Current Topics in Critical Care

Susan M. Hellervik, MSN, ACNP-BC

MICU NP Service

Objectives• Describe current studies related to selected critical

care topics.

• Integrate knowledge of the evidence related to selected critical care topics into practice.

Selected Topics• Use of Beta Blockers in Critical Illness

• Post-Intensive Care Syndrome (PICS)

• Choosing Wisely

Beta Blockers in Critical Care• Critical illness is characterized by increased resting energy

expenditure due to sympathetic activation and a hyper-metabolic state; Beta blockers are known to decrease tissue oxygen consumption.

• Sympathetic overstimulation or prolonged stimulation can lead to cardiovascular and systemic effects that can contribute to morbidity and mortality.

• It has been hypothesized that modulation of this process with the use of beta blockers may have a protective effect on cardiac and systemic effects of sympathetic overstimulation

• Recent studies have investigated the effects of Beta blockers on critically ill patients and sub-groups of patients with septic shock, acute respiratory failure and TBI.

Effects of Sympathetic Overstimulation

Cardiovascular Effects Systemic Effects

• Cardiac depression• Decreased LVEF• Apical ballooning• Myocardial stunning• Apoptosis and necrosis

• Catabolic state• Hyperglycemia• Insulin resistance• Hypercoagulability• Immunosuppression• Enhanced bacterial growth• Other inflammatory

derangements

Special Populations

Sepsis Acute Respiratory Failure TBI

• Early sepsis increases cardiac contractility and HR to meet metabolic demands – these effects are initially beneficial, but these can become deleterious if excessive or prolonged

• Frequent occurrence of COPD exacerbations and cardiac co-morbidities

• Chronic β-2 agonist therapy may increase the incidence of cardiovascular morbidity.

• The use of β-blockers has been shown to be safe and beneficial as the potential benefits may outweigh the risks

• ARDS, independent of etiology is a critical illness accompanied by sympathetic overstimulation, presenting an interesting area of research

• Non-neurologic organ dysfunction due to sympathetic hyperactivity contributes to mortality in severely brain injured patients.

• Catecholamine surges have been observed after TBI and in patients with non-traumatic SAH

• Stress cardiomyopathy and neurologic pulmonary edema contribute to poor outcomes independently of the severity of the initial brain injury.

• Local β- blockade may decrease parenchymal vessel vaso-constriction, reducing secondary brain injury, improving perfusion and oxygenation.

Critical Care, 2011: Christensen, et.al. Preadmission beta-blocker use and 30-day mortality among patients

in intensive care: a cohort study.

• Study of the association between preadmission beta-blocker use and 30-day mortality after ICU care.

• Cohort study, prospectively collected data from population-based medical databases from 3 Danish University hospitals.

• 8,087 patients with a first ICU admission during the study period. Patients < 45 years of age and those admitted for 24hr. post-operative observation and those with incomplete lab data were excluded.

• Current beta-blocker users were defined as those who filled a prescription for beta-blockers in the 60 days prior to ICU admission

• Subgroups of new and long-term users, non-selective beta-blockers, non-selective beta-blockers combined with alpha-adrenergic blockers and cardio selective beta-blockers were examined

• Odds ratio of death was computed for users of beta-blockers compared with non-users, controlling for multiple covariates.

Results

• Inclusion of all 8,087 ICU patients in a logistic regression analysis yielded an adjusted OR of 0.82 (95% confidence interval (CI): 0.71 to 0.94) for beta-blocker users compared with non-users. In the propensity score matched analysis we matched all 1,556 beta-blocker users (19.2% of the entire cohort) with 1,556 non-users; the 30-day mortality was 25.7% among beta-blocker users and 31.4% among non-users (OR 0.74 (95% CI: 0.63 to 0.87)].

• The OR was 0.69 (95% CI: 0.54 to 0.88) for surgical ICU patients and 0.71 (95% CI: 0.51 to 0.98) for medical ICU patients.

