The Hidden Scar

Anesthesia and PTSDCopyright 2019. Randy Cornelius. All Rights Reserved.

Disclosure Statement

I have no financial relationship with any commercial interest related to the content of this activity. I will not discuss off-label use during my presentation

Learner Outcomes

Recognize and identify potential PTSD patients during the pre-anesthetic evaluation utilizing information provided during presentation.

Formulate and implement an anesthetic plan that prevents or minimizes the incidence of emergence delirium in patients with PTSD by utilizing techniques discussed during the presentation.

Identify current PTSD treatment options. Identify the pharmacodynamics of SSRIs, SNRIS, benzodiazepines,

ketamine, and α2- adrenergic agonists as related to impact of PTSD.

Scenario

Female in 30’s going to OR for ortho procedure on forearm r/t gunshot that occurred at work

Pre-op diagnosis of anxiety Discovered military experience Plan is general anesthesia Procedure uneventful Upon arrival to PACU, restless, agitated, not orientated, semi-combative What happened? What could have been done different?

Earliest description in modern era from Civil War (1861-1865) Previously recognized by other names

– Soldier’s heart– Shell shock– Battle fatigue– Concentration-camp syndrome– Rape-trauma syndrome

First appeared in DSM-III in 1980

https://biodynamichealth.com/2013/08/20/the-effects-of-craniosacral-therapy-on-post-traumatic-stress-disorder-symptomology-in-vietnam-combat-veterans/

Diagnostic and Statistical Manual of Mental Disorders (5th edition)

2013 diagnostic criteria revised New category, Trauma- and

Stressor-Related Categories – All conditions in category require

exposure to traumatic or stressful event as diagnostic criterion

Introduced preschool subtype of PTSD for children ages six years and younger

https://www.scientificamerican.com/article/redefining-mental-illness/

Debilitating disorder characterized by re-experiencing, avoidance, negative cognitions/mood, and arousal following exposure to actual or threatened death,

serious injury, or sexual violation

https://depositphotos.com/41545463/stock-photo-ptsd-concept-signs.html

Diagnostic CriteriaCriterion A: Stressor

exposed to: death, threatened death, actual or threatened serious injury, or actual or threatened sexual violence, in the following way(s):– Direct exposure– Witnessing the trauma– Learning that a relative or close friend

was exposed to a trauma– Indirect exposure to aversive details of

the trauma, usually in the course of professional duties

Criterion B: Intrusion symptoms traumatic event is persistently re-

experienced in the following way(s):– Unwanted upsetting memories– Nightmares– Flashbacks– Emotional distress after exposure to

traumatic reminders– Physical reactivity after exposure to

traumatic reminders

Criterion C: Avoidance avoidance of trauma-related

stimuli after the trauma, in the following way(s):– Trauma-related thoughts or

feelings– Trauma-related external

reminders

Criterion D: Negative alterations in cognitions and mood

negative thoughts or feelings that began or worsened after the trauma in the

following way(s):– Inability to recall key features of the

trauma– Overly negative thoughts and

assumptions about oneself or the world– Exaggerated blame of self or others for

causing the trauma– Negative affect– Decreased interest in activities– Feeling isolated– Difficulty experiencing positive affect

Criterion E: Alterations in arousal and reactivity

trauma-related arousal and reactivity that began or worsened after the trauma, in the following way(s):– Irritability or aggression– Risky or destructive behavior– Hypervigilance– Heightened startle reaction

Criterion F: Duration symptoms last for more than 1

month

Criterion G: Functional significance symptoms create distress or

functional impairment

Criterion H: Exclusion symptoms are not due to

medication, substance use, or other illness

SpecificationsDissociative Specification

in addition to meeting criteria for diagnosis, an individual

experiences high levels of either of the following in reaction to

trauma-related stimuli:– Depersonalization. Experience of

being an outside observer of or detached from oneself

– Derealization. Experience of unreality, distance, or distortion

Delayed Specification full diagnostic criteria are not

met until at least six months after the trauma(s), although onset of symptoms may occur immediately

70% of U.S. adults experience some type of traumatic even at least one in their life (223.4 million people)

