1. Sedation in the ICU from A to E
The ABCDE Bundle

2. Salvatore Vitale M.D.
Director Cardio-vascular Anesthesia Westchester Medical Center Assistant Professor Dept. of Anesthesiology New York Medical College Immediate Past President New York State Society of Anesthesiologists

3. Westchester Medical Center
TAVR Team

4. Learning Objectives
Describe current guidelines for the management of pain, agitation, and delirium in adult patients in the intensive care unit
Use validated scales to measure sedation, pain, agitation, and delirium in critically ill patients
Compare the benefits and limitations of available sedatives and analgesics in the acute care, procedural, and surgical settings

5. Goals for Sedation and Analgesia
Prevent pain and anxiety
Decrease oxygen consumption
Decrease the stress response
Patient-ventilator synchrony
Avoid adverse neurocognitive sequelae
Depression
PTSD
Dementia
Anxiety
Rotondi AJ, et al. Crit Care Med. 2002;30:
Weinert C. Curr Opin in Crit Care. 2005;11:
Kress JP, et al. Am J Respir Crit Care Med. 1996;153:

6. Jacobi J, et al. Crit Care Med. 2002;30:119-141
American College of Critical Care Medicine (ACCM) Clinical practice guidelines for the sustained use of sedatives and analgesics in the critically ill adult
Guideline focus
Prolonged sedation and analgesia
Patients older than 12 years
Patients during mechanical ventilation
Assessment and treatment recommendations
Analgesia
Sedation
Delirium
Sleep
Jacobi J, et al. Crit Care Med. 2002;30:

7. What Is the ABCDE Bundle?
ABCDE bundle is designed to:
Standardize care processes
Break the cycle of oversedation and prolonged ventilation
Pull and add pratik’s here.
Vasilevskis EE, et al. Chest. 2010;138(5):

8. What Is in the ABCDE Bundle?
Awakening and Breathing Trial coordination
Coordination/Choice of Sedation
Delirium Monitoring and Management
Early Mobility
Vasilevskis EE, et al. Chest. 2010;138(5):

9. ABCDE
Awakening Breathing Coordination/Choice of Sedation Delirium Monitoring and Management Early Mobilization

10. Daily Sedation Interruption (DSI) Decreases Duration of Mechanical Ventilation
Hold sedation infusion until patient awake and then restart at 50% of the prior dose
“Awake” defined as any 3 of the following:
Open eyes in response to voice
Use eyes to follow investigator on request
Squeeze hand on request
Stick out tongue on request
Fewer diagnostic tests to assess changes in mental status
No increase in rate of agitated-related complications or
episodes of patient-initiated device removal
No increase in PTSD or cardiac ischemia
Kress JP, et al. N Engl J Med. 2000;342:

11. The ABC Trial: Objectives
To determine the efficacy and safety of a protocol linking:
spontaneous awakening trials (SATs) &
spontaneous breathing trials (SBTs)
Ventilator-free days
Duration of mechanical ventilation
ICU and hospital length of stay
Duration of coma and delirium
Long-term neuropsychological outcomes
Girard TD, et al. Lancet. 2008;371:

12. ABC Trial: Main Outcomes
SBT
SAT+SBT
P-value
Ventilator-free days 12 15
0.02
Time-to-Event, days
Successful extubation, days
7.0 5
0.05
ICU discharge, days 13 9
0.02
Hospital discharge, days 19 15
0.04
Death at 1 year, n (%)
97 (58%)
74 (44%)
0.01
Days of brain dysfunction
Coma
3.0
2.0
0.002
Delirium
2.0
2.0
0.50
*Median, except as noted
Girard TD, et al. Lancet. 2008;371:

13. ABC Trial: 1 Year Mortality
Girard TD, et al. Lancet. 2008;371:

14. Canada – 40% get SATs (273 physicians in 2005)1
Daily Sedation Interruption (DSI) Not Standard of Practice at Most Institutions
Canada – 40% get SATs (273 physicians in 2005)1
US – 40% get SATs ( )2
Germany – 34% get SATs (214 ICUs in 2006)3
France – 40–50% deeply sedated with 90% on continuous infusion of sedative/opiate4
1. Mehta S, et al. Crit Care Med. 2006;34:
2. Devlin J. Crit Care Med. 2006;34:
3. Martin J, et al. Crit Care. 2007;11:R124.
4. Payen JF, et al. Anesthesiology. 2007;106:

15. Barriers to Daily Sedation Interruption (Survey of 904 SCCM members)
Increased device removal
Poor nursing acceptance
Compromises patient comfort
Leads to respiratory compromise
Difficult to coordinate with nurse
No benefit
Leads to cardiac ischemia
Leads to PTSD
#1 Barrier
#2 Barrier
#3 Barrier 10 20 30 40 50 60 70
Number of respondents (%)
Clinicians preferring propofol were more likely use daily interruption
than those preferring benzodiazepines (55% vs 40%, P < )
Tanios MA, et al. J Crit Care. 2009;24:66-73. 15

16. Awakening and Breathing (AB) Safety Screens
Breathing Trial
Awakening Trial
No active agitation
Oxygen saturation ≥ 88%
FiO2 ≤ 50%
PEEP ≤ 8 cm H2O
No myocardial ischemia (24h)
Normal intracranial pressure
No significant vasopressor or inotrope use
No active seizures
No active alcohol withdrawal
No active agitation
No active paralytic use
No myocardial ischemia (24h)
Normal intracranial pressure
Girard TD, et al. Lancet. 2008;371(9607):

17. ABCDE
Awakening Breathing Coordination/Choice of Sedation Delirium Monitoring and Management Early Mobilization

18. ICU Sedation: The Balancing Act
Patient Comfort
and Ventilatory Optimization
Oversedation
Prolonged mechanical ventilation
Increased length of stay
Increased risk of complications
- Ventilator-associated pneumonia
Increased diagnostic testing
Inability to evaluate for delirium G O A L
Undersedation
Patient recall
Device removal
Ineffectual mechanical ventilation
Initiation of neuromuscular blockade
Myocardial or cerebral ischemia
Decreased family satisfaction w/care
Jacobi J, et al. Crit Care Med. 2002;30: 18 18

19. Targeted Sedation 30.6% 15.4% 54.0% Undersedated3 Oversedated
Continuous sedation carries the risks associated with oversedation and may increase the duration of mechanical ventilation (MV)1
MV patients accrue significantly more cost during their ICU stay than non-MV patients2
$31,574 versus $12,931, P < 0.001
Sedation should be titrated to achieve a cooperative patient and daily wake-up, a JC requirement1,2
30.6%
15.4%
54.0%
Undersedated3
Oversedated
On Target
1. Kress JP, et al. N Engl J Med. 2000;342:
2. Dasta JF, et al. Crit Care Med. 2005;33:
3. Kaplan LJ, Bailey H. Crit Care. 2000;4(suppl 1):P190.

