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PostOp Delirium for Leadership

Postop, post-operative, post operative, delirium, POD, anesthesia, anesthesiology, CRNA, nurse anesthesia, SRNA, Virginia Commonwealth University, VCU, DNAP, Richmond, Virginia, 2013, Evidence based clinical practice

Tony Amato

on 15 August 2013

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Transcript of PostOp Delirium for Leadership

Is postoperative delirium (POD) a problem?
Is there an association with anesthetic technique?
General Anesthesia
Regional Anesthesia
Incidence of POD & associated clinical outcomes
Acute change in cognition
Inattention, altered LOC, disorganized thinking, cognitive changes, memory deficits, disorientation, or language disturbance
Postoperative Delirium*
Urban Dictionary: The period of disordered cognition in SRNAs following a 12-hour clinical day

Lasts hours or longer
Patient awakens normally from anesthesia.
1, 3
Often involves a lucid post-anesthetic phase which lasts 1–3 days
Studies have demonstrated a wide variance in the incidence of POD, rates of between 5– 15% have been reported.

Associated with long term impairments in cognition in prospective cohort studies.
The exact mechanisms involved in its pathogenesis remain uncertain and there is currently no effective pharmacological therapy for treatment or prevention of delirium. 4
Emergence Delirium
No lucid interval
Lasts approximately 30 minutes.

Emergence delirium is considered more of a concern in pediatric patients.
Postoperative Cognitive Dysfunction
Refers to a more subtle, long-term cognitive impairment noted on neuropsychological tests (eg. MMSE) assessing attention and memory.
Poor short and long term outcomes.
1-3, 5,6
Increased morbidity & mortality
Length of hospital stay, increased associated healthcare costs ($38-$152 billion per year in the US)
Delirium may accelerate the cognitive decline in patients with Alzheimer disease.
Newer evidence is emerging that (younger) patients with delirium may develop a PTSD–like syndrome.
A recent meta-analysis showed a doubling of the hazard ratio for death after an episode of delirium in a mixture of medical and surgical patients (OR 1.95, 95% confidence interval 1.51-2.52) over an average 22.7 month follow-up period.
Proposed Pathophysiology
Central cholingeric defect
Result of energy failure perioperatively from hypoxia or ischemia.
Likely augmented by the direct action of anti-cholinergic medications
Peripheral inflammation
Surgical stress releases pro-
inflammatory cytokines
interleukin 1β and TNFα
Activate CNS microglia further releasing pro-inflammatory cytokines that cause neuronal dysfunction.

Microglia-mediated neuroinflammation via t
oll-like receptor
signaling is a significant contributor
Curcumin, ibudilast
have been shown to interfere with various steps in the proinflammatory microglial activation intracellular signal- ling pathway, disrupting the subsequent neuroinflammatory cascade.
Cognitive reserves
may also be diminished by clinically occult Alzheimer’s disease, Lewy Body, or other central neurodegenerative pathology.
POD Symptoms may be from
of the reciprocal

