Delirium in Critically Ill Mechanically Ventilated Patients Enrolled in the SLEAP Multicenter Randomized Trial

Transcription

1 Delirium in Critically Ill Mechanically Ventilated Patients Enrolled in the SLEAP Multicenter Randomized Trial Geeta Mehta MD, FRCPC And The SLEAP Investigators For the Canadian Critical Care Trials Group CCCF October 31, 2012

2 Disclosures I have no disclosures Funding: Canadian Institutes of Health Research

3 Background Delirium is common in critically ill patients Delirium is associated with worse outcomes Prolonged durations of MV, and lengths of stay Patient and ICU risk factors Sedation minimization may reduce delirium

4 SLEAP - Sedation Lightening and Evaluation of A Protocol All patients managed with an RN driven analgesia/sedation protocol randomized Daily interruption Sedation/analgesia No daily interruption

5 Eligibility Inclusion criteria 18 years MV and anticipated need for MV 48 hours ICU team has decided to initiate continuous opioid and/or benzodiazepine infusion(s) Exclusion criteria Admission after cardiac arrest Traumatic Brain Injury Receiving Neuromuscular blockers Withdrawal or limitation of life support Previous enrolment in SLEAP Enrolment in confounding trial Lack of informed consent

6 Primary Outcome Duration of MV: from intubation to extubation or tracheostomy mask, for 48 hours Secondary outcomes Delirium Intensive Care Delirium Screening Checklist

7 Both groups Nurse-implemented algorithm for management of analgesia and sedation Analgesia: morphine, fentanyl or hydromorphone Sedation: midazolam or lorazepam Sedation Scale: SAS or RASS Ventilator Weaning protocol

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10 Sedation-agitation scale 7 Dangerous Pulling ET, trying to remove catheters, climbing bed agitation rail, striking staff, thrashing 6 Very agitated Not calm, despite verbal reminding; requires physical restraints, biting ET tube 5 Agitated Mildly agitated, attempting to sit up, calms with verbal instructions 4 Calm and cooperative Calm, awakens easily, follows commands 3 Sedated Difficult to arouse, awakens to verbal stimuli or gentle shaking but drifts off again, follows simple commands 2 Very sedated Arouses to physical stimuli but does not communicate nor follow commands, may move spontaneously 1 Unarousable Minimal or no response to noxious stimuli, does not communicate nor follow commands Riker RR et al. Crit Care Med 1999;27:1325

11 Richmond Agitation Sedation Scale +4 Combative Overtly combative, violent, immediate danger to staff +3 Very agitated Pulls or removes tube(s) or catheter(s); aggressive +2 Agitated Frequent non-purposeful movement, fights ventilator +1 Restless Anxious but movements not aggressive, vigorous 0 Alert and Calm Difficult to arouse, awakens to verbal stimuli or gentle shaking but drifts off again, follows simple commands -1 Drowsy Not fully alert, but has sustained awakening (eyeopening/eye contact) to voice ( 10 seconds) -2 Light Sedation Briefly awakens with eye contact to voice (< 10 seconds) -3 Moderate Sedation Movement or eye opening to voice (but no eye contact) -4 Deep Sedation No response to voice, but movement or eye opening to physical stimulation -5 Unarousable No response to voice or physical stimulation Sessler CN et al. AJRCCM 2002;166:1338

12 Intensive Care Delirium Screening Checklist Altered level of consciousness (A-E) If A or B do not complete patient evaluation for the period Inattention Disorientation Hallucination - delusion psychosis Psychomotor agitation or retardation Inappropriate speech or mood Sleep/wake cycle disturbance Symptom fluctuation TOTAL SCORE (0-8) Bergeron et al. ICM 2001;27:859