20. Assessing Agitation and Sedation
Richmond Agitation-Sedation Scale (RASS)
Sessler CN, et al. Am J Respir Crit Care Med ;166(10):
Ely EW, et al. JAMA. 2003;289:
Sedation-Agitation Scale (SAS)
Riker RR, et al. Crit Care Med. 1999;27:
Brandl K, et al. Pharmacotherapy. 2001;21: 20

21. Richmond Agitation Sedation Scale (RASS) *
Score
Term
Description +4
Combative
Overtly combative, violent, immediate danger to staff +3
Very agitated
Pulls or removes tube(s) or catheter(s); aggressive +2
Agitated
Frequent non-purposeful movement, fights ventilator +1
Restless
Anxious but movements not aggressive vigorous
Alert and calm -1
Drowsy
Not fully alert, but has sustained awakening (eye-opening/eye contact) to voice (>10 seconds) -2
Light sedation
Briefly awakens with eye contact to voice (<10 seconds) -3
Moderate sedation
Movement or eye opening to voice (but no eye contact) -4
Deep sedation
No response to voice, but movement or eye opening to physical stimulation -5
Unarousable
No response to voice or physical stimulation

22. Procedure for RASS Assessment
1. Observe patient
Patient is alert, restless, or agitated. (score 0 to +4)
2. If not alert, state patient’s name and say to open eyes and look at speaker.
Patient awakens with sustained eye opening and eye contact. (score –1)
Patient awakens with eye opening and eye contact, but not sustained. (score –2)
Patient has any movement in response to voice but no eye contact. (score –3)
3. When no response to verbal stimulation, physically stimulate patient by shaking shoulder and/or rubbing sternum.
Patient has any movement to physical stimulation. (score –4)
Patient has no response to any stimulation. (score –5)

23. Characteristics of an Ideal Sedative
Rapid onset of action allows rapid recovery after discontinuation
Effective at providing adequate sedation with predictable dose response
Easy to administer
Lack of drug accumulation
Few adverse effects
Minimal adverse interactions with other drugs
Cost-effective
Promotes natural sleep
Ostermann ME, et al. JAMA. 2000;283:
Jacobi J, et al. Crit Care Med. 2002;30:
Dasta JF, et al. Pharmacother. 2006;26:
Nelson LE, et al. Anesthesiol. 2003;98:

24. Patient Comorbidities to Consider
Chronic pain
Organ dysfunction
CV instability
Substance withdrawal
Respiratory insufficiency
Obesity
Obstructive sleep apnea

25. Overview of Presently available Intravenous Agents

26. The Good
a2 Agonist
Propofol
Acetaminophen
NSAIDs
Haldol

27. The Bad
Opiates
Benzodiazepines

28. The Ugly
Flumazenil
Naloxone

29. The Good

30. Dexmedetomidine a2 Agonist
Clinical Effects
Adverse Effects
Antihypertensive
Sedation
Analgesia
Decreased shivering
Anxiolysis
Patient arousability
Potentiate effects of opioids, sedatives, and anesthetics
Decrease sympathetic activity
Hypotension
Hypertension
Nausea
Bradycardia
Dry mouth
Peripheral vasoconstriction at high doses
Kamibayashi T, et al. Anesthesiol. 2000;93:
Bhana N, et al. Drugs. 2000;59(2):

31. Clinical Effects Adverse Effects
Propofol
Clinical Effects Adverse Effects
Sedation
Hypnosis
Anxiolysis
Muscle relaxation
Mild bronchodilation
Decreased ICP
Decreased cerebral metabolic rate
Antiemetic
Pain on injection
Respiratory depression
Hypotension
Decreased myocardial contractility
Increased serum triglycerides
Tolerance
Propofol infusion syndrome
Prolonged effect with high adiposity
Seizures (rare)
Ellett ML. Gastroenterol Nurs. 2010;33(4):
Lundström S, et al. J Pain Symptom Manage. 2010;40(3):

32. Clinical Effects Adverse Effects
Acetaminophen
Clinical Effects Adverse Effects
Available in po and IV forms
Demonstrated effective relief of pain, either alone (mild to moderate pain) or as part of a multimodal regimen (moderate to severe pain)
No delerium
Peak effect: within an hour of administration
Duration of effect: 4 to 6 hours
No significant effect on platelet aggregation5
Potential Hepatotoxicity
Antipyretic effects may mask fever in patients treated for post-surgical pain

33. NSAIDS Ketorolac and Ibuprofen
Lacks respiratory depression
Good pain control
Anti platelet activity
Black box warning for cardiac patients

34. Haloperidol Dopamine Antagonist
Clinical Effects
Adverse Effects
Dysphoria2
Adverse CV effects include QT interval prolongation
Extrapyramidal symptoms, neuroleptic malignant syndrome (rare)1
Metabolism altered by drug-drug interactions2
Hypnotic agent with antipsychotic properties1
For treatment of delirium in critically ill adults1
Does not cause respiratory depression1
1. Harvey MA. Am J Crit Care. 1996;5:7-16.
2. Crippen DW. Crit Care Clin. 1990;6:

35. The Bad

36. Opioids Clinical Effects Adverse Effects Analgesia Hypotension
Bradycardia
Respiratory depression
Tolerance
Constipation
Withdrawal symptoms
Hormonal changes
Sedation
Fentanyl
Morphine
Remifentanyl
Benyamin R, et al. Pain Physician. 2008;11(2 Suppl):S

37. Benzodiazepines Clinical Effects Adverse Effects
Sedation, anxiolysis, and amnesia
Commonly used for long-term sedation
Adverse Effects
Metabolic acidosis (propylene glycol vehicle toxicity)
Retrograde and anterograde amnesia
Delirium
Midazolam
Lorazapam
Olkkola KT, Ahonen J. Handb Exp Pharmacol. 2008;(182):
Wilson KC, et al. Chest. 2005;128(3):

