Immobility

2018 SCCM Clinical Practice Guidelines for the

Prevention and Management of
Pain, Agitation/Sedation, Delirium, Immobility, and Sleep
Disruption in Adult Patients in the ICU
 Introduction

2018 pain, agitation/sedation, delirium, immobility, and sleep disruption

(PADIS) guidelines

• Update of 2013 PAD guidelines by:

– Adding 2 new topics: rehabilitation/mobilization and sleep disruption
– Including patients as collaborators and coauthors
– Adding experts from Europe and Australia

• 37 recommendations and two ungraded good practice statements

– Only 2 of 37 recommendations rated as “strong”

• 32 ungraded statements (nonactionable descriptive questions)

Slide development by: R. Nikooie, MD, C. Chessare, MS, D. Needham, MD, PhD

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 Methods
• Grading of Recommendations Assessment, Development, and Evaluation
(GRADE) methodology
• Chairs, section heads, panel members, ICU survivors, librarian
• Topics selected and prioritized, PICO questions finalized, and then:
– Literature review: 5 electronic databases, 1990 to October 2015
– Evaluation of study (primarily RCT) methodologic rigor: risk of bias
– Formulation of preliminary recommendations: GRADE evidence-to-
decision process
– In-person discussion among full panel (SCCM 2017 Congress)
– Anonymous recommendation voting
– > 80% agreement with > 70% response rate
– 100% of the panel voted (with reminders and prompts)
• ICU survivors participated in every step
Devlin JW, et al. PADIS Method Innovations Paper. Crit Care Med 2018; 46:1457-1463 Slide development by: R. Nikooie, MD, C. Chessare, MS, D. Needham, MD, PhD

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 Formulate Select Rate Systematic Evidence profile 1 Pooled estimate of effect per outcome
question outcomes importance review 2 Quality of evidence per outcome

High
High| Moderate Low|Very low
Moderate | Low
Very low
Outcome1 Critical RCT high
Patient, start observational low
intervention, Outcome2 Critical
comparison, 1. Risk of bias
outcome Outcome3 Important

rate down
2. Inconsistency
(PICO)
Outcome4 Not 3. Indirectness
question
imp 4. Imprecision
ort
an 5. Publication bias
t
Exclude 1. Large effect

rate up
2. Dose response
3. Antagonistic bias
systematic review of evidence

Evidence-to-Decision (EtoD)
framework:
 Balance
benefits/downsides Rate overall quality of
 Quality of evidence evidence
 Values and preferences across outcomes
Section Panel Members
 Resource use (cost)
 Feasibility
 Acceptability
Formulate preliminary Large Electronic voting
recommendation group (blinded to
 For or against an action discussion others voting)
 Strong or conditional
(strength)
© Society of Critical Care Medicine. Final recommendation
Slide courtesy of Waleed Alhazzani, MD, MSc
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 Strong Versus Conditional Recommendations
  Strong Conditional
Patients Applies to almost all patients Applies to most patients
(significant exceptions based on patient
condition, values, and preferences)
Supporting Moderate- to high-quality Conflicting, low quality, insufficient,
evidence across broad populations and/or limited populations
Benefits versus Benefits clearly outweigh May be close balance between benefits
burdens burdens and burdens
Influence of future Limited potential to change Possible/probable potential to change
research recommendation recommendation
Performance or Can be readily adapted in Requires significant deliberation at the
quality indicators most healthcare systems local level based on practice patterns,
patients served, and resource
availability

Balas MC, Weinhouse GL, Denehy L, et al. Interpreting and implementing the 2018 pain, agitation/sedation, delirium, immobility, and sleep disruption
clinical practice guidelines. Crit Care Med. 2018 Sep;46(9):1464-1470.

