**3. Prevention**

#### **3.1 Pre-operative prevention**

Surgery can result in accelerated cognitive and functional decline, and this cognitive impairment after surgery has been associated with increased mortality and disability with deficits in activities of daily living occurring in up to 50% of patients even 12 months after major surgery [29–34]. Patients with a higher physical and cognitive reserve have a protective effect on reducing the risk of developing delirium [35, 36]. Therapeutic approaches for improving cognitive reserve may present opportunities for reducing cognitive impairment after acute stressors, particularly in situations with time available for prehabilitation. An area that is understudied in the transplant population is whether building patients' mental and physical reserve through a prescribed program of cognitive and physical exercise, as well as nutritional optimization can improve long term outcomes. Prehabilitation efforts before surgery thus far have focused on preemptive physical therapy to improve post-surgical functional outcomes. Multiple studies have demonstrated that physical training prior to surgery to build physical reserve can improve functional outcomes after major surgery [37–39]. No work, however, has been done to attenuate the cognitive decline by "exercising the brain" before the physiologic insult that is commonly seen in chronic disease and surgical intervention such as transplantation.

By targeting high-risk individuals, such as those who are frail, encephalopathic, uremic, have a history of alcohol abuse, are of advanced age, and have higher Model for End Stage Liver Disease scores, cognitive reserve could be improved. There are interventions focused on cognitive remediation/rehabilitation that are being studied, which potentially hold promise for improving long-term brain functioning in transplant recipients. Among them, Cognitive Retraining is a novel therapeutic approach. Conceptually, Cognitive Retraining applies well-understood techniques derived from brain plasticity research [40]. The learning theory facilitates improvement in information processing, attention control, aspects of memory, and executive functioning. Research has been performed evaluating the effectiveness of computer-based cognitive remediation on various aspects of neuropsychological functioning including memory, attention, processing speed, and others [41–43]. Based on prior experience with a wide variety of patient populations, there is a high likelihood of fostering improvement in patient outcomes in transplant recipients if applied to high risk individuals at risk for cognitive impairment and delirium during their postoperative recovery.

#### **3.2 Intra-operative management**

It is extremely important for anesthesia providers to practice delirium preventive strategies. There are operative factors that need to be considered that are associated

**135**

prevention.

delirium.

prevention.

**3.3 Post-operative prevention**

*3.3.1 Pharmacologic prophylaxis*

*Delirium Management, Treatment and Prevention Solid Organ Transplantation*

with increased delirium, which include the use of anticholinergic medications, electrolyte disturbances (specifically sodium fluctuations), and the amount of red blood cell transfusions. Efforts to decrease the prevalence of postoperative delirium should focus on limiting patient exposure to deliriogenic medications intra-operatively. The choice of anesthetic does not increase the risk of delirium as there is no conclusive evidence that propofol versus an inhaled based anesthetic changes the incidence of post-operative delirium [44, 45]. However, the level/depth of sedation provided during the operation is associated with delirium development, and therefore instruments such as intra-operative electroencephalography or brain activity monitors have been suggested to mitigate excessive levels of anesthesia helping with delirium prevention post-operatively. [46]. Close attention to electrolyte concentrations and fluctuations intraoperatively is also important. This is especially critical in patients with chronic hyponatremia, and in operations that involve large volume crystalloid resuscitation or excessive blood loss with associated blood product administration. Detailed pre-operative planning to minimize large fluctuations and optimize electrolyte disturbances should be performed with the surgical and anesthesia teams in high-risk individuals. Intra-operative management is an important part of the continuum of care for the transplant patient in delirium

Studies evaluating whether pharmacologic prophylaxis reduced the incidence of delirium have shown mixed results. A large double blind, placebo controlled trial studied prophylactic dexmedetomidine infusion upon arrival to the intensive care unit. The intervention group demonstrated a significant reduction in the incidence of delirium in non-cardiac post-operative elderly patients compared to the control group [47]. Treatment with dexmedetomidine in elderly patients admitted to the intensive care unit after non-cardiac surgery reduced the incidence of delirium from 23 to 9%. Dexmedetomidine also reduced the amount of sedative drugs including narcotics administered. The authors suggested that the delirium reduction seen in the trial could be contributed to a possible neuroprotective effect of dexmedetomidine and/or a reduction in sedation medications. Wide spread clinical use of dexmedetomidine is limited by the fact that it must be used in in an intensive care setting being administered intravenously, as well as the possible cardiopulmonary side effect profile causing respiratory depression, hypotension and bradycardia. However, these results are encouraging for the use of dexmedetomidine in the prophylactic setting in patients at high risk for

