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Postoperative Delirium - VANA

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 14 March 2014

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Transcript of Postoperative Delirium - VANA

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.

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
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
Type of Risk Factors
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
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

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.
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.
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
Limitations include cost, mechanism of gas delivery, recovery/salvage, and an increased density making it a poor choice for patients with pulmonary dysfunction.
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).
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
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
Differentiate post-operative delirium from postoperative cognitive dysfunction and emergence delirium

Describe 4 non-modifiable risk factors known to contribute to post-op delirium.

Develop an anesthetic plan than minimizes the risk of post-op delirium
process of combining the results of different studies to derive a pooled estimate of effect
Trials included must have similar patient groups, interventions, and measure similar end-points
Considered very reliable
Transforms findings of reviewed studies to a common metric & uses statistical tests to determine overall effects
Relative Risk/Risk Ratio
Estimate of the risk of an outcome in patients who are exposed to a risk factor vs. those who are not
Is the PROPORTION of patients with a defined outcome (POD) after exposure to a risk factor (GA) divided by the proportion of patients with the defined outcome (POD) who were not exposed to the risk factor (GA).
RR > 1 : Increased risk with that exposure
RR = 1 : Exposure not associated with the outcome (no risk)
RR < 1 : Reduced risk with that exposure
Induction drugs and benzodiazepines
have properties that may precipitate delirium.
Odds Ratio
Equal to ratio of the odds of an event in an active group divided by odds of an event in control group
An estimation of risk in
case-control studies
Unable to accurately determine incidence rate and risk
Expressed with 95% Confidence Interval: if interval doesn’t include the value of 1, then the association b/w exposure and outcome is significant (at P<0.05)

The Probability of drawing an ace is 4/52 or 1/13, thus the risk of drawing an ace is 1/13 or 7.7%
The Odds of drawing an ace are the # of times an ace will be drawn (4) divided by the number of times they will NOT be drawn (48), thus the odds of drawing an ace are 1/12 (4/48) or 8.3%
For all intents & purposes OR & RR are similar (per Dr. Biddle)

RR vs. OR
Dashed line = overall
line of effect
Size of squares = relative
weight of each study
Solid vertical line =
line of no effect
Diamond = measure of effect
(lateral points = CI)
A study in last month's Anesthesia & Analgesia by Neufeld et al. (2013) found up to 50% of patients over age 65 experienced POD in the PACU
Suggests studies initiating assessments on POD1 after the PACU may miss a significant amount of patients
Pharmacologic Approaches
Modifiable vs. Non-modifiable
Full transcript