Putting the Pieces of the Puzzle Together: A Journey through ABCDEF

Putting the Pieces of the Puzzle Together: A Journey through ABCDEF Kristy Colford RN,BSN, CCRN Clinical Nurse Educator Avera McKennan Intensive Care

Kristy Colford- Have No Disclosures

ZOOM in & ZOOM out A Assess, Prevent, and Manage Pain B Both Spontaneous Awakening Trails and Spontaneous Breathing Trials C Choice of Analgesia and Sedation D Delirium: Assess, Prevent, Manage E Early Mobility and Exercise F Family Engagement and Empowerment Vasilevskis E E Chest 2010;138(5):1224-1233. Davidson J E Am Nurse Today. 2013;8(5):32-38.

Objectives Improve outcomes for patients and families by reliable implementing ABCDEF bundle Reduce length of stay in ICU Reduce time on mechanical ventilator Engaging Families to participate in the care and healing of their love ones Enhancing teamwork through implementation of evidence based team building strategies

Interprofessional Team Definition

Interprofessional Teamwork https://www.youtube.com/watch?v=dvveeokrm48

Improve Patient Comfort, Safety, and Outcomes

Pain Care Bundle Assess Assess pain >4x/shift and PRN Significant pain with NRS >3, BPS >5, or CPOT >2 Treat Treat pain within 30 minutes of detecting significant pain & reassess Non-pharmacological treatment Pharmacological treatment Prevent Administer pre-procedural analgesia and/or non-pharmacological interventions Treat pain first, then sedate Barr J Crit Care Med 2013;41(1):263-306

Pain: Overview Affects majority of ICU patients Patients with diminished communication or cognitive capabilities at risk Reliable and valid pain assessment is foundation for effective pain treatment Choosing the best intervention to treat pain is challenging

Pain Definition Pain is an unpleasant sensory & emotional experience Best reported by person experiencing it Self report is challenging in ICU environment Inability to communicate verbally does not mean individual is not experiencing pain http://www.iasp- pain.org/education/content.aspx?itemnumber=1698&navitemnumber=576 (IASP in Pain 1979;6:249-252) (IASP in Pain 1979;6:249-252)

Self-Report of Pain- Gold Standard 0-10 Numeric Rating Scales 0-10 visually enlarged horizontal NRS most valid & reliable Chanques G Pain 2010;151: 711-721.

Behavioral Pain Scales The Critical Care Pain Observation Tool (CPOT) & the Behavioral Pain Scale (BPS) are the most valid scales for monitoring pain in medical, postoperative, and trauma (except for brain injury) patients unable to self-report in whom motor function is intact & in whom behaviors are observable Barr J Crit Care Med 2013; 41: 263-306

Can t Rely on Vital Signs for Pain Assessment Vital signs should not be used alone to assess pain (-2C). (are not valid pain indicators) Vital signs may be used as a cue to begin further assessment of pain (+2C). Gelinas C, Clin J Pain 2007; 23:497-505 Barr J, Crit Care Med 2013;41(1):263-306 Payen JF Crit Care Med 2001;29: 2258-2263.

The Family can help to identify pain behaviors

Proxy Report of Symptoms Symptom Patient-Family Patient-RN Patient-MD Pain 0.43 0.29 0.40 Tiredness 0.27 0.24 0.52 SOB 0.48 0.18 0.36 Restlessness 0.41 0.15 0.07 Anxiety 0.45 0.22 0.21 Sadness 0.35-0.01 0.04 Hunger 0.23 0.24-0.14 Fear 0.46 0.18 0.05 Thirst 0.29 0.25 0.33 Confusion 0.28 0.32 0.29 Intraclass correlation coefficients.( Hemphill JF. Am Psychol 2003; 58:78 79) Puntillo K Crit Care Med 2012; 40(10): 2760-2767.

Assume Pain is Present When patient unable to use self-report or exhibit behaviors can Assume Pain is Present For example, in patients: Receiving NMBAs That are unresponsive but underlying pathology thought to be painful Undergoing activities/procedures know to be painful

Goal of ICU Sedation Calm Comfortable Cooperative Reduce anxiety and agitation Facilitate mechanical ventilation Decrease traumatic memory of ICU stay and procedures

Negative Consequences of Prolonged, Deep Sedation/Benefits of Light Sedation Deep sedation Reduced six-month survival Hospital mortality Longer duration of mechanical ventilation Longer ICU length of stay Increased physiologic stress in terms of elevated catecholamine concentrations and/or increased oxygen consumption at lighter sedation levels BUT no clear relationship between elevation and clinical outcomes Brook A. Crit Care Med. 1999;27:2609-15. Girard T. Lancet. 2008;371:126-34. Kress J. N Engl J Med. 2000;342:1471-7. Treggiari M. Crit Care Med. 2009;37:2527-34.