There are no data on the use dexmedetomidine use in patients admitted to the intensive care unit following abdominal transplant, but this approach could be applicable to liver transplant patients who remain intubated at the time of intensive care unit admission to be used as sedation instead of fentanyl or propofol. Further work will need to be done to delineate a clinical benefit for routine use of dexme-

A recent randomized controlled trial-The Haloperidol Effectiveness in ICU Delirium (HOPE-ICU) study-showed no difference in days alive and free of delirium between patients prophylactically treated with intravenous haloperidol (2.5 mg every 8 hours) or placebo [48]. At this time, the data are not conclusive to make a formal recommendation for routine pharmacologic prophylaxis for delirium

detomidine in postoperative transplant patients.

*DOI: http://dx.doi.org/10.5772/intechopen.86297*

*Delirium Management, Treatment and Prevention Solid Organ Transplantation DOI: http://dx.doi.org/10.5772/intechopen.86297*

with increased delirium, which include the use of anticholinergic medications, electrolyte disturbances (specifically sodium fluctuations), and the amount of red blood cell transfusions. Efforts to decrease the prevalence of postoperative delirium should focus on limiting patient exposure to deliriogenic medications intra-operatively. The choice of anesthetic does not increase the risk of delirium as there is no conclusive evidence that propofol versus an inhaled based anesthetic changes the incidence of post-operative delirium [44, 45]. However, the level/depth of sedation provided during the operation is associated with delirium development, and therefore instruments such as intra-operative electroencephalography or brain activity monitors have been suggested to mitigate excessive levels of anesthesia helping with delirium prevention post-operatively. [46]. Close attention to electrolyte concentrations and fluctuations intraoperatively is also important. This is especially critical in patients with chronic hyponatremia, and in operations that involve large volume crystalloid resuscitation or excessive blood loss with associated blood product administration. Detailed pre-operative planning to minimize large fluctuations and optimize electrolyte disturbances should be performed with the surgical and anesthesia teams in high-risk individuals. Intra-operative management is an important part of the continuum of care for the transplant patient in delirium prevention.

#### **3.3 Post-operative prevention**

*Perioperative Care for Organ Transplant Recipient*

activity or postictal metal status changes.

**3. Prevention**

**3.1 Pre-operative prevention**

contrasted cerebral, cross sectional imaging should be obtained. In addition, an electroencephalography should be performed if there is clinical concern for seizure

Mental status changes in the transplant recipient can be caused by multiple contributing factors, and a systematic and thoughtful work up is paramount for rapid initiation of treatment. However, the work up for delirium is often negative for any treatable, underlying medical condition. Once all potential medical conditions that can contribute to delirium are evaluated and eliminated as the diagnosis, the focus should shift to optimizing the environment for delirium resolution and cognitive recovery.

Surgery can result in accelerated cognitive and functional decline, and this cognitive impairment after surgery has been associated with increased mortality and disability with deficits in activities of daily living occurring in up to 50% of patients even 12 months after major surgery [29–34]. Patients with a higher physical and cognitive reserve have a protective effect on reducing the risk of developing delirium [35, 36]. Therapeutic approaches for improving cognitive reserve may present opportunities for reducing cognitive impairment after acute stressors, particularly in situations with time available for prehabilitation. An area that is understudied in the transplant population is whether building patients' mental and physical reserve through a prescribed program of cognitive and physical exercise, as well as nutritional optimization can improve long term outcomes. Prehabilitation efforts before surgery thus far have focused on preemptive physical therapy to improve post-surgical functional outcomes. Multiple studies have demonstrated that physical training prior to surgery to build physical reserve can improve functional outcomes after major surgery [37–39]. No work, however, has been done to attenuate the cognitive decline by "exercising the brain" before the physiologic insult that is commonly seen

