzodiazepines and antipsychotics noted significant results in a study
▪ Anticholinergics, anticonvulsants, antidepressants, antiemetics, antiparkinsonians, corticosteroids, H-2 antagonists, and NSAIDs were not significantly associated with delirium in any study noted in the critical review
▪ These studies lack defined controls and numerous variables; therefore, results may not reliably be compared to infer significant findings.
o Critical review conclusions: the currently available epidemiologic evidence of an association of psychoactive medications and delirium is rather weak.
High risk medications specific to the elderly (The Beers Criteria):
• Why the Beers Criteria is important[iv]
o The Beers criteria are based on expert consensus developed through extensive literature reviews identifying medications that may potentially inappropriate in older adults
o Centers for Medicare and Medicaid (CMS) adopted the Beers Criteria in July 1999 for nursing home regulation.
o Studies examining the use of medications found on the list indicate increased provider/facility costs and increased inpatient, outpatient and emergency visits.
o The Beers Criteria was last update via an expert panel examining current literature and professional surveys in 2002
Information about this table- Medications Implicated in Drug-Induced Delirium i
• This in not an all encompassing list; these are medications consistently mentioned in delirium literature
• Just because a patient may be on one or more of these meds, it does not mean it is the absolute cause of delirium
• Medication sensitivity and effect vary greatly from patient to patient, and delirium cases should encompass the patient’s entire medical picture (disease condition, environment, medications, etc.)
Table A- Medications Implicated in Drug-Induced Delirium
|Medication Class |Medication |
|Benzodiazepines | |
| |Lorazepam |
| |Diazepam |
| |Clonazepam |
| |Alprazolam |
| |Triazolam |
| |Clorazepate |
| | |
|Opioids | |
| |Fentanyl * |
| |Meperidine * |
| |Morphine * |
|Corticosteroids | |
| |Prednisone |
| | |
|NSAIDs | |
| |Diclofenac |
| |Ibuprofen |
| |Sulindac |
| |Indomethacin |
| |Salicylic acid |
| |Ketoprofen |
| | |
|Antipsychotics | |
| |Clozapine * ( |
| |Fluphenazine |
| |Haloperidol |
| |Loxapine |
| |Olanzapine ( |
| |Perphenazine |
| |Quetiapine ( |
| |Risperidone |
| |Thioridazine ( |
| |Ziprasidone |
| | |
|Antiarrhythmics | |
| |Amiodarone |
| |Lidocaine |
| |Quinidine |
| |Tocainide |
| | |
|Antiasthmatics | |
| |Theophylline |
| | |
|Anticonvulsants | |
| |Phenytoin |
| |Acetazolamide |
| |Lamotrigine |
| |Pregabalin |
| |Valproic Acid* |
|Medication Class |Medication |
|Antidepressants | |
| |Amitriptyline ( |
| |Desipramine ( |
| |Doxepin ( |
| |Imipramine ( |
| |Protriptyline ( |
| |Mirtazapine ( |
| |Fluoxetine |
| |Paroxetine |
| |Sertraline |
| | |
|Dopaminergic Agents | |
| |Amantadine |
| |Levodpa |
| |Bromocriptine |
| | |
|Antihypertensives | |
| |Enalapril |
| |Captopril |
| |Lisinopril |
| |Reserpine |
| |Clonidine |
| |Methyldopa |
| |Nifedipine |
| |Verapamil |
| |Atenolol |
| |Metoprolol |
| |Propranolol |
| | |
|Anticholinergics | |
| |Atropine ( |
| |Benztropine ( |
| |Scopolamine ( |
| |Tolterodine ( |
| | |
|Antimicrobials | |
| |Tobramycin |
| |Bactrim |
| |Linezolid |
| | |
|Other Agents | |
| |Digoxin |
| |Alcohol withdrawl |
| |Lithium * |
|* Documented incidence from clinical trials |
|( Medications that have anticholinergic effects which can be |
|associated with cognitive impairment |
| |
The Beer’s Criteria and fairly commonly medications iv,[v]
|Drug |Concern |Severity Rating |
|Propoxyphene and combinations |Demonstrates analgesic effects similar to |Low |
| |acetaminophen with adverse effects of narcotics| |
|Indomethacin |Produces most CNS effects of the NSAID class |High |
|Pentazocine |Narcotic with several CNS effects: confusion |High |
| |and hallucinations | |
|Trimethobenzamide |Poor antiemetic effects; potential for EPS |High |
|Muscles relaxants and antispasmodics |Poorly tolerated in elderly; anticholinergic |High |
| |effects; increase fall risk | |
