A Bone to PIC:

Concern for Post-ICU Syndrome

(PICS) in Critically Ill Patients
Elise Mann, PharmD
PGY1 Resident
October 28, 2021
 Learning Objectives

1 2 3
Describe the Evaluate the current Discuss applicable
pathophysiology of primary literature interventions for the
Post-ICU Syndrome regarding Post-ICU critically ill patient
(PICS) including Syndrome prevention population at
cognitive, physical, and and rehabilitation Eskenazi Health
psychological effects 
 PIC Your Own ICU Adventure
You are on your way to go pumpkin
picking with your coworkers when you
are suddenly involved in a serious MVC
and sustain multiple fractures. You are
emergently transported to Eskenazi
Health where you have been sedated,
intubated, and stabilized for the time
being. You are then transferred to the ICU
to be taken care of further by an
interdisciplinary team.

ICU= intensive care unit

MVC= motor vehicle crash
 ICU Mortality Rates
% Mortality
20

18 17.6

16

14
12.4
12

10
35% relative decrease
in mortality
8

0
1998 2012

Zimmerman JE, et al. Crit Care. 2013;17(2).

 We’ve Come A Long Way…

Electronic Minimally Mechanical

Medical Invasive Circulatory
Records Procedures Support

Aneman A, et al. Intensive Care Med. 2018;44(6):799-810.

 Life After Discharge

ICU  Survival  Quality of

Life?

Iwashyna TJ, et al. Semin Respir Crit Care Med. 2012;33(4):327-38.

 The Burden of Survivorship

Iwashyna TJ, et al. Semin Respir Crit Care Med. 2012;33(4):327-38.

 Epidemiology

In the United States, there are 5.7 million admissions

to the ICU annually

4.8 million will survive the hospital stay (84.2%)

50% or more will suffer from PICS after discharge

 PICS Studies Published
140

120

100

80

60

40

20

0
2012 2013 2014 2015 2016 2017 2018 2019 2020 2021
PICS

Cognitive

Physical

Psychological
 Diagnostic Criteria

Hallmark feature: Newly-recognized or worsened cognitive,

physical, or psychological complications after a critical illness

• Long-term acute care rehabilitation

Inclusion • Skilled nursing facilities
• Home

• Traumatic brain injury

Exclusion • Stroke
 Risk Factors

Acute Brain Mechanical

Delirium ARDS
Dysfunction Ventilation

Renal
Glucose
Immobility Replacement Sepsis
Dysregulation
Therapy

Prior Disability Hypotension

ARDS= acute respiratory distress syndrome

PICS

Cognitive

Physical

Psychological
 Cognitive Manifestations
Decreased memory

Clouded thinking

Difficulty talking

Forgetfulness

Poor concentration

Trouble organizing and problem solving

Contributors
Infection

Mechanical
Ischemia
Ventilation

Deep Neuro-
Sedation/Coma inflammation

Delirium
CAM-ICU
Score
RASS Score
 BRAIN-ICU Study
Objective To estimate the prevalence of long-term cognitive impairment after
critical illness

Design Multicenter, prospective cohort study of a diverse population of

critically ill patients 

Endpoints Examined two primary independent risk factors:

• Duration of delirium (# of hospital days with delirium)
• Use of sedative or analgesic medications during hospitalization
Demographic • Included adults admitted to a medical or surgical ICU with
s respiratory failure, cardiogenic shock, or septic shock
• Excluded patients with substantial prior ICU exposure, those who
could not be reliably assess for delirium, difficult patient follow-
up, those unlikely to survive for 24 hours, informed consent could
not be obtained, high risk for preexisting cognitive deficits

Pandharipande P, et al. N Engl J Med. 2013; 369:1306-1316

 BRAIN-ICU Study (cont.)
Results • Delirium developed in 74%
• At 3 months, 40% had Global Cognition Score 1.5 SD lower than the
general population
• At 12 months, deficits remained in ~30% of all patients (both
younger and older)
• Longer duration of delirium independently associated with worse
global cognition
• Use of sedative or analgesic medications was not consistently
associated with cognitive impairment

Conclusions Patients in medical and surgical ICUs are at high risk for long-term
cognitive impairment. A longer duration of delirium in the hospital was
associated with worse global cognition and executive function scores
at 3 and 12 months. 

Pandharipande P, et al. N Engl J Med. 2013; 369:1306-1316

Using what you’ve learned about RASS scoring, what
goal RASS score would you want your nurse to aim
for during your ICU stay?