By targeting high-risk individuals, such as those who are frail, encephalopathic, uremic, have a history of alcohol abuse, are of advanced age, and have higher Model for End Stage Liver Disease scores, cognitive reserve could be improved. There are interventions focused on cognitive remediation/rehabilitation that are being studied, which potentially hold promise for improving long-term brain functioning in transplant recipients. Among them, Cognitive Retraining is a novel therapeutic approach. Conceptually, Cognitive Retraining applies well-understood techniques derived from brain plasticity research [40]. The learning theory facilitates improvement in information processing, attention control, aspects of memory, and executive functioning. Research has been performed evaluating the effectiveness of computer-based cognitive remediation on various aspects of neuropsychological functioning including memory, attention, processing speed, and others [41–43]. Based on prior experience with a wide variety of patient populations, there is a high likelihood of fostering improvement in patient outcomes in transplant recipients if applied to high risk individuals at risk for cognitive impairment and delirium during

It is extremely important for anesthesia providers to practice delirium preventive strategies. There are operative factors that need to be considered that are associated

in chronic disease and surgical intervention such as transplantation.

**134**

their postoperative recovery.

**3.2 Intra-operative management**

#### *3.3.1 Pharmacologic prophylaxis*

Studies evaluating whether pharmacologic prophylaxis reduced the incidence of delirium have shown mixed results. A large double blind, placebo controlled trial studied prophylactic dexmedetomidine infusion upon arrival to the intensive care unit. The intervention group demonstrated a significant reduction in the incidence of delirium in non-cardiac post-operative elderly patients compared to the control group [47]. Treatment with dexmedetomidine in elderly patients admitted to the intensive care unit after non-cardiac surgery reduced the incidence of delirium from 23 to 9%. Dexmedetomidine also reduced the amount of sedative drugs including narcotics administered. The authors suggested that the delirium reduction seen in the trial could be contributed to a possible neuroprotective effect of dexmedetomidine and/or a reduction in sedation medications. Wide spread clinical use of dexmedetomidine is limited by the fact that it must be used in in an intensive care setting being administered intravenously, as well as the possible cardiopulmonary side effect profile causing respiratory depression, hypotension and bradycardia. However, these results are encouraging for the use of dexmedetomidine in the prophylactic setting in patients at high risk for delirium.

There are no data on the use dexmedetomidine use in patients admitted to the intensive care unit following abdominal transplant, but this approach could be applicable to liver transplant patients who remain intubated at the time of intensive care unit admission to be used as sedation instead of fentanyl or propofol. Further work will need to be done to delineate a clinical benefit for routine use of dexmedetomidine in postoperative transplant patients.

A recent randomized controlled trial-The Haloperidol Effectiveness in ICU Delirium (HOPE-ICU) study-showed no difference in days alive and free of delirium between patients prophylactically treated with intravenous haloperidol (2.5 mg every 8 hours) or placebo [48]. At this time, the data are not conclusive to make a formal recommendation for routine pharmacologic prophylaxis for delirium prevention.

#### *3.3.2 Non-pharmacologic prevention*

Implementing non-pharmacologic based prevention bundles for delirium reduction have resulted in improved rates of delirium. The clinical care bundles focus on reducing exposure to and mitigating delirium risk factors such as appropriate pain management, timely Foley catheter removal, re-orientation strategies, and reducing hearing and vision deficits. Implementation of these protocols has reduced delirium rates and total days of delirium in multiple studies [49–51]. There is a growing emphasis on a multimodal approach to pain control to reduce exposure to deliriogenic narcotic pain medication. Multimodal pain control emphasizes opioid reduction with the use of a combination of acetaminophen, non-steroidal anti-inflammatory medications, ketamine, gabapentin and/or regional anesthetic techniques where appropriate. A multi-disciplinary approach with anesthesia, pain specialists and the surgical team should be implemented to optimize post-operative pain control with narcotic avoidance/reduction protocols.