Up to 20% of those will develop PTSD (31.3 million people) Estimated 8% of Americans (24.4 million people) have PTSD at any given time Women twice as likely 60-80% of victims who have a severe traumatic experience will develop PTSD About 50% of all outpatient mental health patients have PTSD

https://www.mbs.ac.uk/news/nine-facts-you-didnt-know-about-an-mba/

Vietnam Veterans – 30% in their lifetime

Gulf War Veterans– 12% in a given year

Operation Iraqi Freedom and Enduring Freedom – 11-20% in a given year

FYI: 2.77 million service members have served on 5.4 million deployments since 2001

https://floridapolitics.com/archives/194236-florida-most-veteran-friendly-state-new-report-shows

Pathophysiology of PTSD Hyperactive glutaminergic response Glutaminergic neurotransmission between hippocampus, amygdala, and medial

prefrontal cortex determine processing stressful stimuli Massive release with impaired reuptake of glutamate increases stimulation of

NMDA receptors Allows substantial influx of calcium ion which potentiates short & long-term

changes to neuronal tissue Glutaminergic excess exclusivity associated with increased intracellular calcium

to cause cellular change and cellular death

www.googleimages.com

www.googleimages.com

Treatment OptionsTrauma-focused Psychotherapies Psychopharmacology

http://www.drcarnazzo.com/cognitive-therapy.html https://www.slideshare.net/aashishparihar/psychopharmacology-69181628

Trauma-focused Psychotherapies

Strongly Recommended Cognitive Behavioral Therapy Cognitive Processing Therapy Cognitive Therapy Prolonged Exposure

Conditionally Recommended Brief Eclectic Psychotherapy Eye Movement Desensitization &

Reprocessing Therapy (EMDR) Narrative Exposure

Psychopharmacology

Selective Serotonin Reuptake Inhibitors

Sertraline (Zoloft) Paroxetine (Paxil) Fluoxetine (Prozac)

Selective Serotonin-norepinephrine Reuptake Inhibitor Venlafaxine (Effexor)

SSRI Mechanism of Action

Selective inhibition of 5-HT (serotonin) reuptake

Leads to increased extracellular serotonin

Causes more action on serotonin receptors on post synaptic side

https://www.youtube.com/watch?v=coIXxdZ2EsA

SNRI Mechanism of Action

Bind at the 5-HT & norepinephrine re-uptake transporters

Preventing re-uptake and subsequent degradation

Leads to accumulation of monoamines in synaptic cleft

https://www.youtube.com/watch?v=coIXxdZ2EsA

Ketamine Clinics

The first evidence from a randomized clinical trial that the analgesic agent ketamine may provide rapid symptom reduction patients with chronic PTSD when delivered IV was published in 2014

Researchers lead by Adriana Feder MD found that IV infusion of ketamine (0.5 mg/kg) was associated with significant and rapid reduction of PTSD symptoms compared with an active control agent

Ketamine clinic in Texas is treating large number of PTSD patients with reportedly great results

Stellate Ganglion Block

Used to treat pain since 1925 First used to treat depression in 1947 First use to treat PTSD in 2008 Typical Stellate Ganglion Block done at C7 Done at C6 for PTSD (called Chicago Block) Appears only to work when administered on the right side

https://www.researchgate.net/figure/Stellate-ganglion-block-technique_fig1_269477576

MDMA

BKA Ecstasy Ring-substituted amphetamine

structurally similar to mescaline Produces altered sensations

increased energy, empathy & pleasure

Used as an adjunct with trauma-focused psychotherapy

Clinical phase-three trial FDA approved

https://www.narconon.org/drug-abuse/ecstasy-effects.html

Medicinal Marijuana

Legalized in over 23 states PTSD is 1 of approved conditions

for usage in some states Literature is suggestive of

potential decrease in symptomology

Notable lack of large-scale trials

https://www.awebtoknow.com/how/10-common-misconceptions-about-medical-marijuana/

PTSD independent predictor for emergence delirium (ED) Emergence from anesthesia more difficult to control than other phases 40% of military anesthesia providers view ED as a moderate-to-high safety risk to

