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Optimizing Patient’s Brain Function After Critical Illness: ICU Management via the Pain, Agitation, and Delirium (PAD) Guidelines and Beyond

one year ago
The medical care of critically ill adults in the ICU centres around managing pain and agitation with analgesics and sedatives, respectively.1 Delirium, a potentially life-threatening complication in ICU patients is often overlooked. Delirium is characterized by the acute onset of brain dysfunction that results in a change in mental status, inattention and either disorganized thinking or an altered level of consciousness.2
 
Delirium in the critically ill: A public health problem
Delirium is now widely recognized as a public health problem in the critically ill because close to 80% of post- ICU survivors have cognitive impairment.2,3 Additionally, critical illness survivors are more likely to suffer from functional impairment with an incidence rate of up to 80%.4 
 
Delirium independently predicts a higher mortality rate and longer hospital stay in ICU patients.5 Additionally, the duration of delirium is not only linked to mortality (Figure 1), ventilation time and prolonged ICU stay,6 but also worsens short- and long-term cognitive and executive functions.7 Furthermore, a study using magnetic resonance imaging (MRI) shows that prolonged delirium is associated with greater brain atrophy, which in turn is associated with cognitive impairment for up to 12 months (Figure 2).8
Fig1_HOS_098

Fig2_HOS_098
 
In view of the explosion of evidence linking delirium in the ICU to increased mortality and morbidity in post-ICU survivors, the recently updated Clinical Practice Guidelines for the Management of Pain, Agitation, and Delirium in Adult Patients in the Intensive Care Unit (ie, ICU PAD guidelines) recommend routine monitoring of delirium in critically ill patients.2

The ABCDEF bundle for improving patient outcomes in the critically ill
According to Professor Ely, the ABCDEF bundle is an evidence-based medical checklist that has evolved over time to provide a comprehensive management of ICU patients.2,9 It aims to provide optimal ICU outcome, safety and comfort in patients with critical illness through:
• A – Assess, prevent and manage pain (optimized pain control)10;
• B – Awakening & Breathing coordination (patient’s readiness to be weaned and extubated via spontaneous awakening trials [SAT] and spontaneous breathing trials [SBT])10;
• C – Choice of sedation (light sedation and avoid benzodiazepine)10;
• D – Delirium monitoring (using the confusion assessment method for the ICU [CAM-ICU])10;
• E – Early mobility and exercise (early initiation of daily activity and exercise)10;
• F – Family empowerment and engagement.10

When implemented as a package, evidence shows that the ABCDEF bundle leads to less delirium, reduced benzodiazepine use, decreased duration of mechanical ventilation and ICU stay, earlier mobility and improved survival.11-15

Addressing the sedation-delirium link
Traditionally, deep sedation strategy is adopted to treat agitation and anxiety; but prolonged, deep sedation can lead to delirium in ICU patients. On the other hand, lighter sedation levels improve patient outcomes such as less delirium, reduced duration of mechanical ventilation and ICU stay.11,14,16
 
In the updated ICU PAD guidelines, the guideline committee recommends a light sedation strategy, and nonbenzodiazepine sedatives (either propofol or dexmedetomidine) are preferred over benzodiazepines (midazolam or lorazepam).2 The evidence for dexmedetomidine is presented in two clinical trials that compared the drug against midazolam and lorazepam. In the first study, Riker et al17 found dexmedetomidine to be similar to midazolam for sedation efficacy, but with less incidence of delirium (prevalence rate 54% for dexmedetomidine vs 76.6% for midazolam; 22.6% difference; p<0.001) (Figure 3). The reduction in incidence of delirium was seen immediately on day 1 of dexmedetomidine administration.