• The OR was 0.99 (95% CI: 0.67 to 1.47) among users of non-selective beta-blockers, and 0.70 (95% CI: 0.58 to 0.83) among users of cardio selective beta-blockers.

• The biological interaction between beta-blocker and statin uses was -11.7% suggesting additional mortality reducing effect from combining beta-blockers and statins

Conclusions

• Beta-blocker use was associated with reduced 30 day mortality in general ICU patients (adjusted OR 0.82)

• The mortality reducing effect was similar among medical and surgical ICU patients and was not restricted to patients admitted with cardiovascular diseases. (adjusted OR 0.69 and 0.71)

• It remains unclear whether an additional beneficial effect of combining beta-blockers and statins, compared to beta-blocker monotherapy, is a true pharmacological effect.

JAMA, 2013 : Morelli et. AlEffect of Heart Rate Control With Esmolol on Hemodynamic

and Clinical Outcomes in Patients With Septic Shock

• Randomized Clinical Trial in a university hospital ICU involving patients in septic shock with a HR ≥ 95 requiring high dose norepinephrine to maintain a MAP ≥ 65 after 24 hours of hemodynamic optimization

• 77 patients randomized to receive continuous esmolol infusion titrated to maintain HR between 80-94 for their ICU stay; 77 patients were randomized to standard treatment.

• Primary outcome: reduction of HR below the threshold of 95 beats/min and maintenance of HR between 80 and 94 by esmolol treatment over a 96 hour period

• Secondary outcomes: hemodynamic and organ function measures; norepinephrine dosages at 24, 48, 72 and 96 hours; and adverse events and mortality occurring within 28 days after randomization

ResultsEsmolol Infusion Standard Treatment P Value

Mortality28 Day %ICU %Hospital %

49.457.167.5

80.588.390.9

P> 0.001P> 0.001P> 0.001

LOS – ICU, DMedianSurvivors

19(11-27)17(9-28)

14(7-25)21(11-34)

P> 0.03P> 0.70

Cause of Death No./Total, (%)Multiple Organ Failure Refractory hypotension Unknown

15/52 (28.8)32/52 (61.6)5/52 (9.6)

26/70 (37.1)44/70 (62.9) P> 0.71

Target heart rate achieved ; Reduced fluid requirement

No clinically relevant differences between groups in other cardiopulmonary variables nor in rescue therapy requirements

Adjusted hazard ratio, 0.39%; 95% CI, 0.26-0.59; P< .001

Conclusions

• Lowering HR improves cardiac efficiency without detrimental effects in tissue perfusion

• 80% mortality rate in the control group is unusually high ; Baseline CV parameters in the control group were slightly worse than in the study group

• The author hypothesized that the non-cardiac effects of esmolol in modulating adverse effects of catecholemines could have contributed to the improvement in mortality.

• More research is needed to investigate this approach on patient outcomes and to reveal the clinical significance of extra-cardiac effects.

Multidisciplinary Respiratory Medicine, 2014 : Kargin, et.al. The safety of beta-blocker use in chronic obstructive pulmonary disease patients with respiratory failure in the intensive care unit.

• Retrospective case-control study, 188 patients enrolled

• Level III closed ICU in a teaching hospital with the same intensivists.

• All COPD patients with ARF who were treated with beta-blockers (case group) and non-beta-blocker HRLDs (control group) were included. Control drugs were diltiazem, digoxin, amiodarone or a combination of these.