patient and staff

https://www.spectatornews.com/opinion/2013/11/06/35123/

Emergence Delirium

An acute alteration in neurological psychomotor functioning consisting of restlessness, confusion, combativeness upon waking up from general

anesthesia

Emergence Delirium

Originally known as postoperative psychosis

First documented in 1819 First ID’d 1960s by Eckenhoff Initially categorized as

pseudopyschological disorder

Facts

3.0-4.7% of general population after general anesthesia, majority in pediatric

Estimated 27% occurrence in combat veterans Maybe as much as 50% among combat injured veterans with PTSD,

anxiety, or depression 78% of Army anesthesia providers encountered occurrences

Risk Factors

Age Benzodiazepines Etomidate or thiopental Volatile anesthetics PTSD, anxiety, depression Surgery type Pain control

Possible Pathophysiology

Commonly used anesthetic agents target receptors located on amygdala & hippocampus

Termination of anesthesia allows agent to leave these areas of the brain, and emergence and awakening follows

Hearing is first sense to return Unfamiliar auditory stimuli trigger exaggerated fear response driven by already

hyper-responsive amygdala Results in altered perception of nonthreatening stimuli

www.googleimages.com

Anesthesia Concerns/Considerations

How to identify individuals who suffer from PTSD

Impact of medications taken for PTSD

http://thlorenz.com/talks/memory-profiling/book/considerations/considerations_0.html

How to Identify PTSD previously listed as an anxiety disorder Known past traumatic event If military (current or prior) ask If suspected, ask “Have you ever had problems waking up from

anesthesia?” Review medication list, look for SSRIs, SNRIs, question if on prazosin

without hx of hypertension

Management of Medications (SSRI/SNRI)

“Should be” continued through perioperative period Interactions:

– Inhibit P450’s : Codeine/oxycodone, β-blocker, warfarin, benzodiazepines & some antiarrhythmic levels may be elevated.

– Tramadol is a serotonin releasing agent and is metabolized by P450 enzymes, therefore run risk of serotonin syndrome

– Up to 1000 interacting medications

Careful of Serotonin Syndrome

Drug induced syndrome Due to increased serotonin concentration in CNS “Classic Triad” clinical features

– Neuromuscular excitation: clonus, hyperreflexia, myoclonus, rigidity, nystagmus

– Autonomic nervous system excitation: hyperthermia, tachycardia, hypertension, GI hypermotility, nausea/vomiting

– Altered mental status: agitation, delirium, restlessness, anxiety Clinical diagnosis

Serotonin Syndrome Treatment

Mild to moderate cases usually resolves in 1-3 days after stopping serotonergic medications

Severe toxicity is medical emergency Supportive care consists of sedation as required to reduce muscle

hyperactivity Preventing hyperthermia is key goal in severe toxicity Serotonin antagonist (particular 5HT2a receptor antagonists) Oral cyproheptadine

Prazosin(Minipres)

α1-adrenoreceptor agonist Prescribed for PTSD related sleep

disorders (70-80% reduction)– Enhanced CNS adrenergic

activity and persistence during sleep

Most readily enters CNS

www.googleimages.com

Prevention of Emergency Delirium

Pre-operative– Identification – Acknowledge anesthesia concerns– Build trusting relationship– Assure safe environment– Include family or “battle buddy”

Medications to Avoid

Benzodiazepines Bind to gamma aminobutyric receptor (GABAa) enhancing binding of

GABA (principal inhibitory neurotransmitter of CNS) Produces anxiolysis, sedation, anterograde amnesia, alcohol

potentiation, & anticonvulsant and skeletal muscle relaxant effects PTSD patients exhibit decrease in benzodiazepine binding sites on

GABAa May reduce some aspects of anxiety, not effective in reducing hyper-

arousal symptoms

Prevention of Emergence Delirium Intraop

– Physiologic causes must first be addressed – Common causes must be ruled out before interventions begin– Identify medications useful in preventing Emergence Delirium r/t PTSD α2- adrenergic agonists Ketamine Promethazine? Droperidol?

