PTSD following surgery -

Cognitive deterioration after ICU hospitalization and surgery

M. A. Papoulas

9th July, 2014

Setting goals for treatment“Quality of outcome in the patient’s point of view is more likely to depend on whether he or she can continue to function as before surgery.”

Post-Traumatic Stress Disorder

• Common anxiety disorder • Exposure to a terrifying event or ordeal• Physical harm• Family members can also develop PTSD • Depression, alcohol abuse, other anxiety disorders

PTSD Criteria

1. Traumatic event, life threatening, distress

2. One or more symptoms of re-experiencing the event

3. Three or more symptoms of avoidance

4. Two or more symptoms of hyperarousal

18-42% of injured patient 1-6 months post injury

2-36% one year post injury

Steel et al. Injury 2011

• Trauma is a disease• Late and long term consequences • Unavailability of proven screening and treatment

strategies• Nationwide US study of injury survivors: PTSD and

depression are independent contributors to the inability to return to work 12 months after injury

Ann Surg 2013

PTSD for surgically Hospitalized survivorsZatzick et al, Ann Surg 2013

Care Intervention

• Delivered in the inpatient ward, outpatient clinic, telephone, community rehabilitation

• Care management, pharmacotherapy, cognitive behavioral therapy (CBT)

• Motivational interview targeting alcohol abuse• Behavioral activation and pleasant activities

PTSD Symptom Severity by Treatment Group

Symptomatic and functional outcomes

Intervention Patients

• Physical function improvement (p < 0.01)• Trend level effect on alcohol consumption and

depression• More like to receive evidence based PTSD

pharmacotherapy• Equally effective in patients with TBI

• Comparative efficacy of treatments for PTSD : a meta-analysis. Van Eten. Clin Psychol Psychother ,1998

Cognitive Behavioral Therapy shows an advantage compared with pharmacotherapy

“Courage is what it takes to stand up and speak. Courage is also what it takes to sit down and listen. “

Rothbaum et al. Biol Psychiatry 2012

Cognitive deterioration after ICU hospitalization and surgery

Post-Hospital Syndrome

• Acquired, transient condition of generalized risk• Vulnerability• Critical 30-day period• 25% of Medicare patients• Deconditioning, sleep deprivation, circadian rhythm,

nutrition, immune function, delirium, oversedation.

NEJM , 2013

Postoperative Cognitive Dysfunction POCD

• Transient Cognitive impairment • Usually resolves by one year• Impairment in memory, concentration and social

integration• MRI and MRS findings • Cognitive decline acceleration, dementia

Surgery, Inflammation and Cognitive Decline

Terrando N. Mayo Clinic Proc. 2001

Systemic Infection and Delirium

• Proinflammatory cytokines and brain communication

• TNF-a persistence in brain for months

• Activated microglia : – Production of inflammatory mediators– Weaken astrocytic tight junctions– Affect neuronal function

Lancet 2010

Acute Care, Critical illness Hospitalization and Cognitive function in Older Adults

• Prospective cohort study• 1994- 2007, n = 2929, > 65 yo, without dementia • Cognitive Ability Screening Instrument (CASI)• Inclusion of participants with 2 or more study visits• Mean follow up 6.1 years

JAMA , 2010

• Noncritical and critical illness hospitalizations were each associated with greater decline in cognitive functioning scores.

• Noncritical illness hospitalizations were significantly associated with incident dementia

• N = 821 patients • MICU or SICU• Evaluation of in-hospital delirium• Global cognition and executive function assessment

3 and 12 months after discharge• Duration of delirium and use of sedative or analgesic

medications

• Duration of coma was not associated with worse global cognition and executive function scores

• No independent association between sedative or analgesic agents and long term global cognition and executive function was found

Duration of Delirium and Global Cognition Score at 12 months

Limitations

• Inability to test patients’ cognition before their emergent illness

• Unable to complete all cognitive tests

• Confounding by death or withdrawal

Alzheimer Disease

• Degenerative disease• Most common form of dementia• High Prevalence• Late onset, sporadic, multifactorial