A. +1
B. 0
C. -2
D. -4
 ABC Trial
Objective To determine the impact of a new directed two-step protocol to
wean patients off of a ventilator
Intervention The protocol involved daily attempts to halt sedation combined
with daily assessments of patients while they are breathing on their
own
Endpoints Primary: Ventilator-free days
Secondary: Length of stay in the ICU and hospital, 28-day and 1-
year survival, duration of coma and delirium; At discharge, 3
months, and 12 months: cognitive function, psychological status,
functional status, quality of life
Demographics Inclusion: recently on mechanical ventilation, requiring mechanical
ventilation for more than 12 hours (but not >2 weeks prior), over 18
years old
Exclusion: admission after cardiopulmonary arrest, inability to
obtain informed consent, existence of an extubation order at the
time of the evaluation
 ABC Trial (cont.)
Spontaneous • Desedated for up to 4 hours
Awakening Trial (SAT)
• Sedatives and analgesics used for sedation were
interrupted (analgesics for pain relief were continued)

• If this was not tolerated, sedatives were restarted at half

the previous rate and titrated back up as needed

Spontaneous Breathing for 2 hours on any one of the following:

Breathing Trial (SBT)
• Pressure supported ventilation (PSV) of <7 cmH2O
*if successful SAT • Continuous positive pressure ventilation (CPAP) of 5
cmH2O
• T-tube circuit
If successful SBT, then clinicians had a final decision
regarding extubation
 ABC Trial (cont.)
Intervention vs. Control
Results
Ventilator-free days 14.7 vs. 11.6
(p=0.02)
Discharge from ICU (days) 9.1 vs. 12.9
(p=0.01)
1-year mortality 44% vs. 55%
(p=0.01)
Duration of coma, RASS -4/-5 (days) 2 vs. 3 (p=0.002)

Duration of delirium, CAM-ICU positive (days) 2 vs. 2 (p=0.5)

Conclusion Use of a protocol that pairs daily spontaneous awakening trials with
daily spontaneous breathing trials for the management of
mechanically ventilated patients in intensive care results in better
outcomes than current standard approaches.
Cognitive
 Interventions- Cognitive
Monitor and Utilize agents Use light or
manage with lower risk minimal
delirium for delirium sedation

Infection Glucose Monitor for

control regulation hypoxia

Extubation
trials
PICS

Cognitive

Physical

Psychological
 Physical Manifestations
Muscle weakness

Neuropathy

Myopathy

Decreased mobility

Difficulty breathing

Sexual dysfunction
Contributors
Lack of
Mobilization
and Exercise

Oversedation Poor Nutrition

Mechanical
ARDS
Ventilation

Infection
Complications
 Early Physical and Occupational Therapy in
Mechanically Ventilated, Critically Ill Patients

Objective Assess the efficacy of combining daily interruption of sedation with

physical and occupational therapy on functional outcomes in
patients receiving mechanical ventilation in intensive care

Intervention Randomly assigned patients to daily interruption of sedation with

early exercise and mobilization OR to daily interruption of sedation
with standard of care therapy
Endpoints Primary: number of patients returning to independent functional
status at hospital discharge
Secondary: duration of delirium and ventilator-free days during the
first 28 days of hospital stay
Demographics Sedated adults (≥18 years of age) in the ICU who had been on
mechanical ventilation for <72h and were expected to continue for
at least 24h and met criteria for baseline functional independence

Schweickert W, et al. Lancet. 2009. 30;373: 1874-82.

 Early Physical and Occupational Therapy in
Mechanically Ventilated, Critically Ill Patients

Intervention vs. Standard Care

Results
Return to independent functional status at 59% vs. 35%
hospital discharge (p=0.02)
Shorter duration of delirium (days) 2 vs. 4 (p=0.02)
More ventilator-free days during 28-day follow- 23.5 vs. 21.1
up period (p=0.05)
Conclusions Interruption of sedation and physical and occupational therapy in the
earliest days of critical illness resulted in better functional outcomes
at hospital discharge, a shorter duration of delirium, and more
ventilator-free days compared with standard care

Schweickert W, et al. Lancet. 2009. 30;373: 1874-82.

Your sedation has become a point of discussion on your
treatment team. What would you like them to do?

