cord cunningham, md, mph lieutenant colonel, us army 1st ......very low-cost medication; generic:...

Cord Cunningham, MD, MPH Lieutenant Colonel, US Army

1st Air Cav Flight Surgeon EMS Physician

Salviens Vita, Serviens Bellatorum

• Opinions or assertions contained herein are the private views of the author and are not to be construed as official or as reflecting the Department of the Army or the Department of Defense.

• No conflicts except my concern and drive to reduce prehospital/battlefield morbidity & mortality

• This reflects the work of many others with special thanks to Major Andy Fisher, MPAS


• Describe the mechanism of action of Ketamine • List the reasons why treating prehospital pain is

important • Identify the types of pain and settings that

Ketamine is better suited than opioids • Explain the safety and efficacy of Ketamine in the

current medical literature • List and describe the complications attributed to

Ketamine and their proof • Discuss the Tactical Combat Casualty Care Triple

Option Analgesia Protocol


• Discussing benefits of Ketamine outside of analgesia such as for Excited Delirium and Drug Assisted Intubation

• The policy changing road map to

overcome existing hurdles of state or facility restrictions on Ketamine use


• Ketamine has great utility in EMS

• Ketamine is very safe

• Dosing range determines effect and duration


• About me • Importance of pain treatment • Background & PK of Ketamine • Terminology & Sedation Spectrum • Safety and Efficacy • Military Ketamine Uses/Data • Conclusion/Discussion


• Board Certified Emergency Physician

• 1 of 5 Active Army EMS Subspecialty Board Certified

• 5 Deployments to Iraq/Afghanistan with 75th Ranger Regiment & USSOCOM

• Medical Director of 15 Air Ambulance Unit and Fort Hood MSTC

• Involvement in many DoD Prehospital initiatives

CoERCCC, MHS Genesis, medical monitor FDP & USAISR CCC research


• Don’t get dead(create another cax)

• Make the blood go round & round

• Make the air go in and out

• Treat pain and ease suffering

• Hand off better than you found it


• Adequate analgesia reduces DVT/PE, catabolic stress response, immunosuppression(Malchow, Crit Care Med)

• Early analgesia linked to lower rates of PTSD(Holbrook, NEJM)

• Easing suffering(as part of beneficence) is a fundamental tenet of medicine

• Morphine and similar opioids have been the de facto battlefield analgesic agent since the Civil War era

• Newer agents have less adverse effects, faster onset time, and more reliable hemodynamic support: LDK, Fentanyl, and OTFC

The psychological responses associated with uncontrolled pain: Anger Increased anxiety Sensitivity to external stimuli Withdrawal from interpersonal contact Self-absorption Depression and despair


Presenter

Presentation Notes

Dismounted complex blast injury that could be seen CONUS as well


• Ketamine first described in 1965. • Regular clinical use in the 1970s. • Classified as a dissociative anesthetic, but

also a analgesic in sub-anesthetic doses. • DEA Schedule III • Traditionally used in the perioperative

setting and emergency department setting. • Very low-cost medication; generic: 10cc

vial average cost <$7

Presenter

Presentation Notes

Ketamine was first described in 1965 and was in regular clinical use by the 1970s. It is classified as a dissociative, however, at sub-anesthetic doses, it provides analgesia. Among its several properties, it inhibits the reuptake of catecholamine. Ketamine is traditionally used in the perioperative or emergency department setting and the the dosing ranges from 1-4.5 mg/kg IV, or 6-13 mg/kg IM. Different literature says once you get 1-1 ½ mg/kg, there will be no change in sedation. It is being used more in the pre-hospital setting both in the military and civilian EMS.


• SOF Tactical Protocols 2008 • 2009 review by Black & McManus ideal

battlefield analgesic(&MCI) • Ranger Medic Protocols 2009 • June 2011 DHB for DoD evaluation as

prehospital analgesic • 14&15 Nov 2011 discussed at the DHB • Feb 2012 deliberated and recommended

to TC3 w/ TBI and eye injury restriction

Presenter

Presentation Notes

Black, Ian H., and John McManus. "Pain management in current combat operations." Prehospital Emergency Care 13.2 (2009): 223-227.