Mental Health After Light or Deep Sedation 137 adults requiring mechanical ventilation-rct Sedation with midazolam Light: Ramsay 1-2, intermittent injection Deep: Ramsay 3-4, continuous infusion Results Primary endpoints (4 weeks after ICU discharge) Trend toward more PTSD symptoms with deep sedation (P=0.07) More trouble remembering the event (P=0.02) More disturbing memories of the ICU (P=0.05) No difference in anxiety or depression scores Other endpoints: light sedation patients averaged 1 day shorter on mechanical ventilation (P = 0.03) 1.5 days shorter length of stay (P = 0.03) Treggiari M. Crit Care Med. 2009;37:2527-34.

Daily Sedation Interruption Decreases Duration of Mechanical Ventilation Hold sedation infusion until patient awake, then restart at 50% of prior dose Awake defined as any 3 of the following: Open eyes in response to voice Use eyes to follow investigator on request Squeeze hand on request Stick out tongue on request Needham D. Crit Care Med. 2012;40:502-9.

PAD Agitation/Sedation Assessment Recommendations Depth and quality of sedation should be routinely assessed in all ICU patients (1B) The RASS & SASS are the most valid and reliable scales for assessing quality and depth of sedation in ICU patients (B) Suggest using objective measures of brain function to adjunctively monitor sedation in patients receiving neuromuscular blocking agents (2B) Use EEG monitoring either to monitor nonconvulsive seizure activity in ICU patients at risk for seizures, or to titrate electrosuppressive medication to achieve burst suppression in ICU patients with elevated intracranial pressure (1A) Barr J. Crit Care Med. 2013;41:263 306.

PAD Depth of Sedation Statements Maintaining light levels of sedation in adult ICU patients is associated with improved clinical outcomes, e.g., shorter duration of mechanical ventilation and shorter ICU lengths of stay (LOS) (B). Maintaining light levels of sedation increases the physiologic stress response, but is not associated with an increased incidence of myocardial ischemia (B). The association between depth of sedation and psychological stress in these patients remains unclear (C). Barr. Crit Care Med. 2013;41:263 306.

Wake Up and Breath Protocol http://www.mc.vanderbilt.edu/icudelirium/docs/wakeupandbreathe.pdf. January 2013.

Things to Consider: Barriers Concern by staff Workload and productivity concerns Fear of patient discomfort and asynchrony Fear of inadvertent extubation Fear of self-extubation during decreased sedation Excuses: Let s just give it one more day. It s late in the day, and we don t have coverage tonight. Ostermann M. JAMA. 2000;283:1451-9. Guttormson J. Intensive Crit Care Nurs. 2010;26:44-50. Tanios M. J Crit Care. 2009;24:66-73.

All ICU patients should be routinely assessed for: Pain (Likert self-report, or BPS/CPOT non-self-report) Agitation/depth of sedation (RASS/SAS) Delirium (CAM-ICU/ICDSC) Important factors influence the choice and dose of analgesia and sedative medications Non-pharmacologic strategies play an important role when managing pain and agitation Barr J. Crit Care Med. 2013;41:263-306.

Use of opioids: IV opioids should be considered first-line analgesics for the treatment of non-neuropathic pain. (+1C) All IV opioids are equally effective when titrated to similar pain scores. (C) Use of non-opioid analgesics: Non-opioid analgesics should be considered to decrease the amount of opioids administered and to decrease opioid-induced adverse effects. (+2C) Barr J. Crit Care Med. 2013;41:263-306.

Use of both opioid and non-opioid analgesics: For invasive and potentially painful procedures, analgesics with or without non-pharmacologic therapy may be administered pre-procedurally. (+2C) Recommended prior to chest tube removal. (+1C) For neuropathic pain, enterally administered gabapentin or carbamazepine should be considered, in addition to IV opioids. (+1A) Barr J. Crit Care Med. 2013;41:263-306.

