Perioperative Anesthesia for Patients with Post-Traumatic Stress Disorder

David StampsCoANA Spring Meeting4 May, 2013

PTSD Defined

o PTSD: Post-traumatic stress disorder is a severe anxiety disorder that can develop after exposure to any event that results in psychological trauma

o DSM: development of characteristic symptoms following exposure to an extreme traumatic stressor involving direct personal experience of an event that involves actual or threatened death or serious injury, or other threat to one's physical integrity; or witnessing an event that involves death, injury, or a threat to the physical integrity of another person; or learning about unexpected or violent death, serious harm, or threat of death or injury experienced by a family member or other close associate (Criterion A1)

PTSD DSM

o Hyperarousal symptoms• Difficulty sleeping• Irritability/anger outbursts• Difficulty concentrating• Hypervigilance• Exaggerated startle response

Hamblen, PhD

PTSD DSM

o Re-experiencing symptoms• Recurrent recollections of event• Recurrent distressing dreams of event• Acting or feeling as if event were occurring• Psy distress at cues resembling event• Psy reactivity to cues

Hamblen, PhD

PTSD DSM

o Avoidance/numbing symptoms• Avoiding thoughts/feelings/conversations• Activities/places/people that cause reminders• Inability to recall part of trauma• Decreased interest in activates• Estrangement• Restricted range of affect• Sense of foreshortened future

Hamblen, PhD

National Comorbidity Surveyo Early 1990's

o Interviews of a representative national sample of 8,098 Americans

o Age 15 to 54 years

o Lifetime PTSD was 7.8% general population• Women (10.4%)• Men (5%)

PTSD Prevalence (NCS-R)o Lifetime PTSD prevalence = 6.8%• 9.7% women• 3.6% men

o Current past year PTSD prevalence = 3.6%• 5.2% women• 1.8% men

Kessler et al, 2005.

We never know who our PTSD pts are going to be or what they will look like

Prevalence Among Children and Adolescentso No population-based epidemiological studies• Studies examined prevalence of PTSD high-risk children;

experienced specific traumatic events, such as abuse or natural disasters• May have a higher prevalence of PTSD than adults in the general

population

• (2003) – Prevalence of PTSD among adolescents• National Survey of Adolescents

• Household probability sample of 4,023 adolescents between the ages of 12 and 17• DSM-IV criteria for PTSD: • Six-month prevalence was estimated to be 3.7% for boys and 6.3% for

girls

National Center for PTSD

Conditional Risk

o 20% of exposed women and 8% of exposed men develop PTSD

o Trauma most likely to cause development• Rape• Physical abuse• Molestation• Threat (weapon)• Sudden loss of a loved one

Kessler et al. 2005

Combat Exposure

o NCS-R• Lifetime prevalence of PTSD = 39% Male combat

veterans• Male combat vs all other male trauma• Higher lifetime PTSD prevalence• Greater likelihood of delayed prevalence• Greater likelihood of unresolved symptoms

Keesler et al 2005

OR/PACU

Post-Operative Definitionso Postoperative Delirium • Acute change in cognition• 24 to 72 hours after surgery• Decreased ability to focus, sustain, or shift

attention• Not explained by preexisting/evolving disorder

i.e. dementia or psychosis

Definitions

o Emergence Delirium (ED) • Psychomotor agitation • Ranging from frequent, nonpurposeful

movement to overt physical aggressiveness • Immediately or shortly after emergence from

anesthesia• Self-limited, may last from minutes to hours

Definitions

o Postoperative Cognitive Dysfunction Decline in cognitive functioning that manifests

after surgery Patient must demonstrate new-onset impaired

functioning that:▪ Affects at least 2 cognitive processes ▪ Persisted for at least 2 weeks,▪ Has been confirmed by some form of objective testing▪ Accompanies a general medical condition or nervous

system dysfunction▪ Not better explained by the presence of▪ Delirium, dementia, or amnestic disorder

Incidence of ED

o Emergence Delirium• 4.7% to 21.3% of adults after general anesthesia• Identified risk factors • Preoperative administration of benzodiazepines• Untreated postoperative pain• PTSD NOT mentioned

o Emergence delirium is associated with multiple adverse outcomes• Self-extubation, unintended removal of lines/tubes,

injury to patient/staff, longer stays PACU• Not associated with greater postoperative mortality in a

population of mixed ages (unlike postoperative delirium)

