Cognitive Dysfunction After Critical Care Illness. Élie AZOULAY, Réanimation Médicale Hôpital Saint-Louis, Université Paris 7, Paris, France, Europe

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Cognitive Dysfunction After Critical Care Illness Élie AZOULAY, Réanimation Médicale Hôpital Saint-Louis, Université Paris 7, Paris, France, Europe

First reported in 1923 as l'illusion des sosies by Capgras and Reboul-Lachaux, in a case report of a 53 year old woman who believed her husband and children had been replaced by doubles. Patients are often paranoid and may suffer from feelings of depersonalisation A patient ventilated/sedated for 10 days was convinced that impostors or doubles have replaced close family

ICU psychosis - Abnormal ICU environment, - Lack of a night or day, - Continuous noise (monitors and alarms)

PTSD-related Symptoms Symptoms of Anxiety Symptoms of Depression The Post- ICU Syndrome Phobia Sleeping pbms Life events (Financial, loss of work)] Guilt HRQoL nightmares, hallucinations, paranoid delusions, sleep disorders confusion.

The post-icu syndrome Stress Acute stress, PTSD-related symptoms PTSD Anxiety and depression Cognitive impairment

My 3-point framework Understanding Acute Stress Dirsorder, acute or chronic (delayed) PTSD Assessing cognitive burden in critical care survivors Risk factors for PTSD and recognizing the triad [sedation-memory-ptsd]

Stress symptoms, acute stress disorder and PTSD It s natural to have some of PTSD symptoms after a dangerous event. Sometimes people have very serious symptoms that go away after a few weeks. This is called acute stress disorder (< 1 month). When the symptoms last more than a few weeks and become a real problem, they might be acute PTSD. After 6 months, we discuss (delayed) PTSD Some people with PTSD don t show any symptoms for weeks or months. This is a major semantic issue

Acute stress reactions occurs within 30 days of a traumatic event Acute Stress Disorder emotional numbing, detachment, reduction in awareness of surroundings, derealization, depersonalization dissociative amnesia. And intrusion, avoidance and increased arousal.

PTSD: not all wounds are visible

What is PTSD? Post-Traumatic Stress Disorder, PTSD, is an anxiety disorder that can develop after seeing/living a terrifying event. When in danger, it s natural to feel afraid. This fear triggers a fight-or-flight response to prepare to defend against the danger or to avoid it. This healthy reaction is meant to protect a person from harm. But in PTSD, people may feel stressed or frightened even when they re no longer in danger. Traumatic events that may trigger PTSD include violent personal assaults, natural or human-caused disasters, accidents, or military combat.

Three groups of symptoms 1. Re-experiencing symptoms (INTRUSION): Flashbacks with racing heart, sweating, Bad dreams and Frightening thoughts. 2. Avoidance symptoms: Staying away from places, events, or objects that are reminders of the experience Feeling strong guilt, depression, numb or worry Losing interest in activities that were enjoyable in the past and having trouble remembering the dangerous event. 3. Hyperarousal symptoms: Being easily startled, Feeling tense or on edge Having difficulty sleeping, and/or having angry outbursts. These symptoms are constant (not triggered). These symptoms make daily tasks hard to do, such as sleeping, eating, or concentrating.

How can we assess if a patient has PTSD? Assessment during structured interview: Structured clinical interview for DSM IV (SCID) Clinician administered PTSD scale (CAPS) Self assessment : Davidson trauma scale (DTS) Impact of invent scale (IES), IES revised (IES-R) Posttraumatic stress syndrome 10 question inventory (PTSS-10) and PTSS-14

Symtoms of Panic attack during or soon after the events Residence Social Support

PTSD in ICU patients: screening vs. diagnostic tools Author, year N Follow-up time point Schelling 1998 1999 80 54 6-10 y 2-9 y Tool Rate of PTSD/PTSS PTSS-10 27.5% 38% Stoll, 1999 52 1-13 y PTSS-10 25% Nelson 2000 24 6-41 m / 39% (Deep sedation) Scragg, 2001 80 5 y IES 15% / 30% Schelling 2001 20 21-49 m PTSS-10 40% (protection by steroids) Kress, 2003 32 1y IES-R 18-50% (protection by sedative interruption Jones, 2003 102 8w 6m IES 51% (delusional memories) Cuthberson, 2004 113 3 m DTS 14-22% (length MV) Capuzzo 84 1w 3m IES 5% Wallen AJCC 2008 100 1 month 13% Kapfhammer, 2004 46 ICU discharge PTSS-10 45% From Jackson et al. Critical Care 2007, 11:R27

Is PTSD a problem? Reduction in HRQoL scores Physical and mental Less autonomy, more pain, more anxiety Sleeping problems Life events Financial, loss of work, problems with partners

Stress = increased levels of cortisol and corticotropin-releasing factor. PTSD, levels of cortisol are low and levels of crf are high.