Avoid deep sedation/coma: Sedative medications should be titrated to maintain lighter levels of sedation, unless clinically contraindicated. (+1B) Use daily awakening or a titrated sedation strategy to maintain patient wakefulness. (1B) Choice of sedative: Non-benzodiazepines may be preferred over benzodiazepines to improve clinical outcomes in mechanically ventilated ICU patients. (+2B) Reduction in sedation requirements: Use of an analgesia-first (i.e., analogsedation) strategy is recommended in mechanically ventilated patients. (+ 2B) Barr J. Crit Care Med. 2013;41:263-306.

Analgo-Sedation Strategies Addressing pain and discomfort first before administering sedatives. Utilization of one drug for two purposes: Pain relief and sedation Usually accomplished with an opioid.

Analgo-Sedation Benefits Limitations Reduces pain and discomfort, which are common causes of agitation Avoids potential sedative-related adverse events: Delirium Hemodynamic instability Metabolic acidosis (lorazepam) Immunomodulation Death (PRIS) May interfere with respiratory drive, gastric motility, nutrition Potential for opioid withdrawal ICU LOS, ventilator time, delirium, VAP, mortality, and cost of care are not consistently reduced Rigorously evaluated only in European ICUs Devabhakthuni S. Ann Pharmacother. 2012;46:530-40.

MENDS Trial: Dexmedetomidine versus Lorazepam Sedation Study Design: Double-blind, randomized, controlled trial of mechanically ventilated medical and surgical ICU patients (N = 106) Results: Dexmedetomidine sedation: more days alive without delirium or coma than with lorazepam (P = 0.01) lower prevalence of coma (P < 0.001) than with lorazepam (P = 0.01) more time spent within sedation goals than with lorazepam (P = 0.04) No differences in 28-day mortality and delirium-free days Incidence of bradycardia and hypotension were similar Pandharipande P. JAMA. 2007;298:2644-53.

SEDCOM Trial: Dexmedetomidine vs Midazolam Sedation Study Design: Double-blind, randomized, multicenter trial comparing longterm (> 24 hr) dexmedetomidine (n = 244) with midazolam (n = 122) Results: No difference between groups in percentage of time patients were in targeted sedation range (P = 0.18) Lower delirium prevalence in the dexmedetomidine group (P 0.001) Shorter sedation duration in the dexmedetomidine group (P = 0.01) Shorter time to extubation in the dexmedetomidine group (P = 0.01) Riker R. JAMA. 2009;301:489-9.

Associated but Nondiagnostic Symptoms of ICU Delirium Hallucinations, delusions Abnormal psychometric activity (e.g., agitation, lethargy) Emotional disturbances (e.g., fear, anger, depression, apathy) Sleep disturbances

Delirium: Epidemiology and Short- Term Outcomes Prevalence 50% to 80% of mechanically ventilated patients 20% to 50% of lower severity patients Associated outcomes Prolonged hospitalization Increased mortality Increased cost Ely E JAMA. 2001;286:2703-2710. Dubois M. Intensive Care Med. 2001;27:1297-1304. Ely E JAMA. 2003;289:2983-2991. Ely E JAMA. 2004;291:1753-1762. Thomason JW. Crit Care. 2005;9:R375-81. Milbrandt EB Crit Care Med. 2004; 32:955-962

Delirium: Long-Term Outcomes Mortality Each day of delirium in the ICU increases the hazard of 1- year mortality by 10% 1 Cognitive Impairment ICU delirium is an independent risk factor for long-term cognitive impairment 2,3 34% with scores similar to traumatic brain injury 24% with scores similar to Alzheimer disease Pisani MA Am J Respir Crit Care Med. 2009;180:1092-1097. Girard T Crit Care Med.2010;38:1513-1520. Pandharipande PP N Engl J Med. 2013;369(14):1306-1316.

PAD Delirium Assessment Recommendations Routinely monitor for delirium in all adult ICU patients (+1B) Use either: Confusion Assessment Method for ICU (CAM-ICU) Intensive Care Delirium Screening Checklist (ICDSC) Barr J Crit Care Med. 2013;41:263-306.