• Demographics, reason for HRLD, cause of ARF, comorbidities, ICU data including (APACHE II) score, type of ventilation, HR, ICU and hospital LOS, and ICU, hospital and 30 day mortality rates

Results

Case Group Control Group P

Patients enrolled 74 114

Pt. characteristics, APACHE II score, HR, rate, duration and type of ventilation, and median length of ICU-hospital stay similar between the groups

Reason for HRLDAtrial Fibrillation %SVT %

2341.9

5054.4

MortalityICU %Hospital %30 days post DC %

17.618.920

15.819.311

P> 0.75P> 0.95P> 0.13

ICU Length of Stay 6 (4–10) 7 (4–10) P> 0.69

Conclusion – Beta blocker use for heart rate control in COPD patients in ICU with ARF is

associated with similar ICU stay length and mortality compared with COPD patients treated

with other HRLDs.

Brain Injury StudiesStudy Author Study Design Groups Outcomes Limitations

Beta-blocker exposure in patients with severe traumatic brain injury (TBI) and cardiac uncoupling.

Riordan, et.al.2007Journal of Trauma and Acute Care Surgery

Retrospective β – Blocker: 138No β-Blocker: 308

Reduced mortality in β – block group despite older, more severely injured patients

Study design

Differentβ - blockers

Beta-blockers in isolated blunt head injury.

Inaba, et.al.2008Journal of the American Collegeof Surgeons

Retrospective β – Blocker: 203No β-Blocker: 953

Reduced mortality in β – block group despite older, more severely injured patients

Study design

Lack of information on β -blockers

Beta-adrenergic blockadeand traumatic brain injury: protective?

Schroeppel, et.al.2010Journal of Trauma and Acute Care Surgery

Retrospective β – Blocker: 506No β-Blocker: 2095

Similar mortalitybetween groups despite older and more severely injured β – blocked patients

Study design

Differentβ - blockers

Coppola, S., Froio, S. and Chiumello, D. β-blockers in critically ill patients: from physiology to clinical evidence. Critical Care.

2015. 19: 119.

Post-Intensive Care Syndrome(PICS)

PICS• There are increasing numbers of ICU survivors. In the US

there are approximately 5.7 million ICU patients annually with approximately 4.8 million survivors.

• Many survivors experience impairment in cognitive function, psychiatric function and physical function.

• PICS is associated with recurrent illness and re-hospitalization, increased mortality, increased healthcare costs

• PICS represents a substantial public health burden due to the presence of neuropsychological and functional disability

• Negative impact on family income in one third to one half of patients and families of survivors.

Lancet Respiratory Medicine, 2014. Jackson, J.C., Pandharipande, P. P., Girard, T.D. et.al.

Depression , Posttraumatic Stress Disorder, and Functional Disability in Survivors of Critical Illness: results from the BRAIN

ICU (Bringing to light the Risk Factors And Incidence of Neuropsychological dysfunction in ICU survivors) Investigation: A

Longitudinal Cohort Study

• Prospective, multisite cohort study of Medical/surgical ICU patients with respiratory failure or shock

• Detailed collection of demographic data and in-hospital variables• Assessment of survivors at 3 and 12 months with measures of depression,

posttraumatic stress disorder and functional disability. • Independent associations between age and delirium duration versus mental

health and functional disabilities were examined.

Results / Conclusions3 Months 12 Months

Mild depression 37% 33%

Depressive symptoms, no hx 30% 29%

PTSD Symptoms 7% 7%

Disabilities in ADL’s 32% 27%

Disabilities in IADL’s 26% 23%

• In contrast with early single-center reports, this study found that depression is

much more common than PTSD after critical illness and is driven by somatic

symptoms indicative of physical disabilities rather than cognitive symptoms.

• Poor mental health and functional disability are common after critical illness

and are persistent.

• Older age was frequently associated with mental health and functional

disabilities, no consistent association was observed between delirium and

these outcomes.