38. Comparison of Clinical Effects
Benzodiazepines
Propofol
Opioids
a2 Agonists
Haloperidol
Sedation X X X X X
Alleviate anxiety1,2 X X
Analgesic properties1-4 X X
Promote arousability during sedation2-4 X
Facilitate ventilation during weaning2-4 X X
Control delirium1-4 X X
1. Blanchard AR. Postgrad Med. 2002;111:59-74.
2. Kamibayashi T, et al. Anesthesiol. 2000;95:
3. Maze M, et al. Anesthetic Pharmacology: Physiologic Principles and
Clinical Practice. Churchill Livingstone; 2004.
4. Maze M, et al. Crit Care Clin. 2001;17:

39. Comparison of Adverse Effects
Benzodiazepines
Propofol
Opioids
a2 Agonists
Haloperidol
Prolonged weaning 1 X X
X *
Respiratory depression 1 X X X
Hypotension 1-3 X X X X X
Constipation 1 X
Deliriogenic X X X
Tachycardia 1
Bradycardia 1 X X X X
*Excluding remifentanil
1. Harvey MA. Am J Crit Care. 1996;5:7-18.
2. Aantaa R, et al. Drugs of the Future. 1993;18:49-56.
3. Maze M, et al. Crit Care Clin. 2001;17:

40. The Ugly

41. Flumazenil
Flumazenil reverses the effects of sedatives from the benzodiazepine group of drugs.

42. Naloxone An opioid antagonist drug developed in the 1960s.
Naloxone is a drug used to counter the effects of opiate overdose, for example heroin or morphine overdose.
Use with caution in the opioid addicted patient
It is not to be confused with naltrexone, an opioid receptor antagonist with qualitatively different effects, used for dependence treatment rather than emergency overdose treatment.

43. ABCDE
Awakening Breathing Coordination/Choice of Sedation Delirium Monitoring and Management Early Mobilization

44. Cardinal Symptoms of Delirium and Coma
Morandi A, et al. Intensive Care Med. 2008;34:

45. ICU Delirium Develops in ~2/3 of critically ill patients
Hypoactive or mixed forms most common
Increased risk
Benzodiazepines
Extended ventilation
Immobility
Associated with weakness
Undiagnosed in up to 72% of cases
Vasilevskis EE, et al. Chest. 2010;138(5):

46. DELIRIUM Less Modifiable More Modifiable Patient Factors
Increased age
Alcohol use
Male gender
Living alone
Smoking
Renal disease
Predisposing Disease
Cardiac disease
Cognitive impairment
(eg, dementia)
Pulmonary disease
Less Modifiable
Acute Illness
Length of stay
Fever
Medicine service
Lack of nutrition
Hypotension
Sepsis
Metabolic disorders
Tubes/catheters
Medications:
Anticholinergics
Corticosteroids
- Benzodiazepines
DELIRIUM
Environment
Admission via ED or through transfer
Isolation
No clock
No daylight
No visitors
Noise
Physical restraints
More
Modifiable
Van Rompaey B, et al. Crit Care. 2009;13:R77.
Inouye SK, et al. JAMA.1996;275:
Skrobik Y. Crit Care Clin. 2009;25:

47. Mechanisms for Delirium in the Critically Ill: Numerous and
Not Clearly Understood
Neurotransmitter imbalance
Neuroinflammation
Blood brain barrier permeability
Impaired oxidative metabolism
Microglial activation
Abnormal levels of large neutral amino acids (eg, tryptophan) and their metabolism (eg, kynurenine pathway)
It’s a bit complicated
Maldonado JR. Crit Care Clin. 2008;24(4):
Pandharipande PP. Intensive Care Med. 2009;35(11):
Adams-Wilson JR, et al. Crit Care Med (in press)

48. During the ICU/Hospital Stay After Hospital Discharge
Sequelae of Delirium
Increased mortality
Longer intubation time
Average 10 additional days in hospital
Higher costs of care
During the ICU/Hospital Stay
Increased mortality
Development of dementia
Long-term cognitive impairment
Requirement for care in chronic care facility
Decreased functional status at 6 months
After Hospital Discharge
Bruno JJ, Warren ML. Crit Care Nurs Clin North Am. 2010;22(2):
Shehabi Y, et al. Crit Care Med. 2010;38(12):
Rockwood K, et al. Age Ageing. 1999;28(6):
Jackson JC, et al. Neuropsychol Rev. 2004;14:87-98.
Nelson JE, et al. Arch Intern Med. 2006;166: 48

49. Delirium Duration and Mortality
Kaplan-Meier Survival Curve
P < 0.001
Each day of delirium in the ICU increases the hazard of mortality by 10%
Pisani MA. Am J Respir Crit Care Med. 2009;180:

50. Worse Long-term Cognitive Performance
Duration of delirium was an independent predictor of cognitive impairment
An increase from 1 day of delirium to 5 days was associated with nearly a 5-point decline in cognitive battery scores
Girard TD, et al. Crit Care Med. 2010;38:
Misak CJ. Am J Respir Crit Care Med. 2004;170(4):

51. Risk Factors Specific for ICU Delirium
Benzodiazepine use4,10
Coma (medical vs. pharmacologic)4,9
Morphine use (?data unclear)
Dementia1,2,3
Hypertension history4,5
Alcoholism3,4
Severity of illness1,4,6,7,8
Age (?pos6,8 /neg2,3,4,9)
Pisani MA, et al. Crit Care Med. 2009;37:
Pisani MA, et al. Arch Intern Med. 2007;167:
Van Rompaey B, et al. Crit Care. 2009;13:R77.
Ouimet S, et al. Intensive Care Med. 2007;33:66-73.
Dubois MJ, et al. Intensive Care Med. 2001;27:
Pandharipande PP, et al. Anesthesiology. 2006;104:21-26.
Pisani MA, et al. Crit Care Med. 2009;37:
Pandharipande PP, et al. Intensive Care Med. 2009;35:
Ely EW, et al. Crit Care Med. 2007;35:
Pandharipande PP, et al. J Trauma. 2008;65:
Coma is an independent risk factor for ICU patients to develop delirium, based upon moderate quality of evidence (B). However, establishing a definitive relationship between various subtypes of coma (i.e. medication-related, structural, neurological, medical) and delirium in ICU patients will require further study.