• March 2012 ASDHA Approval Memo • Initial recommendation was only to

advanced providers(SOF & flight paramedics)

• Oct 2013 Triple Analgesia Option CoTCCC approved 13-04

• Feb 2016 placed in MES Combat Medic


• NMDA receptor antagonist-binds at the phencyclidine site

• Racemic solution (S-ketamine more active)

• Binds mu-receptor(it really is an analgesic) • At higher doses causes corticothalamic

dissociation • Inhibits the reuptake of catecholamines • Bioavailability 100% IV, 93% IM, 45% IN,

30% PR/SL, 20% PO


Anesthesia: Loss of sensation resulting from pharmacologic depression of nerve function or from neurological dysfunction.

Analgesia: A neurological or pharmacologic state in which painful stimuli are so moderated that, though still perceived, they are no longer painful.

Sedation: The act of calming, especially by administration of a sedative.

Fleisher, Lee A.; Miller, Ronald D.; Eriksson, Lars I.; Wiener-Kronish, Jeanine P.; Young, William L. (2009-05-22). Anesthesia E-Book: 2-Volume Set (Kindle Locations 77499-77500). Elsevier Health. Kindle Edition.

Presenter

Presentation Notes

Anesthesia-the loss of sensation from pharmacologic administration. This can come from one or multiple drugs. Analgesia-a state where pain is either no longer painful, but is still perceived. Sedation-the act of calming. This is important as we discuss the use of ketamine.


Presenter

Presentation Notes

According to Green and colleagues in the 2011 CPG for Emergency Department ketamine, no adverse events when ketamine is given in standard doses.


“A large meta-analysis found no dose related adverse events across the standard dosing range, with only unusually high IV doses (ie, initial dose 2.5 mg/kg or total dose 5.0 mg/kg) increasing the risk of vomiting and slightly increasing the risk of apnea and recovery agitation.”

Presenter

Presentation Notes

Here the conclusions noted that 10-20% of adults have emergent issues, but CV/resp events were rare.


• Combined prospective and retrospective, observational study of 1,022 ketamine administrations over 9 years in 2 EDs

• Most common indications → fracture reduction, lac repair


• Hypersalivation occurred in 17 patients (1.7%)

• 7 were suctioned • All received atropine

• 14 patients in study did not receive atropine • None experienced hypersalivation


• Prospectively data collection via Quality Assurance (QA) database

• 191 administrations by 6 nurses • All for procedural sedation • All were non-anesthestist nurses • Only one was an RN (rest were

equivalent of LPN) • Most common indication was abscess

drainage


*None of which required more than supplemental O2 or very transient BVM


• Case series of 9 inadvertent overdoses for procedural sedation in one pediatric ED

• 5x intended dose (n=3) • 10x intended dose (n=5) •

• All experienced prolonged sedation (3 to 24hrs)


• 5x the intended dose (n=3) • Two with transient O2 desaturations that resolved with O2

supplementation • None required BVM

• 10x the intended dose (n=5)

• Two experienced desaturations and received <10 minutes of BVM

• 1 was prophylactically intubated at the providers discretion (no respiratory depression noted)

• 4 were discharged home from the ED (including the one that got intubated)

• 1 was admitted for observation


• 100x the intended dose (n=1) • Nurse mistook vial that was 100 mg/mL for 1 mg/mL • Prophylactically intubated (no respiratory depression noted) • Admitted to the PICU for observation

• All patients were neurologically normal at discharge • 8 patients available for follow-up and were

neurologically normal • Only patient not available was discharged home from the ED

without sequelae


• Inpatient to Outpatient self adminstered

• 25mg IN vs 2mg Versed IN • Focused on aura • Limited study 30 total • No serious adverse events • Ketamine reduced severity p=0.032


“The greater the ignorance, the greater the dogmatism.”

