Sedation Practice in Intensive Care Evaluation Early Goal Directed Sedation SPICE III

Transcription

1 Sedation Practice in Intensive Care Evaluation Early Goal Directed Sedation SPICE III Yahya SHEHABI Professor Intensive Care Medicine Program Medical Director, Critical Care Monash University, Monash Health Clinical School of Medicine, University New South Wales

2 SPICE journey continues

3 SPICE Sub-Studies

4 Why sub-studies? SPICE is a global study SPICE will be a game changer Plausible evidence to cytoprotective including nephroprotective and neuroprotective potential of dexmedetomidine Significant interest in other clinically relevant and important outcomes

5 Comfort and Patient-Centred Care Without Excessive Sedation: The ecash Concept Short title: ecash for patient-centred care Jean-Louis Vincent, 1 Yahya Shehabi, 2 Timothy S Walsh, 3 Pratik P Pandharipande, 4 Jonathan A Ball, 5 Peter Spronk, 6 Dan Longrois, 7 Thomas Strøm, 8 Giorgio Conti, 9 Georg-Christian Funk, 10 Rafael Badenes, 11 Jean Mantz, 12 Claudia Spies, 13 Jukka Takala 14 Accepted for publication ICM 2016

6 Early after ICU admission COMFORT? no yes Pain? Sedation# (light, titrated) no Distress? Anxiety? yes Analgesia (escalated, multimodal) Reassurance Communication yes Trigger of agitation? Modify, control, treat Person centered care (mobility, sleep, orientation, engagement)

7 Hypothesis: MAKE SPICE Major Adverse Kidney Events EGDS and dexmedetomidine reduced acute kidney injury and need for dialysis and thus reduces MAKE Objectives: Evaluate the clinical effectiveness of EGDS and dexmedetomidine on MAKE

8 MAKE SPICE Major Adverse Kidney Events Population : Inclusion criteria Patients randomised in SPICE III study. Exclusion dialysis dependent or with an egfr of less than 15 ml/min/1.72m 2 No documented creatinine within the first 48 hours Sample size 2000 patients to detect a 5% difference in prim outcome at 0.05 and 90% power Randomisation schedule as per SPICE III

9 MAKE SPICE Major Adverse Kidney Events Primary outcome: AKI II+III, dialysis and death within hospital or 28 days Secondary outcomes: AKI as defined by KDIGO stage I, II and III Need for dialysis Duration of dialysis ICU and hospital length of stay Ventilation time Death at hospital discharge or 28 days

10 Interventions and data collection Daily creatinine will be an additional data point Calculate AKI II and III We already collect: Dialysis yes/no Dialysis days Time to extubation ICU and Hospital Time to discharge Hospital mortality

11 MAKE SPICE Major Adverse Kidney Events Funding and endorsement

12 SPICE FANs Functional And Neuropsychologic outcomes Rationale: Trajectory to long-term outcome seems to be dictated early during an episode of critical illness Delayed intervention, following ICU discharge, produced no beneficial outcomes SPICE III is a trial of early intervention achieving light sedation within 12 hours of randomization Significant interest in medium and long-term outcomes in critical illness

13 Hypothesis: SPICE FANs Objectives EGDS with dexmedetomidine as primary sedative improves functional and neuro-psychologic performance 90 days after clinical illness Objectives: Evaluate the effectiveness of EGDS on 1. Functional and neuropsychological performance at 90 days 2. Evaluate the interaction between delirium, delirium duration and FANs

14 SPICE FANs Population Population: Inclusions: Patients randomised in SPICE III in ANZ, UK and Switzerland Exclusion: Patients with poor command of English and/or unable to use internet or Randomisation: Nested within SPICE III with same schedule

15 SPICE FANs Sample size: 630 patients who would be alive at 90 days (to detect a 0.25 SD 80% 0.05) will be included in SPICE III participating sites. This includes 10% inflation for loss of follow-up and a 15% inflation for non-normality.