52. Delirium Assessment Tools
Confusion Assessment Method for the ICU (CAM-ICU)
Ely EW, et al. Crit Care Med. 2001;29:
Ely EW, et al. JAMA. 2001;286:
Intensive Care Delirium Screening Checklist (ICDSC)
Bergeron N, et al. Intensive Care Med ;27:
Ouimet S, et al. Intensive Care Med ;33:

54. Confusion Assessment Method (CAM-ICU)
1. Acute onset of mental status changes or a fluctuating course
and
2. Inattention
and
3. Altered level of
consciousness
4. Disorganized thinking or
= Delirium
Ely EW, et al. Crit Care Med. 2001;29:
Ely EW, et al. JAMA. 2001;286:

56. Delirium Assessment Tools
Confusion Assessment Method for the ICU (CAM-ICU)
Ely EW, et al. Crit Care Med. 2001;29:
Ely EW, et al. JAMA. 2001;286:
Intensive Care Delirium Screening Checklist (ICDSC)
Bergeron N, et al. Intensive Care Med ;27:
Ouimet S, et al. Intensive Care Med ;33:

57. Intensive Care Delirium Screening Checklist
1. Altered level of consciousness 2. Inattention 3. Disorientation 4. Hallucinations 5. Psychomotor agitation or retardation 6. Inappropriate speech 7. Sleep/wake cycle disturbances 8. Symptom fluctuation
Score 1 point for each component present during shift
Score of 1-3 = Subsyndromal Delirium
Score of ≥ 4 = Delirium
Bergeron N, et al. Intensive Care Med. 2001;27:
Ouimet S, et al. Intensive Care Med. 2007;33:

58. Helpful Approach to Delirium Management
Stop
THINK
Lastly, medicate

59. Stop and THINK Do any meds need to be stopped or lowered?
Especially consider sedatives
Is patient on minimal amount necessary?
Daily sedation cessation
Targeted sedation plan
Do sedatives need to be changed?
Toxic Situations
CHF, shock, dehydration
Deliriogenic meds (tight titration)
New organ failure (liver/kidney)
Hypoxemia
Infection/sepsis (nosocomial)
Immobilization
Nonpharm interventions
Hearing aids, glasses, reorient, sleep protocols, music, noise control, ambulation
K+ or electrolyte problems

60. Delirium Nonpharmacologic Interventions
Early mobility – the only nonpharmacologic intervention shown to reduce ICU delirium1
Other interventions:
Environmental changes (eg, noise reduction)
Sensory aids (eg, hearing aids, glasses)
Reorientation and stimulation
Sleep preservation and enhancement
Schweickert WD, et al. Lancet. 2009;373:

61. Sleep Abnormalities in the ICU
More time in light sleep
Less time in deep sleep
More sleep fragmentation
There is little evidence that sedatives in the ICU restore normal sleep
Friese R. Crit Care Med. 2008;36:
Weinhouse GL, Watson PL. Crit Care Clin. 2009;25:

62. Boosting Sleep Quality in ICU
Optimize environmental strategies
Day/night variation, reduce night interruptions, noise reduction
Avoid benzodiazepines (↓ Slow wave sleep (SWS) & REM)
Consider dexmedetomidine (↑ SWS)
GABA receptor agonists (eg, zolpidem)
Sedating antidepressants (eg, trazodone) or antipsychotics
Melatonin
Pilot: may improve sleep quality of ICU COPD patients
GABA receptor agonists that don’t reduce slow wave sleep (like zolpidem)
Weinhouse GL, Watson PL. Crit Care Clinics. 2009;25:
Faulhaber J, et al. Psychopharmacology. 1997;130:
Shilo L, et al. Chronobiol Int. 2000;17:71-76. 62

63. Effect of Common Sedatives and Analgesics on Sleep
There is little evidence that administration of sedatives in
the ICU achieves the restorative function of normal sleep
Benzodiazepines
↑ Stage 2 NREM
↓ Slow wave sleep (SWS) and REM
Propofol
↑ Total sleep time without enhancing REM
↓ SWS
Analgesics
Abnormal sleep architecture
Dexmedetomidine
↑ SWS
Weinhouse GL, et al. Sleep. 2006;29:
Nelson LE, et al. Anesthesiology. 2003;98:

64. Standardized Intervention
Elder Life Program
Targeted Risk Factor
Standardized Intervention
Cognitive impairment
Orientation & therapeutic activity protocol
(discuss current events, word games, reorient, etc)
Sleep deprivation
Sleep enhancement & nonpharm sleep protocol
(noise reduction, back massages, schedule adjustment)
Immobility
Early mobilization protocol
(active ROM, reduce restraint use, ambulation, remove catheters)
Visual impairment
Vision protocol
(glasses, adaptive equipment, reinforce use)
Hearing impairment
Hearing protocol
(amplification devices, hearing aids, earwax disimpaction)
Dehydration
Dehydration protocol
(early recognition of dehydration & volume repletion)
“Targeted risk factors were selected on the basis of evidence of their association with the risk of delirium and because they were amenable to intervention strategies considered feasible in the context of current hospital practice.”
Intervention provided by a trained interdisciplinary team: geriatric nurse specialist, ELP specialists, recreational therapist, PT consultant, geriatrician, trained volunteers.
Inouye SK, et al. N Engl J Med. 1999;340:

65. Results Outcome Intervention Control P-value
Incidence of delirium, N (%)
42 (9.9)
64 (15)
0.02
Total days of delirium
105
161
Episodes of delirium 62 90
0.03
↓ delirium incidence in patients with intermediate baseline risk
Improved orientation score with targeted intervention (P = 0.04)
Reduced rate of sedative use for sleep (P = 0.001)
87% overall adherence to protocol
High baseline risk also had reduced incidence, but not statistically significant
Inouye SK, et al. N Engl J Med. 1999;340:

66. Haloperidol Dopamine Antagonist
Clinical Effects
Adverse Effects
Dysphoria2
Hypnotic agent with antipsychotic properties1
Adverse CV effects include QT interval prolongation
For treatment of delirium in critically ill adults1
Extrapyramidal symptoms,
Neuroleptic malignant syndrome (rare)1
Does not cause respiratory depression1
Metabolism altered by drug-drug interactions2
1. Harvey MA. Am J Crit Care. 1996;5:7-16.
2. Crippen DW. Crit Care Clin. 1990;6:

67. Association Between Intravenous Haloperidol & Prolonged QT Interval
However, ventricular tachyarrhythmia was not detected among 307 patients within a 1 ­year period, although the ECG was continuously monitored for at least 8 hours after intravenous HAL.
The modest nature of QTc prolongation and the apparent absence of ventricular tachyarrhythmia under continuous ECG monitoring indicate that QTc prolongation associated with intravenous HAL is not necessarily dangerous.
However, in an emergency situation, clinicians cannot exclude patients predisposed to torsade de pointes, such as those with inherited ion channel disorders.
Therefore, clinicians should be aware of the association between intravenous HAL and QT prolongation

68. Atypical Antipsychotics
Receptor adherence is variable between agents
Use has increased substantially
Possible safety benefits
Decreased extrapyramidal effects
Little effect on the QTc interval (except ziprasidone)
Less hypotension/fewer orthostatic effects
Less likely to cause neuroleptic malignant syndrome
Possible limitations
No IV formulations available
Little published experience in ICU patients
Troublesome reports of adverse events but most associated with prolonged use in non-delirium patients
Devlin JW, et al. Harv Rev Psychiatry. 2011;19:59-67. 68

69. List of Atypical Antipsychotics
Amisulpride (Solian)
Paliperidone (Invega)
Aripiprazole (Abilify)
Perospirone (Lullan)
Asenapine (Saphris)
Quetiapine (Seroquel)
Blonanserin (Lonasen)
Remoxipride (Roxiam)
Carpipramine (Prazinil)
Risperidone (Risperdal)
Clocapramine (Clofekton)
Sertindole (Serdolect)
Sulpiride (Sulpirid, Eglonyl)
Clotiapine (Entumine)
Clozapine (Clozaril)
Ziprasidone (Geodon, Zeldox)
Iloperidone (Fanapt)
Lurasidone (Latuda)
Zotepine (Nipolept)
Mosapramine (Cremin)
Olanzapine (Zyprexa)

70. Use of Atypical Antipsychotic Therapy Is Increasing90 80 70 60
2001 50
2007
Respondents, % 40 30 20 10
Propofol
Haloperidol
Atypical
Antipsychotics
Benzodiazepines
Ely EW, et al. Crit Care Med. 2004;32:
Patel RP, et al. Crit Care Med. 2009;37:

71. Prophylactic Haloperidol
RCT of short-term low-dose IV haloperidol
Patients
N = 457
Age > 65 years
ICU after noncardiac surgery
Intervention
Haloperidol
0.5 mg IV bolus then
Infusion 0.1 mg/h for 12 hrs
Placebo
Primary endpoint
Incidence of delirium within the first 7 days after surgery
Crit Care Med Mar;40(3):731-9.
Haloperidol prophylaxis decreases delirium incidence in elderly patients after noncardiac surgery: A randomized controlled trial*.
Wang W, Li HL, Wang DX, Zhu X, Li SL, Yao GQ, Chen KS, Gu XE, Zhu SN.
Source
From the Departments of Anesthesiology and Surgical Intensive Care (WW, DXW, SLL, KSC, XEG) and Biostatistics (SNZ), Peking University First Hospital, Beijing, China; Department of Critical Care Medicine (HLL, XZ, GQY), Peking University Third Hospital, Beijing, China.
Abstract
OBJECTIVES:
: To evaluate the efficacy and safety of short-term low-dose intravenous haloperidol for delirium prevention in critically ill elderly patients after noncardiac surgery.
DESIGN:
: Prospective, randomized, double-blind, and placebo-controlled trial in two centers.
SETTING:
: Intensive care units of two large tertiary teaching hospitals.
PATIENTS:
: Four hundred fifty-seven patients 65 yrs or older who were admitted to the intensive care unit after noncardiac surgery.
INTERVENTION:
: Haloperidol (0.5 mg intravenous bolus injection followed by continuous infusion at a rate of 0.1 mg/h for 12 hrs; n = 229) or placebo (n = 228) was randomly administered from intensive care unit admission.
MEASURES:
: The primary end point was the incidence of delirium within the first 7 days after surgery. Secondary end points included time to onset of delirium, number of delirium-free days, length of intensive care unit stay, all-cause 28-day mortality, and adverse events. Delirium was assessed using the confusion assessment method for the intensive care unit.
RESULTS:
: The incidence of delirium during the first 7 days after surgery was 15.3% (35/229) in the haloperidol group and 23.2% (53/228) in the control group (p = .031). The mean time to onset of delirium and the mean number of delirium-free days were significantly longer (6.2 days [95% confidence interval ] vs. 5.7 days [95% confidence interval ]; p = .021; and 6.8 ± 0.5 days vs. 6.7 ± 0.8 days; p = .027, respectively), whereas the median length of intensive care unit stay was significantly shorter (21.3 hrs [95% confidence interval ] vs hrs [95% confidence interval ]; p = .024) in the haloperidol group than in the control group. There was no significant difference with regard to all-cause 28-day mortality between the two groups (0.9% [2/229] vs. 2.6% [6/228]; p = .175). No drug-related side effects were documented.
CONCLUSIONS:
: For elderly patients admitted to intensive care unit after noncardiac surgery, short-term prophylactic administration of low-dose intravenous haloperidol significantly decreased the incidence of postoperative delirium. The therapy was well-tolerated.
Wang W, et al. Crit Care Med. 2012;40(3):