Anesthetic Care of PTSD Ptso Can you devise an anesthetic plan for your

PTSD Pt?• We’ll build toward this

o What research is out there to guide you?• Little to none

o Can you treat PTSD with anesthesia?• Lets address this first

PTSD/Stellate Ganglion Block (SGB)o History• 2003, a published report demonstrated a reduction in

PTSD-associated anxiety by clipping the sympathetic ganglia, via an endoscopic sympathetic block (ESB) at the second thoracic vertebra (T2)

• Most recently, the first successful use of a stellate ganglion block (SGB) for the treatment of PTSD was reported in 2008. Lipov EG, Joshi JR, Lipov SG, Sanders SE, Siroko MK. • Cervical sympathetic blockade in a patient with

posttraumatic stress disorder: a case report. Ann Clin Psychiatry. 2008;20:227–228.10

PTSD/SGB

o PTSD causes an increase in nerve growth factor (NGF)• NGF: protein important part of the development/

survival of nerve cells, especially sensory neurons like those that transmit pain, touch and temperature

• An elevation in NGF has been linked to episodes that stimulate adrenaline

• Growth of nerve shoots/sprouts in the brain=increase in norepinephrine levels

• Lead to the development of pathological states• Local anesthetic injected near the stellate ganglion

reverses this domino effect by lowering NGF concentration

1. Precipitating event, estrogen decrease, nerve trauma, PTSD triggering event

2. NGF increase

3. Retrograde transport of the NGF

1. NGF increase in the stellate ganglion

2. Sprouting of the sympathetic fibers distally

3. Increase in the brain norepinephrine

1. Stellate ganglion block

2. Reduction of NGF decrease in sprouting, reduction of brain norepinephrine and resolution of symptoms

PTSD/SGB

o Study Objective: Report the successful use of stellate ganglion blocks (SGBs) in two patients experiencing symptoms PTSD

o The Post-traumatic Stress Disorder Checklist (PCL) • 17-item psychometric test commonly used to screen

for PTSD

o The PCL administered day prior to treatment, to establish a baseline, day after treatment. The PCL was also utilized during follow-up visits to quantify the patient’s symptomotology

PTSD/SGB: Case 1

o 46-year-old Hispanic male recently retired from the military. Symptoms commenced in the first Gulf War following a close-quarters combat event in an Iraqi-held bunker

o 10 enemy combatants were killed at close range

o Briefly rendered unconscious from an explosion

o The patient was not visibly injured in the assault

PTSD/SGB: Case 1

o In the care of a psychiatrist for over one year

o Medications• Sertraline, quentiapine, trazadone, venlafaxine, and

zolpidem• Quentiapine was prescribed to control PTSD-related

nightmares

o Never diagnosed with any type of thought disorder or other psychotic condition

o Initial pre-injection PCL score was 76/85

o He recounted that since his trigger event he could not recall a time when he slept for more than 2 to 3 hours

PTSD/SGB: Case 2

o 36 year old white male active duty service member• Battle of Fallujah during Operation Iraqi Freedom• Engaged in killing enemy combatants at close range exposed to

“hundreds” of civilian and combatant dead

o In the care of a psychiatrist for 1 year before his SGB

o Symptoms included• Pronounced anxiety symptoms-shortness of breath, heart palpitations,

poor sleep, and nightmares• The patient’s anxiety symptoms were in direct response to a triggering

event, and do not appear to be related to a co-morbid diagnosis

o Medications• Mirtazapine, sertraline, and zolpidem

o His pre-SGB PCL score was 54/85

PTSD/SGB: Case Study Resultso Both patients experienced immediate,

significant and durable relief as measured by the PCL (score minimum 17, maximum 85)• Pt 1:• PCL=25, after 7 months PCL=67• Repeat SGB brought PCL to 23, leveled out at 34• Five minutes after SGB “a cloud had lifted” from his mind• Global feelings of anxiety 8 out of 10 to a 2 out of 10 • Great deal of satisfaction • First time since his symptoms started (18 years ago) he

was able to sleep for 6 to 7 hours • Nightmares diminished in both intensity and frequency

