Sarah V. Cogle, PharmD, BCCCP Assistant Clinical Professor Auburn University Harrison School of Pharmacy Auburn, AL ALSHP Annual Clinical Meeting 2018
I have no actual or potential conflict of interest in relation to this program
Describe clinical presentations of delirium in the adult critically ill patient Review methods for assessing delirium in the adult ICU setting Discuss nonpharmacologic and pharmacologic treatment options for treating ICU delirium
Disturbance in attention and awareness that develops over a short period of time, is a change from the patient s baseline, and may fluctuate throughout the day Patient Presentation Can be agitated, calm, lethargic or alternate between these states May experience hallucinations and/or delusions Neurocognitive Disorders. In: Diagnostic and Statistical Manual of Mental Disorders. 2013:591 643.
Occurs in ~30% of ICU patients Associated with negative outcomes Cognitive impairment post discharge Potentially prolongs hospital stay Increased costs Salluh JI, et al. BMJ. 2015;350:h2538.
I had septic shock 4 years ago from urosepsis and I'm in my 50s I have never felt like myself again. I can't think clearly, my memory has suffered, I am fatigued like never before. This has affected every aspect of my life, I even had to leave my job as an ICU nurse because it was wearing me out I couldn't handle it which kills me I was on a ventilator and heavily sedated for nine days. I experienced what I call a prolonged nightmare. The theme: I was in an experimental hospital to learn what it's like to be completely dependent on someone else. I am a nurse so figured it was my punishment. The nightmare seemed to go on and on with different twists and turns. After I was extubated and sedation was discontinued, I continued to have paranoid delusions about the nurses wanting to harm me... I was hallucinating at times especially at night when I was alone. I saw outlines of skeletons on the wall, heard strange sounds, etc http://www.icudelirium.org/testimonials.html#
2018 Pain, Agitation/sedation, Delirium, Immobility (rehabilitation/mobilization), and Sleep (disruption) (PADIS) Guidelines Published by the Society of Critical Care Medicine (SCCM) Expand upon 2013 SCCM Pain, Agitation, and Sedation (PAD) Guidelines Rehabilitation/mobilization sections added Patients included as collaborators and coauthors International panel of experts
Modifiable Risk Factors Benzodiazepine use Blood Transfusions Nonmodifiable Risk Factors Advanced age Dementia Prior coma Pre ICU emergency surgery or trauma Increasing APACHE and ASA scores
Guidelines evaluated 48 studies with 19,658 patients Consistent associations WITH cognitive impairment at 3 and 12 months post ICU discharge May be associated with longer hospital stay NOT associated with PTSD or post ICU distress Inconsistent associations ICU LOS, discharge disposition to non home locations, depression, functionality/dependence, mortality Associations do not prove causation Highlight areas for future research
All adults should be regularly assessed for delirium using validated tools Confusion Assessment Method for the ICU (CAM ICU) Intensive Care Delirium Screening Checklist (ICDSC) Both are validated in ICU patients Many studies have shown that clinicians fail to recognize delirium without validated screening tools Bergeron N, et al. Intensive Care Med. 2001;27(5):859 864. Ely EW, et al. Crit Care Med. 2001;29(7):1370 1379.
Benefits Detect delirium earlier Correct underlying causes (if possible) Initiate appropriate treatments sooner Limitations Unable to accurately assess delirium in deeply sedated or comatose patients
http://www.icudelirium.org/docs/cam_icu_flowsheet.pdf
Bergeron N, et al. Intensive Care Med. 2001;27(5):859 864
Reduce modifiable risk factors whenever possible Early mobilization whenever feasible Frequent patient reorientation Maintain normal sleep/wake cycles Ensure patients have necessary medical devices Eye glasses, hearing aids
Benefits Decrease delirium duration Shorter ICU stays Decreased mortality Should be used for ALL patients and prophylaxis AND treatment
Cardiac surgery patients on mechanical ventilation Propofol preferred over benzodiazepines for sedation ICU patients on mechanical ventilation Either propofol or dexmedetomidine are preferred over benzodiazepines for sedation
Haloperidol, atypical antipsychotics, dexmedetomidine, statins, and ketamine are NOT recommended to prevent delirium in all critically ill patients Some studies report reduction in delirium incidence No significant benefits in terms of Duration of mechanical ventilation ICU LOS Morality Risks of exposure to these medications in broad populations outweigh the benefit
Present with ICDSC scores 1 3 Occurs in ~30% of patients More likely to die in the ICU, longer LOS, and be discharged to long term care facility Treatment Haloperidol or atypical antipsychotics NOT recommended Inconsistent results from trials, concern for antipsychotic medication related ADRs Other agents (dexmedetomidine, statins, ketamine) have yet to be evaluated in randomized trials
Routine use of antipsychotics, statins, or dexmedetomidine to treat delirium NOT recommended 6 RCTs evaluated for guideline recommendation Haloperidol (n=2), atypical antipsychotics (quetiapine, n=1; ziprasidone, n=1; olanzapine, n=1), and a statin (rosuvastatin, n=1) These agents NOT associated with shorter duration of delirium, reduced duration of mechanical ventilation or ICU LOS, or decreased mortality Open label antipsychotics allowed in each trial for patients experiencing agitation or hallucinationspotential for bias
Typical haloperidol Atypical olanzapine, quetiapine, risperidone, ziprasidone Select patients with delirium may benefit from their use Anxiety, fear, hallucinations, delusions, agitation, danger to themselves or others Use for shortest duration possible Ensure patients are not discharged home on these medications unnecessarily
Prolong QT interval increased risk of arrhythmias Avoid in patients at high risk of torsades de pointes Prolonged QT interval at baseline, known history of torsades de pointes, receiving other medications that can prolong the QT interval Must monitor ECG Barr J, et al. Crit Care Med. 2013;41(1):263 306.