72. Prophylactic Haloperidol
Haloperidol (n = 229)
Placebo
(n = 229)
P-value
7 day delirium incidence (%)
15.3
23.2
0.031
Mean time to delirium onset (days)
6.2
5.7
0.021
Mean time delirium-free (days)
6.8
6.7
0.027
Median ICU LOS (hours)
21.3
23.0
0.024
All-cause 28-day mortality (%)
0.9
2.6
0.175
Prophylactic Haloperidol
Crit Care Med Mar;40(3):731-9.
Haloperidol prophylaxis decreases delirium incidence in elderly patients after noncardiac surgery: A randomized controlled trial*.
Wang W, Li HL, Wang DX, Zhu X, Li SL, Yao GQ, Chen KS, Gu XE, Zhu SN.
Source
From the Departments of Anesthesiology and Surgical Intensive Care (WW, DXW, SLL, KSC, XEG) and Biostatistics (SNZ), Peking University First Hospital, Beijing, China; Department of Critical Care Medicine (HLL, XZ, GQY), Peking University Third Hospital, Beijing, China.
Abstract
OBJECTIVES:
: To evaluate the efficacy and safety of short-term low-dose intravenous haloperidol for delirium prevention in critically ill elderly patients after noncardiac surgery.
DESIGN:
: Prospective, randomized, double-blind, and placebo-controlled trial in two centers.
SETTING:
: Intensive care units of two large tertiary teaching hospitals.
PATIENTS:
: Four hundred fifty-seven patients 65 yrs or older who were admitted to the intensive care unit after noncardiac surgery.
INTERVENTION:
: Haloperidol (0.5 mg intravenous bolus injection followed by continuous infusion at a rate of 0.1 mg/h for 12 hrs; n = 229) or placebo (n = 228) was randomly administered from intensive care unit admission.
MEASURES:
: The primary end point was the incidence of delirium within the first 7 days after surgery. Secondary end points included time to onset of delirium, number of delirium-free days, length of intensive care unit stay, all-cause 28-day mortality, and adverse events. Delirium was assessed using the confusion assessment method for the intensive care unit.
RESULTS:
: The incidence of delirium during the first 7 days after surgery was 15.3% (35/229) in the haloperidol group and 23.2% (53/228) in the control group (p = .031). The mean time to onset of delirium and the mean number of delirium-free days were significantly longer (6.2 days [95% confidence interval ] vs. 5.7 days [95% confidence interval ]; p = .021; and 6.8 ± 0.5 days vs. 6.7 ± 0.8 days; p = .027, respectively), whereas the median length of intensive care unit stay was significantly shorter (21.3 hrs [95% confidence interval ] vs hrs [95% confidence interval ]; p = .024) in the haloperidol group than in the control group. There was no significant difference with regard to all-cause 28-day mortality between the two groups (0.9% [2/229] vs. 2.6% [6/228]; p = .175). No drug-related side effects were documented.
CONCLUSIONS:
: For elderly patients admitted to intensive care unit after noncardiac surgery, short-term prophylactic administration of low-dose intravenous haloperidol significantly decreased the incidence of postoperative delirium. The therapy was well-tolerated.
Wang W, et al. Crit Care Med. 2012;40(3):

73. Delirium + Haloperidol PRN
Quetiapine vs. Placebo
Delirium + Haloperidol PRN
Quetiapine (n = 18)
Placebo (n = 18)
Randomized, double-blind, placebo-controlled
Multisite (3 centers)
36 ICU patients
PO delivery of study drug
Quetiapine dose: mg q12h
Primary outcome: time to first resolution of delirium (ie, first 12-hour period when ICDSC ≤ 3)
Titrated in response to Haldol dosing q50mg intervals every 12 hrs.
IV prn Haldol 1-10,mg up to q2hrs no other antipsychotics or continuous infusions allowed.
10 day treatment
Dosing info From article:
The study drug was continued until one of
the following occurred: (1) the subject was
deemed by the attending intensivist, based on
their clinical judgment, to no longer demonstrate
signs of delirium and, therefore, to no
longer require scheduled therapy with an antipsychotic
agent; (2) 10 days of therapy had
elapsed; (3) ICU discharge occurred; or (4) an
adverse event potentially attributable to the
study drug occurred that warranted discontinuation
of the study drug. Allowing the attending
intensivist to discontinue study drug once
the subject no longer had signs of delirium
was consistent with existing clinical practice
in our institutions. In situations in which 10
days of therapy was reached or the subject was
ready to transfer out of the ICU while still
receiving study drug, the subject’s treatment
assignment was revealed to the attending intensivist
(but not the study team) to help determine
the best course of therapy (which could include
continued therapy with quetiapine).
Limitations: patient safety (3, 41, 44, 48, 49).
A number of potential limitations of
our study must be considered when evaluating
the results. Although adequate to
demonstrate a difference in our primary
outcome, our sample size was not large
enough to reliably detect differences in
any of the efficacy or safety outcomes. In
addition, the multiple analyses that were
completed may have contributed to an
inflated type 1 error. Therefore, our investigation
should be considered a pilot
study. The rigorous study inclusion criteria
that we chose lead to only 14% of
To accommodate the varying duration
of delirium seen in clinical practice, we
did not require a minimum duration of
study drug treatment, instead allowing
the subject’s intensivist to discontinue
study drug when delirium was thought to
have resolved or the subject was ready to
transfer from the ICU. Given its fluctuating
nature, considering delirium resolved
when first noted to be absent may be
premature, but it is a reasonable and reproducible
event. In addition, study drug
may have been discontinued prematurely
in subjects with hypoactive delirium, although
the optimal way to treat these
patients is not well-defined (3, 50–53).
Whereas the same “as-needed” haloperidol
dosing protocol was used for all study
patients, the average dose of haloperidol
that was administered was lower than the
dose recommended in some guidelines
and may reflect increasing safety concerns
among clinicians regarding the use
of high-dose haloperidol therapy (9, 54).
The greater use of haloperidol in patients
receiving placebo could have diminished
the treatment effect of quetiapine that
was observed.
Devlin JW, et al. Crit Care Med. 2010;38(2):

74. Patients with First Resolution of Delirium
Log-Rank
P = 0.001
Placebo
Proportion of Patients with Delirium
Quetiapine
Day During Study Drug Administration
Quetiapine added to as-needed haloperidol results in faster delirium resolution, less agitation, and a greater rate of transfer to home or rehabilitation.
Devlin JW, et al. Crit Care Med. 2010;38: 74

75. Impact of Quetiapine on the Resolution of Individual Delirium Symptoms
Median ICDSC and individual delirium symptoms similar at study baseline
Quetiapine
Placebo
P value
Median time to symptom resolution
Log rank
Inattention
3 hrs
8 hrs
0.10
Disorientation
2 hrs
10 hrs
Symptom fluctuation
4 hrs
14 hrs
0.004
Agitation
5 hrs
1 hrs
0.04
Time with each symptom [median (IQR)]
Comparison of Proportions
47 (0-67)%
78 (43-100)%
0.02
Hallucinations
0 (0-17)%
28 (0-43)%
47 (19-67)%
89 (33-100)%
Devlin JW, et al. Crit Care. 2011;15(5):R215.