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 PICO and Descriptive Questions for PADIS Clinical Practice Guideline
Immobility Sleep
Pain Agitation/Sedation Delirium (Rehab/Mobilization) Disruption
Factors that influence pain Light vs. deep sedation Delirium prediction Rehab/mobilization Comparison of sleep in critically
(performed in or out of bed) ill adults vs.:
Assessment Prevalence, rationale, and • Risk factors vs. different • Healthy adults
• Patient self-report outcomes of physical restraint • Influence of level of rehab/mobilization • Delirium (vs. no delirium)
• Behavioral use arousal on delirium intervention, placebo, or • MV (vs. no MV)
• Proxy reporters assessment sham Prevalence of unusual sleep
• Physiologic measures • Outcomes of delirium

Protocol-based assessment and Daily sedation interruption vs. Delirium assessment using Harm associated with Physiologic/nonphysiologic sleep
management: nurse-protocolized sedation valid tool (vs. no rehab/mobilization (either in monitoring
• Analgesia first assessment) or out of bed)
• Analgosedation

Multimodal analgesia to reduce Mechanically ventilated patients Pharmacologic prevention: Clinical indicators to safely Risk factors affecting ICU sleep
opioid use: after cardiac surgery: • Haloperidol initiate rehab/mobilization quality:
• Acetaminophen • Propofol vs. benzodiazepines • Atypical antipsychotic (either in or our of bed) • Before critical illness
• Nefopam • Statin • ICU-acquired
• Ketamine • Dexmedetomidine Disrupted sleep outcomes:
• Neuropathic analgesia • Ketamine • During ICU admission
• IV lidocaine • After ICU discharge
• NSAID

Procedural analgesia: Mechanically ventilated critically Pharmacologic treatment: Clinical indicators to stop Pharmacologic sleep
• Opioid vs. none ill adults: • Haloperidol rehab/mobilization improvement:
• High- vs. low-dose opioid • Propofol vs. benzodiazepines • Atypical antipsychotic (either in or out of bed) • Melatonin
• Local analgesia • Dexmedetomidine vs. • Statin • Dexmedetomidine
• Nitrous oxide benzodiazepines • Dexmedetomidine • Propofol
• Isoflurane • Propofol vs. • Ketamine
• NSAID (systemic/gel) dexmedetomidine

Nonpharmacologic analgesic Objective sedation monitoring Nonpharmacologic delirium Nonpharmacologic sleep

strategies: tools reduction interventions: improvement:
• Cybertherapy/hypnosis • Single component: Bright • AV vs. PS mode
• Massage light therapy • Adaptive vs. PS mode
• Music • Multicomponent: • Aromatherapy
• Cold therapy ABCDEF bundle • Music
• Relaxation techniques • Noise and light reduction
• Multimodal protocol
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 Why Add “Immobility” to PAD
(Rehabilitation/Mobilization)
• ICU-acquired muscle weakness (ICUAW)
– Present in 25%-50% of critically ill patients
– Associated with long-term survival, physical function, and quality
of life
– Immobility/bed rest is an important risk factor
• Rehab/mobilization also may be beneficial for delirium
• Association of pain and sedation status/practices with ICU
rehab
• 1 actionable (PICO) question plus 3 descriptive questions

Slide development by: R. Nikooie, MD, C. Chessare, MS, D. Needham, MD, PhD

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 Assessing Efficacy of Intervention

PICO Question

P Critically ill adults

I Rehab/mobilization (performed in bed or out of bed)

C Usual care, different rehab/mobilization intervention, placebo, sham

O Patient, family, or health system outcomes

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 Specific Outcomes
• Critical outcomes able to be evaluated:
– Muscle strength at ICU discharge
– Duration of mechanical ventilation
– Quality of life
– Hospital mortality
– Physical function
• Critical outcomes not able to be evaluated because of inadequate
data:
– Cognitive function
– Mental health
– Return to work/economic status
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 Synthesis of RCT Evidence
Substantial heterogeneity* across the PICO question:
• ICU patient populations (P)
• Types and timings of rehab/mobilization interventions (I)
• Comparators for the intervention (C):
– Usual care rehab/mobilization
– Same intervention with reduced duration/frequency
– Later start of the intervention
– Outcomes and related measures (O)
*Affects “consistency” aspect of GRADE for quality of evidence assessment
and limits the inferences/recommendations that can be made.