– Avoid volatile agents– Consider TIVA– Avoid excessive pain or noxious stimuli– Emerge patient during peak time of drug of choice for Emergence Delirium– Utilization of complementary therapy “Vocal/local”

α2- adrenergic agonists Bind to α2 receptors (3 types) α2a mediate sedation, analgesia, &

sympatholysis Highest densities of α2 receptors are in

the pontine locus ceruleus (important source of sympathetic nervous system innervation of forebrain & vital modulator of vigilance)

Stimulation of α2-adrenergic neurons in medullary vasomotor center

Reduces norepinephrine turnover, decreasing central sympathetic outflow from CNS to periphery

https://symbiosisonlinepublishing.com/anesthesiology-painmanagement/anesthesiology-painmanagement45.php

α2 adrenergic agonistsClonidine

α2:α1 specificity ratio of 200:1 Half-life of 12-24 hours 2 mcg/kg after induction (based

on pediatric ED prevention) Give dose preoperatively or small

dose intraop 10-20 min before emergence

May consider small bolus dose as rescue medication

Dexmedetomidine α2:α1 specificity ratio of 1600:1 Half-life of 2-3 hours Approved in 1999 as sedative for ICU

and anesthesia settings 0.5 -1 mcg/kg/hr infusion (typical) 10 to 40 mcg bolus about 10-20

minutes before emergence 0.5 mcg/kg bolus following induction

(based on pediatric ED prevention)

Ketamine Phencyclidine derivative that binds to N-methyl-D-aspartate (NMDA) receptors

and inhibits activation by glutamate and decreases presynaptic release of glutamate

Numerous references name ED as adverse effect of ketamine (patients with psychological & personality disorders, and doses > 2 mg/kg)

Using subanesthetic-dose decreases available glutamate binding sites on NMDA receptors

May suppress conditioned fear responses during emergence delirium by reducing stimulation of amygdala

Controls pain Not a rescue drug Give early intraop; for long cases consider small doses each hour Dose of 0.15 to 0.5mg/kg ideal weight (based on pediatric ED prevention)

Other Medications

Promethazine Phenothiazine Typically used in perianesthesia

for antiemetic properties Give 20-30 min before

emergence

Droperidol Butyrophenone Historically used to treat PONV Carries “black box warning” FDA states black box warning is

not associated with small doses Give 20-30 min before

emergence

Prevention of Emergency Delirium Postoperative Any manifestation must be reported immediately to anesthesia Assume a calm disposition to reduce escalation of event Keep noise level down Provide a quiet environment Staffing consistency Minimize risk of triggering patient

– Use calm quite voices– Remain in front of patient– Avoid touching patient above the waist– If need to stimulate, touch foot with light taps versus torso– Keep syringes out of patient’s visual field

May discharge when normal discharge criteria met

Scenario Follow-up 2018 needs I&D of elbow at ASC In pre-op, informed anesthesia was in treatment for PTSD and had required

assistance waking up from general anesthesia Given total 4 mg versed over 2 doses for regional technique During emergence, became very agitated (OR staff wanted patient to wake up

quickly) Has flashback of shooting “stating could smell gunpowder and see shooter” Anesthesia determined narcotic induced hallucinations and administers narcan

and flumazenil Transferred to nearby ER

Follow Up

Surgery week later for closure Nervous about recurrence Informs anesthesia again about PTSD and anesthesia issues New anesthesia plan developed New anesthesia provider has previous anesthesia provider (with

permission) to see pre-op and case to receive training and experience in prevention of emergence delirium r/t PTSD

No issues report

http://thlorenz.com/talks/memory-profiling/book/considerations/considerations_0.html