PTSD/SGB: Case Study Resultso Pt 2:• Post- injection PCL score =24• Seven months after SGB, PCL score consistent 24.• Patient’s spontaneous comments • “I feel at peace” • “I’m just starting to be aware of how much anxiety I

have been living with” • “My mind is not racing” • He reports feeling like himself, and no longer feels “like

an unpleasant person” • His erectile dysfunction resolved when he discontinued

medications

PTSD/SGB: Case Study Resultso In both instances, the pre-treatment score

suggested a PTSD diagnosis whereas the post-treatment scores did not

o Both patients discontinued all antidepressant and antipsychotic medications while maintaining their improved PCL score

Anesthetic Care of PTSD Ptso Can you devise an anesthetic plan for your PTSD

Pt?• We’ll build toward this

o What research is out there to guide you?• Little to none

o Can you treat PTSD with anesthesia?• Lets address this first

PTSD Study/Military CRNA’s

o Aug 2012 Qualitative study• Describe experiences of 3 Army CRNA’s• Pts with Traumatic Brain Injury (TBI)/PTSD• All pts undergoing general anesthesia• All cases post 9/11• CRNA’s observed cases of pts awakening in

Delirium (10%)• Describe your experiences• Thought processes as to why delirium occurs

Military CRNA’s

o Emergence Delirium defined by study CRNA’s• Pt awakes in violent and thrashing manner• Attempts at self extubation, breath holding, IV

line displacement, assault on OR staff, the want to flee

• Behavior could occur at anytime from end of surgery to the end of PACU stay

Military CRNA’s

o Five themes emerged• Emergence delirium (ED) exists, and to a greater

extent in military personnel.• ED more prevalent in younger population.• TIVA was superior GA for TBI/PTSD pts• Talking to pts pre induction and on emergence

vital• Profound impact of Ketamine

Military CRNA’s

1. ED exists and to higher degree in military than general population

All CRNA’s experienced ED in the target population

All have years of civilian experience and do not see this in that population (extent or degree)

Military CRNA’s

2. ED more prevalent in younger population Could be mere fact that young men are more

prevalent in targeted population Older personnel have greater experience and

time to develop coping strategies

Military CRNA’s

3. TIVA superior to potent inhalational anesthetic

All 3 CRNA’s would preferentially use TIVA for known PTSD/TBI

One says “less than 1% of my TIVA pts have ED”

Military CRNA’s

4. Talking preoperatively/during emergence to Pts

All three CRNA’s agreed beneficial to offer reassuring words to pts before induction

Room quite, reorientation upon emergence Things we all do but with a heightened

awareness than our average pt

Military CRNA’s

5. Ketamine for PTSD/TBI Has role in alleviating ED One CRNA uses 1mg Ketamine per 10mg

Propofol and sufenta Another uses 100mg Ketamine/100mg Propofol

induction and then TIVA

USAFA/VA PTSD/ED experienceo Case Study of USAFA/VA pt with ED• 26 Y/O white male for excision lipomas• VSS, 70”, 235 lbs• Meds• Cyclobenzaprine/Gabapentin/Omeprazole/Prazosin/

Sertraline/Trazadone• KNDA

USAFA/VA PTSD/ED experienceo Med Hx• Tobacco/HTN/GERD/Arthritis• PTSD/TBI

o Surg Hx• Appy/Lipoma• Hx of “waking up” during procedure• Hx of “combative” wakeup

o Anesth plan• LMAC

USAFA/VA PTSD/EDexperienceo Anesthetic• Midazolam2mg/Fentanyl 100Mcg Preop• Propofol infusion, 350mg total• Total case time 58 min• Fast track to ASU as pt appeared to be GTG• 1443 shortly after arrival to ASU• Pt flashback to Iraq war, not orientated to current

date, place, or situation. Taken to PACU for observation

USAFA/VA PTSD/ED experienceo PACU Stay• Immediately given 2mg Midazolam• Usable to take initial vital signs as pt combative