Areas of Dysfunction

Cognitive Psychiatric Physical

Memory Anxiety ICU acquired weakness

Attention Depression Poor mobility / Falls

Processing Speed PTSD Critical illness myopathy, polyneuropathy and combined CIM/CIP

Visuospatial ability Contractures

Executive Functioning Reduced lung function

Malnutrition

Incidence

Neuromyopathy 50%

Clinically significant depression 28%

Anxiety 24%

Clinically significant PTSD 22%

Cognitive Impairment 79%

General Risk Factors • ICU Stay ≥ 48 hours• ≥ 1 instance of delirium• Older Age• Sedation (anticholinergic or benzodiazepine medication)• Mechanical Ventilation

Risk FactorsCognitive Psychiatric Physical

Delirium Severe Sepsis Prolonged mechanical ventilation (> 7 days)

Prior cognitive deficit ARDS Sepsis

Sepsis Trauma Multi-system organ failure

ARDS Hypoglycemia Prolonged bedrest

Hypoxemia Hypoxemia ARDS

Acute brain dysfunction (alcoholism, stroke)

Pre-existing anxiety and depression SIRS

Hypotension Female gender Glucose dysregulation

Glucose dysregulation Age < 50 Use of vasoactive agents

Prolonged mechanical ventilation Lower education level Use of corticosteroids

Cardiac surgery Pre-existing disability/unemployment **Use of neuromuscular blockade has traditionally been associated with neuromuscular weakness but this association remains controversial and unproven

OSA Pre-morbid ETOH abuse

Renal replacement therapy ICU sedative and analgesia use

Medications

Cognitive Dysfunction

• Neuroimaging and neuropsychological investigations reflect a new non-specific acquired brain injury

• Possible etiologies of the acquired brain injury may include:

– Hypoxia (duration has been associated with

– Cytokine activated immune system dysregulation

– Hypotension

– Glucose dysregulation

– Potentially neurotoxic effects of medications

Hypoxemia• Duration associated with adverse cognitive outcomes

• Associated with worse executive functioning at 12-month follow up in ARDS patients

• Hypoxemia contributes to brain injury via biochemical cascade

– Decreased ATP production

– Lactic acidosis

– Excitotoxicity due to excessive release of excitatory neurotransmitters

– Increased Ca influx and intracellular Ca accumulation due to ionic pump failure

– Reperfusion injury

– Necrosis

– Apoptosis

Glucose Dysregulation

• Both hyperglycemia and hypoglycemia are associated with cognitive dysfunction in critically ill patients

• Recent study of ARDS patients showed a serum glucose of > 153mg/dL predicted poor cognitive functioning at 1 year

• In a study of surgical ICU patients, a single episode of hypoglycemia was found to aggravate critical illness–induced neurocognitive dysfunction

• Post-mortem investigation of patients who died in the ICU showed that patients with hyperglycemia had increased microglial activation, increased neuronal apoptosis and increased neuronal damage in the hippocampus and frontal cortex.

Hyperglycemia

• Decreases cerebral blood flow

• Damages the vascular endothelium

• Increased permeability of the blood-brain barrier

• Increases release of excitatory neurotransmitters and subsequent neuronal death

• Results in formation of oxygen radicals, cytolytic proteases and release of pro-inflammatory cytokines resulting in neuronal injury.

Medications• Many medications given to critically ill patients affect neurotransmission

including these that have central anticholinergic effects:

– Tricyclic anti-depressants

– H2 Blockers

– Opiates

– Furosemide

– Benzodiazepines

• Sedatives, narcotics and paralytics have been implicated in the development of delirium

• Excess dopamine is a risk factor for delirium

• Gamma-aminobutyric acid abnormalities can contribute to delirium

Critical Care Medicine 2010. Girard, TD, Jackson, JC, Pandharipande PP, et.al. Delirium as a predictor of long-term

cognitive impairment

• Tested the hypothesis that duration of delirium in the ICU is an independent predictor of long-term cognitive impairment after critical illness requiring mechanical ventilation.

• Prospective cohort study in the Medical ICU of a large community hospital in the US

• Patients mechanically ventilated MICU patients assessed daily for delirium while in the ICU and then underwent comprehensive cognitive assessments 3 and 12 mo. after discharge.