Slide development by: R. Nikooie, MD, C. Chessare, MS, D. Needham, MD, PhD

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 Efficacy and Benefit
1. Muscle strength at ICU discharge (6 RCTs, 304 patients)
– Improved by 6.2 points (95% CI, 1.7 to 10.8; scale is 0 to 60)
– Low quality (statistical heterogeneity, CI includes MCID)

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 Efficacy and Benefit
2. Duration of mechanical ventilation (11 RCTs, 1,128 patients)
– Reduced by 1.3 days (95% CI, 2.4 to 0.2 days)
– Low quality (2 large RCTs, high ROB, competing risk, heterogeneity)

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 Efficacy and Benefit
3. Quality of life (SF-36 physical function) within 2 months (4 RCTs, 303
patients)
– Improved by SMD of 0.64 (95% CI, –0.05 to 1.34), not significant

Slide development by: R. Nikooie, MD, C. Chessare, MS, D. Needham, MD, PhD

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 Efficacy and Benefit
4. Hospital mortality (13 RCTs, 1,421 patients)
– No effect, RR = 0.93 (95% CI, 0.74 to 1.18), moderate quality (CI includes
harm)

Slide development by: R. Nikooie, MD, J. Devlin, PharmD, D. Needham, MD, PhD

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 Efficacy and Benefit
5. Physical function: small N due to heterogeneity in measures, not significant
– Timed Up and Go (TUG) Test, MD 2.22 (95% CI, –4.99 to 9.43, 3 RCTs, 172
patients)

– Physical Function in ICU Test (PFIT), MD –0.19 (95% CI, –0.69 to 0.31, 3 RCTs, 209
patients)

Slide development by: R. Nikooie, MD, C. Chessare, MS, D. Needham, MD, PhD

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 Evidence-to-Decision (EtoD) Summary

• Rehabilitation/mobilization assessed as:

– Feasible
– Acceptable to key stakeholders
– Likely to be cost-effective (based on preliminary data)
• Indirect evidence plus discussion of panel (including ICU
patient):
– Patients probably value the benefits of rehab/mobilization

Slide development by: R. Nikooie, MD, C. Chessare, MS, D. Needham, MD, PhD

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 Recommendation
• Given a small benefit and the low overall quality of evidence, panel
members agreed that:
– Desirable consequences probably outweigh undesirable
consequences.
Formal Recommendation:
We suggest performing rehabilitation or mobilization in critically ill
adults (conditional recommendation, low quality evidence).
• Supports performing rehab/mobilization over usual care or similar
interventions with a reduced duration, frequency, or later onset
• Implementation influenced by feasibility, staffing, and resources
across ICUs
Slide development by: R. Nikooie, MD, C. Chessare, MS, D. Needham, MD, PhD

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 Safety and Risk
Descriptive Question:
Is receiving rehab/mobilization (performed either in bed or out
of bed) commonly associated with patient-related safety
events or harm?
Ungraded Statement:
Serious safety events or harms do not occur commonly during
physical rehab/mobilization.
• Rationale: 10 observational studies and 9 RCTs
– Serious safety events/harms were rare (15 during >
12,200 sessions).
– Most were respiratory-related (4 desaturation and 3
unplanned extubation).
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 Indicators for Initiation

Descriptive Question:
What aspects of patient clinical status are indicators for the
safe initiation of rehab/mobilization (performed either in bed
or out of bed)?
Ungraded Statement:
Major indicators for safely initiating rehab/mobilization
include stability in cardiovascular, respiratory, and neurologic
status.
• Vasoactive infusion and mechanical ventilation are not
barriers to initiation if patient is otherwise stable with use
of these therapies (17 studies, 2,774 patients).
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 Indicators for Stopping

Descriptive Question:
Which aspects of patient clinical status are indicators for
stopping rehab/mobilization (performed either in bed or out
of bed)?
Ungraded Statement:
Major indicators for stopping rehab/mobilization include new
cardiovascular, respiratory, or neurologic instability.
– Other events (eg, fall, medical device
removal/malfunction, patient distress) are also indications
for stopping (14 studies, 2,617 patients).

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 Table 1. Safety Criteria for Start/Stop
Rehab/Mobilization (in Bed or out of Bed)
Safety Criteria Starting a Rehab/Mobilization Session Stopping a Rehab/Mobilization Session

System Start when all of the following are present: Stop when any of the following are present:

Cardiovascular • Heart rate 60-130 beats/min, • Heart rate decreases < 60 or increases > 130 beats/min
• Systolic BP 90-180 mm Hg, or • Systolic BP decreases < 90 or increases > 180 mm Hg
• MAP 60-100 mm Hg • MAP decreases < 60 or increases > 100 mm Hg

