SATs and SBTs: of Guidelines & Implementation CUSP4MVP-VAP SATs and SBTs: of Guidelines & Implementation E. Wesley Ely, MD, MPH Professor of Medicine Vanderbilt University, Nashville, TN VA TN Valley Health Care System GRECC

Disclosures: ICU Physician Vanderbilt - Abbott, Hospira, Orion - NIH and VA U.S. Federal Funding - Author of PAD Guidelines of SCCM 2013 - Chair of SCCM Delirium section for PAD - Co-Chair of SCCM ICU Liberation project to aid world- wide implementation

Pain Agitation Delirium Barr J, et al. Crit Care Med. 2013;41:263-306.

Barr J et al, CCM 2013;41:263-306

New guidelines emphasize individual symptom management OLD (2002) Clinical Practice Guidelines for the sustained use of sedatives and analgesics in the critically ill adult Jacobi, CCM 2002 New (2013) Clinical Practice Guidelines for the management of Pain, Agitation, and Delirium in adult patients in the Intensive Care Unit Barr, CCM 2013

Take Home Message

50-70% Cognitively Impaired © rustyrhodes via Flickr Wolters Intensive Care Med 2013; 39: 376 Jackson AJRCCM 2010; 182: 183 Girard Crit Care Med 2010; 38: 1513

Functionally Impaired 60-80% Functionally Impaired Marcel Oosterwijk via Flickr Latronico Lancet Neurol 2011; 10: 931

ICU Survivorship Family Hobbies Work Iwashyna Annals of Int Med 2010; 153:204-5

“ ...like it was in a huge, empty gray space, sort of like a monstrous underground parking garage with no cars, only me, floating or seeming to float, on something… -SB “The time I spent seems like it was in a huge, empty gray space, sort of like a monstrous underground parking garage with no cars, only me, floating or seeming to float, on something. Every once in a while I would get to an edge of something horrible and once I remember I thought, "if I just let go, then this horror will be over.”” © Travis Smith via Flickr

Cognitive Impairment: Sepsis 25 Before Sepsis After Sepsis p<0.001 20 Mild Cognitive Impairment Moderate/Severe Cog Impairment 15 % survivors cognitively impaired 10 Prospective cohort study of patients enrolled in the health and retirement study, an ongoing cohort of 27,000 community dwelling americans >50 years old. Every two years patients are assessed with good follow-up rates north of 90%. The GRAND IDEA put forth by this paper of ours was that there is a tripling of risk post sepsis (the main admission criteria for ICU patients) of moderate to severe cognitive impairment. That is, a HUGE increase in Demential like illness post ICU, and if delirium is the main risk factor for this, then modifying delirium could have a huge impact on a rising population of demented Americans. 1520 episodes of sepsis in 1194 patients over the 7 year study period 84% had normal cognition at baseline; 7.8% were mildly imparied and 8.7% were moderate/severely impaired This modeling used in this study used within-person variation over time in cognitive function to estimate the impact of severe sepsis and to control for characteristics that did not change over time--in effect the patients served as their on controls over time. Thus, in the LR analysis, patients who developed severe sepsis were at 3.5 (1.78-7.09) times the risk of developing moderate to severe cognitive impariment vs. those non-septic patients. Severe sepsis was highly associated with progression to moderate/severe CI (OR 3.55; CI 1.78-7.09) Patients NOT mechanically ventilated had a 4.4x great odds for developing moderate to severe CI after SS (CI 1.95-9.99) 5 -3 years -1 year +1 year + 3 years Iwashyna T, JAMA 2010;304:1787-1794