Intensive Care Delirium Screening Checklist (ICDSC) 1. Altered level of consciousness 2. Inattention 3. Disorientation 4. Hallucination, delusion, or psychosis 5. Psychomotor agitation or retardation 6. Inappropriate speech or mood 7. Sleep/wake cycle disturbances 8. Symptom fluctuation Figure: www.icudelirium.org Gusmao-Flores D. Crit Care. 2012;16:R115-R125

Anticipating Delirium: Risk Factors Baseline Vulnerability Precipitants Underlying brain disease (dementia, stroke, Parkinson) Increased age Institutionalization Chronic disease (HIV, HTN, ETOH dependency, diabetes, etc.) Visual/hearing deficits Medications Infection Dehydration Immobility/restraints Malnutrition Tubes/catheters Electrolyte imbalance Sleep deprivation

Interventions for Delirium Early mobility and rehabilitation Sleep enhancement (via nonpharm and hygiene) Reducing unnecessary and deliriogenic medications Structured reorientation Adequate oxygenation American Geriatric Society 2014 Guidelines. J Am Geriat Soc. 2016;63(1):142-150. Inouye SK N Engl J Med. 1999;340(9):669-676. McNamara L. Am J Crit Care. 2008;17:576.

Interventions for Delirium Pain management Constipation relief Nutrition and fluid repletion Sensory assistive devices (vision and hearing) Cognitive stimulation/rehabilitation American Geriatric Society 2014 Guidelines. J Am Geriat Soc. 2016;63(1):142-150. Inouye SK N Engl J Med. 1999;340(9):669-676. McNamara L. Am J Crit Care. 2008;17:576.

Early Exercise Patient s functional performance improved Independent functional status at hospital discharge: intervention 59% vs. control 35% Shorter duration of MV Substantial reduction in duration of delirium 2 vs. 4 days Schweickert WD Lancet. 2009;373:1874-1882

Delirium and Sleep in the ICU Sleep and delirium Sleep disruption is a manifestation of delirium Sleep deprivation yields delirium Sleep deprivation and fragmentation commonly occur Etiologies: Loss of night-day cues, constant environmental stimuli Pain, sedatives, MV, stress ICU sleep hygiene programs Decrease both incidence and duration of delirium in patients Nighttime sedation does not promote sleep Alway AE Am J Crit Care. 2013;22(4):357-360. Van Rompaey B Crit Care. 2012;16(3):R73. Kamdar BB Anaesthesia. 2014;69(6):527-531. Patel J Anaesthesia. 2014;69(6):540-549.

ICU Environment, Sleep, and Delirium Daytime Interventions Blinds raised Less than 50% of the day napping Avoid caffeine after 3 PM Nighttime Interventions Before 10 PM Room lights dimmed Room curtain closed Warm bath Unnecessary alarms prevented Room temperature optimized Pain appropriately controlled Television off Result: No difference in perceived sleep quality, but Reductions in delirium/coma incidence (49% vs. 69%) Improved daily noise rating Kamdar BB Crit Care Med. 2014; 41(3):800-809.

Reorienting ICU Patients Before-after observations in 214 ICU patients Interventions: Night environment, music therapy, visual cues (clock) Reorientation with 5 W s and 1 H Who? Who are you? Who is the nurse/physician? What? What happened? Where? Where are you/we? Why? Why did it happen? How? How did it happen? And what is the illness progression? Result: Delirium incidence reduction Pre 35% vs. post 22% Colombo R Minerva Anestesiol. 2012;78:1026-1033.

Helpful Approach to Delirium Management Stop THINK Lastly medicate

Reducing Unnecessary STOP: especially consider sedatives Is your patient on the minimal amount necessary? Review medications Medications Doses adjusted for elderly, renal failure, liver failure Do you have a plan to reduce drug exposure? Spontaneous awakening trial Nurse empowerment to titrate drug to a teamdetermined target level of arousal

What to THINK if positive for delirium Toxic Situations Congestive heart failure, shock, dehydration Deliriogenic medications (tight titration) New organ failure (liver, kidney, etc.) Hypoxemia Infection/sepsis (nosocomial), Immobilization Nonpharmacological interventions K+ or electrolyte problems

Reducing ICU Delirium Treat pain first! Promote consciousness! Prevent delirium Wean MV Increase mobility Increase patient participation Promote patient recovery Reduce complications Improve patient outcomes Collinsworth AW J Intensive Care Med. 2014 Oct 27

Did the Patient Achieve his or her Maximal Mobility Activity Today? YES Mobility is everyone s job! RN, PT, OT, etc. Communicate patient s current mobility status to all ICU team members Encourage patients to perform active movements if possible

Did Our Patient Achieve his or her Maximal Mobility Activity Today? NO! Why not? Was the patient walking before admission? Is the patient hemodynamically stable? Is the patient awake?