Respiratory • Respiratory “.
rate. 5-40
. not be a substitute for• clinical
breaths/min Respiratoryjudgment”
rate decreases < 5 or increases > 40 breaths/min
• SpO2 ≥ 88% • SpO2 decreases < 88%
• FIO2 < 0.6 and PEEP < 10 cm H2O • Concerns about securing ETT or tracheostomy tube
• “All thresholds
Airway should
(ETT or tracheostomy beadequately
tube) interpreted or modified, as needed, in
secured
Neurologic
the context of individual patients’ clinical
• Able to open eyes to voice
symptoms, expected
• Change in level of consciousness
values, recent trends, and any clinician-prescribed goals or targets.”
Other The following should be absent: If following develop and are clinically relevant:
• New or symptomatic arrhythmia • New or symptomatic arrhythmia
• Chest pain with concern for ischemia • Chest pain with concern for ischemia
• Unstable spinal injury or lesion • Ventilator asynchrony
• Unstable fracture • Fall
• Active or uncontrolled GI bleeding • Bleeding
Mobility may be performed with • Medical device removal or malfunction
• Femoral ventricular assist device, except sheath, • Distress reported by patient or clinician
in which hip mobilization is generally avoided
• Continuous renal replacement therapy
• Vasoactive medication infusion

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 Evidence Gaps
• Directions for future research:
– Understanding difference in outcomes by:
o Type, timing, frequency, duration, and intensity of intervention
– Expertise/training of personnel delivering interventions
– Influence of patient condition (eg, pre-ICU functional status,
delirium and sedation, muscle weakness) on outcomes after
rehab/mobilization
– Methods to assess patient experience during rehab/mobilization
– Standard data: intervention, safety, and short- and long-term
outcomes
– Measurement properties of short- and long-term outcome measures

Slide development by: R. Nikooie, MD, C. Chessare, MS, D. Needham, MD, PhD

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 PADIS Guideline Authors
1
John W. Devlin, PharmD (Chair for Overall CPG)
2
Yoanna Skrobik, MD, MSc (Vice-Chair)
21
Dale M. Needham, MD, PhD (Chair, Immobility)
3
Céline Gélinas, RN, PhD (Chair, Pain) 22
Linda Denehy, PT, PhD
4
Aaron M. Joffe, DO 23
Michelle E. Kho, PT, PhD
5
Kathleen A. Puntillo RN, PhD 24
Chris Winkelman, RN, PhD
6
Gerald Chanques, MD, PhD 25
Nathaniel E. Brummel, MD, MSCI
7
Jean-Francois Payen, MD, PhD 26
Jocelyn Harris, OT, PhD
8
Paul M. Szumita, PharmD 27
Julie Lanphere, DO
28
Sina Nikayin, MD (research staff)
9
Pratik P. Pandharipande, MD, MSCI(Chair, Sedation)
10
Richard R. Riker, MD 29
Paula L. Watson, MD, MPH (Co-Chair, Sleep)
11
Michele C. Balas, RN, PhD 30
Gerald L. Weinhouse, MD (Co-Chair, Sleep)
12
Yahya Shehabi, MD, PhD 31
Xavier Drouot, MD, PhD
13
John P. Kress, MD 32
Karen Bosma, MD
14
Bryce R.H. Robinson MD, MS 33
Sharon McKinley, RN, PhD
15
Arjen Slooter, MD, PhD (Chair, Delirium) 34
Waleed Alhazzani, MD, MSc (Chair, Methods)
16
Brenda T. Pun, RN, DNP 35
Mark E. Nunnally, MD
17
Gilles L. Fraser, PharmD, MCCM 36
Bram Rochwerg, MD, MSc
18
Margaret Pisani, MD, MPH 37
John E. Centofanti, MD, MSc
19
Karin J. Neufeld, MD, MPH
20
Mark van den Boogaard, RN, PhD 38
Carrie Price, MLS (medical librarian)
39
Cheryl J. Misak, PhD (patient rep)
40
Ken Kiedrowski, MA (patient rep)
41
Pamela Flood, MD (patient rep)

Slide development by: R. Nikooie, MD, C. Chessare, MS, D. Needham, MD, PhD

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 Acknowledgement

Slide content has been provided by the

PADIS Guideline Leadership.

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For more information on how to implement the 2018
PADIS guidelines, please visit the ICU Liberation
Campaign website: http://www.sccm.org/ICULiberation

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