Survey
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
* Your assessment is very important for improving the workof artificial intelligence, which forms the content of this project
Sedation Practice in Intensive Care Evaluation Early Goal Directed Sedation SPICE III Start-up Initiation Meeting Prof Yahya SHEHABI & Ms Belinda HOWE Disclosure • SPICE Program is endorsed by ANZICS Clinical Trials Group – Managed by the ANZIC RC Monash University • SPICE III RCT is funded by an Australian Government NHMRC Grant • Malaysian SPICE sites funded by IJN Foundation grant • The study drug Dexmedetomidine is provided by Orion to study sites 2 Early Goal Directed Sedation Elements and Hypothesis • It is plausible that strategy combining: – Early commencement of sedative intervention – Effective analgesia – Utilizing dexmedetomidine as a primary sedative agent • Rousable sedation and reduced overall sedation depth • Facilitate wakefulness and ventilation weaning • Reduce overall sedative and opioid load – Targeted light sedation RASS -2 to +1. – Avoiding and minimizing benzodiazepines • Is feasible and likely to reduce early deep sedation and improve clinical outcomes 4 Sedation Practice in Intensive Care Evaluation The SPICE Program Endorsed by the ANZICS Clinical Trials Group Supported by a Project Grant NHMRC 2012 Endorsed by Australian New Zealand Intensive Care Society Clinical Trials Group 6 Hypothesis Early Goal-Directed Sedation (EGDS), compared to standard sedation practice, reduces 90-day all-cause mortality in critically ill patients who require mechanical ventilation Study Aim • To investigate the clinical effectiveness of an Early Goal Directed Sedation Strategy on – 90 day All-Cause mortality – Cognitive function at 180 days – Institutional dependency at 180 days Design • Multi-centre multi-national prospective unblinded randomised controlled trial – Recruit 4000 patients to detect 4.5% ARR in prim outcome with 90% power and α = 0.05 • Central randomisation via secured website – Stratify by site and suspected or proven sepsis • EGDS compared with current practice – Interim analysis at 2000 patients. • Delayed consent Study Population – Who is Included ? 1. Subject has been intubated and is receiving mechanical ventilation 2. The treating clinician expects that the patient will remain intubated until the day after tomorrow (unlikely to be extubated the following day). 3. The patient requires immediate ongoing sedative medication for comfort, safety, and to facilitate the delivery of life support measures. Exclusion Criteria • Age < 18 years • Pregnant and/or lactating • Has been intubated for greater than 12 hours in an intensive care unit (excluding time spent intubated within an operating theatre or transport) • Proven or suspected acute primary brain lesion that may result in global impairment of conscious level or cognition, such as traumatic brain injury, intracranial haemorrhage, stroke, or hypoxic brain injury. 11 Exclusion Criteria • Proven or suspected cervical spinal cord injury or pathology that may result in permanent or prolonged weakness • Admitted as a consequence of a drug overdose or burns • Receiving or expected to need ongoing neuromuscular blockade • Known sensitivity to any of the study medications or the constituents of propofol (egg, soya or peanut protein) 12 Exclusion Criteria • Mean arterial blood pressure (MAP) that is less than 50 mmHg despite adequate resuscitation and vasopressor therapy at time of randomisation • Heart rate less than 55 beats per minute unless the patient is being treated with a beta-blocker or a high grade atrio-ventricular block in the absence of a functioning pacemaker • Acute fulminant hepatic failure 13 Exclusion Criteria • Patient has been receiving full time residential nursing care • Death is deemed to be imminent or inevitable during this admission and either the attending physician, patient or substitute decision maker is not committed to active treatment • Patient has an underlying disease that makes survival to 90 days unlikely • Patient has been previously enrolled in the SPICE study 14 Study measurements At randomization and 4 hrly thereafter • Pain assessment –Visual Analogue Scale in patients able to communicate –Critical Care Pain Observation Tool (CPOT) if patient unable to report pain • Sedation assessment –Richmond Agitation Sedation Scale RASS Within 24 hours of randomization and daily thereafter • Delirium assessment –Confusion Assessment Method in Intensive Care CAM-ICU 16 Study Outcomes Supported by a Project Grant NHMRC 2012 Endorsed by Australian New Zealand Intensive Care Society Clinical Trials Group 1 7 EGDS detailed Algorithm Patient is mechanically ventilated Sedation assessment Pain assessment Clinicians choice Opioid, other On-going Sedation Adequate analgesia RASS ≤ -3 Dexmedetomidine infusion 1 mcg/kg/hr. (No Loading) RASS ≥2 RASS -2 to +1 Propofol 10-70 mg/hr. Stop propofol first ↓ dexmedetomidine 0.2 mcg/kg/hr every 30 minute RASS -2 to +1 Sedation no longer needed Stop Infusion RASS -2 to +1 RASS -2 to +1 Dexmedetomidine 0 – 1 mcg/kg/hr. Propofol 0 – 70 mg/hr. EGDS – when to give propofol ? EGDS When to consider midazolam? • Palliation • Procedures – Tracheostomy, brochoscopy • Convulsions • Agitation unresponsive to EGDS protocol • EGDS at maximum dose not achieving target sedation EGDS Process of Care Managing Agitation Breakthrough delirious agitation is common, particularly during discontinuation of sedative medications. If this occurs, patients in the EGDS arm should have 1. Dexmed at max tolerated preferably > 1 mcg/kg/hr 2. Add ± Propofol infusion as needed up to 200 mg/hr 3. Quetiapine 12.5 to 100 mg per day 4. Haloperidol (up to 5 mg IVI every 4 hours), or both 5. Midazolam at the discretion of the