Peel/Halton 2010 CME Sheldon Cheskes, MD CCFP(EM) FCFP Medical Director Sunnybrook – Osler Centre for Prehospital Care Li Ka Shing Knowledge Institute, St. Michael’s Hospital Co Principal Investigator, Resuscitation Outcomes Consortium, Toronto Regional Rescuenet

Resuscitation Outcomes Consortium (ROC) What Studies Are Coming Down The Pike?

Previous Trials  ROC Epistry: Cardiac Arrest Data Base  ROC PRIMED: Early Vs Late Analysis and use of ITD  ROC HS: Hypertonic Saline in TBI and Hypovolemic Shock

EMS Providers Views  Enjoy taking part in randomized controlled trials  “Lots of work”  “Pain in the  Challenges of randomization, documentation, and CPR process capture

Overwhelming View  Despite findings of previous ROC RCT  “Thirst for a positive trial”

What's Next For ROC EMS Agencies Cardiac Trials  ROC CCC  ROC Amiodarone Trauma Trials  ROC Lactate  ROC Hypotensive Resuscitation

Upcoming Trial Overview  Science  Methodology  EMS Challenges

ROC CCC Trial of Continuous Compressions vs Standard CPR in patient’s with out- of-hospital cardiac arrest

ROC CCC Science  Greater coronary perfusion pressure associated with greater ROSC in animal and human studies  Interruptions in chest compression reduce CPP  Observational studies suggest at least as effective as standard CPR  Observational trials instituted multiple changes? Impact of CCC

ROC CCC Science  Insertion of advanced airway associated with interruption in CPR  CCF (hands on time) increased in sites using CCC model  Increased CCF associated with increased survival from VF/VT

ROC CCC Methodology EMS arrival at patient (>18, non –traumatic cardiac arrest, lack of exclusion criteria) with randomization to: Control group  3 cycles of 2 minutes of standard (30:2) CPR  analysis after each 2 minute CPR cycle  standard site ventilatory treatment

ROC CCC Methodology Randomization Group:  3 cycles of 2 minutes of CPR using continuous compressions with no stops for ventilation  Analysis after each 2 minute CPR cycle

ROC CCC Methodology Ventilation Strategy In Randomization Group:  Sites will choose between two ventilation strategies Positive pressure ventilation  10 ventilations/minute via BVM with no CPR interruptions for ventilations Passive ventilation  Oral airway with oxygen via non re- breather at 15 l/min

ROC CCC Methodology Both Groups:  IV or IO with epinephrine or vasopressin given within 5 minutes of ALS arrival  After advanced airway inserted ventilation rate at 10/minute compression rate at 100/minute (current standard) until ROSC or termination of resuscitation

ROC CCC EMS Challenges  Maximize CPR process files***  Randomization: cluster and frequency of cross over  ALS medics not intubating for first five minutes  Supraglottic airways: advanced or not?  Bagging while doing compressions in unprotected airway

ROC Amiodarone Amiodarone (pm101), lidocaine or neither for out-of-hospital cardiac arrest due to ventricular fibrillation or tachycardia

ROC Amiodarone Science  Little evidence that anti-arrythmics have any impact on survival from OHCA  Given lack of evidence question is not just which anti-arrythmic should be used but should any be used?  Since no evidence of improvement in survival to discharge inclusion of placebo arm is required

ROC Amiodarone Science  Three staged model of cardiac arrest  Antiarrythmics necessary to correct electrical abnormalities  Previous trials of antiarrythmics delayed administration until well into metabolic phase  Optimal approach would be administration during electrical or circulatory phase

ROC Amiodarone Science  ALIVE: amiodarone recipients more likely to survive to hospital  ARREST: similar results to ALIVE  Neither trial designed or powered to evaluate survival to discharge  Occurred in era of “poor CPR” (stacked shocks, shock pauses of greater length, pulse checks)  Late amiodarone! (given after call received, given 10 minutes after IV established)

ROC Amiodarone Science Amiodarone the drug  Amio insoluble in water, polysorbate 80 used as diluent  Makes amio difficult to deliver, drawn up from glass ampules then diluted before use  Tends to foam due to diluent  Incompatible with solutions other then D5W  Diluent (as opposed to drug) causes hypotension and phlebitis

ROC Amiodarone Science Captisol-enabled amiodarone (pm101)  New FDA approved formulation using diluent (captisol)  Diluent clear, hemo and electro inert  Compatible with solutions other then D5W  does not absorb in plastic  pre filled syringe  IV push immediately after IV established

ROC Amiodarone Methodology  Confirmed non traumatic cardiac arrest  BLS CPR, analysis, shock and IV/IO established  After 1st shock**, CPR established, vasopressor flush, study drug x 2 flush while ongoing CPR  2nd analysis if shockable> shock, CPR, advanced airway, vasopressor  3rd analysis if shockable> shock, CPR, study drug x1

ROC Amiodarone Methodology Study Drug Kit Contents

ROC Amiodarone Methodology Rationale for lack of Rescue arm for persistent VF/VT  Further open label doses may risk toxicity  Require un-blinding in field (difficult)  Neither study drug class 1 recommendation  No preclusion to other treatments (EPI, MAG, B Blocker, etc)  Cross-over makes analysis more difficult

ROC Amiodarone EMS Challenges  Timing of Amiodarone delivery (voice, defib, guess!)  Tracking study kits, (remember ITDs!)  Randomization  Focus on early administration (new approach to delivery)  Local REB > will they allow a placebo arm?