Suggested for use in treating delirium in mechanically ventilated patients experiencing agitation that may be limiting liberation from the ventilator Small increase in ventilator free hours in 1 study Dexmedetomidine median 145 hrs vs 128 hrs in placebo group (median difference between groups: 17 hrs; [95% CI, 4 33.2 hrs; p=0.01]) Panel felt possible benefits from dexmedetomidine outweighed possible undesirable consequences Reade MC, et al. JAMA. 2016;315(14):1460 1468.
Proposed mechanism Anti inflammatory actions of statins may decrease delirium Studies have found inconsistent results Some suggest when statins are stopped during critical illness, delirium incidence increases Recent RCT of cardiac surgery patients found use of perioperative atorvastatin did not affect delirium incidence Not routinely recommended for delirium prophylaxis or treatment Billings IV FT, et al. JAMA. 2016;315(9):877 888. Morandi A, et al. Chest. 2011;140(3):580 585. Page VJ, et al. Am J Respir Crit Care Med. 2014;189(6):666 673.
ICU delirium is associated with long term cognitive impairment and potentially with increased hospital stays Nonpharmacologic options should be implemented for all patients to decrease incidence of delirium and for delirium treatment Pharmacologic treatment options (such as antipsychotics) should be reserved for a select group of patients with agitation and related conditions
A 56 year old male is admitted to the medical ICU for community acquired pneumonia. He is mechanically ventilated. On hospital day #4 he becomes very agitated, begins pulling at his tubes and lines and his RN reports he is CAM +. Which of the following is the best option to treat his delirium? A. Nonpharmacologic therapy only B. Nonpharmacologic therapy + antipsychotic agent C. Antipsychotic agent + statin D. Antipsychotic agent
A 56 year old male is admitted to the medical ICU for community acquired pneumonia. He is mechanically ventilated. On hospital day #4 he becomes very agitated, begins pulling at his tubes and lines and his RN reports he is CAM +. Which of the following is the best option to treat his delirium? A. Nonpharmacologic therapy only B. Nonpharmacologic therapy + antipsychotic agent C. Antipsychotic agent + statin D. Antipsychotic agent
Nonpharmacologic therapy is recommended for use in all patients Antipsychotic agents are not routinely recommended for delirium treatment, but this patient is very agitated and is attempting to dislodge his tubes/lines, therefore he would likely benefit from an antipsychotic agent, but used at the lowest effective dose for the shortest time period Statins are not recommended for routine use for delirium treatment
Barr J, Fraser GL, Puntillo K, et al. Clinical practice guidelines for the management of pain, agitation, and delirium in adult patients in the intensive care unit. Crit Care Med. 2013;41(1):263 306. Bergeron N, Dubois MJ, Dumont M, Dial S, Skrobik Y. Intensive Care Delirium Screening Checklist: evaluation of a new screening tool. Intensive Care Med. 2001;27(5):859 864. Billings IV FT, Hendricks PA, Schildcrout JS, et al. High dose perioperative atorvastatin and acute kidney injury following cardiac surgery. JAMA. 2016;315(9):877 888. Devlin JW, Skrobik Y, Gelinas C, et al. Clinical practice guidelines for the prevention and management of pain, agitation/sedation, delirium, immobility, and sleep disruption in adult patients in the ICU. Crit Care Med. 2018;46(9):e825 e873. Ely EW, et al. Delirium as a predictor of mortality in mechanically ventilated patients in the intensive care unit. JAMA. 2004;291:1753 1762. Ely EW, Margolin R, Francis J, et al. Evaluation of delirium in critically ill patients: validation of the Confusion Assessment Method for the Intensive Care Unit (CAM ICU). Crit Care Med. 2001;29(7):1370 1379.
Neurocognitive Disorders. Diagnostic and Statistical Manual of Mental Disorders. Washington DC: American Psychiatric Publishing; 2013:591 643. Page VJ, Davis D, Zhao XB, et al. Statin use and risk of delirium in the critically ill. Am J Respir Crit Care Med. 2014;189(6):666 673. Reade MC, Eastwood GM, Bellomo R, et al. Effect of dexmedetomidine added to standard care on ventilator free time in patients with agitated delirium: a randomized clinical trial. JAMA. 2016;315(14):1460 1468. Morandi A, Hughes CG, Girard TD, et al. Statins and brain dysfunction: a hypothesis to reduce the burden of cognitive impairment in patients who are critically ill. Chest. 2011;140(3):580 585. Patient Testimonials. Nashville, TN. Vanderbilt University Medical Center. 2013; http://www.icudelirium.org/testimonials.html Salluh JI, Wang H, Schneider EB, et al. Outcome of delirium in critically ill patients: a systematic review and meta analysis. BMJ. 2015;350:h2538.
Sarah V. Cogle, PharmD, BCCCP Assistant Clinical Professor Auburn University Harrison School of Pharmacy Auburn, AL ALSHP Annual Clinical Meeting 2018