Presenter

Presentation Notes

Sir William Osler


“Get your facts first, then you can distort them as you please”


• Prospective, observational before and after study of mechanically ventilated pediatric patients with intracranial hypertension

• Hemodyanmics, ICP and CPP were measured before and after ketamine administration


Presenter

Presentation Notes

45 seconds Keith Smith 2009


• Multicenter, randomized, double-blinded trial of narcotic-naïve patients with VAS >60mm

• Patients were given 0.2 mg/kg of ketamine or equivalent placebo

• Then given morphine 3mg every 5min until VAS <30 achieved

• Primary endpoint was total morphine required to achieve VAS goal


Presenter

Presentation Notes

Reduction in their pain VAS


• Secondary safety end-points • No difference in vital signs at T30 • No difference in level of sedation via RASS at T30 • Rates of vomiting were the same between both

groups • Ketamine group experienced more

neuropsychological effects (12 vs 1) • Hallucinations (4) • Dizziness (6) • Double vision (2) • Dysphoria (6) • None of which required intervention


• 0.1-0.3mg/kg IV • <20mg IV & 25mg IM • No major adverse events

(apnea,laryngospasm,MI, HTN emergency)

• Dysphoria & psychomimetic effects with LDK


• Prospective, randomized, controlled, open-label trial of 135 patients receiving prehospital analgesia

• Both arms received an initial 5mg dose of IV morphine

• Patients were then randomized to 10mg IV morphine versus 10-20mg of IV ketamine

• Doses of 5mg morphine or 10mg ketamine were then given every 5 minutes until

• They were pain free, or • An serious adverse event occurred, or • They arrived at the hospital

• Almost all patients also received inhaled methoxyflurane


• Adverse events were similar to previously reported studies

• No major adverse events in either arm

• Addition of inhaled gas anesthetic not done in US EMS but adverse events still small


• Randomized, double-blinded, controlled trial • Primary outcome is the maximal change in

pain scores via NRS from baseline over 120 minutes

• Convenience sample, ages 18-59 with moderate-to-severe abdominal, flank, back or extremity pain

• Randomized to 0.3 mg/kg ketamine (max 25 mg) or 0.1 mg/kg morphine (max 8 mg)

• Patients could request repeat dose of study medication after 20 minutes


• 45 subjects (morphine 21, ketamine 24) • Demographics were similar

• Age (29, 30) • Gender (male 58%, 42%) • Baseline vitals • NRS baseline scores (7.1, 7.1)

Presenter

Presentation Notes

No emergence phenomenon, No statistical difference in pain scores


• Retrospective review of injured Navy-Marine personnel brought to level 1 (equivalence) in Navy or Marine AO over 36 months

• Patients were stratified based on AIS and ISS from data entered prospectively into Navy-Marine CTR EMED system at level 3

• Diagnosis of PTSD was made based on DSM-IV criteria at 1-24 months post-injury

• Patients divided into 2 groups → received morphine at level 1 versus those that did not


• 61% were diagnosed with PTSD in the early pain treatment arm versus 76% in the arm lacking pain treatment

• Remained significant even after stratification by ISS and AIS


• Reviewed records of 603 patients that were burned during OIF/OEF from 2002-2007

• PTSD Military Checklists were available for 241 of the 603

• Of those 241, 147 underwent surgery → 119 received ketamine intra-op versus 28 that did not

• Patients grouped based on TBSA <20% versus >20%


• 25mg IM Ketamine vs 10mg IM Morphine w/ placebo arm

• Tests include M9/M4 simulated marksmanship, malfunctions, target discrimination, MOPP(NBC) & commo

• Greater reported unpleasant side effects nausea, dizzy, blurred vision, and decreased concentration