Combining evidence-based interventions that reduce delirium rates have been shown to be effective and the combination of different strategies can have additive beneficial effects on delirium prevention. The Awakening and Breathing Coordination, Delirium Monitoring/Management, and Early Mobility (ABCDE) bundle is the most described bundle in the literature (**Figure 3**). Initially published in 2011 [52], this bundle has proven to be an effective strategy in delirium prevention. The ABCDE bundle is comprised of a number of interventions shown to improve outcomes in several well-designed clinical trials. The ABCDE bundle is an evidence-based, multicomponent management strategy aimed at reducing sedation exposure, duration of mechanical ventilation and hospital-acquired delirium and weakness. In comparison to standard practice including spontaneous breathing trials and spontaneous awakening trials (but no consistent delirium screening), the ABCDE bundle group experienced less delirium (48.7 vs. 62.3%, P = 0.02) and a lower percent of intensive care unit days spent delirious (33 vs. 50%, P = 0.002) [53]. The "AB" component of the bundle focuses on expedited mechanical ventilation liberation, and has been shown to decrease duration of medical ventilation, duration of coma and mortality [54, 55]. The "C" of the bundle is focused on avoiding over sedation and use of benzodiazepines, which has been shown in clinical trials to decrease delirium and duration of mechanical ventilation [56–58]. The "D" of the bundle refers to regular delirium screening and monitoring. The "E" of the bundle highlights the need for early mobility, which has been shown to decrease duration of delirium, intensive care unit length of stay and mortality [59]. A recent prospective, cohort study evaluated the effects of the ABCDE bundle on delirium rates. After the bundle was implemented, the prevalence of delirium decreased significantly from 38 to 23% (P = 0.01). The number of days with delirium was also reduced from 3.8 to 1.72 days (P = <0.001) [60]. These data support a focused, clinical care bundle approach to delirium prevention and prospective implementation in postoperative solid organ transplant recipients.

#### **4. Treatment and management**

#### **4.1 Management**

Most of the data exploring practice recommendations for delirium management is rooted in the critical care literature. Over the past two decades, significant shifts in practice paradigms have helped reduce the incidence of delirium in the intensive care unit. The major advancements in delirium management and prevention include

**137**

delirium incidence [54, 61].

**E**

*Overview of the ABCDE delirium prevention bundle.*

**Figure 3.**

**D**

**C**

with amount of lorazepam administered [62].

*Delirium Management, Treatment and Prevention Solid Organ Transplantation*

**-Decreases mortality**

 **-Avoid benzodiazepines -Consider dexamedetomidine**

 **-Routine delirium screening -Increases delirium detection**

 **-Reduces delirium rates**

**Awake and Breathing Coordination**

**-Daily spontaneous awakening and breathing trials -Decreases duration of mechanical ventilation**

**Choose light sedation**

**Delirium monitoring and management**

**Early mobility and exercise -Early physical therapy and occupation therapy** 

 **-Coordinate with periods of reduced sedation** 

 **-Reduces delirium rates and mortality** 

 **-Focus on nonpharmocologic treatment** 

the level of sedation delivered while receiving mechanical ventilation. Daily awakening trials where sedation is interrupted to evaluate the ability to liberate from mechanical ventilation coupled with spontaneous breathing trials has been shown in randomized controlled studies to reduce mechanical ventilation days as well as

In addition, the choice of medication for sedation has shifted from benzodiazepines to propofol or dexmedetomidine infusions. This management shift was based on randomized controlled studies evaluating delirium outcomes and rates in patients receiving dexmedetomidine versus lorazepam infusions for sedation. Longer duration of lorazepam exposure was significantly associated with increased rates of delirium [57]. This study of 106 critically ill patients found that the patients receiving dexmedetomidine had more delirium free days compared to the lorazepam group (7 vs. 3, P = 0.01). Not only does duration of benzodiazepine exposure increase the incidence of delirium, it has been shown that delirium risk increases

An unintended consequence of routine intensive care unit care is sleep disruption and interference with sleep quality. Fragmented sleep has been associated with delirium. A focus on promoting and maintaining adequate sleep hygiene is an important delirium preventive measure. Efforts to minimize overnight disruptions and promote normal circadian rhythms have been associated with lower odds of developing delirium. Non-pharmacologic measures should be implemented to aid in sleep quality improvement and maintenance of sleep hygiene such as exposure to natural light, activity/mobility during the day, reduction of nighttime noise, removal of nocturnal stimulation, and reductions in night time nursing disruptions. A quality improvement project aimed at improving sleep by minimizing sleep

*DOI: http://dx.doi.org/10.5772/intechopen.86297*

**A**

**B**

*Delirium Management, Treatment and Prevention Solid Organ Transplantation DOI: http://dx.doi.org/10.5772/intechopen.86297*

**Figure 3.** *Overview of the ABCDE delirium prevention bundle.*

the level of sedation delivered while receiving mechanical ventilation. Daily awakening trials where sedation is interrupted to evaluate the ability to liberate from mechanical ventilation coupled with spontaneous breathing trials has been shown in randomized controlled studies to reduce mechanical ventilation days as well as delirium incidence [54, 61].