treating clinician 2 2 Standard Care Sedation Standard Process of Care Managing Agitation Breakthrough delirious agitation is common, particularly during discontinuation of sedative medications. If this occurs, patients in the standard care arm should have 1.Optimize Propofol, midazolam or both 2.Quetiapine 12.5 to 100 mg per day 3.Haloperidol (up to 5 mg IVI every 4 hours) 4.Dexmedetomidine at the discretion of the treating clinician. Supported by a Project Grant NHMRC 2012 Endorsed by Australian New Zealand Intensive Care Society Clinical Trials Group 2 4 Adrenergic effects of dexmedetomidine BP and HR effects Sedation and analgesia effects Alertness Heart Rate and Blood Pressure Change • • • • • • Patients receiving sedative infusions and analgesics to provide comfort and pain relief. Therefore, a reduction in blood pressure and heart rate is expected with reduced anxiety, agitation and sympathetic drive. Dexmedetomidine is known to produce a reduction in heart rate in most patients. This occurs with doses as low as 0.1 mcg/kg/hr and is dose related to a max of 1 mcg/kg/hr. Peak effect occurs at 8 to 12 hours after initiation of dexmedetomidine. Most patients will have a reduction in Heart Rate (HR) that is NOT clinically relevant i.e. BP is stable and therefore may not require intervention. Less than 5% of patients may have a reduction in HR that may be clinically relevant i.e. HR < 55/min with a low BP and hence needs treatment. It takes 6 to 8 hours for the sympatholytic and bradycardia effect to recover following dexmedetomidine dose reduction or cessation of the infusion. Dexmedetomidine produces a bimodal effect on BP dependent on plasma concentration achieved: – At low dose, 0.1- around 0.7 mcg/kg/hr - produces a dose dependent reduction in BP. – At higher dose, greater than 0.7 mcg/kg/hr - produces a dose dependent increase in BP. Managing HR and BP • HR is < 55/min + adequate BP with CV stability observe (check perfusion status). • • HR is < 55/min + borderline or low BP: – You may give atropine 300 mcg IVI to reduce possible vagal effect. – If no improvement within 5 min, consider a low dose dobutamine 2 mcg/kg/min or adrenaline 0.05 mcg/kg/min (Clinician’s choice). – ? reduce Dexmedetomidine infusion by 0.2 mcg/kg/hr. Please note the long offset time for bradycardia. Maintain RASS target as per protocol. – You may increase dobutamine / adrenaline to the desired effect. • • Low BP + normal HR or borderline bradycardia = treat per usual with fluid boluses and/or vasopressor of choice. – Metaraminol 0.5 mg bolus for immediate temporising effect. – Noradrenaline infusion (0.05 mcg/kg/min for sustained effect Supported by a Project Grant NHMRC 2012 Endorsed by Australian New Zealand Intensive Care Society Clinical Trials Group 3 1 Study Logistics- Screening Screening & randomisation → 24/7 Screen all pts who are commenced on IMV or arrive in ICU on IMV If meet ALL inclusions But have an exclusion → Screening log Access to phone number for queries Study Logistics- Randomisation Login to website https://spicestudy.org Generic logins for randomisation only Enter randomisation information Patients stratified by severe sepsis Pt ID number, allocation on screen & email Dexmedetomidine or Standard Care DEX supplied by Orion - for 10 EGDS pts at a time DEX can be made up as per unit protocol DEX dosing tool is optional DEX dispensing log & reconciliation log - Patient randomised- What Next? SPICE study Tool package - EGDS with DEX or - Standard Care – Clinician’s choice If EGDS with DEX, use DEX stock for study only Commence DEX shortly after randomisation RASS & Pain Assessments RASS most valid and reliable sedation assessment tool for measuring quality & depth of sedation in adult ICU patients (SCCM PAD, 2013) Aim RASS -2 to +1, in both study arms If RASS aim is NOT -2 to +1 e.g. Deep sedation (RASS -3 to -5) document reason -CRF form 3 Pain assessments- YES/ NO based on CCPOT Assess RASS & Pain 4 hourly (±2) from randomisation until ICU discharge or D28-CRF form 3 RASS CAM-ICU the most valid and reliable delirium monitoring tool in adult ICU patients (SCCM PAD, 2013) Perform CAM-ICU only if RASS -2 to +1 Assess once per day minimum Continue until ICU discharge or D28 -CRF form 3 CAM-ICU +ve = Delirium, CAM-ICU –ve = NO Delirium, Unable to assess CAM-ICU Consent Deferred consent - approved by REC Pt randomised & then consultee declaration - Personal consultee - Nominated consultee Pt consent to continue if appropriate Document consent process Consent Pt deceased prior to consent obtained? REC approval data usage Consultee refuses? Clarify: Treatment? Data usage? Follow Up? →Any contact? → Surveys only? Follow Up D90 Follow Up Vital status only Primary outcome is D90 status D180 Follow Up Vital status & location, EQ5D, IQCode Completed over the phone SAEs- Definition Any untoward medical occurrence that: ● Results in death ● Is life-threatening ● Requires inpatient hospitalisation or prolongation of existing hospitalisation ● Results in persistent or significant disability/incapacity ● Is a congenital anomaly/birth defect ● Is an important medical event ICH GCP July 2000 SAEs- Definition Guidance from SPICE DSMC: DO NOT report as SAEs events already defined and reported as study outcomes e.g. mortality, re-admission to ICU DO report as SAEs events which are: Unexpected event Possibly related to the study of concern in the investigator’s judgement AE/SAEs- Definition Bradycardia (HR<55) requiring intervention - pacing, pharmacological support, or modification of dexmeditomidine or other medication dose Hypotension which is clinically significant Is it SAE? Fatal or life threatening If NOT, then AE. AE/SAEs- Definition SPICE study is UNBLINDED → Bias Report equally events in both arms Questions ?