A. Keep me as sedated as possible for as long as possible- I

don’t want to remember this!
B. Abruptly discontinue my sedation medications to increase
my chances of discharging quickly
C. Conduct a spontaneous awakening trial when appropriate
and monitor how I tolerate it
D. Change my sedation medications to allow for light
sedation
Physical
Interventions- Physical

Early Adequate Sedation

Mobilization Nutrition Vacations

Mechanical
Infection Prevent and
Ventilation <7
Control Treat ARDS
Days
How would you like your PT/OT staff to interact with you
during your ICU stay?

A. Visit me every hour on the hour and prioritize constant

mobilization
B. Introduce mobilization early in my care and cautiously
progress to more involved exercises throughout my stay
C. Let me gain strength back by prioritizing bed rest and visit
me prior to discharge to discuss outpatient PT
D. Visit me if they have extra time at the end of the day, but
prioritize patients who “need it more” first
PICS

Cognitive

Physical

Psychological
 Psychological Manifestations

Post-Traumatic Stress Disorder (PTSD)

Depression

Anxiety
Contributors
Delirium

Sleep
Pain
Deprivation

Pre-Existing
ARDS
Comorbidities

Lack of
Communication
 Psychiatric Symptoms after ARDS: a 5-Year
Longitudinal Study

Objective Aimed to characterize anxiety, depression, and PTSD

symptoms after ARDS and determine risk factors for
prolonged psychiatric morbidity

Intervention • Follow-up at 3, 6, 12, 24, 36, 48, and 60 months post-

ARDS
• Trained research staff administered the Hospital Anxiety
and Depression Scale (HADS) and the Impact of Event
Scale-Revised scale (for PTSD symptoms) at each follow-
up visit

Endpoints • HADS Score (anxiety and depression)

• IES-R Score (PTSD)

Bienvenu OJ, et al. Intensive Care Med. 2018 Jan;44(1):38-47.

 Psychiatric Symptoms After ARDS: a 5-Year
Longitudinal Study

Results • 52% had prolonged or recurring psychiatric symptoms

• 38% with anxiety
• 32% with depression
• 23% with PTSD symptoms

Conclusion Clinically significant and long-lasting symptoms of anxiety,

depression, and PTSD are common in the first 5 years after
ARDS

Bienvenu OJ, et al. Intensive Care Med. 2018 Jan;44(1):38-47.

 Psychological
Manifestations

“I was sexually assaulted”

“Visions of big spiders surrounding

me in my room”

“I was on a conveyer belt being fed

into an oven”

Most common: “A nurse is trying to

kill me”
 RACHEL-II Study
Objective To evaluate whether a prospectively collected diary of a
patient’s ICU stay following critical illness will reduce the
development of new onset PTSD

Intervention Receipt of ICU diary containing daily information of

patient’s condition and treatment with appropriate
photographs at 1 month post critical illness
Endpoints Diagnosis of PTSD 3 months post critical illness 

Demographics Inclusion: Patients staying on the ICU for at least 72 hours

(with greater than 24 hours of artificial ventilation)
Exclusion: ICU stay < 72 hours, too confused for informed
consent, pre-existing psychotic illness

Jones C, et al. Crit Care. 2010; 14(5): 168 .

 RACHEL-II Study

Results Incidence of new cases of PTSD (diary vs. control)

• 5% vs. 13% (p=0.02)

Conclusion The provision of an ICU diary is effective in aiding

psychological recovery and reducing the incidence of new
PTSD.

Jones C, et al. Crit Care. 2010; 14(5): 168 .

Your nurse thoughtfully created an ICU Diary for you throughout your stay that
included photographs and detailed descriptions of your procedures and
treatment course. She offers it to you as you prepare for discharge. How do you
respond?

A. Be polite and say thank you, but throw it in your bag and ignore it when you
get home
B. What an invasion of privacy! Ask your nurse to shred this immediately!
C. Show off the cool pictures to your friends and skim the pages
D. Accept the ICU diary and begin processing through the information with your
support system when you are ready
Psychological
Psychological
 Interventions- Psychological

Prevent/Treat Pain
ICU Diaries
ARDS Management

Sleep Follow-Up
Lighting Counseling
Regimen
 Pain Management

PADIS Guidelines- Multimodal Pain Control

• Opioids
• Acetaminophen
• Ibuprofen
• Gabapentin
• Ketamine
• Non-pharmacological
You have been in excruciating pain from your multiple sustained
traumatic injuries. How would you like your treatment team to
address your pain management?