Polymorphism of the glucocorticoid receptor gene Glucocorticoids play a major role in the consolidation and retrieval of traumatic information. Several polymorphisms of the glucocorticoid receptor have been described. One of them, the BclI single-nucleotide polymorphism is associated with hypersensitivity to glucocorticoids and with susceptibility to development of major depression. Patients with PTSD carrying the BclI GG genotype, had lower cortisol levels and showed an inverse relationship to PTSD symptom intensity.

Homozygous carriers of the BclI G allele: 21/126 ICU survivors. Compared to heterozygous/non-carriers of the BclI polymorphism of the glucocorticoid receptor gene : Lower preoperative plasma cortisol levels More long-term traumatic memories from ICU. More common anxiety Higher PTSD symptom scores at ICU discharge Less gain in HRQOL (physical) at 6 months Hauer D, Weis et al. Crit Care Med. 2011 Apr;39(4):643-50.

My 3-point framework Understanding Acute Stress Dirsorder, acute or chronic (delayed) PTSD Assessing cognitive burden in critical care survivors Risk factors for PTSD and recognizing the triad [sedation-memory-ptsd]

Cognitive Impairment 30% at 1y 24% 32% 20% poor memory 38% depression Alteration of attention, visual processing, psychomotor speed, and cognitive flexibility

Crit Care Med 2003; 31:1226 1234 34 ICU survivors (MV) with extensive 6-m follow up ALTERATION OF Psychomotor speed, Visual and working memory, Verbal fluency, visuo-construction

25% of the patients suffer from at least one psychiatric morbidity 1 year after ICU discharge

My 3-point framework Understanding Acute Stress Dirsorder, acute or chronic (delayed) PTSD Assessing cognitive burden in critical care survivors Risk factors for PTSD: Recognizing the triad [sedation-memory-ptsd]

Critical Care 2007, 11:R27 * Absence of clear recall for their time in ICU * Presence of frightening delusional memories such as hallucinations * No recall of ICU admission * Perceived severity (lack of factual memory)

10 studies (455 patients) that assessed neurocognitive Sedation outcome in critically ill and patients. Analgesia Neurocognitive impairement = 25-78% (ARDS)

9 Portuguese ICUs, 313 patients. They did not remember Hospital admission: 40% Time in the hospital before ICU admission: 48% Factual memories: 73% Delusional memories: 39% Intrusive memories: 23% A PTSS-14 score>49 (18%) was associated with not remembering hospital stay before ICU admission.

Systematic literature review, 15 studies Prevalence of PTSD 19-22% Predictors of PTSD: prior psychopathology, greater ICU benzodiazepine administration, and memories of in-icu frightening and/or psychotic experiences. Female sex and younger age were less consistent. Severity of ICU illness was NOT a predictor. PTSD was associated with substantially lower HRQOL

45 ICU survivors ICU discharge 33 had delusional memories from ICU 9 had no factual memories High anxiety levels when poor memory was reported Eight weeks High PTSD scores Increased panic attacks Acute PTSD = - trait anxiety - delusional memories - No recall of factual events

5 Eu ICUs (RACHEL), 238 recovering, postventilated ICU patients. The rate of defined PTSD was 9.2% (3.2-14.8). Determinants of of PTSD were: recall of delusional memories, prolonged sedation, physical restraint with no sedation.

Sedation-Memory-PTSD? Data from three trials Dexmethomedine, JAMA, Pandharipande Daily sedative interruption, NEJM, Kress No sedation, Lancet, Strøm Including long term follow-up in 2/3 No impact on PTSD

Impact of an ICU diary on psych. distress in patients/relatives A diary written by relatives and the staff: HADS, PDEQ, IES 143 patients: 48 in the prediary period, 49 in the diary period, and 46 in the postdiary period. In relatives, severe PTSD after 12 months varied significantly across periods: prediary 80%, diary 31.7%, postdiary 67.6%; p <.0001). Garrouste-Orgeas et al. Crit Care Med. 2012

143 patients, PTSD 27%

Neuropsychological function at 2 and 12m after discharge in ARDS survivors. Memory, verbal fluency, and executive function were impaired in 13%, 16% and 49% of survivors. Long-term cognitive impairment was present in 55 Depression, PTSD, or anxiety was present in 36%, 39%, and 62% of long-term survivors. Aggravating effect of hypoxemia

Duning et al. Diabetes Care 33:639 644, 2010 Correlation of the parameters of glycemic control with Rey Osterrieth Complex Figure Test results in the hypo group

In summary Physical, cognitive and mental health impairments are common and persistent. Memory deficits and ASD/stress/PTSD Cognitive dysfunction needs to be recognized and detected. Relatives have also PTSD Strategies to reduce post-icu burden can be simple

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