ROC Lactate Prehospital lactate for the identification of shock in trauma

ROC Lactate Science  Recent prospective out-of-hospital research suggest HR and hypotension poor predictors of need for intervention in trauma  Hypotension late finding  Delayed identification of hypo-perfusion results in delayed definitive care

ROC Lactate Science  Lactate biomarker of organ oxygen supply/demand mismatch  Elevated in sepsis, MI, trauma  Historically only measured in hospital  Now available point of care (POC) testing of lactate level in prehospital care  To date lactate testing predicts severity of hemorrhage, mortality and need for ICU admission

ROC Lactate Science  Can POC testing be used as a triage tool?  Can we predict patients who will need resuscitative care that would not have been predicted otherwise?

ROC Lactate Methodology Prospective observational study to identify patients suffering from hypo-perfusion secondary to trauma  Included patients meet local TT guidelines:  BP < 100,  Transported to level 1 or 2 trauma center  Died in field or en route  Exclusions >isolated penetrating head injury

ROC Lactate Methodology  Patient identified, IV established, 50 micro liter (drop of blood) applied to POC lactate meter (similar to glucometer)  EMS blinded to result until reach ER  No change in EMS treatment based on POC testing  Second lactate to be drawn in ER

ROC Lactate Methodology ROC Lactate Meter

ROC Lactate EMS Challenges  Pure ALS trial  Need for trauma center transport  Accurate documentation of lactate time of draw  Will medics un-blind and alter treatment?  POC calibration  POC tracking  Blood sample after IV as opposed to before

ROC Hypotensive Resuscitation Field trial of hypotensive resuscitation vs. Standard resuscitation in patients with hemorrhagic shock after trauma-a pilot study

ROC Hypotensive Resuscitation Science  Traditional treatment of trauma patients> aggressive fluid resuscitation to restore circulating volume, SBP  Increasing animal and human studies showing detrimental effects of massive fluid resus prior to hemorrhage control  Associated with cardiac dysfunction, abdominal compartment syndrome, ARDS, hypothermia and coagulopathy

ROC Hypotensive Resuscitation Science  Three RCTS, two observational studies suggest harm of aggressive fluid resuscitation as opposed to no prehospital fluids until hospital arrival  No study shows clear superiority of aggressive fluid resus vs hypotensive resuscitation yet aggressive fluid resus cornerstone of ATLS and PTLS teaching  RCT required to better answer the question

ROC Hypotensive Resuscitation Methodology  Patient with shock after trauma randomized to either standard or hypotensive Resusc arm  Inclusion: blunt or penetrating trauma, age> 15 or 50 kg, SBP 8  Exclusions (many)> fluid started by non ROC agency, ongoing CPR

ROC Hypotensive Resuscitation Methodology  Complete randomization (as opposed to a priori)  Participating agencies carry pre randomized, sealed, numbered containers  Patient randomized and entered once container opened  Containers with 1000 cc or 250 cc iv normal saline bags  EMS will not know randomization until container opened

ROC Hypotensive Resuscitation Methodology Tote bag to hold two Hypotensive Resusc fluid boxes Two cardboard boxes per tote will disguise/blind different size of IV fluid bags

ROC Hypotensive Resuscitation Methodology Once container opened if 1000 cc bag randomized to control arm:  IV fluid given as rapidly as possible until ER arrival  If prehospital volume of 2 liters reached fluid stopped if SBP >110

ROC Hypotensive Resuscitation Methodology If container opened and 250 cc bag randomized to experimental group:  IV hung and if radial pulse or SBP > 70 TKVO fluids  no radial pulse or SBP < 70 begin 250 cc infusion until radial pulse returns or SBP 70  EMS agencies given option of using radial pulse or SBP as means of BP monitoring

ROC Hypotensive Resuscitation Methodology  ALS trial  Significant in-hospital component  Bong  Canister technique  Hypotensive resuscitation in severe head injury?  Tracking of treatment canisters

Other Studies At Various Levels  ROC Hypothermia (PreHospital Hypothermia)  ROC RESUCE (Estrogen Use In Trauma)

EMS Challenges For All ROC Trials  Competing non ROC research  Training and training cycles  REB approvals  Multiple studies…which one do we choose?  SMC requirements for continued participation  Paramedic research burnout  Long down time between recent HS and PRIMED

Questions?