Side Effects of Bed Rest Muscle strength in a healthy person can decrease 1.3% to 3% for every day spent on bedrest.1 Effects are more profound in older people and in those with critical illness.2 A new study suggests that 3% to 11% strength loss occurs for every day in bed in an ICU setting.3 Age and days on bedrest are independent predictors of worsening function. Topp R. Am J Crit Care. Clin Issues 2002. Yende S. Thorax. 2006. Fan E. Am JRespir Crit Care Med. 2014;190:1437-46.

Evidence-Based Benefits of Early Progressive Mobility Decrease ICU and hospital LOS Improve overall physical functioning Decrease duration of mechanical ventilation Decrease incidence of delirium Bailey P. Crit Care Med. 2007;35:139-45. Morris P. Crit Care Med. 2008 Aug;36:2238-43. Schweickert W. Lancet. 2009;373:1874-82.

Early Progressive Mobility in ICU In-bed mobility Passive range-of-motion exercises Turning side to side Sitting on the side of the bed Active strengthening exercises Out-of-bed mobility Standing at bedside Sitting on a regular chair Sitting on a cardiac chair Walking MOBILITY IS EVERYONE S JOB IN THE INTENSIVE CARE UNIT!

Considerations Before Mobilizing Patients in ICU Neurologic: Level of alertness Cardiac: Hemodynamic stability Vasoactive medications Pulmonary: Ventilation/oxygenation needs Risk vs. benefit Guidelines vs. Protocols Fewer absolute contraindications Importance of interdisciplinary collaboration

Perceived Barriers to Progressive Early Mobility Severity of disease Severity of weakness Premorbid level of function ICU culture that promotes bed rest Nutritional state Sleep deprivation Level of delirium Pain Obesity

Absolute Contraindications to Progressive Mobility in ICU Patients on neuromuscular blockade Hemodynamic instability requiring escalating dose or multiple vasopressors Significant oxygenation dysfunction requiring high level of oxygen Unstable fractures Cerebral edema with uncontrolled intracranial pressure Active bleeding Intra-aortic balloon pump on femoral artery Pacer dependent with transvenous temporary pacemaker ECMO with femoral cannulation Femoral arterial sheath Open chest/open abdomen

Characteristics of Patient and Keep ICU patients and families: Informed Family-Centered Care Actively involved in decision-making Actively involved in self management Provide physical comfort /emotional support to patient and families. Maintain clear understanding of patients and families concepts of illness and cultural beliefs. Institute of Medicine. Crossing the Quality Chasm. 2001.

Myths and Misconceptions Family presence interferes with care. Family presence exhausts the patient. Family presence is a burden to families. Family presence spreads infection. Institute for Patient and Family Centered Care http://www.ipfcc.org

Creating the Right Environment Family presence Family and patient engagement Family and patient empowerment

Let s Open the Door Today: Resistance is from healthcare workers! Why? Fear of consequences and failure to understand the importance of families. Family presence at the beside is seen as a privilege, not as a necessary component of the patient s care. Burchardi, H. Intensive Care Med. 2002:28;1371-2. Riccioni L. Trends Anesth and CC. 2014: 4; 182-185.

ICU Flexible Visitation: Patient Decreases: anxiety, confusion, agitation CV complications ICU length of stay Increases: feelings of security patient satisfaction quality and safety Benefits Bell L. AACN practice alert. Nov 2011. Davidson J. Crit Care Med. 2007;35:605-22

Inviting Families and Patients to Engage in Care Focus on activities that actively involve families in the patient s care. Be sensitive - address questions and concerns. Facilitate communication - cultural/spiritual needs. understanding of Develop strategies for family engagement; provide education and role modeling.

How to Engage Family Members Provide brochures-ways that family members can help the patient: Speak softly to patients and use simple words. Re-orient the patient (5 W s + 1H). Talk about family and friends. Bring patient s sensory aides (eyeglasses, hearing aids). Decorate the room with reminders of home. Participate in mobilizing the patient. Document the patient s stay in an ICU diary.

ICU Diaries ICU diaries decrease the incidence of PTSD after an ICU stay. Diary contents: Calendar of events and/or milestones. Photographs, both of the patient and the ICU. Entries from staff and/or family. Utilize preprinted templates or websites Great resource: http://www.icu-diary.org

Family Participation on Rounds Who should participate? Decision makers Patients, whenever possible Invite them to join rounds. Provide an opportunity to ask questions, clarify. Ask them, Do you have any additional concerns? Participation fosters: Bi-directional communication Shared decision-making Davidson J. Crit Care Med. 2007;35:605-22. Cypress B. Dimens Crit Care Nurs. 2012;31:53-64.