A. Pain meds are from wimps!- I want non-pharmacological

options only in order to avoid opioids
B. Treat me with scheduled acetaminophen and PRN opioids
C. Treat me with scheduled and PRN opioids
D. Treat me with scheduled NSAIDs and PRN opioids
Prevention Summary
 Pain

Agitation/Sedation
PADIS
Delirium
Guidelines
Immobility

Sleep
Devlin J, et al. Critical Care Medicine. 2018; 46:9.
 ICU Liberation Bundle

• Assess, prevent, and manage pain

• Both spontaneous awakening and breathing trials
• Choice of analgesia and sedation
• Delirium: assess, prevent, and manage
• Early mobility and exercise
• Family engagement and empowerment
 PICS-F

Cognitive, physical, and psychological

sequelae associated with critical care
hospitalization of the survivor’s family
or caregivers
PICS-F
PICS-F Interventions

Provision of Family Meetings Flexible and

Information with Physician Open Visiting

Shared Decision Proactive Medication

Making Communication Education
After Discharge
Post-ICU • Focused care for patients and
families after critical illness
Recovery • Interdisciplinary team
Clinics • Visits may last multiple hours
• Improve transitions of care
• Decrease readmission rates
• Improve quality of life
Pulmonary/Critical Care Specialist

Nurse

Social Worker

Critical Care Pharmacist

Medical Assistant

Psychologist

CCRC Interdisciplinary Team

 Randomized Clinical Trial of an ICU Recovery
Pilot Program for Survivors of Critical Illness

Objective To examine the effect of an interdisciplinary ICU recovery program on

process measures and clinical outcomes

Design A prospective, single-center, randomized pilot trial

Demographics • Adult patients admitted to the medical ICU for at least 48 hours
• Predicted risk of 30-day hospital readmission of at least 15%

Intervention • Inpatient visit by a nurse practitioner

• Informational pamphlet
• 24 hours a day, 7 days a week phone number for the ICU
recovery team
• Outpatient ICU recovery clinic visit with a critical care physician,
nurse practitioner, pharmacist, psychologist, and case manager

Bloom SL, et al. Critical Care Medicine. 2019; 47:10, 1337-1345.

 Randomized Clinical Trial of an ICU Recovery Pilot
Program for Survivors of Critical Illness (cont.)

Pilot Program vs. Usual Care

Results
Readmitted to the hospital within 30 days of 14.4% vs. 21.5%
discharge (p=0.16)
Readmitted within 7 days of discharge 3.6% vs. 11.6%
(p=0.02)
Median time to readmission 21.5 vs. 7 days
(p=0.03)
Composite outcome of death or 18% vs. 29.8%
readmission within 30 days (p=0.04)
Conclusion A multidisciplinary ICU recovery program can achieve better
outcomes for post ICU recovery than usual care

Bloom SL, et al. Critical Care Medicine. 2019; 47:10, 1337-1345.

 Impact of a Pharmacist Intervention at an ICU
Clinic

Objective To determine the prevalence of specific medication-related

problems detected in patients seen after critical care discharge

Design Single-center
Demographics • 47 patients reviewed at follow-up program after ICU
discharge

Intervention Pharmacists conducted a full medication review, including:

• Medication reconciliation
• Assessing the appropriateness of each prescribed
medication
• Identification of any medication-related problems
• Checking adherence

MacTavish P, et al. BMJ Open Quality. 2019; 8:e000580.

 Impact of a Pharmacist Intervention at an
ICU Clinic (cont.)

Results
Pharmacist-identified medication related 81% of patients
problems
Most common documented problem was drug 29%
omission
Medication-related problems identified as either 64%
moderate or major
Number of pain medications prescribed at (OR 2.02, 95% CI
discharge from intensive care was predictive of 1.14 to 4.26,
needing pharmacist intervention p=0.03)
Conclusions • Medication problems are common following critical care
• Better communication of medication changes to both patients and
their ongoing care providers needed
• Pharmacy intervention may contribute substantially to an ICU recovery
program

MacTavish P, et al. BMJ Open Quality. 2019; 8:e000580.