• Task time slowing • No significant task completion/error ∆

Presenter

Presentation Notes

Medical after-action reports were reviewed for all Ranger casualties who received ketamine at the point of injury for combat wounds from January 2009 to October 2014. Patients and medics were also interviewed.Unit medical protocols authorize ketamine for tourniquet pain, amputations, long-bone fractures, and pain refractory to other agents. Nine of the 11 patients were US Forces; two were local nationals (one female, one male). The average initial dose given intramuscularly was 183 mg, about 2 to 3 mg/kg and intravenously 65 mg, about 1 mg/kg. The patients also received an opioid, a benzodiazepine, or both. There was one episode of apnea that was corrected quickly with stimulus. Eight of the 11 patients required the application of at least one tourniquet; four patients needed between two and four tourniquets to control hemorrhage. Pain was assessed with a subjective 1-10 scale. Before ketamine, the pain was rated as 9-10, with one patient claiming a pain level of 8. Of the US Forces, seven of the nine had no pain after receiving ketamine and two had a pain level of four. Two of the eight had posttraumatic stress disorder.In this small, retrospective sample of combat casualties, ketamine appeared to be a safe and effective battlefield analgesic.


• PJ Experience: Nine patients • Blast (6)-25mg IV (2), 25mg IM (2),

50mg IM (2) *all received opioids prior

• GSW (2) 50mg IM (2) *all received opioids prior

• DNBI (1) 25mg IM, repeat x1

Presenter

Presentation Notes

Butler, Frank K., et al. "A triple-option analgesia plan for tactical combat casualty care: TCCC guidelines change 13-04." J Spec Oper Med 14.1 (2014): 13-25.


• Providing a battlefield analgesia option that does not cause respiratory depression or exacerbate hemorrhagic shock .

• TCCC battlefield analgesia recommendations need to be simplified—there are too many options

• Decrease the amount of opioids medications because they are contraindicated in hemorrhagic shock.

Presenter

Presentation Notes

Again, looking back at the studies, LDK is not superior to opioids and often shows variability of effects. I want to look at the TCCC guidelines on pain managements. providing a battlefield analgesia option that does not cause respiratory depression or exacerbate hemorrhagic shock. TCCC battlefield analgesia recommendations need to be simplified—there are too many options and not enough clear guidance on which to use; and (2) ketamine is presently being used by medics in theater as a battlefield analgesic with excellent results Decrease the amount of opioids medications because they are contraindicated in hemorrhagic shock.


• Ketamine IV → 30 seconds • Ketamine IM → 3-4 minutes • Morphine IV → 5 minutes • Morphine IM → 30-60 minutes • Fentanyl IV → 1-2 minutes • Fentanyl IM → 7-15 minutes • Fentanyl OTFC → 3-15 minutes

Wounded and in pain.

Severe pain. Amputation, Long bone

fracture, Tourniquet, severe pain

Ketamine 50-100 mg IV; 300 mg IM/IN.

Consider Midazolam 0.5-1 mg IV; 2 mg IM.

Minor to moderate pain

Ketamine 0.1-0.25 mg/kg IV; 0.5 mg/kg

IM/IN.

Consider Midazolam 0.5 mg IV; 2 mg IM.

Presenter

Presentation Notes

In the Ranger Regiment, we recently added LDK in lieu of dilaudid. We are not anti-low dose ketamine. We just think it is not adequate for severe pain. I recommend the following. Let’s get away from opioids all together, this may help the medic become more comfortable with ketamine and address the pain issues on the battlefield. For minor to moderate pain, I say LDK instead of an opioid. For severe pain and injuries, use HDK. In addition, I recommend using a small amount of midazolam, anywhere from 0.5-1.0 mg IV. This is a simple, straight forward protocol.


• EMR/EMT/AEMT/NRP

• Minimum psychomotor skills

• EMT=NPA/OPA, PO Glucose/ASA

• 68W requires approx 212 hrs to AEMT

• 68W/EMT giving Ketamine!?


• Ketamine has great utility in EMS-large dose range, shelf stable, multiple routes of admin

• Ketamine is very safe-fewer major adverse events than opoids

• Dosing range determines effect and duration-caution about LDK psychomimetic effects(disarm/safe)


We succeed only as we identify in life, or in war, or in anything else, a single overriding objective, and make all other considerations bend to that one objective. -GEN Dwight D. Eisenhower

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cord cunningham, md, mph lieutenant colonel, us army 1st ......very low-cost medication; generic:...

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