Ely EW, JAMA 2004;291:1753-62

Delirium Duration & Mortality 4 0 vs 1 HR 1.7 1.27-2.29 <0.001 0 vs 2 HR 2.69 1.58-4.57 0 vs 3 HR 3.73 1.92-7.23 p<.001 3 Relative Hazard of Death 2 1 NOTES: Crossing CI of HR from Cox regression happens based on a mathematical formula of Cox regression. Cox regression does not have an intercept in its equation, and lacking intercept does not provide a reference category when CI is shown graphically. For this reason, when a graph is drown, we need to pick an arbitral reference category where CI crosses on X axis, and typical default for this is to use median value of X. For example, HR is set to 1 at the median value (eg delirium duration =2 days), and HR shows relative increase or decrease from HR=1 (delirium duration = 2 days) when showing effect at non-median values. Table 3. Multivariable analysis of cumulative number of delirium days Number of Delirium Days (p .001, Overall) 30–Day Mortality (p .02, Nonlinear Effect)a Remaining Intubated (p .001, Overall) Remaining in Intensive Care Unit (p .02, Overall) HR 95% CI p HR 95% CI p HR 95% CI p 0 vs. 1 day 1.70 1.27–2.29 .001 1.80 1.27–2.55 .001 1.21 1.00–1.47 .05 0 vs. 2 days 2.69 1.58–4.57 .001 2.82 1.67–4.77 .001 1.43 1.02–2.01 .04 0 vs. 3 days 3.73 1.92–7.23 .001 3.88 2.13–7.03 .001 1.61 1.08–2.41 .02 HR, hazard ratio; CI, confidence interval. 1 2 3 4 5 6 Days of Delirium Shehabi Y, et al. CCM 2010; 38:2311–2318

NEJM 2013;369:1306-16 Editorial by M. Herridge

Delirium and Brain Atrophy Figure 2. Representative example of lateral ventricle size in 46-yr-old female and 42-yr-old female intensive care unit (ICU) survivors with no preexisting cognitive impairment: Axial T1-weighted brain images in two ICU survivors. A, Relatively normal ventricular volume (see arrow) in a 46-yr-old female who did not experience delirium in the ICU. Patient had a history of respiratory and heart failure. She was admitted to a medical ICU due to acute respiratory distress syndrome and was subsequently intubated and managed through the ICU without ever developing delirium. B, Enlarged ventricles (see arrow) in a 42-yr-old female who did develop delirium in the ICU. Patient was admitted to the hospital after reporting fever and dyspnea with a chest radiograph and other laboratory data confirming community acquired pneumonia and acute respiratory distress syndrome. The patient was admitted to the ICU and mechanically ventilated, experiencing 12 days of delirium and then resolution. There was no preexisting history of neurological impairment, and surrogate questioning for preexisting cognitive impairment was also negative. (A) 46 year old, no delirium (B) 42 year old, 12 days of delirium Gunther M et al. CCM 2012;40:2022-32

The Picture of Dementia Following ICU Care

Global Cognitive Scores by Age

Global Cognitive Scores by Age and Comorbidity

Primum non Nocere. - Hippocratic Oath Primum non Nocere - Hippocratic Oath - First do no harm “Nothing to Fear but Fear Itself” - FDR inauguration, 1933 - Overcome Fear of ICU Culture Change

So let’s focus on potentially modifiable aspects of care such as potent medications, delirium, and improving care and clinical outcomes…

Building blocks of managing Pain, Agitation & Delirium ABCDEs: Building blocks of managing Pain, Agitation & Delirium E D C B A

Awake and Breathing Coordination Duration of mechanical ventilation Duration of coma Mortality Choose light sedation & avoid benzos Duration of mechanical ventilation Mortality Delirium Delirium monitoring & management  Delirium detection Early Mobility & Environment Duration of delirium Disability ICU Length of Stay Rehospitalization/Mortality Morandi et al Curr Opin Crit Care 2011;17:43-9 Vasilevskis et al Crit Care Med 2010;38:S683-91 Vasilevskis et al Chest 2010;138:1224-1233 Zaal et al, ICM 2013;39:481-88 Colombo et al, Minerva Anest 1012;78:1026-33

Pain, Agitation, and Delirium Are Interrelated Barr J, et al. Crit Care Med. 2013;41:263-306.

“Pain should be routinely monitored in all adult ICU patients” 2013 PAD Guidelines: “Pain should be routinely monitored in all adult ICU patients” Grade 1B Recommendation Crit Care Med. 2013;41:263-308

Pain, Agitation, and Delirium Are Interrelated Barr J, et al. Crit Care Med. 2013;41:263-306.