13 1. Altered level of consciousness: A) No response B) Need for vigorous stimulation to obtain any response signifies severe alteration in LOC precluding evaluation If coma (A) or stupor (B) most of the time period there is no further evaluation during that period. C) Drowsiness or requirement of a mild to moderate stimulation for a response implies an altered level of consciousness and scores 1 point. D) Wakefulness or sleeping state, easily aroused is considered normal and scores no point. E) Hypervigilance is rated as an abnormal level of consciousness and scores 1 point. Only proceed to questions #2-8 if the patient is a score of C, D, or E. 2. Inattention: Difficulty in following a conversation or instructions. Easily distracted by external stimuli. Difficulty in shifting focuses. 3. Disorientation: Any obvious mistake in time, place or person. 4. Hallucination, delusion or psychosis: Unequivocal clinical manifestation of hallucination or of behaviour probably due to hallucination (e.g. trying to catch non-existent object) or delusion. Gross impairment in reality testing. 5. Psychomotor agitation or retardation: Hyperactivity requiring the use of additional sedative drugs or restraints in order to control potential danger to oneself or others (e.g. pulling out iv lines, hitting staff). Hypo-activity or clinically noticeable psychomotor slowing. 6. Inappropriate speech or mood: Inappropriate, disorganised or incoherent speech. Inappropriate display of emotion related to events or situation. 7. Sleep/wake cycle disturbance: Sleeping <4 hours or waking frequently at night. Sleeping during most of the day. 8. Symptom fluctuation: Fluctuation of the manifestation of any item or symptom over 24 hours

14 Daily interruption group Bedside nurses interrupted opioid and benzodiazepine infusions daily Assessed hourly for wakefulness: SAS 4-7 (RASS -1 to +4) and able to perform at least 3 of: 1) eye opening 2) tracking 3) hand squeezing 4) toe moving If infusions no longer required (patient free of discomfort and agitation, SAS 2-5, or RASS -4 to +1), oral or bolus IV therapy used If infusions required, resumed at half prior dose(s), titrated to achieve target level of light sedation

15 423 Patients 214 PS+DI, 209 PS 3 No Delirium data 420 Assessed 31 always A or B 7.4% 226 Delirium 53.8% 163 No Delirium 38.8% 146 subsyndromal delirium 17 never delirium

16 Baseline Characteristics Variable Ever Delirium N=226 Never Delirium N=163 Age (yrs) 57 (46,68) 60 (50,71) P value Female (%) 38.9% 53.4%.005 APACHE II 23 (18,27) 24 (19,29) SOFA day 1 6 (4,9) 7 (4,9) Type of admission (%) Medical Surgical Trauma 78.8% 16.8% 4.4% 89.0% 8.6% 2.4%.03

17 Baseline Characteristics Ever Delirium N=226 Never Delirium N=163 P value Admission Diagnosis (N) Bacterial/viral pneumonia 18.6% 24.5% Sepsis 19.5% 18.4% Other respiratory disease 10.2% 10.4% Aspiration pneumonia 3.5% 4.3% COPD 2.2% 4.9% Pre-ICU Conditions Cigarette smoking 31.5% 16.2%.002 Ethanol use 34.6% 20.9%.009

18 Outcomes

19 Kaplan-Meier Curves - Time to Successful Extubation Successful Extubation in First 28 days of study Delirium Non-Delirium Patients remaining intubated P < No. of patients at risk Delirium Non-delirium Time, days

20 Duration of Mechanical Ventilation and Lengths of Stay 25 Days Delirium Never delirium 5 0 MV ICU LOS Hospital LOS P<.0001

21 Other outcomes Ever delirium Never delirium P Device removal N=226 N=163 value Gastric tube 31 (13.7%) 15 (9.2%).17 ETT 14 (6.2%) 7 (4.3%).41 Urinary catheter 14 (6.2%) 4 (2.4%).08 C-line or A-line 22 (9.7%) 5 (3.1%).01 Head CT or MR, N (%) 41 (18.5%) 19 (11.8%).07 Lumbar puncture, N (%) 11 (4.9%) 2 (1.2%).048 Physical restraint, N (%) 195 (86.3%) 125 (76.7%).01 Study days, median (IQR) 5 (2,9) 2 (1,6) <.0001 Tracheostomy, N (%) 78 (34.5%) 25 (15.5%) <.0001 ICU Mortality, N (%) 40 (17.7%) 37 (22.7%).22

22 Medication administration Ever delirium N=226 Never delirium N=163 P value Midazolam equivalents (mg) Dose/pt/day Infusion, days 104 (356) 5 (3,9) 57 (123) 3 (2,6) <.0001 <.0001 Fentanyl equivalents (mcg) Dose/pt/day Infusion, days 1497 (3564) 6 (3,10) 1150 (2234) 3 (2,7) <.0001 <.0001 Antipsychotic, N (%) 83 (36.7%) 21 (12.9%) <.0001 Anti-cholinergic, N (%) 41 (18.1%) 14 (8.6%).007