and trying to get out of gurney• Asking for location of other soldiers/blood

identification• Pts escort brought to bedside, 2:1 care, constant

reorientation to place/time/situation• Back to ASU at 1448

USAFA/VA PTSD/ED experienceo Discharge from SDS center• 1622• Orientated to place/time/situation• Call back 0955 next day• Slept well• No recall of ED event or any events that happened

after initial midazolam dose preop

o Negative impact• Time, personnel, danger to self and others

USAFA/VA PTSD/ED Case 1o 66 y/o male, ASA III, Prostate Bx

o Violent wake-ups last 2 anes (2 OR personnel to ER)

o Med Hx: OSA/COPD/CAD/HTN/DM/Bipolar/PTSD

o Surg Hx: Cardiac Stent ‘01/Colonoscopy ’12

o Hx of Military assassin/hand to hand combat

USAFA/VA PTSD/ED Case 1o Anes plan: Propofol/ketamine heavy

sedation• 15 min procedure with local most stimulating• Load 100mg Propofol/50mg Ketamine, followed by 2-

3cc bolus strait Propofol• Stopped dosing when local in (10 more minutes)• Total 200mg Propofol/50mg Ketamine

• Fast tracked to ASU, awake, reports “best anes I've had. I don’t feel angry or scared”

• Pain 0/10, Sao2 99%• D/C to home within 1 hr, no ill effects over night, was

“out of it for 24 hrs”

USAFA/VA PTSD/ED Case 1o 35 y/o male, ASA II, gang cyst exc right wrist

o Discussed anes options:• IV Nl surg pref, Lmac not option(per pt), GA

o Med Hx:Tobacco/DM type 2/PTSD/Depression

o Surg Hx: knee arthroscopy ’09, no A/C

o Pt and wife both express concerns about any alternative other than GA (preference)

USAFA/VA PTSD/ED Case 1o Pre-op with 2mg Versed/Fentanyl 100mcgo 1402-Induction Propofol 200mg/lidocaine 50mg/Ketamine

50mg. iGel placed (BIS at 20)o 1417-Propofol/Ketamine at 80mcg/kg/min o 1425 BIS at 29 and pt light, increased infusion to

125mcg/kg/mino 1438 infusion offo 1444 surgery completeo 1449 pt extubated, stable, SV, to PACU calm/alert Total

Propofol 400mg/Ketamine 100mg

USAFA/VA PTSD/ED Case 1o Ketorolac 30mg at end of case

o PACU stay uneventful with D/C to home within 1.5 Hrs. Follow up in AM showed no ill effects with high satisfaction with anesthesia

Anesthetic Care of PTSD Ptso Can you devise an anesthetic plan for your

PTSD Pt?• We’ll now explore this

o What research is out there to guide you?• Little to none

o Can you treat PTSD with anesthesia?• Lets address this first

PTSD/Perioperative Management

o Comorbiditieso Substance abuseo Chronic pain

o Psychoactive medso Anxiety concernso Cognitive function

Perioperative Care

o Comorbidities• Cardiac risk factors (lifestyle factors)• HTN/DM/HLP• COPD/OSA/GERD/Obesity

• Depression• 36% in PTSD pts• 3.5% non• PTSD pts• PTSD/Depression may share common genetic basis

o Substance abuse (veteran study)• Tobacco 3X• ETOH 5X• MJ• Medical/Rec

• Illegal drugs 3X

Perioperative Care

o Chronic pain• Encourage Nx staff to educate pt on taking opioids

preop• Pain eval DOS ASAP

o Psychoactive meds• Careful consideration of medication list• SSRI• SNRI• MAO’s• TCA• Alpha antagonists• Anticonvulsants/Benzo’s• Anitpsychotics

Perioperative Care

o Anxiety considerations• Establishing trust and full explanations• Avoidance of loud noises• Wake pt with verbal stimulus vs touch• Elicit and known triggers• Elicit known wake-up patterns

Perioperative Care

o Cognitive function• PTSD has worse preoperative cognitive function• Measures of verbal memory

• Cognitive function found to be inversely related to PTSD symptoms • Retain/learn new info for short period• Manipulate the info in meaningful way• Produce response based on manipulated info• Decreased cognitive reserve (vs overall intelligence) • Pts vulnerable to post-op cognitive decline