|Flurazepam |Extremely long half-life cause prolonged side |High |
| |effects of sedation and falls | |
|Amitriptyline |Potent anticholinergic; sedating |High |
|Doxepine |Potent anticholinergic; sedating | |
|Meprobamate |Highly addictive anxiolytic |High |
|Specific dosing of benzodiazepines |Doses ranging higher than those suggested |High |
|Lorazepam > 3 mg |demonstrate little benefit with increased side | |
|Oxazepam > 60 mg |effects compared to smaller doses | |
|Alprazolam > 2 mg | | |
|Temazepam > 15 mg | | |
|Triazolam > 0.25 mg | | |
|Long-acting benzodiazepines |Long half-life produces prolonged sedation and |High |
|Chlordiazepoxide |increased risk for falls | |
|Diazepam | | |
|Quazepam | | |
|Halazepam | | |
|Chlorazepate | | |
|Disopyramide |Particular antiarrhythmic may induce heart |High |
| |failure in elderly; also anticholinergic | |
| |effects | |
|Digoxin |Closely monitor renal clearance and levels to |Low |
| |prevent toxicity | |
|Short-acting dipyridamole |Potential for orthostatic hypotenstion; |Low |
| |long-acting formulation only in those with | |
| |prosthetic heart valves | |
|Methyldopa |Bradycardia; may potentiate depression |High |
|Reserpine > 0.25 mg |May induce depression, impotence, sedation, |Low |
| |orthostatic hypotension | |
|Chlorpropamide |Long half-life may prolong hypoglycemia |High |
|GI antispasmodics |Increased anticholinergic effects; efficacy |High |
|Dicyclomine |uncertain | |
|Hyoscyamine | | |
|Belladonna alkaloids | | |
|Clidinium-chlordiazapoxide | | |
|Anticholinergics/Antihistamines |Potent anticholinergic |High |
|Chlorpheniarmine | | |
|Diphenhydramine | | |
|Hydroxyzine | | |
|Cyproheptadine | | |
|Promethazine | | |
|Diphenhydramine |Confusion and sedation; use lowest possible |High |
| |dose in allergic reactions | |
|Ferrous Sulfate > 325 mg/day |High doses not dramatically absorbed; |Low |
| |constipation greatly increased | |
|Barbiturates (except Phenobarbital) |Highly addictive; harmful side effects |High |
|Meperidine |Advantage over other analgesics questionable; |High |
| |increased side effects | |
|Ticlopide |No more efficacious than aspirin for clots; |High |
| |more side effects | |
|Ketorolac |Use (especially long-term) associated with GI |High |
| |side effects | |
|Amphetamines |Addictive; Induce hypertension, angina, and |High |
| |myocardial infarction | |
|Long-term use of NSAIDs |GI bleeds, renal failure, high blood pressure, |High |
| |heart failure | |
|Bisacodyl |Long-term use may exacerbate bowel dysfunction |High |
|Amiodarone |May prolong QT interval; questionable efficacy |High |
| |in elderly | |
|Fluoxetine (daily dosing) |Long half-life may prolong CNS stimulation, |High |
| |sleep disturbances, agitation | |
|Nitrofurantoin |Renal impairment |High |
|Doxazosin |Hypotention; anticholinergic effects |Low |
|Methyltestosterone |Prostatic hypertrophy; cardiac issues |High |
|Short acting nifedipine |Hypotension; constipation |High |
|Clonidine |Hypotension; CNS effects |Low |
|Mineral oil |Risk for aspiration and other side effects |High |
|Cimitidine |Increased CNS effects (confusion); drug |Low |
| |interactions | |
|Ethacrynic acid |Hypertension; fluid imbalances |Low |
|Estrogens only agents |Evidence of carcinogenic potential and lack of |Low |
| |cardio-protective effects in elderly women | |
|Notes: |
|Abbreviations: CNS- central nervous system; NSAIDs- nonsteroidal anti-inflammatory drugs; EPS- extrapyramidal symptoms |
|Anticholinergic effects- may effect several different systems; most notable effects include: ataxia, dry mouth and eyes, blurred vision, |
|constipation, tachycardia, light-headedness urinary retention, confusion, and agitation. |
| | | |
References:
-----------------------
[i] Borovick and Fuller. Drug-Induced Diseases: Prevention, Detection, and Management: 2nd ed. ASHP 2010; Chapter 15: Delirium.
[ii] Girard TD, et al. Crit Care 2008; 12(Suppl 3): S3
[iii] Gaudreau JD, et al. Psychosomatics 2005; 46(6): 302-316
[iv] Fick DM, et al. Arch Intern Med 2003; 163: 2716-2724
[v] PA-PSRS Patient Safety Advisory 2005; Vol 2(4)
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