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Agitation? Delirium? Both? and What to Do About It
Kathryn T. Von Rueden RN, MS, ACNS-BC, FCCM Clinical Nurse Specialist, R Adams Cowley Shock Trauma Center, Assistant Professor University of Maryland, School of Nursing
Delirium: “a part of the scenery ?”
Ely, W: Semin Respir Crit Care Med. 2001;22(2)
Delirium: DSM-IV Diagnostic Criteria
reduced clarity of awareness of the environment reduced ability to focus, sustain, or shift attention Memory deficit, disorientation, language problem Perceptual disturbance Unexplained by a chronic dementia 3. Acute onset (hrs to days) with fluctuating course throughout the day 4. Evidence of an illness, trauma, or drug effect
Agitation: a behavior, not a diagnosis
1. Strong, tumultuous emotions, continual movement, disorientation, inability to listen or follow Fidgeting, pulling at dressings, catheters, sheets, etc. Disorientation Inability to listen, communicate, or follow commands Acute, fluctuating changes in mental status, hallucination and inattention. 1. Hyperactive (20%) 2. Hypoactive (30%) 3. Mixed (50%) Incidence of delirium/ agitation in ICUs
 60-87% of patients requiring mechanical ventilation STC prevalence study:  24% IMC & ICU trauma patients Impact of delirium on patient outcomes

Impact on Resources
 35-40% 1-year mortality, 62% increase from baseline  17.5 million inpatient days  $5-6 billion/yr in Medicare expenses  Increased rates of institutionalization & terminal decline  1 of the 6 leading causes of preventable injury in people over 65 yo
Pathophysiologic Basis of Delirium
Multifactorial !!

 Metabolic & electrolyte imbalances  Medical therapies including drugs  Endorphin hyperfunction  Increased central noradrenergic function  Brain response to infection and injury includes production of inflammatory cytokines, cell infiltration, and tissue damage  Imbalances in synthesis, release, and inactivation of neurotransmitters  Primary neurotransmitter alterations: GABA (γ-aminobutryic acid) & GABA receptors Dopamine Acetylcholine deficiency Serotonin imbalance
Pre-existing / Non-modifiable Risk Factors
 Dementia  Chronic illness (including hypertension)  Advanced age  Depression  Smoking  Alcoholism  Apolipoprotein E4 phenotype  Severity of illness on hospital admission
Hospital Related / Iatrogenic Risk Factors
 Hypoxia  Metabolic disturbances  Electrolyte imbalances  Prolonged restraint use  Sleep deficits  Heart failure  Sepsis  Immobility  Acute infections  Withdrawal syndromes
Assessment of Agitation
1. Consciousness 2. Agitation 3. Anxiety 4. Sleep 5. Pt Vent Synchrony
Delirium Evaluation in ICU
Intensive Care Delirium Screening Checklist (ICDSC) Evidence-Based Strategies to PREVENT & Manage Delirium & Agitation

Pharmacologic / Interdisciplinary Collaborative Interventions
 Correct underlying insult, metabolic or hemodynamic derangements or hypoxemia
 Stop inappropriate medications
 Use sedation protocols & daily interruption of sedation
 Pain control
 Targeted pharmacologic therapy:
• Sedatives: midazolam, lorazepam, propofol • Dopamine receptor blockade: Haloperidol • Alpha-2 agonists: dexmetomidine, clonidine • Antipsychotics: respiridone, olanzapine
Agitation: Drug Management
Short Term < 24 hrs Midazolam Propofol LongTerm > 24 hrs Lorazepam Avoid in elderly ?? Paradoxical early DISinhibition Interfere with sleep architecture Benzodiapines and Delirium, Pandharipande et al Anesthesiology 2006 Lorazepam is an independent risk factor for transitioning to delirium Benzodiapines, Opiods and Delirium, Pisani M et al Crit Care Med 37:177-183, 2009  Increased delirium duration associated with Benzodiazepines &/or opioids (RR 1.64) “may be modifiable risk factors for delirium”
E-B Sedation Management is Based on Objective Assessment!
• Indication: 1st tx pain, physiologic causes • Set Sedation Goal: evaluate daily; use a valid/reliable sedation scale • Sedative selection: consistent with goals • Sedation management strategy: Nurse driven sedation protocol; include pharmacist • Sedation weaning strategy: include SBT Nurse Driven Protocols & Daily Interruption of sedation…… • Decreases days on mechanical vent • Decreases ICU LOS • Decreases Hospital LOS • Decreases VAP Delirium: Drug Management

Predictable side effects, “general safety” Prolongs QTc (greater with IV) Torsades de Pointes Up to 15% in critically ill pts Use with caution if QTc > 450 msec D/C Haldol if QTc increases by >25% Optimize Mg and Ca Atypical (2nd generation) Antipsychotics (6 available in USA): Antagonize multiple receptors eg Alpha 1 & 2, histamine, dopamine D1 Limited data in acute care Unwanted side effects, eg cardiac dysrhythmias, orthostatic hypotension FDA Public Health Advisory: April 2005 Deaths with Antipsychotics in Elderly Patients with Behavioral Disturbances. Atypical Antipsychotics in the Critical Care Population Antihistaminic mechanism of action Short 1/2-life facilitates dose titration Modifying the Incidence of Delirium MIND Study
FDA Approved 1999 Short acting alpha-2 agonist Anxiolytic, anesthetic, hypnotic, analgesic effects Approved for continuous IV < 24 hrs
Ziprasidone vs Haloperidol