Empowering Family Members Family members = patients primary advocates. Provide them the tools and permission to speak up! Create a safe environment to speak openly. Create a culture where it is acceptable for our actions to be questioned. Three key areas: Shared decision-making Safety Future care expectations

Melissa and Doug s Story: Recommendations for Others http://www.icudelirium.org/testimonials.html

Reference: Puntillo K. Am J Crit Care 2001;10:238-251 (Response Procedural Pain) Payen J. Crit Care Med 2001;29:2258-2263 (Behavioral Pain Scale) Gelinas C. Am J Crit Care 2006;15: 420-27 (CPOT Validation) Payen J. Anesthesiology 2009; 111: 1308-16 (Behavioral Pain Scale)Chanques G. Crit Care Med 2010;151: 711-721(Pain Assessment in ICU)Gelinas C. Int J Nursing Stud 2011;48:1495 1504 (Overcoming Barriers to Pain Assessment) Puntillo K. Crit Care Med 2012;40: 2760-2767 (Proxy Pain Reports) Puntillo K. Am J Respir Crit Care Med 2014; 89: 39-47 (New Insights ICU Pain Control) Treggiari M. (Light Sedation) Crit Care Med. 2009;37:2527-34. Pandharipande P. (Lorazepam Predicts Delirium) Anesthesiology. 2006;104:21-6. Seymour C. (Diurnal Sedation and Liberation) Crit Care Med. 2012;40:2788-96. Hager D. (Reducing Deep Sedation ALI) Crit Care Med. 2013;41:1435-42. Shehabi Y. (Goal-Directed Sedation) Crit Care Med. 2013;41:1983-91. Shehabi Y. (Mortality attributed to Delirium) Intensive Care Med. 2013;39:910-8. Tanaka L. (Early Oversedation Outcomes) Crit Care. 2014;18:R156. Burry L. (High Versus Low Sedation Outcomes) Can J Anaesth. 2014;61:619-30. Minhas MA. (Protocolized Sedation) Mayo Clin Proc. 2015;90:613-23. Balzer F. (Early Deep Sedation decrease 2 year survival) Crit Care. 2015;19:197.

Reference Ely E. (SBTs) N Engl J Med. 1996;335:1864-9. Riker R. (SAS) Crit Care Med. 1999; 27:1325-9. Kress J. (SATs) N Engl J Med. 2000;342:1471-7. Sessler C. (RASS) Am J Respir Crit Care Med. 2002, 166:1338-44.Ely E. (RASS) JAMA. 2003;289:2983-91. Girard T. (ABC Study) Lancet. 2008;371:126-34. Strøm T. (No Sedation) Lancet. 2010;375:475-80. Shehabi Y. (Deep Sedation) Am J Respir Crit Care Med. 2012;186:724-31. Balas M. (ABCDE) Crit Care Med. 2013;42:1024-36. Bassett R. (IHI ABCDE Collaborative) Jt Comm J Qual Patient Saf. 2015;41:62-74. Klompas M. (CDC ABCDE Collaborative) Am J Respir Crit Care Med. 2015;191:292-301. Carson S. (Loraz. vs. Propofol DSI) Crit Care Med. 2006;34:1326-32. Pandharipande P. (Loraz.-delir. risk factor) Anesthesiology. 2006;104:21-6. Pandharipande P. (MENDS Trial) JAMA. 2007;298:2644-53. Riker R. (SEDCOM Trial) JAMA. 2009;301:489-9. Treggiari M. (Light vs. Deep Sedation-MH) Crit Care Med. 2009;37:2527-34. Pandharipande P. (MENDS-Outcomes) Crit Care. 2010;14:R38. Strøm T. (No Sedation Protocol) Lancet. 2010;375:475-80. Needham D. (EM-ICU outcomes) Arch Phys Med Rehabil. 2010; 91:536-42. Jakob S. (MIDEX and PRODEX Trials) JAMA. 2012;307:1151-60. Fraser G. (MA-Bnz vs. Non-bnz vs. outcomes) Crit Care Med. 2013; 41:S30-8. Dale C. (PAD protocol vs. outcomes) Ann Am Thorac Soc. 2014;11:367-74.