Perioperative Care

o PTSD NOT a predictor of:• Length of hospital stay• Readmission rate• Certain surgery specific outcomes

o PTSD NOT known to exacerbate symptoms• Studies limited• Only anecdotal cases of surgery exacerbating

symptoms when aspects of perioperative exp similar to the pts traumatic experience

Perioperative Care

Preoperative evaluation Elicit history of PTSD Dx, sleep

disturbances/nightmares▪ Amitriptyline/sertraline

Younger troops much more common than older Vets to have ED

Elicit history of previous anesthetic experiences of ED

Plan care with PACU for this PTSD pt

Perioperative care

Anesthetic Plan Regional L/MAC if possible TIVA for GA▪ Avoidance of Midazolam▪ Propofol/ketamine mix▪ Adequate pain control; especially as many are chronic

pain pts▪ Consider NSAID and long acting opioid ie: morphine

▪ Consider an alpha 2 agonist (dexmetatomidine)▪ Decreases sympathetic tone/cascade

▪ Awake with verbal stimulus/avoid touching head for stimulus

PACU

One-on-one care if possible

Quiet, non-stimulating environment(good luck)

Family in PACU if possible

Frequent reorientation

Consider avoidance of midazolam for emergence delirium Tends to make pts worse or have no effect

Current Research

o Developing Anesthesia as Post Traumatic Stress Disorder (PTSD) Therapy

o Southern California Institute for Research and Education o National Institute of Mental Health (NIMH)

• Purpose This preclinical phase 1 development study in healthy volunteers seeks to identify if low doses of commonly used non-triggering anesthetic agents might have clinical utility for modulating emotional memory processing and to understand the nature of the brain mechanisms of drug action. Optimally, a drug, dose and brain mechanism of action will be identified that will form the foundation for future use in clinical studies of patients with PTSD

• Drug: DexmedetomidineDrug: PropofolDrug: KetamineDrug: Nitrous Oxide

• A low dose of medication is used during scanning after dose piloting outside the scanner for memory effects and tolerability

Current Research

o Ketamine as a Rapid Treatment for Post-traumatic Stress Disorder (PTSD) (KetPTSD)

o Dennis Charney

o Collaborator:• Department of Defense• Purpose The objective of the proposed study is

to test if a single IV dose of ketamine (0.5 mg/kg) decreases symptoms of PTSD

Current Research

o Modafinil in the Treatment of PTSD (Posttraumatic Stress Disorder)

o Biomedical Research Foundation o National Center for Research Resources (NCRR)o National Institute of General Medical Sciences (NIGMS

)o The purpose of this study is to determine if modafinil

is more effective than placebo in the treatment of posttraumatic stress disorder (PTSD) in male combat veterans who have been deployed to Iraq or Afghanistan

Current Research

o Eszopiclone for the Treatment of Posttraumatic Stress Disorder

o Rush University Medical Center

o National Institute of Mental Health (NIMH)

o The purpose of this study is to determine if eszopiclone relative to placebo (sugar pill) is effective and tolerable for people with posttraumatic stress disorder (PTSD)-related sleep disturbance. The investigators will also examine the impact of treatment on sleep patterns, memory recall bias, and level of inflammatory markers (cytokines). The investigators predict eszopiclone will lead to greater improvement than placebo in measures of PTSD symptoms, memory recall bias, and level of inflammatory markers

PTSD Monies

o J $100M PTSD and TBI Study

o In a press release from September 19, 2012, the VA and DoD announced they are investing more than $100 million in research to improve diag nosis and treatment of mild traumatic brain injury (mTBI) and (PTSD)

o “At VA, ensuring that our veterans receive quality care is our highest pri ority,” said Secretary of Veterans Aff airs Eric K. Shinseki. “Investing in innovative research that will lead to treatments for PTSD and TBI is criti cal to providing the care our veterans have earned and deserve.”

PTSD Monies

o An executive order, signed by the President on August 31, 2012, was designed to improve access to mental health services for our veterans, ser vice members, and military families. In that order, the President directed the DoD, the VA, HHS, and the De partment of Education to develop a National Research Action Plan that will include strategies to improve early diagnosis and treatment effec tiveness for TBI and PTSD

Therapy