To date, there are 12 studies published on the use of non-pharmacological prevention strategies in the non-ICU environment, with equal number of studies claiming benefits as those suggesting the intervention has limited or no effect in delirium prevention. The multicomponent protocol consisted of simple techniques applied by the hospital staff, including reorientation, appropriate cognitive stimulation three times a day, the implementation of a non-pharmacologic sleep protocol to help normalize patient’s sleep–wake cycle, early mobilization after surgery or extubation, timely removal of catheters and restraints, correction of sensory deficiencies (i.e., eyeglasses and hearing aids), and early correction of dehydration and electrolyte abnormalities. This has evolved into the Hospital Elder Life Program (HELP) (Inouye and Charpentier 1996, Inouye et al. 1999a, b; Inouye et al. 2000). This program involves the implementation of targeted interventions for known risk factors (i.e., cognitive impairment, sleep deprivation, immobility, dehydration, vision or hearing impairment) for cognitive decline in the elderly by an interdisciplinary team A number of studies have demonstrated the usefulness of the multicomponent approach in preventing delirium (Marcantonio et al. 2001; Tabet et al. 2005; Vidan et al. 2005; Caplan and Harper 2007; Lundstrom et al. 2007; Colombo et al. 2012).

Yet a number of studies have failed to demonstrate the benefits of the multicomponent protocol in delirium prevention (Schindler et al. 1989; Wanich et al. 1992; Milisen et al. 2001; Benedict et al. 2009; Bjorkelund et al. 2010; Gagnon et al. 2012). In fact, recent studies have found that the intervention had no effect on the overall delirium rate (p = 0.84), and made no significant difference on secondary measures (i.e., mean length of hospital stay (p = 0.74), falls (p = 0.43), or discharge to long-term care facilities (p = 0.20) (Holroyd-Leduc et al. 2010a, b). A meta-analysis of published studies found that although the multicomponent interventions appeared to be effective in reducing the incidence of delirium among postoperative patients, it made no difference in a number of important secondary measures, including discharge location or post-discharge dependency, length of hospital stay (p = 0.12), or mortality rate (p = 0.77) between intervention and control groups (Holroyd-Leduc et al. 2010a, b). Of note, a recent study found that the administration of the multicomponent intervention by non-professional, family members lead to a significant reduction in the occurrence of delirium (p = 0.027) (Martinez et al. 2012), suggesting the negative studies mentioned above are a reflection of the mode of administration, rather the approach itself. Of interest, a recent study demonstrated that a relatively simple intervention consisting of daily reorientation, supplemented with environmental, acoustic and visual stimulation significantly lowered the occurrence of delirium (Colombo et al. 2012).

To date, there is only one non-pharmacological intervention that has proven effective in preventing delirium in the intensive care units (ICU). Researchers have found that a combination of early physical and occupational therapy during periods of daily interruption of sedation was accompanied with a significantly greater return to independent functional status (p = 0.02), shorter duration of delirium (p = 0.02), and more ventilator-free days (p = 0.05) (Schweickert et al. 2009). Others have confirmed that a combination of sedation reduction and early mobilization with physical rehabilitation leads to improved outcomes (i.e., lower total amount benzodiazepine use, higher level of functional mobility, and reduction in delirium rates) (Needham and Korupolu 2010).

Finally, some small recent studies have suggested that the use of bright light therapy (i.e., 3000–5000 lux at a distance of 100 cm between light source and patient’s eyes) may be useful in both, prevention (Yang et al. 2012; Chong et al. 2013) and treatment of delirium (Taguchi et al. 2007; Ono et al. 2011). In fact these studies suggest the use of bright light was also associated with an increased mean sleep time (7.7 from 6.4 h; P < 0.05).

In addition, there are a number of steps the primary team can take to effectively decrease the risk of delirium and/or assist in its recovery (Table 12.5). These include conducting an inventory of all pharmacological agents being administered to the patient and discontinuing or substituting potentially offending agents, if possible, especially those with high anticholinergic load. Early discontinuation of all immobilizing lines and devices (e.g., chest tubes, IV lines, bladder catheters), including physical restraints. Early titration of sedation and early mobilization (as described above) has proven to be a key factor in minimizing delirium and improving the odds of return to independent functioning upon discharge home.

Early correction of sensory deficits should be undertaken (e.g., replacement of eyeglasses and hearing aids) as soon as possible. Encouragement of healthy social interaction with family and friends should be made to decrease environmental isolation. Correct malnutrition, dehydration, and electrolyte abnormalities as quickly and safely as possible. Implement environmental manipulations (e.g., increase the amount of natural light during daytime hours, reduce noise levels and artificial lights at nighttime, decrease nighttime tests and procedures) to normalize the sleep–wake cycle and avoid the need of pharmacological sleep agents. In the case of intubated, sedated ICU patients, sedative and pain regimens should be titrated to manage the patients’ symptoms, while allowing for early extubation and mobilization.

The British National Institute for Health and Clinical Excellence (NICE) provided a set of guidelines for the prevention of delirium in elderly at-risk patients, mostly based on the correction of modifiable of factors and the implementation of the multicomponent intervention package (O’Mahony et al. 2011). The full version of these recommendations can be found at <http://​guidance.​nice.​org.​uk/​CG103/​Guidance/​pdf/​English>.

While pharmacological agents may assist in the management of agitated patients and in the correction of the neurotransmitter derangements associated with delirium symptoms (Table 12.2), it is important to note that to date no pharmacological agent has received FDA approval for the prevention or treatment of delirium. Also, a systematic review of prospective delirium trials, including prospective randomized and nonrandomized double-blind, single-blind, and open-label clinical trials of any pharmacological agent for the prevention or treatment of delirium demonstrated that pharmacological strategies (e.g., haloperidol, second-generation antipsychotics, gabapentin, melatonin, single dose of ketamine during anesthetic induction, and dexmedetomidine-based sedation compared with other sedation strategies for mechanically ventilated patients) showed greater success in preventing delirium than in treating it (Friedman et al. 2013).

We base the use of pharmacological agents on the premise that the phenomenon of delirium is caused by an underlying metabolic derangement leading to alterations in the neurotransmitter function and the available evidence-based literature. Thus, this section, we address possible pharmacological interventions, based on the neurotransmitter being targeted.