(cytokine release has been shown to increase dopamine levels centrally).
Inflammation and sedative drugs decrease network integration in the brain
Alter the balance of neural transmission through increases in
tone mediated by
γ-amino-butyric acid (GABA)
in the brain.
3, 6
Avoidance of GABAergic drugs (sevoflurane or propofol) and sedative agents, would reduce the burden of postoperative and intensive care delirium
Risk Factors
Each study carried out assessing risk factors for POD is unique and therefore introduces significant heterogeneity and problems when attempting to generalize a predictive risk model.
Noncardiac Surgery Prediction Rule
: Age, impaired cognitive function, impaired physical function, abnormal laboratory values, alcohol abuse, thoracic surgery, and open-aortic surgery.
most common
independent risk factor for delirium across studies is
preexisting cognitive impairment
Glucose, sodium, potassium, albumin, anemia
May represent underlying severe disease or organ system dysfunction
may be particularly important because of its association with malnutrition, drug binding, fluid management and perioperative mortality
Cardiac Surgery
Impaired cognitive function, low albumin, preoperative depressive symptoms, prior stroke/TIA.
Patient Factors
education level, smokers, comorbidities/ASA status 3 or greater
Physiologic Factors
Inflammation, microembolization, BBB disruption
Intraoperative Factors
Anesthesia, cerebral oxygenation, hypotension, medications
Perioperative Factors
Medication, sleep
Surgery Factors
Highest incidence with hip fracture, vascular, cardiac, emergencies.
Anesthetic Technique
Rudolph JL, Marcantonio ER. Review articles: postoperative delirium: acute change with long-term implications. Anesth Analg 2011;112:1202-1211
Three Key Variables from Noimark
Severity of insult
(eg aortic vs. peripheral vascular procedures)
Rapidity of onset of insult
(eg trauma, emergency)
The patient
Pre-existing cognitive delirium
Male Sex
Affects 7% of those aged over 65 and 25–40% aged over 80 Measuring frailty may be a more sensitive marker of determining post-operative delirium. The most commonly used frailty measure is the five- point score proposed by Fried
1.Mason SE, Noel-Storr A, Ritchie CW. The impact of general and regional anesthesia on the incidence of post-operative cognitive dysfunction and post-operative delirium: a systematic review with meta-analysis. J Alzheimers Dis 2010;22 Suppl 3:67-79.
2.Noimark D. Predicting the onset of delirium in the post-operative patient. Age Ageing 2009;38:368-373.
3.Sanders RD, Pandharipande PP, Davidson AJ, Ma D, Maze M. Anticipating and managing postoperative delirium and cognitive decline in adults. BMJ 2011;343:d4331.
4.Jalleh R, Koh K, Choi B, Liu E, Maddison J, Hutchinson MR. Role of microglia and toll-like receptor 4 in the pathophysiology of delirium. Med Hypotheses 2012;79:735-739.
5.Rudolph JL, Marcantonio ER. Review articles: postoperative delirium: acute change with long-term implications. Anesth Analg 2011;112:1202-1211.
6.Coburn M, Sanders RD, Maze M, Rossaint R. The Hip Fracture Surgery in Elderly Patients (HIPELD) study: protocol for a randomized, multicenter controlled trial evaluating the effect of xenon on postoperative delirium in older patients undergoing hip fracture surgery. Trials 2012;13:180.
7. Amato, AM, Amato RE. Anatomical Illustrations for Postoperative Delirium. 2013. Prezi.com. MRI courtesy of Robin E. Amato, used with permission
8. Baumert, JH. Xenon-based anesthesia: theory and practice. Open Access Surgery 2009:2 5-13
9. Jordan BD, Wright EL. Xenon as an Anesthetic Agent. AANA Journal 2010; 78:5.

Influence neuronal processes
Gene transcription
Receptor efficacy
Synaptic vesicle cycling
Intracellular calcium homeostasis.

GA’s also appear to specifically influence pathways currently linked to POCD through

These effects are not shared by regional anesthetic (RA)
Mason metaanalysis:
5 studies whose outcome was POD
in the incidence of POD between GA vs. regional (0.88, 95% CI = 0.51–1.51).
Inhaled anesthetics
alter electrical activity in the brain and have been associated with amyloid deposition and apoptosis. 5
Induction drugs and benzodiazepines
have properties that may precipitate delirium.

Although regional anesthesia has the potential to reduce this exposure, studies of general versus regional anesthesia have not demonstrated a reduction in delirium

Pain medications may precipitate delirium, particularly


... but so can
uncontrolled pain

Acetaminophen h
as been shown to reduce total opioid needs and improve patient reports of pain in a postoperative random- ized controlled trial.
: international, multicenter, phase 2, prospective, randomized, blinded, parallel group and controlled trial to evaluate the incidence of POD
Uses the
Confusion Assessment Method (CAM)

Older patients undergoing hip fracture surgery under general anesthesia with
xenon or sevoflurane
, for a period of 4 days post surgery (primary outcome) is planned.
Research published showing multiple beneficial effects of the non-GABAergic anesthetic agent XENON. As an inert, noble gas, xenon is not metabolized by the body but yet exerts myriad biological effects, the most notable being anesthesia and organ protection
Xenon is thought to produce anesthesia through targeting either excitatory N-methyl-D-aspartate or two-pore-domain-potassium channels but not GABAA receptors.