In addition, the choice of medication for sedation has shifted from benzodiazepines to propofol or dexmedetomidine infusions. This management shift was based on randomized controlled studies evaluating delirium outcomes and rates in patients receiving dexmedetomidine versus lorazepam infusions for sedation. Longer duration of lorazepam exposure was significantly associated with increased rates of delirium [57]. This study of 106 critically ill patients found that the patients receiving dexmedetomidine had more delirium free days compared to the lorazepam group (7 vs. 3, P = 0.01). Not only does duration of benzodiazepine exposure increase the incidence of delirium, it has been shown that delirium risk increases with amount of lorazepam administered [62].

An unintended consequence of routine intensive care unit care is sleep disruption and interference with sleep quality. Fragmented sleep has been associated with delirium. A focus on promoting and maintaining adequate sleep hygiene is an important delirium preventive measure. Efforts to minimize overnight disruptions and promote normal circadian rhythms have been associated with lower odds of developing delirium. Non-pharmacologic measures should be implemented to aid in sleep quality improvement and maintenance of sleep hygiene such as exposure to natural light, activity/mobility during the day, reduction of nighttime noise, removal of nocturnal stimulation, and reductions in night time nursing disruptions. A quality improvement project aimed at improving sleep by minimizing sleep

*Perioperative Care for Organ Transplant Recipient*

pain control with narcotic avoidance/reduction protocols.

postoperative solid organ transplant recipients.

**4. Treatment and management**

**4.1 Management**

Implementing non-pharmacologic based prevention bundles for delirium reduction have resulted in improved rates of delirium. The clinical care bundles focus on reducing exposure to and mitigating delirium risk factors such as appropriate pain management, timely Foley catheter removal, re-orientation strategies, and reducing hearing and vision deficits. Implementation of these protocols has reduced delirium rates and total days of delirium in multiple studies [49–51]. There is a growing emphasis on a multimodal approach to pain control to reduce exposure to deliriogenic narcotic pain medication. Multimodal pain control emphasizes opioid reduction with the use of a combination of acetaminophen, non-steroidal anti-inflammatory medications, ketamine, gabapentin and/or regional anesthetic techniques where appropriate. A multi-disciplinary approach with anesthesia, pain specialists and the surgical team should be implemented to optimize post-operative

Combining evidence-based interventions that reduce delirium rates have been shown to be effective and the combination of different strategies can have additive beneficial effects on delirium prevention. The Awakening and Breathing Coordination, Delirium Monitoring/Management, and Early Mobility (ABCDE) bundle is the most described bundle in the literature (**Figure 3**). Initially published in 2011 [52], this bundle has proven to be an effective strategy in delirium prevention. The ABCDE bundle is comprised of a number of interventions shown to improve outcomes in several well-designed clinical trials. The ABCDE bundle is an evidence-based, multicomponent management strategy aimed at reducing sedation exposure, duration of mechanical ventilation and hospital-acquired delirium and weakness. In comparison to standard practice including spontaneous breathing trials and spontaneous awakening trials (but no consistent delirium screening), the ABCDE bundle group experienced less delirium (48.7 vs. 62.3%, P = 0.02) and a lower percent of intensive care unit days spent delirious (33 vs. 50%, P = 0.002) [53]. The "AB" component of the bundle focuses on expedited mechanical ventilation liberation, and has been shown to decrease duration of medical ventilation, duration of coma and mortality [54, 55]. The "C" of the bundle is focused on avoiding over sedation and use of benzodiazepines, which has been shown in clinical trials to decrease delirium and duration of mechanical ventilation [56–58]. The "D" of the bundle refers to regular delirium screening and monitoring. The "E" of the bundle highlights the need for early mobility, which has been shown to decrease duration of delirium, intensive care unit length of stay and mortality [59]. A recent prospective, cohort study evaluated the effects of the ABCDE bundle on delirium rates. After the bundle was implemented, the prevalence of delirium decreased significantly from 38 to 23% (P = 0.01). The number of days with delirium was also reduced from 3.8 to 1.72 days (P = <0.001) [60]. These data support a focused, clinical care bundle approach to delirium prevention and prospective implementation in