Fig3_HOS_098

A similar trend in reduction of delirium with dexmedetomidine was also seen in the MENDS (Maximizing Efficacy of Targeted Sedation and Reducing Neurological Dysfunction)18 trial. Compared with lorazepam, dexmedetomidine-treated patients with sepsis had 3.2 more delirium/coma-free days, 1.5 more delirium-free days and 6 more ventilator-free days. The
beneficial effect of dexmedetomidine was even more pronounced in non-septic patients for both delirium/coma-free days and ventilator-free days. Furthermore, the risk of dying at 28 days was reduced by 70% in dexmedetomidine patients with sepsis compared with lorazepam patients.

Early mobilization to lessen delirium
The usual practice of deep sedation and bed rest in ICU patients can adversely impair their physical function and quality of life after discharge. On the other hand, there is increasing evidence suggesting that reduced sedation and early mobilization benefit ICU survivors.19,20 One such study shows that whole body rehabilitation, which consists of interruption of sedation plus physical and occupation therapy in the early days of critical illness, results in better functional outcomes at discharge, a shorter duration of delirium, and more ventilator-free days compared with standard care.21

According to Professor Ely, the following criteria assist the team at his hospital to determine if a patient is suitable for early mobilization: myocardial stability, adequate oxygenation, minimal vasopressor and patient engagement to voice commands.

Summary
The medical care and management of critically ill patients have evolved tremendously such that the American College of Critical Care Medicine, in conjunction with the Society of Critical Care Medicine and the American Society of Health-System Pharmacists saw a need to update the ICU PAD guidelines to reflect the most current and evidence-based practice in critical care. The ABCDEF bundle succinctly captures the important points of the ICU PAD guidelines and provides a framework that allows healthcare professionals in the critical care team to improve mortality and morbidity in ICU patients.

In the updated guidelines, the adverse impact of delirium on post-ICU survivors is given due recognition and several recommendations are made to improve patient safety and comfort. Most importantly, a less sedation strategy is recommended and the use of nonbenzodiazepine sedatives is preferred.

References: 
1. Jacobi J, et al. Crit Care Med 2002;30(1):119–141. 
2. Barr J, et al. Crit Care Med 2013;41(1):263–306. 
3. Girard TD, et al. Crit Care Med 2010;38(7):1513–1520. 
4. Latronico N, Bolton CF. Lancet Neurol 2011;10(10):931–941. 
5. Ely EW, et al. JAMA 2004;291(14):1753–1762.
6. Shehabi Y, et al. Crit Care Med 2010;38(12):2311–2318. 
7. Pandharipande PP, et al. N Engl J Med 2013;369(14):1306–1316. 
8. Gunther ML, et al. Crit Care Med 2012;40(7):2022–2032. 
9. ICU Delirium and Cognitive Impairment Study Group. ABCDEF’s of Prevention and Safety. Available at: www.icudelirium.org/medicalprofessionals.html Accessed 15 October 2015. 
10. Society of Critical Care Medicine ICU Liberation. ABCDEF Bundle Improvement Collaborative. Available at: www.iculiberation.org/About/collaborative/Pages/default.aspx Accessed 15 October 2015. 
11. Dale CR, et al. Ann Am Thorac Soc 2014;11(3):367–374. 
12. Balas MC, et al. Crit Care Med 2014;42(5):1024–1036. 
13. Needham DM, et al. Arch Phys Med Rehabil 2010;91(4):536–542. 
14. Girard TD, et al. Lancet 2008;371(9607):126–134. 
15. Klompas M, et al. Am J Respir Crit Care Med 2015;191(3):292–301. 
16. Treggiari MM, et al. Crit Care Med 2009;37(9):2527–2534. 
17. Riker RR, et al. JAMA 2009;301(5):489–499. 
18. Pandharipande PP, et al. Crit Care 2010;14(2):R38. 
19. Needham DM. JAMA 2008;300(14):1685–1690. 
20. Nydahl P, et al. Crit Care Med 2014;42(5):1178–1186. 
21. Schweickert WD, et al. Lancet 2009;373(9678):1874–1882.

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