Xenon anesthesia is rapid onset, cadiostable and xenon is not thought to disturb autoregulation of organ blood flow. Furthermore, xenon protects the brain, heart and kidney from diverse toxic insults including ischemia
Xenon exerts a diverse array of neuroprotective effects (for example, induction of B-cell lymphoma-extra large (Bcl-xl), phosphorylated cAMP response element binding protein (pCREB) and hypoxia-inducible factor (HIF)-1α cell survival proteins) and importantly synergizes with other neuro-protective strategies (for example, hypothermia and α2 agonists). 6
Confusion Assessment Method (CAM),
(based on DSM-IIIR criteria)
Algorithm for the diagnosis of delirium

Adds objective assessments for
attention, consciousness,
(even if non-verbal).
Acetylcholinesterase inhibitors
are medications used to stabilize cognitive function in patients with Alzheimer disease.

Prevention or treatment of delirium with acetylcholinesterase inhibitors
should be avoided
is an alpha-2 adrenergic receptor agonist used for sedation.

Reduces the rate of delirium
(vs. midazolam and lorazepam) in the

An RCT of
intraoperative sedation
with dexmedetomidine, propofol, or midazolam found that dexmedetomidine was associated with a
lower incidence of POD
Because of the low risk of adverse events,
nonpharmacological methods
are recommended as a first step.
Cognitive stimulation
Improve Sensory Input
Avoidance of psychoactive medication
Fluid & Nutrition
Avoidance of hospital complications
When nonpharmacological interventions are not sufficient,
antipsychotics are considered the first line
for management of agitation associated with POD

is a high-potency
dopamine antagonist
(anti- psychotic) medication

In a single-site study,
haloperidol did NOT reduce the
of delirium after hip fracture
Did reduce
severity and duration

POD is a problem, in terms of both short and long-terms patient morbidity and mortality and the associated healthcare costs.
No evidence exists at this time to suggest that one anesthetic technique is superior to another in the prevention of POD, however identification of at-risk patients and avoidance of modifiable risk factors may help decrease the incidence.
General anesthesia (compared to RA) may increase the risk of developing POCD...
... however this has not been shown for POD.

This data would suggest use of regional anesthesia wherever possible especially in at-risk individuals or surgerical procedures.
Novel anesthetics, such as Xenon gas, in place of volatile anesthetics may play a role in POD avoidance in the future
POD is
attributed to anesthetic agents, in which case it would be referred to as emergence delirium (a subtype of substance-induced delirium.
General Anesthetics
The learner will differentiate post-operative delirium from postoperative cognitive dysfunction and emergence delirium.
The learner will describe 2 of 4 theorized pathophysiologic mechanisms of post-operative delirium.
The learner will extrapolate and recite 4 non-modifiable risk factors known to contribute to post-op delirium.
The learner will classify 3 anesthetic factors that may contribute to the development of post-op delirium.
The learner will be develop an anesthetic plan that minimizes the risk of post-op delirium.

1.Which of the following is NOT associated with post-operative delirium?

A. Acute changes in cognition, including fluctuating consciousness or disordered thinking
B. An onset immediately after surgery lasting approximately 30 minutes
C. Incidence increases with age
D. Occurs with both regional AND general anesthesia

Answer: B. An onset immediately after surgery lasting approximately 30 minutes.

2. Which of the following accurately describes a patient with post operative delirium?
A. 61 year old who wakes up normally after receiving GA for a hip fracture who presents on POD 1 with altered cognition and disordered thinking and memory deficits.
B. A 4 year old who received sevoflurane for a BMT who wakes up with severe agitation and confusion.
C. A 74 year old who had GA for a lumbar fusion 3 months ago who has suffered from memory and attention deficits since her surgery
D. A patient who just received versed in the holding area and is now confused and agitated while awaiting the start of their surgery.

Answer: A
3. Which of the following is NOT a proposed physiologic mechanism of POD?

A central cholinergic defect
B. Pro-inflammatory cytokines released as a result of surgical stress
C. Imbalance of GABA affecting neural transmission
D. Stimulation of NMDA Receptor

Answer: D
4. Which of the following are modifiable risk factors known to contribute to the development of POD? (Select FOUR)

A. Age
B. Smoking
C. Use of versed for pre-medication
D. Lack of Sleep
E. Intraoperative Hypotension
F. Male Sex

Answer: B, C, D, E

5. Knowing the risk factors in the development of POD, which of the following scenarios is LEAST likely to be associated with POD?