• 126 pts., 99 survived > 3 mo. Long-term cognitive outcomes were obtained for 77 (78%) of patients.

Results / Conclusions

3 Months 12 Months

Cognitive Impairment 79% 71%

Severe Impairment 62% 36%

Median length of delirium – 2 days (1-5)

After adjusting for age, education, pre-existing cognitive

Function, severity of illness, severe sepsis and exposure to

sedative medications in the ICU, increasing duration of delirium

Was an independent predictor of worse cognitive function.

Length of mechanical ventilation was not associated with long-term

cognitive impairment.

PICS Diagnostic EvaluationCognitive Psychiatric Physical

Modified Mini-Mental State examination (MMSE)

Clinical Assessment/Formal Mental Health screening

Physical exam

Mini-Cog Hospital anxiety and depression scale PT/OT eval

Montreal Cognitive Assessment (MoCA)* Preferred due to assessment of executive function, more sensitive test for mild impairment

Beck Depression Inventory PFT’sExercise tolerance test

Post-traumatic stress syndrome 10-questions inventory (PTSS-10)

Nutrition assessment

Rule out other causes (Pre-existing conditions, organic causes: stroke, hyper/hypothyroidism, B12 deficiency, anemia, cancer, OSA)

Electromyography and nerve conduction tests are unnecessary as the result does not alter the treatment)

Prevention

• Awakening and Breathing Coordination

• Delirium monitoring and management

• Early ambulation / physical therapy

• Light sedation

• Avoidance of hypoxemia and hypoglycemia

• ICU Diaries

Recovery

• Some patients recover to pre-illness level of function, some remain fixed and some decline. Recovery is often slow.

• Cognitive rehab is rarely used with ICU survivors because of barriers including regulatory requirements for acute inpatient rehabilitation

• Patient can use strategies to maximize existing skills / abilities

• Develop new skills that offset the impact of cognitive dysfunction (memory books, planners, etc.)

• Small pilot study (RETURN) published in 2012 demonstrated significant improvement at 3 month follow up with an approach to rehabilitation of executive function called Goal Management Training.

PICS Care

• Clinics created to address morbidities associated with PICS

• Present in the UK and parts of Europe for the last 20 years, typically home based or nurse led.

• Only recently developed in the United States.

• Critical Care Recovery Center (CCRC) was developed in 2011 using a collaborative care model by the Pulmonary Critical Care and Geriatrics divisions at the Indiana University School of Medicine

• 2012 ICU Recovery Center at Vanderbilt

ICU Recovery Center at Vanderbilt

• Multidisciplinary approach to improving the long-term outcomes of patients after ICU discharge:

– Pulmonary functioning

– Overall physical health

– Cognitive functioning and mental health

– Medication safety and reconciliation

– Degree of return to basic daily function

• Patients referred from all adult ICU’s

• Eligible patients are those with:

– Severe ARDS or Sepsis

– Those requiring mechanical ventilation and/or patients with delirium

• On-going data collection to evaluate outcomes

• Barriers include recruitment, attendance, funding.

Multidisciplinary Team Clinic Visit Components

Critical Care Pulmonologist Formal medical evaluation including full history and physical exam, PFT’s, Exercise tolerance test (6 minute walk)

Acute Care Nurse Practitioner Medication review and reconciliation

Clinical Pharmacist Neurocognitive Exam

Nurse Case Manager Meeting with Case Manager

Neuropsychologist Referrals for therapy, equipment, home care and medical sub-specialties as needed.