16 SPICE FANs Main outcomes Primary outcomes: This will be the functional capacity assessed at 90 days following randomisation. Secondary outcomes: Executive function at hospital discharge and 90 days following randomisation Memory at hospital discharge or 28 days and at 90 days following randomization PTSD score at hospital discharge or 28 days following randomisation The interaction between delirium and delirium duration and each of the above outcomes measures at 90 days following randomisation

17 SPICE FANs Main outcomes Interventions: 1. Functional status: Functional Status Score for ICU (FSS-ICU) Assessed daily till discharge from ICU At hospital discharge or 28 days following rand At 90 days following randomisation

18 FSS-ICU John Hopkins Outcome after Critical illness and surgery group Good criterion-concurrent validity compared to the PFIT (which they have stated is the gold standard) at both awakening (rho = 0.87, p<0.005) and ICU discharge (rho 0.85, p<0.005) Good construct validity when compared to manual muscle testing (MRC sum score) (rho = 0.69, 95% CI = 0.50, 0.83, P <0.005).

19 FSS-ICU 0-7 for each domain

20 Executive function and Memory Assessed online at hospital discharge and 90 days following randomisation Cambridge Cognition inventory Online via a secured website Academic collaboration Per patient fee

21 Executive function and Memory Cambridge Cloud Programme Attention is assessed by Reaction Time (Processing and Psychomotor Speed) Rapid Visual Information Processing (Sustained Attention) Memory is assessed by: Paired Associates Learning Executive function and decision making: Spatial Working Memory & strategy Attention Switching Task (Attention Switching) One Touch Stocking of Cambridge (Planning)

22 PTSD 28 days/hospital discharge and at 90 days following randomisation Try to avoid situations or things that remind you of the traumatic event Not remember important parts of the traumatic event View yourself, others and the world in a negative way Lose interest in activities you used to enjoy and feel detached from family and friends Feel a sense of emotional numbness, feel irritable or have angry or violent outbursts Engage in dangerous or self-destructive behaviour Feel as if you're constantly on guard or alert for signs of danger and startle easily Have trouble sleeping or concentrating

23 FANs Logistics Significant additional follow-up Seeking funding to support Per patient payment Cambridge Cognitive testing

24 SPICE PASS Pressor Agents and Septic Shock

25

26

27 SPICE PASS Pressor Agents and Septic Shock Background and Rationale: Animal studies suggests improved dose response to vasopressors in patients receiving dexmedetomidine B Blockers seems to produce beneficial effects in patients with septic shock Dexmedetomidine known to produce reduction in HR and BP Effect of dexmedetomidine in septic shock patients remain uncertain

28 Hypothesis: SPICE PASS Hypothesis and Objectives EGDS doesn t worsen hypotension or increase vasopressor requirements within 48 hours following randomisation Objectives: Evaluate the clinical effectiveness of EGDS on MAP and vasopressor needs

29 Inclusions: SPICE PASS Population Patients randomised in SPICE III and Receiving vasopressors for at least 4 hours Stratified into sepsis or no sepsis Exclusion: patients co-enrolled with ADRENAL Small sample of patients 90% power to detect a >3 mmhg difference in MAP and/or 3 mcg/min difference in NA infusion.

30 Primary outcomes: SPICE PASS Outcomes This will be the difference in mean arterial pressure (MAP) between the two groups Secondary outcomes: This will be the difference in noradrenaline dose between the two groups Tertiary outcomes: This will be the difference in the MAP to noradrenaline ratio

31 SPICE PASS Interventions Specific data will be collected for 48 hrs Hourly BP Hourly NA, Ad, VP Hourly dobutamine, other inotropes Sedative infusions hourly cumulative dose Outcome data Lactate Time to vasopressor free target MAP Time to extubation

32 SPICE PASS Logistics Funding Endorsement

33 Thank you Questions?