76. Rivastigmine for Delirium?
FDA approved for dementia of Alzheimer’s or Parkinson’s
Cholinesterase inhibitor
Result
Mortality (vs placebo): 22% vs 8%, P = 0.07
Delirium (vs placebo): 5 vs 3 days, P = 0.06
Conclusion:
Need RCTs for delirium as endpoint
Don’t use rivastigmine for ICU delirium
Survival (%)
Time (days after inclusion)
Lancet Nov 27;376(9755): Epub 2010 Nov 4.
Effect of rivastigmine as an adjunct to usual care with haloperidol on duration of delirium and mortality in critically ill patients: a multicentre, double-blind, placebo-controlled randomised trial.
van Eijk MM, Roes KC, Honing ML, Kuiper MA, Karakus A, van der Jagt M, Spronk PE, van Gool WA, van der Mast RC, Kesecioglu J, Slooter AJ.
Source
Department of Intensive Care Medicine, University Medical Centre, Utrecht, Netherlands.
Abstract
BACKGROUND:
Delirium is frequently diagnosed in critically ill patients and is associated with adverse outcome. Impaired cholinergic neurotransmission seems to have an important role in the development of delirium. We aimed to establish the effect of the cholinesterase inhibitor rivastigmine on the duration of delirium in critically ill patients.
METHODS:
Patients (aged ≥18 years) who were diagnosed with delirium were enrolled from six intensive care units in the Netherlands, and treated between November, 2008, and January, Patients were randomised (1:1 ratio) to receive an increasing dose of rivastigmine or placebo, starting at 0·75 mL (1·5 mg rivastigmine) twice daily and increasing in increments to 3 mL (6 mg rivastigmine) twice daily from day 10 onwards, as an adjunct to usual care based on haloperidol. The trial pharmacist generated the randomisation sequence by computer, and consecutively numbered bottles of the study drug according to this sequence to conceal allocation. The primary outcome was the duration of delirium during hospital admission. Analysis was by intention to treat. Duration of delirium was censored for patients who died or were discharged from hospital while delirious. Patients, medical staff, and investigators were masked to treatment allocation. Members of the data safety and monitoring board (DSMB) were unmasked and did interim analyses every 3 months. This trial is registered with ClinicalTrials.gov, number NCT
FINDINGS:
Although a sample size of 440 patients was planned, after inclusion of 104 patients with delirium who were eligible for the intention-to-treat analysis (n=54 on rivastigmine, n=50 on placebo), the DSMB recommended that the trial be halted because mortality in the rivastigmine group (n=12, 22%) was higher than in the placebo group (n=4, 8%; p=0·07). Median duration of delirium was longer in the rivastigmine group (5·0 days, IQR 2·7-14·2) than in the placebo group (3·0 days, IQR 1·0-9·3; p=0·06).
INTERPRETATION:
Rivastigmine did not decrease duration of delirium and might have increased mortality so we do not recommend use of rivastigmine to treat delirium in critically ill patients.
Accessed March 2012.
Van Eijk MM, et al. Lancet ;376(9755):

77. Before Considering a Pharmacologic Treatment for Delirium…
Does your patient have delirium?
Assessed with scale?
Which type of delirium?
Hyperactive
Hypoactive
Mixed hyperactive-hypoactive
Have the underlying causes of delirium been identified and reversed/treated?
Have non-pharmacologic strategies been optimized?
Inouye SK, et al. N Engl J Med. 1999;340:

78. Antipsychotic Therapy
Rule Out Dementia
Antipsychotic drugs are not approved for the treatment of dementia-related psychosis
No drug is approved for dementia-related psychosis
Elderly patients with dementia-related psychosis treated with antipsychotic drugs are at an increased risk of death
Physicians considering antipsychotics for elderly patients with dementia-related psychosis should discuss this increased risk of mortality with their patients, patients’ families, and caregivers
Antipsychotics.
Accessed March 2012.

79. ABCDE
Awakening Breathing Coordination/ Choice of Sedation Delirium Monitoring and Management Early Mobilization

80. Early Mobilization Patient Selection
Inclusion criteria
Medical ICU
Adults (≥ 18 years of age)
On MV < 72 h, expected to continue for at least 24 h
Met criteria for baseline functional independence (Barthel Index score ≥ 70)
Exclusion criteria
Rapidly developing
Neuromuscular disease
Cardiopulmonary arrest
Irreversible disorders with estimated 6-month mortality > 50%
Raised intracranial pressure
Absent limbs
Enrollment in another trial
Schweickert WD, et al. Lancet. 2009;373:

81. Early Mobilization Trial Design
104 sedated patients with daily interruption
Early exercise and mobilization (PT & OT; intervention; n = 49)
PT & OT as ordered by the primary care team (control; n = 55)
Primary endpoint: number of patients returning to independent functional status at hospital discharge
Ability to perform 6 activities of daily living
Ability to walk independently
Assessors blinded to treatment assignment
Secondary endpoints
Duration of delirium during first 28 days of hospital stay
Ventilator-free days during first 28 days of hospital stay
Schweickert WD, et al. Lancet. 2009;373:

82. Perform Safety Screen First
*Range of motion may be started in comatose patients, but not considered Early Exercise/Mobility
Pass
Fail
Exercise/Mobility Therapy
Too Ill for Exercise/Mobility
Schweickert WD, et al. Lancet. 2009;373:

83. Early Mobilization Protocol: Result
Return to independent functional status at discharge
59% in intervention group
35% in control group (P = 0.02)
Schweickert WD, et al. Lancet. 2009;373:

84. Early PT and OT in Mechanically Ventilated ICU Patients
All Patients
P = 0.93
P = 0.08
P = 0.02
P = 0.02
Two center trial of 104 adult patients on mechanical ventilation for less than 72 hrs, randomized to early exercise and mobilization (PT and OT) during periods of daily interruption of sedation or to daily interruption of sedation with therapy as ordered by the primary care team.
Schweickert WD, et al. Lancet. 2009;373(9678):

85. Protocol for Early Mobility Therapy Acute Respiratory Failure Patients
Morris PE, et al. Crit Care Med. 2008;36(8):

86. Early Mobility Therapy Results
Primary Endpoint: more protocol patients received PT than did usual care (80% vs. 47%, P ≤ 0.001)
Usual Care*
(n = 135)
Protocol*
(n = 145)
P-Value
Days to first out of bed
11.3
5.0
0.001
Ventilator days
10.2
8.8
0.163
ICU LOS days
6.9
5.5
0.025
Hospital LOS days
14.5
11.2
0.006 *
Values adjusted for BMI, Acute Physiology & Chronic Health Evaluation II, and vasopressor
Morris PE, et al. Crit Care Med. 2008;36(8):

