Pharmacological risk reduction

Recommendations

All patients at risk of delirium should have a medication review conducted by an experienced healthcare professional.

Good Practice

Areas with patients at high risk of delirium, such as trauma orthopaedic wards, should have protocols for commonly required medication (eg analgesia and anti-emesis) that contain choices for first-line treatments which minimise the risk of causing delirium.

See the evidence base in section 5.2 SIGN 157 here 

Observational evidence suggests that exposure to certain medicines increases the odds of delirium developing and that medication review can decrease rates of delirium.^80-83

An approach to medication review and prescribing in people who are experiencing, or are at increased risk of, delirium, covers three broad areas.

• Any changes in medications, including over-the-counter and herbal medications. Commencement of new medications, changes in dosage of medication or abrupt withdrawal of medication could result in delirium ^84,85
• Changes in how the body handles and is affected by medication. The natural physiology of ageing can result in medication, which has been beneficial without side effects for years, now causing or contributing to delirium.  The same can also be said for acute derangements in physiology seen with illness ⁸⁴
• Delirium risk should be considered when assessing the risks and benefits of commencing a new medication.^81,84

Benzodiazepines markedly increase the odds of delirium developing in a variety of settings (OR 3.0 95% CI 1.3 to 6.8) and should not be used unless in specific circumstances such as management of alcohol withdrawal or acute seizure management.⁸¹

Opiates can also cause delirium but they remain a vital class of drug for treating pain.  It is important to remember that pain in itself can precipitate delirium. 

A systematic review cited an OR of delirium associated with treatment with opioids of 2.5 (95% CI 1.2 to 5.2).⁸¹ However, the main opioid in the review, which carries the highest risk, is pethidine (OR 2.7, 95% CI 1.3 to 5.5), which is anticholinergic and rarely used in the UK.  More commonly used opioids such as morphine (OR of delirium 1.2, 95% CI 0.6 to 2.4) and fentanyl (OR of delirium 1.5, 95% CI 0.6 to 4.2) were not significantly associated with delirium.⁸¹

The opioid with the lowest odds of causing delirium was oxycodone but this still had a confidence interval that crossed 1 (OR 0.7, 95% CI 0.3 to 1.6).⁸¹

When using opiate analgesia titrate to the minimal effective dose to achieve pain control and minimise side effects. 

If opiates are used laxatives should be prescribed to prevent constipation which can contribute to delirium.

Optimising the dose of analgesic and sedative drugs in a critical care setting is advocated.⁸⁶

Daily sedative interruption or nurse-protocolised sedation to facilitate spontaneous breathing trials and daily mobilisation have been associated with improved outcomes, although not directly delirium.⁸⁶

The NHSScotland polypharmacy guideline contains information on medication to avoid or reduce in older people, some of which is aimed at reducing falls by reducing medications that can cause delirium. Medications recommended to avoid, stop or reduce the dose if possible include:

• tricyclic antidepressants
• anticholinergic medications
• benzodiazepines
• antihistamines
• tramadol.

The guideline also contains practical information on how to safely reduce chronic medication with potential for withdrawal such as benzodiazepines_.⁸⁷

No antipsychotics are licensed for the prophylaxis of delirium. There is insufficient evidence of benefit to recommend the use of antipsychotic prophylaxis in patients at risk of developing delirium.

See the evidence base in section 5.2, SIGN 157 here 

There remains controversy over whether dexmedetomidine can reduce the incidence of delirium in both critically ill patients and those in the perioperative setting. 

Many of the trials which indicate a benefit have used other sedative agents, including benzodiazepines in the control group.  It remains unclear if dexmedetomidine reduces delirium or merely reduces the need for delirogenic drugs.  Since there are potential physiological concerns relating to the widespread adoption of dexmedetomidine for prophylaxis, in addition to cost implications, it cannot be recommended for the prevention of delirium. 

See the evidence base in section 5.3, SIGN 157here 

Ketamine

One systematic review included four RCTs which reported the incidence of postoperative delirium when comparing ketamine to placebo.  Overall, the incidence of postoperative delirium did not differ between the control and intervention groups. The quality of each RCT was low, so the review concluded that the effect of ketamine on postoperative delirium is unclear.  The largest RCT reported an increase in postoperative hallucinations and nightmares with ketamine use.¹⁰⁶

Melatonin 

Systematic reviews identified four RCTs on the use of melatonin to prevent delirium in medical and surgical settings.^63,107,108 Results were inconclusive. 

One small RCT in 88 patients found a melatonin receptor agonist reduced the incidence (24.4% v 46.5%) and duration (0.78 v 1.4 days) of delirium in critically ill patients.¹⁰⁹