Discussion of topics such as work re-entry and end-of-life care

Team discussion of each aspect of the patients recovery

Preparation of a summary of the findings and recommendations for the patient’s Primary Care Provider

Pharmacy Outcomes

Intervention % Patients

Identification of adverse drug events 14%

Adverse drug event prevented 6%

Drug-drug interactions 0%

Increase medication dose 12%

Decrease medication dose 5%

Medication discontinued 43% mean 1.3

New medication ordered 33% mean 1.2

Medication lab monitoring ordered 12%

Pill box provided 8%

Flu shot administered 30%

Choosing Wisely

American Thoracic Society - June 2014American Association of Critical Care Nurses - March 2014

American College of Chest Physicians - April 2014Society of Critical Care Medicine - March 2014

Background

• Critical Care Societies Collaborative

• Included representation from all four societies

• Spanned the clinical disciplines of critical care medicine, including internal medicine, surgery, anesthesiology, emergency medicine and critical care nursing.

• Focus on recommendations that were: Correct, Important, Germane to Critical Care Practice, Novel

• Five categories: Diagnostic tests, therapies, procedures, end of life care and structures of care.

• Criteria: Strength of evidence, prevalence, aggregate cost, relevance and innovation.

Recommendations

1) Do not transfuse RBC’s in hemodynamically stable, non-bleeding ICU patients with an Hgb concentration greater than 7mg/dl.

2) Do not order diagnostic tests at regular intervals (such as every day) but rather in response to specific clinical questions.

3) Do not use parenteral nutrition in adequately nourished critically ill patients within the first 7 days of an ICU stay.

4) Do not deeply sedate mechanically ventilated patients without a specific indication and without daily attempts to lighten sedation.

5) Do not continue life support for patients at high risk for death or severely impaired functional recovery without offering patients and their families the alternative of care focused entirely on comfort.

Journal of Hospital Medicine, 2015: Corson, et. al. A Multifaceted Hospitalist Quality Improvement Intervention:

Decreased Frequency of Common Labs

• QI Intervention including audit, feedback and reporting of the frequency that common labs were ordered as daily by the hospitalist group.

• Pre-post analysis comparing a cohort of patients in 10 month baseline and 7 month intervention periods.

• Primary endpoint was number of common labs ordered per patient-day. Secondary endpoints included length of stay, hospital mortality, 30-day readmission, blood transfusion, amount of blood transfused and laboratory costs per patient.

ResultsBaseline n=7824 Intervention n=5759

Common labs/pt. day (mean) 2.06 1.84↓ 10.7%

P > 0.01

Hospital Mortality % 2.2 1.8 P=0.1

Vol. blood in pts. receiving blood transfusion

↓ 127.2 ml P=0.06

LOSReadmission Rate

No significant changeNo significant change

Hospital Direct Cost ↓ $16.19 / admission Annualized $151,682

Conclusion:

• This QI intervention in a community hospital was associated with a statistically

significant, but modest, decrease in the number of ordered lab tests and hospital

costs.

• No effect was seen on hospital LOS, mortality or readmission rates.

• An intervention focused on daily labs can be effective in safely reducing

healthcare waste without compromising quality of care.

Annals of the American Thoracic Society, 2014: Admon, A.J and Cooke, C.R. Will Choosing Wisely Improve Quality and

Lower Costs of Care for Patients with Critical Illness?

For the critical care lists to have an impact on costs and quality, two things must occur:

• Providers whose practice is discordant with the list must adhere to it when making decisions, and

• Those decisions must lead to improvements in the quality of care at lower costs.

Some feel that the campaign will do little to change provider behavior and that even if behavior change occurs that the ultimate impacts on cost and quality will be lower than expected.

Increasing the Impact of the Top-5 List for Critical Care

• Pay for performance - Based on strong evidence, link to outcomes of importance that are measurable. (limiting TPN, sedation, transfusion)

• Integrate the Top-5 list into the EMR via prompts, order sets.

• Increase awareness of costs of labs, routine diagnostics

• Create cognitive aids, checklists for use at the bedside

• Public posting of Top-5 list to encourage conversations

• Use the campaign to facilitate implementation of other practice guidelines and bundles.

• Don’t stop at 5. Use this platform to build relationships between stakeholders at every level of the healthcare system to achieve system-wide improvements in quality.