87. Post-Intensive Care Syndrome (PICS)
SCCM Task Force on Long-Term Outcomes
“Post-intensive care syndrome (PICS) was agreed upon as the recommended term to describe new or worsening problems in physical, cognitive, or mental health status arising after a critical illness and persisting beyond acute care hospitalization.
The term could be applied to either a survivor or family member- PICS-F.”
A task force was convened by the Society of Critical Care Medicine to address the long-term outcomes from critical illness. Key stakeholders were invited to participate from healthcare agencies, disciplines of palliative care, rehabilitative therapy, physiatrists, hospitalists and research funding agencies. The research was reviewed. Future directions were planned. It was clear that more attention needs to be made to assess, treat, and prevent the long-term consequences of critical illness. This means partnering with our colleagues outside of the ICU to provide smooth transitions across levels of acuity during handoffs. The major implications during the ICU stay are family inclusion in care and communication, appropriate sedation and early mobility while maintaining cognitive activities.
Needham DM, et al. Crit Care Med. 2012;40(2):

88. PICS Consequences Post Intensive Care Syndrome (PICS) Family (PICS-F)
Mental Health
Anxiety/ASD
PTSD
Depression
Complicated Grief
Survivor
(PICS)
Cognitive Impairments
Executive Function
Memory
Attention
Physical Impairments
Pulmonary
Neuromuscular
Physical Function
Needham DM, et al. Crit Care Med. 2012;40(2):
Desai SV, et al. Crit Care Med. 2011;39(2):
Davidson JE, et al. Crit Care Med. 2012;40(2):

89. Benefits of ABCDE Protocol
Morandi A, et al. Curr Opin Crit Care. 2011;17:43-49.

90. Quality Improvement Project: Implementing ABCDE
Multidisciplinary team focused on reducing heavy sedation, using SAT-SBT protocol and increasing MICU staffing to include full-time physical and occupational therapists with new consultation guidelines
Results:
Delirium decreased
Sedation use decreased
Physical mobility improvement
Decrease hospital length of stay
Increased MICU admissions
Needham DM, et al. Arch Phys Med Rehabil. 2010;91(4):
Needham DM, et al. Top Stroke Rehabil. 2010;17(4):

91. Results of ICU Quality Initiative
Top Stroke Rehabil Jul-Aug;17(4):
Rehabilitation quality improvement in an intensive care unit setting: implementation of a quality improvement model.
Needham DM, Korupolu R.
Source
Division of Pulmonary & Critical Care Medicine, Johns Hopkins University, Baltimore, MD, USA.
Abstract
OBJECTIVE:
There are barriers to providing early physical medicine and rehabilitation (PM&R) in the intensive care unit (ICU). We present a specific model for undertaking quality improvement (QI) projects and a case study focused on QI for early PM&R in the ICU.
METHODS:
The QI project was undertaken using a 4-step model: (1) summarizing the evidence, (2) identifying barriers, (3) establishing performance measures, and (4) ensuring patients receive the intervention. To evaluate the application and outcomes of this model, we present data collected during a 4-month QI period versus an immediately preceding 3-month control period.
RESULTS:
Deep sedation was a major barrier to early PM&R that was addressed in the QI project. Compared to the control period, there was a decrease in medical ICU (MICU) days with any benzodiazepine use (73% vs 96% of days, P = .03) and narcotic use (77% vs 96%, P = .05) and improved delirium status (MICU days without delirium, 53% vs 21%, P = .003). In addition, more QI patients had physical therapy consultations (93% vs 59%, P = .004) and greater number of rehabilitation treatments with higher functional mobility (treatments involving sitting or greater mobility, 78% vs 56%, P = .03). Hospital data for the QI period demonstrated a decrease in average length of stay in the MICU (4.9 vs 7.0 days, P = .02) and hospital (14.1 vs 17.2, P = .03) compared to the prior year.
CONCLUSION:
A structured QI model can be applied to implementation of early PM&R in the ICU resulting in markedly improved delirium status, delivery of PM&R, functional mobility, and length of stay.
Needham DM, et al. Top Stroke Rehabil. 2010;17(4):

92. Results of ICU Quality Initiative (cont)
Top Stroke Rehabil Jul-Aug;17(4):
Rehabilitation quality improvement in an intensive care unit setting: implementation of a quality improvement model.
Needham DM, Korupolu R.
Source
Division of Pulmonary & Critical Care Medicine, Johns Hopkins University, Baltimore, MD, USA.
Abstract
OBJECTIVE:
There are barriers to providing early physical medicine and rehabilitation (PM&R) in the intensive care unit (ICU). We present a specific model for undertaking quality improvement (QI) projects and a case study focused on QI for early PM&R in the ICU.
METHODS:
The QI project was undertaken using a 4-step model: (1) summarizing the evidence, (2) identifying barriers, (3) establishing performance measures, and (4) ensuring patients receive the intervention. To evaluate the application and outcomes of this model, we present data collected during a 4-month QI period versus an immediately preceding 3-month control period.
RESULTS:
Deep sedation was a major barrier to early PM&R that was addressed in the QI project. Compared to the control period, there was a decrease in medical ICU (MICU) days with any benzodiazepine use (73% vs 96% of days, P = .03) and narcotic use (77% vs 96%, P = .05) and improved delirium status (MICU days without delirium, 53% vs 21%, P = .003). In addition, more QI patients had physical therapy consultations (93% vs 59%, P = .004) and greater number of rehabilitation treatments with higher functional mobility (treatments involving sitting or greater mobility, 78% vs 56%, P = .03). Hospital data for the QI period demonstrated a decrease in average length of stay in the MICU (4.9 vs 7.0 days, P = .02) and hospital (14.1 vs 17.2, P = .03) compared to the prior year.
CONCLUSION:
A structured QI model can be applied to implementation of early PM&R in the ICU resulting in markedly improved delirium status, delivery of PM&R, functional mobility, and length of stay.
Needham DM, et al. Top Stroke Rehabil. 2010;17(4):

93. Conclusions
Untargeted sedation in the ICU is common, and it is associated with negative sequelae
Be familiar with the ABCDE protocol
Titrate all sedative medications using a validated assessment tool to keep patients comfortable and arousable if possible
Use of benzodiazepines should be minimized 93

94. Conclusions
Consider nonpharmacological management of delirium and reduce exposure to risk factors
Typical and atypical antipsychotic medications may be used to treat delirium if nonpharmacological interventions are not adequate
Early mobility in ICU patients decreases delirium and improves functional outcomes at discharge
Recognize PICS exists for patients and families

95. Thanks