Targeted Level of Consciousness Choose Target RASS Assess Actual RASS Modify treatment so Actual = Target

Grade 1B Recommendation 2013 PAD Guidelines: “We recommend either daily sedation interruption or a light level of target sedation be routinely used…” Grade 1B Recommendation Crit Care Med. 2013;41:263-308

Grade 1B Recommendation 2013 PAD Guidelines: “We recommend that sedative medications be titrated to maintain a light* rather than deep level of sedation” Grade 1B Recommendation *Light sedation = RASS 0 to -2 Crit Care Med. 2013;41:263-308

Awake and Breathing Coordination Duration of mechanical ventilation Duration of coma Mortality Choose light sedation & avoid benzos Duration of mechanical ventilation Mortality Delirium Delirium monitoring & management  Delirium detection Early Mobility & Environment Duration of delirium Disability ICU Length of Stay Rehospitalization/Mortality Morandi et al Curr Opin Crit Care 2011;17:43-9 Vasilevskis et al Crit Care Med 2010;38:S683-91 Vasilevskis et al Chest 2010;138:1224-1233 Zaal et al, ICM 2013;39:481-88 Colombo et al, Minerva Anest 1012;78:1026-33

2 days Liberating from Ventilator SBT reduced weaning time by = 100 80 p<.001 60 Patients on Ventilator (%) 40 Control (n =151) 20 Protocol (n =149) 30 20 10 15 5 25 Time (Days) Ely EW, et al. N Engl J Med 1996;335:1864-9

2 days Liberating from Sedation SAT reduced ventilator time by = 100 80 60 Patients on Ventilator (%) 40 Control (n=60) Adjusted p<.001 20 Protocol (n=68) 5 10 15 20 25 30 Time (Days) Kress JP, et al. N Engl J Med 2000;342:1471-7

SAT + SBT = 4 day shorter ICU/hosp LOS

ABC Trial: One-Year Survival 100 NNT=7 80 ABC approach (n=167) 60 Patients Alive (%) 40 Control (n=168) 20 p=.01 60 120 180 240 300 360 Days Girard TD, et al. Lancet 2008;371:126-34

Sedation Interruption in SLEAP Mehta S, JAMA 2012;308:1985-92

Benzodiazepine Use in Trials * Study Control Treatment Kress NEJM 2000 90 mg/day 53 mg/day Girard ABC Lancet 2007 84 mg/day 54 mg/day Mehta SLEAP JAMA 2012 82 mg/day 102 mg/day OSCILLATE NEJM 2013 141 mg/day 199 mg/day * All values converted and expressed as mean midazolam dose per patient, median for ABC study were 8 mg and 5 mg, respectively

SPICE Study – first 48 hours mean 50 mg/d benzos Pratik wrote: I just read the Shehabi SPICE study (AJRCCM 2012) showing early deep sedation is associated with mortality (apart from delayed extubation) in detail and recommend it as reading for those who have not. Its got some neat data about sedation practices (albeit in Australia/NZ) that still supports low implementation of targeted sedation and of SATs (20% in Australia). There are also some nice descriptive data about prevalence of delirium over time. In this study early deep sedation (first 48 hours) was not associated with delirium. Some of you may be asked about this on the podium one day so I thought I’d share a few thoughts. Also these delirium results are different from the diurnal sedation paper we just published in CCM (Seymour et al.) but they are answering different questions tham we did. 1.       They defined deep sedation of RASS -3 to -5 so its not just coma 2.       Delirium was measured only in patients who were RASS -2 to +1. So some cases Im sure got missed at -3 and then in the more positive range of the RASS 3.       All sedatives were lumped together in the delirium analysis since they chose the risk factor of deep sedation irrespective of how you got there. They did separate out the sedatives for the liberation from MV outcome and found that midazolam but not propofol was associated with the outcome. 4.       There may have been some missing delirium assessments even in the RASS -2 to +1 range- perhaps those were the aberrant UTAs that show up which almost always tend to be CAM positive. They clearly mention the number of missing values on day 1 on the study but not during the outcome phase. Pratik Shehabi AJRCCM 2012;186:724-31