MENDS Trial:

Lorazapam vs Dexmedetomidine
Dexmedetomidine vs midazolam
Evidence-based Non-Pharmacologic / Nursing Driven Interventions E-B Practice Guideline: acute confusion/delirium (Sendelbach S)

1. Identify & Modify Risk Factors
 Hypoxia  Metabolic disturbances  Electrolyte imbalances  Sleep deficits  Heart failure  Sepsis  Prolonged restraint use  Immobility  Acute infections  Withdrawal syndromes  Seizures  Dehydration  Hyperthermia  Head trauma  Vascular disorders  Intracranial lesions  Medications 2. Re-orientation to person, place & time (B2)
3. Promote un-interrupted sleep (B2)
4. Promote a healing environment
5. Minimize urinary catheters & restraints (A2)
6. Assure appropriate nutrition (A2)
7. Early mobilization (A2)
8. Geriatric specialist consult/ involvement
9. At least daily assessment using an objective & validated tool
10. Educate nurses and physicians re: Delirium risk factors, prevention, treatment and care (B2)
SCCM Updated Guideline (in press)

AACN Practice Alert ( 11-11)
Best Practice: What we should be doing!:
Daily Interdisciplinary Rounds
Discuss results of delirium assessment on all patients. ID patients with high number of risk factors for development or persistence of delirium. Review sedation & analgesia therapy Minimum doses to achieve comfort Implement strategies for tight titration; Nurse-driven, pt-targeted sedation delivery with daily sedation vacations Consider the benefit & risk of adding medications that might spare the use of sedatives & avoid respiratory suppression, Eg. haloperidol or atypical antipsychotics

AACN Practice Alert: Delirium assessment and management. Nov.2011
Alexander E: Delirium in the ICU: Medications as risk factors. Crit Care Nurs 2009;29:85-87
Allen, J., Alexander, E. Prevention, Recognition, and Management of Delirium in the Intensive Care Unit.
AACN Advanced
Banerjee, A. Girard TD, Jackson JC, Pandharipande PP The complex interplay between delirium, sedation, and early mobility during critical illness: applications in the trauma unit Cur Opin Anaesth. 2011,24 (2 )195–201. Bourne R, Tahir T, et al: Drug treatment of delirium: Past, present and future J Psychosom Res 2008;65:273-282 Bruno JJ, Warren ML: Intensive care unit delirium. Crit Care Clin NA. 2010 22:161-178. DeJong M, Burns S, et al, Development of the AACN Sedation Assessment Scale for Critically Ill Patients. Am J Crit Care. 2005;14: 531-544 Delirium: prevention, early recognition and treatment. In Tullman D, et al: Evidence based geriatric nursing protocols for best practice. 2008 Devlin J, Fong J, et al: Assessment of delirium in the ICU: Nursing practices and perceptions. Am J Crit Care 2008;17:555-566 Devlin JW, Roberts RJ, Fong JJ, et al. Efficacy and safety of quetiapine in critically ill patients with delirium: a prospective, multicenter, randomized, double-blind, placebocontrolled pilot study. Crit Care Med 2010; 38:419-427. Fuchs E, VonRueden K: Sedation management in the mechanically ventilated critically ill patient. AACN Adv Crit Care 2008;19:421-432 Girard TD, Jackson JC, Pandharipande PP, et al. Delirium as a predictor of long-term cognitive impairment in survivors of critical illness. Crit Care Med 2010; 38:1513-1520. Girard TD, Pandharipande PP, Carson SS, et al. Feasibility, efficacy, and safety of antipsychotics for intensive care unit delirium: the MIND randomized, placebo-controlled trial. Crit Care Med 2010; 38:428-437. Guenther U, Popp J, Koecher L, et al. Validity and reliability of the CAM-ICU Flowsheet to diagnose delirium in surgical ICU patients. J Crit Care 2010; 25:144-151 (Excellent website with multiple resources)
Lat I, McMillian W, et al: Impact of delirium on clinical outcomes in mechanically ventilated surgical and
trauma patients. Crit Care Med 2009;37:1898-1905
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approach. Curr Opin Crit Care 2011, 17:43–49.
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Dysfunction, JAMA 2007;298:2644.
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Riker R, Shehabi Y et al: Safety and Efficacy of Dexmedetomidine Compared With Midazolam
JAMA 2009;301:489.
Sendelbach S, Guthrie PF: Evidence-based practice guideline: Acute confusion/delirium. University of Iowa
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Corchrane Database of Systematic Reviews, 2009
Interventions for preventing delirium in hospitalized patients
Benzodiazepines for delirium
Antipsychotics for delirium
Multidisciplinary team interventions fir the management of delirium in hospitalized patients


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