Contact Information

Randy-cornelius@hotmail.com

ReferencesAmerican Psychiatric Association. (2013). Diagnostic and Statistical Manual of Mental Disorders (5th ed).Buckley, N., Dawson, A., & Isbister, G. (2014). Serotonin syndrome. British Medical Journal, 348, 33-35Chambers, R., Bremner, J., Mofhaddam, B., Southwick, S., Charney, D., & Krystal, J. (1999). Glutamate and post-traumatic stress disorder: toward a psychology of dissociation. Semin Clin Neuropsychiatry, 4(4), 274-281.Hanafy, M., El-Zahaby, H., & Swellam, A. (2004). The effect of dexmedetomidine on the emergence agitation associated with desflurane anaesthesia in children. English Journal of Anaesthesia, 20, 135-140.Hintzsche, K.(2018). Subanesthetic-dose ketamine to decrease emergence delirium in the surgical patient with posttraumatic stress disorder. AANA Journal, 86(3), 220-224.Kulka, P., Bressem, M., & Tryba, M. (2001). Clonidine prevents sevoflurane-induced agitation in children. Anesthesia Analgesia, 93, 335-338.Lipov, E., & Kelzenberg, B. (2012). Sympathetic system modulation to treat post-traumatic stress disorder (PTSD): A review of clinical evidence and neurobiology. Journal of Affective Disorders, 142, 1-5.Lovestrand, D., Phipps, P., & Lovestrand, S. (2013). Posttraumatic stress disorder and anesthesia emergence. AANA Journal, 81(3), 199-203.Lovestrand, D., Lovestrand, S., Deaumont, D., & Yost, J. (2017). Management of Emergence delirium in adult ptsd patients: Recommendations for practice. Journal of PeriAnesthesia Nursing, 32(4),356-366.McGuire, J. (2012). The incidence of and risk factors for emergence delirium in the U.S. military combat veterans. Journal of PeriAnesthesia Nursing, 27(4), 236-245

ReferencesRaskind, M., Peskind, E., Chow, B., Harris, C., Davis-Karim, A., Holmes, H., Hart, K., McFall, M., Mellman, T., Reist, C., Romesser, J.,Rosenheck, R., et al. (2018). Trial of prazosin for post-traumatic stress disorder in military veterans. New England Journal of Medicine, 378, 507-517.Ravindrand, L. & Stein, M. (2009). Pharmacology of PTSD: premises, principles, ,and priorities. Brain Res, 1293, 24-39.Thal, S., & Lommen, M. (2018). Current perspective on mdma-assisted psychotherapy for postraumatic stress disorder. Journal of Contemporary Psychotherapy, 48(2), 99-108.Umholtz, M., Cilnyk, J., Wang, C., Porhomayon, J., Pourafkari, L., & Nader, N. (2016). Postanesthesia emergence in patients with post-traumatic stress disorder. Journal of Clinical Anesthesia, 34, 3-10.Viswanath, O., Kemer, B., Jean, Y., Soto, R., & Rosen, G. (2015). Emergence delirium: a narrative review. Journal of Anesthesiology & Clinical Science, 4. doi:10.7243/2049-9752-4-2.Wheat, L., Turner, B., Diaz, A., Maani, C. (2018). Military service members and emergence delirium screening: An evidence-based practice project. Journal of PeriAnesthesia Nursing, 33(5), 608-615.www.apa.org/ptsd-guidelinewww.forbes.comwww.healmyptsd.comwww.ptsd.va.govYarnell, S. (2015). The use od medicinal marijuana for posttraumatic stress disorder: A review of the current literature. The Primary Care Companion for CNS Disorders, 17(3), doi: 10.4088/PCC.15r01786

Slide Number 1Disclosure StatementLearner OutcomesScenarioSlide Number 5Diagnostic and Statistical Manual of Mental Disorders (5th edition)Slide Number 7Diagnostic CriteriaSlide Number 9Slide Number 10Slide Number 11SpecificationsSlide Number 13Slide Number 14Slide Number 15Slide Number 16Treatment OptionsTrauma-focused PsychotherapiesPsychopharmacologySSRI Mechanism of ActionSNRI Mechanism of ActionKetamine ClinicsStellate Ganglion BlockMDMA�Medicinal Marijuana�Slide Number 26Emergence DeliriumEmergence DeliriumFacts Risk FactorsPossible Pathophysiology Anesthesia Concerns/ConsiderationsHow to IdentifyManagement of Medications (SSRI/SNRI)Careful of Serotonin SyndromeSerotonin Syndrome TreatmentPrazosin(Minipres)Prevention of Emergency Delirium Medications to AvoidPrevention of Emergence Delirium α2- adrenergic agonistsα2 adrenergic agonistsKetamineOther Medications Prevention of Emergency Delirium Scenario Follow-upFollow UpSlide Number 48Contact InformationReferencesReferences