Eskenazi Health Critical Care
Recovery Center (CCRC)

Eskenazi Health received the 2017 THRIVE

Innovation Award from the Society of
Critical Care Medicine

Recognizes the nation's first collaborative

care concept targeting the extensive
cognitive, physical, and psychological
recovery needs of intensive care unit
survivors
 CCRC Model

Initial Visit Follow-up Family Personalized

Conference Care Plan
 CCRC Pharmacist Interventions
• Medication histories
• SSRI initiation
• Immunization interventions
• Transitions of care
• De-prescribing
• ICU delirium
• PPIs
• Anticholinergics
 Clinical Pharmacist Services Within Intensive Care Recovery
Clinics: An Opinion of the Critical Care Practice and Research
Network of the American College of Clinical Pharmacy
Mohammad RA, Betthauser KD, Bookstaver-Korona R, Coe AB, Hatton-Kolpek J, Fristchle AC, Jagow B, Kenes
M, MacTavish P, Slampak-Cindric AA, Whitten JA, Jones C, Simonelli R, Rowlands I, Stollings JL

Objective Describe ICU recovery clinic pharmacists’ activities, roles, and

perceived barriers and facilitators to practicing in ICU recovery
clinics across different institutions

Methods • An expert panel of ICU recovery clinic pharmacists completed a

15-item survey
• Survey items addressed the pharmacists’ years in practice,
education and training, activities performed, their perceptions of
facilitators and barriers to practicing in an ICU recovery clinic
setting, and general ICU recovery clinic characteristics.

Mohammad RA, et al. Pharmacotherapy. 2020; 3(7):1369-79.

 Clinical Pharmacist Services Within Intensive Care Recovery
Clinics: An Opinion of the Critical Care Practice and Research
Network of the American College of Clinical Pharmacy
(cont.)

Results • 78% of pharmacists always performed medication reconciliation

and a comprehensive medication review in each patient visit

• Need for medication education was the most prevalent item

found in patient comprehensive medication reviews

• The main facilitators for pharmacists’ successful participation in

an ICU recovery clinic were incorporation into clinic workflow,
support from other health care providers, and adequate space to
see patients

• The ICU recovery clinic pharmacists perceived the top barriers to

be lack of dedicated time and inadequate billing for services

Mohammad RA, et al. Pharmacotherapy. 2020; 3(7):1369-79.

 CCRC Future Directions

Dr. Khan’s research focuses on

developing a biomarker profile
among delirious patients in the
ICU to predict their risk of PICS
You’ve finally recovered enough to discharge home! How do
you plan to manage your healthcare moving forward?

A. I’ve spent so much time in the hospital this year already…

I don’t want to see any more doctors
B. Attend an initial follow-up appointment with my PCP after
discharge to address transitions of care needs
C. Follow-up in an ICU recovery clinic for a comprehensive
assessment and to create a personalized care plan
D. Ask to stay in the hospital for as long as possible so I can
continue to receive around the clock care
 Room for Growth
Additional presentation of PICS in COVID-19 survivors

Lessons from other clinics

Provider status and ability to bill for services

Telemedicine
 The Big PICture
PICS is comprised of serious and multifaceted
consequences and is greatly impacted by the healthcare a
patient receives in the ICU

Pharmacists play a vital role in optimizing medication

therapy in the ICU and reducing the risk of cognitive,
physical, and psychological effects

Outpatient PICS clinics improve patient outcomes and

quality of life
 PIC Your Own ICU Adventure
Where did you end up?

 
0 Points 1 Point 2 Points 3 Points
Question 1 D C A B
Question 2 A and B -- D C
Question 3 C A and D -- B
Question 4 B A C D
Question 5 A -- C B and D
Question 6 A and D -- B C
 PIC Your Own ICU Adventure
Where did you end up?

0-9 points= Your stay in the ICU lead to speech

difficulty, forgetfulness, neuropathy, and severe
muscle weakness that effects your ability to walk.
Your delirium flashbacks effect your ability to hold a
job or maintain your relationships.
 PIC Your Own ICU Adventure
Where did you end up?

10-15 points= You struggle with mild depression and

anxiety and notice some clouded thinking. You follow
up with Ally and Jessie in the CCRC, reconcile your
medications, and notice improvement in your
symptoms within a few months.
 PIC Your Own ICU Adventure
Where did you end up?

≥16 points= You discharge with some questions and

concerns but read your ICU Diary to fill in the gaps
and thank your PT/OT on the way out for their
support this month. Congratulations- you’re on your
way to a full recovery!
 A Bone to PIC:
Concern for Post-ICU Syndrome
(PICS) in Critically Ill Patients
Elise Mann, PharmD
PGY1 Resident
October 28, 2021