Most of the data exploring practice recommendations for delirium management is rooted in the critical care literature. Over the past two decades, significant shifts in practice paradigms have helped reduce the incidence of delirium in the intensive care unit. The major advancements in delirium management and prevention include

*3.3.2 Non-pharmacologic prevention*

**136**

disruptions and promoting normal circadian rhythms using non-pharmacological sleep aids has been shown to decrease the incidence of delirium and improve daily delirium free status [63].

Early mobilization is also an important strategy for delirium prevention. A trial of early mobilization that randomized hemodynamically stable patients to daily sedation interruptions timed with physical and occupation therapy versus usual care without early mobilization therapy achieved a two-day reduction in delirium duration in the treatment arm (days with delirium: 2 vs. 4 days, P = 0.03) [59]. In addition, early mobilization in this study reduced the time in the intensive care unit with delirium (33% of patients in the intervention group were diagnosed with delirium vs. 57% of patients in the control group were diagnosed with delirium, P = 0.02), as well as time in the hospital with delirium (28% of patients in the intervention group were diagnosed with delirium vs. 41% of patients in the control group were diagnosed with delirium, P = 0.01). Therapy included passive range of motion, active range of motion, and activities of daily living training depending on the patients' level of sedation and ability. In another recent randomized controlled trial of surgical critically ill patients, early goal-directed mobilization reduced the incidence of delirium and increased the number of delirium free days in the intensive care unit when compared to usual care [64].

#### **4.2 Pharmacologic treatment**

Currently, there are no evidence-based guidelines regarding specific pharmacological agents for delirium treatment. The current first line agents used in the treatment of hyperactive delirium are antipsychotic medications including haloperidol, olanzapine and quetiapine. Of note, neither antipsychotics nor dexmedetomidine have FDA approval for the treatment of delirium. In an international survey of 1521 intensivists, 65% reported that they treat delirium in the intensive care unit with haloperidol and 53% reported that they treat delirium with atypical antipsychotic medications [65], but there is no evidence-based literature showing efficacy of these medications for delirium treatment and symptom resolution. Despite current practice patterns, there are few data to support their definitive use in treating delirium.

A recent study evaluating the treatment of delirium with haloperidol (2.5–5 mg every 8 h) versus olanzapine (5 mg daily) showed no difference in length of delirium in 73 critically ill patients [66]. Furthermore, in a randomized, double blind, placebo-controlled trial, patients with acute respiratory failure or shock and hypoactive or hyperactive delirium were assigned to receive intravenous boluses of haloperidol (maximum dose, 20 mg daily), ziprasidone (maximum dose, 40 mg daily), or placebo [67]. The primary end point was the number of days alive without delirium or coma during the 14-day intervention period. The use of haloperidol or ziprasidone, as compared with placebo, in patients with acute respiratory failure or shock and hypoactive or hyperactive delirium in the intensive care unit did not significantly alter the duration of delirium. This randomized, placebo-controlled trial of intravenous antipsychotic medications for the treatment of delirium in critically ill patients showed that pharmacologic treatment was no different than placebo [67].

Dexmedetomidine in delirium management has gained popularity over the past several years. A recent trial studied dexmedetomidine in mechanically ventilated patients who were unable to be weaned from mechanical ventilation due to hyperactive delirium. This study, Dexmedetomidine to Lessen ICU Agitation trial, randomized patients to receive 7 days of intravenous dexmedetomidine (up to 1.5 μg/kg/h) or placebo. Patients treated with dexmedetomidine had fewer days requiring ventilator

**139**

**5. Outcomes**

outcomes.

executive functioning [70].

ensure optimal functional recovery.