23 Coma Ever delirium Never delirium P Coma N=226 N=163 value Patients, N (%) 74 (32.7%) 37 (22.7%).030 Days, mean (SD) 1.6 (4.7) 0.7 (2.0).039 Occurred prior to delirium 38 (51.4%) Coma due to sedation Patients, N (%) 59 (26.1%) 27 (16.6%).025 Days, mean (SD) 1.2 (4.0) 0.5 (1.7).048 Occurred prior to delirium 33 (55.9%)

24 Kaplan-Meier Curves - Time to Successful Extubation Successful Extubation in First 28 days of study No Delirium, No Coma Delirium, No Coma Delirium, Coma No Delirium, Coma Patients remaining intubated P < No. of patients at risk No Delirium, No Coma Delirium, No Coma Delirium, Coma No Delirium, Coma Time, days

25 Comparison of PS+DI vs. PS groups PS+DI N=214 PS N=209 Patients with 1 day delirium, N (%) 113 (53.3) 113 (54.3) Patient-days with delirium, median (IQR) 1 (0,2) 1 (0,3) Patients with 1 day sub-syndromal delirium, N (%) 74 (34.9) 72 (34.6) Patient-days sub-syndromal delirium, median (IQR) 2 (1,4) 3 (1,5)* Coma, N (%) 66 (31.0) 71 (34.0) Patient-days with coma, median (IQR) 0 (0,1) 0 (0,1) Patients who received 1 dose AP, N (%) 52 (24.4) 54 (25.8) Days patients received 1 dose AP, median (IQR) 0 (0,0) 0 (0,1) *P=.03

26 Delirium risk factors Univariate Gender M>F Alcohol MV duration Coma BZD dose: Quartiles 3 & 4 Opioid dose Anticholinergics Antipsychotics Physical restraint Multivariate Age APACHE II Tobacco Dementia history Alcohol OR 1.89 P=.027 Coma OR 2.02 P=.011

27 Conclusions 53.8% of mechanically ventilated patients had delirium on 1 or more days Delirious patients longer durations of MV, ICU, Hospital LOS More accidental vascular catheter removals More tracheostomies More restraint use Received more benzodiazepines, opioids, antipsychotics, and anti-cholinergics More commonly had coma

28 Conclusions No difference in delirium between PS+DI and PS group Between delirious and non-delirious patients, there was no difference in Neurologic evaluation Discharge destination Mortality

29 SLEAP Steering Committee Sangeeta Mehta Lisa Burry Marilyn Steinberg Deborah Cook Maureen Meade Paul Hebert Karen Antoni Dean Fergusson

30 Investigators MSH UHN-TGH UHN-TWH Tufts Medical Center St Joseph s Med Center Long Beach Memorial Sunnybrook HSC St Paul s Hospital St Michael s Hospital WC Mackenzie HSC Hamilton HSC Winnipeg HSC Maisonneuve-Rosemont Royal Columbian Surrey Memorial Hospital Royal Alexandra Marilyn Steinberg, Lisa Burry Paulina Farias, John Granton, Margaret Herridge Paulina Farias, Niall Ferguson John Devlin, Russ Roberts France Clarke, Ellen McDonald, Deborah Cook Hyunsoon Park, Maged Tanios Nicole Marinoff, Rob Fowler Betty-Jean Ashley, Peter Dodek Kerri Poretta, Yoon Lee, Orla Smith, Karen Burns Michael Jacka Lori Hand, Maureen Meade Wendy Janz, Kendiss Olafson Johanne Harvey, Yoanna Skrobik Steven Reynolds, Sean Keenan Steven Reynolds, Sean Keenan Patricia Thompson, Jim Kutsogiannis

31 Data Monitoring Committee Jesse Hall MD Scott Epstein MD Rollin Brant PhD

32 Thank-you!

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34 Ventilator weaning Weaning mode: PEEP with PS Daily screen for trial of unassisted breathing UBT: T-tube, a tracheostomy tube, or CPAP 5 cmh 2 O Awake Cough with suctioning PaO 2 60, SpO 2 90%, FiO2 0.4 PEEP 10 cm H 2 O RR 35 VE 15 L/min No inotropes or vasopressors Mean arterial pressure > 60 mmhg No myocardial ischemia

35 Patients remaining alive Mortality by Delirium duration

36 Mortality risk factors Univariate Age APACHE II Vasopressors Renal replacement MV duration Coma BZD dose: Quartiles 2 & 3 Physical restraint Multivariate APACHE II MV duration Opioid dose Antipsychotics Coma