ReferencesCoppola, S., Froio, S. and Chiumello, D. β-blockers in critically ill patients:

from physiology to clinical evidence. Critical Care. 2015. 19: 119.

Morelli, A. Ertmer, C., Westphal, M. et.al. Effect of Heart Rate Control With Esmolol on Hemodynamic and Clinical Outcomes in Patients With Septic Shock A Randomized Clinical Trial. JAMA. 2013; 310 (16): 1683-1691.

Kargin, F., Takir, HB, Salturk, C. et.al. The safety of beta-blocker use in chronic obstructive pulmonary disease patients with respiratory failure in the intensive care unit. Multidisciplinary Respiratory Medicine. 2014; 9:8.

Christensen, S., Johansen, MB., Tonnesen E. et.al. Preadmission beta-blocker use and 30-day mortality among patients in intensive care: a cohort study. Critical Care. 2011; 15:R87

Corson, A.H., Fan, V.S., White, T. et.al. A Multifaceted Hospitalist Quality Improvement Intervention: Decreased Frequency of Common Labs. Journal of Hospital Medicine. 2015; 10 (6) 390-395

References, cont. Halpern, S.D., Becker, D., Curtis, J.R. et. al. An Official American Thoracic

Society/American Association of Critical-Care Nurses/American College of Chest Physicians/Society of Critical Care Medicine Policy Statement: The Choosing Wisely Top 5 List in Critical Care Medicine. American Journal of Respiratory and Critical Care Medicine. 2014; 190 (7) 818-826.

Admon, A.J. and Cooke, C.R. Will Choosing Wisely Improve Quality and Lower Costs of Care for Patients with Critical Illness? Annals of the American Thoracic Society. 2014; 11 (5), 823-827.

Jackson, J.C., Pandharipande, P. P., Girard, T.D. et.al. Depression , Posttraumatic Stress Disorder, and Functional Disability in Survivors of Critical Illness: results from the BRAIN ICU (Bringing to light the Risk Factors And Incidence of Neuropsychological dysfunction in ICU survivors) Investigation: A Longitudinal Cohort Study. Lancet Respiratory Medicine, 2014. May; 2(5) 369-379.

References, cont. Jackson, James C. and Ely, E. Wesley. Cognitive Impairment after Critical

Illness: Etiologies, Risk Factors, and Future Directions. Seminars in Respiratory Critical Care Medicine. 2013; 34: 216-222.

Mikkelsen, M.E., Netzer, G and Iwashyna, T. Post-intensive care syndrome (PICS). UpToDate.

http://www.uptodate.com.proxy.library.vanderbilt.edu/contents/post-intensive-care-syndrome-pics?source=search_result&search=post-intensive+care+syndrome&selectedTitle=1~4.

Khan, B.A., Lasiter, S and Boustani, M.A. The Critical Care Recovery Center:An Innovative Collaborative Care Model for ICU Survivors. AmericanJournal of Nursing. 2015 Vol.115, No.3 24-31.

Jackson, JC, Ely EW, Morey MC, et.al. Cognitive and physical rehabilitation ofintensive care unit survivors: results of the RETURN randomizedcontrolled pilot investigation. Critical Care Medicine 2012;40:1088-1097

References, cont.

Girard, TD, Jackson, JC, Pandeharipande, PP. et.al. Delirium as a predictor of long term cognitive impairment in survivors of critical illness. Critical Care Medicine. 2010; 38 (7): 1513-1520.

Stollings, JL, Huggins, EL, Jackson, JC and Sevin, CM. It Takes a Team: Contributions of Each Team Member in a PICS Clinic Model. Society of Critical Care Medicine, Critical Connections. 2015. Accepted for publication.

Huggins, EL, Stollings, JL, Jackson, JC and Sevin, CM. Models for a PICS Clinic:

Targeted Goals and Barriers. Society of Critical Care Medicine, Critical Connections. 2015. Accepted for publication