*Delirium Management, Treatment and Prevention Solid Organ Transplantation*

support and had faster resolution of delirium symptoms (23 vs. 40 h, P = 0.01) [68]. Dexmedetomidine must be administered as an infusion, which means the drug can only be given to patients having critical care needs. Alternative oral alpha-2 agonists exist, including clonidine or guanfacine, which could facilitate therapy in non- intensive care unit settings or during transition of care. However, these agents have not been rigorously studied in regards to delirium treatment and prevention as options for

As strong evidence supporting the use of single pharmacological agents in delirium is lacking, preventive strategies and non-pharmacologic treatment

bundles, such as the ABCDE bundle as discussed above, should be incorporated into

Cognitive and physical dysfunction is a common sequela for patients following a prolonged course of delirium. Recently, efforts have been made to minimize the long-term effects of delirium through exercises focused on orientation, memory, attention, and problem solving. A recent study implemented a graded cognitive therapy protocol with varying degrees of intensity guided by the patient's RASS assessment immediately preceding the session [69]. Examples of the cognitive therapy performed in this study included matrix puzzles, noun list recall, paragraph recall, letter-number sequence, and pattern recognition. The authors showed that following discharge from the intensive care unit, combined cognitive and physical therapy was associated with improved executive functioning at the time of hospital discharge [69]. These data suggest that once a patient is able to participate in therapy following delirium recovery, efforts should be made to incorporate cognitive rehabilitation as an integral part of the recovery process to maximize functional

Extending beyond inpatient rehabilitation, research has been conducted into performing cognitive rehabilitation following hospital discharge in patients who suffered from delirium [70]. In this study the rehabilitation program was provided over a 12-week period after discharge in each patient's home and integrated both traditional "face-to-face" interventions as well as telephone and video-based interventions for cognitive, physical and functional rehabilitation. The cognitive training was based on the goal-management training (GMT) protocol, a focused and theoretically derived stepwise approach to the rehabilitation of executive function. The GMT sessions build on one another to increase the "dose" of rehabilitation delivered. These cognitive sessions resulted in improved scoring on tests evaluating

Based on studies in non-transplant populations, it would appear that transplant

As patients are recovering from delirium and transitioning to cognitive rehabilitation, it is important to focus on the completion of the treatment for any underlying condition, like sepsis, that lead to or contributed to delirium development to

Delirium in the postoperative setting significantly impacts outcomes. Delirium is a predictor of mortality in hospitalized patients [61], and mortality increases

patients could similarly benefit from both inpatient and outpatient cognitive rehabilitation following delirium recovery in order to optimize long-term outcomes

and maximize quality of life following transplantation.

*DOI: http://dx.doi.org/10.5772/intechopen.86297*

oral transition or alternatives to dexmedetomidine.

delirium prevention and management algorithms.

**4.3 Cognitive therapy following delirium**

#### *Delirium Management, Treatment and Prevention Solid Organ Transplantation DOI: http://dx.doi.org/10.5772/intechopen.86297*

support and had faster resolution of delirium symptoms (23 vs. 40 h, P = 0.01) [68]. Dexmedetomidine must be administered as an infusion, which means the drug can only be given to patients having critical care needs. Alternative oral alpha-2 agonists exist, including clonidine or guanfacine, which could facilitate therapy in non- intensive care unit settings or during transition of care. However, these agents have not been rigorously studied in regards to delirium treatment and prevention as options for oral transition or alternatives to dexmedetomidine.

As strong evidence supporting the use of single pharmacological agents in delirium is lacking, preventive strategies and non-pharmacologic treatment bundles, such as the ABCDE bundle as discussed above, should be incorporated into delirium prevention and management algorithms.

#### **4.3 Cognitive therapy following delirium**

*Perioperative Care for Organ Transplant Recipient*

sive care unit when compared to usual care [64].

**4.2 Pharmacologic treatment**

delirium free status [63].

disruptions and promoting normal circadian rhythms using non-pharmacological sleep aids has been shown to decrease the incidence of delirium and improve daily

Early mobilization is also an important strategy for delirium prevention. A trial of early mobilization that randomized hemodynamically stable patients to daily sedation interruptions timed with physical and occupation therapy versus usual care without early mobilization therapy achieved a two-day reduction in delirium duration in the treatment arm (days with delirium: 2 vs. 4 days, P = 0.03) [59]. In addition, early mobilization in this study reduced the time in the intensive care unit with delirium (33% of patients in the intervention group were diagnosed with delirium vs. 57% of patients in the control group were diagnosed with delirium, P = 0.02), as well as time in the hospital with delirium (28% of patients in the intervention group were diagnosed with delirium vs. 41% of patients in the control group were diagnosed with delirium, P = 0.01). Therapy included passive range of motion, active range of motion, and activities of daily living training depending on the patients' level of sedation and ability. In another recent randomized controlled trial of surgical critically ill patients, early goal-directed mobilization reduced the incidence of delirium and increased the number of delirium free days in the inten-