Alzheimer’s Disease and Anesthesia

Marie P. et al. Neuroscience, 2011

Modulation of Murine Alzheimer Pathogenesis and Behavior by Surgery

• Animal Protocols (WT and x3TgAD)• Surgery and anesthetic exposure- 3 groups

1. Desflurane only

2. Desflurane and Surgery

3. Air controls

Tang et al. Ann Surg, 2013

Behavioral Testing

Learning and Memory testing

MWM Quantifies Cognition

• Escape from pool• Reference memory• Swim speed • Working memory

Motor and Coordination Assessment

Results

Mean Trials per Platform

Mean swim speed

Mean ratio of target/opp

pTau

Aβ plaques

16 w PO

Controls Desflurane Surgery

Top 10 Myths Regarding Sedation and Delirium in the ICU

1. All Mechanically Ventilated ICU Patients Require Sedatives

2. It Is Easier to Care for Deeply Sedated ICU Patients

3. Only Surgical ICU Patients Experience Pain

4. Sedatives Help to Facilitate Sleep in ICU Patients

Peitz GJ. Crit Care Med 2013

5. Delirium is a Benign and Expected Side Effect of Being in the ICU

6. Delirium Assessment and Recognition is Consistent and Uniform

7. All ICU Delirium is Similar and Can be Managed Effectively by Medications

8. Daily Interruptions of Sedative Medications are Unsafe

9. Sedative and Analgesics Do Not Accumulate with Prolonged Use

10. Deep Sedation and Amnesia Derived From Sedative Administration in ICU Result in Improved Psychological Outcomes, especially PTSD

Anesthesiol. 2011

1970s More sedation

1980s Perhaps less sedation?

1999 More control of sedation

2000 A daily wake up trial

2008 A daily wake up trial and spontaneous breathing trial

2010 No sedation

Undersedation versus oversedationTRENDS

Daily interruption of sedative infusions in critically ill patients undergoing mechanical ventilation

“Wake up trial”, pause of sedation and analgesicsKress NEJM, 2000

Endpoints of daily interruption of sedative drugs in ICU

1. Decreased duration of mechanical ventilation (more than 2 days)

2. Decreased length of ICU stay (3.5 days)

3. Practical

4. Cost-effective

5. Acceptable sedation minimizing adverse effects

6. Early detection of neurologic dysfunction

What is ICU Delirium?

• Delirium is a common clinical syndrome• Inattention and acute cognitive dysfunction• Disruption of neurotransmission• Hypoactive, Hyperactive, Mixed• Think rapid onset, inattention, clouding of

consciousness, fluctuation

Why monitor for Delirium?

• 50-80% of ventilated patients develop delirium

• 20-50% of lower severity ICU patients develop delirium

• Delirium leads to increased mortality, longer hospital stay, poorer recovery, higher costs, long term neurocognitive problems.

Ely EW. JAMA, 2001

A two step approach to Assess Consciousness

Step 1

Level of Consciousness (arousal)

RASS- Sedation assessment

Step 2

Content of Consciousness (delirium)

CAM- ICU Confusion assessment

• Delirium in critically ill patients: impact on long-term health-related quality of life and cognitive functioning. van den Boogaard M, et al. Crit Care Med. 2012

• Posttraumatic stress, anxiety and depression symptoms in patients during the first year post intensive care unit discharge. Myhren H, et al. Crit Care. 2010

• Dexmedetomidine vs midazolam or propofol for sedation during prolonged mechanical ventilation: two randomized controlled trials. Jakob SM, et al. JAMA. 2012

• The association between brain volumes, delirium duration, and cognitive outcomes in intensive care unit survivors: the VISIONS cohort magnetic resonance imaging study*. Gunther ML, et al.Crit Care Med. 2012

Take-home Message

• Awareness

• Direct research at the contributing factors

• Creation of rehabilitation programs

Thank You