A. An elderly patient with pre-existing cognitive dysfunction, such as alzheimer’s

B. An emergent surgery for hip-fracture in which a patient was given versed and general anesthesia

C. A young, highly-educated ASA 1 female patient with an elective removal of a cyst under local anesthesia

D. A frail 60 year old male with hypoalbuminemia undergoing a long fem-pop bypass with significant intraoperative hypotension

Answer: C
6. Select the TRUE statement

A. Due to the increased incidence of POD with the use of opioids, all opioids should be avoided in at-risk surgical patients

B. Because regional anesthesia techniques lack the central anticholinergic effects of general anesthesia that are known to contribute to POD, regional anesthesia has a decreased incidence of POD and is the preferred method

C. Versed can help avoid POD in at-risk patients via its effects at the GABA-receptor

D. Current evidence suggests there is no difference in the incidence of POD regardless of whether general or regional anesthesia is used

Answer: D
7. Which of the following are anesthetic factors that may contribute to the development of POD? (Select 3)

A. Use of sevoflurane as the primary anesthetic
B. Increased duration of anesthesia
C. Administration of cognitively-active medications
D. Low albumin
E. Use of a BIS monitor

Answer: A, B, C
8. Your patient with Alzheimer’s is at risk for developing POD. What aspects of the anesthetic care plan would be most appropriate to implement for this patient? (Select TWO)
A. Consider the use of an acetylcholinesterase inhibitor
B. Utilization of precedex instead of versed for sedation
C. Utilization of prophylactic haloperidol as a first-line intervention
D. Increase cognitive stimulation and ensure the patient has his hearing aids and glasses perioperatively
E. Perform the surgery with neuraxial anesthesia. The platelets are low, but the benefits outweigh the risks.

Answer: B, D
9. Which of the following is used to assess for delirium?

A. CAM-ICU scale
E. The International Standardized Delirium Score
F. Mini-Mental State Exam (MMSE)

Answer: A
10. Which of the following are TRUE regarding xenon anesthesia? (Select THREE)

A. Is an inert, noble gas that is not metabolized by the body with rapid onset/offset
B. Has no biological effects, so its utility is limited in anesthesia
C. Provides a myriad of biological effects, most notably anesthesia and organ protection
D. Is postulated to work on GABA receptor, just like propofol and benzodiazepines
E. May preserve autoregulation, and protect the brain, heart, and kidneys from ischemic damage during surgery

Answer: A, C, E
Odorless, nonpungent, nontoxic, nonexplosive, envi- ronmentally friendly, and unlikely to undergo biotransformation has fueled more studies for the use of xenon.
Noble (inert) gases are stable due to a fully occupied outer shell of electrons, which means they are mostly nonreactive, or inert, to forming bonds with other elements. 9
A naturally occurring element, it is not a pollutant or an occupationally haz- ardous gas, nor does it contribute to global warming or the greenhouse gas effect.
In contrast, N2O is 230 times more potent as a greenhouse gas than is carbon dioxide, taking 120 years to break down. 9
Goto et al. found that emergence from xenon anesthesia is 2 or 3 times faster than that from comparable MACs of nitrous oxide/isoflurane and nitrous oxide/sevoflurane anesthesia. 9
Analgesic potency 1.5 times that of nitrous oxide. 9
Doesn't trigger MH, & diffusion hypoxia is unlikely during recovery from xenon anesthesia. 9
The Good
The Bad
Xenon is a naturally occurring element that comprises 0.0000086%, or 0.05 parts per million, of air. Indeed, the rarity of this element is the basis for its name.
Associated costs with the introduction of any new anesthetic agent are involve the purchase of new equipment such as vaporizers, monitors, and anesthesia machines.
1 L of xenon costs approximately $20 today, vs. with pennies per liter for nitrous oxide.
One study by Nakata and associates46 found that the cost of xenon anesthesia in a 40-year-old, ASA physical status I man weighing 70 kg costs $356 for 240 minutes of closed-circuit anesthesia. In comparison, closed-circuit anesthesia with nitrous oxide and isoflurane costs only $52. 9
After 4 hours in a completely closed system, becomes comparable in cost to other anesthetics.
This gives xenon a clear edge in settings such as cardiac and neurological surgery, in which prolonged administration of anesthesia is required and rapid emergence is beneficial.
High incidence of postoperative nausea and vomiting.
Increases pulmonary resistance due to its greater density.
Poor choice for COPD, MO, premies, airway tumors
Diffuses into closed spaces (poor choice for surgeries at risk for VAE).
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