Currently, there are no evidence-based guidelines regarding specific pharmacological agents for delirium treatment. The current first line agents used in the treatment of hyperactive delirium are antipsychotic medications including haloperidol, olanzapine and quetiapine. Of note, neither antipsychotics nor dexmedetomidine have FDA approval for the treatment of delirium. In an international survey of 1521 intensivists, 65% reported that they treat delirium in the intensive care unit with haloperidol and 53% reported that they treat delirium with atypical antipsychotic medications [65], but there is no evidence-based literature showing efficacy of these medications for delirium treatment and symptom resolution. Despite current practice patterns, there are few data to support their definitive use in treating

A recent study evaluating the treatment of delirium with haloperidol (2.5–5 mg

Dexmedetomidine in delirium management has gained popularity over the past several years. A recent trial studied dexmedetomidine in mechanically ventilated patients who were unable to be weaned from mechanical ventilation due to hyperactive delirium. This study, Dexmedetomidine to Lessen ICU Agitation trial, randomized patients to receive 7 days of intravenous dexmedetomidine (up to 1.5 μg/kg/h) or placebo. Patients treated with dexmedetomidine had fewer days requiring ventilator

every 8 h) versus olanzapine (5 mg daily) showed no difference in length of delirium in 73 critically ill patients [66]. Furthermore, in a randomized, double blind, placebo-controlled trial, patients with acute respiratory failure or shock and hypoactive or hyperactive delirium were assigned to receive intravenous boluses of haloperidol (maximum dose, 20 mg daily), ziprasidone (maximum dose, 40 mg daily), or placebo [67]. The primary end point was the number of days alive without delirium or coma during the 14-day intervention period. The use of haloperidol or ziprasidone, as compared with placebo, in patients with acute respiratory failure or shock and hypoactive or hyperactive delirium in the intensive care unit did not significantly alter the duration of delirium. This randomized, placebo-controlled trial of intravenous antipsychotic medications for the treatment of delirium in critically ill patients showed that pharmacologic treatment was no different than

**138**

placebo [67].

delirium.

Cognitive and physical dysfunction is a common sequela for patients following a prolonged course of delirium. Recently, efforts have been made to minimize the long-term effects of delirium through exercises focused on orientation, memory, attention, and problem solving. A recent study implemented a graded cognitive therapy protocol with varying degrees of intensity guided by the patient's RASS assessment immediately preceding the session [69]. Examples of the cognitive therapy performed in this study included matrix puzzles, noun list recall, paragraph recall, letter-number sequence, and pattern recognition. The authors showed that following discharge from the intensive care unit, combined cognitive and physical therapy was associated with improved executive functioning at the time of hospital discharge [69]. These data suggest that once a patient is able to participate in therapy following delirium recovery, efforts should be made to incorporate cognitive rehabilitation as an integral part of the recovery process to maximize functional outcomes.

Extending beyond inpatient rehabilitation, research has been conducted into performing cognitive rehabilitation following hospital discharge in patients who suffered from delirium [70]. In this study the rehabilitation program was provided over a 12-week period after discharge in each patient's home and integrated both traditional "face-to-face" interventions as well as telephone and video-based interventions for cognitive, physical and functional rehabilitation. The cognitive training was based on the goal-management training (GMT) protocol, a focused and theoretically derived stepwise approach to the rehabilitation of executive function. The GMT sessions build on one another to increase the "dose" of rehabilitation delivered. These cognitive sessions resulted in improved scoring on tests evaluating executive functioning [70].

Based on studies in non-transplant populations, it would appear that transplant patients could similarly benefit from both inpatient and outpatient cognitive rehabilitation following delirium recovery in order to optimize long-term outcomes and maximize quality of life following transplantation.

As patients are recovering from delirium and transitioning to cognitive rehabilitation, it is important to focus on the completion of the treatment for any underlying condition, like sepsis, that lead to or contributed to delirium development to ensure optimal functional recovery.