Awake and Breathing Coordination Duration of mechanical ventilation Duration of coma Mortality Choose light sedation & avoid benzos Duration of mechanical ventilation Mortality Delirium Delirium monitoring & management  Delirium detection Early Mobility & Environment Duration of delirium Disability ICU Length of Stay Rehospitalization/Mortality Morandi et al Curr Opin Crit Care 2011;17:43-9 Vasilevskis et al Crit Care Med 2010;38:S683-91 Vasilevskis et al Chest 2010;138:1224-1233 Zaal et al, ICM 2013;39:481-88 Colombo et al, Minerva Anest 1012;78:1026-33

No Sedation: ICU Length of Stay 100 80 Control (n=58) 60 Patients Remaining in ICU (%) 40 Intervention (n=55) 20 9.7 days ICU stay reduced by 7 14 21 28 Days Strom T, et al. Lancet 2010;375:475-80

Grade 2B Recommendation 2013 PAD Guidelines: “We suggest that sedation strategies using non-benzodiazepines (propofol or dexmedetomidine) may be preferred over sedation with benzodiazepines (midazolam or lorazepam)” Grade 2B Recommendation Crit Care Med. 2013;41:263-308

Pain, Agitation, and Delirium Are Interrelated Barr J, et al. Crit Care Med. 2013;41:263-306.

Awake and Breathing Coordination Duration of mechanical ventilation Duration of coma Mortality Choose light sedation & avoid benzos Duration of mechanical ventilation Mortality Delirium Delirium monitoring & management  Delirium detection Early Mobility & Environment Duration of delirium Disability ICU Length of Stay Rehospitalization/Mortality Morandi et al Curr Opin Crit Care 2011;17:43-9 Vasilevskis et al Crit Care Med 2010;38:S683-91 Vasilevskis et al Chest 2010;138:1224-1233 Zaal et al, ICM 2013;39:481-88 Colombo et al, Minerva Anest 1012;78:1026-33

Cardinal Symptoms of Delirium and Coma Morandi A, et al. Intensive Care Med. 2008;34:1907-1915.

“We recommend routine monitoring for delirium in adult ICU patients” 2013 PAD Guidelines: “We recommend routine monitoring for delirium in adult ICU patients” Grade 1B Recommendation Crit Care Med. 2013;41:263-308

Delirium and Executive Function

If delirium is not screened for using a validated delirium screening tool it is missed ~75% of time. Inouye SK Arch Intern Med. 2001;161:2467-2473. Devlin JW Crit Care Med. 2007;35:2721-2724. Spronk PE Intensive Care Med. 2009;35:1276-1280. van Eijk MM Crit Care Med. 2009;37:1881-1885.

Ely EW, JAMA 2001;286:2703-10

Ely EW, JAMA 2003;289:2983-91 The Miraculous Haul of Fishes, by Henry Tanner, who was the first African American to become a member of the National Academy of Design. This from 1927 confirmed his reputation as the foremost biblical painter of his day. Probably from Luke 5:1-11 (maybe from John’s story, but details make Luke more likely).

Don’t forget about Dr. DRE Diseases Sepsis, COPD, CHF Drug Removal SATs and stopping benzodiazepines/ narcotics Environment Immobilization, sleep and day/night, hearing aids, glasses, noise Medical Intensive Care Unit

Brain Road Map (A framework for bedside rounds) 1. Where is the patient going? Target RASS 2. Where is the patient now? Current RASS Current CAM-ICU © Brian Sloan via Flickr 3. How did they get there? Drugs

Jiro Dreams of Sushi - Tokyo Excellence Aristotle: “We are what we repeatedly do. Excellence is not an act, but a habit” Jiro Dreams of Sushi - Tokyo

Building blocks of managing Pain, Agitation & Delirium ABCDEs: Building blocks of managing Pain, Agitation & Delirium E D C B A

“ “ I survived and that is the main thing. And I am so grateful to God that I survived and am now off all oxygen and consider myself all well except that I can’t remember to take my medications... -SB © Cappi Thompson via Flickr

The ICU Delirium and Cognitive Impairment Study Group at the Loveless Café, Nashville TN

ICU Delirium and Cognitive Impairment Study Group: selected local members Pratik Pandharipande Jim Jackson Jin Han Ed Vasilevskis Chris Hughes Alessandro Morandi Paula Watson Lorraine Ware Gordon Bernard Bob Dittus Ted Speroff Wes Ely Leanne Boehm Joyce Okahashi Cayce Strength Brenda Pun Lauren Hardy Amy Lipsey Ryan Black Jessica McCurley Michael Santoro Carrie Jones Morgan Crawford Mayur Patel Tim Girard John Gore Baxter Rogers Stephan Heckers Cathy Fuchs Heidi Smith Ty Berutti Brad Strohler Elizabeth Card Jennifer Thompson Ayumi Shintani Stephanie Hamilton

Key Epidemiological Points: Patients suffer from long-lasting and disabling aspects of critical illness that demand our attention as a medical community Acquired or accelerated cognitive impairment is a major public health problem following ICU care for both the old and young This cognitive impairment appears most pronounced in domains of executive dysfunction and memory Frontal lobe and hippocampal atrophy are being consistently found in recent studies This injury is likely distinct from or complementary to Alzheimer’s pathology, though we are in our infancy in learning about this entity (e.g., large pathology study under review) Delirium and drug exposure appear to be the most modifiable aspects of care, with need for more trials to delineate next steps

Key Management Points: Establish an overarching protocolized approach to daily ICU patient management using 2013 PAD Guidelines Assess & treat pain first (may be sufficient) If patient remains agitated after adequately treating pain, use prn/bolus sedation initially, if frequent boluses (>3/hr) use continuous sedation Avoid benzodiazepines in most patients Turn off sedation daily and restart only if needed at lowest dose to maintain chosen target level of consciousness Deep sedation (RASS -4/-5) appears harmful; target awake/alert Screen for delirium (CAM-ICU or ICDSC); If delirious, first seek reversible causes and attempt non-pharmacologic management Use the ABCDEs to improve outcomes for your patients

CUSP4MVP-VAP project measures As part of this project, teams will collect and receive reports for metrics to support your improvement efforts. We held calls with your data facilitator. The data collection tool, including instructions are available at: https://armstrongresearch.hopkinsmedicine.org/cusp4mvp/datatools.aspx   Medical Intensive Care Unit

CUSP4MVP Data Collection Sedation and Delirium 1) Percentage of RASS/SAS actual being {-1, 0, 1} or {4, 5} 2) Percentage of achieving RASS/SAS target Distribution of RASS/SAS actual scores 4) Delirium assessment compliance rate 5) Percentage of incorrectly reporting CAM-ICU/ ASE UTA (higher is worse) 6) Percentage of CAM-ICU negative or ASE <=2 (no delirium) Medical Intensive Care Unit

CUSP4MVP Data Collection SAT/SBT (next call on March 18) (1) SAT compliance rate (2) SBT compliance rate (3) SAT contraindication rate (4) SBT contraindication rate (5) Percentage of ventilated patient days without sedation (6) SBT with Seds off compliance rate (7) SAT contraindication distribution plot and table (counts and percentages) (8) SBT contraindication distribution plot and table (counts and percentages) Medical Intensive Care Unit

Your Next Steps: Share your protocols regarding sedation and delirium management; will share with other participating teams Email to CUSP4MVP@jhmi.edu Review data collection requirements and develop plan to collect and submit data. Medical Intensive Care Unit

Reminder: By Content Call, Module 5 (April 1, 2014): Watch the Science of Safety (SOS) Video http://www.ahrq.gov/professionals/education/curriculum- tools/cusptoolkit/videos/04a_scisafety/index.html Develop a method to deliver the SOS Video to your entire unit’s staff Administer the SSA and submit aggregated results to CE Facilitate at least one team meeting

Next Call March 18, 2014 SAT / SBT Dr Mike Klompas